Pharmacokinetics, Tolerability, and Safety of Esmethadone in Subjects with Chronic Kidney Disease or Hepatic Impairment.

BACKGROUND AND OBJECTIVES: Esmethadone (dextromethadone; d-methadone; S-methadone (+)-methadone; REL-1017) is a low potency N-methyl-D-aspartate (NMDA) receptor channel blocker that showed a rapid and sustained adjunctive antidepressant effects in patients with major depressive disorder with inadequate response to ongoing serotonergic antidepressant treatment. Previous studies indicated that esmethadone is partially excreted by the kidney (53.9% of the dose) and by the liver (39.1% of the dose). METHODS: Here we studied the pharmacokinetics and safety of esmethadone after a single oral dose of 25 mg in subjects with different stages of kidney and liver impairment. RESULTS: In subjects with a mild and moderate decrease in glomerular fraction rate (GFR), esmethadone Cmax and AUC0-inf values did not differ compared with healthy subjects. In patients with severe renal impairment, the ratios of Cmax and AUC0-inf values compared with healthy subjects were above 100% (138.22-176.85%) and, while modest, these increases reached statistical significance. In subjects with end stage renal disease (ESRD) undergoing intermittent hemodialysis (IHD), Cmax and AUC0-inf values were not statistically different compared with healthy subjects. IHD did not modified plasma total esmethadone concentrations in blood exiting versus entering the dialyzer. Dose adjustment is not warranted in subjects with mild-to-moderate impaired renal function. Dose reduction may be considered for select patients with severe renal disfunction. In subjects with mild-or-moderate hepatic impairment, Cmax and AUC0-inf were approximately 20-30% lower compared with healthy controls. The drug free fraction increased with the severity of hepatic impairment, from 5.4% in healthy controls to 8.3% in subjects with moderate hepatic impairment. CONCLUSION: Mild and moderate hepatic impairment has a minimal to modest impact on exposure to total or unbound esmethadone and dose adjustments are not warranted in subjects with mild and moderate hepatic impairment. Administration of esmethadone was well tolerated in healthy adult subjects, in subjects with mild or moderate hepatic impairment, and in subjects with mild moderate or severe renal impairment, including patients with ESRF undergoing dialysis.

Federal opioid agonist therapy policy: interrupted time series analysis of the impact of the methadone exemption removal across eight provinces in Canada.

BACKGROUND: Federal deregulation of opioid agonist therapies are an attractive policy option to improve access to opioid use disorder care and achieve widespread beneficial impacts on growing opioid-related harms. There have been few evaluations of such policy interventions and understanding effects can help policy planning across jurisdictions. METHODS: Using health administrative data from eight of ten Canadian provinces, this study evaluated the impacts of Health Canada's decision in May 2018 to rescind the requirement for Canadian health professionals to obtain an exemption from the Canadian Drugs and Substance Act to prescribe methadone for opioid use disorder. Over the study period of June 2017 to May 2019, we used descriptive statistics to capture overall trends in the number of agonist therapy prescribers across provinces and we used interrupted time series analysis to determine the effect of this decision on the trajectories of the agonist therapy prescribing workforces. RESULTS: There were important baseline differences in the numbers of agonist therapy prescribers. The province with the highest concentration of prescribers had 7.5 more prescribers per 100,000 residents compared to the province with the lowest. All provinces showed encouraging growth in the number of prescribers through the study period, though the fastest growing province grew 4.5 times more than the slowest. Interrupted time series analyses demonstrated a range of effects of the federal policy intervention on the provinces, from clearly positive changes to possibly negative effects. CONCLUSIONS: Federal drug regulation policy change interacted in complex ways with provincial health professional regulation and healthcare delivery, kaleidoscoping the effects of federal policy intervention. For Canada and other health systems such as the US, federal policy must account for significant subnational variation in OUD epidemiology and drug regulation to maximize intended beneficial effects and mitigate the risks of negative effects.

