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Vincent Lo Re III,1,2,* Noelle M Cocoros,3,4,* Rebecca A Hubbard,2 Sarah K Dutcher,5 Craig W Newcomb,2 John G Connolly,3,4 Silvia Perez-Vilar,5 Dena M Carbonari,2 Maria E Kempner,3,4 José J Hernández-Muñoz,5 Andrew B Petrone,3,4 Allyson M Pishko,6 Meighan E Rogers Driscoll,3,4 James T Brash,7 Sean Burnett,8,9 Catherine Cohet,10 Matthew Dahl,8,11 Terese A DeFor,12 Antonella Delmestri,13 Djeneba Audrey Djibo,14 Talita Duarte-Salles,15,16 Laura B Harrington,17 Melissa Kampman,18 Jennifer L Kuntz,19 Xavier Kurz,10 Núria Mercadé-Besora,15 Pamala A Pawloski,12 Peter R Rijnbeek,16 Sarah Seager,7 Claudia A Steiner,20,21 Katia Verhamme,16 Fangyun Wu,8,22 Yunping Zhou,23 Edward Burn,13 J Michael Paterson,8,22,* Daniel Prieto-Alhambra13,16,* 1Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 2Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 3Department of Population Medicine, Harvard Medical School, Boston, MA, USA; 4Harvard Pilgrim Healthcare Institute, Boston, MA, USA; 5Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA; 6Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 7IQVIA, Real World Solutions, Brighton, UK; 8Canadian Network for Observational Drug Effect Studies (CNODES), Toronto, Ontario, Canada; 9Therapeutics Initiative, University of British Columbia, Vancouver, British Columbia, Canada; 10Data Analytics and Methods Task Force, European Medicines Agency, Amsterdam, Netherlands; 11Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, Manitoba, Canada; 12HealthPartners Institute, Bloomington, MN, USA; 13Pharmaco- and Device Epidemiology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK; 14CVS Health, Blue Bell, PA, USA; 15Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 16Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands; 17Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA; 18Health Canada, Ottawa, Ontario, Canada; 19Kaiser Permanente Northwest Center for Health Research, Portland, OR, USA; 20Kaiser Permanente Colorado Institute for Health Research, Aurora, CO, USA; 21Colorado Permanente Medical Group, Denver, CO, USA; 22ICES, Toronto, Ontario, Canada; 23Humana Healthcare Research, Inc., Louisville, KY, USA*These authors contributed equally to this workCorrespondence: Vincent Lo Re III, Division of Infectious Diseases, Department of Medicine, Division of Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-6021, USA, Fax +1 215 573 5315, Email vincentl@pennmedicine.upenn.eduPurpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability.Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE.Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09– 0.13%) in Canada to 1.01% (0.97– 1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21– 0.26%) in Canada to 0.84% (0.80– 0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06– 0.07%) in England to 1.04% (1.01– 1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24– 0.26%) in England to 1.02% (0.99– 1.04%) in the US.Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.Plain Language Summary: Cohort studies of patients diagnosed with COVID-19 in both the ambulatory and hospital settings have suggested that SARS-CoV-2 infection promotes hypercoagulability that could lead to arterial or venous thromboembolism. However, few studies have examined how the risk of thromboembolism with COVID-19 has evolved over time across different countries. A new collaboration was established among the regulatory authorities of Canada, Europe, and the US within the International Coalition of Medicines Regulatory Authorities to evaluate the 90-day risk of both arterial and venous thromboembolism after initial diagnosis of COVID-19 in the ambulatory or hospital setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. The study found that there was variability in the risk of both arterial and venous thromboembolism by month across the countries among patients initially diagnosed with COVID-19 in the ambulatory or hospital setting. Differences in the healthcare systems, prevalence of comorbidities in the study cohorts, and approaches to the case definitions of thromboembolism likely contributed to the variability in estimates of thromboembolism risk across the countries.Keywords: COVID-19, ischemic stroke, myocardial infarction, thromboembolism, venous thromboembolism

Background: A relation between provider volume and outcome of total joint replacement (TJR) has not been demonstrated in Canada. Given the recent increase in TJR, changing patient characteristics and small sizes of previous Ontario studies, we reassessed whether adverse outcomes of TJR are related to hospital and surgeon procedure volumes.Methods: We included all Ontarians aged 20 years and older who underwent a unilateral elective primary total hip replacement (THR) or total knee replacement (TKR) between April 2000 and March 2004. The main data sources were hospital discharge abstracts and physician billings. We defined provider volume as the average annual number of primary and revision procedures performed by hospitals and surgeons during the study period. We assessed the association between procedure volumes and acute length of hospital stay (ALOS) and between volume and rate of surgical complications during the index admission; death within 90 days of operation; readmission for amputation, fusion or excision within 1 year; and revision arthroplasty within 1 year. We adjusted for age, sex, comorbidity, arthritis type, teaching hospital status and discharge disposition. The analyses of hospital volume were adjusted for surgeon volume and vice versa.Results: We included 20,290 patients who received THR and 27,217 who received TKR. Patient age, sex and comorbidity were significant predictors of complications and mortality. There were no associations between provider volume and mortality. Findings for other outcomes were mixed. Surgeon procedure volume was related to rates of revision THR but not to rates of revision TKR. Shorter ALOS was associated with male sex, younger age, fewer comorbidities, discharge to a rehabilitation unit or facility and greater surgeon volume.Conclusion: Patient characteristics were significant predictors of complications, ALOS and mortality after primary TJR. Evidence for a relation between provider volume and outcome was limited and inconsistent. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that although smoking during pregnancy has declined in North America, this has more to do with falling rates of smoking initiation among women of childbearing age than with increased rates of pregnancy-related smoking cessation. One possible explanation is poor exposure to effective stop-smoking strategies. Better information about women who smoke during pregnancy may help target these interventions more effectively.Methods: The study was a cross-sectional, self-administered survey of a consecutive sample of 916 (40.4% of eligible) women who delivered healthy babies in 1997-98 at a tertiary teaching hospital in Hamilton, Ontario. Our main focus was on health behaviours (smoking, drinking, eating, and exercise habits) before and during pregnancy; but we also included questions about the presence of (other) children and (other) smokers in the household, perceived health status, the subject's age and level of education, and whether or not the present pregnancy was planned. Factors associated with pregnancy-related smoking cessation were identified using multiple logistic regression.Results: Respondents were better educated and healthier, but smoked at rates similar to women of childbearing age in Hamilton at the time of the survey. Two thirds of prior smokers or 20% of respondents overall continued to smoke during pregnancy. After adjustment for other factors, three factors were associated with ongoing smoking during pregnancy: having other smokers in the household; having other children in the household; and not having post-secondary education.Conclusions: Many pregnant smokers are not being reached by current stop-smoking strategies. New ways to help these women and their partners are needed. [ABSTRACT FROM AUTHOR]

Importance: Community Paramedicine at Clinic (CP@clinic) is a chronic disease prevention program that decreases 911 calls for emergency medical services, but its wider system effects are unknown., Objective: To evaluate the effects of CP@clinic vs usual care on individual-level health service utilization outcomes., Design, Setting, and Participants: This open-label, pragmatic cluster randomized clinical trial evaluated all residents 55 years or older in 30 social housing buildings in Ontario, Canada, that had (1) a unique postal code, (2) at least 50 apartments, (3) 60% or more residents 55 years or older, and (4) a similar building for pairing (15 intervention and 15 control buildings, pair-matched randomization). The 12-month intervention had a staggered start date from January 1, 2015, to December 1, 2015, and ended between December 31, 2015, and November 30, 2016. Administrative health data analysis was conducted in May 2022., Intervention: CP@clinic was a health promotion and disease prevention program led by specially trained community paramedics who held weekly drop-in sessions in social housing buildings. These paramedics conducted 1-on-1 risk assessments, provided health education and referrals to relevant community resources, and, with consent, sent assessments to family physicians. Control buildings received usual care (universal health care, including free primary and specialty medical care)., Main Outcome and Measures: Individual-level health service utilization was measured from administrative health data, with ED visits via ambulance as the primary outcome; secondary outcomes included ED visits for any reason, primary care visits, hospitalizations, length of hospital stay, laboratory tests, receipt of home care, transfer to long-term care, and medication initiation. Generalized estimating equations were used to estimate intervention effects on individual-level health service utilization, accounting for trial design and individual-level baselines., Results: The 30 social housing buildings had 3695 residents (1846 control and 1849 intervention participants; mean [SD] age, 72.8 [9.1] years; 2400 [65.0%] female). Intention-to-treat analysis found no significant difference in ED visits by ambulance (445 of 1849 [24.1%] vs 463 of 1846 [25.1%]; adjusted odds ratio [AOR], 0.97; 95% CI, 0.89-1.05) but found higher antihypertensive medication initiation (74 of 500 [14.8%] vs 47 of 552 [8.5%]; AOR, 1.74; 95% CI, 1.19-2.53) and lower anticoagulant initiation (48 of 1481 [3.2%] vs 69 of 1442 [4.8%]; AOR, 0.68; 95% CI, 0.53-0.86) in the intervention arm vs the control arm. CP@clinic attendance was associated with higher incidence of primary care visits (adjusted incidence rate ratio, 1.10; 95% CI, 1.03-1.17), higher odds of receiving home care (AOR, 1.07; 95% CI, 1.01-1.13), and lower odds of long-term care transfers (AOR, 0.32; 95% CI, 0.13-0.81)., Conclusions and Relevance: In this cluster randomized clinical trial of CP@clinic, the intervention did not affect the rate of ED visits by ambulance; however, there were increased primary care visits and connections to home care services, which may have increased antihypertensive medication initiation and reduced long-term care transfers from social housing. Health policymakers should consider CP@clinic's impact as an upstream approach to improve care for older adults with low income., Trial Registration: ClinicalTrials.gov Identifier: NCT02152891.

