Search

The COVID-19 pandemic was associated with increases in the prevalence of depression and anxiety among children and young adults. We studied whether the pandemic was associated with changes in prescription benzodiazepine use. We conducted a population-based study of benzodiazepine dispensing to children and young adults ≤ 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 prescription benzodiazepine dispensing occurred, and interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected benzodiazepine use. A structural break occurs where there is a sudden change in the trend of a time series. We observed an immediate decline in benzodiazepine dispensing of 23.6 per 100,000 (95% confidence interval [CI]: -33.6 to -21.2) associated with a structural break in April 2020, followed by a monthly decrease in the trend of 0.3 per 100,000 (95% CI: -0.74 to 0.14). Lower than expected benzodiazepine dispensing rates were observed each month of the pandemic from April 2020 onward, with relative percent differences ranging from - 7.4% (95% CI: -10.1% to - 4.7%) to -20.9% (95% CI: -23.2% to -18.6%). Results were generally similar in analyses stratified by sex, age, neighbourhood income quintile, and urban versus rural residence. Further research is required to understand the clinical implications of these findings and whether these trends were sustained with further follow-up., (© 2024. The Author(s).)

Objectives: Adherence to medications is important for the management of chronic diseases. Although the proportion of days covered (PDC) is a common metric for measuring adherence, it may be insufficient to distinguish relevant differences in medication-taking behavior. Group-based trajectory models (GBTMs) have been used to better represent adherence over time. This study aims to examine adherence patterns 1 year after initiation among users of sodium-glucose cotransporter 2 (SGLT2) inhibitors using GBTMs and evaluate the ability of baseline characteristics to predict adherence trajectory., Study Design: SGLT2 inhibitor new-user cohort study from 2014 to 2018., Methods: We calculated 12-month PDC and categorized patients with PDC of 80% or greater as adherent. We performed multivariable logistic regression on adherence status controlling for baseline covariates. GBTMs were fit to identify adherence patterns 12 months following SGLT2 inhibitor initiation. Five multinomial logistic regression models including different subsets of predictors were used to predict adherence trajectory group assignment., Results: In a cohort of 228,363 SGLT2 inhibitor users, the mean PDC was 57%, with 36% of the cohort being adherent. Overall, women and patients with anxiety or depression were less likely to be adherent. Six patterns of SGLT2 inhibitor adherence were identified with GBTMs: 1 fill (PDC = 0.08), early discontinuation (PDC = 0.22), consistently low adherence (PDC = 0.35), moderate adherence (PDC = 0.48), high adherence (PDC = 0.79), and near-perfect adherence (PDC = 0.95). All prediction models showed poor predictive accuracy (0.35)., Conclusions: We found wide variation in adherence patterns among SGLT2 inhibitor users in a national cohort. Predictors from a health care claims database were unable to accurately predict adherence trajectory.

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., (© 2024. The Author(s).)

Objective: Digital substance use treatment programs present an opportunity to provide nonresidential care for people with problematic substance use. In June 2021, the provincial government in Ontario provided free access to Breaking Free Online (BFO), a digital behavioral change program for people with substance use disorders., Methods: An observational study was conducted with retrospective data to characterize clients' use and engagement patterns in BFO and examine changes in self-reported outcomes., Results: In total, 6,370 individuals registered for BFO between June 2021 and October 2022, of whom 3,650 completed the intake assessment. Most of these clients were self-referred (64%), with 37% having been referred by health service providers. More than one-half of the clients (52%) resided in Ontario West or East regions. Support for addressing problematic alcohol use was the most requested program (40%). By October 2022, about 44% of the clients had completed between one and four of 12 program strategies. Analysis revealed significant changes in pre-post scores across four validated scales (p<0.001), indicating a decrease in anxiety and depression, an increase in quality of life, an improvement in recovery progression, and a decrease in severity of symptoms associated with substance use disorders., Conclusions: BFO clients with higher completion rates had the most improvement across the scales used; however, clients with lower and medium completion rates also had improvements. Because of the shame and stigma associated with substance use, digital supports with low barriers to entry can help support the autonomy, privacy, and preferences of individuals seeking help for problematic substance use., Competing Interests: The authors report no financial relationships with commercial interests.

Purpose: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors., Methods: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion., Results: In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures., Conclusion: For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: There is limited knowledge on international trends in topical calcineurin inhibitor (TCI) utilization. Objective: To describe international TCI utilization trends from 2012 to 2019 and evaluate the relationship of country-level economic status, geographic location, and atopic dermatitis (AD) disease burden with drug utilization. Methods: We used IQVIA MIDAS ® pharmaceutical quarterly sales data to attain country-level purchasing of TCIs in grams from 2012 to 2019. A multivariable linear regression estimated the association between countries' sociodemographic index (SDI), AD disability-adjusted life year (DALY) rates, and geographic location with TCI utilization. Results: A total of 68 countries were included in our analysis. From 2012 to 2019, overall TCI utilization increased by 66% but remained 11.2 times higher in high-sociodemographic compared with low-middle/low-sociodemographic countries. SDI and geographic location were associated with greater TCI utilization in multivariable analyses, whereas AD DALY rates were not. High-SDI countries used 21,476 grams (95% confidence interval [CI]: 11,915 to 31,036) and high-middle SDI countries used 9,403 grams (95% CI: -393 to 19,200) more TCIs per 100,000 people compared with low-middle/low-SDI countries, respectively. Northern hemisphere countries used 8,588 grams more TCIs per 100,000 people (95% CI: 612 to 16,564). Conclusions: We demonstrated greater TCI utilization among high-SDI compared with lower SDI countries.

Study Design: Descriptive repeated-cross sectional retrospective longitudinal cohort study., Objective: To investigate the impact of the COVID-19 pandemic on homecare services in individuals with traumatic or non-traumatic Spinal Cord Injury (SCI)., Setting: Health administrative database in Ontario, Canada., Methods: A repeated cross-sectional study using linked health administrative databases from March 2015 to June 2022. Monthly homecare utilization was assessed in 3381 adults with SCI using Autoregressive Integrated Moving Average (ARIMA) models., Results: Compared to pre-pandemic levels, between March 2020 to June 2022, the traumatic group experienced a decrease in personal and/or homemaking services, as well as an increase in nursing visits from April 2020-March 2022 and June 2022. Case management increased at various times for the traumatic group, however therapies decreased in May 2020 only. The non-traumatic group experienced a decrease in personal and/or homemaking services in July 2020, as well as an increase in nursing visits from March 2020 to February 2021 and sporadically throughout 2020. Case management also increased at certain points for the non-traumatic group, but therapies decreased in April 2020, July 2020, and September 2021., Conclusion: The traumatic group had decreases in personal and/or homemaking services. Both groups had increases in nursing services, increases in case management, and minimal decreases in therapies at varying times during the pandemic. Investigation is warranted to understand the root cause of these changes, and if they resulted in adverse outcomes., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug's safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11-16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3-15.4%), neutropenia was 7.1% (95% CI, 4.6-10.4%), and anemia was 11.3% (95% CI, 8.0-15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians.

