Opioid-related deaths between 2019 and 2021 across 9 Canadian provinces and territories.

BACKGROUND: The drug toxicity crisis continues to accelerate across Canada, with rapid increases in opioid-related harms following the onset of the COVID-19 pandemic. We sought to describe trends in the burden of opioid-related deaths across Canada throughout the pandemic, comparing these trends by province or territory, age, and sex. METHODS: We conducted a repeated cross-sectional analysis of accidental opioid-related deaths between Jan. 1, 2019, and Dec. 31, 2021, across 9 Canadian provinces and territories using aggregated national data. Our primary measure was the burden of premature opioid-related death, measured by potential years of life lost. Our secondary measure was the proportion of all deaths attributable to opioids; we used the Cochrane-Armitage test for trend to compare proportions. RESULTS: Between 2019 and 2021, the annual number of opioid-related deaths increased from 3007 to 6222 and years of life lost increased from 126 115 to 256 336 (from 3.5 to 7.0 yr of life lost per 1000 population). In 2021, the highest number of years of life lost was among males (181 525 yr) and people aged 30-39 years (87 045 yr). In 2019, we found that 1.7% of all deaths among those younger than 85 years were related to opioids, rising to 3.2% in 2021. Significant increases in the proportion of deaths related to opioids were observed across all age groups (p < 0.001), representing 29.3% and 29.0% of deaths among people aged 20-29 and 30-39 years in 2021, respectively. INTERPRETATION: Across Canada, the burden of premature opioid-related deaths doubled between 2019 and 2021, representing more than one-quarter of deaths among younger adults. The disproportionate loss of life in this demographic group highlights the critical need for targeted prevention efforts.

Impact of COVID-19 pandemic on prescription stimulant use among children and youth: a population-based study.

COVID-19 associated public health measures and school closures exacerbated symptoms in some children and youth with attention-deficit hyperactivity disorder (ADHD). Less well understood is how the pandemic influenced patterns of prescription stimulant use. We conducted a population-based study of stimulant dispensing to children and youth ≤ 24 years old between January 1, 2013, and June 30, 2022. We used structural break analyses to identify the pandemic month(s) when changes in the dispensing of stimulants occurred. We used interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected stimulant use. Our main outcome was the change in the monthly rate of stimulant use per 100,000 children and youth. Following an initial immediate decline of 60.1 individuals per 100,000 (95% confidence interval [CI] - 99.0 to - 21.2), the monthly rate of stimulant dispensing increased by 11.8 individuals per 100,000 (95% CI 10.0-13.6), with the greatest increases in trend observed among females, individuals in the highest income neighbourhoods, and those aged 20 to 24. Observed rates were between 3.9% (95% CI 1.7-6.2%) and 36.9% (95% CI 34.3-39.5%) higher than predicted among females from June 2020 onward and between 7.1% (95% CI 4.2-10.0%) and 50.7% (95% CI 47.0-54.4%) higher than expected among individuals aged 20-24 from May 2020 onward. Additional research is needed to ascertain the appropriateness of stimulant use and to develop strategies supporting children and youth with ADHD during future periods of long-term stressors.

Prescription of oxycodone versus codeine after childbirth and risk of persistent opioid use: a population-based cohort study.

BACKGROUND: Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined whether initiation of oxycodone after delivery was associated with an increased risk of persistent opioid use relative to initiation of codeine. METHODS: We conducted a population-based cohort study of people who filled a prescription for either codeine or oxycodone within 7 days of discharge from hospital after delivery between Sept. 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, defined as 1 or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and 1 or more additional prescriptions in the 91 to 365 days thereafter. We used inverse probability of treatment weighting to assess the risk of persistent postpartum opioid use, comparing people who initiated oxycodone with those who initiated codeine. RESULTS: Over the 8-year study period, we identified 70 607 people who filled an opioid prescription within 7 days of discharge from hospital: 21 308 (30.2%) received codeine and 49 299 (69.8%) oxycodone. Compared with people who filled a prescription for codeine, receipt of oxycodone was not associated with persistent opioid use (relative risk [RR] 1.04, 95% confidence interval [CI] 0.91-1.20). We found an association between a prescription for oxycodone and persistent use after vaginal delivery (RR 1.63, 95% CI 1.31-2.03), but not after cesarean delivery (RR 0.85, 95% CI 0.73-1.00). INTERPRETATION: Initiation of oxycodone (v. codeine) was not associated with an increased risk of persistent opioid use, except after vaginal delivery.