Objective: To describe family physicians who primarily practise in a walk-in clinic setting and compare them with family physicians who provide longitudinal care., Design: A cross-sectional study that linked results from a 2019 physician survey to provincial administrative health care data in Ontario. The characteristics, practice patterns, and patients of physicians primarily working in a walk-in clinic setting were compared with those of family physicians providing longitudinal care., Setting: Ontario., Participants: Physicians who primarily worked in a walk-in clinic setting in 2019, as indicated by an annual physician survey., Main Outcome Measures: Physician demographic and practice characteristics, as well as their patients' demographic and health care utilization characteristics, were reported according to whether the physician was a walk-in clinic physician or a family physician who provided longitudinal care., Results: Compared with the 9137 family physicians providing longitudinal care, the 597 physicians who self-identified as practising primarily in walk-in clinics were more frequently male (67% vs 49%) and more likely to speak a language other than English or French (43% vs 32%). Walk-in clinic physicians tended to have more encounters with patients who were younger (mean 37 vs 47 years), who had lower levels of prior health care utilization (15% vs 19% in highest band), who resided in large urban areas (87% vs 77%), and who lived in highly ethnically diverse neighbourhoods (45% vs 35%). Walk-in clinic physicians tended to have more encounters with unattached patients (33% vs 17%) and with patients attached to another physician outside their group (54% vs 18%)., Conclusion: Physicians who primarily work in walk-in clinics saw many patients from historically underserved groups and many patients who were attached to another family physician., (Copyright © 2024 the College of Family Physicians of Canada.)

Background and Purpose:  Total hip arthroplasty (THA) can be performed through various surgical approaches, including direct anterior (DAA). DAA-THA may offer faster recovery but carries a higher risk of complications, which may be mitigated by surgeon volume and experience. We examined the association of surgeons' annual surgical volume with major complications after DAA-THA in a population-based sample., Methods:  A population-based retrospective cohort study was carried out on primary DAA-THA patients in Ontario between April 2016 and March 2021. We used restricted cubic splines to visually define the association between annual DAA surgeon volume and the risk of major surgical complications (fractures, dislocations, infections, and revisions) within 1 year of surgery. We further compared the complication rates amongst different DAA volume categories (< 30, 30-60, and > 60 cases/year)., Results: The study encompassed 9,672 DAA-THA patients (52% female, median age 67 years). We showed a sharp decline in the probability of complications as the surgical volume of DAA-THA increased within the lower range of 0-30 cases/year; the probability slightly increased after the surgical volume exceeded 60 cases/year. The overall complication rates were 3.09%, 2.24%, and 2.18% for the surgical experience group of < 30 cases/year, 30-60 cases/year, and > 60 cases/year, respectively., Conclusion:  There was an inverse relationship between surgical volume and complication rates in DAA-THA within the lower volume ranges. Maintaining a surgical volume of at least 30 DAA-THA cases/year can minimize complications, emphasizing the importance of surgical volume in this approach.

