Search

Importance: Many US states are substantially increasing community-based naloxone distribution, supported in part through settlements from opioid manufacturers and distributors., Objectives: To evaluate the potential impact of increased naloxone availability on opioid overdose deaths (OODs) and explore strategies to enhance this impact by integrating interventions to address solitary drug use., Design, Setting, and Participants: This decision analytical modeling study used PROFOUND (Prevention and Rescue of Fentanyl and Other Opioid Overdoses Using Optimized Naloxone Distribution Strategies), a previously published simulation model, to forecast annual OODs between January 2023 and December 2025. The simulated study population included individuals from Rhode Island who misused opioids and stimulants and were at risk for opioid overdose., Exposures: The study modeled expanded naloxone distribution supported by the state's opioid settlement (50 000 naloxone nasal spray kits each year). Two approaches to expanding naloxone distribution were evaluated: one based on historical spatial patterns of naloxone distribution (supply-based approach) and one based on the spatial distribution of individuals at risk (demand-based approach). In addition, hypothetical interventions to enhance the likelihood of witnessed overdoses in private or semiprivate settings were considered., Main Outcomes and Measures: Annual number of OODs and ratio of fatal to nonfatal opioid overdoses., Results: Modeling results indicated that distributing more naloxone supported by the state's opioid settlement could reduce OODs by 6.3% (95% simulation interval [SI], 0.3%-13.7%) and 8.8% (95% SI, 1.8%-17.5%) in 2025 with the supply-based and demand-based approaches, respectively. However, increasing witnessed overdoses by 20% to 60% demonstrated greater potential for reducing OODs, ranging from 8.5% (95% SI, 0.0%-20.3%) to 24.1% (95% SI, 8.6%-39.3%). Notably, synergistic associations were observed when combining both interventions: increased naloxone distribution with the 2 approaches and a 60% increase in witnessed overdoses could reduce OODs in 2025 by 33.5% (95% SI, 17.1%-50.4%) and 37.4% (95% SI, 19.6%-56.3%), respectively., Conclusions and Relevance: These findings suggest that interventions to address solitary drug use are needed to maximize the impact of continued efforts to increase community-based naloxone distribution, which may be particularly important for jurisdictions that have strong community-based naloxone distribution programs.

Importance: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown., Objective: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments., Design, Setting, and Participants: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024., Exposure: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg)., Main Outcomes and Measures: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity., Results: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P < .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P < .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P < .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure., Conclusions and Relevance: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients., Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Importance: In 2017, the US Food and Drug Administration (FDA) approved a monthly injectable form of buprenorphine, extended-release buprenorphine; published data show that extended-release buprenorphine is effective compared with no treatment, but its current cost is higher and current retention is lower than that of transmucosal buprenorphine. Preliminary research suggests that extended-release buprenorphine may be an important addition to treatment options, but the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine remains unclear., Objective: To evaluate the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine., Design, Setting, and Participants: This economic evaluation used a state transition model starting in 2019 to simulate the lifetime of a closed cohort of individuals with OUD presenting for evaluation for opioid agonist treatment with buprenorphine. The data sources used to estimate model parameters included cohort studies, clinical trials, and administrative data. The model relied on pharmaceutical costs from the Federal Supply Schedule and health care utilization costs from published studies. Data were analyzed from September 2021 to January 2023., Interventions: No treatment, treatment with transmucosal buprenorphine, or treatment with extended-release buprenorphine., Main Outcomes and Measures: Mean lifetime costs per person, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs)., Results: The simulated cohort included 100 000 patients with OUD receiving (61% male; mean [SD] age, 38 [11] years) or not receiving medication treatment (58% male, mean [SD] age, 48 [18] years). Compared with no medication treatment, treatment with transmucosal buprenorphine yielded an ICER of $19 740 per QALY. Compared with treatment with transmucosal buprenorphine, treatment with extended-release buprenorphine yielded lower effectiveness by 0.03 QALYs per person at higher cost, suggesting that treatment with extended-release buprenorphine was dominated and not preferred. In probabilistic sensitivity analyses, treatment with transmucosal buprenorphine was the preferred strategy 60% of the time. Treatment with extended-release buprenorphine was cost-effective compared with treatment with transmucosal buprenorphine at a $100 000 per QALY willingness-to-pay threshold only after substantial changes in key parameters., Conclusions and Relevance: In this economic evaluation of extended-release buprenorphine compared with transmucosal buprenorphine for the treatment of OUD, extended-release buprenorphine was not associated with efficient allocation of limited resources when transmucosal buprenorphine was available. Future initiatives should aim to improve retention rates or decrease costs associated with extended-release buprenorphine.

