Implementation of pharmaceutical alternatives to a toxic drug supply in British Columbia: A mixed methods study.

BACKGROUND: North America has been in an unrelenting overdose crisis for almost a decade. British Columbia (BC), Canada declared a public health emergency due to overdoses in 2016. Risk Mitigation Guidance (RMG) for prescribing pharmaceutical opioids, stimulants and benzodiazepine alternatives to the toxic drug supply ("safer supply") was implemented in March 2020 in an attempt to reduce harms of COVID-19 and overdose deaths in BC during dual declared public health emergencies. Our objective was to describe early implementation of RMG among prescribers in BC. METHODS: We conducted a convergent mixed methods study drawing population-level linked administrative health data and qualitative interviews with 17 prescribers. The Consolidated Framework for Implementation Research (CFIR) informs our work. The study utilized seven linked databases, capturing the characteristics of prescribers for people with substance use disorder to describe the characteristics of those prescribing under the RMG using univariate summary statistics and logistic regression analysis. For the qualitative analysis, we drew on interpretative descriptive methodology to identify barriers and facilitators to implementation. RESULTS: Analysis of administrative databases demonstrated limited uptake of the intervention outside large urban centres and a highly specific profile of urban prescribers, with larger and more complex caseloads associated with RMG prescribing. Nurse practitioners were three times more likely to prescribe than general practitioners. Qualitatively, the study identified five themes related to the five CFIR domains: 1) RMG is helpful but controversial; 2) Motivations and challenges to prescribing; 3) New options and opportunities for care but not enough to 'win the arms race'; 4) Lack of implementation support and resources; 5) Limited infrastructure. CONCLUSIONS: BC's implementation of RMG was limited in scope, prescriber uptake and geographic scale up. Systemic, organizational and individual barriers and facilitators point to the importance of engaging professional regulatory colleges, implementation planning and organizational infrastructure to ensure effective implementation and adaptation to context.

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.

The effect of a methadone reformulation on opioid agonist treatment outcomes: A population-based study in British Columbia, Canada, 2013-14.

INTRODUCTION: The province of British Columbia, Canada, changed the existing oral anhydrous methadone solution to a 10-times more concentrated pre-mixed solution, Methadose®, on February 1, 2014. We aimed to assess the immediate effects of the methadone reformulation on missed doses, days off methadone, changes in medication dosing and dispensations of opioids for pain, and hospitalizations and mortality among all people receiving treatment at or near the time of the change. METHODS: We conducted a population-based retrospective cohort study including all individuals receiving at least one methadone dispensation in the 12 months prior to the study period. We executed a difference-in-differences analysis by estimating a multivariate regression model to compare outcomes in the three months before and after the reformulation (November 1, 2013 to April 30, 2014) versus a time-lagged control cohort with similar characteristics observed during an equivalent nonoverlapping interval. We used daily individual-level linked health administrative data capturing missed doses, days off methadone, changes in methadone dosing, concurrent dispensations of opioids for pain, hospitalizations, and mortality. We stratified the cohorts into three subgroups: (i) those receiving OAT for ≥12 months; (ii) those receiving OAT for <12 months; and (iii) those not receiving OAT at the start of the study period. We conducted sensitivity analyses and placebo tests to assess the robustness of our results. RESULTS: Among the 16,339 individuals receiving methadone during the study period, the reformulation was associated with more instances of methadone dose increases (34.5% [95% Confidence Interval (CI): 27.4%, 41.5%]). For those retained in treatment ≥12 months prior to the study period (n = 7449), the reformulation was associated with more instances of methadone dose increases (50.2% [39.5%, 60.8%]) and dispensations of opioids for pain (62.2% [40.8%, 83.5%]), as well as an increase in missed doses (41.9% [29.1%, 54.7%]) and days off methadone (62.6% [39.7%, 85.4%]). We found no statistically significant change in risk of hospitalization or mortality. Sensitivity analyses supported our results. CONCLUSION: Our results reinforce the need expressed by people receiving methadone for greater client involvement in the planning and implementation of regulatory changes that may impact client care, especially those patients with a relatively long treatment history.

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.

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.

Estimates of opioid use disorder prevalence from a regression-based multi-sample stratified capture-recapture analysis.

