Interventional pain blocks in Ontario: a population-based cross-sectional study on 2019 procedural volumes, clustering, and physician billings.

PURPOSE: Multidisciplinary chronic pain management includes pharmacologic, psychological, and interventional strategies. In Canada, the use of interventional pain blocks (PBs) has increased in recent years. We sought to determine the distribution and clustering of PBs among physicians in Ontario, and to examine differences in the patient and physician characteristics by volume of PBs administered. METHODS: We conducted a population-based cross-sectional study of PBs administered for chronic pain to Ontario residents between 1 January and 31 December 2019. Our primary outcome was the total number of PBs administered in an outpatient setting for chronic pain by eligible physicians. We used Lorenz curves, overall and stratified by PB type and physician specialty, to examine clustering of PBs among physicians, and compared patient and physician characteristics using standardized differences. RESULTS: Among physicians who provided PBs, provision was highly clustered, with the top 1% of physicians providing 39% of blocks. In these high-volume PB providers, the majority of whom were general practitioners (88.4%), PBs made up the vast majority (median [interquartile range (IQR)], 87% [84-89]) of their billings, with the majority of the patients in their practices (63.0%) receiving at least one PB in 2019. Patients who received a PB from a high-volume provider had a higher annual frequency of visit for PBs (median [IQR], 10 [3-23]) and number of PBs administered per visit (median [IQR], 5 [4-6]). CONCLUSION: Pain block administration is highly clustered in Ontario, with many patients receiving PBs in ways that are not supported by best evidence. Further research is required to determine whether the Ontario fee-for-service model of billing has created a suboptimal use of these health care resources.

RéSUMé: OBJECTIF: La prise en charge multidisciplinaire de la douleur chronique comprend des stratégies pharmacologiques, psychologiques et interventionnelles. Au Canada, l'utilisation de blocs interventionnels pour la douleur (PB pour 'pain block') a augmenté au cours des dernières années. Nous avons cherché à déterminer la répartition et le regroupement des PB parmi les médecins en Ontario, et à examiner les différences dans les caractéristiques de la patientèle et des médecins selon le volume de blocs administrés. MéTHODE: Nous avons mené une étude transversale basée sur la population des PB administrés pour traiter la douleur chronique aux personnes résidant en Ontario entre le 1er janvier et le 31 décembre 2019. Notre critère d'évaluation principal était le nombre total de blocs pour la douleur administrés en ambulatoire pour la douleur chronique par des médecins éligibles. Nous avons utilisé les courbes de Lorenz, globalement et stratifiées par type de blocs pour la douleur et par spécialité médicale, pour examiner le regroupement des PB parmi les médecins, et comparé les caractéristiques de la patientèle et des médecins en utilisant des différences standardisées. RéSULTATS: Parmi les médecins qui réalisaient des PB, l'offre était fortement regroupée, le 1 % supérieur des médecins réalisant 39 % des blocs. Parmi ces médecins réalisant un volume élevé de PB, dont la majorité étaient des médecins généralistes (88,4 %), les PB représentaient la grande majorité ([écart interquartile (ÉIQ)] médian, 87 % [84-89]) de leur facturation, la majorité (63,0 %) des patient·es de leur cabinet recevant au moins un bloc pour la douleur en 2019. Les patient·es qui ont reçu un PB d'un prestataire à volume élevé avaient une fréquence annuelle de visite plus élevée pour les PB (médiane [ÉIQ], 10 [3-23]) et un nombre plus élevé de PB administrés par visite (médiane [ÉIQ], 5 [4-6]). CONCLUSION: L'administration de blocs pour la douleur est fortement concentrée en Ontario, bon nombre de patient·es recevant des PB d'une manière qui n'est pas appuyée par les meilleures données probantes. D'autres recherches sont nécessaires pour déterminer si le modèle de facturation à l'acte de l'Ontario a créé une utilisation sous-optimale de ces ressources en soins de santé.

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 Rates of Opioid Agonist Treatment and Opioid-Related Deaths for Youths in Ontario, Canada, 2013-2021.