Opioid Use and the Risk of Ventricular Arrhythmias: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between opioid use and the risk of ventricular arrhythmias (VA) is poorly understood. AIMS: The objective of this study was to synthesize the evidence on the risk of VA associated with opioid use. MATERIALS & METHODS: We systematically searched the Cochrane Library, Embase, MEDLINE, and CINAHL databases in July 2022. Risk of bias was assessed using the Cochrane risk for bias tool for randomized controlled trials (RCTs) and ROBINS-I for observational studies. Certainty of evidence was assessed using GRADE. RESULTS: We included 15 studies (12 observational, 2 post hoc analyses of RCTs, 1 RCT). Most studies focused on opioid use for maintenance therapy (n = 9), comparing methadone to buprenorphine (n = 13), and reported QTc prolongation (n = 13). Six observational studies had a critical risk of bias, and one RCT was at high risk of bias. Two studies could not be included in the meta-analysis as they reported a different outcome and studied an opioid antagonist. Meta-analysis of 13 studies indicated that the use of methadone was associated with an increased risk of VA compared to the use of buprenorphine, morphine, placebo, or levacetylmethadol (risk ratio [RR], 2.39; 95% CI, 1.31-4.35; I2 = 60%). The pooled estimate varied greatly between observational studies (RR, 2.12; 95% CI, 1.15-3.91; I2 = 62%) and RCTs (RR, 14.09; 95% CI, 1.52-130.61; I2 = 0%), but both indicated an increased risk. CONCLUSION: In this systematic review and meta-analysis, we found that methadone use is associated with more than twice the risk of VA compared to comparators. However, our findings should be interpreted cautiously given the limited quality of the available evidence.

'I'm on the coast and I'm on methadone': A qualitative study examining access to opioid agonist treatment in rural and coastal British Columbia.

INTRODUCTION: Despite rural regions being disproportionately impacted by the toxic drug supply, little is known about the contextual factors influencing access to opioid agonist treatment (OAT) specific to rural residents. The present study examines these factors in a rural and coastal setting in British Columbia, Canada. METHODS: The qualitative methods were used to examine the barriers and facilitators to OAT access. Between July and October 2021, semi-structured interviews were conducted with people who use drugs who reside in a rural and coastal community. Thematic analysis was used to identify emergent themes and subthemes. Results were corroborated by the research team and a local community advisory board. RESULTS: Twenty-seven (n = 27) participants described both limiting and facilitating factors that influenced OAT accessibility. Access was less challenging when participants' OAT dispensing pharmacy was in close proximity, had extended hours of operation, or when pharmacies provided delivery services. Barriers to OAT access identified by participants included the high cost of transportation, residing or working in remote communities and few local OAT prescribers. A variety of treatment motivations and goals that impacted OAT satisfaction are also highlighted. CONCLUSION: This study demonstrates that patient satisfaction with OAT service access in a rural and coastal setting is multi-factorial and geographic proximity alone does not fully explain OAT accessibility issues in these settings. Accessibility to OAT may be improved through delivery services, expanded OAT prescribing authorisation beyond physician-only regulations, health authorities covering transportation costs and continual assurance that prescribing practices meet individuals' goals. INTRODUCTION: Bien que les régions rurales soient touchées de manière disproportionnée par l'approvisionnement en drogues toxiques, on sait peu de choses sur les facteurs contextuels qui influencent l'accès au traitement par agoniste opioïde (TAO) spécifique aux résidents ruraux. La présente étude examine ces facteurs dans un contexte rural et côtier en Colombie-Britannique, au Canada. MTHODES: Des méthodes qualitatives ont été utilisées pour examiner les obstacles et les facilitateurs de l'accès aux TAO. Entre juillet et octobre 2021, des entretiens semi-structurés ont été menés avec des personnes qui consomment des drogues résidant dans une communauté rurale et côtière. L'analyse thématique a été utilisée pour identifier les thèmes et sous-thèmes émergents. Les résultats ont été corroborés par l'équipe de recherche et un comité consultatif communautaire local. RSULTATS: Vingt-sept (n = 27) participants ont décrit les facteurs limitants et facilitants qui ont influé sur l'accessibilité au TAO. L'accès était moins difficile lorsque la pharmacie du TAO des participants était proche, avait des heures d'ouverture prolongées ou lorsque les pharmacies offraient des services de livraison. Parmi les obstacles à l'accès au TAO mentionnés par les participants, il y avait le coût élevé du transport, le fait de résider ou de travailler dans des collectivités éloignées et la rareté des prescripteurs locaux du TAO. Les participants ont également fait état de divers objectifs et motivations liés au traitement qui ont eu une incidence sur la satisfaction à l'égard du TAO. CONCLUSION: Cette étude démontre que la satisfaction des patients à l'égard de l'accès aux services du TAO en milieu rural et côtier est multifactorielle et que la proximité géographique n'explique pas à elle seule les problèmes d'accessibilité au TAO dans ces milieux. Cette accessibilité peut être améliorée par des services de livraison, l'élargissement de l'autorisation de prescrire un TAO au-delà des règlements réservés aux médecins, la prise en charge des coûts de transport par les autorités sanitaires et l'assurance continue que les pratiques de prescription répondent aux objectifs des individus.

