Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.

BACKGROUND: Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS: In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS: During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS: In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Syringe reuse among people who inject drugs in rural Appalachian Kentucky.

BACKGROUND: Personal syringe reuse (i.e., reuse of one's own syringes) can place people who inject drugs at increased risk for infectious disease but has received relatively little attention in published literature. The purpose of this study is to identify factors associated with syringe reuse among people who inject drugs in rural Kentucky. METHODS: Participants (n = 238) completed interviewer-administered questionnaires on syringe reuse and demographic, behavioral, and service access characteristics. Unadjusted negative binomial regression with cluster-robust standard errors was used to model the associations with a logged offset for number of injections in the past 30 days. RESULTS: The average age of the sample was 35 and 59.7 % were male. Most participants (77.7 %) reused syringes at least once in the past 30 days, using each syringe a median of three times. Reuse was higher among those who were older and reported a higher street price for syringes. Syringe reuse was lower among people who were within walking distance to a syringe service program (SSP) and who obtained most of their syringes from SSPs or pharmacies. CONCLUSION: Syringe reuse among people who inject drugs in rural Kentucky is common. However, these data suggest that increased access to syringes from SSPs and pharmacies, as well as policy-level interventions that reduce street syringe price, might reduce syringe reuse and related harms.

Utilization of long-acting injectable monthly depot buprenorphine for opioid use disorder (OUD) in Kentucky, before and after COVID-19 related buprenorphine access policy changes.

INTRODUCTION: Long-acting injectable buprenorphine (LAI-bup) formulations have advantages over transmucosal buprenorphine (TM-bup), but barriers may limit their utilization. Several policies shifted during the COVID-19 pandemic to promote buprenorphine access. The federal government expanded telemedicine treatment for opioid use disorder and Kentucky (KY) Medicaid lifted prior authorization requirements (PAs) for LAI-bup (i.e., Sublocade®). This retrospective cohort study evaluated changes in LAI-bup access, utilization, and retention before and after these policy changes in KY. METHODS: Individual-level TM-bup and LAI-bup dispensing record data from KY's prescription drug monitoring program examined LAI-bup utilization and retention, without a >30-day gap in coverage, for patients starting a new episode of LAI-bup treatment. Two key time periods were examined: pre-policy changes (Apr 1, 2019 - Dec 31, 2019) and post-policy changes (Apr 1, 2020 - Dec 31, 2020). Data on PA requests among Medicaid managed care organizations and availability of LAI-bup Risk Evaluation and Mitigation Strategy (REMS)-certified pharmacies were also obtained. A multivariable Cox proportional hazard regression model analysis compared pre- versus post-policy period treatment discontinuation. RESULTS: The number of patients initiating LAI-bup increased from 211 to 481 over the two periods. By the end of the post-policy period, 24.3 % of eligible patients were retained on LAI-bup, versus 12.5 % in the pre-policy change period. The adjusted hazard ratio, comparing discontinuation during the post- versus pre-policy change periods, was 0.70 (95 % confidence interval: 0.55-0.89). There were also more REMS-certified pharmacies and providers in the post-policy change period. CONCLUSIONS: LAI-bup access, utilization, and retention increased after several policy changes.

Effects of the Communities that Heal (CTH) intervention on perceived opioid-related community stigma in the HEALing Communities Study: results of a multi-site, community-level, cluster-randomized trial.

Background: Community stigma against people with opioid use disorder (OUD) and intervention stigma (e.g., toward naloxone) exacerbate the opioid overdose crisis. We examined the effects of the Communities that HEAL (CTH) intervention on perceived opioid-related community stigma by stakeholders in the HEALing Communities Study (HCS). Methods: We collected three surveys from community coalition members in 66 communities across four states participating in HCS. Communities were randomized into Intervention (Wave 1) or Wait-list Control (Wave 2) arms. We conducted multilevel linear mixed models to compare changes in primary outcomes of community stigma toward people treated for OUD, naloxone, and medication for opioid use disorder (MOUD) by arm from time 1 (before the start of the intervention) to time 3 (end of the intervention period in the Intervention arm). Findings: Intervention stakeholders reported a larger decrease in perceived community stigma toward people treated for OUD (adjusted mean change (AMC) -3.20 [95% C.I. -4.43, -1.98]) and toward MOUD (AMC -0.33 [95% C.I. -0.56, -0.09]) than stakeholders in Wait-list Control communities (AMC -0.18 [95% C.I. -1.38, 1.02], p = 0.0007 and AMC 0.11 [95% C.I. -0.09, 0.31], p = 0.0066). The relationship between intervention status and change in stigma toward MOUD was moderated by rural-urban status (urban AMC -0.59 [95% CI, -0.87, -0.32], rural AMC not sig.) and state. The difference in stigma toward naloxone between Intervention and Wait-list Control stakeholders was not statistically significant (p = 0.18). Interpretation: The CTH intervention decreased stakeholder perceptions of community stigma toward people treated for OUD and stigma toward MOUD. Implementing the CTH intervention in other communities could decrease OUD stigma across diverse settings nationally. Funding: US National Institute on Drug Abuse.

