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Infective endocarditis associated with injection drug use (IDU-IE) is markedly increasing in the United States and Canada. Long-term outcomes are dismal and stem from insufficient substance use disorder treatment. In this review, we summarize the principles of antimicrobial and surgical management for infective endocarditis associated with injection drug use. We discuss approaches to opioid use disorder care and harm reduction in the inpatient setting and review opportunities to address preventable infections among persons injecting drugs. We highlight barriers to implementing optimal treatment and consider novel approaches that may reshape infective endocarditis associated with injection drug use treatment in coming years.

Background Untreated opioid use disorder (OUD) affects the care of HIV/HCV co-infected people who inject opioids. Despite active injection opioid use, there is evidence of increasing engagement in HIV care and adherence to HIV medications among HIV/HCV co-infected persons. However, less than one-half of this population is offered HCV treatment onsite. Treatment for OUD is also rare and largely occurs offsite. Integrating buprenorphine-naloxone (BUP-NX) into onsite care for HIV/HCV co-infected persons may improve outcomes, but the clinical impact and costs are unknown. We evaluated the clinical impact, costs, and cost-effectiveness of integrating (BUP-NX) into onsite HIV/HCV treatment compared with the status quo of offsite referral for medications for OUD. Methods We used a Monte Carlo microsimulation of HCV to compare two strategies for people who inject opioids: 1) standard HIV care with onsite HCV treatment and referral to offsite OUD care (status quo) and 2) standard HIV care with onsite HCV and BUP-NX treatment (integrated care). Both strategies assume that all individuals are already in HIV care. Data from national databases, clinical trials, and cohorts informed model inputs. Outcomes included mortality, HCV reinfection, quality-adjusted life years (QALYs), costs (2017 US dollars), and incremental cost-effectiveness ratios. Results Integrated care reduced HCV reinfections by 7%, cases of cirrhosis by 1%, and liver-related deaths by 3%. Compared to the status quo, this strategy also resulted in an estimated 11/1,000 fewer non-liver attributable deaths at one year and 28/1,000 fewer of these deaths at five years, at a cost-effectiveness ratio of $57,100/QALY. Integrated care remained cost-effective in sensitivity analyses that varied the proportion of the population actively injecting opioids, availability of BUP-NX, and quality of life weights. Conclusions Integrating BUP-NX for OUD into treatment for HIV/HCV co-infected adults who inject opioids increases life expectancy and is cost-effective at a $100,000/QALY threshold.

Background and aims While prescribed and illicit opioid use are primary drivers of the national surges in overdose deaths, opioid overdose deaths in which stimulants are also present are increasing in the U.S. We determined the social determinants and sociodemographic factors associated with opioid-only versus polysubstance opioid overdose deaths in Massachusetts. Particular attention was focused on the role of stimulants in opioid overdose deaths. Methods We analyzed all opioid-related overdose deaths from 2014 to 2015 in an individually-linked population database in Massachusetts. We used linked postmortem toxicology data to identify drugs present at the time of death. We constructed a multinomial logistic regression model to identify factors associated with three mutually exclusive overdose death groups based on toxicological results: opioid-related deaths with (1) opioids only present, (2) opioids and other substances not including stimulants, and (3) opioids and stimulants with or without other substances. Results Between 2014 and 2015, there were 2,244 opioid-related overdose deaths in Massachusetts that had accompanying toxicology results. Toxicology reports indicated that 17% had opioids only, 36% had opioids plus stimulants, and 46% had opioids plus another non-stimulant substance. Persons older than 24 years, non-rural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone. Conclusions Polysubstance opioid overdose is increasingly common in the US. Addressing modifiable social determinants of health, including barriers to mental health services and homelessness, is important to reduce polysubstance use and overdose deaths.

