Faculty Bibliography

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0.0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1.36, 95% CI 1.10-1.68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0.44). Opioid-negative urine samples (p<0.0001) and opioid-abstinent days (p<0.0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0.0012), then converged by week 24 (p=0.20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

BACKGROUND: Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data supporting its effectiveness in U.S. criminal justice populations are limited. METHODS: In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS: A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02). CONCLUSIONS: In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).

BACKGROUND: Buprenorphine maintenance for opioid dependence remains of limited availability among underserved populations, despite increases in US opioid misuse and overdose deaths. Low threshold primary care treatment models including the use of unobserved, "home," buprenorphine induction may simplify initiation of care and improve access. Unobserved induction and long-term treatment outcomes have not been reported recently among large, naturalistic cohorts treated in low threshold safety net primary care settings. METHODS: This prospective clinical registry cohort design estimated rates of induction-related adverse events, treatment retention, and urine opioid results for opioid dependent adults offered buprenorphine maintenance in a New York City public hospital primary care office-based practice from 2006 to 2013. This clinic relied on typical ambulatory care individual provider-patient visits, prescribed unobserved induction exclusively, saw patients no more than weekly, and did not require additional psychosocial treatment. Unobserved induction consisted of an in-person screening and diagnostic visit followed by a 1-week buprenorphine written prescription, with pamphlet, and telephone support. Primary outcomes analyzed were rates of induction-related adverse events (AE), week 1 drop-out, and long-term treatment retention. Factors associated with treatment retention were examined using a Cox proportional hazard model among inductions and all patients. Secondary outcomes included overall clinic retention, buprenorphine dosages, and urine sample results. RESULTS: Of the 485 total patients in our registry, 306 were inducted, and 179 were transfers already on buprenorphine. Post-induction (n = 306), week 1 drop-out was 17%. Rates of any induction-related AE were 12%; serious adverse events, 0%; precipitated withdrawal, 3%; prolonged withdrawal, 4%. Treatment retention was a median 38 weeks (range 0-320) for inductions, compared to 110 (0-354) weeks for transfers and 57 for the entire clinic population. Older age, later years of first clinic visit (vs. 2006-2007), and baseline heroin abstinence were associated with increased treatment retention overall. CONCLUSIONS: Unobserved "home" buprenorphine induction in a public sector primary care setting appeared a feasible and safe clinical practice. Post-induction treatment retention of a median 38 weeks was in line with previous naturalistic studies of real-world office-based opioid treatment. Low threshold treatment protocols, as compared to national guidelines, may compliment recently increased prescriber patient limits and expand access to buprenorphine among public sector opioid use disorder patients.

INTRODUCTION/BACKGROUND:Expanding access to medication for opioid use disorder (MOUD) to people involved in the carceral system is a priority for the New Hampshire Department of Corrections (NHDOC), where more than 40% of residents have an opioid use disorder (OUD). NHDOC participated in the multi-site Justice Community Opioid Innovation Network (JCOIN) clinical trial, "Long-acting buprenorphine vs. naltrexone opioid treatments in criminal justice system-involved adults (EXIT-CJS)". We examine the contributing factors to the expansion of the NHDOC MOUD program from 2021 to 2023, including participation in EXIT-CJS, which occurred from 2019 to 2024. METHODS:Data on quarterly MOUD prescribing and EXIT-CJS enrollments were abstracted from the NHDOC medical records from July 1, 2021- December 31, 2023 as part of a quality improvement initiative. To examine factors influencing expansion of the program, conversations were conducted with NHDOC leadership team and clinical staff. RESULTS:From 2021 to 2023, the quarterly number of patients treated with MOUD at the NHDOC increased by more than 400% from a total of 165 patients in July-September 2021, to 685 patients in October-December 2023. At the policy level, elimination of the federal DATA-Waiver (X-Waiver) Program allowed additional providers to prescribe MOUD. At the organizational level, support from NHDOC leadership, including Medical and Forensics and the Commissioner's Office, encouraged broader engagement in MOUD from providers, multidisciplinary staff, and security. This work was augmented through receipt of State Opioid Response (SOR) dollars with a requirement to continue to advance education for NHDOC staff on the efficacy of MOUD. Resulting discussions between medical providers, experts on addiction treatment, staff and residents supported a culture change in attitudes about MOUD. During this same time window, the NHDOC made significant adjustments in the distribution of MOUD by adjusting the nursing administration process thus reducing the stigma associated with being a patient on MOUD and treating MOUD medication administration like all other medical conditions. DISCUSSION/CONCLUSIONS:Policy-related, organizational, and individual factors contributed to the expansion of the MOUD program at the NHDOC. EXIT-CJS recruitment occurred synergistically with the expansion of the MOUD program. As NHDOC was engaged as a site in EXIT-CJS, study recruitment increased awareness of extended-release treatment options among residents and staff.