Importance: Data suggest that the opioid crisis in North America has recently been reflected in opioid-related mortality among youths. Despite recommendation for its use, youths encounter barriers to accessing OAT, including stigma, burden of witnessed dosing, and lack of availability of youth-oriented services and prescribers comfortable treating this population. Objective: To compare rates of opioid agonist treatment (OAT) and opioid-related mortality between youths aged 15 to 24 years and adults aged 25 to 44 years in Ontario, Canada, over time. Design, Setting, and Participants: This cross-sectional analysis of rates of OAT and opioid-related deaths between 2013 and 2021 used data obtained from the Ontario Drug Policy Research Network, Public Health Ontario, and Statistics Canada. Individuals included in the analysis were aged 15 to 44 years and residing in Ontario, the most populous province in Canada. Exposures: Youths aged 15 to 24 years compared with adults aged 25 to 44 years. Main Outcomes and Measures: OAT (methadone, buprenorphine, and slow-release oral morphine) per 1000 population and opioid-related deaths per 100 000 population. Results: Between 2013 and 2021, 1021 youths aged 15 to 24 years died from opioid toxicity; 710 were male (69.5%). In the final year of the study period, 225 youths (146 male [64.9%]) died from opioid toxicity, and 2717 (1494 male [55.0%]) were dispensed OAT. Over the study period, the rate of opioid-related deaths among youths in Ontario increased 369.2% from 2.6 to 12.2 per 100 000 population (48 to 225 total deaths) and the rate of OAT use decreased 55.9% from 3.4 to 1.5 per 1000 (6236 to 2717 individuals). For adults aged 25 to 44 years, the rate of opioid-related deaths increased 371.8% from 7.8 to 36.8 per 100 000 (283 to 1502 deaths), and the rate of OAT increased 27.8% from 7.9 to 10.1 per 1000 population (28 667 to 41 200 individuals). Trends for youths and adults persisted across both sexes. Conclusions and Relevance: The findings of this study suggest that opioid-related deaths are increasing among youths while OAT use is paradoxically declining. The reasons for these observed trends require further investigation, including a consideration of changing trends in opioid use and opioid use disorder among youths, barriers to OAT, and opportunities to optimize care and reduce harms for youths who use substances.

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.

Use of injections for chronic pain from 2010 to 2019 in Ontario, Canada.

PURPOSE: The management of chronic pain often involves interventional procedures such as injections. Nevertheless, there have been concerns raised regarding the frequency with which these injections are being performed. We conducted a descriptive study to examine trends in the use of pain injections over a ten-year time period in Ontario, Canada. METHODS: We used provincial administrative data to conduct a retrospective observational study of the most common pain injections performed from 2010 to 2019 in Ontario. We determined the frequency of pain injections and their associated physician billings from physician billing data. RESULTS: A total of 18,050,058 pain injections were included in this study with an associated total cost of CAD 865,431,605. There was a threefold increase in the number of blocks performed annually and associated costs, rising from 1,009,324 blocks (CAD 50,026,678) in 2010 to 3,198,679 blocks (CAD 156,809,081) in 2019. The majority of injections were performed by general practioners (70.8%), followed by anesthesiologists (8.3%). CONCLUSION: This descriptive study revealed a rapid increase in the frequency of pain injections performed in Ontario from 2010 to 2019. Given the associated costs and potential risks, this warrants further investigation to ensure that these interventions are being administered appropriately.

RéSUMé: OBJECTIF: La prise en charge de la douleur chronique implique souvent des procédures interventionnelles telles que des injections. Néanmoins, des préoccupations ont été soulevées quant à la fréquence à laquelle ces injections sont administrées. Nous avons réalisé une étude descriptive pour examiner les tendances dans l'utilisation d'injections pour soulager la douleur sur une période de dix ans en Ontario, au Canada. MéTHODE: Nous avons utilisé les données administratives provinciales pour réaliser une étude observationnelle rétrospective des injections pour soulager la douleur les plus courantes effectuées de 2010 à 2019 en Ontario. Nous avons déterminé la fréquence des injections pour soulager la douleur et les facturations des médecins associées à partir des données de facturation des médecins. RéSULTATS: Au total, 18 050 058 injections pour soulager la douleur ont été incluses dans cette étude, avec un coût total associé de 865 431 605 CAD. Le nombre de blocs exécutés chaque année et les coûts associés ont triplé, passant de 1 009 324 blocs (50 026 678 CAD) en 2010 à 3 198 679 blocs (156 809 081 CAD) en 2019. La majorité des injections ont été administrées par des médecins généralistes (70,8 %), suivis par des anesthésiologistes (8,3 %). CONCLUSION: Cette étude descriptive a révélé une augmentation rapide de la fréquence des injections pour soulager la douleur et administrées en Ontario de 2010 à 2019. Compte tenu des coûts associés et des risques potentiels, cela justifie une enquête plus approfondie pour s'assurer que ces interventions sont administrées de manière appropriée.

