Opioid Agonist Research Articles

Distrust in the Health Care System and Adherence to Direct-Acting Antiviral Therapy among People with Hepatitis C Virus Who Inject Drugs.

This study is a secondary analysis of a randomized clinical trial (October 2013-April 2017) involving 150 People Who Inject Drugs (PWIDs) with hepatitis C virus (HCV) seen in opioid agonist treatment programs in the Bronx, New York, and investigates the impact of distrust in the healthcare system on adherence to Direct-Acting Antivirals (DAAs) HCV treatment therapy among PWIDs. The distrust was scaled on a 9-item instrument and the adherence to DAA medications was measured using electronic blister packs. This study demonstrated a significant inverse relationship between levels of distrust and medication adherence: 71.8 ± 2.2% (se) vs. 77.9 ± 1.8%, p = 0.024 between participants with higher and lower distrust levels. Despite the absence of significant association of distrust with sociodemographic or substance use characteristics, these findings suggest that building trust within the healthcare system is paramount for improving adherence to DAAs among PWIDs. The results call for a healthcare approach that emphasizes trust-building through patient-centered care, sensitivity training, peer support, and health system reform to effectively address the treatment needs of this marginalized population.

Non-injection drug use among incarcerated people in Iran: Findings from three consecutive national bio-behavioral surveys

BackgroundPrisons often serve as high-risk environments for drug use, and incarcerated people are at a high risk for substance use-related mental and physical harms. This study aimed to determine the prevalence of non-injection drug use inside the prison and its related factors among incarcerated people in Iran.MethodsWe utilized data from three national bio-behavioral surveillance surveys conducted among incarcerated people in Iran in 2009, 2013, and 2017. Eligibility criteria were being ≥ 18 years old, providing informed consent, and being incarcerated for over a week. Overall, 17,228 participants across all surveys were recruited through a multi-stage random sampling approach. Each participant underwent a face-to-face interview and HIV test. The primary objective of the study was to assess self-reported non-injection drug use within the prison environment within the last month. A multivariable logistic regression model was built to determine associated covariates with drug use inside prison and an adjusted odds ratio (aOR) with 95% confidence intervals (CI) were reported.ResultThe prevalence of non-injection drug use inside the prison was 24.1% (95% CI 23.5, 24.7) with a significant decreasing trend (39.7% in 2009, 17.8% in 2013, 14.0% in 2017; p-value < 0.001). Overall, 44.0% of those who used drugs were also receiving opioid agonist therapy (OAT) and we noted that in 2017, 75.1% of those on OAT used stimulants. In the multivariable logistic regression model, the year of interview (2013: aOR = 1.43 and 2009: aOR = 5.60), younger age (19–29: aOR = 1.14 and 30–40: aOR = 1.37), male sex (aOR = 3.35), < high school education (aOR = 1.31), having a history of previous incarceration (aOR = 1.26), and having a history of lifetime HIV testing (aOR = 1.76) were significantly and positively associated with recent non-injection drug use inside the prison.ConclusionsApproximately one in four incarcerated people in Iran reported drug use within the last month inside prisons. While a declining trend in non-injection drug use was noted, substantial gaps persist in harm reduction programs within Iranian prisons. In particular, there is a pressing need for improvements in drug treatment programs, focusing on the integration of initiatives specifically designed for people who use stimulants.