Impact of the Communities That HEAL Intervention on Buprenorphine-Waivered Practitioners and Buprenorphine Prescribing: A Prespecified Secondary Analysis of the HCS Randomized Clinical Trial.

Importance: Buprenorphine significantly reduces opioid-related overdose mortality. From 2002 to 2022, the Drug Addiction Treatment Act of 2000 (DATA 2000) required qualified practitioners to receive a waiver from the Drug Enforcement Agency to prescribe buprenorphine for treatment of opioid use disorder. During this period, waiver uptake among practitioners was modest; subsequent changes need to be examined. Objective: To determine whether the Communities That HEAL (CTH) intervention increased the rate of practitioners with DATA 2000 waivers and buprenorphine prescribing. Design, Setting, and Participants: This prespecified secondary analysis of the HEALing Communities Study, a multisite, 2-arm, parallel, community-level, cluster randomized, open, wait-list-controlled comparison clinical trial was designed to assess the effectiveness of the CTH intervention and was conducted between January 1, 2020, to December 31, 2023, in 67 communities in Kentucky, Massachusetts, New York, and Ohio, accounting for approximately 8.2 million adults. The participants in this trial were communities consisting of counties (n = 48) and municipalities (n = 19). Trial arm randomization was conducted using a covariate constrained randomization procedure stratified by state. Each state was balanced by community characteristics including urban/rural classification, fatal opioid overdose rate, and community population. Thirty-four communities were randomized to the intervention and 33 to wait-list control arms. Data analysis was conducted between March 20 and September 29, 2023, with a focus on the comparison period from July 1, 2021, to June 30, 2022. Intervention: Waiver trainings and other educational trainings were offered or supported by the HEALing Communities Study research sites in each state to help build practitioner capacity. Main Outcomes and Measures: The rate of practitioners with a DATA 2000 waiver (overall, and stratified by 30-, 100-, and 275-patient limits) per 100 000 adult residents aged 18 years or older during July 1, 2021, to June 30, 2022, were compared between the intervention and wait-list control communities. The rate of buprenorphine prescribing among those waivered practitioners was also compared between the intervention and wait-list control communities. Intention-to-treat and per-protocol analyses were performed. Results: A total of 8 166 963 individuals aged 18 years or older were residents of the 67 communities studied. There was no evidence of an effect of the CTH intervention on the adjusted rate of practitioners with a DATA 2000 waiver (adjusted relative rate [ARR], 1.04; 95% CI, 0.94-1.14) or the adjusted rate of practitioners with a DATA 2000 waiver who actively prescribed buprenorphine (ARR, 0.97; 95% CI, 0.86-1.10). Conclusions and Relevance: In this randomized clinical trial, the CTH intervention was not associated with increases in the rate of practitioners with a DATA 2000 waiver or buprenorphine prescribing among those waivered practitioners. Supporting practitioners to prescribe buprenorphine remains a critical yet challenging step in the continuum of care to treat opioid use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT04111939.

Medications for opioid use disorder associated with reduced readmissions for patients with severe injection-related infections: A matched cohort study.

