Characteristics, treatment patterns and retention with extended-release subcutaneous buprenorphine for opioid use disorder: A population-based cohort study in Ontario, Canada.

BACKGROUND: Uptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT. METHODS: We conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns. RESULTS: 2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66-428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg. CONCLUSIONS: On average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals.

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.

Assessing the impact of the slow-release oral morphine drug shortages in Ontario, Canada: A population-based time series analysis.

BACKGROUND: Slow-release oral morphine (SROM) is used to manage pain, and as opioid agonist treatment (OAT). Between 2017 and 2021 in Canada, several drug shortages occurred for Kadian© (SROM-24). The purpose of this study was to evaluate the impact of these shortages on people's ability to remain on this medication. METHODS: We conducted a retrospective population-based time series analysis of SROM-24 dispensed between January 1, 2014, and December 31, 2021, in Ontario, Canada. Using interventional autoregressive integrated moving average models (ARIMA) models, we evaluated the association between SROM-24 drug shortages and treatment discontinuation. Analyses were also stratified by the SROM-24 indication (pain or OAT). RESULTS: We identified 22,479 SROM-24 recipients, of which one-third (33.9%) were aged 65 or above and just over half (51.9%) were female. In our primary analysis of monthly SROM-24 discontinuation, we observed a significant sustained monthly increase following the shortages in November 2019 (+0.29%/month; 95% CI: 0.16%, 0.43%; p < .001) with significant sudden, temporary changes following the shortages in March 2020 (+2.00%; 95% CI: 0.95%, 3.05%; p < .001), July 2021 (+3.53%; 95% CI: 2.20%, 4.86%; p < .001), and August 2021 (+4.98%; 95% CI: 3.49%, 6.47%; p < .001). Similar results were observed in our stratified analyses, with sustained high rates of discontinuation among people accessing SROM-24 as OAT. CONCLUSIONS: The SROM-24 shortages resulted in significant treatment disruptions across all recipients. These findings have important implications for those with few treatment alternatives, including people using SROM-24 as OAT who are at risk of adverse outcomes following treatment disruptions.

The epidemiology of benzodiazepine-related toxicity in Ontario, Canada: a population-based descriptive study.

OBJECTIVES: Despite the widespread use of prescription benzodiazepines, there are few studies examining trends and patterns of benzodiazepine-related toxicity. We describe the epidemiology of benzodiazepine-related toxicity in Ontario, Canada. METHODS: We conducted a population-based, cross-sectional study of Ontario residents who had an emergency department visit or hospitalization for benzodiazepine-related toxicity between January 1, 2013 and December 31, 2020. We reported annual crude and age-standardized rates of benzodiazepine-related toxicity overall, by age, and by sex. In each year, we characterized the history of benzodiazepine and opioid prescribing among people who experienced benzodiazepine-related toxicity, and reported the percentage of encounters with opioid, alcohol, or stimulant co-involvement. RESULTS: Between 2013 and 2020, there were 32,674 benzodiazepine-related toxicity encounters among 25,979 Ontarians. During this period, the crude rate of benzodiazepine-related toxicity declined overall, from 28.0 to 26.1 per 100,000 population (age-standardized rate: 27.8 to 26.4 per 100,000), but increased among young adults aged 19 to 24 (39.9 to 66.6 per 100,000 population). Moreover, by 2020, the percentage of encounters associated with active benzodiazepine prescriptions had declined to 48.9%, while the percentage of encounters that had opioid, stimulant, or alcohol co-involvement rose to 28.8%. CONCLUSION: Benzodiazepine-related toxicity has declined in Ontario overall, but has increased among youth and young adults. Furthermore, there is growing co-involvement of opioids, stimulants, and alcohol, which may reflect the recent emergence of benzodiazepines in the unregulated drug supply. Multifaceted public health initiatives comprising harm reduction, mental health supports, and promotion of appropriate prescribing are needed to reduce benzodiazepine-related harm.