Lost in transition: A protocol for a retrospective, longitudinal cohort study for addressing challenges in opioid treatment for transition-age adults.

BACKGROUND: In the United States, there has been a concerning rise in the prevalence of opioid use disorders (OUD) among transition-age (TA) adults, 18 to 25-years old, with a disproportionate impact on individuals and families covered by Medicaid. Of equal concern, the treatment system continues to underperform for many young people, emphasizing the need to address the treatment challenges faced by this vulnerable population at a pivotal juncture in their life course. Pharmacotherapy is the most effective treatment for OUD, yet notably, observational studies reveal gaps in the receipt of and retention in medications for opioid use disorder (MOUD), resulting in poor outcomes for many TA adults in treatment. Few current studies on OUD treatment quality explicitly consider the influence of individual, organizational, and contextual factors, especially for young people whose social roles and institutional ties remain in flux. METHODS: We introduce a retrospective, longitudinal cohort design to study treatment quality practices and outcomes among approximately 65,000 TA adults entering treatment for OUD between 2012 and 2025 in New York. We propose to combine data from multiple sources, including Medicaid claims and encounter data and a state registry of substance use disorder (SUD) treatment episodes, to examine three aspects of OUD treatment quality: 1) MOUD use, including MOUD option (e.g., buprenorphine, methadone, or extended-release [XR] naltrexone); 2) adherence to pharmacotherapy and retention in treatment; and 3) adverse events (e.g., overdoses). Using rigorous analytical methods, we will provide insights into how variation in treatment practices and outcomes are structured more broadly by multilevel processes related to communities, treatment programs, and characteristics of the patient, as well as their complex interplay. DISCUSSION: Our findings will inform clinical decision making by patients and providers as well as public health responses to the rising number of young adults seeking treatment for OUD amidst the opioid and polysubstance overdose crisis in the U.S.

DNA methylation patterns in umbilical cord blood from infants of methadone maintained opioid dependent mothers.

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference > + 2, < - 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention.

Spatial inequities in access to medications for treatment of opioid use disorder highlight scarcity of methadone providers under counterfactual scenarios.

Access to treatment and medication for opioid use disorder (MOUD) is essential in reducing opioid use and associated behavioral risks, such as syringe sharing among persons who inject drugs (PWID). Syringe sharing among PWID carries high risk of transmission of serious infections such as hepatitis C and HIV. MOUD resources, such as methadone provider clinics, however, are often unavailable to PWID due to barriers like long travel distance to the nearest methadone provider and the required frequency of clinic visits. The goal of this study is to examine the uncertainty in the effects of travel distance in initiating and continuing methadone treatment and how these interact with different spatial distributions of methadone providers to impact co-injection (syringe sharing) risks. A baseline scenario of spatial access was established using the existing locations of methadone providers in a geographical area of metropolitan Chicago, Illinois, USA. Next, different counterfactual scenarios redistributed the locations of methadone providers in this geographic area according to the densities of both the general adult population and according to the PWID population per zip code. We define different reasonable methadone access assumptions as the combinations of short, medium, and long travel distance preferences combined with three urban/suburban travel distance preference. Our modeling results show that when there is a low travel distance preference for accessing methadone providers, distributing providers near areas that have the greatest need (defined by density of PWID) is best at reducing syringe sharing behaviors. However, this strategy also decreases access across suburban locales, posing even greater difficulty in regions with fewer transit options and providers. As such, without an adequate number of providers to give equitable coverage across the region, spatial distribution cannot be optimized to provide equitable access to all PWID. Our study has important implications for increasing interest in methadone as a resurgent treatment for MOUD in the United States and for guiding policy toward improving access to MOUD among PWID.