INTRODUCTION: Hospitalizations due to severe injection-related infections (SIRIs) and patient-directed discharge (PDD) in people who inject drugs (PWID) are increasing, but research on readmission outcomes at PDD is limited. In this retrospective, matched cohort study we evaluated predictors of 30-day readmission by discharge status among PWID. METHODS: Among patients diagnosed with SIRIs at a tertiary hospital, Fisher's exact tests assessed differences in readmission rates by discharge status. Medications for opioid use disorder (MOUD) at discharge was defined as either having a buprenorphine dose dispensed within 24 h of discharge and buprenorphine being included in the discharge summary as a prescription, or a methadone dose dispensed inpatient within 24 h of discharge. Logistic regression analyses evaluated predictors of readmission outcomes. RESULTS: Among 148 PWID with SIRI diagnosis, 30-day readmission rate following PDD was higher than standard discharge (25.7 % vs. 9.5 %, p = 0.016) and MOUD decreased odds of 30-day readmission (OR = 0.32, 95 % CI: 0.12,0.83, p = 0.012). >7 missed days of antibiotic treatment increased odds of 30-day readmission (OR 4.65, 95 % CI: 1.14, 31.72, p = 0.030) within PDD patients. CONCLUSIONS: PDD carries higher 30-day readmission rate compared to standard discharge. Strategies to reduce PDD rates and increase MOUD initiation may improve readmission outcomes.

Extended-release Buprenorphine Administered at Discharge in Hospitalized Persons With Opioid Use Disorder: A Case Series.

INTRODUCTION: Monthly subcutaneous injectable buprenorphine (XR-Bup) is an option for treatment of opioid use disorder (OUD) that addresses some sublingual buprenorphine adherence barriers and is infrequently offered to hospitalized patients with OUD. METHODS: A retrospective case series was performed for patients receiving XR-Bup upon discharge from 1 academic medical center. Demographic information, diagnoses, follow-up, and documented factors informing the selection of XR-Bup were extracted from the electronic health record. RESULTS: In 1 year, 37 hospitalized patients with OUD received XR-Bup at discharge. The average age was 37.6 years, and patients were primarily Medicaid insured with an injection-related infection. The most common documented factors informing the selection of XR-Bup were as follows: previous sublingual buprenorphine adherence barriers, concurrent stimulant use disorder, and patient preference. Sixty-four percent of patients scheduled for follow-up attended appointments, and 55% received a second dose of XR-Bup. CONCLUSIONS: Subcutaneous injectable buprenorphine is an option for OUD treatment among hospitalized patients providing 30 or more days of buprenorphine coverage in the postdischarge period.

Pain Management in Patients With Opioid Use Disorder on Extended-release Buprenorphine: A Case Report.

ABSTRACT: Persons with opioid use disorder (OUD) are receiving extended-release buprenorphine (ER-buprenorphine) for treatment of OUD. There are no clinical guidelines for management of patients with OUD on ER-buprenorphine experiencing acute or chronic pain. This case report describes 3 patient-involved, multidisciplinary approaches for pain management in various clinical scenarios, including a scheduled knee replacement, emergent surgery for an ischemic limb, and management of chronic pain from metastatic malignancy. These cases illustrate that adequate analgesia for patients who have received ER-buprenorphine is possible, and approaches can be individualized, with shared decision making between providers and patients addressing all barriers to optimize treatment outcomes. Options for acute pain management that can be considered include supplemental sublingual buprenorphine, nonopioid adjuncts, and short courses of full opioid agonists. Potential barriers that impact OUD and acute/chronic pain are provider bias, limited access to palliative care clinicians with addiction medicine training, and payor restrictions to adding sublingual buprenorphine for patients that are on ER-buprenorphine. Additional training for clinicians and other members of the health care team is recommended to improve patient-involved care of persons with OUD experiencing pain.

Get It in Writing: How to Make Medications for Opioid Use Disorder Available During Incarceration.

In a case example from the Kentucky HEALing Communities Study, extensive resources were deployed to address structural barriers and facilitate the provision of medication for opioid use disorder (OUD) in an urban county jail. However, implementation was unsuccessful, and this case example emphasizes the importance of including evidence-based medication for OUD (MOUD) treatment in the scope of work of jails' contracted medical providers. The privatization of correctional health care services allows local governments with opioid abatement funds to incorporate requirements into medical provider contracts to screen all people entering jails for OUD and to offer MOUD at intake, throughout incarceration, and upon release to everyone for whom it is clinically indicated. We provide sample contractual language that can be added to requests for medical provider proposals to help drive the private correctional health care market toward integrating MOUD treatment into their standard of care. This approach also could expedite efforts to scale up broad MOUD access across U.S. jails through sharing of workflows and best practices among the small group of national correctional health care companies contracted with jails in states with broad mandates, such as Massachusetts. Clinical Trial Registration: NCT04111939.