Initiation of opioid agonist therapy after hospital visits for opioid poisonings in Ontario.

BACKGROUND: Emergency department visits and hospital admissions for opioid toxicity are opportunities to initiate opioid agonist therapy (OAT), which reduces morbidity and mortality in patients with opioid use disorder (OUD). The study objectives were to evaluate OAT initiation rates after a hospital encounter for opioid toxicity in Ontario, Canada, and determine whether publication of a 2018 Canadian OUD management guideline was associated with increased initiation. METHODS: We conducted a retrospective, population-based serial cross-sectional study of hospital encounters for opioid toxicity among patients with OUD between Jan. 1, 2013, and Mar. 31, 2020, in Ontario, Canada. The primary outcome was OAT initiation (methadone, buprenorphine-naloxone, or slow-release oral morphine) within 7 days of discharge, measured quarterly. We examined the impact of the release of the OUD management guideline on OAT initiation rates using Autoregressive Integrated Moving Average models. RESULTS: Among 20 702 hospital visits for opioid toxicity among patients with OUD, the median age was 35 years, and 65.1% were male. Over the study period, the percentage of visits leading to OAT initiation within 7 days rose from 1.7% or less (Q1 2013) to 5.6% (Q1 2020); however, the publication of the Canadian OUD management guideline was not associated with a significant increase in these rates (0.14% slope change, 95% confidence interval -0.11% to 0.38%; p = 0.3). INTERPRETATION: Among hospital encounters for opioid toxicity, despite rising prevalence over time, only 1 in 18 patients were dispensed OAT within a week of discharge in early 2020. These findings highlight missed opportunities to initiate therapies proven to reduce mortality in patients with OUD.

Predictors of fatal and nonfatal overdose after prescription of opioids for chronic pain: a systematic review and meta-analysis of observational studies.

BACKGROUND: Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids. METHODS: We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose. INTERPRETATION: We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/).

Impact of a Publicly-Funded Pharmacare Program on Prescription Stimulant use Among Children and Youth: A Population-Based Observational Natural Experiment.

OBJECTIVE: Stimulants are first-line pharmacotherapy for individuals with attention-deficit hyperactivity disorder. However, disparities in drug coverage may contribute to inequitable treatment access. In January 2018, the government of Ontario, Canada, implemented a publicly-funded program (OHIP+) providing universal access to medications at no cost to children and youth between the ages of 0 and 24. In April 2019, the program was amended to cover only children and youth without private insurance. We studied whether these policy changes were associated with changes in prescription stimulant dispensing to Ontario children and youth. METHODS: We conducted a population-based observational natural experiment study of stimulant dispensing to children and youth in Ontario between January 2013 and March 2020. We used interventional autoregressive integrated moving average models to estimate the association between OHIP+ and its subsequent modification with stimulant dispensing trends. RESULTS: The implementation of OHIP+ was associated with a significant immediate increase in the monthly rate of stimulant dispensing of 53.6 individuals per 100,000 population (95% confidence interval [CI], 36.8 to 70.5 per 100,000) and a 14.2% (95% CI, 12.8% to 15.6%) relative percent increase in stimulant dispensing rates between December 2017 and March 2019 (1198.6 vs. 1368.7 per 100,000 population). The April 2019 OHIP+ program amendment was associated with an increase in monthly stimulant dispensing trends of 10.2 individuals per 100,000 population (95% CI, 5.0 to 15.5), with rates increasing 7.5% (95% CI, 6.2% to 8.7%) between March 2019 and March 2020 (1368.7 vs. 1470.8 per 100,000 population). These associations were most pronounced among males, children and youth living in the highest income neighbourhoods and individuals aged 20 to 24. CONCLUSION: A publicly-funded pharmacare program was associated with more children and youth being dispensed stimulants.