RéSUMé: OBJECTIFS: Malgré l'utilisation généralisée des benzodiazépines sur ordonnance, peu d'études portent sur les tendances et les schémas de toxicité de ces médicaments. Nous décrivons l'épidémiologie de la toxicité liée aux benzodiazépines en Ontario, au Canada. MéTHODE: Nous avons mené une étude populationnelle transversale des résidentes et résidents de l'Ontario ayant visité le service des urgences ou été hospitalisés pour toxicité liée aux benzodiazépines entre le 1er janvier 2013 et le 31 décembre 2020. Nous avons rapporté globalement, par âge et par sexe les taux annuels de toxicité liée aux benzodiazépines, bruts et standardisés pour l'âge. Pour chaque année, nous avons caractérisé les antécédents de prescription de benzodiazépines et d'opioïdes chez les personnes ayant présenté une toxicité liée aux benzodiazépines, et rapporté le pourcentage de rencontres présentant une co-implication avec les opioïdes, l'alcool ou les stimulants. RéSULTATS: Entre 2013 et 2020, il y a eu 32 674 rencontres pour toxicité liée aux benzodiazépines avec 25 979 Ontariens et Ontariennes. Durant cette période, le taux brut de toxicité liée aux benzodiazépines a baissé dans l'ensemble, passant de 28 à 26,1 pour 100 000 habitants (taux standardisé pour l'âge : 27,8 à 26,4 p. 100 000), mais il a augmenté chez les jeunes adultes de 19 à 24 ans (de 39,9 à 66,6 p. 100 000). De plus, en 2020, le pourcentage de rencontres associées à des ordonnances actives de benzodiazépines avait baissé à 48,9 %, tandis que le pourcentage de rencontres présentant une co-implication avec les opioïdes, les stimulants ou l'alcool avait augmenté à 28,8 %. CONCLUSION: La toxicité liée aux benzodiazépines a diminué en Ontario dans l'ensemble, mais elle a augmenté chez les jeunes et les jeunes adultes. De plus, cette toxicité présente une co-implication croissante avec les opioïdes, les stimulants ou l'alcool, ce qui peut refléter l'émergence récente des benzodiazépines dans l'approvisionnement non réglementé en drogues. Des initiatives de santé publique multidimensionnelles incluant la réduction des méfaits, le soutien en santé mentale et la promotion de la prescription appropriée sont nécessaires pour réduire les méfaits liés aux benzodiazépines.

Changing patterns of opioid initiation for pain management in Ontario, Canada: A population-based cross-sectional study.

INTRODUCTION: The recent publication of a national guideline and quality standards in Canada have provided clinicians with new, evidence-based recommendations on safe, appropriate opioid use. We sought to characterize how well opioid initiation practices aligned with these recommendations before and following their release. METHODS: We conducted a population-based study among people initiating opioids prior to the release of national guidelines (April 2015-March 2016; fiscal year [FY] 2015) and in the most recent year available (January-December 2019) in Ontario, Canada. We used linked administrative claims data to ascertain the apparent indication for opioid therapy, and characterized the initial daily dose (milligrams morphine or equivalent; MME) and prescription duration for each indication. RESULTS: In FY2015, 653,885 individuals commenced opioids, compared to 571,652 in 2019. Over time, there were small overall reductions in the prevalence of initial daily doses exceeding 50MME (23.9% vs. 20.1%) and durations exceeding 7 days (17.4% vs. 14.8%); but the magnitude of the reductions varied widely by indication. The prevalence of high dose (>50MME) initial prescriptions reduced significantly across all indications, with the exception of dentist-prescribed opioids (13.6% vs. 12.1% above 50MME). In contrast, there was little change in initial durations exceeding 7 days across most indications, with the exception of some surgical indications (e.g. common excision; 9.3% vs. 6.2%) and among those in palliative care (35.2% vs. 29.2%). CONCLUSION: Despite some modest reductions in initiation of high dose and long duration prescription opioids between 2015 and 2019, clinical practice is highly variable, with opioid prescribing practices influenced by clinical indication. These findings may help identify medical specialties well-suited to targeted interventions to promote safer opioid prescribing.