Contributions of a central registry to monitor methadone -treatment through the HEALing Communities Study.

OBJECTIVE: To describe the process of establishing a Methadone Central Registry (MCR) as part of the HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) and to support recommendations with evidence of its functionality relative to Medicaid claims data for monitoring utilization of methadone, an evidence-based treatment for opioid use disorder. DESIGN AND PARTICIPANTS: The manuscript authors were active participants in establishing the MCR and include representation from state government, Opioid Treatment Programs (OTPs), and HCS university partners. Secondary data were obtained from Kentucky's (KY's) MCR and Medicaid claims from July 2020 through June 2021. The functionality of data obtained from the MCR, as measured by data completeness and timeliness, is compared with Medicaid claims, the current standard. MAIN OUTCOMES: Central registry and Medicaid data were each aggregated statewide and at the HCS-KY county level. Dual levels of analysis were selected to inform stakeholders at the study and state levels. Descriptive statistics were calculated for the number of patients in methadone treatment. RESULTS: Statewide, the MCR provided a daily record of all individuals receiving methadone through an OTP within 72 hours. In contrast, Medicaid claims processing lagged 9 months and captured 57-62 percent of patients in the MCR. CONCLUSIONS: Replacing a fax-based system, an MCR meets the converging need of providers, regulatory authorities, and researchers to monitor utilization, patient dual enrollment, and treatment outcomes. Implementation strategies included key stakeholder engagement, state partner leadership, training, and federal funding. Adoption of an MCR is recommended.

Telemedicine Buprenorphine Initiation and Retention in Opioid Use Disorder Treatment for Medicaid Enrollees.

Importance: Early COVID-19 mitigation strategies placed an additional burden on individuals seeking care for opioid use disorder (OUD). Telemedicine provided a way to initiate and maintain transmucosal buprenorphine treatment of OUD. Objective: To examine associations between transmucosal buprenorphine OUD treatment modality (telemedicine vs traditional) during the COVID-19 public health emergency and the health outcomes of treatment retention and opioid-related nonfatal overdose. Design, Setting, and Participants: This retrospective cohort study was conducted using Medicaid claims and enrollment data from November 1, 2019, to December 31, 2020, for individuals aged 18 to 64 years from Kentucky and Ohio. Data were collected and analyzed in June 2022, with data updated during revision in August 2023. Exposures: The primary exposure of interest was the modality of the transmucosal buprenorphine OUD treatment initiation. Relevant patient demographic and comorbidity characteristics were included in regression models. Main Outcomes and Measures: There were 2 main outcomes of interest: retention in treatment after initiation and opioid-related nonfatal overdose after initiation. For outcomes measured after initiation, a 90-day follow-up period was used. The main analysis used a new-user study design; transmucosal buprenorphine OUD treatment initiation was defined as initiation after more than a 60-day gap in buprenorphine treatment. In addition, uptake of telemedicine for buprenorphine was examined, overall and within patients initiating treatment, across quarters in 2020. Results: This study included 41 266 individuals in Kentucky (21 269 women [51.5%]; mean [SD] age, 37.9 [9.0] years) and 50 648 individuals in Ohio (26 425 women [52.2%]; mean [SD] age, 37.1 [9.3] years) who received buprenorphine in 2020, with 18 250 and 24 741 people initiating buprenorphine in Kentucky and Ohio, respectively. Telemedicine buprenorphine initiations increased sharply at the beginning of 2020. Compared with nontelemedicine initiation, telemedicine initiation was associated with better odds of 90-day retention with buprenorphine in both states (Kentucky: adjusted odds ratio, 1.13 [95% CI, 1.01-1.27]; Ohio: adjusted odds ratio, 1.19 [95% CI, 1.06-1.32]) in a regression analysis adjusting for patient demographic and comorbidity characteristics. Telemedicine initiation was not associated with opioid-related nonfatal overdose (Kentucky: adjusted odds ratio, 0.89 [95% CI, 0.56-1.40]; Ohio: adjusted odds ratio, 1.08 [95% CI, 0.83-1.41]). Conclusions and Relevance: In this cohort study of Medicaid enrollees receiving buprenorphine for OUD, telemedicine buprenorphine initiation was associated with retention in treatment early during the COVID-19 pandemic. These findings add to the literature demonstrating positive outcomes associated with the use of telemedicine for treatment of OUD.

The policy landscape for naloxone distribution in four states highly impacted by fatal opioid overdoses.

