Alpha-1 adrenergic antagonists and the risk of hospitalization or death in non-hospitalized patients with COVID-19: A population-based study.

BACKGROUND: Alpha-1 receptor antagonists may interfere with IL-6 signaling and could therefore be a potential treatment for COVID-19. However, the effectiveness of these drugs in mitigating the risk of clinical deterioration among non-hospitalized patients with COVID-19 is unknown. OBJECTIVES: The aim of this study is to examine the association between alpha-1 antagonist exposure and the 30-day risk of a hospital encounter or death in nonhospitalized patients with COVID-19. METHODS: We conducted a population-based cohort study of Ontario residents aged 35 years and older who were eligible for public drug coverage and who had a positive test for SARS-CoV-2 between January 1, 2020, and March 1, 2021. We matched each individual receiving an alpha-1 antagonist at the time of their positive test with two non-exposed individuals using propensity scores. Our outcome was a composite of a hospital admission, emergency department visit, or death, 1 to 30 days following the positive test. RESULTS: We matched 3289 alpha-1 antagonist exposed patients to 6189 unexposed patients. Overall, there was no difference in the 30-day risk of the primary outcome among patients exposed to alpha-1 antagonists at the time of their diagnosis relative to unexposed individuals (28.8% vs. 28.0%; OR 1.00, 95% CI 0.91 to 1.11). In a secondary analysis, individuals exposed to alpha-1 antagonists had a lower risk of death in the 30 days following a COVID diagnosis (OR 0.79; 95% CI 0.66 to 0.93). CONCLUSION: Alpha-1 antagonists did not mitigate the 30-day risk of clinical deterioration in non-hospitalized patients with COVID-19. Our findings do not support the general repurposing of alpha-1 antagonists as a treatment for such patients, although there may be subgroups of patients in whom further research is warranted.

Trends in opioid toxicities among people with and without opioid use disorder and the impact of the COVID-19 pandemic in Ontario, Canada: A population-based analysis.

BACKGROUND: Across Canada, the COVID-19 pandemic occurred amidst an ongoing drug toxicity crisis. Although elevated rates of substance-related harms have been observed nationally, it remains unknown if the pandemic state of emergency led to disproportionate increases in opioid toxicities among people with opioid use disorder (OUD) compared to those without. METHODS: We conducted a population-based repeated cross-sectional time series analysis of fatal and non-fatal opioid toxicities between January 1, 2014, and December 31, 2021, in Ontario, Canada. We used interventional autoregressive integrated moving average models to examine the impact of the pandemic on monthly rates of opioid toxicities per 100,000 Ontario residents stratified by people with and without OUD. RESULTS: We identified 80,296 opioid toxicities of which 53.5 % occurred among people with OUD. Among 52,052 unique individuals, 60.5 % were male and 46.2 % were 25-44 years old. Between January 2014 and December 2021, the rate of opioid toxicities increased from 2.6 to 10.5 per 100,000 (rate ratio [RR]=4.07). The magnitude of this increase differed among people with OUD (0.8 to 7.4 per 100,000; RR=9.35) and without OUD (1.8 to 3.1 per 100,000; RR=1.74). We observed a significant ramp increase in the overall rate of opioid toxicities following the declaration of the pandemic emergency in March 2020 (+0.19 per 100,000 monthly, 95 % CI: 0.029, 0.36, p = 0.021). In a stratified analysis, we found a similar ramp increase among people with OUD (+0.19 per 100,000 monthly, 95 % CI: 0.10, 0.28, p < 0.001); however, this was not observed among people without OUD (p = 0.95). CONCLUSIONS: The rate of opioid toxicities accelerated across Ontario following the pandemic-related state of emergency, with the majority of this increase among people with OUD. The important differences observed among people with OUD compared with those without, highlights the critical need for improved access to harm reduction and treatment interventions among this population.

Patterns of publicly funded naltrexone use among patients diagnosed with alcohol use disorder in Ontario.