Background: Public funding of cataract surgery provided in private, for-profit surgical centres increased to help mitigate surgical backlogs during the COVID-19 pandemic in Ontario, Canada. We sought to compare the socioeconomic status of patients who underwent cataract surgery in not-for-profit public hospitals with those who underwent this surgery in private for-profit surgical centres and to evaluate whether differences in access by socioeconomic status decreased after the infusion of public funding for private, for-profit centres., Methods: We conducted a population-based study of all cataract operations in Ontario, Canada, between January 2017 and March 2022. We analyzed differences in socioeconomic status among patients who accessed surgery at not-for-profit public hospitals versus those who accessed it at private for-profit surgical centres before and during the period of expanded public funding for private for-profit centres., Results: Overall, 935 729 cataract surgeries occurred during the study period. Within private for-profit surgical centres, the rate of cataract surgeries rose 22.0% during the funding change period for patients in the highest socioeconomic status quintile, whereas, for patients in the lowest socioeconomic status quintile, the rate fell 8.5%. In contrast, within public hospitals, the rate of surgery decreased similarly among patients of all quintiles of socioeconomic status. During the funding change period, 92 809 fewer cataract operations were performed than expected. This trend was associated with socioeconomic status, particularly within private for-profit surgical centres, where patients with the highest socioeconomic status were the only group to have an increase in cataract operations., Interpretation: After increased public funding for private, for-profit surgical centres, patient socioeconomic status was associated with access to cataract surgery in these centres, but not in public hospitals. Addressing the factors underlying this incongruity is vital to ensure access to surgery and maintain public confidence in the cataract surgery system., Competing Interests: Competing interests:: Jonathan Irish is a board member with the Canadian Cancer Society. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: In 2020, the Ministry of Health (MoH) in Ontario, Canada, introduced a virtual urgent care (VUC) pilot program to provide alternative access to urgent care services and reduce the need for in-person emergency department (ED) visits for patients with low acuity health concerns., Objective: This study aims to compare the 30-day costs associated with VUC and in-person ED encounters from an MoH perspective., Methods: Using administrative data from Ontario (the most populous province of Canada), a population-based, matched cohort study of Ontarians who used VUC services from December 2020 to September 2021 was conducted. As it was expected that VUC and in-person ED users would be different, two cohorts of VUC users were defined: (1) those who were promptly referred to an ED by a VUC provider and subsequently presented to an ED within 72 hours (these patients were matched to in-person ED users with any discharge disposition) and (2) those seen by a VUC provider with no referral to an in-person ED (these patients were matched to patients who presented in-person to the ED and were discharged home by the ED physician). Bootstrap techniques were used to compare the 30-day mean costs of VUC (operational costs to set up the VUC program plus health care expenditures) versus in-person ED care (health care expenditures) from an MoH perspective. All costs are expressed in Canadian dollars (a currency exchange rate of CAD $1=US $0.76 is applicable)., Results: We matched 2129 patients who presented to an ED within 72 hours of VUC referral and 14,179 patients seen by a VUC provider without a referral to an ED. Our matched populations represented 99% (2129/2150) of eligible VUC patients referred to the ED by their VUC provider and 98% (14,179/14,498) of eligible VUC patients not referred to the ED by their VUC provider. Compared to matched in-person ED patients, 30-day costs per patient were significantly higher for the cohort of VUC patients who presented to an ED within 72 hours of VUC referral ($2805 vs $2299; difference of $506, 95% CI $139-$885) and significantly lower for the VUC cohort of patients who did not require ED referral ($907 vs $1270; difference of $362, 95% CI 284-$446). Overall, the absolute 30-day costs associated with the 2 VUC cohorts were $18.9 million (ie, $6.0 million + $12.9 million) versus $22.9 million ($4.9 million + $18.0 million) for the 2 in-person ED cohorts., Conclusions: This costing evaluation supports the use of VUC as most complaints were addressed without referral to ED. Future research should evaluate targeted applications of VUC (eg, VUC models led by nurse practitioners or physician assistants with support from ED physicians) to inform future resource allocation and policy decisions., (©Jean-Eric Tarride, Justin N Hall, Shawn Mondoux, Katie N Dainty, Joy McCarron, J Michael Paterson, Lesley Plumptre, Emily Borgundvaag, Howard Ovens, Shelley L McLeod. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.07.2024.)