Importance: Most prisons and jails in the US discontinue medications for opioid use disorder (MOUD) upon incarceration and do not initiate MOUD prior to release., Objective: To model the association of MOUD access during incarceration and at release with population-level overdose mortality and OUD-related treatment costs in Massachusetts., Design, Setting, and Participants: This economic evaluation used simulation modeling and cost-effectiveness with costs and quality-adjusted life-years (QALYs) discounted at 3% to compare MOUD treatment strategies in a corrections cohort and an open cohort representing individuals with OUD in Massachusetts. Data were analyzed between July 1, 2021, and September 30, 2022., Exposures: Three strategies were compared: (1) no MOUD provided during incarceration or at release, (2) extended-release (XR) naltrexone offered only at release from incarceration, and (3) all 3 MOUDs (naltrexone, buprenorphine, and methadone) offered at intake., Main Outcomes and Measures: Treatment starts and retention, fatal overdoses, life-years and QALYs, costs, and incremental cost-effectiveness ratios (ICERs)., Results: Among 30 000 simulated incarcerated individuals with OUD, offering no MOUD was associated with 40 927 (95% uncertainty interval [UI], 39 001-42 082) MOUD treatment starts over a 5-year period and 1259 (95% UI, 1130-1323) overdose deaths after 5 years. Over 5 years, offering XR-naltrexone at release led to 10 466 (95% UI, 8515-12 201) additional treatment starts, 40 (95% UI, 16-50) fewer overdose deaths, and 0.08 (95% UI, 0.05-0.11) QALYs gained per person, at an incremental cost of $2723 (95% UI, $141-$5244) per person. In comparison, offering all 3 MOUDs at intake led to 11 923 (95% UI, 10 861-12 911) additional treatment starts, compared with offering no MOUD, 83 (95% UI, 72-91) fewer overdose deaths, and 0.12 (95% UI, 0.10-0.17) QALYs per person gained, at an incremental cost of $852 (95% UI, $14-$1703) per person. Thus, XR-naltrexone only was a dominated strategy (both less effective and more costly) and the ICER of all 3 MOUDs compared with no MOUD was $7252 (95% UI, $140-$10 018) per QALY. Among everyone with OUD in Massachusetts, XR-naltrexone only averted 95 overdose deaths over 5 years (95% UI, 85-169)-a 0.9% decrease in state-level overdose mortality-while the all-MOUD strategy averted 192 overdose deaths (95% UI, 156-200)-a 1.8% decrease., Conclusions and Relevance: The findings of this simulation-modeling economic study suggest that offering any MOUD to incarcerated individuals with OUD would prevent overdose deaths and that offering all 3 MOUDs would prevent more deaths and save money compared with an XR-naltrexone-only strategy.

Importance: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown., Objective: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids., Design, Setting, and Participants: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine the following treatment strategies: (1) PCP services with external referral to addiction care (status quo), (2) PCP services plus onsite buprenorphine prescribing with referral to offsite harm reduction kits (BUP), and (3) PCP services plus onsite buprenorphine prescribing and harm reduction kits (BUP plus HR). Model inputs were derived from clinical trials and observational cohorts, and costs were discounted annually at 3%. The cost-effectiveness was evaluated over a lifetime from the modified health care sector perspective, and sensitivity analyses were performed to address uncertainty. Model simulation began January 1, 2021, and ran for the entire lifetime of the cohort., Main Outcomes and Measures: Life-years (LYs), hospitalizations, mortality from sequelae (overdose, severe skin and soft tissue infections, and endocarditis), costs, and incremental cost-effectiveness ratios (ICERs)., Results: The simulated cohort included 2.25 million people and reflected the age and gender of US persons who inject opioids. Status quo resulted in 6.56 discounted LYs at a discounted cost of $203 500 per person (95% credible interval, $203 000-$222 000). Each strategy extended discounted life expectancy: BUP by 0.16 years and BUP plus HR by 0.17 years. Compared with status quo, BUP plus HR reduced sequelae-related mortality by 33%. The mean discounted lifetime cost per person of BUP and BUP plus HR were more than that of the status quo strategy. The dominating strategy was BUP plus HR. Compared with status quo, BUP plus HR was cost-effective (ICER, $34 400 per LY). During a 5-year time horizon, BUP plus HR cost an individual PCP practice approximately $13 000., Conclusions and Relevance: This modeling study of integrated addiction service in primary care found improved clinical outcomes and modestly increased costs. The integration of addiction service into primary care practices should be a health care system priority.