Risk of SARS-CoV-2 infection following initial COVID-19 vaccination: Population-based cohort study.

BACKGROUND: Anecdotally there are reports of newly diagnosed SARS-CoV-2 infection shortly after vaccination. This has led some to speculate that vaccination itself might inadvertently increase the short-term risk of COVID potentially due to airborne spread at mass vaccination clinics or relaxation of precautions following vaccination. We explored whether receipt of vaccination was associated with a short-term increase in the risk of being diagnosed with COVID-19 and if differences exist between vaccination settings. METHODS: We conducted a cohort study in Ontario, Canada to compare the risk of SARS-CoV-2 infection within 21 days of receiving a first vaccination, according to the setting in which vaccines were administered between March 1, 2021 and May 6, 2021. We used linked population-wide vaccination, laboratory testing, and health administrative databases. We created a 1:1 matched comparison group of unexposed individuals. We reported the overall risk of infection calculated at 3, 7, 10, 14, 18, and 21 days. This was completed overall and by setting of vaccine receipt. RESULTS: We identified 4,798,430 Ontario residents who received their first dose of a COVID-19 vaccine. In the primary analysis, the rate of SARS-CoV-2 infection was significantly lower among vaccine recipients vs non-recipients at all the post-vaccination time points. Analysis stratified by vaccination setting found that mass vaccination clinics, pharmacies, and physician offices were consistent with the main findings. Individuals who received their first vaccine dose in congregate residential settings had a higher rate of SARS-CoV-2 infection at 7 days (HR 1.35, 95% CI 1.00-1.83) and 10 days (HR 1.49, 95% CI 1.03-2.15). CONCLUSION: In this population-based cohort study, we found that there was no increased risk of SARS-CoV2 infection after vaccination suggesting no broad transmission of disease at time of vaccination. Some evidence of increased risk among those vaccinated in congregate settings, highlighting the need to consider opportunities for supporting safe vaccine administration in these settings. Given ongoing and future immunization programs, the results support the need for continued vigilance during any mass vaccination processes and education regarding the delayed nature of protection following vaccination.

Responding to Ontario's Overdose Crisis in the Context of the COVID-19 Pandemic.

The COVID-19 pandemic has exacerbated the overdose crisis in Canada. Using data from ICES and the Office of the Chief Coroner of Ontario, the authors characterized changing patterns of medication use and health services utilization during the pandemic. This analysis suggests that responses to the overdose crisis must confront the rapidly changing unregulated drug supply with a tailored response that addresses varied population needs, expands accessible treatment and harm reduction services and responds to the missed opportunities for engagement and support within various healthcare settings.

Impact of the COVID-19 pandemic on the prevalence of opioid agonist therapy discontinuation in Ontario, Canada: A population-based time series analysis.

BACKGROUND: We assessed the impact of COVID-19, which includes the declaration of a state of emergency and subsequent release of pandemic-specific OAT guidance (March 17, 2020 to March 23, 2020) on the prevalence of OAT discontinuation. METHODS: We conducted a population-based time series analysis using interventional autoregressive integrated moving average models among Ontario residents who were stable (>60 days of continuous use) and not yet stable on OAT. Specifically, we examined whether COVID-19 impacted the weekly percentage of individuals who discontinued OAT, overall and stratified by treatment type (methadone vs. buprenorphine/naloxone). Additionally, we compared demographic characteristics and patient outcomes among people stable on OAT who discontinued treatment during (March 17, 2020 to November 30, 2020) and prior (July 3, 2019 to March 16, 2020) to the pandemic. RESULTS: The weekly prevalence of OAT discontinuation across the study period ranged between 0.6% and 1.1%, among those stable on treatment compared to 7.3% and 16.6%, among those not stable on treatment. Following COVID-19, there was no significant change in the percentage of Ontarians who discontinued OAT, regardless of whether they were stabilized on treatment. Among those stable on OAT, a similar proportion of patients restarted therapy and experienced opioid-related harm following an OAT discontinuation. However, mortality following OAT discontinuation must be noted, as approximately 1.4% and 0.8% of people who discontinued methadone and buprenorphine/naloxone respectively, died within 30 days of discontinuation. CONCLUSIONS: Trends in the prevalence of OAT discontinuation did not significantly change during the first eight months of the COVID-19 pandemic.