Background: Immigrants and refugees face unique challenges navigating the health care system to manage severe arthritis, because of unfamiliarity, lack of awareness of surgical options, or access. The purpose of this study was to assess total knee arthroplasty (TKA) uptake, surgical outcomes, and hospital utilization among immigrants and refugees compared with Canadian-born patients., Methods: We included all adults undergoing primary TKA from January 2011 to December 2020 in Ontario. Cohorts were defined as Canadian-born or immigrants and refugees. We assessed change in yearly TKA utilization for trend. We compared differences in 1-year revision, infection rates, 30-day venous thromboembolism (VTE), presentation to emergency department, and hospital readmission between matched Canadian-born and immigrant and refugee groups., Results: We included 158 031 TKA procedures. A total of 11 973 (7.6%) patients were in the immigrant and refugee group, and 146 058 (92.4%) patients were in the Canadian-born group. The proportion of TKAs in Ontario performed among immigrants and refugees nearly doubled over the 10-year study period ( p < 0.001). After matching, immigrants were at relatively lower risk of 1-year revision (0.9% v. 1.6%, p < 0.001), infection ( p < 0.001), death ( p = 0.004), and surgical complications ( p < 0.001). No differences were observed in rates of 30-day VTE or length of hospital stay. Immigrants were more likely to be discharged to rehabilitation ( p < 0.001) and less likely to present to the emergency department ( p < 0.001) than Canadian-born patients., Conclusion: Compared with Canadian-born patients, immigrants and refugees have favourable surgical outcomes and similar rates of resource utilization after TKA. We observed an underutilization of these procedures in Ontario relative to their proportion of the population. This may reflect differences in perceptions of chronic pain or barriers accessing arthroplasty., Competing Interests: Competing interests:: J. Michael Paterson reports research funding from Arthritis Society Canada and the Canadian Institutes of Health Research. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

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.)

Introduction: Previous research has suggested that how physicians are paid may affect the completeness of billing claims for estimating chronic disease. The purpose of this study is to estimate the completeness of physician billings for diabetes case ascertainment., Methods: We used administrative data from eight Canadian provinces covering the period 1 April 2014 to 31 March 2016. The patient cohort was stratified into two mutually exclusive groups based on their physician remuneration type: fee-for-service (FFS), for those paid only on that basis; and non-fee-for-service (NFFS). Using diabetes prescription drug data as our reference data source, we evaluated whether completeness of disease case ascertainment varied with payment type. Diabetes incidence rates were then adjusted for completeness of ascertainment., Results: The cohort comprised 86 110 patients. Overall, equal proportions received their diabetes medications from FFS and NFFS physicians. Overall, physician payment method had little impact upon the percentage of missed diabetes cases (FFS, 14.8%; NFFS, 12.2%). However, the difference in missed cases between FFS and NFFS varied widely by province, ranging from -1.0% in Nova Scotia to 29.9% in Newfoundland and Labrador. The difference between the observed and adjusted disease incidence rates also varied by province, ranging from 22% in Prince Edward Island to 4% in Nova Scotia., Conclusion: The difference in the loss of cases by physician remuneration method varied across jurisdictions. This loss may contribute to an underestimation of disease incidence. The method we used could be applied to other chronic diseases for which drug therapy could serve as reference data source., Competing Interests: The authors have no conflicts of interest to declare.