Background: Expanding access to naloxone is one of the most impactful interventions in decreasing opioid-related mortality. However, state distribution rates of naloxone are insufficient to meet community need. The current study sought to better understand this gap by focusing on state policies that may facilitate or impede naloxone distribution in four states highly impacted by fatal opioid overdoses - Kentucky, Massachusetts, New York, and Ohio. Methods: We provide a descriptive analysis of the policy landscape impacting naloxone distribution through pharmacy and community channels in the four states participating in the HEALing Communities Study (HCS). Publicly available data and the expertise of the research team were used to describe each state's naloxone access laws (NALs), Medicaid coverage of naloxone, and community overdose education and naloxone distribution infrastructure. Data presented in this study represent the most current policy landscape through September 2022. Results: Variation exists between specific components of the NALs of each state, the structure of Medicaid coverage of naloxone, and the community distribution infrastructure networks. Massachusetts and New York have a statewide standing order, but other states use different strategies short of a statewide standing order to expand access to naloxone. Quantity limits specific to naloxone may limit access to Medicaid beneficiaries in some states. Conclusion: States participating in the HCS have developed innovative but different mechanisms to ensure naloxone access. Policies were dynamic and moved towards greater access. Research should consider the policy landscape in the implementation and sustainability of interventions as well as the analysis of outcomes.

Management of Infective Endocarditis in People Who Inject Drugs: A Scientific Statement From the American Heart Association.

BACKGROUND: The American Heart Association has sponsored both guidelines and scientific statements that address the diagnosis, management, and prevention of infective endocarditis. As a result of the unprecedented and increasing incidence of infective endocarditis cases among people who inject drugs, the American Heart Association sponsored this original scientific statement. It provides a more in-depth focus on the management of infective endocarditis among this unique population than what has been provided in prior American Heart Association infective endocarditis-related documents. METHODS: A writing group was named and consisted of recognized experts in the fields of infectious diseases, cardiology, addiction medicine, and cardiovascular surgery in October 2021. A literature search was conducted in Embase on November 19, 2021, and multiple terms were used, with 1345 English-language articles identified after removal of duplicates. CONCLUSIONS: Management of infective endocarditis in people who inject drugs is complex and requires a unique approach in all aspects of care. Clinicians must appreciate that it requires involvement of a variety of specialists and that consultation by addiction-trained clinicians is as important as that of more traditional members of the endocarditis team to improve infective endocarditis outcomes. Preventive measures are critical in people who inject drugs and are cured of an initial bout of infective endocarditis because they remain at extremely high risk for subsequent bouts of infective endocarditis, regardless of whether injection drug use is continued.

Design and protocol of the Buprenorphine plus Outpatient Parenteral Antimicrobial Therapy (B-OPAT) study: a randomized clinical trial of integrated outpatient treatment of opioid use disorder and severe, injection-related infections.

Introduction: A marked increase in hospitalizations for severe, injection-related infections (SIRI) has been associated with the opioid epidemic. Outpatient parenteral antibiotic therapy (OPAT) is typically not offered to persons with opioid use disorder (OUD) and SIRI, though increasing evidence suggests it may be feasible and safe. This study evaluates the efficacy and cost-effectiveness of an integrated care model combining Buprenorphine treatment of OUD with OPAT for SIRI (B-OPAT) compared with treatment as usual on key OUD, infectious disease, and health economic outcomes. B-OPAT expands and incorporates key elements of established clinical models, including inpatient initiation of buprenorphine for OUD, inpatient infectious disease consultation for SIRI, office-based treatment of OUD, and OPAT, and includes more frequent clinical outpatient visits than standard OPAT. A qualitative evaluation is included to contextualize effectiveness outcomes and identify barriers and facilitators to intervention adoption and implementation. Methods: B-OPAT is a single-site, randomized, parallel-group, superiority trial recruiting 90 adult inpatients hospitalized with OUD and SIRI who require at least 2 weeks of intravenous (IV) antibiotic therapy. After screening, eligible participants are randomized 1:1 to either discharge once medically stable to an integrated outpatient treatment care model combining Buprenorphine and OPAT (B-OPAT) or to Treatment As Usual (TAU). The primary outcome measure is the proportion of urine samples negative for illicit opioids in the 12 weeks after discharge from the hospital. Key secondary OUD outcomes include self-reported number of days of illicit opioid abstinence and 12-week retention in buprenorphine treatment. The infection outcomes are completion of recommended IV antibiotic therapy, peripherally inserted central catheter (PICC) complications, and readmission related to primary SIRI. Conclusions: The B-OPAT study will help address the important question of whether it is clinically effective and cost-effective to discharge persons with OUD and SIRI to an integrated outpatient care model combining OUD treatment with OPAT relative to TAU (Clinicaltrials.gov Identifier: NCT04677114).