Impact of the COVID-19 pandemic on the provision of take-home doses of opioid agonist therapy in Ontario, Canada: A population-based time-series analysis.

BACKGROUND: In March 2020, the Ontario government declared a state of emergency due to the growing risk of COVID-19. In response, new guidance for the management of opioid agonist therapy (OAT) was released, which included the expansion of eligibility for take-home doses. We investigated the impact of these changes on trends in the distribution of take-home doses of OAT. METHODS: We conducted a population-based time series analysis among residents of Ontario, Canada who were dispensed OAT between June 25, 2019 and November 30, 2020. For each week of the study period, we calculated the percentage of people dispensed (a) methadone and (b) buprenorphine/naloxone by the number of take-home doses received. We used interventional autoregressive integrated moving average models to estimate changes in the percentage of people dispensed each category of take-home doses in the weeks following the declaration of the state of emergency and release of the OAT dispensing guidance. RESULTS: Following the state of emergency and release of the OAT dispensing guidance, there was a significant increase in the percentage of Ontarians dispensed 7 to 13 (3.6% increase; p = 0.033) and 14 or more (0.8% increase; p<0.001) take-home doses of methadone, and in the percentage of people dispensed 7 to 13 (4.3% increase; p = 0.001), 14 to 27 (2.8% increase; p<0.001), and 28 or more (0.3% increase; p = 0.008) take-home doses of buprenorphine/naloxone. There were significant decreases in the percentage of Ontarians receiving daily dispensed buprenorphine/naloxone (-3.1%; p = 0.001), as well as the percentage dispensed 1 to 6 take-home doses of methadone (-4.5%; p = 0.001) and buprenorphine/naloxone (-4.9%; p = 0.001). CONCLUSION: The new guidance for dispensing OAT in Ontario resulted in increases in the duration of take-home doses of methadone and buprenorphine/naloxone supplied. However, given that changes were small, strategies to improve retention in OAT and ensure equitable access to take-home dosing should continue.

Duration of use and outcomes among people with opioid use disorder initiating methadone and buprenorphine in Ontario: a population-based propensity-score matched cohort study.

AIMS: To characterize comparative risks and benefits of methadone versus buprenorphine/naloxone in a contemporary cohort where the unregulated drug supply is dominated by fentanyl. DESIGN, SETTING AND PARTICIPANTS: Population-based propensity-score matched cohort study conducted in Ontario, Canada among people aged 18+ initiating opioid agonist therapy (OAT) for an opioid use disorder between October 2016 and December 2018 (n = 18 880). INTERVENTION: Initiation of methadone versus buprenorphine/naloxone. MEASUREMENTS: The primary outcome was opioid overdose (fatal and non-fatal) while on treatment, with secondary outcomes including opioid overdose (first 30 days of treatment), treatment discontinuation, health-care interactions related to treatment of opioid use disorder, receiving a weekly supply of take-home doses and opioid overdose within 30 days of treatment discontinuation. Outcomes were assessed over 1 year. FINDINGS: Overall, 7517 people initiating buprenorphine were matched to an equal number of methadone-treated individuals. Risk of opioid overdose while on treatment [hazard ratio (HR) = 0.50; 95% confidence interval (CI) = 0.37-0.68] or within the first 30 days of treatment (HR = 0.51, 95% CI = 0.31-0.85) was lower among buprenorphine recipients compared to methadone recipients. In secondary analyses, people initiating buprenorphine had a higher risk of treatment discontinuation within the first year (median time to discontinuation 104 versus 265 days, HR = 1.43, 95% CI = 1.37-1.49), had lower rates of health-care interactions for OUD (186.4 versus 254.3 per person-year; rate ratio = 0.73; 95% CI = 0.72-0.75), and a higher rate of receiving weekly take-home doses (HR = 2.33; 95% CI = 2.20-2.46). Overdose rates in the period following OAT discontinuation were higher than those observed while on treatment, but did not differ significantly by OAT type. CONCLUSIONS: Although treatment retention is higher among methadone recipients, overdose risk is also elevated compared to buprenorphine recipients. These findings demonstrate the benefits of any OAT on avoidance of overdose, particularly following treatment discontinuation and with the increasingly unpredictable drug supply in North America.