Geographic variation and sociodemographic correlates of prescription psychotropic drug use among children and youth in Ontario, Canada: a population-based study.

BACKGROUND: Population-based research examining geographic variability in psychotropic medication dispensing to children and youth and the sociodemographic correlates of such variation is lacking. Variation in psychotropic use could reflect disparities in access to non-pharmacologic interventions and identify potentially concerning use patterns. METHODS: We conducted a population-based study of all Ontario residents aged 0 to 24 years who were dispensed a benzodiazepine, stimulant, antipsychotic or antidepressant between January 1, 2018, and December 31, 2018. We conducted small-area variation analyses and identified determinants of dispensing using negative binomial generalized estimating equation models. RESULTS: The age- and sex-standardized rate of psychotropic dispensing to children and youth was 76.8 (range 41.7 to 144.4) prescriptions per 1000 population, with large variation in psychotropic dispensing across Ontario's census divisions. Males had higher antipsychotic [rate ratio (RR) 1.40; 95% confidence interval (CI) 1.36 to 1.44) and stimulant (RR 1.75; 95% CI 1.70 to 1.80) dispensing rates relative to females, with less use of benzodiazepines (RR 0.85; 95% CI 0.83 to 0.88) and antidepressants (RR 0.81; 95% CI 0.80 to 0.82). Lower antipsychotic dispensing was observed in the highest income neighbourhoods (RR 0.72; 95% CI 0.70 to 0.75) relative to the lowest. Benzodiazepine (RR 1.12; 95% CI 1.01 to 1.24) and stimulant (RR 1.11; 95% CI 1.01 to 1.23) dispensing increased with the density of mental health services in census divisions, whereas antipsychotic use decreased (RR 0.82; 95% CI 0.73 to 0.91). The regional density of child and adolescent psychiatrists and developmental pediatricians (RR 1.00; 95% CI 0.99 to 1.01) was not associated with psychotropic dispensing. CONCLUSION: We found significant variation in psychotropic dispensing among young Ontarians. Targeted investment in regions with long wait times for publicly-funded non-pharmacological interventions and novel collaborative service models may minimize variability and promote best practices in using psychotropics among children and youth.

Impact of a publicly-funded pharmacare program policy on benzodiazepine dispensing among children and youth: a population-based natural experiment.

BACKGROUND: In January 2018, the Government of Ontario, Canada, initiated a universal pharmacare program (OHIP+) for all individuals aged 24 years and younger. In April 2019, the program was amended to cover only children and youth without private insurance. Because benzodiazepines are commonly prescribed to children and youth despite their potential hazards, we examined whether changes in publicly-funded drug coverage influenced benzodiazepine dispensing trends in this demographic. METHODS: We conducted a population-based natural experiment study of benzodiazepine dispensing to children and youth in Ontario between January 2013 and March 2020. We used interventional autoregressive integrated moving average models to estimate the impact of OHIP + and its subsequent modification on these trends. RESULTS: The implementation of OHIP + was associated with an immediate increase in the monthly rate of benzodiazepine dispensing of 12.9 individuals per 100,000 population (95% confidence interval [CI]; 7.5 to 18.3 per 100,000). Benzodiazepine dispensing rates rose from 214.2 to 241.5 per 100,000 from December 2017 to March 2019, a 12.8% (95% CI 9.6-16.0%) increase. In stratified analyses, increases were most pronounced among females, children and youth living in the lowest income neighbourhoods and individuals aged 20 to 24. The April 2019 modification to OHIP + was not associated with changes in monthly benzodiazepine dispensing trends (0.39 individuals per 100,000; 95% CI -1.3 to 2.1 per 100,000). However, rates remained elevated relative to the period preceding OHIP + implementation. CONCLUSIONS: Implementation of a publicly-funded pharmacare program resulted in more children and youth being prescribed benzodiazepines.

Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy : A Propensity Score-Matched Cohort Study.