Medicare Payment for Opioid Treatment Programs.

Importance: Medicare began paying for medications for opioid use disorder (MOUD) at opioid treatment programs (OTPs) that dispense methadone and other MOUD in January 2020. There has been little research describing the response to this payment change and whether it resulted in more patients receiving MOUD or just a shift in who pays for this care. Objective: To describe how many and which Medicare beneficiaries receive care from OTPs and how this compares to those receiving MOUD in other settings. Design, Setting, and Participants: This cross-sectional study included all patients receiving MOUD care identified in 2019-2022 100% US Medicare Parts B and D claims. Patients receiving care in an OTP who were dually insured with Medicare and Medicaid in the 2019-2020 Transformed Medicaid Statistical Information System were also included. Exposure: Receiving MOUD care in an OTP. Main Outcomes and Measures: Comparisons of 2022 beneficiaries treated in OTPs vs other non-OTP settings in 2022. Results: The share of Medicare beneficiaries treated by OTPs rose steadily from 4 per 10 000 (14 160 beneficiaries) in January 2020 to 7 per 10 000 (25 596 beneficiaries) in August 2020, then plateaued through December 2022; of 38 870 patients (23% ≥66 years; 35% female) treated at an OTP in 2022, 96% received methadone. Patients in OTPs, compared to those receiving MOUD in other settings, were more likely be 65 years and younger (65% vs 62%; P < .001), less likely to be White (72% vs 82%; P < .001), and more likely to be an urban resident (86% vs 74%; P < .001). When Medicare OTP coverage began, there was no associated drop in the number of dually insured patients with Medicaid with an OTP claim. Of the 1854 OTPs, 1115 (60%) billed Medicare in 2022, with the share billing Medicare ranging from 13% to 100% across states. Conclusions and Relevance: This study showed that since the initiation of Medicare OTP coverage in 2020, there has been a rapid increase in the number of Medicare beneficiaries with claims for OTP services for MOUD, and most OTPs have begun billing Medicare. Patients in OTPs were more likely to be urban residents and members of racial or ethnic minority groups than the patients receiving other forms of MOUD.

A Novel Use of the "3-Day Rule": Post-discharge Methadone Dosing in the Emergency Department.

Introduction: Methadone is a medically necessary and lifesaving medication for many patients with opioid use disorder. To adequately address these patients' needs, methadone should be offered in the hospital, but barriers exist that limit its continuation upon discharge. The code of federal regulations allows for methadone dosing as an inpatient as well as outpatient dispensing for up to three days to facilitate linkage to treatment. As a quality initiative, we created a new workflow for discharging patients on methadone to return to the emergency department (ED) for uninterrupted dosing. Methods: Our addiction medicine team changed hospital methadone policy to better allow hospitalization as a window of opportunity to start methadone. This necessitated the creation of a warm-handoff process to link patients to methadone clinics if that linkage could not happen immediately on discharge. Thus, our team created the "ED Bridge" process, which uses the "3-day rule" to dispense methadone from the ED post hospital discharge. We then followed every patient we directed through this workflow as an observational cohort for outcomes and trends. Results: Of the patients for whom ED bridge dosing was planned, 40.4% completed all bridge dosing and an additional 17.3% received at least one but not all bridge doses. Established methadone patients made up 38.1% of successful linkages, and 61.9% were patients who were newly started on methadone in the hospital. Conclusion: Improving methadone as a treatment option remains an ongoing issue for policymakers and advocates. Our ED bridge workflow allows us to expand access and continuation of methadone now using existing laws and regulations, and to better use hospitals as a point of entry into methadone treatment.

Opioid Overdose After Medication for Opioid Use Disorder Initiation Following Hospitalization or ED Visit.