Association Between Increased Dispensing of Opioid Agonist Therapy Take-Home Doses and Opioid Overdose and Treatment Interruption and Discontinuation.

Importance: During the COVID-19 pandemic, modified guidance for opioid agonist therapy (OAT) allowed prescribers to increase the number of take-home doses to promote treatment retention. Whether this was associated with an increased risk of overdose is unclear. Objective: To evaluate whether increased take-home doses of OAT early in the COVID-19 pandemic was associated with treatment retention and opioid-related harm. Design, Setting, and Participants: A retrospective propensity-weighted cohort study of 21 297 people actively receiving OAT on March 21, 2020, in Ontario, Canada. Changes in OAT take-home dose frequency were assessed between March 22, 2020, and April 21, 2020, and individuals were observed for up to 180 days to assess outcomes (last date of follow-up, October 18, 2020). Exposures: Exposure was defined as extended take-home doses in the first month of the pandemic within each of 4 cohorts based on OAT type and baseline take-home dose frequency (daily dispensed methadone, 5-6 take-home doses of methadone, daily dispensed buprenorphine/naloxone, and 5-6 take-home doses of buprenorphine/naloxone). Main Outcomes and Measures: Primary outcomes were opioid overdose, interruption in OAT, and OAT discontinuation. Results: Among 16 862 methadone and 4435 buprenorphine/naloxone recipients, the median age ranged between 38 and 42 years, and 29.1% to 38.2% were women. Among individuals receiving daily dispensed methadone (n = 5852), initiation of take-home doses was significantly associated with lower risks of opioid overdose (6.9% vs 9.5%/person-year; weighted hazard ratio [HR], 0.73 [95% CI, 0.56-0.96]), treatment discontinuation (51.0% vs 63.6%/person-year; weighted HR, 0.80 [95% CI, 0.72-0.90]), and treatment interruption (19.0% vs 23.9%/person-year; weighted HR, 0.80 [95% CI, 0.67-0.95]) compared with no change in take-home doses. Among individuals receiving daily dispensed buprenorphine/naloxone (n = 662), there was no significant difference in any outcomes between exposure groups. Among individuals receiving weekly dispensed OAT (n = 11 010 for methadone; n = 3773 for buprenorphine/naloxone), extended take-home methadone doses were significantly associated with lower risks of OAT discontinuation (14.1% vs 19.6%/person-year; weighted HR, 0.72 [95% CI, 0.62-0.84]) and interruption in therapy (5.1% vs 7.4%/person-year; weighted HR, 0.69 [95% CI, 0.53-0.90]), and extended take-home doses of buprenorphine/naloxone were significantly associated with lower risk of interruption in therapy (9.5% vs 12.9%/person-year; weighted HR, 0.74 [95% CI, 0.56-0.99]) compared with no change in take-home doses. Other primary outcomes were not significantly different between groups. Conclusions and Relevance: In Ontario, Canada, during the COVID-19 pandemic, dispensing of increased take-home doses of opioid agonist therapy was significantly associated with lower rates of treatment interruption and discontinuation among some subsets of patients receiving opioid agonist therapy, and there were no statistically significant increases in opioid-related overdoses over 6 months of follow-up. These findings may be susceptible to residual confounding and should be interpreted cautiously.

Characterizing safer supply prescribing of immediate release hydromorphone for individuals with opioid use disorder across Ontario, Canada.

