Effect of oral naloxone on opioid-induced constipation in methadone maintenance treatment patients, a double-blind, placebo-control, clinical trial.

BACKGROUND: Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. METHOD: Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. RESULTS: The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5 mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS. CONCLUSION: Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS.

Leveraging prescription monitoring program data to evaluate the implementation of buprenorphine telehealth flexibilities: An interrupted time series analysis in Texas.

Background: In March 2020, policy changes by the Substance Abuse and Mental Health Services Administration and the Drug Enforcement Administration aimed to maintain access to office-based opioid treatment services by easing telehealth buprenorphine prescribing restrictions. However, the effectiveness of these changes remains largely unmeasured. The objective of this study was to measure the effectiveness of COVID-19-related telehealth flexibilities in an all-payer cohort from the Texas Prescription Monitoring Program. Methods: Using Texas Prescription Monitoring Program data, we identified oral buprenorphine and buprenorphine/naloxone prescriptions dispensed in Texas between September 1, 2019, and September 26, 2020. Weekly counts of prescriptions, prescribing physicians, and dispensing pharmacies were analyzed. An autoregressive integrated moving average (ARIMA) model estimated changes in prescription volume between pre-implementation (September 1, 2019 - February 15, 2020) and post-implementation (April 12, 2020 - September 26, 2020) periods. Results: Pre-flexibility, an average of 8898 (SD: 342) buprenorphine prescriptions were dispensed to 7829 (SD: 326) patients weekly. This declined to 8360 (SD: 247) prescriptions and 7661 (SD: 229) patients post-flexibility. Adjusted for seasonality, this represented a statistically significant average decline of -257.27 (95% CI: -426.06, -88.49) patients and -647.01 (95% CI: -856.67, -437.36) prescriptions per week. Discussion: Our results suggest a modest decline in buprenorphine dispensing volume early in the COVID-19 pandemic. While difficult to assess its significance, it can be assumed that telehealth flexibilities mitigated a potentially larger decline. Future research should explore system and individual-level barriers to telehealth utilization.

Integrated exercise program in opioid agonist therapy clinics and effect on psychological distress: study protocol for a randomized controlled trial (BAReAktiv).

BACKGROUND: Substance use disorder is associated with unhealthy lifestyle choices, resulting in adverse social and health consequences. People with opioid use disorder receiving opioid agonist therapy, in particular, have high morbidity and reduced quality of life. Physical activity is recommended as an adjunctive treatment for people with substance use disorder, but there is minimal evidence from randomized controlled trials on the effects of this among people with substance use disorder receiving opioid agonist therapy. METHODS: BAReAktiv is a multicentre randomized controlled trial. The study aims to recruit 324 patients receiving opioid agonist therapy (parallel groups randomized 1:1 to integrated exercise intervention or control, superiority trial). A 16-week group-based integrated exercise intervention with workouts twice a week. The exercise program consists of endurance and resistance training. The target group will be patients 18 years and older receiving opioid agonist therapy in outpatient clinics in several centers in Western Norway. The primary outcome of the study is the effect on psychological distress measured by Hopkins' symptom checklist with ten items. Secondary outcome measures include physical functioning assessed with a 4-min step test, activity level, fatigue symptoms, quality of life, and changes in inflammation markers. This study will provide improved knowledge on the effects of an integrated exercise program in opioid agonist therapy. DISCUSSION: Systematically integrating exercise programs for people receiving opioid agonist therapy could lead to a shift towards a stronger focus on health behaviors in outpatient care. Integrating exercise could benefit patient recovery and reduce disease burden. Further scale-up will be considered if the provided exercise program is safe and effective. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05242848. Registered on February 16, 2022.

Healthcare provider perspectives on emergency department-initiated buprenorphine/naloxone: a qualitative study.