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.

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.

Effectiveness of a fourth dose of covid-19 mRNA vaccine against the omicron variant among long term care residents in Ontario, Canada: test negative design study.

OBJECTIVES: To estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant. DESIGN: Test negative design. SETTING: Long term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022. PARTICIPANTS: After exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included. MAIN OUTCOME MEASURES: Laboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously. RESULTS: 13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes. CONCLUSIONS: The findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown.

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.

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.

The effects of COVID-19 on the dispensing rates of antidepressants and benzodiazepines in Canada.

BACKGROUND: Population studies have shown that rates of depressive and anxious symptoms have increased as a result of COVID-19. We analyzed trends in the dispensing rates of antidepressants and benzodiazepines in Canada to determine whether the pandemic has caused changes in rates of pharmacological treatment for depression and anxiety. METHODS: We conducted a population-based, cross-sectional time-series analysis of antidepressants and benzodiazepines dispensed monthly by Canadian community pharmacies between January 2017 and December 2020. We used March 2020 as the intervention month to determine if there were any significant changes in the national rate of antidepressant and benzodiazepine tablets dispensed as the result of the COVID-19 pandemic. RESULTS: There was a temporary reduction in the dispensing rate of antidepressants in April 2020 (from 489 tablets per 100 in March 2020 to 356 tablets per 100 in April 2020; p ≤ .0001); however, the rate returned to its previous level by August 2020. There were no detectable deviations in benzodiazepine dispensing after the declaration of the state of emergency in Ontario. CONCLUSIONS: Despite the increased reporting of depressive and anxious symptoms during the COVID-19 pandemic, there have been no changes in the dispensing trends of medications used to treat these disorders. As the pandemic continues to evolve, future research is needed to monitor the prevalence of depression and anxiety, and associated medication use, in the Canadian population.

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.

The impact of proposed regulatory changes and rescheduling on low-dose codeine purchasing in Canada: a time-series analysis.

BACKGROUND: Low-dose codeine products can be purchased without a prescription in most of Canada. We explored trends in the purchasing of these products across the Canadian provinces from 2014 to 2019, evaluating the impact of Health Canada's 2016 announcement of a proposed regulatory change and the 2017 opening of a 60-day public comment period, as well as the impact of Manitoba's 2016 policy change requiring a prescription for the purchase of all codeine products in that province. METHODS: We evaluated population-adjusted monthly purchasing of codeine products from January 2014 to October 2019 using the IQVIA Canadian Drug Store and Hospital Purchases Audit database, stratified by province and over-the-counter (OTC) status. The primary outcomes were change in the monthly volume of low-dose codeine purchased after the 2016 federal regulatory proposal and the 2017 period of public comment across the provinces. Our secondary analysis was the impact of Manitoba's policy change in February 2016 requiring a prescription for low-dose codeine. We conducted a time-series analysis using interventional autoregressive integrated moving average models. RESULTS: Over the study period, 24 120 kg of codeine (3.025 billion units) and 937 867 kg of acetaminophen were sold as OTC, low-dose codeine products across the Canadian provinces. Health Canada's 2016 announcement did not significantly affect OTC codeine purchasing (p = 0.57). The initiation of a 60-day public comment period was associated with a roughly 44% decrease in OTC codeine purchasing (p = 0.03). In Manitoba, purchasing of the same codeine formulations decreased after rescheduling in February 2016 (p < 0.001). We observed no significant change in the rate of purchasing of higher dose codeine formulations in response to scheduling changes in Manitoba (p = 0.22). INTERPRETATION: Although Health Canada's 2016 announcement of a proposed regulatory change did not appear to have an effect on OTC codeine purchasing nationally, the 60-day comment period was associated with a decrease in purchasing. Further, Manitoba's 2016 policy change was associated with a significant and sustained decrease in the overall volume of codeine purchased. Given the potential risks of codeine dependence and acetaminophen toxicity with these products, a national rescheduling strategy should be considered.

