Modelling the combined impact of interventions in averting deaths during a synthetic-opioid overdose epidemic.

The province of British Columbia (BC) Canada has experienced a rapid increase in illicit drug overdoses and deaths during the last 4 years, with a provincial emergency declared in April 2016. These deaths have been driven primarily by the introduction of synthetic opioids into the illicit opioid supply. This study aimed to measure the combined impact of large-scale opioid overdose interventions implemented in BC between April 2016 and December 2017 on the number of deaths averted. We expanded on the mathematical modelling methodology of our previous study to construct a Bayesian hierarchical latent Markov process model to estimate monthly overdose and overdose-death risk, along with the impact of interventions. Overdose events and overdose-related deaths in BC from January 2012 to December 2017. The interventions considered were take-home naloxone kits, overdose prevention/supervised consumption sites and opioid agonist therapy MEASUREMENTS: Counterfactual simulations were performed with the fitted model to estimate the number of death events averted for each intervention and in combination. Between April 2016 and December 2017, BC observed 2177 overdose deaths (77% fentanyl-detected). During the same period, an estimated 3030 (2900-3240) death events were averted by all interventions combined. In isolation, 1580 (1480-1740) were averted by take-home naloxone, 230 (160-350) by overdose prevention services and 590 (510-720) were averted by opioid agonist therapy. A combined intervention approach has been effective in averting overdose deaths during British Columbia's opioid overdose crisis in the period since declaration of a public health emergency (April 2016-December 2017). However, the absolute numbers of overdose deaths have not changed.

Irvine MA ，Kuo M ，Buxton JA ，Balshaw R ，Otterstatter M ，Macdougall L ，Milloy MJ ，Bharmal A ，Henry B ，Tyndall M ，Coombs D ，Gilbert M ... -  《-》

Distribution of take-home opioid antagonist kits during a synthetic opioid epidemic in British Columbia, Canada: a modelling study.

Illicit use of high-potency synthetic opioids has become a global issue over the past decade. This misuse is particularly pronounced in British Columbia, Canada, where a rapid increase in availability of fentanyl and other synthetic opioids in the local illicit drug supply during 2016 led to a substantial increase in overdoses and deaths. In response, distribution of take-home naloxone (THN) overdose prevention kits was scaled up (6·4-fold increase) throughout the province. The aim of this study was to estimate the impact of the THN programme in terms of the number of deaths averted over the study period. We estimated the impact of THN kits on the ongoing epidemic among people who use illicit opioids in British Columbia and explored counterfactual scenarios for the provincial response. A Markov chain model was constructed explicitly including opioid-related deaths, fentanyl-related deaths, ambulance-attended overdoses, and uses of THN kits. The model was calibrated in a Bayesian framework incorporating population data between Jan 1, 2012, and Oct 31, 2016. 22 499 ambulance-attended overdoses and 2121 illicit drug-related deaths (677 [32%] deaths related to fentanyl) were recorded in the study period, mostly since January, 2016. In the same period, 19 074 THN kits were distributed. We estimate that 298 deaths (95% credible interval [CrI] 91-474) were averted by the THN programme. Of these deaths, 226 (95% CrI 125-340) were averted in 2016, following a rapid scale-up in distribution of kits. We infer a rapid increase in fentanyl adulterant at the beginning of 2016, with an estimated 2·3 times (95% CrI 2·0-2·9) increase from 2015 to 2016. Counterfactual modelling indicated that an earlier scale-up of the programme would have averted an additional 118 deaths (95% CrI 64-207). Our model also indicated that the increase in deaths could parsimoniously be explained through a change in the fentanyl-related overdose rate alone. The THN programme substantially reduced the number of overdose deaths during a period of rapid increase in the number of illicit drug overdoses due to fentanyl in British Columbia. However, earlier adoption and distribution of the THN intervention might have had an even greater impact on overdose deaths. Our findings show the value of a fast and effective response at the start of a synthetic opioid epidemic. We also believe that multiple interventions are needed to achieve an optimal impact. Canadian Institutes of Health Research Partnerships for Health Systems Improvement programme (grant 318068) and Natural Science and Engineering Research Council of Canada (grant 04611).

Irvine MA ，Buxton JA ，Otterstatter M ，Balshaw R ，Gustafson R ，Tyndall M ，Kendall P ，Kerr T ，Gilbert M ，Coombs D ... -  《The Lancet Regional Health》

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

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

Gallant K ，Lukeman R 《Harm Reduction Journal》

Accessing Take-Home Naloxone in British Columbia and the role of community pharmacies: Results from the analysis of administrative data.

Moustaqim-Barrette A ，Papamihali K ，Mamdani Z ，Williams S ，Buxton JA ... -  《PLoS One》

Estimating naloxone need in the USA across fentanyl, heroin, and prescription opioid epidemics: a modelling study.

The US overdose crisis is driven by fentanyl, heroin, and prescription opioids. One evidence-based policy response has been to broaden naloxone distribution, but how much naloxone a community would need to reduce the incidence of fatal overdose is unclear. We aimed to estimate state-level US naloxone need in 2017 across three main naloxone access points (community-based programmes, provider prescription, and pharmacy-initiated distribution) and by dominant opioid epidemic type (fentanyl, heroin, and prescription opioid). In this modelling study, we developed, parameterised, and applied a mechanistic model of risk of opioid overdose and used it to estimate the expected reduction in opioid overdose mortality after deployment of a given number of two-dose naloxone kits. We performed a literature review and used a modified-Delphi panel to inform parameter definitions. We refined an established model of the population at risk of overdose by incorporating changes in the toxicity of the illicit drug supply and in the naloxone access point, then calibrated the model to 2017 using data obtained from proprietary data sources, state health departments, and national surveys for 12 US states that were representative of each epidemic type. We used counterfactual modelling to project the effect of increased naloxone distribution on the estimated number of opioid overdose deaths averted with naloxone and the number of naloxone kits needed to be available for at least 80% of witnessed opioid overdoses, by US state and access point. Need for naloxone differed by epidemic type, with fentanyl epidemics having the consistently highest probability of naloxone use during witnessed overdose events (range 58-76% across the three modelled states in this category) and prescription opioid-dominated epidemics having the lowest (range 0-20%). Overall, in 2017, community-based and pharmacy-initiated naloxone access points had higher probability of naloxone use in witnessed overdose and higher numbers of deaths averted per 100 000 people in state-specific results with these two access points than with provider-prescribed access only. To achieve a target of naloxone use in 80% of witnessed overdoses, need varied from no additional kits (estimated as sufficient) to 1270 kits needed per 100 000 population across the 12 modelled states annually. In 2017, only Arizona had sufficient kits to meet this target. Opioid epidemic type and how naloxone is accessed have large effects on the number of naloxone kits that need to be distributed, the probability of naloxone use, and the number of deaths due to overdose averted. The extent of naloxone distribution, especially through community-based programmes and pharmacy-initiated access points, warrants substantial expansion in nearly every US state. National Institute of Health, National Institute on Drug Abuse.

Irvine MA ，Oller D ，Boggis J ，Bishop B ，Coombs D ，Wheeler E ，Doe-Simkins M ，Walley AY ，Marshall BDL ，Bratberg J ，Green TC ... -  《The Lancet Regional Health》