Importance: Hospitalizations related to opioid use disorder (OUD) represent an opportunity to initiate medication for OUD (MOUD). Objective: To assess whether starting MOUD after a hospitalization or emergency department (ED) visit is associated with the odds of fatal and nonfatal opioid overdose at 6 and 12 months. Design, Setting, and Participants: This population-based cohort study used data from the Oregon Comprehensive Opioid Risk Registry, which links all payer claims data to other administrative health datasets, for individuals aged 18 years or older who had diagnosis codes related to OUD recorded at an index ED visit or hospitalization from January 2017 to December 2019. Data were analyzed between May 2023 and January 2024. Exposures: Receipt of MOUD within the 7 days after an OUD-related hospital visit. Main Outcomes and Measures: The primary outcome was fatal or nonfatal overdose at 6 and 12 months after discharge. Sample characteristics, including age, sex, insurance plan, number of comorbidities, and opioid-related overdose events, were stratified by receipt or nonreceipt of MOUD within 7 days after an OUD-related hospital visit. A logistic regression model was used to investigate the association between receipt of MOUD and having an opioid overdose event. Results: The study included 22 235 patients (53.1% female; 25.0% aged 25-39 years) who had an OUD-related hospital visit during the study period. Overall, 1184 patients (5.3%) received MOUD within 7 days of their ED visit or hospitalization. Of these patients, 683 (57.7%) received buprenorphine, 463 (39.1%) received methadone, and 46 (3.9%) received long-acting injectable naltrexone. Patients who received MOUD within 7 days after discharge had lower adjusted odds of fatal or nonfatal overdose at 6 months compared with those who did not (adjusted odds ratio [AOR], 0.63; 95% CI, 0.41-0.97). At 12 months, there was no difference in adjusted odds of fatal or nonfatal overdose between these groups (AOR, 0.79; 95% CI, 0.58-1.08). Patients had a lower risk of fatal or nonfatal overdose at 6 months associated with buprenorphine use (AOR, 0.50; 95% CI, 0.27-0.95) but not with methadone use (AOR, 0.57; 95% CI, 0.28-1.17). Conclusions and Relevance: In this cohort study of individuals with an OUD-related hospital visit, initiation of MOUD was associated with reduced odds of opioid-related overdose at 6 months. Hospitals should consider implementing programs and protocols to offer initiation of MOUD to patients with OUD who present for care.

Treatment non-adherence among methadone maintenance patients and associated factors: a multicenter, cross-sectional study in Vietnam.

OBJECTIVE: This multicenter, cross-sectional study was conducted to investigate the prevalence of treatment non-adherence and its associated factors among methadone maintenance patients in Vietnam. METHODS: This secondary data analysis was conducted using the data from a previous study. Six hundred patients were interviewed face-to-face to collect data on their demographic characteristics and social support. Information about the treatment characteristics and patients' non-adherence was gathered from medical records and books monitoring their treatment process. Treatment non-adherence was defined as missing at least one methadone dose in the last three months. RESULTS: The overall prevalence of non-adherence was 45.7%. The average social support score of patients who completely adhered to treatment was significantly higher than that of those who did not (p < 0.001). In the multivariate logistic regression model, for each one-unit increase in social support (one score), treatment time (a year), and patient's monthly income (one million Vietnam dongs), the odds of non-adherence decreased by 28% (aOR = 0.72, 95%CI 0.59-0.88, p = 0.002), 15% (aOR = 0.85, 95%CI 0.80-0.91, p < 0.001) and 9% (aOR = 0.91, 95%CI 0.85-0.97, p = 0.004), respectively. Patients living in Son La (a mountainous province) were 1.72 times (95%CI 1.09-2.71) more likely to be non-adherent as compared to those in other areas (p = 0.020). As per univariate analyses, other associated factors could be age, education level, family monthly income, occupation, and opioid relapse (p < 0.001). CONCLUSIONS: A high non-adherence rate was found among Vietnamese methadone maintenance patients. Interventions involving social support, occupation, income, and education are needed to improve their treatment adherence.

Medication for Opioid Use Disorder After Serious Injection-Related Infections in Massachusetts.

