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Comparative effectiveness of maintenance doses of opioid agonist treatment among individuals with opioid use disorder: a target trial emulation protocol using a population-based observational study

Por: Zanette · M. · Min · J. E. · Homayra · F. · Bach · P. · Socias · M. E. · Bruneau · J. · Korthuis · P. T. · Karim · E. · Seaman · S. · Bozinoff · N. · Kennedy · M. C. · Nosyk · B.
Introduction

Opioid agonist treatment (OAT) prescribing patterns have shifted in recent years in British Columbia (BC), Canada due to the increasingly toxic unregulated drug supply. Experimental evidence to support guidelines on the effectiveness of maintaining clients at different maintenance dosage levels is incomplete and outdated for the fentanyl era. Our objective is to assess the risk of treatment discontinuation and mortality among individuals receiving different maintenance dosage strategies for OAT with methadone, buprenorphine/naloxone or slow-release oral morphine (SROM) at the population level in BC, Canada.

Methods and analysis

We propose a retrospective population-level study of BC residents initiating OAT on methadone, buprenorphine/naloxone or SROM between 1 January 2010 and 31 December 2022 who were ≥18 years of age with no known pregnancy, no history of cancer diagnosis or receiving palliative care and not currently incarcerated. Our study will employ health administrative databases linked at the individual level to emulate a target trial per OAT type where individuals will be assigned to discrete maintenance dosing strategies, according to the full range observed in BC during the study period. Primary outcomes include treatment discontinuation and all-cause mortality. To determine the effectiveness of alternative maintenance doses, we will emulate a ‘per-protocol’ trial using a clone-censor-weight approach to adjust for measured time-dependent confounding by indication.

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. All data are deidentified, securely stored and accessed in accordance with provincial privacy regulations. Results will be disseminated and shared with local advocacy groups and decision-makers, developers of national and international clinical guidelines, presented at national and international conferences and published in peer-reviewed journals electronically and in print.

The changing role of substances: trends, characteristics of individuals and prior healthcare utilization among individuals with accidental substance-related toxicity deaths in Ontario Canada

by Shaleesa Ledlie, Alice Holton, Pamela Leece, Bisola Hamzat, Joanna Yang, Gillian Kolla, Nikki Bozinoff, Rob Boyd, Mike Franklyn, Ashley Smoke, Paul Newcombe, Tara Gomes

Objective

To investigate trends and the circumstances surrounding fatal substance-related toxicities directly attributed to alcohol, stimulants, benzodiazepines or opioids and combinations of substances in Ontario, Canada.

Methods

We conducted a population-based cross-sectional study of all accidental substance-related toxicity deaths in Ontario, Canada from January 1, 2018 to June 30, 2022. We reported monthly rates of substance-related toxicity deaths and investigated the combination of substances most commonly involved in deaths. Demographic characteristics, location of incident, and prior healthcare encounters for non-fatal toxicities and substance use disorders were examined.

Results

Overall, 10,022 accidental substance-related toxicity deaths occurred, with the annual number of deaths nearly doubling between the first and last 12 months of the study period (N = 1,570–2,702). Opioids were directly involved in the majority of deaths (84.1%; N = 8,431), followed by stimulants (60.9%; N = 6,108), alcohol (13.4%; N = 1,346) and benzodiazepines (7.8%; N = 782). In total, 56.9% (N = 5,698) of deaths involved combinations of substances. Approximately one-fifth of individuals were treated in a hospital setting for a substance-related toxicity in the past year, with the majority being opioid-related (17.4%; N = 1,748). Finally, 60.9% (N = 6,098) of people had a substance use disorder diagnosis at time of death.

Conclusions

Our study shows not only the enormous loss of life from substance-related toxicities but also the growing importance of combinations of substances in these deaths. A large proportion of people had previously interacted within an hospital setting for prior substance-related toxicity events or related to a substance use disorder, representing important missed intervention points in providing appropriate care.

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