BACKGROUND: Take-home buprenorphine/naloxone is an effective method of initiating opioid agonist therapy in the Emergency Department (ED) that requires ED healthcare worker buy-in for large-scale implementation. We aimed to investigate healthcare workers perceptions of ED take-home buprenorphine/naloxone, as well as barriers and facilitators from an ED healthcare worker perspective. METHODS: In the context of a take-home buprenorphine/naloxone feasibility study at a tertiary care teaching hospital we conducted a descriptive qualitative study. We conducted one-on-one in person or telephone interviews and focus groups with ED healthcare workers who cared for patients given take-home buprenorphine/naloxone in the feasibility study at Vancouver General Hospital from July 2019 to March 2020. We conducted 37 healthcare worker interviews from December 2019 to July 2020. We audio recorded interviews and focus groups and transcribed them verbatim. We completed interviews until we reached thematic saturation. DATA ANALYSIS: We inductively coded a sample of transcripts to generate a provisional coding structure and to identify emerging themes, which were reviewed by our multidisciplinary team. We then used the final coding structure to analyze the transcripts. We present our findings descriptively. RESULTS: Participants identified a number of context-specific facilitators and barriers to take-home buprenorphine/naloxone provision in the ED. Participants highlighted ED conditions having either facilitative or prohibitive effects: provision of buprenorphine/naloxone was feasible when ED volume was low and space was available but became less so as ED volume increased and space decreased. Similarly, participants noted that patient-related factors could have a facilitative or prohibitive effect, such as willingness to wait (willing to stay in the ED for study-related activities and buprenorphine/naloxone initiation activities), receptiveness to buprenorphine/naloxone, and comprehension of the instructions. As for staff-related factors, time was identified as a consistent barrier. Time included time available and time required to initiate buprenorphine/naloxone (including time building rapport). Healthcare worker familiarity with buprenorphine/naloxone was noted as either a facilitating factor or a barrier, and healthcare workers indicated that ongoing training would have been advantageous. Many healthcare workers identified that the ED is an important first point of contact for the target patient population. CONCLUSION: Integrating a buprenorphine/naloxone program into ED care requires organizational supports (e.g., for managing buprenorphine/naloxone within limitations of ED volume, space, and time), and ongoing education of healthcare workers to minimize identified barriers.

Telehealth Use and Health Equity for Mental Health and Substance Use Disorder During the COVID-19 Pandemic: A Systematic Review.

Background: As a result of the COVID-19 public health emergency (PHE), telehealth utilization accelerated to facilitate health care management and minimize risk. However, those with mental health conditions and substance use disorders (SUD)-who represent a vulnerable population, and members of underrepresented minorities (e.g., rural, racial/ethnic minorities, the elderly)-may not benefit from telehealth equally. Objective: To evaluate health equality in clinical effectiveness and utilization measures associated with telehealth for clinical management of mental health disorders and SUD to identify emerging patterns for underrepresented groups stratified by race/ethnicity, gender, age, rural status, insurance, sexual minorities, and social vulnerability. Methods: We performed a systematic review in PubMed, Embase, Cochrane Central Register of Controlled Trials, and CINAHL through November 2022. Studies included those with telehealth, COVID-19, health equity, and mental health or SUD treatment/care concepts. Our outcomes included general clinical measures, mental health or SUD clinical measures, and operational measures. Results: Of the 2,740 studies screened, 25 met eligibility criteria. The majority of studies (n = 20) evaluated telehealth for mental health conditions, while the remaining five studies evaluated telehealth for opioid use disorder/dependence. The most common study outcomes were utilization measures (n = 19) or demographic predictors of telehealth utilization (n = 3). Groups that consistently demonstrated less telehealth utilization during the PHE included rural residents, older populations, and Black/African American minorities. Conclusions: We observed evidence of inequities in telehealth utilization among several underrepresented groups. Future efforts should focus on measuring the contribution of utilization disparities on outcomes and strategies to mitigate disparities in implementation.

Incidence of hepatitis C virus infection in the prison setting: The SToP-C study.