AIMS: Naltrexone is recommended first-line to manage alcohol use disorder (AUD). With previous studies indicating poor retention on naltrexone, we determined duration of naltrexone use and assessed the association between prescription setting and time to discontinuation in Ontario. METHODS: We conducted a retrospective population-based cohort study among Ontario public drug beneficiaries diagnosed with AUD who initiated publicly funded naltrexone from June 2018 to September 2019. The primary outcome was time to naltrexone discontinuation, with a secondary analysis assessing receipt of at least one prescription refill. We used Cox proportional hazards models and logistic regression to test the association between prescription setting and each medication persistence outcome. RESULTS: Among 2531 new naltrexone patients with AUD, the median duration of naltrexone use was 31 days and 394 (15.6%) continued naltrexone for 6 months or longer. There was no association between setting of initiation and duration of naltrexone use; however, those initiating naltrexone following an acute inpatient hospital stay were more likely to fill a second prescription (aOR 1.43, 95% CI 0.96-2.14), while those initiating after an ED visit were less likely to be dispensed a second prescription (aOR = 0.69, 95% CI 0.52-0.90) compared to those starting in a physician's office. CONCLUSION: Persistence on naltrexone to treat an AUD is low, regardless of the setting of initiation. Further research is needed to elucidate the barriers encountered by patients with AUD that lead to poor treatment persistence in order to develop interventions that facilitate patient-centered access to evidence-based treatment for AUD in the province.

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.

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.

Initiations of safer supply hydromorphone increased during the COVID-19 pandemic in Ontario: An interrupted time series analysis.

AIMS: Calls to prescribe safer supply hydromorphone (SSHM) as an alternative to the toxic drug supply increased during the COVID-19 pandemic but it is unknown whether prescribing behaviour was altered. We aimed to evaluate how the number of new SSHM dispensations changed during the pandemic in Ontario. METHODS: We conducted a retrospective interrupted time-series analysis using provincial administrative databases. We counted new SSHM dispensations in successive 28-day periods from March 22, 2016 to August 30, 2021. We used segmented Poisson regression methods to test for both a change in level and trend of new dispensations before and after March 17, 2020, the date Ontario's pandemic-related emergency was declared. We adjusted the models to account for seasonality and assessed for over-dispersion and residual autocorrelation. We used counterfactual analysis methods to estimate the number of new dispensations attributable to the pandemic. RESULTS: We identified 1489 new SSHM dispensations during the study period (434 [mean of 8 per 28-day period] before and 1055 [mean of 56 per 28-day period] during the pandemic). Median age of individuals initiating SSHM was 40 (interquartile interval 33-48) with 61.7% (N = 919) male sex. Before the pandemic, there was a small trend of increased prescribing (incidence rate ratio [IRR] per period 1.002; 95% confidence interval [95CI] 1.001-1.002; p<0.001), with a change in level (immediate increase) at the pandemic date (relative increase in IRR 1.674; 95CI 1.206-2.322; p = 0.002). The trend during the pandemic was not statistically significant (relative increase in IRR 1.000; 95CI 1.000-1.001; p = 0.251). We estimated 511 (95CI 327-695) new dispensations would not have occurred without the pandemic. CONCLUSION: The pandemic led to an abrupt increase in SSHM prescribing in Ontario, although the rate of increase was similar before and during the pandemic. The absolute number of individuals who accessed SSHM remained low throughout the pandemic.

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.

Trends in varying modes of drug use in opioid toxicity deaths in Ontario from 2017 to 2021.

BACKGROUND: Preliminary data indicate a shift toward inhalation instead of injection in opioid toxicity deaths. Understanding changing modes of drug use is essential to addressing the North American drug toxicity crisis driven primarily by unregulated fentanyl. This study aims to comprehensively characterize this shift across Ontario, Canada. METHODS: We conducted a population-based repeated cross-sectional study of accidental opioid toxicity deaths in Ontario from July 1, 2017 to June 30, 2021. For each quarter of the study period, the number and percent of deaths by mode of drug use (inhalation only, injection only, both or other) were reported. Descriptive characteristics were reported in the last two years of the study. RESULTS: There were 6687 accidental opioid toxicity deaths in Ontario over the study period, with a 62.1 % increase in the quarterly number of deaths observed. The prevalence of deaths where inhalation was the only mode of drug use almost doubled, rising from 22.0 % to 43.5 %. There was a corresponding 64.4 % decrease in opioid toxicity deaths with indication of injection alone (29.0 % to 10.3 %). CONCLUSIONS: This study reveals a shift in mode of drug use toward inhalation that is increasingly contributing to opioid toxicity deaths in Ontario. Understanding the shifts in patterns of opioid use serves to provide essential insights into more effective harm reduction and treatment approaches to address the drug toxicity crisis.

Impact of national recommendations for routine pertussis vaccination during pregnancy on infant pertussis in Ontario, Canada: a population-based time-series study.