BACKGROUND AND AIMS/OBJECTIVE:It is unclear if findings from randomized controlled trials (RCT) of medications for opioid use disorder apply to real-world settings. We estimated the effectiveness of buprenorphine-naloxone (BUP-NX) versus extended-release naltrexone (XR-NTX) on treatment interruption in a RCT and an observational study based on real-world data. DESIGN/METHODS:Target trial emulation to harmonize the protocol and statistical analyses of X:BOT (target trial) and the observational study (observational emulation). Baseline was randomization in the target trial and medically managed opioid withdrawal (MMOW) discharge in the observational emulation. SETTINGS/METHODS:X:BOT trial and Massachusetts Public Health Data Warehouse observational data (United States). PARTICIPANTS/METHODS:The target trial included all X:BOT participants. The observational emulation trial included MMOW discharges from January 2014 to May 2016. MEASUREMENTS/METHODS:Treatment strategies were BUP-NX versus XR-NTX initiation within 28 days of baseline. The outcome was treatment interruption (earliest of treatment discontinuation, incarceration, MMOW readmission, death). We estimated the 24-week risk and risk difference. FINDINGS/RESULTS:In the target trial, 94% (269/287) and 66% (187/283) of participants randomized to BUP-NX or XR-NTX initiated their assigned treatment within 28 days, respectively. In the observational emulation, BUP-NX and XR-NTX were initiated within 28 days in 9% (5209/59 076) and 3% (1813/59 076) of MMOW discharges, respectively. The adjusted 24-week treatment interruption risks (95% confidence interval) for BUP-NX and XR-NTX were 68% (60%,77%) and 72% (60%,83%) in the target trial [risk difference, -4 percentage points (pp; -17 pp,11 pp)] and 82% (81%,83%) and 93% (92%,95%) in the observational emulation [risk difference,-11 pp (-13 pp,-10 pp)]. CONCLUSIONS:Buprenorphine-naloxone might be superior to extended-release naltrexone in real-world settings where the majority of people struggle to remain on medications for opioid use disorder. Buprenorphine-naloxone initiators had a lower risk of treatment interruption than extended-release naltrexone initiators in an observational emulation, but similar risks in a randomized controlled trial, although confidence intervals were wide. Trial participation, study size and residual confounding may explain these differences.