People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP-C study enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3-6 months (October-2014 to November-2019). Participants eligible for this analysis included those at-risk of HCV primary infection (anti-HCV negative) or re-infection (anti-HCV positive, HCV RNA negative) with follow-up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person-years of follow-up). Overall HCV incidence was 6.11/100 person-years (95%CI: 5.07-7.35), with higher rate of re-infection (9.34/100 person-years; 95%CI: 7.15-12.19) than primary infection (4.60/100 person-years; 95%CI: 3.56-5.96). In total population (n = 1643), HCV risk was significantly higher among participants injecting drugs in prison [vs. no injecting; adjusted hazard ratio (aHR): 10.55, 95%CI: 5.88-18.92), and those who were released and re-incarcerated during follow-up (vs. remained incarcerated; aHR: 1.60, 95%CI: 1.03-2.49). Among participants who injected recently (during past month, n = 321), HCV risk was reduced among those receiving high-dosage opioid agonist therapy (OAT), i.e. methadone ≥60 mg/day or buprenorphine ≥16 mg/day, (vs. no OAT, aHR: 0.11, 95%CI: 0.02-0.80) and increased among those sharing needles/syringes without consistent use of disinfectant to clean injecting equipment (vs. no sharing, HR: 4.60, 95%CI: 1.35-15.66). This study demonstrated high HCV transmission risk in prison, particularly among people injecting drugs. High-dosage OAT was protective, but improved OAT coverage and needle/syringe programmes to reduce sharing injecting equipment are required.

Recovery Capital Gains May Precede Craving Reduction in Opioid Use Disorder.

Purpose: Cravings for drugs and alcohol have been significantly associated with worse treatment outcomes. We investigated if improvements in recovery capital (RC) (eg, a measure of social capital/network, financial resources, education, and cultural factors) over time were associated with decreased reported cravings. Patients and Methods: The original cohort consisted of 133 participants (63 females) with opioid use disorder seeking outpatient treatment, who completed the Assessment of Recovery Capital (ARC) (range 0 to 50) and the Brief Addiction Monitor (BAM) thrice over the 6-month study. Intervention was medication and case management. Analysis included one-way mixed models testing change over time for ARC total scores and single question craving rating (5-point Likert scale). Cross-lagged panel estimates used structural equation models with variables z-scored, allowing for path coefficient evaluation as standard deviations (sd). Results: Total ARC significantly increased over the study (χ2 = 33.77, df = 2, p < 0.0001), with baseline of 36.6 (n = 114, sd = 11.1) and 6-month of 41.2 (n = 107, sd = 9.5). Craving also changed significantly (χ2 = 8.51, df = 2, p < 0.015), with baseline of 1.1 (n = 101, sd = 1.2) and 6-month of 0.9 (n = 107, sd = 1.1). The cross-lag from baseline RC to 3-month craving was significant (ß = -0.28, SE = 0.11, z = -2.53, p < 0.011). The converse was not true; baseline craving did not affect later RC. Results were similarly significant when comparing 3-month to 6-month. The majority of sample was on buprenorphine. Conclusion: As RC improves, the reported cravings at both 3- and 6-month study time points are significantly reduced. When evaluated inversely, there was not a significant association with baseline cravings and follow-up RC. Significant path coefficients provide an estimation of a directional effect from increased RC towards craving reduction.

Buprenorphine deregulation as an opioid crisis policy response - A comparative analysis between France and the United States.

BACKGROUND: In passing the Maintstreaming Addiction Treatment Act, the United States has abolished its federal X waiver, considered a major barrier to the wider buprenorphine prescribing needed to respond to opioid-related harms. Advocates for this policy have drawn on the French response of deregulating buprenorphine prescribing to address increasing overdose mortality around the turn of the millennium. So far, such policy advocacy has incompletely accounted for contextual and health system differences between the two countries. METHODS: Using the health system dynamics framework, this analysis compares France from 1995 to 2003 (the relevant period of buprenorphine reform) to the US from 2018 until today (the comparison period to explore potential impacts of reform). We used it to guide examination of a) contextual issues relating to opioid use epidemiology and b) health system factors including prescriber supply, sector organization, and insurance coverage for primary care to draw relevant policy learning for the contemporary US. RESULTS: We identified that the US had a 22.5-fold higher mortality rate and a 2.3-fold higher opioid use disorder (OUD) rate compared to France, despite having rates of prescribed buprenorphine per-capita higher than, and per-person with OUD comparable to, than that of France. These wide gulfs between the scales and nature of the problems between France and the US suggest that relaxing restrictions on buprenorphine prescribing through abolishing the X waiver will be insufficient for achieving hoped-for reductions in overdose mortality. CONCLUSION: Health system strengthening with a focus on improvements in primary care prescriber supply, coverage, and coordination are likely higher yield policy complements to relaxing buprenorphine regulation. Such an approach would better prepare the US to adapt to ongoing dynamics and uncertainties in the opioid crisis and to optimize the already relatively high levels of buprenorphine prescribing.