BACKGROUND: An epidemic of opioid overdose has spread across North America, with illicit drug-related overdose emerging as a leading cause of death in recent years. Estimates of opioid use disorder (OUD) prevalence at the level of the public health service delivery area are needed to project resource needs and identify priority areas for targeted intervention. Our objective is to estimate the annual prevalence of OUD in British Columbia (BC), Canada, from 2000 to 2017. METHODS: We performed a multi-sample stratified capture-recapture analysis to estimate OUD prevalence in BC. The analysis included individuals identified from 3 administrative databases for 2000-2011 and 4 databases for 2012-2017, linked at the individual level. Negative binomial regression models on the counts of individuals within these strata were used to estimate prevalence, adjusting for dependency between databases. RESULTS: OUD prevalence in BC among people aged 12 years or older was 1.00 % (N = 34,663 individuals) in 2000 and increased to 1.54 % (N = 61,080) in 2011. Between 2013 and 2017 prevalence increased from 1.57 % (95 % confidence interval: 1.56-1.58) to 1.92 % (1.89-1.95; N = 83,760; 82,492-84,855). The greatest increases in prevalence were observed among males 12-30 years old and 31-44 years old, with 43.2 % and 40.2 % increases from 2013 to 2017. CONCLUSIONS: In BC, the OUD prevalence was 1.92 % among people 12 years or older in 2017. We estimated that prevalence has nearly doubled since 2000, with the highest increases in prevalence observed among males under 45.

Non-disclosure of drug use in outpatient health care settings: Findings from a prospective cohort study in Vancouver, Canada.

BACKGROUND: Illicit drug use is associated with severe health-related harms, yet people who use drugs (PWUD) face substantial barriers to healthcare. We sought to identify factors associated with disclosure of drug use to a healthcare provider and describe differences in self-reported quality of care received based on disclosure status. METHODS: A client-reported experience questionnaire on healthcare access and quality, adapted from the World Health Organization Survey on Health and Health System Responsiveness, was administered within two ongoing prospective cohort studies of PWUD in Vancouver, Canada. Respondents not currently receiving addiction treatment were asked about experience of care and drug use disclosure to their most commonly accessed outpatient healthcare provider in the past 6 months. We used an adjusted logistic regression model to identify client characteristics associated with disclosure. RESULTS: From a total of 261 respondents (34.1% female), less than half (n = 125, 47.8%) reported disclosing drug use to their healthcare provider. Indigenous participants were less likely to disclose compared to non-Indigenous participants (adjusted OR: 0.55, 95% confidence interval: 0.30, 0.97). Disclosure was associated with lower self-reported quality of care (overall rating: disclosed 8.2 vs. did not disclose 8.8, p = 0.04). CONCLUSIONS: In a sample of PWUD accessing outpatient healthcare services, we observed low rates of drug use disclosure, particularly for Indigenous respondents, and reduced quality of care for those who disclosed. These findings highlight the need for culturally safe and non-stigmatizing care to address pervasive stereotyping in the healthcare system and improved screening for substance use disorder in outpatient healthcare services.

Socioeconomic status and environmental noise exposure in Montreal, Canada.

BACKGROUND: This study's objective was to determine whether socioeconomically deprived populations are exposed to greater levels of environmental noise. METHODS: Indicators of socioeconomic status were correlated with LAeq24h noise levels estimated with a land-use regression model at a small geographic scale. RESULTS: We found that noise exposure was associated with all socioeconomic indicators, with the strongest correlations found for median household income, proportion of people who spend over 30% of their income on housing, proportion of people below the low income boundary and with a social deprivation index combining several socio-economic variables. CONCLUSION: Our results were inconsistent with a number of studies performed elsewhere, indicating that locally conducted studies are imperative to assessing whether this double burden of noise exposure and low socioeconomic status exists in other contexts. The primary implication of our study is that noise exposure represents an environmental injustice in Montreal, which is an issue that merits both investigation and concern.

Discrimination of grassland species and their classification in botanical families by laboratory scale NIR hyperspectral imaging: preliminary results.

The objective of this study was to discriminate by a NIR line scan hyperspectral imaging, taxonomic plant families comprised of different grassland species. Plants were collected from semi-natural meadows of the National Apuseni Park, Apuseni Mountains, Gârda area (Romania) according to botanical families. Chemometric tools such as PLS-DA were used to discriminate distinct grassland species, and assign the different species to botanical families. Species within the Poacea family and other Botanical families could be distinguished (R(2)=0.91 and 0.90, respectively) with greater accuracy than those species in the Fabacea family (R(2)=0.60). A correct classification rate of 99% was obtained in the assignment of the various species to the proper family. Moreover a complete study based on wavelength selection has been performed in order to identify the chemical compound related to each botanical family and therefore to the possible toxicity of the plant. This work could be considered as a first step for the development of a complete procedure for the detection and quantification of possible toxic species in semi-natural meadows used by grazing animals.