Importance: Serious injection-related infections (SIRIs) cause significant morbidity and mortality. Medication for opioid use disorder (MOUD) improves outcomes but is underused. Understanding MOUD treatment after SIRIs could inform interventions to close this gap. Objectives: To examine rehospitalization, death rates, and MOUD receipt for individuals with SIRIs and to assess characteristics associated with MOUD receipt. Design, Setting, and Participants: This retrospective cohort study used the Massachusetts Public Health Data Warehouse, which included all individuals with a claim in the All-Payer Claims Database and is linked to individual-level data from multiple government agencies, to assess individuals aged 18 to 64 years with opioid use disorder and hospitalization for endocarditis, osteomyelitis, epidural abscess, septic arthritis, or bloodstream infection (ie, SIRI) between July 1, 2014, and December 31, 2019. Data analysis was performed from November 2021 to May 2023. Exposure: Demographic and clinical factors potentially associated with posthospitalization MOUD receipt. Main Outcomes and Measures: The main outcome was MOUD receipt measured weekly in the 12 months after hospitalization. We used zero-inflated negative binomial regression to examine characteristics associated with any MOUD receipt and rates of treatment in the 12 months after hospitalization. Secondary outcomes were receipt of any buprenorphine formulation, methadone, and extended-release naltrexone examined individually. Results: Among 8769 individuals (mean [SD] age, 43.2 [12.0] years; 5066 [57.8%] male) who survived a SIRI hospitalization, 4305 (49.1%) received MOUD, 5919 (67.5%) were rehospitalized, and 973 (11.1%) died within 12 months. Of those treated with MOUD in the 12 months after hospitalization, the mean (SD) number of MOUD initiations during follow-up was 3.0 (1.7), with 956 of 4305 individuals (22.2%) receiving treatment at least 80% of the time. MOUD treatment after SIRI hospitalization was significantly associated with MOUD in the prior 6 months (buprenorphine: adjusted odds ratio [AOR], 16.51; 95% CI, 13.81-19.74; methadone: AOR, 28.46; 95% CI, 22.41-36.14; or naltrexone: AOR, 2.05; 95% CI, 1.56-2.69). Prior buprenorphine (incident rate ratio [IRR], 1.17; 95% CI, 1.11-1.24) or methadone (IRR, 1.89; 95% CI, 1.79-2.01) use was associated with higher treatment rates after hospitalization, and prior naltrexone use (IRR, 0.86; 95% CI, 0.77-0.95) was associated with lower rates. Conclusions and Relevance: This study found that in the year after a SIRI hospitalization in Massachusetts, mortality and rehospitalization were common, and only half of patients received MOUD. Treatment with MOUD before a SIRI was associated with posthospitalization MOUD initiation and time receiving MOUD. Efforts are needed to initiate MOUD treatment during SIRI hospitalizations and subsequently retain patients in treatment.

Considerations when prescribing opioid agonist therapies for people living with HIV.

INTRODUCTION: Medications for opioid use disorder (MOUD) include opioid agonist therapies (OAT) (buprenorphine and methadone), and opioid antagonists (extended-release naltrexone). All forms of MOUD improve opioid use disorder (OUD) and HIV outcomes. However, the integration of services for HIV and OUD remains inadequate. Persistent barriers to accessing MOUD underscore the immediate necessity of addressing pharmacoequity in the treatment of OUD in persons with HIV (PWH). AREAS COVERED: In this review article, we specifically focus on OAT among PWH, as it is the most commonly utilized form of MOUD. Specifically, we delineate the intersection of HIV and OUD services, emphasizing their integration into the United States Ending the HIV Epidemic (EHE) plan by offering comprehensive screening, testing, and treatment for both HIV and OUD. We identify potential drug interactions of OAT with antiretroviral therapy (ART), address disparities in OAT access, and present the practical benefits of long-acting formulations of buprenorphine, ART, and pre-exposure prophylaxis for improving HIV prevention and treatment and OUD management. EXPERT OPINION: Optimizing OUD outcomes in PWH necessitates careful attention to diagnosing OUD, initiating OUD treatment, and ensuring medication retention. Innovative approaches to healthcare delivery, such as mobile pharmacies, can integrate both OUD and HIV and reach underserved populations.

Accessing opioid agonist treatment in prison in England and Scotland remains problematic - the views of people with lived experience.