Sublingual/Buccal buprenorphine and dental problems: a pharmacovigilance study.

BACKGROUND: The association between dental problems and sublingual/buccal buprenorphine is unclear. We conducted an analysis of dental adverse drug reactions reported with sublingual/buccal buprenorphine in VigiBase®, the pharmacovigilance database of the World Health Organization. RESEARCH DESIGN AND METHODS: We performed disproportionality analyses to compare the reporting rates of dental problems with sublingual/buccal buprenorphine, compared to other buprenorphine formulations and methadone. Significant signals were considered if the lower boundary of the 95% confidence interval of the Reporting Odds Ratio (ROR) was > 1; cases were ≥ 3 and p-value <0.05. We conducted sensitivity analyses by calculating the ROR according to the reporter's qualification and the reporting continent (United States of America and Europe). RESULTS: We included 30,769 reports with all buprenorphine forms. We found 20 cases of dental problems with sublingual/buccal buprenorphine. Sublingual/buccal buprenorphine was associated with an overreporting of dental problems compared to other buprenorphine formulations (ROR = 15.10; 95% CI [7.50-30.39]; p < 0.005) and compared to methadone (ROR = 6.02; 95% CI [3.21-11.30]; p < 0.005). Overreporting of dental problems was consistent in sensitivity analyses, except in Europe compared with other buprenorphine formulations and with methadone. CONCLUSIONS: Sublingual/buccal buprenorphine might increase the risk of reporting dental problems. However, these results do not modify the benefits of sublingual/buccal buprenorphine in the treatment of opioid use disorders.

Cost-effectiveness of integrated treatment for hepatitis C virus (HCV) among people who inject drugs in Norway: An economic evaluation of the INTRO-HCV trial.

BACKGROUND AND AIMS: The INTRO-HCV randomized controlled trial conducted in Norway over 2017-2019 found that integrated treatment, compared with standard-of-care hospital treatment, for hepatitis C virus (HCV) with direct-acting antivirals (DAAs) improved treatment outcomes among people who inject drugs (PWID). We evaluated cost-effectiveness of the INTRO-HCV intervention. DESIGN: A Markov health state transition model of HCV disease progression and treatment with cost-effectiveness analysis from the health-provider perspective. Primary cost, utility, and health outcome data were derived from the trial. Costs and health benefits (quality-adjusted life-years, QALYs) were tracked over 50 years. Probabilistic and univariate sensitivity analyses investigated DAA price reductions and variations in HCV treatment and disease care cost assumptions, using costs from different countries (Norway, United Kingdom, United States, France, Australia). SETTING AND PARTICIPANTS: PWID attending community-based drug treatment centers for people with opioid dependence in Norway. MEASUREMENTS: Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, compared against a conventional (€70 000/QALY) willingness-to-pay threshold for Norway and lower (€20 000/QALY) threshold common among high-income countries. FINDINGS: Integrated treatment resulted in an ICER of €13 300/QALY gained, with 99% and 71% probability of being cost-effective against conventional and lower willingness-to-pay thresholds, respectively. A 30% lower DAA price reduced the ICER to €6 900/QALY gained, with 91% probability of being cost-effective at the lower willingness-to-pay threshold. A 60% and 90% lower DAA price had 36% and >99% probability of being cost-saving, respectively. Sensitivity analyses suggest integrated treatment was cost-effective at the lower willingness-to-pay threshold (>60% probability) across different assumptions on HCV treatment and disease care costs with 30% DAA price reduction, and became cost-saving with 60%-90% price reductions. CONCLUSIONS: Integrated hepatitis C virus treatment for people who inject drugs in community settings is likely cost-effective compared with standard-of-care referral pathways in Norway and may be cost-saving in settings with particular characteristics.