BACKGROUND: In response to the ongoing overdose crisis, some clinicians in Canada have started prescribing immediate release hydromorphone (IRH) as an alternative to the toxic unregulated drug supply. This practice is often referred to as safer supply. We aimed to identify and characterize patients receiving safer supply IRH and their prescribers in Ontario. METHODS: Using provincial administrative health data, we identified individuals with opioid use disorder prescribed safer supply IRH from January 2016 to March 2020 and reported the number of initiations over time. We summarized demographic, health, and medication use characteristics among patients who received safer supply IRH, and examined select clinical outcomes including retention and death. Finally, we characterized prescribers of safer supply IRH and compared frequent and infrequent prescribers. RESULTS: We identified 534 initiations of safer supply IRH (447 distinct individuals) from 155 prescribers. Initiations increased over time with a peak in the third quarter of 2019 (103 initiations). Patients' median age was 42 (interquartile range [IQR] 34-50), and most were male (60.2%), urban residents, (96.2%), and in the lowest neighborhood income quintile (55.7%), with 13.9% having overdosed in the previous one year. The prevalence of HIV was 13.9%. The median duration on IRH was 272 days (IQR 30-1,244) and OAT was co-prescribed in 62.9% of courses. Death while receiving IRH or within 7 days of discontinuation was rare (≤5 courses;≤0.94 per person-year for each). CONCLUSIONS: Clinicians are increasingly prescribing safer supply IRH in Ontario. Patients prescribed safer supply IRH had demographic and clinical characteristics associated with high risk of death from opioid-related overdose. Short-term deaths among people receiving safer supply IRH were rare.

Trends in Hospitalizations for Serious Infections Among People With Opioid Use Disorder in Ontario, Canada.

OBJECTIVES: Opioid use among people who inject drugs can lead to serious complications, including infections. We sought to study trends in rates of these complications among people with an opioid use disorder (OUD) and the sequelae of those hospitalizations. METHODS: We analyzed all inpatient hospitalizations for serious infections (infective endocarditis [IE], spinal infections, nonvertebral bone infections, and skin or soft tissue infections) among people with OUD in Ontario between 2013 and 2019. We reported the population adjusted rate of hospitalizations for serious infections annually, stratified by type of infection and prevalence of prior opioid agonist therapy and hydromorphone prescribing. We reported characteristics of hospitalizations and 30-day mortality in the most recent 2 years. RESULTS: Among people with OUD there was a 167% increase in rates of IE (7.7-20.6 per million residents; P < 0.01), a 394% increase in rates of spinal infections (3.4-16.8 per million residents; P < 0.01), a 191% increase in rates of nonvertebral bone infections (8.9 to 25.9 per million residents; P < 0.01), and a 147% increase in infections of the skin or soft tissue (32.1-79.4 per million residents; P < 0.01) over 7 years in Ontario. Death in-hospital and within 30 days of discharge was highest among those with IE (11.5% and 15.9%, respectively), and lower among those with other infections (<5%). CONCLUSIONS: Rates of serious infections among people with OUD are rising, placing a significant burden on patients. These findings suggest that early intervention and treatment of infections in this population are needed to prevent downstream harm.

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.

Dental Opioid Prescription Characteristics and the Risk of New, Persistent Use.

INTRODUCTION: Dentists are a common source of opioid exposure. This study investigates the association between initial dental opioid prescription characteristics and subsequent persistent use and examines the rate of opioid overdose after initiation. METHODS: A retrospective cohort study was conducted among Ontario residents who were dispensed an initial opioid prescription originating from a dentist between October 2014 and September 2018 (data were analyzed in October 2019-May 2020). Exposures were characterized on the basis of the average daily dose in milligram morphine equivalents and the duration and formulation (long versus short acting) of the initial prescription. New, persistent use was defined as ≥1 opioid prescription within 90 days and another within 91-365 days after the initial prescription. The rate of an opioid overdose within 90 days after initiation was examined. RESULTS: Among 786,125 Ontarians who initiated a dentist-prescribed opioid, 34,880 (4.4%) developed persistent use, whereas 140 (0.72 per 1,000 person-years) had evidence of an overdose within 90 days. People dispensed an initial daily dose >90 milligram morphine equivalents (n=5,644, 0.7%) had significantly greater odds of persistence (AOR=1.20, 95% CI=1.07, 1.34) than those dispensed ≤20 milligram morphine equivalents (n=179,884, 22.9%). Persistence was also significantly associated with receiving longer prescription durations and a long-acting opioid on initiation. CONCLUSIONS: Among people who initiated a dentist-prescribed opioid, 1 in 23 experienced persistent use, and persistence was associated with the characteristics of the prescription. Prescribing lower doses, prescribing for shorter durations, and avoiding long-acting formulations may be an opportunity to lessen the risk of persistent opioid use.