Projected impact of biosimilar substitution policies on drug use and costs in Ontario, Canada: a cross-sectional time series analysis.

BACKGROUND: Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada. METHODS: We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine. RESULTS: In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab). INTERPRETATION: Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients.

Trends and outcomes of serious complications associated with non-fatal opioid overdoses in Ontario, Canada.

BACKGROUND: Non-fatal opioid overdoses can lead to serious complications and consequently, long-term health effects. We sought to characterize trends of hospitalizations for serious complications associated with opioid overdoses in Ontario, Canada and report health services utilization and mortality in the year following hospital discharge. METHODS: We conducted a cross-sectional study in Ontario among individuals who experienced a hospitalization for a serious complication (required intubation, rhabdomyolysis, or a brain injury) associated with an opioid overdose between 2010 and 2019. We examined inpatient characteristics at the time of hospital admission, and health services utilization and mortality rates in the year following hospital discharge. RESULTS: The rate of hospitalizations for serious complications associated with opioid overdoses increased by 66.7 % from 1.8 per 100,000 population in 2010 to 3.0 per 100,000 population in 2019 in Ontario. Individuals that were discharged alive from hospital experienced high health services utilization in the following year; 71.2 % (N = 953 of 1,338) visited the emergency department (ED), 34.2 % (N = 458) were admitted to hospital, and 16.4 % (N = 219) were treated in hospital for an opioid overdose. However only a quarter of individuals (N = 332; 24.8 %) initiated on opioid agonist therapy within 90 days. Additionally, 8.0 % (N = 127) of hospitalizations resulted in death within 1 year. CONCLUSIONS: This study highlights increasing rates of serious complications associated with opioid overdoses, with a high demand of health services and a high mortality rate in the following year. These findings highlight an ongoing need for support and harm reduction services to allow for early intervention and follow-up care.

Effect of listing strategies on utilization of antitumor necrosis factor biologics infliximab and etanercept: a cross-sectional analysis from Ontario, Canada.

BACKGROUND: Use of costly biologic drugs for the treatment of chronic inflammatory diseases has increased significantly in recent years. However, biosimilar drugs offer an opportunity to ensure health system sustainability with robust uptake. OBJECTIVE: To study the effect of formulary listing strategies on the use of infliximab and etanercept innovator and biosimilar biologics. METHODS: This is a cross-sectional study of individuals in Ontario, Canada, dispensed a biologic prescription for infliximab or etanercept through Ontario's public drug program between January 1, 2010, and June 30, 2019. Quarterly utilization and costs were forecasted using Holt-Winters' exponential smoothing models to the second quarter (Q2) of 2022. Secondary analyses explored utilization for rheumatic conditions (RC) and inflammatory bowel disease (IBD). RESULTS: From Q1 2010 to Q2 2019, infliximab and etanercept users increased by 75.7% (n = 4,073 to 7,158), with a forecasted increase of 13.7% (n = 8,142; 95% CI = 7,438-8,847) by Q2 2022. Biosimilar users represented 13.8% (n = 539 of 3,905) of total infliximab users in Q2 2019, although this differed by indication with 6.9% for IBD (n = 187 of 2,712) and 26.6% for RC (n = 203 of 764). Etanercept biosimilar users represented 20.2% (n = 659 of 3,256) of total etanercept users for RC in Q2 2019. Biologics expenditures increased 109.7% during the study, amounting to $49.9 million in Q2 2019. CONCLUSIONS: Despite differing reimbursement restrictions between innovator infliximab and etanercept biologics, the uptake of their biosimilars was low and not noticeably different in the treatment of RC. Dynamic policy strategies are needed to improve the uptake of biosimilars, particularly for IBD. DISCLOSURES: Funding for this study was contributed by the Ontario Ministry of Health. The authors have no conflicts of interest to disclose.