Integrating Harm Reduction into Medical Care: Lessons from Three Models.

BACKGROUND: Substance use disorders (SUDs) are at a national high, with significant morbidity and mortality. Harm reduction, a public-health strategy aimed at reducing the negative consequences of a risky behavior without necessarily eliminating the behavior, represents a useful approach to engage patients with SUDs in care. The objective of this article is to describe how 3 medical practices operationalized harm reduction as a framework toward patient care and identify the common practices undertaken across these settings to integrate harm reduction and medical care. METHODS: We conducted a qualitative study using in-depth, semistructured interviews with 20 staff and providers at 3 integrated harm reduction and medical care sites across New York State from March to June 2021. Interview questions focused on how harm reduction approaches were implemented, how harm reduction philosophies were demonstrated in practice, and barriers to adoption. RESULTS: The interviews resulted in 8 main themes of integrated harm reduction medical care: 1) role of provider as both learner and informer; 2) pragmatic measures of success; 3) collaborative and interdisciplinary care teams; 4) developing a stigma-free culture; 5) creating a comfortable and welcoming physical space; 6) low-threshold care with flexible scheduling; and; 7) reaching beyond the clinic to disseminate harm reduction orientation; and 8) creating robust referral networks to enhance transitions of care. These themes existed at the patient-provider level (#1 to 3), the organizational level (#4 to 6), and the level extending beyond the clinic (#7 to 8). CONCLUSIONS: All 3 sites followed 8 common themes in delivering harm reduction-informed care, most of which are consistent with the broader movement toward patient-centered care. These practices demonstrate how medical providers may overcome some of the barriers imposed by the medical model and successfully integrate harm reduction as an orienting framework toward care delivery.

Smartphone intervention to optimize medication-assisted treatment outcomes for opioid use disorder: study protocol for a randomized controlled trial.

BACKGROUND: Opioids accounted for 75% of drug overdoses in the USA in 2020, with rural states particularly impacted by the opioid crisis. While medication-assisted treatment (MAT) with Suboxone remains one of the more efficacious treatments for opioid use disorder (OUD), approximately 40% of people receiving Suboxone for outpatient MAT for OUD (MOUD) relapse within the first 6 months of treatment. We developed the smartphone app-based intervention OptiMAT as an adjunctive intervention to improve MOUD outcomes. The aims of this study are to (1) evaluate the efficacy of adjunctive OptiMAT use in reducing opioid misuse among people receiving MOUD and (2) evaluate the role of specific OptiMAT features in reducing opioid misuse, including the use of GPS-driven just-in-time intervention. METHODS: We will conduct a two-arm, single-blind, randomized controlled trial of adults receiving outpatient MOUD in the greater Little Rock AR area. Participants are English-speaking adults ages 18 or older recently enrolled in outpatient MOUD at one of our participating study clinics. Participants will be allocated via 1:1 randomized block design to (1) MOUD with adjunctive use of OptiMAT (MOUD+OptiMAT) or (2) MOUD without OptiMAT (MOUD-only). Our blinded research statistician will evaluate differences between the two groups in opioid misuse (as determined by quantitative urinalysis conducted by clinical lab staff blinded to group membership) during the 6-months following study enrolment. Secondary analyses will evaluate if OptiMAT-usage patterns within the MOUD+OptiMAT group predict opioid misuse or continued abstinence. DISCUSSION: This study will test if adjunctive use of OptiMAT improve MOUD outcomes. Study findings could lead to expansion of OptiMAT into rural clinical settings, and the identification of OptiMAT features which best predict positive clinical outcome could lead to refinement of this and similar smartphone app-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05336188 , registered March 21, 2022.

Strategies to recruit rural primary care providers to implement a medication for opioid use disorder (MOUD) focused integrated care model.