BACKGROUND: In February 2018, Canada's National Advisory Committee on Immunization (NACI) recommended antenatal tetanus-diphtheria-acellular pertussis (Tdap) immunization in every pregnancy regardless of previous Tdap immunization history. We examined the impact of the NACI recommendation on rates of infant pertussis in Ontario, Canada. METHODS: We conducted a population-based time-series study of all live births in Ontario between August 1, 2011 and February 28, 2020. We used interventional autoregressive integrated moving average models to examine the impact of the NACI recommendation on monthly rates of pertussis among infants ≤ 3 months of age. RESULTS: We observed 675 incident cases of pertussis among 1,368,024 infants 3 months of age or less between August 2011 and February 2020. The average monthly percent change in infant pertussis during the period up to and including publication of the NACI guidance and the period following publication were 0.0% (95% CI: -0.4-0.3%) and - 0.8% (95% CI -2.3% to -0.1%), respectively. Following interventional ARIMA modelling, publication of the NACI guidance was not associated with a statistically significant decrease in the monthly pertussis incidence trend (-0.67 cases per 100,000 infants; p = 0.73). CONCLUSION: Publication of national recommendations for antenatal Tdap immunization in every pregnancy did not significantly reduce infant pertussis rates. This may reflect the persistently low rate of antenatal vaccination following publication of the recommendations. Expanding the scope of practice of allied health care providers to include antenatal Tdap immunization and patient education regarding antenatal pertussis immunization should be considered to further optimize uptake of vaccination.

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.

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.

Indicators of publicly funded prescription opioid use among persons with traumatic spinal cord injury in Ontario, Canada.

OBJECTIVE: To describe the proportion and identify predictors of community-dwelling individuals with traumatic spinal cord injury (TSCI) who were dispensed ≥1 publicly funded opioid in the year after injury using a retrospective cohort study. SETTING: Ontario, Canada. PARTICIPANTS, INTERVENTIONS, OUTCOME MEASURES: We used administrative data to identify predictors of receiving publicly funded prescription opioids during the year after injury for individuals who were injured between April 2004 and March 2015. Our outcome was modeled using robust Poisson multivariable regression and we reported adjusted relative risks (aRR) with 95% confidence intervals. RESULTS: In our retrospective cohort of 934 individuals with TSCI who were eligible for the provincial drug program, 510 (55%) received ≥1 prescription opioid in the year after their injury. Most individuals were male (71%) and the median age was 63 years (interquartile range: 42-72). Being male (aRR 1.15, 95% confidence interval [CI] 1.01-1.31), having chronic obstructive pulmonary disease (aRR 1.25, 95% CI 1.05-1.50), and using prescription opioids before injury (aRR 1.46, 95% CI 1.29-1.66) were significantly associated with receiving opioids in the year after TSCI. Short durations of hospital stay after injury were also identified as being a significant risk factor of outpatient opioid use (aRR = 1.28, 95% CI = 1.08-1.51) when compared to longer hospital stays. CONCLUSION: This study presented evidence showing that most individuals eligible for Ontario's public drug program who experienced a TSCI used opioids in the year following their injury. Due to the paucity of research on this population and their potential for elevated risks of adverse events, it is important for additional studies to be conducted on opioid use in this population to understand short-term and long-term risks and benefits.

Impact of policy changes and drug shortages on acamprosate and naltrexone use in Ontario, Canada.

BACKGROUND: Acamprosate and naltrexone, evidence-based pharmacotherapies for alcohol use disorder (AUD), are publicly covered by the Ontario Drug Benefit (ODB) programs; however, their availability has changed over time, with expanded formulary access in July 2018, followed by an acamprosate shortage in February 2019 and ending in July 2020. We evaluated the impact of these events on the use of these medications in Ontario, Canada. METHODS: We conducted a time-series analysis among individuals with AUD dispensed acamprosate or naltrexone through the ODB from July 2016 to December 2020. Outcomes included monthly rates of those with AUD on therapy (primary), and rate of initiation (secondary) overall and by treatment type. We used autoregressive moving average models to evaluate the impact of expanded coverage and the acamprosate shortage on rates of use, and reported characteristics at first dispensation. RESULTS: Over the study period, 10,637 individuals (61.0% male) initiated acamprosate or naltrexone. Expanded coverage increased monthly utilization rates of acamprosate (p = 0.0004), naltrexone (p < 0.0001), and either AUD pharmacotherapy (p < 0.0001). The acamprosate shortage led to a 98.1% reduction in acamprosate use (p = 0.0003) but did not impact naltrexone (p = 0.51). Our secondary analysis yielded consistent results with respect to the shortage; however, the expanded formulary listing did not impact the rate of new acamprosate patients (p = 0.3). By December 2020, 5.3% of ODB recipients with AUD were accessing pharmacotherapy. CONCLUSIONS: Although coverage expansion increased access to medications that treat AUD, the shortage of acamprosate led to large reductions in its use, with no responsive increase in naltrexone prescribing.