Hyperalgesia in Patients With a History of Opioid Use Disorder

Short-term and long-term opioid treatment have been associated with increased pain sensitivity (ie, opioid-induced hyperalgesia). Treatment of opioid use disorder (OUD) mainly involves maintenance with methadone and buprenorphine, and observations of heightened cold pain sensitivity among patients are often considered evidence of opioid-induced hyperalgesia. To critically examine the evidence that hyperalgesia in patients with OUD is related to opioid use. Web of Science, PubMed, and Embase between March 1, 2023, and April 12, 2024, were searched. Studies assessing cold pressor test (CPT) pain responses during treatment seeking, pharmacological treatment, or abstinence in patients with OUD history were included. Multilevel random-effects models with robust variance estimation were used for all analyses. Study quality was rated with the JBI checklist. Funnel plots and Egger regression tests were used to assess reporting bias. Main outcomes were pain threshold, tolerance, and intensity in patients and healthy controls, and unstandardized, standardized (Hedges g), and percentage differences (%Δ) in these measures between patients and controls. The association between pain sensitivity and opioid tolerance, withdrawal, and abstinence indices was tested with meta-regression. Thirty-nine studies (1385 patients, 741 controls) met the inclusion criteria. Most studies reported CPT data on patients undergoing opioid agonist treatment. These patients had a mean 2- to 3-seconds lower pain threshold (95% CI, -4 to -1; t test P = .01; %Δ, -22%; g = -0.5) and 29-seconds lower pain tolerance (95% CI, -39 to -18; t test P < .001; %Δ, -52%; g = -0.9) than controls. Egger tests suggested that these differences may be overestimated. There were some concerns of bias due to inadequate sample matching and participant dropout. Meta-regressions yielded no clear support for hyperalgesia being opioid related. Patients receiving opioid agonist treatment for OUD are hypersensitive to cold pain. It remains unclear whether hyperalgesia develops prior to, independent of, or as a result of long-term opioid treatment. Regardless, future studies should investigate the impact of hyperalgesia on patients' well-being and treatment outcomes.

An individual-based dynamic model to assess interventions to mitigate opioid overdose risk

BackgroundIllicit opioid overdose continues to rise in North America and is a leading cause of death. Mathematical modeling is a valuable tool to investigate the epidemiology of this public health issue, as it can characterize key features of population outcomes and quantify the broader effect of structural and interventional changes on overdose mortality. The aim of this study is to quantify and predict the impact of key harm reduction strategies at differing levels of scale-up on fatal and nonfatal overdose among a population of people engaging in unregulated opioid use in Toronto.MethodsAn individual-based model for opioid overdose was built featuring demographic and behavioural variation among members of the population. Key individual attributes known to scale the risk of fatal and nonfatal overdose were identified and incorporated into a dynamic modeling framework, wherein every member of the simulated population encompasses a set of distinct characteristics that govern demographics, intervention usage, and overdose incidence. The model was parametrized to fatal and nonfatal overdose events reported in Toronto in 2019. The interventions considered were opioid agonist therapy (OAT), supervised consumption sites (SCS), take-home naloxone (THN), drug-checking, and reducing fentanyl in the drug supply. Harm reduction scenarios were explored relative to a baseline model to examine the impact of each intervention being scaled from 0% use to 100% use on overdose events.ResultsModel simulations resulted in 3690.6 nonfatal and 295.4 fatal overdoses, coinciding with 2019 data from Toronto. From this baseline, at full scale-up, 290 deaths were averted by THN, 248 from eliminating fentanyl from the drug supply, 124 from SCS use, 173 from OAT, and 100 by drug-checking services. Drug-checking and reducing fentanyl in the drug supply were the only harm reduction strategies that reduced the number of nonfatal overdoses.ConclusionsWithin a multi-faceted harm reduction approach, scaling up take-home naloxone, and reducing fentanyl in the drug supply led to the largest reduction in opioid overdose fatality in Toronto. Detailed model simulation studies provide an additional tool to assess and inform public health policy on harm reduction.

Effects of chronic naltrexone treatment on relapse-related behavior and neural responses to fentanyl in awake nonhuman primates.

Naltrexone, an opioid antagonist that blocks the reinforcing properties of opioid agonists, is often prescribed to preclude relapse to opioid use disorder (OUD) following detoxification. However, few laboratory studies have directly investigated the ability of naltrexone to alter relapse-inducing effects of opioid agonists, including their priming strength in reinstatement studies and their impact in brain regions known to be involved in drug-induced reinforcement in MRI studies. Here we directly address this issue by investigating the effects of continuous exposure to naltrexone on 1) fentanyl-induced reinstatement of drug-seeking behavior, 2) fentanyl-induced patterns of blood oxygenation level dependent (BOLD) activation in the nucleus accumbens (NAcc), and 3) fentanyl-induced changes in NAcc functional connectivity (FC) in awake non-human primates that are engaged in ongoing opioid self-administration studies. We found that naltrexone antagonizes the priming strength of fentanyl as shown by a rightward shift in its reinstatement dose-effect curve and that naltrexone surmountably antagonizes the BOLD response induced by fentanyl. However, while naltrexone also countered fentanyl's effects on NAcc FC, the effects were not surmounted by a higher dose of fentanyl. Together, these data suggest that, in contrast to naltrexone's modulation of fentanyl's effects on behavior and BOLD responses, their interactive effects on FC between multiple brain regions do not reflect their receptor-mediated activity. Additionally, we demonstrated opposing effects in the absence and presence of naltrexone on NAcc FC at baseline (i.e., in the absence of any fentanyl prime) suggesting that naltrexone alters FC at baseline, even though naltrexone appears behaviorally silent in the absence of an agonist prime. Together these data provide additional insight into ways in which naltrexone interacts with opioid agonists, both behaviorally and in the brain. Further understanding the effects of opioid agonists on patterns of FC could help elucidate our understanding of the neural processes that contribute to the initiation of and relapse to opioid-seeking behavior in OUD.

Opioid agonist treatment outcomes among individuals with a history of nonfatal overdose: Findings from a pragmatic, pan-Canadian, randomized control trial.

History of nonfatal overdose (NFO) is common among people who use opioids, but little is known about opioid agonist treatment (OAT) outcomes for this high-risk subpopulation. The objective of this study was to investigate the relative effectiveness of buprenorphine/naloxone and methadone on retention and suppression of opioid use among individuals with opioid use disorder (OUD) and history of NFO. Secondary analysis of a pan-Canadian pragmatic trial comparing flexible take-home buprenorphine/naloxone and supervised methadone for people with OUD and history of NFO. Logistic regression was used to examine the impact of OAT on retention in the assigned or in any OAT at 24 weeks and analysis of covariance was used to examine the mean difference in opioid use between treatment arms. Of the 272 randomized participants, 155 (57%) reported at least one NFO at baseline. Retention rates in the assigned treatment were 17.7% in the buprenorphine/naloxone group and 18.4% in the methadone group (adjusted odds ratio [AOR] = 0.54, 95% CI: 0.17-1.54). Rates of retention in any OAT were 28% and 20% in the buprenorphine/naloxone and methadone arms, respectively (AOR = 1.55, 95% CI: 0.65-3.78). There was an 11.9% adjusted mean difference in opioid-free urine drug tests, favoring the buprenorphine/naloxone arm (95% CI: 3.5-20.3; p = .0057). Among adults with OUD and a history of overdose, overall retention rates were low but improved when retention in any treatment was considered. These findings highlight the importance of flexibility and patient-centered care to improve retention and other treatment outcomes in this population.

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

BackgroundFederal 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.MethodsUsing 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.ResultsThere 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.ConclusionsFederal 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.

Selective opioid agonist Taphalgin® as a component of postoperative analgesia in various surgical areas: “NIKITA” observational multicenter study

Introduction. The role of peptides in antinociceptive system regulation has became a subject of interest for scientists worldwide. The first registered peptide analgesic tyrosyl-D-arginyl-phenylalanyl-glycinamide acetate which currently can be used in clinical practice was developed in Russia under the name Taphalgin® (PharmFirma “Sotex”, Russia). The effectiveness and safety of this pharmaceutical in postoperative pain management was evaluated in the all-Russia multicenter prospective observation program NICITA (Non-interventional Clinical Trial of Taphalgin ®).Aim. To analyze the effectiveness and safety of Taphalgin® in postoperative pain management in various surgical fields.Materials and methods. The observational program NICITA included 887 patients including patients with malignant tumors of various locations from 15 study centers in different Russian cities. All patients underwent surgical interventions in various anatomical areas under general, regional and combination anesthesia. The principal scheme of postoperative pain management was based on the multimodal approach which included peptide opioid agonist alongside acetaminophen, cyclooxygenase inhibitors in combination with regional anesthesia or without it. The study also included patients who underwent small-volume surgeries, and pain was managed through Taphalgin® monotherapy with subsequent switch to cyclooxygenase inhibitors. The primary endpoint of the NICITA observational program was response to therapy after the first Taphalgin® administration. Decreased pain syndrome per the numerical rating scale 15–60 min after subcutaneous injection and maintenance of analgesic effect 3 h later were considered treatment response. The secondary endpoints included mean time to analgesia start after administration of the 1st single drug dose (in min), duration of effect, types and frequency of adverse reactions including serious in the central nervous system, pulmonary system, gastrointestinal tract developed during the observational program, as well as patient and research physician satisfaction with pain management. To evaluate the significance of pain intensity change at rest and in motion in time, analysis of variance with repeat measurements was used; for pairwise comparison of two time periods, Student’s t-test for dependent samples was used. The differences were considered significant at p = 0.05.Results. Statistically significant decrease in pain intensity in the total patient group was observed 15 minutes after Taphalgin® administration; it reached its minimum 40 min after the injection (р &lt;0.05). The percentage of patients responding to analgesic therapy with Taphalgin® was 96.5 %. During administration of the drug, insignificant decrease (10–15 mmHg) in arterial blood pressure (1.7 % of cases) and vertigo (1 % of cases) were observed. In some patients, several adverse reactions were observed. Satisfaction with analgesic effect of Taphalgin® was relatively high both in patients and research physicians.Conclusion. Taphalgin® has pronounced analgesic effect and is effective for pain management after surgical interventions of various volumes and injury level. The use of this drug is associated with low rate of adverse reactions and absence of pulmonary depression characterizing opioid agonists. Therefore, Taphalgin® can be recommended for clinical use for postoperative pain management after various types of surgical interventions.

Implementation of time-limited parenteral hydromorphone in people with treatment-resistant injecting opioid use disorder: a protocol for a single-site, uncontrolled, open-label study to assess feasibility, safety and cost

IntroductionSupervised injectable opioid treatment (SIOT) is an evidence-based intervention targeting opioid-dependent people for whom existing treatments have been ineffective. This project will primarily assess the feasibility and the acceptability of...

Key phosphorylation sites for robust β-arrestin2 binding at the MOR revisited

Desensitisation of the mu-opioid receptor (MOR) is proposed to underlie the initiation of opioid analgesic tolerance and previous work has shown that agonist-induced phosphorylation of the MOR C-tail contributes to this desensitisation. Moreover, phosphorylation is important for β-arrestin recruitment to the receptor, and ligands of different efficacies induce distinct phosphorylation barcodes. The C-tail 370TREHPSTANT379 motif harbours Ser/Thr residues important for these regulatory functions. 375Ser is the primary phosphorylation site of a ligand-dependent, hierarchical, and sequential process, whereby flanking 370Thr, 376Thr and 379Thr get subsequently and rapidly phosphorylated. Here we used GRK KO cells, phosphosite specific antibodies and site-directed mutagenesis to evaluate the contribution of the different GRK subfamilies to ligand-induced phosphorylation barcodes and β-arrestin2 recruitment. We show that both GRK2/3 and GRK5/6 subfamilies promote phosphorylation of 370Thr and 375Ser. Importantly, only GRK2/3 induce phosphorylation of 376Thr and 379Thr, and we identify these residues as key sites to promote robust β-arrestin recruitment to the MOR. These data provide insight into the mechanisms of MOR regulation and suggest that the cellular complement of GRK subfamilies plays an important role in determining the tissue responses of opioid agonists.

New Challenges and Opportunities for Opioid Agonist Treatment Access and Retention: A Scoping Review

New Challenges and Opportunities for Opioid Agonist Treatment Access and Retention: A Scoping Review

Functional differences in the mu opioid receptor SNP 118A>G are dependent on receptor splice-variant andagonist-specific recruitment of β-arrestin.

The OPRM1 gene codes for the mu opioid receptor (MOR) and polymorphisms are associated with complex patient clinical responses. The most studied single nucleotide polymorphism (SNP) in OPRM1 is adenine (A) substituted by guanine (G) at position 118 (118A>G, rs1799971) leading to a substitution of asparagine (Asn) for aspartic acid (Asp) at position 40 in the N terminus of the resulting protein. To date, no structural explanation for the associated clinical responses resulting from the 118A>G polymorphism has been proposed. We utilized computational modeling paired with functional cellular assays to predict unstructured N- and C-terminal regions of MOR-1. Using molecular docking and post-docking energy minimizations with morphine, we show that the extracellular substitution of Asn at position 40 alters the cytoplasmic C-terminal conformation, while leaving the G-protein binding interface unaffected. A real-time BRET assay measuring G-protein and β-arrestin association with MOR r generated data that tested this prediction. Consistent with this in silico prediction, we show changes in morphine-mediated β-arrestin association with receptor variants with little change in morphine-mediated G-protein association comparing MOR-1 wild type (WT) to MOR-1118A>G. We tested the system with different opioid agonists, the OPRM1 118A>G SNP, and different MOR splice variants (MOR-1 and MOR-1O). These results are consistent with the observation that patients with the 118A>G OPRM1 allele respond more readily to fentanyl than to morphine. In conclusion, the 118A>G substitution alters receptor responses to opioids through variable C-terminal domain movements that are agonist and splice variant dependent.

Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators.

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

Trends in central nervous system-active polypharmacy among people with multiple sclerosis

Background: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS. Objective: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS. Methods: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants. Results: The number of subjects included at each time point ranged from 23,917 subjects in 2008 to 55,797 subjects in 2021. In 2021, subjects with CNS-active polypharmacy were more likely to be 46–65 years of age and have CNS-related comorbidities compared to those without CNS-active polypharmacy. From 2008 to 2021, the age-adjusted prevalence of CNS-active polypharmacy among female subjects increased from 19.8% (95% confidence interval (CI) = 19.1–20.4) to 26.4% (95% CI = 25.9–26.8) versus 15.9% (95% CI = 14.8–17.0) to 18.6% (95% CI = 17.9–19.2) in male subjects. Conclusion: The prevalence of CNS-active polypharmacy has increased among people with MS with a growing disparity by sex.

Perinatal injectable opioid agonist therapy (iOAT) treatment experience: A qualitative study

Perinatal injectable opioid agonist therapy (iOAT) treatment experience: A qualitative study

Initiation of Buprenorphine Treatment of Opioid Use Disorder in Pediatric Emergency Departments.

Pediatric emergency departments (EDs) in the United States are facing a rise in the number of children and adolescents who present with opioid use disorder (OUD), often driven by illicitly manufactured fentanyl. Medication treatment of pediatric OUD in the ED setting is often limited to symptomatic treatment of opioid withdrawal. Pediatric patients are rarely offered medications for OUD, especially in the ED setting. Buprenorphine is a partial opioid agonist that is Food and Drug Administration-approved for the treatment of OUD in patients aged 16 years and older. Adult studies have demonstrated that ED initiation of medication for OUD such as buprenorphine is feasible, safely treats withdrawal symptoms, and can improve patient compliance with outpatient follow-up. However, initiation of buprenorphine in the ED has not been well-studied in the pediatric population. We present 2 cases of adolescent patients, a 16-year-old male and 17-year-old female, who presented to the ED with opioid withdrawal. They were both diagnosed with severe OUD because of their use of counterfeit pills containing fentanyl. Both patients were successfully started on buprenorphine/naloxone in the pediatric ED before transitioning to an outpatient addiction clinic for continued treatment. The case series demonstrates the feasibility of ED-based buprenorphine initiation for adolescents, an important and timely intervention for adolescents with OUD.

Buprenorphine for acute pain in older adults: a systematic review with meta-analysis.

Buprenorphine, a partial opioid agonist, has emerging evidence as an alternative to full agonist opioids for treatment of acute pain. This systematic review aimed to evaluate the safety and efficacy of buprenorphine for acute pain in older adults. PubMed Medline, Embase, Cochrane Central Register of Controlled Trials, CINHAL, Web of Science database, and Google Scholar were searched. We included articles that reported buprenorphine as an intervention to treat acute pain among patients 60 years or older. Primary outcome was difference in pain scores for patients treated with buprenorphine compared to other analgesia. Secondary outcomes included adverse events, opioid consumption, and patient satisfaction. Meta-analysis was conducted on difference in pain scores and differences in nausea and vomiting. Twenty-two studies were included (n = 2610). Buprenorphine was administered as nerve blocks in six studies, transdermal in eight, intravenous or intramuscular in five, sublingual in two studies, and both intravenous and sublingual in one study. 10 out of 20 (50%) studies found improved pain control in buprenorphine groups. Meta-analysis found no significant difference in pain scores between buprenorphine and control analgesia at 24 hours (Cohen's d = -0.29 [95% CI -0.85 to 0.27]) and 7 days (Cohen's d = -0.89 [95% CI -2.66-0.88]). Six studies (54.5%) found reduced opioid consumption in patients receiving buprenorphine. There was no difference in adverse effects in most studies. This review did not find buprenorphine to be superior to alternative analgesia; however the mixed results provide scientific rationale for future studies testing buprenorphine in older populations.

Low-Dose Buprenorphine Initiation for Hospitalized Patients With Chronic Pain and Opioid Use Disorder or Opioid Misuse: Protocol for an Open-Label, Parallel-Group, Effectiveness-Implementation Randomized Controlled Trial.