Importance: In 2021, the state of Rhode Island distributed 10 000 additional naloxone kits compared with the prior year through partnerships with community-based organizations., Objective: To compare various strategies to increase naloxone distribution through community-based programs in Rhode Island to identify one most effective and efficient strategy in preventing opioid overdose deaths (OODs)., Design, Setting, and Participants: In this decision analytical model study conducted from January 2016 to December 2022, a spatial microsimulation model with an integrated decision tree was developed and calibrated to compare the outcomes of alternative strategies for distributing 10 000 additional naloxone kits annually among all individuals at risk for opioid overdose in Rhode Island., Interventions: Distribution of 10 000 additional naloxone kits annually, focusing on people who inject drugs, people who use illicit opioids and stimulants, individuals at various levels of risk for opioid overdose, or people who misuse prescription opioids vs no additional kits (status quo). Two expanded distribution implementation approaches were considered: one consistent with the current spatial distribution patterns for each distribution program type (supply-based approach) and one consistent with the current spatial distribution of individuals in each of the risk groups, assuming that programs could direct the additional kits to new geographic areas if required (demand-based approach)., Main Outcomes and Measures: Witnessed OODs, cost per OOD averted (efficiency), geospatial health inequality measured by the Theil index, and between-group variance for OOD rates., Results: A total of 63 131 simulated individuals were estimated to be at risk for opioid overdose in Rhode Island based on current population data. With the supply-based approach, prioritizing additional naloxone kits to people who use illicit drugs averted more witnessed OODs by an estimated mean of 18.9% (95% simulation interval [SI], 13.1%-30.7%) annually. Expanded naloxone distribution using the demand-based approach and focusing on people who inject drugs had the best outcomes across all scenarios, averting an estimated mean of 25.3% (95% SI, 13.1%-37.6%) of witnessed OODs annually, at the lowest mean incremental cost of $27 312 per OOD averted. Other strategies were associated with fewer OODs averted at higher costs but showed similar patterns of improved outcomes and lower unit costs if kits could be reallocated to areas with greater need. The demand-based approach reduced geospatial inequality in OOD rates in all scenarios compared with the supply-based approach and status quo., Conclusions and Relevance: In this decision analytical model study, variations in the effectiveness, efficiency, and health inequality of the different naloxone distribution expansion strategies and approaches were identified. Future efforts should be prioritized for people at highest risk for overdose (those who inject drugs or use illicit drugs) and redirected toward areas with the greatest need. These findings may inform future naloxone distribution priority settings.