Impact of the COVID-19 Controlled Drugs and Substances Act exemption on pharmacist prescribing of opioids, benzodiazepines and stimulants in Ontario: A cross-sectional time-series analysis.

Background: Due to the coronavirus disease 2019 (COVID-19) pandemic, Health Canada issued an exemption to the Controlled Drugs and Substances Act (CDSA) on March 19, 2020, enabling pharmacists to act as prescribers of controlled substances to support continuity of care. Our study investigates utilization of the CDSA exemption by Ontario pharmacists with the intent to inform policy on pharmacist scope of practice and to improve future patient outcomes. Methods: We conducted a time-series analysis of pharmacist-prescribed opioid, benzodiazepine and stimulant claims data using Ontario Narcotics Monitoring System (NMS) data between January 2019 and December 2021. We used ARIMA modelling to measure the change to these classes of claims and to opioid claims containing quantities greater than a 30-day supply. Results: Postexemption, the average weekly number of pharmacist-prescribed opioid, benzodiazepine and stimulant claims rose by 146% (160 to 393 claims/week), 960% (49 to 515 claims/week) and 2150% (8 to 177 claims/week), respectively. There was a 2-week lag period between the time of announcement and the statistically significant increase in claims on April 5, 2020(p < 0.0001). The total number of claims for opioid quantities exceeding a 30-day supply decreased by 60%. Cumulative pharmacist-prescribed claims accounted for under 2% of the total NMS claims. Interpretation: Ontario pharmacists used the CDSA exemption but were prescribing at low rates. These findings suggest an effective change to pharmacy practice as the low rates show pharmacists used the exemption as a last line of defense. This may lead to further studies exploring treatment breaks during the COVID-19 pandemic and future changes to pharmacist scope to benefit patients.

Role of the posterior deep deltoid ligament in ankle fracture stability: A biomechanical cadaver study.

BACKGROUND: The deltoid ligament is a key component of ankle fracture stability. Clinical tests to assess deltoid ligament injury have low specificity. In supination external-rotation (SER) type-IV ankle fractures, there is either a medial malleolus fracture or deltoid ligament injury. These injuries are often considered unstable, requiring surgical stabilisation. We look to identify the anatomical basis for this instability. This study investigates the anatomical basis for such instability by re-creating SER type ankle fractures in a standardised cadaveric study model, investigating the anatomical basis for such instability. AIM: To investigate the anatomical basis for fracture instability in SER type ankle fractures. METHODS: Four matched pairs of cadaveric limbs were tested for stability both when axially loaded and under external rotation stress. Four matched pairs of cadaveric limbs (8 specimens) were tested for stability when axially loaded to 750 N with a custom rig. Specimens were tested through increasing stages of SER injury in a stepwise fashion before restoring the lateral side with open reduction and internal fixation (ORIF). Clinical photographs and radiographs were recorded at each step. We defined instability in accordance with well accepted radiological parameters: > 4 mm medial clear space opening on a mortise-view radiograph or > 7 degrees of talar tilt. RESULTS: All specimens with an intact posterior deep deltoid ligament were stable. Once the posterior deep deltoid ligament was sectioned there was instability in all specimens. Stabilisation of the lateral side prevented talar shift, but not talar tilt. CONCLUSION: If the posterior deep deltoid ligament is intact then SER fractures can be managed without surgery. If the posterior deep deltoid is incompetent, ORIF and cautious rehabilitation is recommended because the talus can still tilt in the mortise.

Clinical outcomes and health care costs among people entering a safer opioid supply program in Ontario.