Background and Aims While the United States is in the midst of an overdose epidemic, effective treatments are underutilized and commonly discontinued. Innovations in medication delivery, including an extended-release formulations, have the potential to improve treatment access and reduce discontinuation. We sought to assess extended-release buprenorphine discontinuation among individuals with opioid use disorder (OUD) in a real-world, nationally representative cohort. Setting United States Participants Commercially insured individuals initiating one of four FDA-approved medications for opioid use disorder (MOUD) in 2018: extended-release buprenorphine, extended-release naltrexone, mucosal buprenorphine (mono- or co-formulated with naloxone), or methadone. Measurements Our primary outcome was medication discontinuation, defined as a gap of more than 14 days between the end of one prescription or administration and the subsequent dose. Findings We identified 14,358 individuals initiating MOUD in 2018, including 204 (1%) extended-release buprenorphine, 1,173 (8%) extended-release naltrexone, 12,171 (85%) mucosal buprenorphine, and 810 (6%) methadone initiations. Three months after initiation, 50% (95% confidence interval [CI] 40%-60%) of extended-release buprenorphine, 64% (95% CI 61%-69%) of extended-release naltrexone, 34% (95% CI 33%-35%) of mucosal buprenorphine, and 58% (95% CI 54%-62%) of methadone initiators had discontinued treatment. Conclusions Across all treatment groups, medication discontinuation was high, and in this sample of early adopters with limited follow-up time, we found no evidence that extended-release buprenorphine offered a retention advantage compared to other MOUD in real-world settings. Retention continues to represent a major obstacle to treatment effectiveness, and interventions are needed to address this challenge even as new MOUD formulations become available.

To determine the association between immunosuppression and time to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) clearance, we studied 3758 adults retested following initial SARS-CoV-2 infection. Cox proportional hazards models demonstrated delayed PCR clearance with older age, multiple comorbidities, and solid organ transplant but not by degree of immunocompromise. These findings challenge current retesting practices., Few studies support SARS-CoV-2 retesting practices to end isolation. Among 3758 adults retested after SARS-CoV-2 infection, we observed delayed PCR clearance with older age, multiple comorbidities and solid organ transplant, but not other immunocompromising conditions. This challenges current retesting guidance., Graphical Abstract Graphical Abstract

BACKGROUND AND AIMS: Some adolescents and young adults (termed ‘youth’) prescribed an opioid will develop opioid use disorder or experience overdose. This study aimed to identify patient and prescription characteristics associated with subsequent risk of opioid use disorder or overdose during the year after an opioid is first dispensed. DESIGN: Retrospective cohort study. SETTING: Commercial health insurance claims in a large US database from 2006 to 2016. PARTICIPANTS: Youth aged 11–25 years filling an initial opioid prescription. EXPOSURES: Patient (sociodemographic information, and physical and mental health diagnoses) and prescription characteristics (opioid formulation, dose, and duration). MEASUREMENT: The primary outcome was development of an ‘opioid-related complication’ (a diagnosis of opioid use disorder or opioid-related overdose) during the subsequent 12 months. Exposures of interest were patient (sociodemographic information, and physical and mental health diagnoses) and prescription characteristics (opioid formulation, dose, and duration). FINDINGS: Among 3,278,990 youth filling an initial opioid prescription, median age was 18 years (IQR, 16–21) and 56.1% were female. During the subsequent 12 months, 10,405 (0.3%) youth experienced an opioid-related complication. Conditions associated with increased risk included mood/anxiety disorders (aRR, 4.45 [95% CI, 4.25–4.66]) and substance use (aRR, 20.77 [95% CI, 19.74–21.84]). Comorbid substance use disorders were present among 72.8% of youth experiencing an opioid-related complication and included alcohol (33.4%), cannabis (33.0%), nicotine (43.2%), and other substance use disorders (75.5%). Long-acting opioids (aRR, 2.59 [95% CI, 2.18–3.09]) and longer durations were associated with increased risk (7–14 days: aRR, 1.15 [95% CI, 1.08–1.22]; ≥15 days: aRR, 1.96 [95% CI, 1.80–2.12]) compared to short-acting formulations and durations ≤3 days, respectively. CONCLUSIONS: Complications after an initial opioid prescription are relatively rare. Screening for mental health conditions and substance use before prescribing might identify youth at risk for OUD and overdose. Clinicians might mitigate the risk by prescribing short-acting opioids for short durations.

Business Not as Usual Persons with substance use disorders — particularly those in living conditions that increase Covid risk — should be prioritized to receive SARS-CoV-2 vaccines, and vaccine-rol...

SARS-CoV-2 Vaccination and Vulnerable Populations In this audio interview conducted on December 9, 2020, the editors are joined by Dr. Joshua Barocas, an infectious disease specialist at Boston Med...