Importance: Emerging evidence supports the use of outpatient parenteral antimicrobial therapy (OPAT) and, in many cases, partial oral antibiotic therapy for the treatment of injection drug use-associated infective endocarditis (IDU-IE); however, long-term outcomes and cost-effectiveness remain unknown., Objective: To compare the added value of inpatient addiction care services and the cost-effectiveness and clinical outcomes of alternative antibiotic treatment strategies for patients with IDU-IE., Design, Setting, and Participants: This decision analytical modeling study used a validated microsimulation model to compare antibiotic treatment strategies for patients with IDU-IE. Model inputs were derived from clinical trials and observational cohort studies. The model included all patients with injection opioid drug use (N = 5 million) in the US who were eligible to receive OPAT either in the home or at a postacute care facility. Costs were annually discounted at 3%. Cost-effectiveness was evaluated from a health care sector perspective over a lifetime starting in 2020. Probabilistic sensitivity, scenario, and threshold analyses were performed to address uncertainty., Interventions: The model simulated 4 treatment strategies: (1) 4 to 6 weeks of inpatient intravenous (IV) antibiotic therapy along with opioid detoxification (usual care strategy), (2) 4 to 6 weeks of inpatient IV antibiotic therapy along with inpatient addiction care services that offered medication for opioid use disorder (usual care/addiction care strategy), (3) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by OPAT (OPAT strategy), and (4) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by partial oral antibiotic therapy (partial oral antibiotic strategy)., Main Outcomes and Measures: Mean percentage of patients completing treatment for IDU-IE, deaths associated with IDU-IE, life expectancy (measured in life-years [LYs]), mean cost per person, and incremental cost-effectiveness ratios (ICERs)., Results: All modeled scenarios were initialized with 5 million individuals (mean age, 42 years; range, 18-64 years; 70% male) who had a history of injection opioid drug use. The usual care strategy resulted in 18.63 LYs at a cost of $416 570 per person, with 77.6% of hospitalized patients completing treatment. Life expectancy was extended by each alternative strategy. The partial oral antibiotic strategy yielded the highest treatment completion rate (80.3%) compared with the OPAT strategy (78.8%) and the usual care/addiction care strategy (77.6%). The OPAT strategy was the least expensive at $412 150 per person. Compared with the OPAT strategy, the partial oral antibiotic strategy had an ICER of $163 370 per LY. Increasing IDU-IE treatment uptake and decreasing treatment discontinuation made the partial oral antibiotic strategy more cost-effective compared with the OPAT strategy. When assuming that all patients with IDU-IE were eligible to receive partial oral antibiotic therapy, the strategy was cost-saving and resulted in 0.0247 additional discounted LYs. When treatment discontinuation was decreased from 3.30% to 2.65% per week, the partial oral antibiotic strategy was cost-effective compared with OPAT at the $100 000 per LY threshold., Conclusions and Relevance: In this decision analytical modeling study, incorporation of OPAT or partial oral antibiotic approaches along with addiction care services for the treatment of patients with IDU-IE was associated with increases in the number of people completing treatment, decreases in mortality, and savings in cost compared with the usual care strategy of providing inpatient IV antibiotic therapy alone.

Importance: With recent surges in COVID-19 incidence and vaccine authorization for children aged 5 to 11 years, elementary schools face decisions about requirements for masking and other mitigation measures. These decisions require explicit determination of community objectives (eg, acceptable risk level for in-school SARS-CoV-2 transmission) and quantitative estimates of the consequences of changing mitigation measures., Objective: To estimate the association between adding or removing in-school mitigation measures (eg, masks) and COVID-19 outcomes within an elementary school community at varying student vaccination and local incidence rates., Design, Setting, and Participants: This decision analytic model used an agent-based model to simulate SARS-CoV-2 transmission within a school community, with a simulated population of students, teachers and staff, and their household members (ie, immediate school community). Transmission was evaluated for a range of observed local COVID-19 incidence (0-50 cases per 100 000 residents per day, assuming 33% of all infections detected). The population used in the model reflected the mean size of a US elementary school, including 638 students and 60 educators and staff members in 6 grades with 5 classes per grade., Exposures: Variant infectiousness (representing wild-type virus, Alpha variant, and Delta variant), mitigation effectiveness (0%-100% reduction in the in-school secondary attack rate, representing increasingly intensive combinations of mitigations including masking and ventilation), and student vaccination levels were varied., Main Outcomes and Measures: The main outcomes were (1) probability of at least 1 in-school transmission per month and (2) mean increase in total infections per month among the immediate school community associated with a reduction in mitigation; multiple decision thresholds were estimated for objectives associated with each outcome. Sensitivity analyses on adult vaccination uptake, vaccination effectiveness, and testing approaches (for selected scenarios) were conducted., Results: With student vaccination coverage of 70% or less and moderate assumptions about mitigation effectiveness (eg, masking), mitigation could only be reduced when local case incidence was 14 or fewer cases per 100 000 residents per day to keep the mean additional cases associated with reducing mitigation to 5 or fewer cases per month. To keep the probability of any in-school transmission to less than 50% per month, the local case incidence would have to be 4 or fewer cases per 100 000 residents per day., Conclusions and Relevance: In this study, in-school mitigation measures (eg, masks) and student vaccinations were associated with substantial reductions in transmissions and infections, but the level of reduction varied across local incidence. These findings underscore the potential role for responsive plans that deploy mitigation strategies based on local COVID-19 incidence, vaccine uptake, and explicit consideration of community objectives.