Background: Access to providers and programs that provide medications for opioid use disorder (MOUD) remains a systemic barrier for patients with opioid use disorder (OUD), particularly if they live in rural areas. The Rural Access to Medication Assisted Treatment (MAT) in Pennsylvania Project (Project RAMP) addressed this problem with a multisystem partnership that recruited, trained, and supported rural primary care providers to provide MOUD and implement an integrated care model (ICM) for patients with OUD. Given the demonstrated efficacy of Project RAMP, this article summarizes our recruitment strategies, including feasibility concerns for further expansion into other regions. Methods: The approach for recruiting implementation sites included two phases: partner outreach and site identification. Once recruited, the Systems Transformation Framework guided planning and implementation activities. Recruitment and implementation activities were assessed with implementation trackers and evaluated by providers via key informant interviews (KIIs). Results: Project RAMP recruited 26 primary care practices from 13 counties, including nine health systems and two private practice groups-exceeding the original target of 24 sites. There was a median of 49 days from first contact to project onboarding. A total of 108 primary care practices spanning 22 health systems declined participation. Findings from the KIIs highlighted the value of engaging PCPs by connecting to a shared vision (i.e., improving the quality of patient care) as well as addressing perceived participation barriers (e.g., offering concierge technical assistance to address lack of training or resources). Conclusion: Findings highlight how successful recruitment activities should leverage the support of health system leadership. Findings also emphasize that aiding recruitment and engagement efforts successfully addressed prescribers' perceived barriers to providing MOUD as well as facilitating better communication among administrators, PCPs, behavioral health professionals, care managers, and patients.Plain Language Summary: Opioid use disorder (OUD) is one of the leading causes of preventable illness and death. The standard of care for OUD is the provision of medications for opioid use disorder (MOUD) and the application of an integrative integrated care model (ICM) where behavioral health is blended with specialized medical services. Unfortunately, access to providers and healthcare facilities that provide MOUD or apply an ICM remains a systemic barrier for patients with OUD, particularly if they live in rural areas. Although there is no one-size-fits-all approach to implementing MOUD in primary care, findings from Project The Rural Access to Medication Assisted Treatment (MAT) in Pennsylvania Project (Project RAMP) highlight strategies that may improve future MOUD and ICM implementation efforts in similar rural contexts. Specifically, future efforts to increase MOUD capacity by recruiting new providers should be prepared to leverage health system leadership, address provider barriers via training and expert consultation, and facilitate connections to local behavioral health providers. This approach may be helpful to others recruiting health systems and primary care practices to implement new care models to use MOUD in treating patients with OUD.

Exploring patient experience and satisfaction with depot buprenorphine formulations: A mixed-methods study.

INTRODUCTION: The introduction of depot buprenorphine for the treatment of opioid dependence allows for reduced dosing frequency compared with conventional treatments, such as oral methadone and sublingual buprenorphine-naloxone. Reduced dosing frequency is perceived to reduce issues such as high out-of-pocket costs, frequent attendance to pharmacies, stigmatisation and the risk of diversion for unsanctioned opioid use. This study aims to explore the experiences of patients receiving depot buprenorphine from an Australian publicly operated drug and alcohol service. METHODS: Participants were recruited from the service over a 5-week period in 2021. Twenty-eight participants consented to be involved in a mixed methods quantitative verbal survey and qualitative interview process. RESULTS: The majority of participants reported satisfaction with depot buprenorphine across the domains of efficacy, convenience and global satisfaction. Participants perceived benefits as increased convenience, reduced stigmatisation and the inability to 'skip' daily Medication Assisted Treatment for Opioid Dependence (MATOD) doses. There were mixed experiences with the ability for depot buprenorphine to 'hold' participants throughout the dosing interval. Reduced contact and disconnection from healthcare services were reported as an issue for some participants when initiating depot buprenorphine. DISCUSSION AND CONCLUSIONS: Patient perceptions of depot buprenorphine appear to be deeply rooted in prior experience with 'conventional' MATOD treatments. Depot buprenorphine is seen to be beneficial socially, personally, and financially by the majority of patients interviewed. The potential for disconnection from services and mixed experiences of efficacy throughout the dosing period may negatively influence patient experience.

Impact of Stigma on Clinician Training for Opioid Use Disorder Care: A Qualitative Study in a Primary Care Learning Collaborative.

PURPOSE: We undertook a study to examine how stigma influences the uptake of training on medication for opioid use disorder (MOUD) in primary care academic programs. METHODS: We conducted a qualitative study of 23 key stakeholders responsible for implementing MOUD training in their academic primary care training programs that were participants in a learning collaborative in 2018. We assessed barriers to and facilitators of successful program implementation and used an integrated approach to develop a codebook and analyze the data. RESULTS: Participants represented the family medicine, internal medicine, and physician assistant fields, and they included trainees. Most participants described clinician and institutional attitudes, misperceptions, and biases that enabled or hindered MOUD training. Perceptions included concerns that patients with OUD are "manipulative" or "drug seeking." Elements of stigma in the origin domain (ie, beliefs by primary care clinicians or the community that OUD is a choice and not a disease), the enacted domain (eg, hospital bylaws banning MOUD and clinicians declining to obtain an X-Waiver to prescribe MOUD), and the intersectional domain (eg, inadequate attention to patient needs) were perceived as major barriers to MOUD training by most respondents. Participants described strategies that improved the uptake of training, including giving attention to clinician concerns, clarifying the biology of OUD, and ameliorating clinician fears of being ill equipped to provide care for patients. CONCLUSIONS: OUD-related stigma was commonly reported in training programs and impeded the uptake of MOUD training. Potential strategies to address stigma in the training context, beyond providing content on effective evidence-based treatments, include addressing the concerns of primary care clinicians and incorporating the chronic care framework into OUD treatment.

Side Effects of Chronic Methadone Use in Opioid Addiction: A Scoping Review on Hematological Derangements.

BACKGROUND: Per oral methadone maintenance therapy [MMT] was introduced as part of harm reduction strategy to manage rising numbers of HIV infections caused by intravenous use of illicit drugs. METHOD: We aim to review published articles related to the side effects of long-term methadone therapy, focusing on hematological derangements in human studies published between 1 January 2000 till 31 January 2021. RESULTS: Our search databases include Web of Science, Scopus, and Medline. Our search yielded 971 articles, of which 55 articles were related to the effects of MMT on various organ systems: cardiovascular [n=12], respiratory [n=1], endocrine [n=10], central nervous system [n=12], neurobehavioral [n=10], gastrointestinal [n=1], and bone [n=1]. There were eight articles specifically related to the hematological side effects of chronic methadone therapy that include [i] immune system hyperactivation, [ii] reduced circulating lymphocytes, and [iii] increased blood viscosity. CONCLUSION: In view of all foreseeable health risks seen with prolonged methadone therapy, pharmacological modulation is warranted to find a better substitute for managing patients with opioid dependence.

Methadone Maintenance Treatment Discontinuation Among Young People who use Opioids in Vancouver, Canada.

OBJECTIVE: Retaining adolescents and young adults (AYA) in medications for opioid use disorder (MOUD), like methadone maintenance treatment (MMT), is critical to reducing toxic drug fatalities. This analysis sought to identify factors associated with MMT discontinuation among AYA. METHOD: Data were derived from the At-Risk Youth Study, a prospective cohort study of street-involved AYA in Vancouver, Canada, between December 2005 and June 2018. Multivariable extended Cox regression identified factors associated with time to MMT discontinuation among AYA who recently initiated MMT. In subanalysis, multivariable extended Cox regression analysis identified factors associated with time to "actionable" MMT discontinuation, which could be addressed through policy changes. RESULTS: A total of 308 participants reported recent MMT during the study period. Participants were excluded if they reported MMT in the past 6 months at baseline and were retained in MMT (n = 94, 30.5%); were missing MMT status data (n = 43, 14.0%); or completed an MMT taper (n = 11, 3.6%). Of the remaining 160 participants who initiated MMT over the study period, 102 (63.8%) discontinued MMT accounting for 119 unique discontinuation events. In multivariable extended Cox regression, MMT discontinuation was positively associated with recent weekly crystal methamphetamine use (adjusted hazard ratio [AHR] = 1.67, 95% confidence interval [CI]: 1.19 to 2.35), but negatively associated with age of first "hard" drug use (per year older) (AHR = 0.95, 95% CI: 0.90 to 1.00) and female sex (AHR = 0.66, 95% CI: 0.44 to 0.99). In subanalysis, recent weekly crystal methamphetamine use (AHR = 4.61, 95% CI: 1.78 to 11.9) and weekly heroin or fentanyl use (AHR = 3.37, 95% CI: 1.21 to 9.38) were positively associated with "actionable" MMT discontinuation, while older age (AHR = 0.87, 95% CI: 0.76 to 0.99) was negatively associated. CONCLUSIONS: Efforts to revise MMT programming; provide access to a range of MOUD, harm reduction, and treatments; and explore coprescribing stimulants to AYA with concurrent stimulant use may improve treatment retention and reduce toxic drug fatalities.

'As for dignity and respect . me bollix': A human rights-based exploration of service user narratives in Irish methadone maintenance treatment.

INTRODUCTION: This paper explores the narratives of service users of contemporary methadone maintenance treatment services (MMT) in the Republic of Ireland to obtain their perspectives in the context of them negotiating their right to health METHODS: Participants were recruited and interviewed by a former service user of MMT services. In-depth qualitative interviews were conducted with 40 current and recent users of MMT services RESULTS: Participants overwhelmingly reported a reduced sense of personal agency because of their experiences in MMT treatment. Participants observed that their perceptions of treatment were forged by a sense of reduced autonomy, coercive and disrespectful approaches from healthcare workers. Within a system which the participants considered to be failing, the services that they accessed were predicated on a process of reward and punishment, where best practice was often ignored by practitioners, all of which resulted in adverse consequences for service users DISCUSSION: The findings indicate that there is a significant 'chasm' between human rights, policy and best practice and how these are operationalised within the structures and practices of Irish MMT services. The treatment of service users, based on human rights principles such as equality, respect, autonomy, empowerment and personal choice remains aspirational and is unlikely to be fulfilled without addressing more systemic challenges such as funding, training of staff, service culture, governance and independent oversight of MMT services.

Personality dysfunction in opiate addicts on opioid substitution treatment and the risk of HCV infection.

Background: Impulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding the transmission of infectious diseases either sexually or by intravenous drug abuse. Objective: The aim of this study was to analyze the association between hepatitis C virus (HCV) infection and personality dysfunction in opiate addicts on opioid substitution treatment. Methods: This was a cross-sectional, observational investigation of patients over 18 years of age who were actively participating in opioid substitution treatment at five centers in Bosnia and Herzegovina. The occurrence of HCV infection was the primary study outcome, and personality functioning, the main independent variable, was assessed using the Severity Indices of Personality Problems (SIPP-118) questionnaire. The association between scores of personality functioning domains items and HCV infection status was determined by binary logistic regression analysis. Results: Patients on opioid substitution therapy with HCV infection more frequently had personality disorders (OR 2.168, 95% CI 1.161-4.05) and were treated longer than patients without HCV infection (OR 1.076, 95% CI 1.015-1.14). HCV infection was associated with lower self-respect (OR 0.946, 95% CI 0.906-0.988), decreased capacity to have enduring relationships with other people (OR 0.878, 95% CI 0.797-0.966), and lower capability to cooperate with others (OR 0.933, 95%CI 0.888-0.98). On the other hand, except for self-respect, other elements of the Identity Integration domain (enjoyment, purposefulness, stable self-image, and self-reflexive functioning), when more functional, increased the risk of HCV infection. Conclusions: Our study demonstrates that opiate addicts on opioid substitution treatment have a higher risk of HCV infection if their personality is dysfunctional, especially in the aspects of self-respect, enduring relationships, and cooperativity. The risk is even higher in addicts who have an established diagnosis of any kind of personality disorder.