Background: As COVID-19 surged in people experiencing homelessness, leaders at Boston Medical Center (BMC), New England’s largest safety-net hospital, developed a program to care for them.Aim: Provide an opportunity for COVID-infected people experiencing homelessness to isolate and receive care until no longer contagiousSetting: A decommissioned hospital building.Participants: COVID-infected people experiencing homelessnessProgram Description: Care was provided by physician volunteers and furloughed staff. Care focused on allowing isolation, managing COVID-19 symptoms, harm-reduction interventions, and addressing problems related to substance use and mental illness.Program evaluation: Among 226 patients who received care, 65% were referred from BMC. Five percent were transferred to the hospital for a complication that appeared COVID-related. There were no deaths, but 7 patients had non-fatal overdoses. Seventy-nine % had at least one diagnosis of mental illness, and 42% reported actively using at least one substance at the time of admission. Thirty % had at least one mental health diagnosis plus active substance use.Discussion: This hospital-based COVID Recuperation Unit was rapidly deployed, provided safe isolation for 226 patients over 8 weeks, treated frequent SUD and mental illness, and helped prevent the hospital’s acute-care bed capacity from being overwhelmed during the peak of the COVID-19 epidemic.

In response to the opioid crisis, IDSA and HIVMA established a working group to drive an evidence- and human rights-based response to illicit drug use and associated infectious diseases. Infectious diseases and HIV physicians have an opportunity to intervene, addressing both conditions. IDSA and HIVMA have developed a policy agenda highlighting evidence-based practices that need further dissemination. This paper reviews (1) programs most relevant to infectious diseases in the 2018 SUPPORT Act; (2) opportunities offered by the “End the HIV Epidemic” initiative; and (3) policy changes necessary to affect the trajectory of the opioid epidemic and associated infections. Issues addressed include leveraging harm reduction tools and improving integrated prevention and treatment services for the infectious diseases and substance use disorder care continuum. By strengthening collaborations between infectious diseases and addiction specialists, including increasing training in substance use disorder treatment among infectious diseases and addiction specialists, we can decrease morbidity and mortality associated with these overlapping epidemics.

We compared oropharyngeal swab test performance with nasopharyngeal testing for discontinuation of transmission-based COVID-19 precautions. We performed a retrospective review of confirmed COVID-19-positive patients who received paired nasopharyngeal and oropharyngeal SARS-CoV-2 tests for clearance from isolation from May 4, 2020, to May 26, 2020. Using nasopharyngeal swabs as the reference standard, we calculated the sensitivity, specificity, and negative predictive value of oropharyngeal swabs. We also calculated the kappa between the 2 tests. A total of 189 paired samples were collected from 74 patients. Oropharyngeal swab sensitivity was 38%, specificity was 87%, and negative predictive value was 70%. The kappa was 0.25. Our study suggests that oropharyngeal swabs are inferior to nasopharyngeal swabs for test-based clearance from COVID-19 isolation.

Highlights • The HEALing Communities Study (HCS) is designed to implement and evaluate the Communities That HEAL (CTH) intervention to reduce opioid overdose deaths. • The HCS includes a health economics study. • Costs of CTH will be estimated for multiple perspectives. • The health economics study includes cost-effectiveness analyses and simulation modeling., Background The HEALing Communities Study (HCS) is designed to implement and evaluate the Communities That HEAL (CTH) intervention, a conceptually driven framework to assist communities in selecting and adopting evidence-based practices to reduce opioid overdose deaths. The goal of the HCS is to produce generalizable information for policy makers and community stakeholders seeking to implement CTH or a similar community intervention. To support this objective, one aim of the HCS is a health economics study (HES), the results of which will inform decisions around fiscal feasibility and sustainability relevant to other community settings. Methods The HES is integrated into the HCS design: an unblinded, multisite, parallel arm, cluster randomized, wait list–controlled trial of the CTH intervention implemented in 67 communities in four U.S. states: Kentucky, Massachusetts, New York, and Ohio. The objectives of the HES are to estimate the economic costs to communities of implementing and sustaining CTH; estimate broader societal costs associated with CTH; estimate the cost-effectiveness of CTH for overdose deaths avoided; and use simulation modeling to evaluate the short- and long-term health and economic impact of CTH, including future overdose deaths avoided and quality-adjusted life years saved, and to develop a simulation policy tool for communities that seek to implement CTH or a similar community intervention. Discussion The HCS offers an unprecedented opportunity to conduct health economics research on solutions to the opioid crisis and to increase understanding of the impact and value of complex, community-level interventions.