Importance: In 2020 and early 2021, the National Football League (NFL) and National Collegiate Athletic Association (NCAA) opted to host football games in stadiums across the country. The in-person attendance of games varied with time and from county to county. There is currently no evidence on whether limited in-person attendance of games is associated with COVID-19 case numbers on a county-level., Objective: To assess whether NFL and NCAA football games with limited in-person attendance were associated with increased COVID-19 cases in the counties they were held compared with a matched set of counties., Design, Setting, and Participants: In this time-series cross-sectional study, every county hosting NFL or NCAA games with in-person attendance (treated group) in 2020 and 2021 was matched with a county that that did not host a game on the corresponding day but had an identical game history for up to 14 days prior (control group). A standard matching method was used to further refine this matched set so that the treated and matched control counties had similar population size, nonpharmaceutical interventions in place, and COVID-19 trends. The association of hosting games with in-person attendance with COVID-19 cases was assessed using a difference-in-difference estimator. Data were analyzed from August 29 to December 28, 2020., Exposures: Hosting NFL or NCAA games., Main Outcomes and Measures: The main outcome was estimation of new COVID-19 cases per 100 000 residents at the county level reported up to 14 days after a game among counties with NFL and NCAA games with in-person attendance., Results: A total of 528 games with in-person attendance (101 NFL games [19.1%]; 427 NCAA games [80.9%]) were included. The matching algorithm returned 361 matching sets of counties. The median (interquartile range [IQR]) number of attendance for NFL games was 9949 (6000 to 13 797) people. The median number of attendance for NCAA games was not available, and attendance was recorded as a binary variable. The median (IQR) daily new COVID-19 cases in treatment group counties hosting games was 26.14 (10.77-50.25) cases per 100 000 residents on game day. The median (IQR) daily new COVID-19 cases in control group counties where no games were played was 24.11 (9.64-48.55) cases per 100 000 residents on game day. The treatment effect size ranged from -5.17 to 4.72, with a mean (SD) of 1.21 (2.67) cases per 100 000 residents, within the 14-day period in all counties hosting the games, and the daily treatment effect trend remained relatively steady during this period., Conclusions and Relevance: This cross-sectional study did not find a consistent increase in the daily COVID-19 cases per 100 000 residents in counties where NFL and NCAA games were held with limited in-person attendance. These findings suggest that NFL and NCAA football games hosted with limited in-person attendance were not associated with substantial risk for increased local COVID-19 cases.

Importance: The United States is experiencing a crisis of opioid overdose. In response, the US Department of Health and Human Services has defined a goal to reduce overdose mortality by 40% by 2022., Objective: To identify specific combinations of 3 interventions (initiating more people to medications for opioid use disorder [MOUD], increasing 6-month retention with MOUD, and increasing naloxone distribution) associated with at least a 40% reduction in opioid overdose in simulated populations., Design, Setting, and Participants: This decision analytical model used a dynamic population-level state-transition model to project outcomes over a 2-year horizon. Each intervention scenario was compared with the counterfactual of no intervention in simulated urban and rural communities in Massachusetts. Simulation modeling was used to determine the associations of community-level interventions with opioid overdose rates. The 3 examined interventions were initiation of more people to MOUD, increasing individuals' retention with MOUD, and increasing distribution of naloxone. Data were analyzed from July to November 2020., Main Outcomes and Measures: Reduction in overdose mortality, medication treatment capacity needs, and naloxone needs., Results: No single intervention was associated with a 40% reduction in overdose mortality in the simulated communities. Reaching this goal required use of MOUD and naloxone. Achieving a 40% reduction required that 10% to 15% of the estimated OUD population not already receiving MOUD initiate MOUD every month, with 45% to 60%% retention for at least 6 months, and increased naloxone distribution. In all feasible settings and scenarios, attaining a 40% reduction in overdose mortality required that in every month, at least 10% of the population with OUD who were not currently receiving treatment initiate an MOUD., Conclusions and Relevance: In this modeling study, only communities with increased capacity for treating with MOUD and increased MOUD retention experienced a 40% decrease in overdose mortality. These findings could provide a framework for developing community-level interventions to reduce opioid overdose death.