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.

Impact of policy changes on the provision of naloxone by pharmacies in Ontario, Canada: a population-based time-series analysis.

BACKGROUND AND AIMS: In June 2016, the Ontario, Canada government implemented the Ontario Naloxone Program for Pharmacies (ONPP), authorizing pharmacists to provide injectable naloxone kits at no charge to all Ontario residents. In March 2018, the program was amended to include intranasal naloxone and remove the requirement to present a government health card to the dispensing pharmacist. We examined whether these changes increased naloxone dispensing through the ONPP. DESIGN: Population-based time-series analysis using interventional autoregressive integrated moving average models. SETTING: Ontario, Canada. PARTICIPANTS: All Ontario residents between 1 July 2016 and 31 March 2020. MEASUREMENTS: Monthly rates of pharmacy naloxone dispensing. FINDINGS: Overall, 199 484 individuals were dispensed a naloxone kit during the study period. In the main analysis, the rate of pharmacy naloxone dispensing increased by 65.1% following program changes (55.6-91.8 kits per 100 000 population between February 2018 and May 2018; P = 0.01). In subgroup analyses, naloxone dispensing increased among individuals receiving opioid agonist therapy (OAT) (3374.9-7264.2 kits per 100 000 OAT recipients; P = 0.04) among individuals receiving other prescription opioids (192.8-381.8 kits per 100 000 population prescribed opioids; P < 0.01), among individuals with past opioid exposure (134.7-205.6 kits per 100 000 population with past opioid exposure; P < 0.01) and in urban centers (56.2-91.4 kits per 100 000 population; P < 0.01). We did not observe a clear impact on pharmacy-dispensed naloxone to individuals with no or unknown opioid exposure (34.4-39.3 kits per 100 000 population with no/unknown opioid exposure; P = 0.42) and in rural regions (50.4-97.2 kits per 100 000 population; P = 0.09). CONCLUSIONS: Changes to the Ontario Naloxone Program for Pharmacies to add intranasal naloxone and remove the requirement to present a government health card appeared to increase pharmacy-based naloxone dispensing uptake in Ontario, Canada, particularly among individuals at high risk of inadvertent opioid overdose.

Geographic variation in the provision of naloxone by pharmacies in Ontario, Canada: A population-based small area variation analysis.

BACKGROUND: Regional variation in pharmacy-dispensed naloxone rates could create access disparities that undermine the effectiveness of this approach. We explored individual and public health unit (PHU)-level determinants of regional variation in naloxone distribution through the Ontario Naloxone Program for Pharmacies. METHODS: We conducted a population-based study between April 1, 2017 and March 31, 2018. We calculated age- and sex-standardized pharmacy-dispensed naloxone rates for the 35 Ontario PHUs, and identified determinants of these rates using generalized estimating equations negative binomial regression. RESULTS: The age- and sex-standardized pharmacy-dispensed naloxone rate in Ontario was 5.5 (range 1.8-11.6) kits per 1000 population. Variables associated with higher naloxone dispensing rates included opioid use disorder history [rate ratio (RR) 2.27; 95% confidence interval (CI) 1.75-2.96], opioid agonist therapy (RR 11.17; 95% CI 7.15-17.44), and PHU opioid overdose rate (RR 1.09 per 10 deaths; 95% CI 1.06-1.13). Pharmacy-dispensed naloxone rates were lower in rural areas (RR 0.83; 95% CI 0.73-0.94) and among individuals dispensed one (RR 0.72; 95% CI 0.65-0.79), two to five (RR 0.67; 95% CI 0.54-0.84) or 6-10 (RR 0.92; 95% CI 0.74-1.14) opioids in the prior year relative to those receiving no opioids. CONCLUSION: Pharmacy-dispensed naloxone programs are important components of a public health response to the opioid overdose crisis. We found considerable variation in pharmacy-dispensed naloxone rates that could limit program effectiveness, particularly in rural settings with limited access to health and harm reduction services..