Background An epidemic of opioid overdose has spread across North America, with illicit drug-related overdose emerging as a leading cause of death in recent years. Estimates of opioid use disorder (OUD) prevalence at the level of the public health service delivery area are needed to project resource needs and identify priority areas for targeted intervention. Our objective is to estimate the annual prevalence of OUD in British Columbia (BC), Canada, from 2000 to 2017. Methods We performed a multi-sample stratified capture-recapture analysis to estimate OUD prevalence in BC. The analysis included individuals identified from 3 administrative databases for 2000–2011 and 4 databases for 2012–2017, linked at the individual level. Negative binomial regression models on the counts of individuals within these strata were used to estimate prevalence, adjusting for dependency between databases. Results OUD prevalence in BC among people aged 12 years or older was 1.00 % (N = 34,663 individuals) in 2000 and increased to 1.54 % (N = 61,080) in 2011. Between 2013 and 2017 prevalence increased from 1.57 % (95 % confidence interval: 1.56–1.58) to 1.92 % (1.89–1.95; N = 83,760; 82,492-84,855). The greatest increases in prevalence were observed among males 12–30 years old and 31–44 years old, with 43.2 % and 40.2 % increases from 2013 to 2017. Conclusions In BC, the OUD prevalence was 1.92 % among people 12 years or older in 2017. We estimated that prevalence has nearly doubled since 2000, with the highest increases in prevalence observed among males under 45.

A Homeless Man with Covid-19 A 66-year-old homeless man was evaluated for cough and rhinorrhea during the Covid-19 pandemic. He had tested positive for SARS-CoV-2 through a universal testing progra...

Background The expansion of the US opioid epidemic has led to significant increases in infections, such as infective endocarditis (IE), which is tied to injection behaviors. We aimed to estimate the population-level IE mortality rate among people who inject opioids and compare the risk of IE death against the risks of death from other causes. Methods We developed a microsimulation model of the natural history of injection opioid use. We defined injection behavior profiles by both injection frequency and injection techniques. We accounted for competing risks of death and populated the model with primary and published data. We modeled cohorts of 1 million individuals with different injection behavior profiles until age 60 years. We combined model-generated estimates with published data to project the total expected number of IE deaths in the United States by 2030. Results The probabilities of death from IE by age 60 years for 20-, 30-, and 40-year-old men with high-frequency use with higher infection risk techniques compared to lower risk techniques for IE were 53.8% versus 3.7%, 51.4% versus 3.1%, and 44.5% versus 2.2%, respectively. The predicted population-level attributable fraction of 10-year mortality from IE among all risk groups was 20%. We estimated that approximately 257 800 people are expected to die from IE by 2030. Conclusions The expected burden of IE among people who inject opioids in the United States is large. Adopting a harm reduction approach, including through expansion of syringe service programs, to address injection behaviors could have a major impact on decreasing the mortality rate associated with the opioid epidemic.

Background Inpatient treatment for substance use disorders is a collection of strategies ranging from short term detoxification to longer term residential treatment. How those with opioid use disorder (OUD) navigate this inpatient treatment system after an encounter for detoxification and subsequent risk of opioid-related overdose is not well understood. Methods We used a comprehensive Massachusetts database to characterize the movement of people with OUD through inpatient care from 2013 to 2015, identifying admissions to inpatient detoxification, subsequent inpatient care, and opioid overdose while navigating treatment. We measured the person-years accumulated during each transition period to calculate rates of opioid-related overdose, and investigated how overdose differed in select populations. Results Sixty-one percent of inpatient detoxification admissions resulted in a subsequent inpatient detoxification admission without progressing to further inpatient care. Overall, there were 287 fatal and 7337 non-fatal overdoses. Persons exiting treatment after detoxification had the greatest risk of overdose (17.3 per 100 person-years) compared to those who exited after subsequent inpatient care (ranging from 5.9 to 6.6 overdoses per 100 person-years). Non-Hispanic whites were most at risk for opioid related overdose with 16 overdoses per 100 person-years and non-Hispanic blacks had the lowest risk with 5 overdoses per 100 person-years. Conclusions The majority of inpatient detoxification admissions do not progress to further inpatient care. Recurrent inpatient detoxification admission is common, likely signifying relapse. Rather than functioning as the first step to inpatient care, inpatient detoxification might be more effective as a venue for implementing strategies to expand addiction services or treatment such as medications for opioid use disorder.