Buprenorphine is an effective medication for both opioid use disorder (OUD) and chronic pain (CP), but transitioning from full opioid agonists to buprenorphine, a partial opioid agonist, can be challenging. Preliminary studies suggest that low-dose buprenorphine initiation can overcome some challenges in starting treatment, but no randomized controlled trials have compared low-dose and standard buprenorphine initiation approaches regarding effectiveness and safety or examined implementation in hospital settings. In a pragmatic open-label hybrid type I effectiveness-implementation trial based in a single urban health system, 270 hospitalized patients with (a) CP and (b) OUD or opioid misuse are being randomized to buprenorphine treatment initiation using 5-day low-dose or standard initiation protocols. Outcomes include buprenorphine treatment uptake (primary), defined as receiving buprenorphine treatment 7 days after enrollment, and other OUD and pain outcomes at 1-, 3-, and 6-month follow-up (secondary). Data collection will also include safety measures, implementation of low-dose initiation protocols, patient acceptability, and cost-effectiveness. Comparing strategies in a randomized clinical trial will provide the most definitive data to date regarding the effectiveness and safety of low-dose buprenorphine initiation. The study will also provide important data on treating CP at a time that clinical guidelines are evolving to center buprenorphine as a preferred opioid for CP.

Client preferences for the design and delivery of injectable opioid agonist treatment services: Results from a best-worst scaling task.

Clinical trials support injectable opioid agonist treatment (iOAT) for individuals with opioid use disorder (OUD) for whom other pharmacological management approaches are not well-suited. However, despite substantial research indicating that person-centered care improves engagement, retention and health outcomes for individuals with OUD, structural requirements (e.g. drug policies) often dictate how iOAT must be delivered, regardless of client preferences. This study aimed to quantify clients' iOAT delivery preferences to improve client engagement and retention. Cross-sectional preference elicitation survey. Metro Vancouver, British Columbia, Canada. 124 current and former iOAT clients. Participants completed a demographic questionnaire package and an interviewer-led preference elicitation survey (case 2 best-worst scaling task). Latent class analysis was used to identify distinct preference groups and explore demographic differences between preference groups. Most participants (n = 100; 81%) were current iOAT clients. Latent class analysis identified two distinct groups of client preferences: (1) autonomous decision-makers (n = 73; 59%) and (2) shared decision-makers (n = 51; 41%). These groups had different preferences for how medication type and dosage were selected. Both groups prioritized access to take-home medication (i.e. carries), the ability to set their own schedule, receiving iOAT in a space they like and having other services available at iOAT clinics. Compared with shared decision-makers, fewer autonomous decision-makers identified as a cis-male/man and reported flexible preferences. Injectable opioid agonist treatment (iOAT) clients surveyed in Vancouver, Canada, appear to prefer greater autonomy than they currently have in choosing OAT medication type, dosage and treatment schedule.

Correlates of stocking naloxone: a cross-sectional survey of community pharmacists.

Provision of take-home naloxone (THN) and overdose education reduces opioid-related mortality. In Australia, from July 2022, all Australian community pharmacies were eligible to supply naloxone for free through the nationalTHN Program. This study aimed to identify naloxone stocking rates and correlates of stocking naloxone across Australian pharmacies. Data were collected from a representative sample of Australian pharmacists in Victoria, New South Wales, Queensland and Western Australia via an online survey. Data collected included pharmacy and pharmacist characteristics and services offered within the pharmacy, including needle and syringe programs, opioid agonist treatment (OAT) and stocking naloxone. Binary probit regression analysis was used to identify correlates of stocking naloxone after controlling for key covariates. Data from 530 pharmacists were analysed. In total, 321 pharmacies (60.6%) reported stocking naloxone. Chain pharmacies and pharmacies that provided OAT had a greater probability of stocking naloxone (B = 0.307, 95%CI: [0.057, 0.556], and B = 0.543, 95%CI: [0.308, 0.777] respectively). Most (61.7%) pharmacists felt comfortable discussing overdose prevention with patients who use prescription opioids, and this comfort was associated with a higher probability of stocking naloxone (B = 0.392, 95%CI: 0.128, 0.655). Comfort discussing overdose prevention with people who use illicit opioids was lower (49.4%) and was not associated with stocking naloxone. There is scope to increase stocking of naloxone and comfort with overdose prevention, particularly through addressing comfort working with higher risk groups such as people who use illicit opioids.