BACKGROUND: An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter. OBJECTIVE: To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy. DESIGN: Population-based, matched, cohort study. SETTING: Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020. PATIENTS: Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday. MEASUREMENTS: The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups. RESULTS: A total of 25 077 propensity score-matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]). LIMITATION: Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events. CONCLUSION: Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Circumcision and Risk of HIV among Males from Ontario, Canada.

PURPOSE: Randomized trials from Africa demonstrate that circumcision reduces the risk of acquiring human immunodeficiency virus (HIV) among males. However, few studies have examined this association in Western populations. We sought to evaluate the association between circumcision and the risk of acquiring HIV among males from Ontario, Canada. MATERIALS AND METHODS: We conducted a population-based matched cohort study of residents in Ontario, Canada. We identified males born in Ontario who underwent circumcision at any age between 1991 and 2017. The comparison group consisted of age-matched males who did not undergo circumcision. The primary outcome was incident HIV. We used cause-specific hazard models to evaluate the hazard of incident HIV. We performed several sensitivity analyses to evaluate the robustness of our results: matching on institution of birth, varying the minimum followup period, and simulating various false-negative and false-positive thresholds. RESULTS: We studied 569,950 males, including 203,588 who underwent circumcision and 366,362 who did not. The vast majority of circumcisions (83%) were performed prior to age 1 year. In the primary analysis, we found no significant difference in the risk of HIV between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.72 to 1.35). In none of the sensitivity analyses did we find an association between circumcision and risk of HIV. CONCLUSIONS: We found that circumcision was not independently associated with the risk of acquiring HIV among males from Ontario, Canada. Our results are consistent with clinical guidelines that emphasize safe-sex practices and counseling over circumcision as an intervention to reduce the risk of HIV.

Comparative benefits and harms of individual opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised trials.

BACKGROUND: Most systematic reviews of opioids for chronic pain have pooled treatment effects across individual opioids under the assumption they provide similar benefits and harms. We examined the comparative effects of individual opioids for chronic non-cancer pain through a network meta-analysis of randomised controlled trials. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials to March 2021 for studies that enrolled patients with chronic non-cancer pain, randomised them to receive different opioids, or opioids vs placebo, and followed them for at least 4 weeks. Certainty of evidence was evaluated using the GRADE approach. RESULTS: We identified 82 eligible trials (22 619 participants) that evaluated 14 opioids. Compared with placebo, several opioids showed superiority to others for analgesia and improvement in physical function; however, when restricted to pooled-effect estimates supported by moderate certainty evidence, no differences between opioids were evident. Among opioids with moderate certainty evidence, all increased the risk of gastrointestinal adverse events compared with placebo, although no opioids were more harmful than others. Low to very low certainty evidence suggests that extended-release vs immediate-release opioids may provide similar benefits for pain relief and physical functioning, and gastrointestinal harms. CONCLUSIONS: Our findings support the pooling of effect estimates across different types and formulations of opioids to inform effectiveness for chronic non-cancer pain.

Metronidazole-associated Neurologic Events: A Nested Case-control Study.

BACKGROUND: Case reports have described instances of peripheral and central nervous system toxicity during treatment with metronidazole; however, no large-scale studies have examined this association. METHODS: We conducted a population-based nested case-control study of adults aged 66 years or older living in Ontario, Canada, between 1 April 2003 and 31 March 2017. Cases were individuals who attended hospital for any of cerebellar dysfunction, encephalopathy, or peripheral neuropathy within 100 days of a prescription for either metronidazole or clindamycin. We matched each case patient with up to 10 event-free control subjects who also received metronidazole or clindamycin. We used conditional logistic regression to test the association between metronidazole exposure and neurologic events, with clindamycin as the reference exposure. RESULTS: We identified 1212 cases with recent use of either metronidazole or clindamycin and 12 098 controls. Neurologic adverse events were associated with an increased odds of metronidazole exposure compared to clindamycin (odds ratio [OR], 1.72 [95% confidence interval {CI}, 1.53-1.94]), which persisted after accounting for patient demographics, comorbidities, and other medication exposures (adjusted odds ratio [aOR], 1.43 [95% CI, 1.26-1.63]). We found a consistent association limited to either central (aOR, 1.46 [95% CI, 1.27-1.68]) or peripheral (aOR, 1.34 [95% CI, 1.02-1.76]) nervous system events. Among metronidazole recipients, the overall incidence of neurologic events at 100 days was approximately 0.25%. CONCLUSIONS: Metronidazole is associated with an increased risk of adverse peripheral and central nervous system events relative to clindamycin. Clinicians and patients should be aware of these rare but potentially serious adverse events.