PURPOSE: The purpose of this paper is to examine lived experiences of opioid agonist treatment (OAT) during and immediately following release from detention in prisons in England and Scotland. DESIGN/METHODOLOGY/APPROACH: Surveys were completed by serving prisoners in both countries and by those recently released from prison (England only). The survey findings were discussed in focus groups of people with lived experience. The combined findings from the surveys and focus groups were shared with an expert group of prison OAT providers and people with lived experience with the purpose of making recommendations for more accessible and effective OAT in custodial environments and continuity of OAT on release. FINDINGS: The quality and accessibility of OAT varied considerably between establishments. It was reported to be harder to access OAT in Scottish prisons. It was often hard for people in prison to get the dosage of OAT they felt they needed and it was generally harder to access buprenorphine than methadone in English prisons. Only Scottish people in prison were aware of long-lasting forms of buprenorphine. People in English prisons had mixed experiences of the help available in prison, with no improvement recorded since a 2016 study. People in Scottish prisons were more likely to rate the help available as poor. RESEARCH LIMITATIONS/IMPLICATIONS: The number of people accessed while actually in prison (73) was reduced by the impact of the pandemic, making it more difficult to access people in prison and because some were resistant to participating on the basis that they had already been consulted for a wide variety of research projects focused on the impact of COVID. The Scottish cohort (a total of 19 individuals comprising 14 survey respondents and five focus group members) is clearly too small a number on which to base robust claims about differences in OAT provision between the English and Scottish prison systems.. PRACTICAL IMPLICATIONS: The study identifies key barriers to accessing OAT in prisons and suggests key components of more user-friendly approaches. SOCIAL IMPLICATIONS: This study provides an overview of the recent lived experiences of people accessing OAT in prison and on release and offers valuable recommendations on how to make service provision more effective and consistent. ORIGINALITY/VALUE: This study provides an overview of the recent lived experiences of people accessing OAT in prison and on release in England and Scotland and offers valuable recommendations on how to make service provision more effective and consistent.

Methadone versus other opioids for refractory malignant bone pain: a pilot randomised controlled study.

PURPOSE: Refractory cancer-induced bone pain (CIBP) affects a patient's functional capacity and quality of life, but there is limited evidence to guide opioid choice. We assessed the feasibility, tolerability and possible efficacy of methadone rotation (MR) compared to other opioid rotations (OOR) in this cohort. METHODS: Adults with CIBP and worst pain intensity ≥ 4/10 and/or opioid toxicity graded ≥ 2 on the Common Terminology Criteria for Adverse Events were randomised 1:1 to methadone or another opioid rotation. Standardised assessment tools were used at pre-defined study time points up to 14 days. RESULTS: Of 51 eligible participants, 38 (74.5%) consented, and 29 (76.3%, MR: 14, OOR: 15) completed the fourteen days follow-up post-opioid rotation. Both groups displayed significant reduction in average (MR: d = - 1.2, p = 0.003, OOR: d = - 0.8, p = 0.015) and worst pain (MR: d = - 0.9, p = 0.042, OOR: d = - 0.6, p = 0.048) and total pain interference score (MR: d = - 1.1, p = 0.042, OOR: d = - 0.7, p = 0.007). Oral morphine equivalent daily dose was reduced significantly in MR compared to the OOR group (d = - 0.8, p = 0.05). The incidence of opioid-related adverse events following MR was unchanged but lower in the OOR group (d = 0.9, 95% CI 0.1,1.7, p = 0.022). There were no within-group or between-group differences in satisfaction with analgesia at the end of the study. CONCLUSION: This pilot study demonstrated that MR and OOR in patients with refractory CIBP are feasible, safe and acceptable to patients. Appropriately powered multi-centre randomised controlled studies are needed to confirm the efficacy of MR and OOR in this cohort. TRIAL REGISTRATION: ACTRN12621000141842 registered 11 February 2021.

Effects of prenatal exposure to methadone or buprenorphine and maternal separation on anxiety-like behavior in rats.

BACKGROUND: The use of medications for opioid use disorder such as methadone or buprenorphine is increasing among pregnant women. However, long-term effects of this treatment on the children's health are not well understood. A key challenge is distinguishing the effects of opioid exposure from other confounding factors associated with human opioid use, such as reduced maternal care. In this study, we therefore used a multi-risk factor design to examine anxiety-like behavior in rats prenatally exposed to methadone or buprenorphine, with or without maternal separation the first two weeks after birth. METHODS: Female Sprague Dawley rats were exposed to methadone (10mg/kg/day), buprenorphine (1mg/kg/day) or sterile water throughout gestation. Half of the offspring in each litter experienced maternal separation for 3h per day from postnatal day 2 to 12. Male and female offspring (6-9 weeks) were tested in the open field, light-dark transition and elevated plus maze tests to assess anxiety-like behavior. RESULTS: Offspring exposed to buprenorphine and not subjected to maternal separation displayed increased anxiety-like behavior in 3 out of 6 outcomes in the light-dark transition and elevated plus maze tests. Maternal separation did not exacerbate, but rather diminished this behavior. Males and females responded differently to methadone, with a trend towards reduced anxiety for males and increased anxiety for females. CONCLUSIONS: Prenatal exposure to methadone or buprenorphine may increase the risk of developing anxiety-like behavior later in life, but the effect depends on specific subgroup characteristics. Further research is required to draw definitive conclusions.