Background Endocarditis, once predominately found in older adults, is increasingly common among younger persons who inject drugs. Untreated opioid use disorder (OUD) complicates endocarditis management. We aimed to determine if rates of overdose and rehospitalization differ between persons with OUD with endocarditis who are initiated on medications for OUD (MOUDs) within 30 days of hospital discharge and those who are not. Methods We performed a retrospective cohort study using a large commercial health insurance claims database of persons ≥18 years between July 1, 2010, and June 30, 2016. Primary outcomes included opioid-related overdoses and 1-year all-cause rehospitalization. We calculated incidence rates for the primary outcomes and developed Cox hazards models to predict time from discharge to each primary outcome as a function of receipt of MOUDs. Results The cohort included 768 individuals (mean age 39 years, 51% male). Only 5.7% of people received MOUDs in the 30 days following hospitalization. The opioid-related overdose rate among those who did receive MOUDs in the 30 days following hospitalization was lower than among those who did not (5.8 per 100 person-years [95% confidence interval [CI], 5.1–6.4] vs 7.3 per 100-person years [95% CI, 7.1–7.5], respectively). The rate of 1-year rehospitalization among those who received MOUDs was also lower than those who did not (162.0 per 100 person-years [95% CI, 157.4–166.6] vs 255.4 per 100 person-years [95% CI, 254.0–256.8], respectively). In the Cox hazards models, the receipt of MOUDs was not associated with either of the outcomes. Conclusions MOUD receipt following endocarditis may improve important health-related outcomes in commercially insured persons with OUD.

OBJECTIVES: The global pandemic of coronavirus disease 2019 (Covid-19) may disproportionately affect persons in congregate settings, including those in residential substance use treatment facilities. To limit the spread of SARS-CoV-2 through congregate settings, universal testing may be necessary. We aimed to determine the point prevalence of SARS-CoV-2 in a residential treatment program setting and to understand the unique challenges of Covid-19 transmission in this setting. METHODS: We performed a case series of SARS-CoV-2 rT-PCR testing via nasopharyngeal in a residential substance use treatment program for women in Boston. Staff and residents of the treatment program were tested for SARS-CoV-2. The primary outcome was SARS-CoV-2 test result. RESULTS: A total of 31 residents and staff were tested. Twenty-seven percent (6/22) of the residents and 44% (4/9) of staff tested positive for SARS-CoV-2. All of the SARS-CoV-2 positive residents resided in the same residential unit. Two positive cases resided together with two negative cases in a 4-person room. Two other positive cases resided together in a 2-person room. One positive case resided with two negative cases in a 3-person room. One positive case resided with a negative case in a 2-person room. Based on test results, residents were cohorted by infection status and continued to participate in addiction treatment on-site. CONCLUSIONS: SARS-CoV-2 infection was common among staff and residents within a residential substance use treatment program for women in Boston. Universal SARS-CoV-2 testing in residential substance use programs can be instituted to reduce the risk of further transmission and continue addiction treatment programming when accompanied by adequate space, supplies, and staffing.

Objectives. To estimate the annual prevalence of opioid use disorder (OUD) in Massachusetts from 2011 to 2015. Methods. We performed a multisample stratified capture–recapture analysis to estimate OUD prevalence in Massachusetts. Individuals identified from 6 administrative databases for 2011 to 2012 and 7 databases for 2013 to 2015 were linked at the individual level and included in the analysis. Individuals were stratified by age group, sex, and county of residence. Results. The OUD prevalence in Massachusetts among people aged 11 years or older was 2.72% in 2011 and 2.87% in 2012. Between 2013 and 2015, the prevalence increased from 3.87% to 4.60%. The greatest increase in prevalence was observed among those in the youngest age group (11–25 years), a 76% increase from 2011 to 2012 and a 42% increase from 2013 to 2015. Conclusions. In Massachusetts, the OUD prevalence was 4.6% among people 11 years or older in 2015. The number of individuals with OUD is likely increasing, particularly among young people.