INTRODUCTION/BACKGROUND:Most Americans now access social media platforms, including YouTube, to obtain health information. However, few studies have evaluated the quality of YouTube content related to opioid use disorder (OUD), including medications for OUD (MOUD; buprenorphine) and harm reduction resources (e.g., naloxone). The purpose of this cross-sectional analysis was to assess the quality, accuracy, and reliability of MOUD and harm reduction-related video content available on YouTube. METHODS:The study team conducted a YouTube search between June 2022 and July 2022 using key words related to MOUD and harm reduction content (e.g., "suboxone," "methadone," "Narcan"). The 5 most viewed videos from each search term were analyzed for quality (i.e., Global Quality Scale; GQS), accuracy (i.e., JAMA Benchmark Criteria), and reliability (i.e., DISCERN). Videos that were non-English, duplicate, or that did not directly mention OUD, MOUD, or harm reduction were excluded from the review (N = 6). RESULTS:YouTube videos (N = 70) were mostly produced by medical professionals (27.1 %), independent nonmedical users (21.4 %; e.g., vloggers, individuals documenting their experiences), medical organizations (17.1 %; e.g., hospitals, treatment programs), and/or media (14.3 %; e.g., news agencies). The target audience was primarily the general public (65.7 %), people who use opioids (20.0 %), and healthcare providers (10.0 %). Videos containing MOUD content (N = 64, 61.4 %) mostly focused on suboxone (25.0 %), methadone (23.4 %), Sublocade (14.1 %), and subutex/buprenorphine (14.1 %). The median quality score was 2 based on the GQS with 3 videos receiving the highest quality rating (5). Two videos were highly rated for accuracy per all three JAMA Benchmark criteria. Videos produced by nonmedical educational channels had the highest overall reliability scores on the DISCERN criteria (median 4), followed by medical professionals (median 3), and medical organizations (median 2.5). CONCLUSION/CONCLUSIONS:The overall quality, accuracy, and reliability of MOUD and harm reduction related content posted on YouTube is poor. The lack of evidence-based content posted on YouTube reinforces the need for public health expert involvement in disseminating guideline-based content on social media.

BACKGROUND:Offering medications for opioid use disorder (MOUD) in carceral settings significantly reduces overdose. However, it is unknown to what extent individuals in jails continue MOUD once they leave incarceration. We aimed to assess the relationship between in-jail MOUD and MOUD continuity in the month following release. METHODS:We conducted a retrospective cohort study of linked NYC jail-based electronic health records and community Medicaid OUD treatment claims for individuals with OUD discharged from jail between 2011 and 2017. We compared receipt of MOUD within 30 days of release, among those with and without MOUD at release from jail. We tested for effect modification based on MOUD receipt prior to incarceration and assessed factors associated with treatment discontinuation. RESULTS:Of 28,298 eligible incarcerations, 52.8 % received MOUD at release. 30 % of incarcerations with MOUD at release received community-based MOUD within 30 days, compared to 7 % of incarcerations without MOUD (Risk Ratio: 2.62 (2.44-2.82)). Most (69 %) with MOUD claims prior to incarceration who received in-jail MOUD continued treatment in the community, compared to 9 % of those without prior MOUD. Those who received methadone (vs. buprenorphine), were younger, Non-Hispanic Black and with no history of MOUD were less likely to continue MOUD following release. CONCLUSIONS:MOUD maintenance in jail is strongly associated with MOUD continuity upon release. Still, findings highlight a gap in treatment continuity upon-reentry, especially among those who initiate MOUD in jail. In the wake of worsening overdose deaths and troubling disparities, improving MOUD continuity among this population remains an urgent priority.

Medications for opioid use disorder (MOUD) increase retention in care and decrease mortality during active treatment; however, information about the comparative effectiveness of different forms of MOUD is sparse. Observational comparative effectiveness studies are subject to many types of bias; a robust framework to minimize bias would improve the quality of comparative effectiveness evidence. This paper discusses the use of target trial emulation as a framework to conduct comparative effectiveness studies of MOUD with administrative data. Using examples from our planned research project comparing buprenorphine-naloxone and extended-release naltrexone with respect to the rates of MOUD discontinuation, we provide a primer on the challenges and approaches to employing target trial emulation in the study of MOUD.

BACKGROUND:Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD). METHODS:This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups. RESULTS:MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release. CONCLUSION/CONCLUSIONS:MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs.

BACKGROUND:High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized. METHODS:A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template. RESULTS:A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention. CONCLUSIONS:Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary.