Healthcare staff's perspectives on long-acting injectable buprenorphine treatment: a qualitative interview study.

BACKGROUND: Long-acting injectable buprenorphine (LAIB) formulations are a novel treatment approach in opioid agonist treatment (OAT), which provide patients with a steady dose administered weekly or monthly and thus reduce the need for frequent clinic visits. Several studies have analyzed patient experiences of LAIB but the perspective of OAT staff is unknown. This study aimed to explore how healthcare staff working in OAT clinics in Sweden perceive and manage treatment with LAIB. METHODS: Individual qualitative interviews were conducted with OAT physicians (n = 10) in tandem with nine focus group sessions with OAT nurses and other staff categories (n = 41). The data was analyzed with thematic text analysis. RESULTS: Five central themes were identified in the data: (1) advantages and disadvantages of LAIB, (2) patient categories that may or may not need LAIB, (3) patients' degrees of medication choice, (4) keeping tabs, control and treatment alliance, and (5) LAIB's impact on risk and enabling environments in OAT. Overall staff found more advantages than disadvantages with LAIB and considered that patients with ongoing substance use and low adherence were most likely to benefit from LAIB. However, less frequent visits were viewed as problematic in terms of developing a treatment alliance and being able to keep tabs on patients' clinical status. Clinics differed regarding patients' degrees of choice in medication, which varied from limited to extensive. LAIB affected both risk and enabling environments in OAT. CONCLUSIONS: LAIB may strengthen the enabling environment in OAT for some patients by reducing clinic visits, exposure to risk environments, and the pressure to divert medication. A continued discussion about the prerequisites and rationale for LAIB implementation is needed in policy and practice.

Mediating effect of craving on the impact of buprenorphine/naloxone and methadone treatment on opioid use: Results from a randomized controlled trial.

BACKGROUND: The relationship between opioid craving and opioid use is unclear. We sought to determine to what extent craving mediated the relationship between opioid agonist therapy and changes in opioid use. METHODS: Data came from a pragmatic, 24-week, pan-Canadian, multi-centric, open-label, randomized controlled trial comparing flexible buprenorphine/naloxone take-home doses to standard supervised methadone models of care for the treatment of prescription-type opioid use disorder. Participants were randomly allocated to buprenorphine/naloxone or methadone models of care. 270 people with prescription-type opioid use disorder were included in analyses. There were 93 women (34.4%) and 2 transgender (0.7%) participants. Most participants were white (67.4%), 45.9% reported unstable living conditions, and 44.8% had psychiatric comorbidities. Generalized linear mixed models followed by mediation analysis estimated the direct effect of treatment group on Timeline Followback-reported next-week opioid use and the indirect effect through past 24-hour opioid craving measured using the Brief Substance Craving Scale at week 2, 6, 10, 14, 18 and 22. RESULTS: Upon mediation analysis, the average direct effect of treatment on opioid use was 0.465 (95 % CI = 0.183 to 0.751, p < 0.001). The average causal mediated effect was 0.144 (95 % CI = 0.021 to 0.110; p < 0.001). Craving accounted for 23.6 % of the effect of treatment on opioid use (p < 0.001). CONCLUSIONS: Past 24-hour craving was associated with increased next-week opioid use; however, craving only partially mediated the effect of buprenorphine/naloxone and methadone on next-week opioid use. Research is needed to develop a comprehensive understanding of factors mediating opioid use during opioid agonist therapy.

Neonatal Abstinence Syndrome and Corresponding Pharmacotherapy Approaches from 2 University-affiliated Neonatal Intensive Care Units in Puerto Rico (2018-2020).

OBJECTIVE: Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms suffered by neonates exposed to drugs in utero. Several studies have widely described NAS incidence and treatment approach; however, little is known regarding the incidence and manifestations of this disease in Puerto Rico (PR). The principal aim of this study was to describe NAS incidence in the neonatal units of hospitals affiliated with the University of PR in terms of occurrence, clinical manifestations, and treatment approaches. METHODS: Our study evaluated the medical records of NAS babies diagnosed from 2018 through 2020 at 2 hospitals affiliated with the University of PR Medical Sciences Campus. Descriptive and inferential statistics were employed to analyze trends. RESULTS: We identified 12 neonates diagnosed with NAS, 5 with low birthweights (<2500 g); for a NAS incidence of 2 cases per 1000 admitted for the 3 years of recollected data. The urine toxicology results revealed that 9 had experienced intrauterine polydrug exposure. Phenobarbital loading dose were determined on the day of diagnosis (indicated by Finnegan score). The first manifestation of NAS symptoms varied: 8 neonates showed symptoms within 48 hours after birth, whereas 4 had withdrawal symptoms within 72-120 hours of their births. Differences between dosing practices and guidelines were observed, ranging from a 0.69% to a 25% difference during treatment initiation. CONCLUSION: Further research on the incidence of NAS in PR (national level) is needed for a deeper understanding that we hope will lead to the development of enhanced treatment protocols in PR.

Fentanyl abuse proportion in methadone maintenance treatment, and patients' knowledge about its risks.

INTRODUCTION: Fentanyl is not yet routinely monitored among methadone maintenance treatment (MMT) patients in Israel. We aimed 1. to evaluate urine fentanyl proportion changes over 3 years and characterize patients' characteristics 2. To study patients' self-report on fentanyl usage, and compare knowledge about fentanyl risk, before and following brief educational intervention. METHODS: Fentanyl in the urine of all current MMT patients was tested every 3 months year between 2021 and 2023, and patients with positive urine fentanyl were characterized. Current patients were interviewed using a fentanyl knowledge questionnaire (effects, indications, and risks) before and following an explanation session. RESULTS: Proportion of fentanyl ranged between 9.8 and 15.1%, and patients with urine positive for fentanyl (September 2023) were characterized as having positive urine for pregabalin, cocaine, and benzodiazepine (logistic regression). Of the current 260 patients (87% compliance), 78(30%) self-reported of fentanyl lifetime use ("Ever"), and 182 "never" use. The "Ever" group had higher Knowledge scores than the "Never", both groups improved following the explanatory session (repeated measure). The "Ever" group patients were found with urine positive for cannabis and benzodiazepine on admission to MMT, they were younger, did not manage to gain take-home dose privileges and had a higher fentanyl knowledge score (logistic regression). CONCLUSIONS: In the absence of routine fentanyl tests, a high knowledge score, shorter duration in MMT, benzodiazepine usage on admission, and current cannabis usage, may hint of the possibility of fentanyl abuse.

Outcome in methadone maintenance treatment of immigrants from the former Union of Soviet Socialist Republics.

CONTEXT: Immigrants from the former Union of Soviet Socialist Republics (USSR) are more prevalent in Methadone maintenance treatment (MMT) in Israel than their percentage in the general population. AIMS: To compare their characteristics and outcomes to those of Israeli-born and other immigrant patients. METHODS: Retention and survival since admission (June/1993-Dec/2022) until leaving treatment (for retention), or at the end of follow-up were analyzed. Vital data was taken from a national registry. Predictors were estimated using Kaplan-Meier and Cox regression models. RESULTS: The USSR patients (N = 262) compared with other immigrants (N = 132) and Israeli-born (N = 696) were more educated (≥ 12y) (p < 0.001), admitted to MMT at a younger age (p < 0.001), following a shorter duration of opioid usage (p < 0.001). More of them ever injected drugs (p < 0.001) and ever drank alcohol (p < 0.001). One-year retention was comparable (77.2% vs. 75.6% and 72%, p = 0.2) as did opioid discontinuation in those who stayed (p = 0.2). Former USSR patients had longer cumulative retention of their first admission (p = 0.05) with comparable overall retention since first admission, and survival, although the age of death was younger. Specific origin within the former USSR found immigrants from the Russian Federation with the best outcome, and those from Ukraine as having high HIV seropositive and shorter retention. CONCLUSIONS: Despite several characteristics known to be associated with poor outcomes, former USSR immigrants showed better adherence to MMT, reflected by their longer cumulative retention in their first admission, lower rate of readmissions, and a comparable survival and overall retention in treatment. An in depth study is needed in order to understand why they decease at a younger age.

Comparison of analgesic efficacy of tramadol, morphine and methadone in cats undergoing ovariohysterectomy.

OBJECTIVES: The aim of this study was to compare the analgesic efficacy and the effect on physiological variables and behavior of the use of tramadol, methadone and morphine as preoperative analgesia in healthy cats undergoing elective ovariohysterectomy. METHODS: Cats undergoing ovariohysterectomy were randomly assigned to receive one of the following premedication treatments intramuscularly: methadone (0.2 mg/kg; n = 10); morphine (0.2 mg/kg; n = 10); or tramadol (3 mg/kg; n = 10). Induction of anesthesia was done with propofol, and maintenance of anesthesia was done with isoflurane. Intraoperative heart rate, arterial blood pressure, respiratory rate, end-tidal isoflurane concentration and frequency of rescue analgesia (fentanyl 2.5 µg/kg) were compared between groups. Postoperative analgesia was assessed using the UNESP-Botucatu Multidimensional Composite Pain Scale, and perioperative serum glucose, cortisol concentrations and postoperative rescue analgesia were evaluated. RESULTS: Intraoperative rescue analgesia was required in 76.5% of cats at some time during surgery, and 27% of cats required postoperative rescue analgesia up to 6 h after extubation. There were no significant differences between groups with respect to intraoperative and postoperative rescue analgesia, pain scale scores and end-tidal isoflurane concentrations. In the immediate postoperative period, after extubation, most of the patients presented with hypothermia; however, 1-6 h postoperatively, hyperthermia was observed in most of the patients, and was most common in the tramadol group. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of this study, methadone, morphine and tramadol produced satisfactory postoperative analgesia in most of the cats undergoing ovariohysterectomy, and the effects lasted up to 6 h postoperatively. Intraoperative analgesia was not sufficient in most cases. Significant cardiovascular or respiratory effects contraindicating the use of these drugs were not found. Postanesthetic hyperthermia occurred with all opioids studied and was more frequent in the tramadol group.

Evaluation of urinary trace element levels in patients with opioid use disorder undergoing methadone treatment in western Iran.

The monitoring of essential and toxic elements in patients with Opioid Use Disorder (OUD) undergoing methadone treatment (MT) is important, and there is limited previous research on the urinary levels of these elements in MT patients. Therefore, the present study aimed to analyze certain elements in the context of methadone treatment compared to a healthy group. In this study, patients with opioid use disorder undergoing MT (n = 67) were compared with a healthy group of companions (n = 62) in terms of urinary concentrations of some essential elements (selenium (Se), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), calcium (Ca)) and toxic elements (lead (Pb), cadmium (Cd), arsenic (As), and chromium (Cr)). Urine samples were prepared using the acid digestion method with a mixture of nitric acid and perchloric acid and assessed using the ICP-MS method. Our results showed that the two groups had no significant differences in terms of gender, education level, occupation, and smoking status. Urinary concentrations of Se, Cu, and Fe levels were significantly lower in the MT group compared to the healthy subjects. However, the concentrations of Pb, Cd, As, Mn, Cr, and Ca in the MT group were higher than in the healthy group (p < 0.05). No significant difference was established between the levels of Zn in the two groups (p = 0.232). The results of regression analysis revealed that the differences between the concentration levels of all metals (except Zn) between two groups were still remained significant after adjusting for all variables (p < 0.05). The data obtained in the current study showed lower urinary concentrations of some essential elements and higher levels of some toxic elements in the MT group compared to the healthy subjects. These findings should be incorporated into harm-reduction interventions.

Prison Buprenorphine Implementation and Postrelease Opioid Use Disorder Outcomes.

Importance: Agonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone. Objective: To evaluate postrelease outcomes after buprenorphine implementation. Design, Setting, and Participants: This cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024. Exposure: April 2019 implementation of buprenorphine during incarceration. Main Outcomes and Measures: Receipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation. Results: A total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected. Conclusions and Relevance: In this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.

Integrating methadone into primary care settings in Ukraine: effects on provider stigma and knowledge.

INTRODUCTION: Stigma has undermined the scale-up of evidence-based HIV prevention and treatment. Negative beliefs influence clinicians' discriminatory behaviour and ultimately have wide-ranging effects across the HIV prevention and treatment continuum. Stigma among clinicians can be mitigated in several ways, including through interpersonal contact. In this study, we test whether interactions with people who inject drugs (PWID) influence attitudes of both direct and indirect providers of opioid agonist therapies (OATs) within the same primary care clinics (PCCs) where OAT is newly introduced. METHODS: In a cluster randomized controlled trial integrating OAT and HIV care into PCCs in Ukraine, clinicians at 24 integrated care sites (two sites in 12 regions) from January 2018 to August 2022 completed a structured survey at baseline, 12 and 24 months. The survey included feeling thermometers and standardized scales related to clinician attitudes towards patients and evidence-based care. Nested linear mixed-effects models were used to examine changes in mean scores over three timepoints for both direct and indirect clinicians. RESULTS: There were fewer significant changes in any of the scales for direct providers (n = 87) than for indirect providers (n = 155). Direct providers became less tough-minded about substance use disorders (p = 0.002), had less negative opinions about PWID (p = 0.006) and improved their beliefs regarding OAT maintenance (p<0.001) and medical information (p = 0.004). Indirect providers reported improvements in most stigma constructs, including a significant decrease in prejudice (p<0.001), discrimination (p = 0.001), shame (p = 0.007) and fear (p = 0.001) towards PWID. CONCLUSIONS: Integrating OAT services within primary settings was associated with significantly reduced stigma constructs and improved attitudes towards PWID, possibly through increased intergroup contact between PWID and general clinical staff. Unlike most stigma reduction interventions, re-engineering clinical processes so that PWID receive their care in PCCs emerges as a multilevel stigma reduction intervention through the integration of specialized services in PCCs. Integration influences different types of stigma, and has positive effects not only on health outcomes, but also improves clinician attitudes and efficiently reduces clinician stigma.

Is pain empathy associated with pain indices and trauma history? A comparison between patients receiving methadone maintenance treatment and healthy controls.

BACKGROUND: To study whether pain empathy and theory of mind (ToM) are related to pain indices and trauma experience, we studied opioid users receiving methadone maintenance treatment (MMT), a population with a history of traumas and a high prevalence of chronic pain. METHODS: MMT patients (n = 53), substance abuse-free, with no impaired cognition (Montreal Cognitive Assessment (MoCA) ≥24), were compared to healthy controls (HC) matched by age and gender (n = 66). All participants were assessed using Reading the Mind in the Eyes (RMET) for ToM, empathy (Interpersonal Reactivity Index [IRI], Empathy Quotient Scale for Adults [EQ60]), and Pain Empathy [PE task]). An algometer was used for pain pressure threshold, and supra-pain threshold was rated using a visual analog scale (VAS). Catastrophizing, McGill pain, Negative life events (NLE), and MoCA questionnaires were administered. Substance abuse was tested in the urine of MMT patients and self-reported by HC. RESULTS: MMT, compared to HC, were less educated with more NLE and a lower RMET (logistic regression). Groups had comparable empathy and pain indices, except for higher supra-threshold VAS rating and catastrophizing in univariate analyses. Pain empathy (PE) correlated with NLE in HC, and in MMT, with catastrophizing, which correlated with NLE, perceived stress, and pain intensity. Higher empathy was observed in 18 participants with a history of sexual abuse (83.3 % belong to the MMT group). CONCLUSIONS: Pain Empathy was found to be associated with personal suffering experience in both groups, as reflected by correlations with NLE in HC and with catastrophizing, which correlates with NLE, stress, and pain intensity, in MMT.

Assessing the impact of public funding in alleviating participant reduction and improving the retention rate in methadone maintenance treatment clinics in Taiwan: an interrupted time series analysis.

BACKGROUND: Given the steady decline in patient numbers at methadone maintenance treatment (MMT) clinics in Taiwan since 2013, the government initiated Patients' Medical Expenditure Supplements (PMES) in January 2019 and the MMT Clinics Accessibility Maintenance Program (MCAM) in September 2019. This study aims to evaluate the impact of the PMES and MCAM on the enrollment and retention of patients attending MMT clinics and whether there are differential impacts on MMT clinics with different capacities. METHODS: The monthly average number of daily participants and 3-month retention rate from 2013 to 2019 were extracted from MMT databases and subjected to single interrupted time series analysis. Pre-PMES (from February 2013 to December 2018) was contrasted with post-PMES, either from January 2019 to December 2019 for clinics funded solely by the PMES or from January 2019 to August 2019 for clinics with additional MCAM. Pre-MCAM (from January 2019 to August 2019) was contrasted with post-MCAM (from September 2019 to December 2019). Based on the monthly average number of daily patients in 2018, each MMT clinic was categorized as tiny (1-50), small (51-100), medium (101-150), or large (151-700) for subsequent stratification analysis. RESULTS: In terms of participant numbers after the PMES intervention, a level elevation and slope increase were detected in the clinics at every scale except medium in MMT clinics funded solely by PMES. In MMT clinics with subsequent MCAM, a level elevation was only detected in small-scale clinics, and a slope increase in the participant numbers was detected in tiny- and small-scale clinics. The slope decrease was also detected in medium-scale clinics. In terms of the 3-month retention rate, a post-PMES level elevation was detected at almost every scale of the clinics, and a slope decrease was detected in the overall and tiny-scale clinics for both types of clinics. CONCLUSIONS: Supplementing the cost of a broad treatment repertoire enhances the enrollment of people with heroin use in MMTs. Further funding of human resources is vital for MMT clinics to keep up with the increasing numbers of participants and their retention.

Diffusion of medications for opioid use disorder treatment in jail settings: a convergent mixed methods study of jail staff perspectives.

BACKGROUND: Implementation of medications for opioid use disorder (MOUD) in jails varies by facility and across states. Organizational climate, including staff attitudes toward change and exposure to education, can influence perceptions of innovations like MOUD in jails. Using a mixed methods design, we aimed to understand the association between organizational climate and jail staff perceptions of MOUD. METHODS: Jail staff (n = 111) who operate MOUD programs in 6 Massachusetts jails completed surveys that included the Organizational Readiness for Implementing Change (ORIC) survey. Random effects logistic regression models assessed associations between organizational climate and several outcomes of perceived MOUD efficacy, acceptability, and knowledge, while controlling for covariates. Jail staff (N = 61) participated in qualitative interviews and focus groups focused on organizational climate and knowledge diffusion, which we analyzed using inductive and deductive methods. RESULTS: The results indicate that organizational change readiness on the ORIC was associated with positive perceptions of MOUD, and educational resources facilitated MOUD implementation. Greater ORIC was associated with higher perception of methadone as highly acceptable for jail populations (Odds ratio [OR] 2.3, 95% Confidence Interval [CI] 1.2 to 4.4), and high knowledge of methadone (OR 2.3, 95% CI 1.1 to 4.9), with similar magnitude of effects for buprenorphine. High levels of training for jail staff on methadone and buprenorphine were also associated with higher knowledge of these medications (Methadone: OR 7.2, 95% CI 2.2 to 23.2; Buprenorphine: OR 3.4, 95% CI 1.2 to 9.5). Qualitative results point towards the importance of organizational climate and elucidate educational strategies to improve staff perceptions of MOUD. CONCLUSION: Results underscore the importance of organizational climate for successful implementation of jail MOUD programs and provide support for medication-specific educational resources as a facilitator of successful MOUD implementation in jail settings. Findings highlight implementation strategies that may improve jail staff perceptions of MOUD.

Canadian Addiction Treatment Centre (CATC) opioid agonist treatment cohort in Ontario, Canada.

PURPOSE: The Canadian Addiction Treatment Centre (CATC) cohort was established during a period of increased provision of opioid agonist treatment (OAT), to study patient outcomes and trends related to the treatment of opioid use disorder (OUD) in Canada. The CATC cohort's strengths lie in its unique physician network, shared care model and event-level data, making it valuable for validation and integration studies. The CATC cohort is a valuable resource for examining OAT outcomes, providing insights into substance use trends and the impact of service-level factors. PARTICIPANTS: The CATC cohort comprises 32 246 people who received OAT prescriptions between April 2014 and February 2021, with ongoing tri-annual updates planned until 2027. The cohort includes data from all CATC clinics' electronic medical records and includes demographic information and OAT clinical indicators. FINDINGS TO DATE: This cohort profile describes the demographic and clinical characteristics of patients being treated in a large OAT physician network. As well, we report the longitudinal OAT retention by treatment type during a time of increasing exposure to a contaminated dangerous drug supply. Notable findings also include retention differences between methadone (32% of patients at 1 year) and buprenorphine (20% at 1 year). Previously published research from this cohort indicated that patient-level factors associated with retention include geographic location, concurrent substance use and prior treatment attempts. Service-level factors such as telemedicine delivery and frequency of urine drug screenings also influence retention. Additionally, the cohort identified rising OAT participation and a substantial increase in fentanyl use during the COVID-19 pandemic. FUTURE PLANS: Future research objectives are the longitudinal evaluation of retention and flexible modelling techniques that account for the changes as patients are treated with OAT. Furthermore, future research aims are the use of conditional models, and linkage with provincial-level administrative datasets.

Estimated effectiveness and cost-effectiveness of opioid use disorder treatment under proposed U.S. regulatory relaxations: A model-based analysis.

AIM: To assess the effectiveness and cost-effectiveness of buprenorphine and methadone treatment in the U.S. if exemptions expanding coverage for substance use disorder services via telehealth and allowing opioid treatment programs to supply a greater number of take-home doses of medications for opioid use disorder (OUD) continue (Notice of Proposed Rule Making, NPRM). DESIGN SETTING AND PARTICIPANTS: Model-based analysis of buprenorphine and methadone treatment for a cohort of 100,000 individuals with OUD, varying treatment retention and overdose risk among individuals receiving and not receiving methadone treatment compared to the status quo (no NPRM). INTERVENTION: Buprenorphine and methadone treatment under NPRM. MEASUREMENTS: Fatal and nonfatal overdoses and deaths over five years, discounted lifetime per person QALYs and costs. FINDINGS: For buprenorphine treatment under the status quo, 1.21 QALYs are gained at a cost of $19,200/QALY gained compared to no treatment; with 20% higher treatment retention, 1.28 QALYs are gained at a cost of $17,900/QALY gained compared to no treatment, and the strategy dominates the status quo. For methadone treatment under the status quo, 1.11 QALYs are gained at a cost of $17,900/QALY gained compared to no treatment. In all scenarios, methadone provision cost less than $20,000/QALY gained compared to no treatment, and less than $50,000/QALY gained compared to status quo methadone treatment. CONCLUSIONS: Buprenorphine and methadone OUD treatment under NPRM are likely to be effective and cost-effective. Increases in overdose risk with take-home methadone would reduce health benefits. Clinical and technological strategies could mitigate this risk.

The effects of OPRM1 118A>G on methadone response in pain management in advanced cancer at end of life.

Cancer pain is the most feared symptom at end of life. Methadone has advantages over other opioids but is associated with significant variability in clinical response, making dosing challenging in practice. OPRM1 is the most studied pharmacogene associated with the pharmacodynamics of opioids, however reports on the association of the A118G polymorphism on opioid dose requirements are conflicting, with no reports including methadone as the primary intervention. This association study on OPRM1 A118G and response to methadone for pain management, includes a review of this genetic factor's role in inter-patient variability. Fifty-four adult patients with advanced cancer were recruited in a prospective, multi-centre, open label dose individualization study. Patient characteristics were not shown to influence methadone response, and no significant associations were observed for methadone dose or pain score. The findings of our review of association studies for OPRM1 A118G in advanced cancer pain demonstrate the importance of taking ancestry into account. While our sample size was small, our results were consistent with European populations, but in contrast to studies in Chinese patients, where carriers of the A118G polymorphism were associated with higher opioid dose requirements. Pharmacogenetic studies in palliative care are challenging, continued contribution will support future genotype-based drug dosing guidelines.

Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients.

Methadone (R,S-methadone) can prolong the QT interval. R-methadone inhibits cardiac potassium channel function less than S-methadone. We tested if switching from methadone to R-methadone would reduce corrected QT (QTc) intervals in methadone maintenance treatment (MMT) patients. Nine patients, with automatically read QTc intervals ≥450 ms, were required to detect a 20 ms (clinically relevant) reduction in QTc intervals with 15 ms standard deviation (SD) and 90% power. Nine stabilized MMT patients, using median (range) 70 (40-120) mg methadone, were included. Data (ECG recordings, serum samples, and withdrawal symptoms) were collected both before drug intake (Cmin ) and at 3 h after drug intake (Cmax ), and were collected on the day before the switch from methadone to equipotent R-methadone dose and at 14 and 28 days after the switch. A cardiologist calculated QTc intervals retrospectively. Serum electrolytes and methadone concentrations were measured. Mean QTc intervals at Cmin were 472 ms and 422 ms on methadone (automatically and manually read) and 414 ms on R-methadone (manually read). Mean (SD) change in QTc intervals was -8 (10) ms (p = 0.047) at Cmin but non-significant at Cmax . R-methadone showed a concentration-dependent relationship with QTc intervals. Switching to R-methadone reduced QTc intervals, but far less than the 20 ms considered clinically relevant.

Association of random and observed urine drug screening with long-term retention in opioid treatment programs.

BACKGROUND: In the US, opioid treatment providers (OTPs) have wide latitude to perform urine drug screening (UDS) and discharge clients for positive results. OTP clients have identified randomized and directly observed UDS as potentially stigmatizing, but little research has examined the association between UDS modality and retention in OTPs. METHODS: This cross-sectional study uses the 2016-2017 NDATSS wave among OTPs that administered methadone. The exposure was a 4-level variable based on whether OTPs had a high percentage (≥ 90% of clients) who experienced randomized, observed, both, or neither modality of UDS. The outcome was the proportion of clients retained in treatment 1 year or longer (long-term retention). Analyses were conducted using fractional logit regression with survey weighting and presented as percentages and 95% confidence intervals. We also present how policies for involuntary clinic discharge modify these effects. RESULTS: 150 OTPs were eligible with a median of 310 clients. 40 (27%) OTPs did not highly utilize either randomized or observed UDS, 22 (15%) only highly utilized observed UDS, 42 (28%) only highly utilized randomized UDS and 46 (31%) utilized both practices on ≥ 90% of clients. Adjusted estimates for long-term retention ranged from 57.7% in OTPs that conducted both randomized and observed UDS on ≥ 90% of clients and 70.4% in OTPs that did not highly utilize these practices. Involuntary discharge may moderate this relationship. CONCLUSION: Findings showed an association between high utilization of randomized and observed UDS and decreased long-term retention, suggesting that UDS modality may impact long-term OTP retention.