HIV clinic-based extended-release naltrexone versus treatment as usual for people with HIV and opioid use disorder: a non-blinded, randomized non-inferiority trial.

BACKGROUND AND AIM: Opioid agonist medications for treatment of opioid use disorder (OUD) can improve human immunodeficiency virus (HIV) outcomes and reduce opioid use. We tested whether outpatient antagonist treatment with naltrexone could achieve similar results. DESIGN: Open-label, non-inferiority randomized trial. SETTING: Six US HIV primary care clinics. PARTICIPANTS: A total of 114 participants with untreated HIV and OUD (62% male; 56% black, 12% Hispanic; positive for fentanyl (62%), other opioids (47%) and cocaine (60%) at baseline). Enrollment halted early due to slow recruitment. INTERVENTION: HIV clinic-based extended-release naltrexone (XR-NTX; n = 55) versus treatment as usual (TAU) with buprenorphine or methadone (TAU; n = 59). MEASUREMENTS: Treatment group differences were compared for the primary outcome of viral suppression (HIV RNA ≤ 200 copies/ml) at 24 weeks and secondary outcomes included past 30-day use of opioids at 24 weeks. FINDINGS: Fewer XR-NTX participants initiated medication compared with TAU participants (47 versus 73%). The primary outcome of viral suppression was comparable for XR-NTX (52.7%) and TAU (49.2%) [risk ratio (RR) = 1.064; 95% confidence interval (CI) = 0.748, 1.514] at 24 weeks. Non-inferiority could not be demonstrated, as the lower confidence limit of the RR did not exceed the pre-specified margin of 0.75 in intention-to-treat (ITT) analysis. The main secondary outcome of past 30-day opioid use was comparable for XR-NTX versus TAU (11.7 versus 14.8 days; mean difference = -3.1; 95% CI = -8.7, 1.1) in ITT analysis. Among those initiating medication, XR-NTX resulted in fewer days of opioid use compared with TAU in the past 30 days (6.0 versus 13.6, mean difference = -7.6; 95% CI = -13.8, -0.2). CONCLUSIONS: A randomized controlled trial found supportive, but not conclusive, evidence that human immunodeficiency virus clinic-based extended-release naltrexone is not inferior to treatment as usual for facilitating human immunodeficiency virus viral suppression. Participants who initiated extended-release naltrexone used fewer opioids than those who received treatment as usual.

Rural-urban differences in hospitalizations for opioid use-associated infective endocarditis in Kentucky, 2016-2019.

PURPOSE: In 2016, the US rate of opioid use-associated infective endocarditis (OUA IE) hospitalizations was 3.86/100,000 for rural and 3.49/100,000 for urban residents. This study estimates the Kentucky OUA IE hospitalization rates, 2016-2019, describing differences in rural-urban residency trends, demographics, relevant comorbidities, and discharge disposition. OUA IE hospitalization rates between counties with and without syringe services programs (SSPs) are also compared. METHODS: We used Kentucky statewide inpatient discharge records from 2016 to 2019. An OUA IE hospitalization was identified by an infective endocarditis discharge diagnosis in any diagnosis field and a concurrent diagnosis indicating opioid use. Rurality was determined based on the 2013 Rural-Urban Continuum Codes (RUCC). FINDINGS: Kentucky's rate of OUA IE hospitalizations in 2016 was 8.9/100,000, with no significant variation between rural and urban residents. By 2019, the average rate for urban residents doubled to 17.9/100,000, significantly higher than the rural resident rate, 13.2/100,000. There were no significant rural-urban differences in percentages of those with concurrent diagnoses of HIV (<1%) or HCV (>60%). Counties that established SSPs in 2017-2018 had a 39.4% increase in OUA IE rates from 2016 to 2019, while counties without SSPs had a 79.5% increase. CONCLUSION: The estimated 2016 Kentucky rates of OUA IE hospitalizations are 2 times higher than reported national rates, highlighting Kentucky as one of the areas most affected by this particular opioid use disorder complication. Despite challenges and barriers to the effectiveness of SSPs as a harm reduction measure, our study suggests a positive effect that should be further investigated.