Inequities in access to primary care among opioid recipients in Ontario, Canada: A population-based cohort study.

BACKGROUND: Stigma and high-care needs can present barriers to the provision of high-quality primary care for people with opioid use disorder (OUD) and those prescribed opioids for chronic pain. We explored the likelihood of securing a new primary care provider (PCP) among people with varying histories of opioid use who had recently lost access to their PCP. METHODS AND FINDINGS: We conducted a retrospective cohort study using linked administrative data among residents of Ontario, Canada whose enrolment with a physician practicing in a primary care enrolment model (PEM) was terminated between January 2016 and December 2017. We assigned individuals to 3 groups based upon their opioid use on the date enrolment ended: long-term opioid pain therapy (OPT), opioid agonist therapy (OAT), or no opioid. We fit multivariable models assessing the primary outcome of primary care reattachment within 1 year, adjusting for demographic characteristics, clinical comorbidities, and health services utilization. Secondary outcomes included rates of emergency department (ED) visits and opioid toxicity events. Among 154,970 Ontarians who lost their PCP, 1,727 (1.1%) were OAT recipients, 3,644 (2.4%) were receiving long-term OPT, and 149,599 (96.5%) had no recent prescription opioid exposure. In general, OAT recipients were younger (median age 36) than those receiving long-term OPT (59 years) and those with no recent prescription opioid exposure (44 years). In all exposure groups, the majority of individuals had their enrolment terminated by their physician (range 78.1% to 88.8%). In the primary analysis, as compared to those not receiving opioids, OAT recipients were significantly less likely to find a PCP within 1 year (adjusted hazard ratio [aHR] 0.55, 95% confidence interval [CI] 0.50 to 0.61, p < 0.0001). We observed no significant difference between long-term OPT and opioid unexposed individuals (aHR 0.96; 95% CI 0.92 to 1.01, p = 0.12). In our secondary analysis comparing the period of PCP loss to the year prior, we found that rates of ED visits were elevated among people not receiving opioids (adjusted rate ratio (aRR) 1.20, 95% CI 1.18 to 1.22, p < 0.0001) and people receiving long-term OPT (aRR 1.37, 95% CI 1.28 to 1.48, p < 0.0001). We found no such increase among OAT recipients, and no significant increase in opioid toxicity events in the period following provider loss for any exposure group. The main limitation of our findings relates to their generalizability outside of PEMs and in jurisdictions with different financial incentives incorporated into primary care provision. CONCLUSIONS: In this study, we observed gaps in access to primary care among people who receive prescription opioids, particularly among OAT recipients. Ongoing efforts are needed to address the stigma, discrimination, and financial disincentives that may introduce barriers to the healthcare system, and to facilitate access to high-quality, consistent primary care services for chronic pain patients and those with OUD.

Initial opioid prescription patterns and the risk of ongoing use and adverse outcomes.

PURPOSE: As clinical practice moves towards more judicious opioid prescribing, physicians require information on how to safely initiate opioids. The objective of this study was to examine the association between initial opioid prescription characteristics and risks of harm and long-term use. METHODS: We conducted a population-based retrospective cohort study among Ontario residents newly dispensed an opioid for pain between July 2013 and March 2016. The primary exposure was the average daily opioid dose dispensed at initiation (in milligram morphine equivalents; MME), with secondary exposures including the initial prescription's duration and formulation. The primary outcome was fatal or non-fatal opioid overdose. A secondary analysis studied continued opioid use for at least 1 year. RESULTS: Among the 2 021 371 individuals meeting our inclusion criteria, 1121 (0.56 per 1000 person-years) experienced an opioid overdose within 1 year and 64 013 (3.17%) continued treatment for at least 1 year. Higher initial daily dose, longer prescription duration, and receipt of a long-acting formulation at initiation were significantly associated with higher hazard of overdose. Compared to daily doses of 20 MME or lower, initial doses exceeding 200 MME daily were associated with a particularly high hazard of overdose (aHR 2.97, 95% confidence interval [CI] 1.62 to 5.44). In the secondary analysis, there were similar associations between initial dose, duration, and formulation and long-term use. CONCLUSIONS: Although the absolute risk of an opioid overdose within the first year of prescription opioid use is low, better alignment of opioid initiation practices with guidelines may reduce opioid-related harm.

