Patients' perspectives on buprenorphine subcutaneous implant: a case series.

BACKGROUND: Considering the enormous burden represented by the opioid use disorder (OUD), it is important to always consider, when implementing opioid agonist therapy (OAT), the potential impact on patient's adherence, quality of life, and detoxification. Thus, the purpose of the study is to evaluate how the introduction of a novel OAT approach influences these key factors in the management of OUD. CASE PRESENTATION: This article marks the pioneering use of OAT through buprenorphine implant in Europe and delves into the experience of six patients diagnosed with OUD at a relatively young age. The patients, comprising both males and a female, are of Caucasian Italian and African Italian ancestry (case 4) and exhibit an age range from 23 to 63, with an average drug abuse history of 19 ± 12 years. All patients were on stable traditional OAT before transitioning to buprenorphine implants. Despite the heterogeneity in social and educational backgrounds, health status, and drug abuse initiation histories, the case series reveals consistent positive treatment outcomes such as detoxification, absence of withdrawal symptoms and of side effects. Notably, all patients reported experiencing a newfound sense of freedom and improved quality of life. CONCLUSIONS: These results emphasise the promising impact of OAT via buprenorphine implants in enhancing the well-being and quality of life in the context of OUD.

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.

Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.

Long-acting injectable depot buprenorphine from a harm reduction perspective in patients with ongoing substance use and multiple psychiatric comorbidities: a qualitative interview study.

BACKGROUND: Long-acting injectable depot buprenorphine may increase access to opioid agonist treatment (OAT) for patients with opioid use disorder in different treatment phases. The aim of this study was to explore the experiences of depot buprenorphine among Swedish patients with ongoing substance use and multiple psychiatric comorbidities. METHOD: Semi-structured qualitative interviews were conducted with OAT patients with experience of depot buprenorphine. Recruitment took place at two OAT clinics with a harm reduction focus, specializing in the treatment of patients with ongoing substance use and multiple comorbidities. Nineteen participants were included, 12 men and seven women, with a mean age of 41 years (range 24-56 years), and a mean of 21 years (5-35 years) of experience with illicit substance use. All participants had ongoing substance use and psychiatric comorbidities such as ADHD, anxiety, mood, psychotic and eating disorders. Interviews were transcribed verbatim. Thematic content analysis was conducted both manually and using qualitative data analysis software. RESULTS: Participants reported social benefits and positive changes in self-perception and identity. In particular, depot buprenorphine contributed to a realization that it was possible to make life changes and engage in activities not related to substance use. Another positive aspect that emerged from the interviews was a noticeable relief from perceived pressure to divert OAT medication, while some expressed the lack of income from diverted oral/sublingual OAT medication as a negative, but still acceptable, consequence of the depot buprenorphine. Many participants considered that the information provided prior to starting depot buprenorphine was insufficient. Also, not all patients found depot buprenorphine suitable, and those who experienced coercion exhibited particularly negative attitudes towards the medication. CONCLUSIONS: OAT patients with ongoing substance use and multiple psychiatric comorbidities reported clear benefits of depot buprenorphine, including changes in self-perception which has been theorized to play an important role in recovery. Clinicians should consider the specific information needs of this population and the extensive diversion of traditional OAT medications in this population to improve the treatment experience and outcomes. Overall, depot buprenorphine is a valuable treatment option for a population in need of harm reduction and may also contribute to psychological changes that may facilitate recovery in those with the greatest need.

Network Analysis of Medical Claims Data Suggests Network-Based, Regional Targeting and Intervention Delivery Strategies to Increase Access to Office Based Opioid Treatment (OBOT) for Opioid Use Disorder (OUD).

Opioid overdose and Opioid Use Disorder (OUD) statistics underscore an urgent need to significantly expand access to evidence-based OUD treatment. Office Based Opioid Treatment (OBOT) has proven effective for treating OUD. However, limited access to these treatments persists. Recognizing the need for significant investment in clinical, behavioral, and translational research, the Indiana State Department of Health and Indiana University embarked on a research initiative supported by the "Responding to the Addictions Crisis" Grand Challenge Program. This brief presents recommendations based on existing research and our own analyses of medical claims data in Indiana, where opioid misuse is high and treatment access is limited. The recommendations cover target providers, intervention focus, priority regions, and delivery methods.

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.

Tools to implement measurement-based care (MBC) in the treatment of opioid use disorder (OUD): toward a consensus.

BACKGROUND: The prevalence and associated overdose death rates from opioid use disorder (OUD) have dramatically increased in the last decade. Despite more available treatments than 20 years ago, treatment access and high discontinuation rates are challenges, as are personalized medication dosing and making timely treatment changes when treatments fail. In other fields such as depression, brief measures to address these tasks combined with an action plan-so-called measurement-based care (MBC)-have been associated with better outcomes. This workgroup aimed to determine whether brief measures can be identified for using MBC for optimizing dosing or informing treatment decisions in OUD. METHODS: The National Institute on Drug Abuse Center for the Clinical Trials Network (NIDA CCTN) in 2022 convened a small workgroup to develop consensus about clinically usable measures to improve the quality of treatment delivery with MBC methods for OUD. Two clinical tasks were addressed: (1) to identify the optimal dose of medications for OUD for each patient and (2) to estimate the effectiveness of a treatment for a particular patient once implemented, in a more granular fashion than the binary categories of early or sustained remission or no remission found in The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). DISCUSSION: Five parameters were recommended to personalize medication dose adjustment: withdrawal symptoms, opioid use, magnitude (severity and duration) of the subjective effects when opioids are used, craving, and side effects. A brief rating of each OUD-specific parameter to adjust dosing and a global assessment or verbal question for side-effects was viewed as sufficient. Whether these ratings produce better outcomes (e.g., treatment engagement and retention) in practice deserves study. There was consensus that core signs and symptoms of OUD based on some of the 5 DSM-5 domains (e.g., craving, withdrawal) should be the basis for assessing treatment outcome. No existing brief measure was found to meet all the consensus recommendations. Next steps would be to select, adapt or develop de novo items/brief scales to inform clinical decision-making about dose and treatment effectiveness. Psychometric testing, assessment of acceptability and whether the use of such scales produces better symptom control, quality of life (QoL), daily function or better prognosis as compared to treatment as usual deserves investigation.

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.

Pharmacotherapy for opioid use disorder in pregnancy.

PURPOSE OF REVIEW: Opioid use disorder (OUD) in pregnancy has significantly increased in the last decade, impacting 8.2 per 1000 deliveries. OUD carries significant risk of morbidity and mortality for both the birthing person and neonate, but outcomes for both are improved with opioid agonist treatment (OAT). Here, we describe the recommended forms of OAT in pregnancy, updates to the literature, and alternate OAT strategies, and share practical peripartum considerations for patients on OAT. RECENT FINDINGS: Recent studies comparing buprenorphine and methadone have reaffirmed previous findings that buprenorphine is associated with superior outcomes for the neonate, without clear differences in morbidity or mortality for the birthing person. Optimal initiation and dosing of OAT remains unclear, with several recent studies evaluating methods of initiation, as well as a potential role for higher and more rapid dosing in the fentanyl era. Alternative products such as buprenorphine-naloxone and extended-release buprenorphine are of significant research interest, though randomized prospective data are not yet available. SUMMARY: Buprenorphine and methadone are standard of care for treatment of OUD during pregnancy, and multiple patient factors impact the optimal choice. Insufficient data exist to recommend alternative agents as a primary strategy currently. All patients with OUD in pregnancy should be counseled regarding OAT. VIDEO: http://links.lww.com/COOG/A94.

Naltrexone Compared With Buprenorphine or Methadone in Pregnancy: A Systematic Review.

OBJECTIVE: Although naltrexone is an evidence-based medication for opioid use disorder (MOUD), few data are available with use in pregnancy. Our objective was to assess outcomes of pregnant individuals with opioid use disorder (OUD) taking naltrexone compared with those taking methadone or buprenorphine. DATA SOURCES: We undertook a systematic review using electronic database search (PubMed, CINAHL, EMBASE, PsycInfo), conference proceedings, and trial registries including ClinicalTrials.gov . METHODS OF STUDY SELECTION: We conducted an electronic search of research articles through May 2023 for randomized controlled trials, prospective cohort, and retrospective cohort studies of naltrexone (oral, implant, or extended release) compared with methadone or buprenorphine (sublingual or extended release) among pregnant individuals with OUD. After double review of all articles, we abstracted obstetric (primary outcome: gestational age at delivery), neonatal (primary outcome: neonatal abstinence syndrome [NAS]), and substance use outcomes. TABULATION, INTEGRATION, AND RESULTS: Five studies met eligibility criteria; four were retrospective cohort studies, and one was a prospective cohort study. Four studies included data on gestational age at delivery (weeks) with no difference detected between the two groups in any study (mean difference ranging -0.20, 95% CI, -1.49-1.09 to 0.8, 95% CI, -0.15 to 1.75). Three studies included data on NAS with all studies detecting a lower risk in the naltrexone group compared with methadone or buprenorphine (relative risk ranging from 0.08, 95% CI, 0.01-1.16 to 0.15, 95% CI, 0.06-0.36). Most studies (four of five) had a moderate or high potential for selection bias primarily driven by small sample size and lack of controlling for confounders. CONCLUSION: Although the evidence base is limited, available data suggest that naltrexone use in pregnancy is a reasonable MOUD option with reassuring perinatal outcomes. To enhance confidence in this conclusion and to assess substance use outcomes, further comparative studies of pregnant people with OUD taking naltrexone and other MOUD types are needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, 42017074249.

Pharmacokinetic-pharmacodynamic analysis of drug liking blockade by buprenorphine subcutaneous depot (CAM2038) in participants with opioid use disorder.

Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (Imax) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (Emax) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations of buprenorphine plasma concentration and drug liking Emax VAS score after hydromorphone 18 mg administration in 47 non-treatment-seeking adults with moderate to severe OUD in a phase 2 study. Analysis used non-|linear mixed-effects modeling (NONMEM®). The final Imax model adequately described the PK/PD relationship between buprenorphine plasma concentration and drug liking Emax VAS score. Simulations showed drug liking was effectively blocked at low buprenorphine plasma concentrations (0.4 ng/mL) where the upper 95% confidence interval of the drug liking Emax VAS score was below the pre-defined 11-point complete blockade threshold. The buprenorphine plasma concentration required to achieve 90% of the maximal effect (IC90) of drug liking was 0.675 ng/mL. Interindividual variability in responses to buprenorphine was observed; some participants experienced fluctuating responses, and a few did not achieve drug liking blockade even with higher buprenorphine plasma concentrations. This affirms the need to individualize treatment and titrate doses for optimal treatment outcomes. PK/PD models were also developed for desire to use VAS and Clinical Opiate Withdrawal Scale (COWS) scores, with results aligned to those for drug liking.

Implementation of an education session on buprenorphine induction in the emergency department, a resident-led initiative.

INTRODUCTION: Many physicians including emergency medicine physicians report insufficient training and education on prescribing buprenorphine for opioid use disorder. As emergency departments implement buprenorphine induction protocols, educational sessions can provide physicians with further familiarity with the treatment of opioid use disorder. This quality improvement project aimed to address the barrier of physician education in the implementation of buprenorphine initiation in the emergency department and presents a model for resident-led education sessions of emergency medicine physicians. METHODS: The project was a resident-led educational quality improvement project on educating members of the Department of Emergency Medicine on buprenorphine induction. The thirty-minute educational session included a pre-test survey, lecture, practice case workshop, questions, post-test survey, and a discussion. The survey questions were designed for physicians including residents and faculty, but medical students were invited to complete the session. RESULTS: Physicians including faculty and resident physicians responded positively to the educational survey, with an increase from 42.5 to 100% responding that they understood the risks and benefits of prescribing buprenorphine in the emergency department pre and post-survey respectively. Based on post-survey results, 88.5% of physicians responded that they planned to prescribe buprenorphine in the emergency department for patients meeting clinical criteria after completing the educational session. CONCLUSION: The results suggest that a resident-led training session can encourage peer involvement in buprenorphine induction to treat opioid use disorder in the emergency department.

A Systematic Review of State Office-Based Buprenorphine Treatment Laws Effective During 2022: Counseling, Dosage, and Visit Frequency Requirements.

BACKGROUND: Buprenorphine is among the most effective treatments for opioid use disorder. Even though the federal government recently eliminated the waiver requirement and patient limits applicable to office-based buprenorphine treatment (OBBT), among other settings, some states may still have policies imposing requirements on OBBT providers not required by federal law. METHODS: We collected statutes and regulations from 50 US states and the District of Columbia (ie, 51 jurisdictions) between August 11 and November 30, 2022 using the Nexis Uni legal database and search terms related to OBBT counseling, dosage, and/or frequency of visits. We then used template analysis, a mixed deductive-inductive qualitative method, to analyze legal content. RESULTS: Ten jurisdictions (20%) in 2022 had an OBBT counseling, dosage, and/or visit frequency requirement. Four jurisdictions had at least one law in each OBBT policy category examined. One-fifth of jurisdictions have OBBT policies not required under federal law. Five of these jurisdictions are among those with the highest overdose death rates per capita, according to publicly available data from 2021. Some OBBT requirements could potentially limit clinician interest in offering buprenorphine treatment or result in inadequate care (eg, if dosage limitations are too low.). CONCLUSIONS: Even though a federal waiver is no longer required for OBBT, our results suggests that at least some jurisdictions have other OBBT requirements, such as counseling, dosage, and/or frequency requirements. Given the severity of the ongoing opioid overdose crisis, policymakers should carefully consider the extent to which OBBT requirements are evidence based.