Importance: Whereas outpatient treatment with medication for opioid use disorder (MOUD) is evidence based, there is a large network of inpatient facilities in the US that are reimbursed by commercial insurers and do not typically offer MOUD., Objective: To compare the rates of opioid-related overdose and all-cause hospitalization after outpatient MOUD treatment vs inpatient care., Design, Setting, and Participants: This comparative effectiveness research study used deidentified claims of commercially insured individuals in the US from the MarketScan Commercial Claims and Encounters Database from January 1, 2010, to December 31, 2017, to obtain a sample of 37 090 individuals with opioid use disorder who initiated treatment with inpatient care and/or MOUD. Data were analyzed from October 1, 2019, to May 1, 2020. To address nonrandom treatment assignment, individuals with opioid use disorder who initiated MOUD or who entered inpatient care were matched 1:1 based on propensity scores., Exposures: The independent variable of interest was the type of treatment initiated. Individuals could initiate 1 of 5 potential treatments: (1) outpatient MOUD, (2) short-term inpatient care, (3) short-term inpatient care followed by outpatient MOUD within 30 days, (4) long-term inpatient care, or (5) long-term inpatient care followed by outpatient MOUD within 30 days., Main Outcomes and Measures: Opioid-related overdose and all-cause hospitalization at any point within the 12 months after treatment of opioid use disorder. The hazard for each outcome was estimated using a time-to-event Cox proportional hazards regression model., Results: The cohort included 37 090 individuals matched 1:1 between inpatient and outpatient treatment (20 723 [56%] were younger than 30 years; 23 250 [63%] were male). After propensity score matching, compared with the inpatient treatments, initiation of outpatient MOUD alone was followed by the lowest 1-year overdose rate (2.2 [95% CI, 2.0-2.5] per 100 person-years vs 3.5 [95% CI, 2.7-4.4] to 7.0 [95% CI, 4.6-10.7] per 100 person-years) and hospitalization rate (39 [95% CI, 38-40] per 100 person-years vs 57 [95% CI, 54-61] to 74 [95% CI, 73-76] per 100 person-years). Outpatient MOUD was also associated with the lowest hazard of these events compared with inpatient care, which had hazard ratios ranging from 1.71 (95% CI, 1.35-2.17) to 2.67 (95% CI, 1.68-4.23) for overdose and 1.33 (95% CI, 1.23-1.44) to 1.90 (95% CI, 1.83-1.97) for hospitalizations., Conclusions and Relevance: The results of this comparative effectiveness research study suggest that lower rates of subsequent overdose and hospitalization are associated with outpatient MOUD compared with short- or long-term inpatient care. When patients and clinicians have a choice of treatment, outpatient MOUD treatment may be associated with lower overdose and hospitalization on balance. Future research should assess which patients benefit most from inpatient care and how best to leverage existing inpatient treatment infrastructure.

Importance: Although hospitalizations for injection drug use-associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown., Objective: To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality., Design, Setting, and Participants: This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use treatment data from Massachusetts between January 1, 2011, and December 31, 2015; IDU-IE-related discharges between July 1, 2011, and June, 30, 2015, were analyzed. All Massachusetts residents aged 18 to 64 years with a first hospitalization for IDU-IE were included; IDU-IE was defined as any hospitalization with a diagnosis of endocarditis and at least 1 claim in the prior 6 months for OUD, drug use, or hepatitis C and with 2-month survival after hospital discharge. Data were analyzed from November 11, 2018, to June 23, 2020., Exposure: Receipt of MOUD, defined as any treatment with methadone, buprenorphine, or naltrexone, within 3 months after hospital discharge excluding discharge month for IDU-IE., Main Outcomes and Measures: The main outcome was all-cause mortality. The proportion of patients who received MOUD in the 3 months after hospital discharge was calculated. Multivariable Cox proportional hazard regression models were used to examine the association of MOUD receipt with mortality, adjusting for sex, age, medical and psychiatric comorbidities, and homelessness. In the secondary analysis, receipt of MOUD was considered as a monthly time-varying exposure., Results: Of 679 individuals with IDU-IE, 413 (60.8%) were male, the mean (SD) age was 39.2 (12.1) years, 298 (43.9%) were aged 18 to 34 years, 419 (72.3) had mental illness, and 209 (30.8) experienced homelessness. A total of 134 individuals (19.7%) received MOUD in the 3 months before hospitalization and 165 (24.3%) in the 3 months after hospital discharge. Of those who received MOUD after discharge, 112 (67.9%) received buprenorphine. The crude mortality rate was 9.2 deaths per 100 person-years. MOUD receipt within 3 months after discharge was not associated with reduced mortality (adjusted hazard ratio, 1.29; 95% CI, 0.61-2.72); however, MOUD receipt was associated with reduced mortality in the month that MOUD was received (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.89)., Conclusions and Relevance: In this cohort study, receipt of MOUD was associated with reduced mortality after hospitalization for injection drug use-associated endocarditis only in the month it was received. Efforts to improve MOUD initiation and retention after IDU-IE hospitalization may be beneficial.