New Opioid Use after Invasive Mechanical Ventilation and Hospital Discharge.

Rationale: Patients who receive invasive mechanical ventilation (IMV) are usually exposed to opioids as part of their sedation regimen. The rates of posthospital prescribing of opioids are unknown.Objectives: To determine the frequency of persistent posthospital opioid use among patients who received IMV.Methods: We assessed opioid-naive adults who were admitted to an ICU, received IMV, and survived at least 7 days after hospital discharge in Ontario, Canada over a 26-month period (February, 2013 through March, 2015). The primary outcome was new, persistent opioid use during the year after discharge. We assessed factors associated with persistent use by multivariable logistic regression. Patients receiving IMV were also compared with matched hospitalized patients who did not receive intensive care (non-ICU).Measurements and Main Results: Among 25,085 opioid-naive patients on IMV, 5,007 (20.0%; 95% confidence interval [CI], 19.5-20.5) filled a prescription for opioids in the 7 days after hospital discharge. During the next year, 648 (2.6%; 95% CI, 2.4-2.8) of the IMV cohort met criteria for new, persistent opioid use. The patient characteristic most strongly associated with persistent use in the IMV cohort was being a surgical (vs. medical) patient (adjusted odds ratio, 3.29; 95% CI, 2.72-3.97). The rate of persistent use was slightly higher than for matched non-ICU patients (2.6% vs. 1.5%; adjusted odds ratio, 1.37 [95% CI, 1.19-1.58]).Conclusions: A total of 20% of IMV patients received a prescription for opioids after hospital discharge, and 2.6% met criteria for persistent use, an average of 300 new persistent users per year in a population of 14 million. Receipt of surgery was the factor most strongly associated with persistent use.

One-Year Mortality After Emergency Department Visit for Nonfatal Opioid Poisoning: A Population-Based Analysis.

STUDY OBJECTIVE: We aim to characterize the incidence and risk factors for opioid-related and all-cause mortality in the year after an emergency department (ED) visit for nonfatal opioid poisoning by conducting a population-based study. METHODS: We used linked health care databases in Ontario, Canada, to identify individuals who attended an ED for nonfatal opioid poisoning between January 1, 2015, and December 31, 2016. Using Cox proportional hazards regression, we examined predictors of mortality in the year after discharge (ED or hospital, if admitted). RESULTS: In this cohort (n=6,140), 327 individuals (5.3%) died of any cause and 118 (1.9%) died of opioid-related causes within 1 year. Adjusting for other covariates, we found that health service use in the first week was not protective for opioid-related death (hazard ratio [HR] 0.70; 95% confidence interval [CI] 0.47 to 1.06) or all-cause mortality (HR 0.98; 95% CI 0.78 to 1.24). In exploring other covariates, predictors of opioid-related mortality included male sex (HR 1.98; 95% CI 1.32 to 2.97) and using opioid agonist therapy (HR 1.79; 95% CI 1.15 to 2.80) or benzodiazepine (HR 1.54; 95% CI 1.02 to 2.31) in the 12 months before the index event. Assessment by a family physician in the previous 12 months was associated with a lower risk of opioid-related and all-cause mortality (HR 0.58, 95% CI 0.39 to 0.86; and HR 0.63, 95% CI 0.49 to 0.82, respectively). CONCLUSION: We identified predictors of opioid-related and all-cause mortality after ED presentation for opioid poisoning. Several predictors of mortality may facilitate targeted interventions.