Assessing the impact of an opioid prescribing guideline for dentists in Ontario, Canada.

BACKGROUND: The Royal College of Dental Surgeons of Ontario introduced a new dental opioid prescribing guideline in November 2015. The authors examined whether introduction of this guideline was associated with changes in opioid prescribing patterns. METHODS: The authors conducted a population-based, cross-sectional time series study of Ontarians who received opioids prescribed by dentists from July 1, 2012 through September 30, 2017. They examined the impact of the guideline on dental prescribing patterns by calculating the monthly rate of opioid dispensing from dentists per 100,000 population, as well as the population exposure to opioids expressed as milligram morphine equivalents per 100 population. RESULTS: Ontario dentists issued 1,571,897 opioid prescriptions to 1,157,102 patients over the study period. The guideline was not associated with a change in opioid dispensing rates, but it was associated with a significant reduction in the volume of opioids dispensed (28.1% reduction, from 22.1 to 15.9 milligram morphine equivalents per 100 population from October 2015 through September 2017; P = .01). CONCLUSIONS: Introduction of the prescribing guideline was associated with no change in the rate of opioid prescribing by dentists, but it was associated with a roughly 25% reduction in the volume of opioids prescribed. PRACTICAL IMPLICATIONS: Introduction of the new opioid prescribing guideline for Ontario dentists was associated with a reduction in the overall volume of opioids dispensed.

The uptake of the pharmacy-dispensed naloxone kit program in Ontario: A population-based study.

BACKGROUND: Naloxone is a life-saving antidote for opioid overdoses. In June 2016, the Ontario government implemented the Ontario Naloxone Program for Pharmacies (ONPP) to enhance access to naloxone. OBJECTIVE: We examined the initial uptake of naloxone through the ONPP and characteristics of the individuals receiving and pharmacies dispensing naloxone kits. METHODS: We conducted a population-based study of all Ontario residents who received a naloxone kit between July 1, 2016 and March 31, 2018. This involved 1) a cross-sectional analysis of monthly rates of kits dispensed; and 2) a descriptive analysis of all individuals and pharmacies who accessed and dispensed naloxone, respectively. We stratified individuals according to their opioid exposure as: prescription opioid agonist therapy (OAT) recipients, prescription opioid recipients, those with past opioid exposure and those with no/unknown opioid exposure. We calculated a Lorenz curve comparing the cumulative percent of naloxone-dispensing pharmacies and cumulative percent of naloxone kits dispensed and the corresponding Gini coefficient. RESULTS: Naloxone dispensing through the ONPP increased considerably from 1.9 to 54.3 kits per 100,000 residents over the study period. In this time, 2,729 community pharmacies dispensed 91,069 kits to 67,910 unique individuals. Uptake was highest among prescription OAT recipients (40.7% of OAT recipients dispensed at least one kit), compared with 1.6% of prescription opioid recipients, 1.0% of those with past opioid exposure and 0.3% with no/unknown opioid exposure. Naloxone dispensing was highly clustered among pharmacies (Gini = 0.78), with 55.6% of Ontario pharmacies dispensing naloxone, and one-third (33.7%) of kits dispensed by the top 1.0% of naloxone-dispensing pharmacies. CONCLUSION: The ONPP launch led to a rapid increase in the number of naloxone kits dispensed in Ontario. Although the program successfully engaged people prescribed OAT, efforts to increase uptake among others at risk of opioid overdose appear warranted. Opportunities for expanding pharmacy participation should be identified and pursued.