Objectives: To evaluate whether providing family physicians with feedback on their antibiotic prescribing compared with that of their peers reduces antibiotic prescriptions. To also identify effects on antibiotic prescribing from case-mix adjusted feedback reports and messages emphasising antibiotic associated harms., Design: Pragmatic, factorial randomised controlled trial., Setting: Primary care physicians in Ontario, Canada PARTICIPANTS: All primary care physicians were randomly assigned a group if they were eligible and actively prescribing antibiotics to patients 65 years or older. Physicians were excluded if had already volunteered to receive antibiotic prescribing feedback from another agency, or had opted out of the trial., Intervention: A letter was mailed in January 2022 to physicians with peer comparison antibiotic prescribing feedback compared with the control group who did not receive a letter (4:1 allocation). The intervention group was further randomised in a 2x2 factorial trial to evaluate case-mix adjusted versus unadjusted comparators, and emphasis, or not, on harms of antibiotics., Main Outcome Measures: Antibiotic prescribing rate per 1000 patient visits for patients 65 years or older six months after intervention. Analysis was in the modified intention-to-treat population using Poisson regression., Results: 5046 physicians were included and analysed: 1005 in control group and 4041 in intervention group (1016 case-mix adjusted data and harms messaging, 1006 with case-mix adjusted data and no harms messaging, 1006 unadjusted data and harms messaging, and 1013 unadjusted data and no harms messaging). At six months, mean antibiotic prescribing rate was 59.4 (standard deviation 42.0) in the control group and 56.0 (39.2) in the intervention group (relative rate 0.95 (95% confidence interval 0.94 to 0.96). Unnecessary antibiotic prescribing (0.89 (0.86 to 0.92)), prolonged duration prescriptions defined as more than seven days (0.85 (0.83 to 0.87)), and broad spectrum prescribing (0.94 (0.92 to 0.95)) were also significantly lower in the intervention group compared with the control group. Results were consistent at 12 months post intervention. No significant effect was seen for including emphasis on harms messaging. A small increase in antibiotic prescribing with case-mix adjusted reports was noted (1.01 (1.00 to 1.03))., Conclusions: Peer comparison audit and feedback letters significantly reduced overall antibiotic prescribing with no benefit of case-mix adjustment or harms messaging. Antibiotic prescribing audit and feedback is a scalable and effective intervention and should be a routine quality improvement initiative in primary care., Trial Registration: ClinicalTrials.gov NCT04594200., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding by the Canadian Institute for Health Research; JAL reports financial compensation for expert testimony by the Ontario Hospital Association, Ontario Ministry of the Attorney General, Seneca College and Choosing Wisely Canada. TG reports financial compensation from the Ontario Ministry of Health, Ontario College of Pharmacists, the Canadian Agency for Drugs and Technologies in Health, and Indigenous Services Canada. All other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High-quality primary care is associated with better health outcomes and more efficient and equitable health system performance. However, the rate of primary care attachment is falling, and timely access to primary care is worsening, driving many patients to use walk-in clinics for their comprehensive primary care needs. This study sought to explore the experiences and perceived roles and responsibilities of walk-in physicians in this current climate. Methods: Qualitative interviews were conducted with nineteen physicians currently providing walk-in care in Ontario, Canada between May and December 2022., Results: Limited capacity for continuity and comprehensiveness of care were identified as major sources of professional tension for walk-in physicians. Divergent perspectives on their roles were anchored in how physicians viewed their professional identity. Some saw providing continuous and comprehensive care as an infringement on their professional role; others saw their professional role as more flexible and responsive to population needs. Regardless of their professional identity, participants reported feeling ill-equipped to manage the swell of unattached patients, citing a lack of time, resources, connectivity to the system, and remuneration flexibility. Conclusions: As practice demands of walk-in clinics change, an evolution in the professional roles and responsibilities of walk-in physicians follows. However, the resources, structure, and incentives of walk-in care have not evolved to reflect this, leaving physicians to set their own professional boundaries with patients. This results in increasing variations in care and confusion across the primary care sector around who is responsible for what, when, and how., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Terpou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: We assessed protection from coronavirus disease 2019 (COVID-19) vaccines and/or prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection against Omicron-associated severe outcomes during successive sublineage-predominant periods., Methods: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, polymerase chain reaction (PCR)-tested adults aged ≥50 years in Ontario, Canada, between 2 January 2022 and 30 June 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection., Results: We included 18 526 cases with Omicron-associated severe outcomes and 90 778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95% confidence interval [CI] 63%-72%; fourth-dose, 6-month: 80%, 95% CI 77%-83%) but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95% CI 48%-67%; 12-month: 49%, 95% CI 41%-56%; fourth-dose, 6-month: 62%, 95% CI 56%-68%, 12-months: 51%, 95% CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95% CI 36%-75%; fourth-dose, 6-month: 63%, 95% CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95% CI 79%-96%). Prior infection alone did not confer lasting protection., Conclusions: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review., Competing Interests: Potential conflicts of interest. N. L. has previously received honoraria for consultancy work, speaking in educational programs, and/or travel support from: Shionogi Inc., Gilead Sciences Canada Inc., Janssen Inc., GlaxoSmithKline plc., Sanofi Pasteur Ltd., F. Hoffmann-La Roche Ltd., Genentech Inc., CIDARA Therapeutics Inc., Clarion Healthcare, bioStrategies, Technospert, Aligos; all unrelated to this work. K. W. is a shareholder and board member and Co-founder and Chief Scientific Officer of CANImmunize Inc. and has served on independent scientific advisory boards for Medicago (Independent Data Monitoring Committee) and Moderna (Global Advisory Core Consultancy Group). J. G. reports a position as a paid consultant scientific editor for GIDEON Informatics, Inc., which is unrelated to the current work. S. E. W. reports being a co-investigator on a grant related to public health surveillance of invasive pneumococcal disease (no involvement in administration of funds) for the Canadian Immunization Research Network and a co-investigator on a grant on immunization data in Canada (no involvement in administration of funds) for CIRN; travel support to attend the Future of Vaccinology conference in October 2023 as an invited speaker from McMaster University (Hamilton, ON) and a role as an unpaid volunteer member for Canada's National Advisory Committee on Immunization (NACI). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest A.M.D. has received ­compensation from the British Journal of Dermatology (Section Editor), American Academy of Dermatology (guidelines writer), Canadian Dermatology Today (manuscript writer) and Canadian Agency for Drugs and Technologies in Health (consultant); he has received research grants to his institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes for Health Research, US National Institutes of Health and Physicians Services Incorporated Foundation. K.S.T. has received research grants to her institution from the National Institute for Health Research and the British Skin Foundation.

Background: The drug toxicity crisis continues to accelerate across Canada, with rapid increases in opioid-related harms following the onset of the COVID-19 pandemic. We sought to describe trends in the burden of opioid-related deaths across Canada throughout the pandemic, comparing these trends by province or territory, age, and sex., Methods: We conducted a repeated cross-sectional analysis of accidental opioid-related deaths between Jan. 1, 2019, and Dec. 31, 2021, across 9 Canadian provinces and territories using aggregated national data. Our primary measure was the burden of premature opioid-related death, measured by potential years of life lost. Our secondary measure was the proportion of all deaths attributable to opioids; we used the Cochrane-Armitage test for trend to compare proportions., Results: Between 2019 and 2021, the annual number of opioid-related deaths increased from 3007 to 6222 and years of life lost increased from 126 115 to 256 336 (from 3.5 to 7.0 yr of life lost per 1000 population). In 2021, the highest number of years of life lost was among males (181 525 yr) and people aged 30-39 years (87 045 yr). In 2019, we found that 1.7% of all deaths among those younger than 85 years were related to opioids, rising to 3.2% in 2021. Significant increases in the proportion of deaths related to opioids were observed across all age groups ( p < 0.001), representing 29.3% and 29.0% of deaths among people aged 20-29 and 30-39 years in 2021, respectively., Interpretation: Across Canada, the burden of premature opioid-related deaths doubled between 2019 and 2021, representing more than one-quarter of deaths among younger adults. The disproportionate loss of life in this demographic group highlights the critical need for targeted prevention efforts., Competing Interests: Competing interests:: David Juurlink is a member of Physicians for Responsible Opioid Prescribing and the American College of Medical Toxicology. Both groups have publicly available positions on this issue. He has also received payment from law firms for lectures and medicolegal opinions regarding the safety and effectiveness of analgesics, including opioids. Mina Tadrous reports consulting fees from Health Canada and the Canadian Agency for Drugs and Technologies in Health (CADTH). Tara Gomes reports funding from the Ontario College of Pharmacists and CADTH, consulting fees from the Province of British Columbia, honoraria from Indigenous Services Canada, and payment for expert testimony from the Office of the Chief Coroner of Ontario. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: Variations in primary care practices may explain some differences in health outcomes during the COVID-19 pandemic. We sought to evaluate the characteristics of primary care practices by the proportion of patients unvaccinated against SARS-CoV-2., Methods: We conducted a population-based, cross-sectional cohort study using linked administrative data sets in Ontario, Canada. We calculated the percentage of patients unvaccinated against SARS-CoV-2 enrolled with each comprehensive-care family physician, ranked physicians according to the proportion of patients unvaccinated, and identified physicians in the top 10% (v. the other 90%). We compared characteristics of family physicians and their patients in these 2 groups using standardized differences., Results: We analyzed 9060 family physicians with 10 837 909 enrolled patients. Family physicians with the largest proportion (top 10%) of unvaccinated patients ( n = 906) were more likely to be male, to have trained outside of Canada, to be older, and to work in an enhanced fee-for-service model than those in the remaining 90%. Vaccine coverage (≥ 2 doses of SARS-CoV-2 vaccine) was 74% among patients of physicians with the largest proportion of unvaccinated patients, compared with 87% in the remaining patient population. Patients in the top 10% group tended to be younger and live in areas with higher levels of ethnic diversity and immigration and lower incomes., Interpretation: Primary care practices with the largest proportion of patients unvaccinated against SARS-CoV-2 served marginalized communities and were less likely to use team-based care models. These findings can guide resource planning and help tailor interventions to integrate public health priorities within primary care practices., Competing Interests: Competing interests:: Michael Green reports research support from the Ontario Ministry of Health and the Canadian Institutes of Health Research (CIHR). He is president and board chair of the College of Family Physicians of Canada and sits on the board of AMS Healthcare. Tara Kiran reports honoraria from the Ontario College of Family Physicians, the Ontario Medical Association, the Canadian Medical Association, the Canadian College of Family Physicians, and the Association of Family Health Teams of Ontario. Mina Tadrous reports consulting fees from the Canadian Agency for Drugs and Technologies in Health and Health Canada. Dominik Nowak reports consulting fees from the Alliance for Healthier Communities, the Centre for Effective Practice, the Ontario College of Family Physicians, the Ontario Medical Association, TELUS, and Women’s College Hospital. He is president-elect of the Ontario Medical Association. Holly Witteman is supported by a Canada Research Chair and reports an honorarium from Stanford University. Isaac Bogoch reports research funding from CIHR and consulting fees from the Weapons Threat Reduction Program. David Kaplan reports travel support from the Public Health Agency of Canada; he is chair of the Post–COVID-19 Condition guideline advisory committee and sits on the board of directors with the Musical Stage Company. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

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., (© 2024 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Background: Actinic Keratoses (AK) are precancerous lesions that can lead to Squamous Cell Carcinoma. International differences in the utilization of topical medications to treat AK are not well described., Objectives: To describe international differences in topical AK medication utilization, including associations of countries' economic status with AK medication utilization., Methods: We used IQVIA MIDAS pharmaceutical sales data for 65 countries (42 high-income, 24 middle-income) from April 2011 to December 2021. We calculated each country's quarterly utilization of medications in grams per 1000 population. We used univariable linear regression to assess the association between country economic status and AK medication utilization., Results: High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60)., Limitations: Missing medication utilization data for some countries., Conclusion: High-income countries use more topical AK therapies than middle-income countries., Competing Interests: MT received consulting fees from CADTH and Health Canada. NJL is a trustee of the British Association of Dermatologists. AMD has received compensation from the British Journal of Dermatology (reviewer and Section Editor), American Academy of Dermatology (guidelines writer), National Eczema Association (grant reviewer), Canadian Dermatology Today (manuscript writer) and Canadian Agency for Drugs and Technologies in Health (consultant). AMD has received research grants to his institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes for Health Research, US National Institutes of Health and Physicians Services Incorporated Foundation., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Background: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives., Methods: We conducted a cohort study of Optum's de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups., Results: Of the 87 130 adherent patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95% CI 0.96-1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95% CI 0.97-1.12)., Conclusions: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system., (© 2024 John Wiley & Sons Ltd.)

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity. Through this exercise, we aimed to gain insight into consensus building and deliberation processes and to identify efficiencies in the application of the rating tool. An experienced facilitator led a multidisciplinary committee, consisting of 11 Canadian experts, through consensus building, deliberation, and prioritization. A total of nine RWE proposals were evaluated and prioritized as low (n = 4), medium (n = 3), or high (n = 2) priority. Through an iterative process, efficiencies and recommendations to improve the rating tool and associated procedures were identified. The refined MCDA rating tool can help decision-makers prioritize important and feasible RWE studies for research and can enable the use of RWE for the life-cycle evaluation of cancer drugs.

Importance: Drug shortages are a chronic and worsening issue that compromises patient safety. Despite the destabilizing impact of the COVID-19 pandemic on pharmaceutical production, it remains unclear whether issues affecting the drug supply chain were more likely to result in meaningful shortages during the pandemic., Objective: To estimate the proportion of supply chain issue reports associated with drug shortages overall and with the COVID-19 pandemic., Design, Setting, and Participants: This longitudinal cross-sectional study used data from the IQVIA Multinational Integrated Data Analysis database, comprising more than 85% of drug purchases by US pharmacies from wholesalers and manufacturers, from 2017 to 2021. Data were analyzed from January to May 2023., Exposure: Presence of a supply chain issue report to the US Food and Drug Administration or the American Society of Health-Systems Pharmacists (ASHP)., Main Outcomes and Measures: The main outcome was drug shortage, defined as at least 33% decrease in units purchased within 6 months of a supply chain issue report. Random-effects logistic regression models compared the marginal odds of shortages for drugs with vs without reports. Interaction terms assessed heterogeneity prior to vs during the COVID-19 pandemic and by drug characteristics (formulation, age, essential medicine status, clinician- vs self-administered, sales volume, and number of manufacturers)., Results: A total of 571 drugs exposed to 731 supply chain issue reports were matched to 7296 comparison medications with no reports. After adjusting for drug characteristics, 13.7% (95% CI, 10.4%-17.8%) of supply chain issue reports were associated with subsequent drug shortages vs 4.1% (95% CI, 3.6%-4.8%) of comparators (marginal odds ratio [mOR], 3.7 [95% CI, 2.6-5.1]). Shortages increased among both drugs with and without reports in February to April 2020 (34.2% of drugs with supply chain issue reports and 9.5% of comparison drugs; mOR, 4.9 [95% CI, 2.1-11.6]), and then decreased after May 2020 (9.8% of drugs with reports and 3.6% of comparison drugs; mOR, 2.9 [95% CI, 1.6-5.3]). Significant associations were identified by formulation (parenteral mOR, 1.9 [95% CI, 1.1-3.2] vs oral mOR, 5.4 [95% CI, 3.3-8.8]; P for interaction = .008), WHO essential medicine status (essential mOR, 2.2 [95% CI, 1.3-5.2] vs nonessential mOR, 4.6 [95% CI, 3.2-6.7]; P = .02), and for brand-name vs generic status (brand-name mOR, 8.1 [95% CI, 4.0-16.0] vs generic mOR, 2.4 [95% CI, 1.7-3.6]; P = .002)., Conclusions and Relevance: In this national cross-sectional study, supply chain issues associated with drug shortages increased at the beginning of the COVID-19 pandemic. Ongoing policy work is needed to protect US drug supplies from future shocks and to prioritize clinically valuable drugs at greatest shortage risk.

Objectives: Evidence concerning the effect of statins in primary prevention of cardiovascular disease (CVD) among older adults is lacking. Using Quebec population-wide administrative data, we emulated a hypothetical randomized trial including older adults >65 years on April 1, 2013, with no CVD history and no statin use in the previous year., Study Design and Setting: We included individuals who initiated statins and classified them as exposed if they were using statin at least 3 months after initiation and nonexposed otherwise. We followed them until March 31, 2018. The primary outcome was the composite endpoint of coronary events (myocardial infarction, coronary bypass, and percutaneous coronary intervention), stroke, and all-cause mortality. The intention-to-treat (ITT) effect was estimated with adjusted Cox models and per-protocol effect with inverse probability of censoring weighting., Results: A total of 65,096 individuals were included (mean age = 71.0 ± 5.5, female = 55.0%) and 93.7% were exposed. Whereas we observed a reduction in the composite outcome (ITT-hazard ratio (HR) = 0.75; 95% CI: 0.68-0.83) and mortality (ITT-HR = 0.69; 95% CI: 0.61-0.77) among exposed, coronary events increased (ITT-HR = 1.46; 95% CI: 1.09-1.94). All multibias E-values were low indicating that the results were not robust to unmeasured confounding, selection, and misclassification biases simultaneously., Conclusion: We cannot conclude on the effectiveness of statins in primary prevention of CVD among older adults. We caution that an in-depth reflection on sources of biases and careful interpretation of results are always required in observational studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the distribution and spending by cost-effectiveness category among those drugs with the highest public spending levels in Canada., Design: Repeated cross-sectional study., Setting: The Canadian provinces of Manitoba, Ontario, New Brunswick, Nova Scotia, Prince Edward Island and Newfoundland., Main Outcomes and Measures: Cost-effectiveness assessments by the Canadian Agency for Drugs and Technologies in Health (CADTH) for top-100 brand-name outpatient drugs by gross public plan spending in any year between 2015 and 2021 in Canada Institute for Health Information's National Prescription Drug Utilization Information System data. Gross public plan spending by cost-effectiveness category., Results: From 2015 to 2021, 152 brand-name drugs occupied a top-100 rank and were included in the analysis. Of those, 117 had been assessed by CADTH. During the 7-year period, there was an increase in both top-100 drugs with cost-effective (from 18 to 24) and cost-ineffective (from 29 to 41) assessments, while drugs not assessed or with an unclear assessment declined (from 31 to 19 and from 22 to 16, respectively). As a share of spending on top-100 drugs with an assessment, spending on cost-effective drugs was mostly stable at 40%-46% from 2015 to 2021, while spending on cost-ineffective drugs increased from 30% to 45%., Conclusion: A large and growing share of public drug spending has been allocated to cost-ineffective drugs in Canada. Dedicating large budgets to such treatments prevents spending with greater health impact elsewhere in the healthcare system and could restrain the capacity to pay for groundbreaking pharmaceutical innovation in the future., Competing Interests: Competing interests: ÉG, SR, YZ and KP are employees of the Patented Medicine Prices Review Board, an independent quasi-judicial agency of the Federal Government of Canada. SR was a negotiating member of the pan-Canadian Pharmaceutical Alliance (pCPA) on behalf of British Columbia PharmaCare from 2016 to 2022. KP was a negotiating member of the pCPA on behalf of the New Brunswick Drug Plan from 2011 to 2021. MT has received consulting fees from Health Canada, CADTH and Green Shield Canada., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare myocarditis/pericarditis risk after COVID-19 mRNA vaccination versus SARS-CoV-2 infection, and to assess if myocarditis/pericarditis risk varies by vaccine dosing interval., Methods: In this retrospective cohort study, we used linked databases in Quebec, Ontario, and British Columbia between January 26, 2020, and September 9, 2021. We included individuals aged 12 or above who received an mRNA vaccine as the second dose or were SARS-CoV-2-positive by RT-PCR. The outcome was hospitalization/emergency department visit for myocarditis/pericarditis within 21 days of exposure. We calculated age- and sex-stratified incidence ratios (IRs) of myocarditis/pericarditis following mRNA vaccination versus SARS-CoV-2 infection. We also calculated myocarditis/pericarditis incidence by vaccine type, homologous/heterologous schedule, and dosing interval. We pooled province-specific estimates using meta-analysis., Results: Following 18,860,817 mRNA vaccinations and 860,335 SARS-CoV-2 infections, we observed 686 and 160 myocarditis/pericarditis cases, respectively. Myocarditis/pericarditis incidence was lower after vaccination than infection (IR [BNT162b2/SARS-CoV-2], 0.14; 95%CI, 0.07-0.29; IR [mRNA-1273/SARS-CoV-2], 0.28; 95%CI, 0.20-0.39). Within the vaccinated cohort, myocarditis/pericarditis incidence was lower with longer dosing intervals; IR (56 or more days/15-30 days) was 0.28 (95%CI, 0.19-0.41) for BNT162b2 and 0.26 (95%CI, 0.18-0.38) for mRNA-1273., Conclusion: Myocarditis/pericarditis risk was lower after mRNA vaccination than SARS-CoV-2 infection, and with longer intervals between primary vaccine doses., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Naveed Z. Janjua reports a relationship with 10.13039/100006483AbbVie Inc that includes: consulting or advisory and speaking and lecture fees. Naveed Z. Janjua reports a relationship with 10.13039/100005564Gilead Sciences that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024 Published by Elsevier Ltd.)

Background: During the height of the global COVID-19 pandemic, the test-negative design (TND) was extensively used in many countries to evaluate COVID-19 vaccine effectiveness (VE). Typically, the TND involves the recruitment of care-seeking individuals who meet a common clinical case definition. All participants are then tested for an infection of interest., Objectives: To review and describe the variation in TND methodology, and disclosure of potential biases, as applied to the evaluation of COVID-19 VE during the early vaccination phase of the pandemic., Methods: We conducted a systematic review by searching four biomedical databases using defined keywords to identify peer-reviewed articles published between January 1, 2020, and January 25, 2022. We included only original articles that employed a TND to estimate VE of COVID-19 vaccines in which cases and controls were evaluated based on SARS-CoV-2 laboratory test results., Results: We identified 96 studies, 35 of which met the defined criteria. Most studies were from North America (16 studies) and targeted the general population (28 studies). Outcome case definitions were based primarily on COVID-19-like symptoms; however, several papers did not consider or specify symptoms. Cases and controls had the same inclusion criteria in only half of the studies. Most studies relied upon administrative or hospital databases assembled for a different (non-evaluation) clinical purpose. Potential unmeasured confounding (20 studies), misclassification of current SARS-CoV-2 infection (16 studies) and selection bias (10 studies) were disclosed as limitations by some studies., Conclusion: We observed potentially meaningful deviations from the validated design in the application of the TND during the COVID-19 pandemic., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mireille E. Schnitzer reports financial support was provided by Canadian Institutes of Health Research. Denis Talbot reports financial support was provided by Canadian Institutes of Health Research. Gaston De Serres reports financial support was provided by Canadian Institutes of Health Research. Cong Jiang reports financial support was provided by Canadian Institutes of Health Research. Anita Koushik reports financial support was provided by Canadian Institutes of Health Research. Joanna Merckx reports financial support was provided by Canadian Institutes of Health Research. Danuta M. Skowronski reports financial support was provided by Canadian Institutes of Health Research. Mina Tadrous reports financial support was provided by Canadian Institutes of Health Research. Denis Talbot reports financial support was provided by Fonds de recherche du Québec – Santé. Miceline Mesidor reports financial support was provided by Fonds de recherche du Québec – Santé. Danuta M Skowronski reports financial support was provided by BCCDC Foundation for Public Health., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Monovalent and bivalent mRNA COVID-19 booster doses provided similar strong initial protection against severe outcomes. Uncertainty remains around waning of protection from these vaccines., Competing Interests: Potential conflicts of interest . K. W. is a shareholder and board member of CANImmunize Inc and has served on independent scientific advisory boards for Medicago and Moderna. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Competing Interests: Mina Tadrous received consulting fees from CADTH and Health Canada unrelated to this work. The other authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To assess the impact of the COVID-19 pandemic on prescription drug use and costs., Design: Interrupted time series analysis of comprehensive administrative health data linkages in British Columbia, Canada, from 1 January 2018 to 28 March 2021., Setting: Retrospective population-based analysis of all prescription drugs dispensed in community pharmacies and outpatient hospital pharmacies and irrespective of the drug insurance payer., Participants: Between 4.30 and 4.37 million individuals (52% women) actively registered with the publicly funded medical services plan., Intervention: COVID-19 pandemic and associated mitigation measures., Main Outcome Measures: Weekly dispensing rates and costs, both overall and stratified by therapeutic groups and pharmacological subgroups, before and after the declaration of the public health emergency related to the COVID-19 pandemic. Relative changes in post-COVID-19 outcomes were expressed as ratios of observed to expected rates., Results: After the onset of the pandemic and subsequent COVID-19 mitigation measures, overall medication dispensing rates dropped by 2.4% (p<0.01), followed by a sustained weekly increase to return to predicted levels by the end of January 2021. We observed abrupt level decreases in antibacterials (30.3%, p<0.01) and antivirals (22.4%, p<0.01) that remained below counterfactuals over the first year of the pandemic. In contrast, there was a week-to-week trend increase in nervous system drugs, yielding an overall increase of 7.3% (p<0.01). No trend changes in the dispensing of respiratory system agents, ACE inhibitors, antidiabetic drugs and antidepressants were detected., Conclusion: The COVID-19 pandemic impact on prescription drug dispensing was heterogeneous across medication subgroups. As data become available, dispensing trends in nervous system agents, antibiotics and antivirals warrant further monitoring and investigation., Competing Interests: Competing interests: ML has consulted for Health Canada and the Hospital Employees’ Union. He has provided expert witness testimony for the Attorney General of Canada and the Federation of Post-Secondary Educators. MT has received consultant fees from the Canadian Agency for Drugs and Technologies in Health and Green Shield Canada. No other competing interests were declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Valsartan was recalled by the US Food and Drug Administration in July 2018 for carcinogenic impurities, resulting in a drug shortage and management challenges for valsartan users. The influence of the valsartan recall on clinical outcomes is unknown. We compared the risk of adverse events between hypertensive patients using valsartan and a propensity score-matched group using nonrecalled angiotensin receptor blockers and angiotensin-converting enzyme inhibitors., Methods and Results: We used Optum's deidentified Clinformatics Datamart (July 2017-January 2019). Hypertensive patients who received valsartan or nonrecalled angiotensin receptor blockers/angiotensin-converting enzyme inhibitors for 1 year before and on the recall date were compared. Primary outcomes were measured in the 6 months following the recall and included: (1) a composite measure of all-cause hospitalization, all-cause emergency department visit, and all-cause urgent care visit, and (2) a composite cardiac event measure of hospitalizations for acute myocardial infarction and hospitalizations/emergency department visits/urgent care visits for stroke/transient ischemic attack, heart failure, or hypertension. We compared the risk of outcomes between treatment groups using Cox proportional hazard models. Of the hypertensive patients, 76 934 received valsartan, and 509 472 received a nonrecalled angiotensin receptor blocker/angiotensin-converting enzyme inhibitor. Valsartan use at the time of recall was associated with a higher risk of all-cause hospitalization, emergency department use, or urgent care use (hazard ratio [HR], 1.02 [95% CI, 1.00-1.04]) and the composite of cardiac events (HR, 1.22 [95% CI, 1.15-1.29]) within 6 months after the recall., Conclusions: The valsartan recall and shortage affected hypertensive patients. Local- and national-level systems need to be enhanced to protect patients from drug shortages by providing safe and reliable medication alternatives.

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., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The primary objective of this review is to examine which disease-modifying antirheumatic drugs (DMARDs) and biologics used to treat pregnant individuals with rheumatic conditions have been reported in observational studies using population-based health administrative data. The secondary objective is to describe which adverse pregnancy outcomes (both maternal and neonatal) have been reported, their definitions, and corresponding diagnostic and/or procedural codes., Introduction: Pregnant individuals are typically excluded from drug trials due to unknown potential risks to both the pregnant person and fetus, leaving most antirheumatic drugs understudied for use in pregnancy. Despite these substantial knowledge gaps, most pregnant individuals continue to be maintained on antirheumatic medications due to the benefits generally outweighing the risks. In contrast to previous systematic reviews of findings from randomized trials, our scoping review aims to leverage this real-world data to generate real-world evidence of antirheumatic drug safety during pregnancy., Inclusion Criteria: Articles must report on observational studies using population-based health administrative data from pregnant individuals with rheumatic conditions (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and psoriatic arthritis) receiving antirheumatic drug therapy (DMARDs and biologics). Randomized trials, reviews, case studies, opinion pieces, and abstracts will be excluded., Methods: Electronic databases (MEDLINE [Ovid], Embase [Ovid], CINAHL [EBSCOhost]) and gray literature (OpenGrey, Health Services Research Projects in Progress, World Health Organization Library, and Google Scholar) will be searched for relevant evidence. Search terms will combine 4 concepts: rheumatic diseases, drug therapy, pregnancy, and health care administrative data. Identified articles will be independently screened, selected, and extracted by 2 researchers. Data will be analyzed descriptively and presented in tables., Review Registration: Open Science Framework https://osf.io/5e6tp., Competing Interests: The authors declare no conflict of interest in this project., (Copyright © 2023 JBI.)

Objective: To determine if metformin use is associated with a lower rate of overactive bladder (OAB) medication use. Metformin facilitates the proliferation and migration of stem cells, which have been shown to improve bladder overactivity in animal models., Methods: We conducted a retrospective nested case-control cohort study using population-based health-care administrative databases. Our cohort included patients with diabetes mellitus type 2 (DM2) ≥69years. Cases received a prescription for an OAB medication, matched with up to 4 controls based on age, sex, and DM2 diagnosis date. Exposure was a new prescription for metformin prior to receiving an OAB medication. Adjusted odds ratios were estimated using conditional logistic regression. Sensitivity analysis was done to assess the relationship between cumulative days' supply of metformin and use of OAB medications., Results: Within our cohort of 2,233,084 patients with DM2, there were 16,549 case subjects who received a prescription for an OAB medication, and 64,171 matched controls. We found a positive association between OAB medication use and metformin use (adjusted odds ratios=1.07, 95% CI=1.03-1.12). Summed days' supply of metformin was also associated with OAB medication use, except when summed metformin days was >2220., Conclusion: Older patients with DM2 exposed to metformin had a slightly higher rate of OAB medication use, until 2220+ days' metformin supply, whereafter no association was found. This suggests no protective role for metformin in the prevention of OAB in this patient population., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: e-Prescribing is designed to assist in facilitating safe and appropriate prescriptions for patients. Currently, it is unknown to what extent e-prescribing for opioids influences experiences and outcomes. To address this gap, a rapid scoping review was conducted., Objective: This rapid scoping review aims to (1) explore how e-prescribing has been used clinically; (2) examine the effects of e-prescribing on clinical outcomes, the patient or clinician experience, service delivery, and policy; and (3) identify current gaps in the present literature to inform future studies and recommendations., Methods: A rapid scoping review was conducted following the guidance of the JBI 2020 scoping review methodology and the World Health Organization guide to rapid reviews. A comprehensive literature search was completed by an expert librarian from inception until November 16, 2022. Three databases were electronically searched: MEDLINE (Ovid), Embase (Ovid), and Scopus (Elsevier). The search criteria were as follows: (1) e-prescribing programs targeted to the use or misuse of opioids, including those that were complemented or accompanied by clinically focused initiatives, and (2) a primary research study of experimental, quasi-experimental, observational, qualitative, or mixed methods design. An additional criterion of an ambulatory component of e-prescribing (eg, e-prescribing occurred upon discharge from acute care) was added at the full-text stage. No language limitations or filters were applied. All articles were double screened by trained reviewers. Gray literature was manually searched by a single reviewer. Data were synthesized using a descriptive approach., Results: Upon completing screening, 34 articles met the inclusion criteria: 32 (94%) peer-reviewed studies and 2 (6%) gray literature documents (1 thesis study and 1 report). All 33 studies had a quantitative component, with most highlighting e-prescribing from acute care settings to community settings (n=12, 36%). Only 1 (3%) of the 34 articles provided evidence on e-prescribing in a primary care setting. Minimal prescriber, pharmacist, and clinical population characteristics were reported. The main outcomes identified were related to opioid prescribing rates, alerts (eg, adverse drug events and drug-drug interactions), the quantity and duration of opioid prescriptions, the adoption of e-prescribing technology, attitudes toward e-prescribing, and potential challenges with the implementation of e-prescribing into clinical practice. e-Prescribing, including key features such as alerts and dose order sets, may reduce prescribing errors., Conclusions: This rapid scoping review highlights initial promising results with e-prescribing and opioid therapy management. It is important that future work explores the experience of prescribers, pharmacists, and patients using e-prescribing for opioid therapy management with an emphasis on prescribers in the community and primary care. Developing a common set of quality indicators for e-prescribing of opioids will help build a stronger evidence base. Understanding implementation considerations will be of importance as the technology is integrated into clinical practice and health systems., (©Sara J T Guilcher, Stephanie R Cimino, Mina Tadrous, Lisa M McCarthy, Jessica Riad, Andrea C Tricco, Simon Hagens, Jennifer Lien, Sukirtha Tharmalingam, Tara Gomes. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.12.2023.)

Background: To curb the growing impact of drug shortages, Health Canada developed the Tiered Notification and Communication Framework which assigns potential shortages a corresponding tiered status. Tier-3 is assigned to shortages with the greatest potential impact on the healthcare system. This study aims to describe drug purchasing trends in response to Tier-3 shortages using three case-examples., Methods: We conducted a time-series analysis of monthly purchasing data for three out of 17 Tier-3 drug shortages (hydralazine, sarilumab, and medroxyprogesterone acetate) with publicly available reports in July 2021 and available IQVIA MIDAS data from January 2016 to December 2021. We assessed percent changes in purchasing at 1-, 3-, and 6-months after the onset of each Tier-3 drug shortage and interventional ARIMA modelling was used to assess the statistical significance., Results: Medroxyprogesterone acetate experienced a significant shift (p = 0.0370) in purchasing following its shortage, and the 1-, 3-, and 6-month percent changes were +14.9%, +6.8% and -3.1%, respectively. Hydralazine and sarilumab did not show a significant shift. The 1-, 3-, and 6-month percent changes for hydralazine were +15.5%, +10.2%, and +9.6% respectively and +25.2%, +45.1% and +39.2 for sarilumab., Conclusions: These results indicate that drugs assigned a Tier-3 status may not show declines in purchasing in the months following status assignment, which may be due to policy responses following the assignment. However, more insight is needed into the mechanisms through which these policy measures impact shortages and whether they are functioning as intended., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Santhireswaran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic was associated with increases in the prevalence of depression, anxiety and behavioural problems among children and youth. Less well understood is the influence of the pandemic on antidepressant and antipsychotic use among children. This is important, as it is possible that antidepressants and antipsychotics were used as a "stop-gap" measure to treat mental health symptoms when in-person access to outpatient care and school-based supportive services was disrupted. Furthermore, antipsychotics and antidepressants have been associated with harm in children and youth. We examined trends in dispensing of these medications two years following the pandemic among children 18 years of age and under in Ontario, Canada., Methods: We conducted a population-based time-series study of antidepressant and antipsychotic medication dispensing to children and adolescents ≤18 years old between September 1, 2014, and March 31, 2022. We measured monthly population-adjusted rates of antidepressant and antipsychotics obtained from the IQVIA Geographic Prescription Monitor (GPM) database. We used structural break analyses to identify the pandemic month(s) when changes in the dispensing of antidepressants and antipsychotics occurred. We used interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected use of these drugs., Results: Overall, we found higher-than-expected dispensing of antidepressants and antipsychotics in children and youth. Specifically, we observed an immediate step decrease in antidepressant dispensing associated with a structural break in April 2020 (-55.8 units per 1,000 individuals; 95% confidence intervals [CI] CI: -117.4 to 5.8), followed by an increased monthly trend in the rate of antidepressant dispensing of 13.0 units per 1,000 individuals (95% CI: 10.2-15.9). Antidepressant dispensing was consistently greater than predicted from September 2020 onward. Antipsychotic dispensing increased immediately following a June 2020 structural break (26.4 units per 1,000 individuals; 95% CI: 15.8-36.9) and did not change appreciably thereafter. Antipsychotic dispensing was higher than predicted at all time points from June 2020 onward., Conclusion: We found higher-than-expected dispensing of antidepressants and antipsychotics in children and youth. These increases were sustained through nearly two years of observation and are especially concerning in light of the potential for harm with the long-term use of antipsychotics in children. Further research is required to understand the clinical implications of these findings., Competing Interests: MP has received consulting fees for unrelated work from Addis & Associates/Roche and the Government of Nova Scotia, and has received grant funding from Autism Speaks. MT has received consulting fees for unrelated work from Green Shield Canada and the Canadian Agency for Drugs and Technologies in Health. TG has received funding from the Ontario Ministry of Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Antoniou, Pajer, Gardner, Penner, Lunsky, Tadrous, Mamdani, Gozdyra, Juurlink and Gomes.)

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., (© 2023. The Author(s).)

Importance: The study team previously showed that maternal mRNA COVID-19 vaccination during pregnancy confers protection against SARS-CoV-2 infection and COVID-19-related hospital admission in newborns and young infants. In this study, the study team evaluated newborn and early infant safety outcomes following maternal messenger RNA (mRNA) COVID-19 vaccination during pregnancy, for which there is limited comparative epidemiological evidence., Objective: To determine if maternal mRNA COVID-19 vaccination during pregnancy is associated with adverse newborn and early infant outcomes., Design, Setting, and Participants: This population-based retrospective cohort study took place in Ontario, Canada, using multiple linked health administrative databases. Singleton live births with an expected delivery date between May 1, 2021, and September 2, 2022, were included. Data were analyzed from January 2023 through March 2023., Exposure: Maternal mRNA COVID-19 vaccination (1 or more doses) during pregnancy., Main Outcomes and Measures: Severe neonatal morbidity (SNM), neonatal death, neonatal intensive care unit (NICU) admission, neonatal readmission, and hospital admission up to 6 months of age. The study team calculated inverse probability of treatment weighted risk ratios (RRs) and fit weighted Cox proportional hazards regression models comparing outcomes in infants of mothers who received COVID-19 vaccination during pregnancy with those who received no COVID-19 vaccine doses before delivery., Results: In total, 142 006 infants (72 595 male [51%]; mean [SD] gestational age at birth, 38.7 [1.7] weeks) were included; 85 670 were exposed to 1 or more COVID-19 vaccine doses in utero (60%). Infants of vaccinated mothers had lower risks of SNM (vaccine exposed 7.3% vs vaccine unexposed 8.3%; adjusted RR [aRR], 0.86; 95% CI, 0.83-0.90), neonatal death (0.09% vs 0.16%; aRR, 0.47; 95% CI, 0.33-0.65), and NICU admission (11.4% vs 13.1%; aRR, 0.86; 95% CI, 0.83-0.89). There was no association between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted hazard ratio, 1.03; 95% CI, 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; adjusted hazard ratio, 1.01; 95% CI, 0.96-1.05)., Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of SNM, neonatal death, and NICU admission. In addition, neonatal and 6-month readmissions were not increased in infants of mothers vaccinated during pregnancy.

Importance: Virtual visits became more common after the COVID-19 pandemic, but it is unclear in what context they are best used., Objective: To investigate whether there was a difference in subsequent emergency department use between patients who had a virtual visit with their own family physician vs those who had virtual visits with an outside physician., Design, Setting, and Participants: This propensity score-matched cohort study was conducted among all Ontario residents attached to a family physician as of April 1, 2021, who had a virtual family physician visit in the subsequent year (to March 31, 2022)., Exposure: The type of virtual family physician visit, with own or outside physician, was determined. In a secondary analysis, own physician visits were compared with visits with a physician working in direct-to-consumer telemedicine., Main Outcome and Measure: The primary outcome was an emergency department visit within 7 days after the virtual visit., Results: Among 5 229 240 Ontario residents with a family physician and virtual visit, 4 173 869 patients (79.8%) had a virtual encounter with their own physician (mean [SD] age, 49.3 [21.5] years; 2 420 712 females [58.0%]) and 1 055 371 patients (20.2%) had an encounter with an outside physician (mean [SD] age, 41.8 [20.9] years; 605 614 females [57.4%]). In the matched cohort of 1 885 966 patients, those who saw an outside physician were 66% more likely to visit an emergency department within 7 days than those who had a virtual visit with their own physician (30 748 of 942 983 patients [3.3%] vs 18 519 of 942 983 patients [2.0%]; risk difference, 1.3% [95% CI, 1.2%-1.3%]; relative risk, 1.66 [95% CI, 1.63-1.69]). The increase in the risk of emergency department visits was greater when comparing 30 216 patients with definite direct-to-consumer telemedicine visits with 30 216 patients with own physician visits (risk difference, 4.1% [95% CI, 3.8%-4.5%]; relative risk, 2.99 [95% CI, 2.74-3.27])., Conclusions and Relevance: In this study, patients whose virtual visit was with an outside physician were more likely to visit an emergency department in the next 7 days than those whose virtual visit was with their own family physician. These findings suggest that primary care virtual visits may be best used within an existing clinical relationship.

Background: Globally, pharmaceutical companies offer patient support programs in tandem with their products, which aim to enhance medication adherence and patient experience through education, training, support and financial assistance. We sought to identify the proportion and characteristics of such patient support programs in Canada and to describe the nature of supports provided., Methods: We conducted a crosssectional study to identify and characterize all marketed prescription drugs available in Canada as of Aug. 23, 2022, using the Health Canada Drug Product and CompuScript databases. To describe the nature of supports provided, we conducted a content analysis of publicly available patient support program websites and Web-based documents. Using logistic regression, we identified characteristics of drugs associated with having a patient support program including brand-name or branded generic (generic medications with a proprietary name), orphan (medications for rare diseases) or biologic drug status; estimated total cost of prescriptions dispensed at retail pharmacies; and price per unit., Results: Of the 2556 prescription drugs marketed by 89 companies in the study period, 256 (10.0%) had a patient support program in Canada. Many of the 89 drug manufacturers ( n = 55, 61.8%) offered at least 1 patient support program, frequently relying on third-party administrators for delivery. Brandname and branded generic medications, biologic agents and drugs with orphan status were more likely to have a patient support program than generic drugs. Compared with drugs priced $1.01-$10.00 per unit, drugs priced $10.01-$100.00 per unit were nearly 8 times more likely to have a patient support program (adjusted odds ratio 7.54, 95% confidence interval 4.07- 14.64). Most sampled patient support programs included reimbursement navigation ( n = 231, 90.2%) and clinical case management ( n = 223, 87.1%)., Interpretation: About 1 in 10 drugs marketed in Canada has a manufacturersponsored patient support program, but these are concentrated around brand-name, branded generic, biologic and high-cost drugs, often for rare diseases. To understand the impact of patient support programs on health outcomes and sustainable access to cost-effective medicines, greater transparency and independent evaluation of patient support programs is necessary., Competing Interests: Competing interests: Joel Lexchin received payments for writing briefs on the role of promotion in generating prescriptions for 2 legal firms. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Marc-André Gagnon reports research funding from the Social Sciences and Humanities Research Council, Canadian Institutes of Health Research (CIHR) and the Faculty of Public Affairs at Carleton University. Mina Tadrous reports research funding from the Ontario Ministry of Health and CIHR, as well as consulting fees from the Canadian Agency for Drugs and Technologies in Health, Health Canada and Green Shield Canada. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Latent class growth analysis is increasingly proposed as a solution to summarize the observed longitudinal treatment into a few distinct groups. When latent class growth analysis is combined with standard approaches like Cox proportional hazards models, confounding bias is not properly addressed because of time-varying covariates that have a double role of confounders and mediators. We propose to use latent class growth analysis to classify individuals into a few latent classes based on their medication adherence pattern, then choose a working marginal structural model that relates the outcome to these groups. The parameter of interest is defined as a projection of the true marginal structural model onto the chosen working model. Simulation studies are used to illustrate our approach and compare it with unadjusted, baseline covariates adjusted, time-varying covariates adjusted, and inverse probability of trajectory groups weighted adjusted models. Our proposed approach yielded estimators with little or no bias and appropriate coverage of confidence intervals in these simulations. We applied our latent class growth analysis and marginal structural model approach to a database comprising information on 52,790 individuals from the province of Quebec, Canada, aged more than 65 and who were statin initiators to estimate the effect of statin-usage trajectories on a first cardiovascular event., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Melanie Penner has received consulting fees for unrelated work from Addis & Associates/Roche and from the Government of Nova Scotia. Mina Tadrous has received consulting fees for unrelated work from Green Shield Canada and the Canadian Agency for Drugs and Technologies in Health. Tara Gomes has received funding from the Ontario MOH for unrelated work.

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Academic detailing, an educational outreach service for family physicians, was funded by the Ontario government to address gaps in opioid prescribing and pain management. We sought to evaluate the impact of academic detailing on opioid prescribing, and to understand how and why academic detailing may have influenced opioid prescribing., Methods: In this mixed-methods study, we collected quantitative and qualitative data concurrently from 2017 to 2019 in Ontario, Canada. We analyzed prescribing outcomes descriptively for a sample of participating physicians and compared them with a matched control group. We invited physicians to participate in qualitative interviews to discuss their experiences in academic detailing. Development and analysis of qualitative interviews was informed by the Theoretical Domains Framework. We triangulated qualitative and quantitative findings to understand the mechanisms that drove changes in opioid prescribing., Results: Physicians receiving academic detailing ( n = 238) achieved a greater reduction in opioid prescribing than matched controls ( n = 238). Seventeen physicians completed interviews and reported that academic detailing addressed barriers to pain care, including lack of confidence, difficult interactions with patients and prescribing and tapering decisions. Academic detailing reinforced knowledge about opioid prescribing and pain management. Discussion of complex patients and talking points to use during challenging conversations were described as key drivers of practice change., Interpretation: The findings of this real-world, mixed-methods evaluation explain how an academic detailing service addressed key barriers and enablers to limit high-risk opioid prescribing in primary care. This nuanced understanding will be used to inform, spread and scale academic detailing., Competing Interests: Competing interests: Noah Ivers reports funding from the Canadian Institutes of Health Research, outside the submitted work. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)