Perspectives on extended-release naltrexone induction among patients living with HIV and opioid use disorder: a qualitative analysis.

BACKGROUND: The CHOICES study randomized participants with HIV and opioid use disorder (OUD) to HIV clinic-based extended-release naltrexone (XR-NTX), which requires complete cessation of opioid use, versus treatment-as-usual (i.e., buprenorphine, methadone). Study participants randomized to XR-NTX were interviewed to assess their experiences with successful and unsuccessful XR-NTX induction. METHODS: Semi-structured qualitative interviews were completed with a convenience sample of study participants with HIV and OUD (n = 37) randomized to XR-NTX in five HIV clinics between 2018 and 2019. All participants approached agreed to be interviewed. Interviews were digitally recorded, professionally transcribed, and analyzed using thematic analysis. RESULTS: Participants included women (43%), African Americans (62%) and Hispanics (16%), between 27 to 69 years of age. Individuals who completed XR-NTX induction (n = 20) reported experiencing (1) readiness for change, (2) a supportive environment during withdrawal including comfort medications, and (3) caring interactions with staff. Four contrasting themes emerged among participants (n = 17) who did not complete induction: (1) concern and anxiety about withdrawal including past negative experiences, (2) ambivalence about or reluctance to stop opioids, (3) concerns about XR-NTX effects, and (4) preferences for other medications. CONCLUSIONS: The results highlight opportunities to improve initiation of XR-NTX in high-need groups. Addressing expectations regarding induction may enhance XR-NTX initiation rates. Trial Registration ClinicalTrials.gov: NCT03275350. Registered September 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03275350?term=extended+release+naltrexone&cond=Opioid+Use .

Long-acting buprenorphine injectables: Opportunity to improve opioid use disorder treatment among rural populations.

The opioid epidemic continues with escalating overdose deaths further exacerbated by the coronavirus pandemic, despite having efficacious medication treatments for opioid use disorder (MOUD). Most persons with OUD remain undiagnosed, without ever receiving MOUD, and even among those who initiate MOUD, retention is infrequently longer than 6 months (Williams et al., 2019). Treatment access remains particularly problematic in rural areas that often have few providers and limited resources (Ghertner, 2019). There are two new injectable long-acting buprenorphine (LAB) formulations recently approved in the United States and abroad (Lofwall et al., 2018; Walsh et al., 2017; Haight et al., 2019). They hold promise to improve treatment access and retention by decreasing risks of nonadherence, diversion and misuse and may be particularly attractive during a pandemic in order to minimize provider and pharmacy contacts (Roberts et al., 2020) and help improve access to care in rural areas. There are several ongoing evaluations of LAB injectables in large multi-site randomized clinical trials sponsored by the National Institute on Drug Abuse and Veterans Administration Office of Research and Development in settings with special populations that exist in both urban and rural settings. Understanding the potential clinical benefits of LAB injectables along the care continuum, particularly for rural areas is essential to successful implementation in the complex healthcare system.

Buprenorphine Induction in Persons With Opioid Use Disorder Hospitalized with Acute Hepatitis A.

BACKGROUND: It is not known whether buprenorphine/naloxone (bup/nx) can be safely initiated in hospitalized patients with acute hepatitis A infection. We assessed liver function and tolerability of bup/nx induction in patients with acute Hepatitis A Virus (HAV). METHODS: Retrospective review of patients (N = 31) admitted to a tertiary care facility for acute HAV who were evaluated by an addiction medicine consultant. RESULTS: No significant difference was seen in aspartate aminotransferase, alanine aminotransferase, total bilirubin, or INR trends in patients receiving bup/nx during hospitalization versus those not receiving bup/nx. Nausea was the most common reported symptom in patients receiving bup/nx. DISCUSSION AND CONCLUSIONS: With careful monitoring and induction dose adjustment, bup/nx can be administered to patients with acute HAV without hepatic encephalopathy. Similarly, patients on bup/nx before hospitalization should not have this medication held in the setting of acute HAV. SCIENTIFIC SIGNIFICANCE: This strategy may engage patients with acute HAV in treatment of OUD earlier and minimize disruptions in treatment.