Infectious diseases (ID) physicians are increasingly responsible for the management of infectious consequences of substance use disorders (SUD). While we are often consulted for diagnosis and treatment of the infectious disease, it is clear that successful management of these infections requires a holistic approach, including acknowledgement and treatment of the underlying SUD. As we have learned through years of treating human immunodeficiency virus and hepatitis C virus infections, ID physicians have unique expertise in addressing both the infection and the complex biopsychosocial factors that underpin the infection. Many ID physicians have incorporated the management of addiction as part of their scope of practice, and here we seek to give a name and define the role of these ID/addiction dual specialists. We define the potential role of ID/addiction physicians in clinical care, health administration, and research, as well as provide recommendations to bolster the supply and reach of this burgeoning subspecialty.

Background and aims Liver disease in people living with HIV co-infected with hepatitis C virus is a source of morbidity and mortality in Russia. HIV accelerates liver fibrosis in the setting of HCV co-infection and alcohol use. Zinc deficiency is common among people living with HIV and may be a factor that facilitates the underlying mechanisms of liver fibrosis. We investigated the association between zinc deficiency and advanced liver fibrosis in a cohort of HIV/HCV co-infected persons reporting heavy drinking in Russia. Methods This is a secondary data analysis of baseline data from 204 anti-retroviral treatment naive HIV/HCV co-infected Russians with heavy drinking that were recruited into a clinical trial of zinc supplementation. The primary outcome of interest in this cross-sectional study was advanced liver fibrosis. Zinc deficiency, the main independent variable, was defined as plasma zinc

Background Skin and soft tissue infections (SSTI) are common complications of injection drug use. We aimed to determine if rehospitalization and recurrent SSTI differ among persons with opioid use disorder (OUD) hospitalized for SSTI who are initiated on MOUD within 30 days of discharge and those who are not. Methods We performed a retrospective analysis of commercially insured adults aged 18 years and older in the U.S. with OUD and hospitalization for injection-related SSTI from 2010–2017. The primary exposure was initiation of MOUD in the 30 days following hospitalization for SSTI. The primary outcomes included 30-day and 1-year 1) all-cause rehospitalization and 2) recurrent SSTI. We calculated the incidence rates for the two groups: MOUD group and no MOUD group for the primary outcomes. We developed Cox models to determine if rehospitalization and recurrent SSTI differ between the two groups. Results Only 5.5 % (357/6538) of people received MOUD in the month following their index SSTI hospitalization. 30-day rehospitalization incidence was higher in the MOUD group compared to no MOUD (35.9 vs 27.5 per 100 person-30 days) and one-year SSTI recurrence was lower (10.3 vs 18.7 per 100 person-years). In multivariable modeling, the MOUD group remained at significantly higher risk of 30-day rehospitalization compared to the no MOUD group and at lower risk for one-year SSTI recurrence. Conclusions MOUD receipt following SSTI hospitalization decreases risk of recurrent SSTI among persons with OUD. Further expansion of these in-hospital services could provide an effective tool in the U.S. response to the opioid epidemic.

BACKGROUND: Not enough evidence exists to compare buprenorphine–naloxone with extended-release naltrexone for treating opioid use disorder. OBJECTIVE: To evaluate the relative cost-effectiveness of buprenorphine–naloxone versus extended-release naltrexone. DESIGN: Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs. DATA SOURCES: Study instruments. TARGET POPULATION: Adults with opioid use disorder. TIME HORIZON: 24-week intervention with an additional 12 weeks of observation. PERSPECTIVE: Health care sector and societal. INTERVENTIONS: Buprenorphine–naloxone and extended-release naltrexone. OUTCOME MEASURES: Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids. RESULTS OF BASE-CASE ANALYSIS: Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine–naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective. RESULTS OF SENSITIVITY ANALYSIS: The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation. LIMITATION: Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs. CONCLUSION: Buprenorphine–naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone.