Opioid Coprescription Through Risk Mitigation Guidance and Opioid Agonist Treatment Receipt.

Importance: At the onset of the COVID-19 pandemic, the government of British Columbia, Canada, released clinical guidance to support physicians and nurse practitioners in prescribing pharmaceutical alternatives to the toxic drug supply. These alternatives included opioids and other medications under the risk mitigation guidance (RMG), a limited form of prescribed safer supply, designed to reduce the risk of SARS-CoV-2 infection and harms associated with illicit drug use. Many clinicians chose to coprescribe opioid medications under RMG alongside opioid agonist treatment (OAT). Objective: To examine whether prescription of hydromorphone tablets or sustained-release oral morphine (opioid RMG) and OAT coprescription compared with OAT alone is associated with subsequent OAT receipt. Design, Setting, and Participants: This population-based, retrospective cohort study was conducted from March 27, 2020, to August 31, 2021, included individuals from 10 linked health administrative databases from British Columbia, Canada. Individuals who were receiving OAT at opioid RMG initiation and individuals who were receiving OAT and eligible but unexposed to opioid RMG were propensity score matched at opioid RMG initiation on sociodemographic and clinical variables. Data were analyzed between January 2023 and February 2024. Exposure: Opioid RMG receipt (≥4 days, 1-3 days, or 0 days of opioid RMG dispensed) in a given week. Main Outcome and Measures: The main outcome was OAT receipt, defined as at least 1 dispensed dose of OAT in the subsequent week. A marginal structural modeling approach was used to control for potential time-varying confounding. Results: A total of 4636 individuals (2955 [64%] male; median age, 38 [31-47] years after matching) were receiving OAT at the time of first opioid RMG dispensation (2281 receiving ongoing OAT and 2352 initiating RMG and OAT concurrently). Opioid RMG receipt of 1 to 3 days in a given week increased the probability of OAT receipt by 27% in the subsequent week (adjusted risk ratio, 1.27; 95% CI, 1.25-1.30), whereas receipt of opioid RMG for 4 days or more resulted in a 46% increase in the probability of OAT receipt in the subsequent week (adjusted risk ratio, 1.46; 95% CI, 1.43-1.49) compared with those not receiving opioid RMG. The biological gradient was robust to different exposure classifications, and the association was stronger among those initiating opioid RMG and OAT concurrently. Conclusions and Relevance: This cohort study, which acknowledged the intermittent use of both medications, demonstrated that individuals who were coprescribed opioid RMG had higher adjusted probability of continued OAT receipt or reengagement compared with those not receiving opioid RMG.

Prescribing practices in opioid agonist treatment and changes in compliance to clinical dosing guidelines in British Columbia, Canada.

BACKGROUND AND AIM: In British Columbia, Canada, clinical guidelines for the treatment of opioid use disorders (OUD) were updated in 2017, during a period in which the potency and composition of the illicit drug supply changed rapidly. We aimed to describe changes in opioid agonist treatment (OAT) prescribing practices at the population level in a setting in which fentanyl and its analogs have become the primary illicit opioid of use. DESIGN, SETTING AND PARTICIPANTS: This was a population-based retrospective cohort study using three linked health administrative databases in British Columbia (BC), Canada. All individuals with at least one OAT dispensation in BC between 1 January 2014 and 31 August 2021 took part. MEASUREMENTS: To assess changes in OAT prescribing practices over time, we calculated initiation doses, dose titration intervals, maintenance doses and take-home dosing intervals stratified by medication [methadone, buprenorphine-naloxone and slow-release oral morphine (SROM)] according to recommended guidelines. FINDINGS: A total of 265 410 OAT episodes (57.5% on methadone, 34.5% on buprenorphine-naloxone and 8.0% on SROM) were initiated during the study period. Compared with the guideline recommendation, observed initiation doses were higher among all medications from 2014 (2017 for SROM) to 2021 (buprenorphine-naloxone: 14-29%; methadone: 53-66%; SROM: 26-55%). Titration intervals were shorter for all medications, consistent with guidelines for buprenorphine-naloxone (26-49%), but shorter than recommended for methadone or SROM (28-51% and 12-41%, respectively). Higher maintenance dosing was observed for methadone (68-78%) and SROM (3-21%). Take-home allowances extending beyond the recommended guideline length increased across medications (buprenorphine-naloxone: 18-35%; methadone: 50-64%; SROM: 34-39%). Changes in prescribing patterns were similar for first-time OAT initiators. CONCLUSION: In British Columbia, Canada, from 2014 to 2021, prescribers of opioid agonist treatment (OAT) appeared to initiate both new and experienced OAT clients at higher doses than guideline recommendations, titrate them more rapidly and maintain clients at higher doses. Take-home dose allowances also gradually increased.

What is the ideal time to begin tapering opioid agonist treatment? A protocol for a retrospective population-based comparative effectiveness study in British Columbia, Canada.

INTRODUCTION: Opioid agonist treatment (OAT) tapering involves a gradual reduction in daily medication dose to ultimately reach a state of opioid abstinence. Due to the high risk of relapse and overdose after tapering, this practice is not recommended by clinical guidelines, however, clients may still request to taper off medication. The ideal time to initiate an OAT taper is not known. However, ethically, taper plans should acknowledge clients' preferences and autonomy but apply principles of shared informed decision-making regarding safety and efficacy. Linked population-level data capturing real-world tapering practices provide a valuable opportunity to improve existing evidence on when to contemplate starting an OAT taper. Our objective is to determine the comparative effectiveness of alternative times from OAT initiation at which a taper can be initiated, with a primary outcome of taper completion, as observed in clinical practice in British Columbia (BC), Canada. METHODS AND ANALYSIS: We propose a population-level retrospective observational study with a linkage of eight provincial health administrative databases in BC, Canada (01 January 2010 to 17 March 2020). Our primary outcomes include taper completion and all-cause mortality during treatment. We propose a 'per-protocol' target trial to compare different durations to taper initiation on the likelihood of taper completion. A range of sensitivity analyses will be used to assess the heterogeneity and robustness of the results including assessment of effectiveness and safety. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.

Influence of physician networks on the implementation of pharmaceutical alternatives to a toxic drug supply in British Columbia.

BACKGROUND: Characterizing the diffusion of adopted changes in policy and clinical practice can inform enhanced implementation strategies to ensure prompt uptake in public health emergencies and other rapidly evolving disease areas. A novel guidance document was introduced at the onset of the COVID-19 pandemic in British Columbia (BC), Canada, which supported clinicians to prescribe opioids, stimulants, and benzodiazepines. We aimed to determine the extent to which uptake and discontinuation of an initial attempt at a prescribed safer supply (PSS) program were influenced through networks of prescribers. METHODS: We executed a retrospective population-based study using linked health administrative data that captured all clinicians who prescribed to at least one client with a substance use disorder from March 27, 2020, to August 31, 2021. Our main exposure was the prescribing patterns of an individuals' peers, defined as the proportion of a prescribers' professional network (based on shared clients), which had previously prescribed PSS, updated monthly. The primary outcome measured whether a clinician had prescribed their initial PSS prescription during a given calendar month. The secondary outcome was the discontinuation of PSS prescribing, defined as an absence for PSS prescriptions for at least 3 months. We estimated logistic regression models using generalized estimated equations on monthly repeated measurements to determine and characterize the extent to which peer networks influenced the initiation and discontinuation of PSS prescribing, controlling for network, clinician, and caseload characteristics. Innovators were defined as individuals initiating PSS prior to May 2020, and early adopters were individuals initiating PSS after. RESULTS: Among 14,137 prescribers treating clients with substance use disorder, there were 228 innovators of prescribed safer supply and 1062 early adopters through the end of study follow-up, but 653 (50.6%) were no longer prescribing by August 2021. Prescribers with over 20% of peers whom had adopted PSS had a nearly fourfold higher adjusted odds of PSS prescribing themselves (aOR: 3.79, 95% CI: (3.15, 4.56)), compared to those with no connected safer supply prescribers. CONCLUSIONS: The uptake of PSS in BC was highly dependent on the behavior of prescribers' peer networks. Future implementation strategies to support PSS or other policies would benefit from leveraging networks of prescribers.

Effect of Risk Mitigation Guidance opioid and stimulant dispensations on mortality and acute care visits during dual public health emergencies: retrospective cohort study.

OBJECTIVE: To determine the effect of opioid and stimulant Risk Mitigation Guidance (RMG) dispensations on mortality and acute care visits during the dual public health emergencies of overdose and covid-19. DESIGN: Population based retrospective cohort study. SETTING: British Columbia, Canada. PARTICIPANTS: 5882 people with opioid or stimulant use disorder who received RMG prescriptions for opioids (n=5356) and/or stimulants (n=1061) (535 received both) from 27 March 2020 to 31 August 2021. MAIN OUTCOME MEASURES: All cause and overdose specific mortality and acute care visits in the week after RMG opioid or stimulant dispensation. RMG recipients were matched 1:1 with controls through use of high dimensional propensity score matching. Marginal structural models, executed on weekly time steps, were used to measure the effect of dispensations on outcomes. RESULTS: RMG opioid dispensations of one day or more were associated with reduced all cause mortality (adjusted hazard ratio 0.39, 95% confidence interval 0.25 to 0.60) and overdose related mortality (0.45, 0.27 to 0.75) in the subsequent week. Dispensations of RMG stimulants (≥1 days) were not significantly associated with reduced all cause mortality (adjusted hazard ratio 0.50, 0.20 to 1.23) or overdose related mortality (0.53, 0.18 to 1.56). The protective effect of RMG opioid dispensations increased with the number of days the medications were dispensed in a given week. People who received four or more days of RMG opioid dispensations had reduced all cause mortality (adjusted hazard ratio 0.09, 0.04 to 0.21) and overdose related mortality (0.11, 0.04 to 0.32) compared with the control group. Opioid RMG dispensations did not significantly modify the odds of all cause or overdose related acute care visits. Dispensations of RMG stimulants were associated with a significant decrease in the odds of acute care visits for any cause but did not affect the odds of overdose related acute care visits. CONCLUSIONS: RMG opioid dispensations were associated with reduced overdose related and all cause mortality among a sample of people with opioid use disorder. Pharmaceutical alternatives to the illegal drug supply are promising interventions to reduce mortality in people with opioid use disorder.

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.

Opioid agonist therapy and mortality among First Nations and other residents with concurrent alcohol use disorder in British Columbia, Canada: A population-based cohort study.

BACKGROUND: Despite the prevalence of alcohol use among people with opioid use disorder (PWOUD) engaged in opioid agonist therapy (OAT), clinical care guidance for concurrent alcohol use disorder (AUD) and OUD is scarce. We assessed the prevalence and risk of mortality for concurrent AUD among PWOUD who accessed OAT in British Columbia (BC). METHODS: Data were obtained from six linked population-level health administrative datasets to identify PWOUD from January 1996 to March 2020. All-cause age and sex standardized mortality ratios (SMR) were calculated to determine the mortality risk by OAT status (on vs. discontinued), stratified by First Nations and other residents with concurrent AUD and OUD. Adjusted risk ratios compared the relative risk of mortality by AUD status (AUD detected vs. not) among First Nations and other residents. RESULTS: We identified 62,110 PWOUD who received OAT, including 6305 (10.2%) First Nations. OAT substantially lowered the SMR among First Nations (SMR=6.6, 95% CI: 5.4-8.1) and other residents (SMR=6.6; 95% CI: 6.2-7.0) with concurrent AUD and OUD, compared to those who discontinued (SMR=22.7, 95% CI: 20.4-25.1, SMR=17.5, 95% CI: 16.8-18.2 respectively). The risk of mortality was 1.9 (95% CI: 1.6-2.2) times higher for First Nations and 2.0 (95% CI: 1.8-2.2) times higher for other residents with concurrent OUD and AUD compared to those without an indication of AUD. CONCLUSIONS: The protective effect of OAT remained despite the presence of a concurrent AUD among both First Nations and other residents with OUD. Findings have implications for clinical care management of concurrent disorders.

Comparative effectiveness of urine drug screening strategies alongside opioid agonist treatment in British Columbia, Canada: a population-based observational study protocol.

INTRODUCTION: Urine drug tests (UDTs) are commonly used for monitoring opioid agonist treatment (OAT) responses, supporting the clinical decision for take-home doses and monitoring potential diversion. However, there is limited evidence supporting the utility of mandatory UDTs-particularly the impact of UDT frequency on OAT retention. Real-world evidence can inform patient-centred approaches to OAT and improve current strategies to address the ongoing opioid public health emergency. Our objective is to determine the safety and comparative effectiveness of alternative UDT monitoring strategies as observed in clinical practice among OAT clients in British Columbia, Canada from 2010 to 2020. METHODS AND ANALYSIS: We propose a population-level retrospective cohort study of all individuals 18 years of age or older who initiated OAT from 1 January 2010 to 17 March 2020. The study will draw on eight linked health administrative databases from British Columbia. Our primary outcomes include OAT discontinuation and all-cause mortality. To determine the effectiveness of the intervention, we will emulate a 'per-protocol' target trial using a clone censoring approach to compare fixed and dynamic UDT monitoring strategies. A range of sensitivity analyses will be executed to determine the robustness of our results. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.

Incremental expenditures attributable to daily dispensation and witnessed ingestion for opioid agonist treatment in British Columbia: 2014-20.

BACKGROUND AND AIM: While daily witnessed opioid agonist treatment (OAT) ingestion is common in British Columbia (BC), Canada, and elsewhere, sparse evidence supports this resource-intensive practice. Many settings across North America relaxed restrictions for take-home dosing during the COVID-19 pandemic and have reported consistent or improved patient outcomes. This study measured excess expenditures attributed to daily witnessed pharmacy dispensing compared with weekly or biweekly dispensation schedules. DESIGN, SETTING AND PARTICIPANTS: This study was a population-level retrospective analysis. We included all methadone, buprenorphine/naloxone and slow-release oral morphine dispensations in BC from 1 January 2014 to 30 December 2020. A total of 24 357 107 OAT dispensations among 51 195 unique individuals with 122 793 person-years of follow-up were included during the study period. MEASUREMENTS: Total expenditures for each person-week of OAT with an estimated expenditure under two scenarios are as follows: (1) a weekly dispensation scenario and (2) a biweekly dispensation scenario. FINDINGS: We estimated excess expenditures attributable to current dispensing practices of between $38 million (2014) and $47.4 million (2018) compared with a hypothetical weekly dispensing schedule, and $43.9 million (2014) to $54.9 million (2018) compared with biweekly dispensing. The majority of these expenditures (58-64%) were attributed to pharmacy dispensing fees ($23 million in 2014 to $30 million in 2018 compared with weekly dispensing; $26.6 million in 2014 to $34.7 million in 2018 compared with biweekly dispensing). CONCLUSION: Daily witnessed opioid agonist treatment ingestion results in more than $30 million in excess expenditures annually in the province of British Columbia, Canada compared with the costs of weekly or biweekly dispensation schedules.

Validation and endorsement of health system performance measures for opioid use disorder in British Columbia, Canada: A Delphi panel study.

Background: Limited data exists on the performance of the healthcare system in opioid use disorder (OUD). We evaluated the face validity and potential risks of a set of health system performance measures for OUD collaboratively with clinicians, policymakers and people with lived experience of opioid use (PWLE) in the interest of establishing an endorsed set of measures for public reporting. Methods: Through a two-stage Delphi-panel approach, a panel of clinical and policy experts validated and considered 102 previously constructed OUD performance measures for endorsement using information on measurement construction, sensitivity analyses, quality of evidence, predictive validity, and feedback from local PWLE. We collected quantitative and qualitative survey responses from 49 clinicians and policymakers, and 11 PWLE. We conducted inductive and deductive thematic analysis to present qualitative responses. Results: A total of 37 measures of 102 were strongly endorsed (9/13 cascade of care, 2/27 clinical guideline compliance, 17/44 healthcare integration, and 9/18 healthcare utilization measures). Thematic analysis of responses revealed several themes regarding measurement validity, unintended consequences, and key contextual considerations. Overall, measures related to the cascade of care (excluding opioid agonist treatment dose tapering) received strong endorsements. PWLE highlighted barriers to accessing treatment, undignified aspects of treatment, and lack of a full continuum of care as their concerns. Conclusion: We defined 37 endorsed health system performance measures for OUD and presented a range of perspectives on their validity and use. These measures provide critical considerations for health system improvement in the care of people with OUD.

Assessing the determinants of completing OAT induction and long-term retention: A population-based study in British Columbia, Canada.

BACKGROUND: Pharmacological treatments for opioid use disorder are essential, life-saving medications, yet successful induction of them and long-term retention on them is limited in many settings. Induction into opioid agonist treatment (OAT) features the highest risk of mortality throughout the treatment course, and greatest risk of discontinuation. We aimed to identify determinants of completing OAT induction and, among those completing induction, time to OAT discontinuation in British Columbia (BC), Canada. METHODS: We conducted a retrospective study using linked population-level health administrative databases to capture all individuals in BC receiving at least one OAT dispensation from January 1, 2008, to September 30, 2018. We constructed covariates capturing client demographics, clinical history, and characteristics of the treatment episode and the primary prescribing physician. We estimated a two-part model to identify determinants of the probability of completing induction using a generalized linear mixed model with logit link and the time to OAT discontinuation among those completing induction using a Cox proportional hazards frailty model. RESULTS: We observed 220,474 OAT episodes (73.9% initiated with methadone, 24.7% with buprenorphine, and 1.4% with slow-release oral morphine) among 45,608 individuals over the study period. Less than 60% of all OAT episodes completed induction (59.0% for methadone episodes, 56.7% for buprenorphine/naloxone, 41.0% for slow-release oral morphine) and half of all episodes that completed induction reached the minimum effective dosage (51.0% for methadone episodes [60 mg/day], 48.2% for buprenorphine/naloxone [12 mg/day], 59.4% for slow-release oral morphine [240 mg/day]). In multiple regression analysis, the adjusted odds of completing induction with buprenorphine improved over time, exceeding that of methadone in 2018: 1.46 (1.40, 1.51). For those who completed induction, buprenorphine use was associated with shorter times to discontinuation throughout the study period, but the estimated rate of discontinuation decreased over time (adjusted hazard ratio, vs. methadone in 2008: 2.50 (2.35, 2.66); in 2018: 1.79 (1.74, 1.85)). CONCLUSION: We found low rates of completing OAT induction and, for those who did complete it, low rates of reaching the minimum effective dose.

Human Immunodeficiency Virus transmission by HIV Risk Group and Along the HIV Care Continuum: A Contrast of 6 US Cities.

BACKGROUND: Understanding the sources of HIV transmission provides a basis for prioritizing HIV prevention resources in specific geographic regions and populations. This study estimated the number, proportion, and rate of HIV transmissions attributable to individuals along the HIV care continuum within different HIV transmission risk groups in 6 US cities. METHODS: We used a dynamic, compartmental HIV transmission model that draws on racial behavior-specific or ethnic behavior-specific and risk behavior-specific linkage to HIV care and use of HIV prevention services from local, state, and national surveillance sources. We estimated the rate and number of HIV transmissions attributable to individuals in the stage of acute undiagnosed HIV, nonacute undiagnosed HIV, HIV diagnosed but antiretroviral therapy (ART) naïve, off ART, and on ART, stratified by HIV transmission group for the 2019 calendar year. RESULTS: Individuals with undiagnosed nonacute HIV infection accounted for the highest proportion of total transmissions in every city, ranging from 36.8% (26.7%-44.9%) in New York City to 64.9% (47.0%-71.6%) in Baltimore. Individuals who had discontinued ART contributed to the second highest percentage of total infections in 4 of 6 cities. Individuals with acute HIV had the highest transmission rate per 100 person-years, ranging from 76.4 (58.9-135.9) in Miami to 160.2 (85.7-302.8) in Baltimore. CONCLUSION: These findings underline the importance of both early diagnosis and improved ART retention for ending the HIV epidemic in the United States. Differences in the sources of transmission across cities indicate that localized priority setting to effectively address diverse microepidemics at different stages of epidemic control is necessary.

Opioid agonist treatment uptake within provincial correctional facilities in British Columbia, Canada.

BACKGROUND AND AIMS: Multiple interventions and policy changes related to opioid agonist treatment (OAT) have been introduced in British Columbia, Canada to increase engagement and retention in OAT. We aimed to estimate the impact of policy changes and the announcement of the opioid overdose-related public health emergency on the use of OAT for incarcerated individuals with opioid use disorder. DESIGN: Interrupted time-series analysis. Events of interest included the expansion of buprenorphine/naloxone into provincial health-care insurance coverage in October 2015 and the public health emergency declared in April 2016. SETTING AND PARTICIPANTS: Our study included 9220 incarcerated individuals from 12 provincial corrections facilities in British Columbia, Canada for a total of 75 649 calendar months of incarceration. MEASUREMENTS: Monthly measures of OAT use during incarceration from 1 January 2013 to 30 September 2017. We estimated changes in OAT use, controlling for individual and facility-level factors, using a general estimating equation, specified with a logit link and an autoregressive correlation matrix. FINDINGS: After the provincial health insurance coverage expansion, a sharp increase in OAT use during incarceration was observed [adjusted odds ratio (aOR) = 1.16, 95% confidence interval (CI) = 1.13, 1.19]. The public health emergency coincided with an immediate but temporary increase in OAT receipt (aOR = 1.34, 95% CI = 1.22, 1.47). During the entire study period, we estimated a 10-fold increase in the adjusted odds of OAT use during incarceration (aOR = 10.10, 95% CI = 8.98, 11.37). CONCLUSION: Following an expansion of health-care insurance coverage to include buprenorphine/naloxone, receipt of opioid agonist treatment (OAT) within correctional facilities in British Columbia, Canada increased, largely driven by an increase in buprenorphine/naloxone prescriptions among individuals without recent OAT experience.

Opioid analgesic prescribing for opioid-naïve individuals prior to identification of opioid use disorder in British Columbia, Canada.

BACKGROUND AND AIMS: Prescription opioid analgesics have contributed to the development of opioid use disorder (OUD) in many individuals. We aimed to characterize non-cancer opioid prescribing for opioid-naive individuals prior to OUD identification. DESIGN: Population-based retrospective cohort study using six linked health administrative databases. SETTING: British Columbia (BC), Canada. PARTICIPANTS: People with OUD between 1 January 2001 and 30 September 2018 who initiated opioid analgesic therapy for non-cancer pain prior to OUD identification. MEASUREMENTS: Dose (morphine milligram equivalent per day), days prescribed and clinical guideline non-concordance for initial opioid prescriptions (dose ≥ 90 morphine milligram equivalent per day; ≥ 7 days prescribed; concomitant sedative prescription). We estimated the probability of non-concordant initial prescriptions by source (inpatient post-discharge, non-inpatient acute, non-acute) using logistic regression, adjusting for individual characteristics and comorbidities. FINDINGS: Among 66 372 individuals identified with OUD from 2001 to 2018, 21 331 (32.1%) received opioid analgesics prior to OUD identification. This proportion increased from 3.0% in 2001 to 41.0% in 2011, before decreasing to 34.2% in 2017. Roughly half of opioid prescriptions were attributed to non-acute care visits, peaking at 56.8% in 2007, while the proportion from inpatient visits increased from 19.7% in 2001 to 28.5% in 2017. The predicted probability of receiving non-guideline concordant prescriptions declined over time-periods across all three measures for inpatient and non-inpatient acute care, while remaining stable for non-acute care. In particular, the predicted probability of receiving ≥ 7-day prescriptions following inpatient visits decreased from 53.3% [95% confidence interval (CI) = 50.9, 55.8%] in 2001-06 to 37.2% (95% CI = 33.9, 40.5%) in 2013-18. CONCLUSIONS: Among the 66 372 individuals in British Columbia, Canada diagnosed with opioid use disorder between 2001 and 2018, more than 32% were earlier prescribed non-cancer opioid analgesics. The proportion who had received an opioid analgesic prescription prior to OUD identification peaked at more than 40% in 2011, before stabilizing between 2011 and 2016 and declining thereafter. Guideline concordance improved over time for high-dose and concomitant sedative prescribing.

The effect of British Columbia's Pharmacare coverage expansion for opioid agonist treatment.

Opioid agonist treatment (OAT) is the evidence-based standard of care for people with opioid use disorder. In British Columbia, Canada, only social assistance registrants received full coverage for OAT prior to the introduction of the Pharmacare Plan G coverage expansion on February 1st, 2017. We aimed to determine the effect of the coverage expansion on OAT initiation, re-initiation, and retention. Using linked population-level data, we executed a difference-in-differences analysis to compare outcomes of individuals eligible for the additional coverage and social assistance registrants already receiving the most generous coverage for OAT prior to the policy change, adjusting for individual and prescriber characteristics. We found Plan G coverage expansion significantly increased OAT retention. Specifically, coverage expansion decreased the number of OAT episode discontinuations by 12.8% (95% CI: 8.4%, 17.2%).

Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study.

OBJECTIVE: To compare the risk of mortality among people with opioid use disorder on and off opioid agonist treatment (OAT) in a setting with a high prevalence of illicitly manufactured fentanyl and other potent synthetic opioids in the illicit drug supply. DESIGN: Population based retrospective cohort study. SETTING: Individual level linkage of five health administrative datasets capturing drug dispensations, hospital admissions, physician billing records, ambulatory care reports, and deaths in British Columbia, Canada. PARTICIPANTS: 55 347 people with opioid use disorder who received OAT between 1 January 1996 and 30 September 2018. MAIN OUTCOME MEASURES: All cause and cause specific crude mortality rates (per 1000 person years) to determine absolute risk of mortality and all cause age and sex standardised mortality ratios to determine relative risk of mortality compared with the general population. Mortality risk was calculated according to treatment status (on OAT, off OAT), time since starting and stopping treatment (1, 2, 3-4, 5-12, >12 weeks), and medication type (methadone, buprenorphine/naloxone). Adjusted risk ratios compared the relative risk of mortality on and off OAT over time as fentanyl became more prevalent in the illicit drug supply. RESULTS: 7030 (12.7%) of 55 347 OAT recipients died during follow-up. The all cause standardised mortality ratio was substantially lower on OAT (4.6, 95% confidence interval 4.4 to 4.8) than off OAT (9.7, 9.5 to 10.0). In a period of increasing prevalence of fentanyl, the relative risk of mortality off OAT was 2.1 (95% confidence interval 1.8 to 2.4) times higher than on OAT before the introduction of fentanyl, increasing to 3.4 (2.8 to 4.3) at the end of the study period (65% increase in relative risk). CONCLUSIONS: Retention on OAT is associated with substantial reductions in the risk of mortality for people with opioid use disorder. The protective effect of OAT on mortality increased as fentanyl and other synthetic opioids became common in the illicit drug supply, whereas the risk of mortality remained high off OAT. As fentanyl becomes more widespread globally, these findings highlight the importance of interventions that improve retention on opioid agonist treatment and prevent recipients from stopping treatment.

Ending the Epidemic in America Will Not Happen if the Status Quo Continues: Modeled Projections for Human Immunodeficiency Virus Incidence in 6 US Cities.

We estimated 10-year (2020-2030) trajectories for human immunodeficiency virus incidence in 6 US cities. Estimated incidence will only decrease in 2 of 6 cities, with the overall population-weighted incidence decreasing 3.1% (95% credible interval [CrI], -1.0% to 8.5%) by 2025, and 4.3% (95% CrI, -2.6% to 12.7%) by 2030 across cities. Targeted, context-specific combination implementation strategies will be necessary to meet the newly established national targets.

Geographic variation in the costs of medical care for people living with HIV in British Columbia, Canada.

BACKGROUND: Regional variation in medical care costs can indicate heterogeneity in clinical practice, inequities in access, or inefficiencies in service delivery. We aimed to estimate regional variation in medical costs for people living with HIV (PLHIV), adjusting for demographics and case-mix. METHODS: We conducted a retrospective cohort study using linked health administrative databases of PLHIV, from 2010 to 2014, in British Columbia (BC), Canada. Quarterly health care costs (2018 CAD) were derived from inpatient, outpatient, prescription drugs, antiretroviral therapy (ART), and HIV diagnostics. We used a two-part model with a logit link for the probability of incurring costs, and a log link and gamma distribution for observations with positive costs. We also estimated quarterly utilization rates for hospitalization-, physician billing- and prescription drug-days. Primary variables were indicators of individuals' Health Service Delivery Area (HSDA). We adjusted cost and utilization estimates for demographic characteristics, HIV-disease progression, and comorbidities. RESULTS: Our cohort included 9577 PLHIV (median age 45.5 years, 80% male). Adjusted total quarterly costs for all 16 HSDAs were within 20% of the provincial mean, 8/16 for hospitalization costs, 16/16 for physician billing costs and 10/16 for prescription drug costs. Northern Interior and Northeast HSDAs had 38 and 44% lower quarterly non-ART prescription drug costs, and 2 and 5% higher quarterly inpatient costs, respectively. CONCLUSIONS: We observed limited variation in medical care costs and utilization among PLHIV in BC. However, lower levels of outpatient care and higher levels of inpatient care indicate possible barriers to accessing care among PLHIV in the most rural regions of the province.

Why Maximizing Quality-Adjusted Life Years, rather than Reducing HIV Incidence, Must Remain Our Objective in Addressing the HIV/AIDS Epidemic.

With efficacious behavioral, biomedical, and structural interventions available, combination implementation strategies are being implemented to combat HIV/AIDS across settings internationally. However, priority statements from national and international bodies make it unclear whether the objective should be the reduction in HIV incidence or the maximization of health, most commonly measured with quality-adjusted life years (QALYs). Building off a model-based evaluation of HIV care interventions in British Columbia, Canada, we compare the optimal sets of interventions that would be identified using HIV infections averted, and QALYs as the primary outcome in a cost-effectiveness analysis. We found an explicit focus on averting new infections undervalues the health benefits derived from antiretroviral therapy, resulting in suboptimal and potentially harmful funding recommendations.

Characterizing Human Immunodeficiency Virus Antiretroviral Therapy Interruption and Resulting Disease Progression Using Population-Level Data in British Columbia, 1996-2015.

BACKGROUND: Suboptimal retention is among the biggest challenges to realize the full benefits of combination antiretroviral therapy (ART). We aimed to describe ART interruption patterns and identify determinants of disease progression while off ART in British Columbia, Canada. METHODS: With population-level data on ART utilization and laboratory testing in British Columbia (1996-2015), we described the timing, frequency, and duration of ART interruptions (a gap of ≥90 days in ART dispensation records). A 4-state continuous-time Markov model was implemented to identify determinants of disease progression during individuals' first ART interruption episode. Disease progression was measured according to CD4-based state transitions (cells/µL: ≥500 to 200-499; 200-499 to <200; ≥500 to death; 200-499 to death; and <200 to death). RESULTS: Among individuals initiating ART, 3129 (38.6%) interrupted ART over a median 8-year follow-up (interquartile range [IQR], 4.3-13.5 years). Those interrupting ART had a median of 1 interruption (IQR, 1.0-3.0), with the first interruption occurring 12.8 (IQR, 4.0-36.1) months after ART initiation, lasting for 7.5 (IQR, 4.1-20.3) months. The proportion of individuals interrupting ART within the first year of ART initiation decreased over time; however, the absolute number of individuals interrupting ART remained high. In a multivariable analysis, age, historical plasma viral load, and ART regimen changes prior to interruption were associated with increased hazard of CD4 decline and death. CONCLUSIONS: Our results demonstrate that ART interruptions are common even in a high-resource setting with universal free access to human immunodeficiency virus care. Further efforts are needed to promote ART reengagement and may consider prioritizing individuals with poorer prognostic factors.