The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies.

Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD. This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.

Comparative Analysis of Instrumental Variables on the Assignment of Buprenorphine/Naloxone or Methadone for the Treatment of Opioid Use Disorder.

BACKGROUND: Instrumental variable (IV) analysis provides an alternative set of identification assumptions in the presence of uncontrolled confounding when attempting to estimate causal effects. Our objective was to evaluate the suitability of measures of prescriber preference and calendar time as potential IVs to evaluate the comparative effectiveness of buprenorphine/naloxone versus methadone for treatment of opioid use disorder (OUD). METHODS: Using linked population-level health administrative data, we constructed five IVs: prescribing preference at the individual, facility, and region levels (continuous and categorical variables), calendar time, and a binary prescriber's preference IV in analyzing the treatment assignment-treatment discontinuation association using both incident-user and prevalent-new-user designs. Using published guidelines, we assessed and compared each IV according to the four assumptions for IVs, employing both empirical assessment and content expertise. We evaluated the robustness of results using sensitivity analyses. RESULTS: The study sample included 35,904 incident users (43.3% on buprenorphine/naloxone) initiated on opioid agonist treatment by 1585 prescribers during the study period. While all candidate IVs were strong (A1) according to conventional criteria, by expert opinion, we found no evidence against assumptions of exclusion (A2), independence (A3), monotonicity (A4a), and homogeneity (A4b) for prescribing preference-based IV. Some criteria were violated for the calendar time-based IV. We determined that preference in provider-level prescribing, measured on a continuous scale, was the most suitable IV for comparative effectiveness of buprenorphine/naloxone and methadone for the treatment of OUD. CONCLUSIONS: Our results suggest that prescriber's preference measures are suitable IVs in comparative effectiveness studies of treatment for OUD.

Activity space during treatment with medication for opioid use disorder: Relationships with personality, mood, and drug use.

INTRODUCTION: Activity space in people with substance use disorders (SUDs) has been assessed for theoretical reasons and for detection/prevention of relapse. In this observational study, we relate passively obtained activity space measures to mental states and behaviors relevant to the success of treatment for opioid use disorder. Our long-term goal is to use such data to assess risk in real time and to recognize when SUD patients might benefit from a just-in-time intervention. METHODS: We used GPS data from 238 urban residents in the first 16 weeks of stabilization on medication for opioid use disorder to test preregistered hypotheses about activity space (distance traveled, number of locations, time spent moving, and psychosocial-hazard levels of neighborhoods where participants spent time) in relation to certain static variables (personality, mood propensities) and time-varying treatment-relevant behaviors such as craving and use of opioids and cocaine. RESULTS: The most consistent findings were that 1) mobility decreased over the course of the study; 2) neuroticism was associated with overall lower mobility; 3) trait-like positive mood (averaged from momentary ratings) was associated with higher mobility; 4) participants who used cocaine more frequently had lower mobility; 5) early in treatment, participants spent less time moving (i.e., were more sedentary) on days when they were craving. Some of these findings were in the expected direction (i.e., the ones involving neuroticism and positive mood), and some were opposite to the expected direction (i.e., we expected cocaine use to be associated with higher mobility); others (e.g., changes in mobility over time or in relation to craving) involved nondirectional hypotheses. CONCLUSIONS: Real-time information that patients actively provide is valuable for assessing their current state, but providing this information can be burdensome. The current results indicate that certain static or passively obtained data (personality variables and GPS-derived mobility information) are relevant to time-varying, treatment-relevant mental states and drug-related behavior, and therefore might be useful when incorporated into algorithms for detecting need for intervention in real time. Further research should assess how population-specific these relationships are, and how these passive measures can best be combined with low temporal-density, actively-provided data to obtain valid, reliable assessments with minimal burden.

Dispensing Methadone at Hospital Discharge: One Hospital's Approach to Implementing the "72-hour Rule" Change.

OBJECTIVES: Methadone for opioid use disorder treatment in ambulatory settings is restricted to federally licensed opioid treatment programs (OTPs) in the United States. However, these restrictions do not apply during hospitalization. A recent change to the rule governing methadone in non-OTP settings created an opportunity to dispense methadone at hospital discharge for up to 72 hours. METHODS: Here, we describe one hospital's approach to dispensing methadone at discharge in alignment with the "72-hour rule," including implementation challenges and considerations for other hospitals planning on adopting this practice. Implementation included creating a workflow and detailed documents outlining dispensing procedure, educating interprofessional staff, and coordinating with local OTPs. RESULTS: Our experiences highlight the importance of pharmacy champions to support implementation and interdisciplinary staff education, the need to consider electronic health record capabilities, and the importance of having policies and practices that support appropriate interpretation of the "72-hour rule" renewal timeline. CONCLUSIONS: Exceptions to federal regulations allow greater flexibility in discharge planning for patients with opioid use disorder; however, dispensation workflow falls outside standard hospital care and may be challenging to implement.

Evaluation of Low-dose Buprenorphine Initiation With Buprenorphine Buccal Films in Hospitalized Patients: A Retrospective Cohort Study.

OBJECTIVE: Low-dose buprenorphine initiation (LDBI) strategies to transition patients from full opioid agonists to buprenorphine have previously been described using sublingual films, intravenous solution, transdermal patches, and, more recently, buccal films. The objective of this study was to describe the effectiveness of LDBI using novel titration schedules with buccal films. METHODS: This is a retrospective cohort study of hospitalized patients with opioid use disorder (OUD) or physiologic dependence to opioids who underwent LDBI with buprenorphine buccal films at NYU Langone Health. Two LDBI protocols were evaluated, including a short titration schedule over 4 days and a long schedule over 7 days. The primary outcomes of interest included LDBI completion rates and incidence of opioid withdrawal. RESULTS: Forty-two patients underwent 46 LDBIs at NYU Langone Health between October 2020 and April 2022. The cohort comprised patients with OUD (57%), chronic pain with OUD (33%), and chronic pain without OUD (10%). Indications for LDBI most commonly included co-occurring pain precluding discontinuation of full opioid agonists (72%), prior history of precipitated withdrawal (30%), and methadone use (23%). The overall completion rate of LDBI was 78%. Withdrawal was encountered in 33% of patients; however, only 2 patients required LDBI discontinuation as a result. On multivariate analysis, a diagnosis of OUD was independently associated with withdrawal during LDBI. CONCLUSIONS: Buprenorphine buccal films can successfully be used off-label to facilitate LDBI in the hospital setting. We present 4- and 7-day titration protocols, which were well-tolerated, and provide practical considerations for use.

Low-dose Induction of Buprenorphine in Pregnancy: A Case Series.

BACKGROUND: Because of a risk of precipitated withdrawal occurring from buprenorphine induction in people who use fentanyl, low-dose inductions are becoming increasingly common. However, little evidence exists on the use of this method in pregnant people. METHODS: We conducted a case series of all pregnant people treated for opioid use disorder with low-dose buprenorphine induction at the University of Maryland Medical Center between January 1, 2021, and August 22, 2022. Primary outcome was completion of induction regimen. Secondary outcomes were self-report of withdrawal, continuation of buprenorphine until delivery, and return to or continuation of illicit opioid use. RESULTS: Six pregnant people were prescribed a total of 10 buprenorphine inductions. Five of the 6 pregnant people (83.3%) completed at least 1 induction, none of whom experienced precipitated withdrawal. Two of 6 (33.3%) continued buprenorphine until the time of delivery, and 1 of 6 (16.7%) abstained from illicit opioid use. CONCLUSIONS: The low-dose buprenorphine induction regimen described was successful in 5 of 6 pregnant individuals. Further research, particularly regarding continuation rates, is needed.

Negative Urgency Linked to Craving and Substance Use Among Adults on Buprenorphine or Methadone.

Despite the effectiveness of medication-assisted treatment (MAT), adults receiving MAT experience opioid cravings and engage in non-opioid illicit substance use that increases the risk of relapse and overdose. The current study examines whether negative urgency, defined as the tendency to act impulsively in response to intense negative emotion, is a risk factor for opioid cravings and non-opioid illicit substance use. Fifty-eight adults (predominately White cis-gender females) receiving MAT (with buprenorphine or methadone) were recruited from online substance use forums and asked to complete self-report questionnaires on negative urgency (UPPS-P Impulsive Behavior Scale), past 3-month opioid cravings (ASSIST-Alcohol, Smoking, and Substance Involvement Screening Test), and non-opioid illicit substance use (e.g., amphetamines, cocaine, benzodiazepines). Results revealed that negative urgency was associated with past 3-month opioid cravings, as well as past month illicit stimulant use (not benzodiazepine use). These results may indicate that individuals high in negative urgency would benefit from receiving extra intervention during MAT.