BACKGROUND: London InterCommunity Health Centre (LIHC) launched a safer opioid supply (SOS) program in 2016, where clients are prescribed pharmaceutical opioids and provided with comprehensive health and social supports. We sought to evaluate the impact of this program on health services utilization and health care costs. METHODS: We conducted an interrupted time series analysis of London, Ontario, residents who received a diagnosis of opioid use disorder (OUD) and who entered the SOS program between January 2016 and March 2019, and a comparison group of individuals matched on demographic and clinical characteristics who were not exposed to the program. Primary outcomes were emergency department (ED) visits, hospital admissions, admissions for infections and health care costs. We used autoregressive integrated moving average (ARIMA) models to evaluate the impact of SOS initiation and compared outcome rates in the year before and after cohort entry. RESULTS: In the time series analysis, rates of ED visits (-14 visits/100, 95% confidence interval [CI] -26 to -2; p = 0.02), hospital admissions (-5 admissions/100, 95% CI -9 to -2; p = 0.005) and health care costs not related to primary care or outpatient medications (-$922/person, 95% CI -$1577 to -$268; p = 0.008) declined significantly after entry into the SOS program (n = 82), with no significant change in rates of infections (-1.6 infections/100, 95% CI -4.0 to 0.8; p = 0.2). In the year after cohort entry, the rate of ED visits (rate ratio [RR] 0.69, 95% CI 0.53 to 0.90), hospital admissions (RR 0.46, 95% CI 0.29 to 0.74), admissions for incident infections (RR 0.51, 95% CI 0.27 to 0.96) and total health care costs not related to primary care or outpatient medications ($15 635 v. $7310/person-year; p = 0.002) declined significantly among SOS clients compared with the year before. We observed no significant change in any of the primary outcomes among unexposed individuals (n = 303). INTERPRETATION: Although additional research is needed, this preliminary evidence indicates that SOS programs can play an important role in the expansion of treatment and harm-reduction options available to assist people who use drugs and who are at high risk of drug poisoning.

The Risk of Ventricular Dysrhythmia or Sudden Death in Patients Receiving Serotonin Reuptake Inhibitors With Methadone: A Population-Based Study.

Background: Methadone is associated with ventricular dysrhythmias and sudden death. Serotonin reuptake inhibitors (SRIs) may increase the risk of these events either by inhibiting metabolism of methadone's proarrhythmic (S)-enantiomer, additive QT interval prolongation, or both. We sought to determine whether certain SRIs were associated with a higher risk of methadone-related ventricular dysrhythmias or sudden death. Methods: We conducted a nested case-control study of Ontario residents receiving methadone between April 1, 1996 and December 31, 2017. Cases, defined as patients who died of sudden cardiac death or were hospitalized with a ventricular dysrhythmia while on methadone, were matched with up to four controls who also received methadone on age, sex, and a disease risk score. We determined the odds ratio (OR) and p-value functions for the association between methadone-related cardiotoxicity and treatment with SRIs known to inhibit metabolism of (S)-methadone (paroxetine, fluvoxamine, sertraline) or prolong the QT interval (citalopram and escitalopram). Patients who were not treated with an SRI served as the reference group. Results: During the study period, we identified 626 cases and 2,299 matched controls. Following multivariable adjustment, we found that recent use of sertraline, fluvoxamine or paroxetine (adjusted OR 1.30; 95% confidence intervals [CI] 0.90-1.86) and citalopram and escitalopram (adjusted OR 1.26; 95% CI 0.97-1.63) were associated with small increases in the risk methadone-related cardiac toxicity, an assertion supported by the corresponding p-value functions. Interpretation: Certain SRIs may be associated with a small increase in cardiac toxicity in methadone-treated patients.

Regional differences in access to direct-acting antiviral treatments for hepatitis C across Ontario: A cross-sectional study.

Background: Direct-acting antivirals (DAAs) are curative treatments for hepatitis C virus (HCV) infection, a condition affecting over 100,000 Ontarians. Although DAAs are covered under the public drug programs in Ontario, receiving prescriptions depends on access to healthcare. The aim of this study is to understand the relationship between DAA treatment rates and distance to prescriber in Ontario, Canada. Methods: We conducted a cross-sectional study and identified patients who filled a DAA prescription through the Ontario Drug Benefit (ODB) in 2019. We calculated crude (per 100,000 ODB recipients) and adjusted (by a regional HCV infection rate) DAA treatment rates by public health unit (PHU). We reported median distances to provider for all visit types, in-person visits, virtual visits, and proportions of visits that were virtual. Results: In 2019, the crude DAA treatment rate for Ontario is 83.0 patients per 100,000 ODB recipients. The HCV-adjusted DAA treatment rate ranges from 28.2 (Northwestern Ontario) to 188.5 (Eastern Ontario) per 100,000. In our primary analysis, patients in rural PHUs, including Northwestern and Porcupine, were among the highest median distances to prescriber for all visit types (1,195 km and 556 km, respectively). These PHUs also had the highest proportions of virtual visits (greater than 60%). Urban PHUs, such as Toronto and Ottawa, had smaller median distances for all visit types, with smaller proportions of virtual visits (10.8% and 12.4%, respectively). Conclusion: We observed heterogeneity in treatment rates, distance to DAA prescribers and use of virtual care in the management of HCV. Increasing use of telemedicine in regions with limited utilization of DAAs may improve access.

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.