Receipt of medications for opioid use disorder before and after incarceration in Massachusetts State prisons, 2014-2019.

BACKGROUND: Little is known about how use patterns of medications for opioid use disorder (MOUDs) evolve from pre-incarceration to post-incarceration among incarcerated individuals with opioid use disorder. This article describes pre- and post-incarceration MOUD receipt during a period when naltrexone was the only type of MOUD offered in a state prison system, the Massachusetts Department of Correction (MADOC). METHODS: A retrospective cohort study of individuals with opioid use disorder who had an incarceration episode in MADOC during January 2015 to March 2019. The data source was the Massachusetts Public Health Data Warehouse, a multi-sector data platform that links individual-level data from multiple statewide datasets. We described patterns of MOUD receipt during the four weeks prior to and after an incarceration episode. Multivariable logistic regression models characterized predictors of post-incarceration MOUD receipt. RESULTS: In the male sample (n=691 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (14.3 % to 18.3 %), naltrexone increased (5.0 % to 10.5 %), and methadone decreased (4.7 % to 1.7 %). Similarly, in the female sample (n=892 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (10.3 % to 12.3 %, naltrexone increased (4.5 % to 9.3 %), and methadone decreased (5.0 % to 2.9 %). Much of the post-release naltrexone receipt occurred among participants in MADOC's pre-release naltrexone program. CONCLUSIONS: MOUD receipt was low but increased slightly in the post-incarceration period. This change was driven by increases in buprenorphine and naltrexone and despite decreases in methadone.

Effect of Acupuncture for Methadone Reduction : A Randomized Clinical Trial.

BACKGROUND: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. OBJECTIVE: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. DESIGN: Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123). SETTING: 6 MMT clinics in China. PARTICIPANTS: Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. INTERVENTION: Acupuncture or sham acupuncture 3 times a week for 8 weeks. MEASUREMENTS: The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). RESULTS: Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of -11.7 mm VAS (CI, -18.7 to -4.8 mm; P < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. LIMITATION: Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. CONCLUSION: Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Post-operative pain control in patients on buprenorphine or methadone for opioid use disorder.

OBJECTIVE: This study aimed to determine whether there is a difference in pain scores and opioid consumption after elective surgery in patients maintained on methadone or buprenorphine for opioid use disorder (OUD). Additionally, we investigated the impact of continuing or discontinuing methadone or buprenorphine on post-operative pain outcomes. DESIGN: A single-center retrospective cohort study. SETTING: Tertiary care medical center. PATIENTS AND PARTICIPANTS: Adults aged 18 years or older with OUD maintained on buprenorphine or methadone who underwent elective surgery between January 1, 2017, and January 1, 2021. INTERVENTIONS: Patients were identified through electronic medical records, and demographic and clinical data were collected. MAIN OUTCOME MEASURES: The primary outcome was opioid consumption at 24 hours post-operatively, measured in milligram morphine equivalents. The secondary outcome was opioid consumption and pain scores up to 72 hours post-operatively, assessed using a numeric rating scale. RESULTS: This study included 366 patients (64 percent on buprenorphine and 36 percent on methadone). Opioid utilization significantly increased when buprenorphine was not administered post-operatively. Both groups exhibited comparable total opioid consumption during the post-operative period. In the buprenorphine cohort, pain scores differed significantly based on the receipt of medications for OUD post-operatively. CONCLUSIONS: This study reinforces existing evidence supporting the continuation of medications for opioid use disorder, specifically buprenorphine and methadone, during the perioperative period. Dissemination of guideline recommendations is essential to ensure optimal post-operative pain management for this patient population.