Comprehensive Drug-Class Review Framework for improved evidence-based drug policy and formulary modernization.

Formularies are used by payers to optimize access and ensure the appropriate use of medications. Lack of follow-up and re-evaluation can lead to outdated formularies that are not reflective of current evidence. Formulary modernization, an approach to re-align formularies with current evidence has proven successful. The Ontario Drug Policy Research Network (ODPRN) launched a framework for conducting comprehensive drug-class reviews. This commentary describes the individual components of this framework and lessons learned through completion of 12 reviews between 2013 and 2016. We present the ODPRN drug-class review of treatments for chronic hepatitis B as a case example to illustrate the components and impact. The incorporation of foundational health technology assessment components such as economic evaluations and knowledge synthesis with contextualizing evidence such as patient and clinician perspectives (through qualitative studies), real-world evidence (through data analytics), and cross-jurisdictional comparisons (through environmental scans and data analytics), successfully developed jurisdictionally specific policy recommendations grounded in up-to-date evidence. The ODPRN framework for conducting comprehensive drug-class reviews is a robust and feasible approach to conduct formulary modernization. This framework allows for actionable and specific policies which are likely to be considered by decision makers. Adoption of similar frameworks in other jurisdictions may improve uptake of evidence-informed policy recommendations.

Response to "understanding the behavioural determinants of opioid prescribing among family physicians: a qualitative study".

The 2017 Canadian opioid Guideline made both strong recommendations, indicating that all or almost all fully informed patients would choose the recommended course of action, and weak recommendations, in which different choices are appropriate for individual patients based on their values and preferences. The Guideline's recommendation to taper legacy patients prescribed high-dose opioid therapy is weak, and mandatory tapering is expressly discouraged.

ST-elevation in ethylene glycol toxicity mimicking myocardial infarction.

Electrocardiographic changes due to ethylene glycol toxicity are described in a 37-year-old woman who presented with intentional overdose. She received prompt treatment with dialysis and fomepizole, which reversed profound metabolic acidosis. ST-elevation in leads I, aVL, and aVR were observed 87 h after admission along with diffuse repolarization abnormalities. Coronary angiography found no evidence of coronary artery disease, and echocardiogram revealed normal left ventricle size and a mildly hypokinetic basal inferior wall. Diffuse repolarization abnormalities persisted for several days. Review of literature supports the diagnosis of myocarditis induced by toxic metabolites of ethylene glycol in context of hepatic and renal failure.

Impact of delisting high-strength opioid formulations from a public drug benefit formulary on opioid utilization in Ontario, Canada.

PURPOSE: High-strength opioid formulations were delisted (removed) from Ontario's public drug formulary in January 2017, except for palliative patients. We evaluated the impact of this policy on opioid utilization and dosing. METHODS: We conducted a longitudinal study among patients receiving publicly funded, high-strength opioids from August 2016 to July 2017. The primary outcome measure was weekly median daily opioid dose (in milligrams of morphine or equivalent; MME) of (1) publicly funded and (2) all opioid prescriptions irrespective of funding source, evaluated using interrupted time series analyses and stratified by palliative care status. RESULTS: Following policy implementation, the weekly median daily dose of publicly funded opioids decreased immediately among non-palliative patients by 10 MME (95% confidence limit [CL], -16.8 to -3.1) from a pre-intervention dose of 424.5 MME (95% CL, 417.8-431.2) and fell gradually among palliative patients by 3.9 MME per week (95% CL, -5.5 to -2.3) from a pre-intervention dose of 450.1 MME (95% CL, 432.5-467.7). In contrast, among all opioid prescriptions, gradual reductions in weekly median daily doses were observed only for non-palliative patients, which decreased by 0.7 MME per week (95% CL, -1.3 to -0.2) from a pre-intervention dose of 426.2 MME (95% CL, 420.9-431.5). CONCLUSION: The delisting of publicly-funded, high-strength opioids was accompanied by changes in funding source and small reductions in the weekly median daily doses dispensed. Although observed dose reductions of less than 1 MME weekly are likely not clinically relevant, safety implications of these changes require further monitoring.