Background: Ranitidine was the most prescribed histamine-2 receptor antagonist (H 2 RA) in Canada when recalled in 2019 because of potential carcinogenicity. We sought to compare geographic and temporal patterns in use of prescription ranitidine and 3 other HRAs and estimated population exposure to ranitidine in 6 provinces between 1996 and 2019., Methods: This population-based serial cross-sectional study used prescription claims for H 2 RAs dispensed from community pharmacies in Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta and British Columbia. We estimated the period prevalence of ranitidine use per 100 population by province, age category and sex. We estimated exposure to ranitidine between 2015 and 2019 using defined daily doses (DDDs)., Results: Overall, 2.4 million ranitidine prescriptions were dispensed to patients aged 65 years and older, and 1.7 million were dispensed to younger adults. Among older adults, the median period prevalence of ranitidine use among females was 16% (interquartile range [IQR] 13%-27%) higher than among males. Among younger adults, the median prevalence was 50% (IQR 37%-70%) higher among females. Among older adults, between 1996 and 1999, use was highest in Nova Scotia (33%) and Ontario (30%), lower in the prairies (Manitoba [18%], Saskatchewan [26%], Alberta [17%]) and lowest in BC (11%). By 2015-2019, use of ranitidine among older adults dropped by at least 50% in all provinces except BC. We estimate that at least 142 million DDDs of prescribed ranitidine were consumed annually in 6 provinces (2015-2019)., Interpretation: Over the 24-year period in 6 provinces, patients aged 65 years and older were dispensed 2.4 million prescriptions of ranitidine and younger adults were dispensed 1.7 million prescriptions of ranitidine. These estimates of ranitidine exposure can be used for planning studies of cancer risk and identifying target populations for cancer surveillance., Competing Interests: Competing interests: Laura Targownik has served on advisory boards or created educational materials for Janssen AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Roche Canada, Sandoz Canada, JAMP Pharmaceuticals and Celltrion Pharmaceuticals. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Virtual urgent care (VUC) is intended to support diversion of patients with low-acuity complaints and reduce the need for in-person emergency department visits. We aimed to describe subsequent health care utilization and outcomes of patients who used VUC compared with similar patients who had an in-person emergency department visit., Methods: We used patient-level encounter data that were prospectively collected for patients using VUC services provided by 14 pilot programs in Ontario, Canada. We linked the data to provincial administrative databases to identify subsequent 30-day health care utilization and outcomes. We defined 2 subgroups of VUC users; those with a documented prompt referral to an emergency department by a VUC provider, and those without. We matched patients in each cohort to an equal number of patients presenting to an emergency department in person, based on encounter date, medical concern and the logit of a propensity score. For the subgroup of patients not promptly referred to an emergency department, we matched patients to those who were seen in an emergency department and then discharged home., Results: Of the 19 595 patient VUC visits linked to administrative data, we matched 2129 patients promptly referred to the emergency department by a VUC provider to patients presenting to the emergency department in person. Index visit hospital admissions (9.4% v. 8.7%), 30-day emergency department visits (17.0% v. 17.5%), and hospital admissions (12.9% v. 11.0%) were similar between the groups. We matched 14 179 patients who were seen by a VUC provider with no documented referral to the emergency department. Patients seen by VUC were more likely to have a subsequent in-person emergency department visit within 72 hours (13.7% v. 7.0%), 7 days (16.5% v. 10.3%) and 30 days (21.9% v. 17.9%), but hospital admissions were similar within 72 hours (1.1% v. 1.3%), and higher within 30 days for patients who were discharged home from the emergency department (2.6% v. 3.4%)., Interpretation: The impact of the provincial VUC pilot program on subsequent health care utilization was limited. There is a need to better understand the inherent limitations of virtual care and ensure future virtual providers have timely access to in-person outpatient resources, to prevent subsequent emergency department visits., Competing Interests: Competing interests: Joy McCarron is a paid employee of Ontario Health. Shawn Mondoux reports research funding from the Juravinski Research Institute and PSI Foundation, as well as travel support from Mitacs. Howard Ovens is a paid advisor to the Ministry of Health and in that capacity has provided executive sponsorship for the virtual urgent care evaluation. No oher competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Accurate coding of diagnoses of SARS-CoV-2 infection in administrative data benefits population-based studies about the epidemiology, treatment and outcomes of COVID-19. We describe the validity of diagnoses of SARS-CoV-2 infection recorded in hospital discharge abstracts, emergency department records and outpatient physician service claims from 3 Canadian provinces., Methods: In this cohort study, population-based inpatient, emergency department and outpatient records were linked to SARS-CoV-2 polymerase chain reaction (PCR; reference standard) test results from British Columbia, Manitoba and Ontario for Apr. 1, 2020, to Mar. 31, 2021. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of diagnoses of SARS-CoV-2 infection were estimated for each quarter in the study period, overall and by province, age group and sex., Results: Our study encompassed more than 13 million SARS-CoV-2 PCR test results. Specificity and NPV of diagnoses of SARS-CoV-2 infection were consistently high (i.e., most estimates were > 95%). Overall sensitivity estimates were 86.2%, 60.4% and 20.3% in the first quarter for inpatient, emergency department and outpatient cohorts, and 66.2%, 47.5% and 25.0% in the last quarter, respectively. For inpatients, overall PPV estimates ranged from 50.0% to 66.4%. For emergency department patients, overall PPV estimates were 76.9% and 68.3% in the first and last quarters, respectively. For outpatients, PPV estimates were 6.8% and 29.1% in the first and last quarters, respectively., Interpretation: We found variations in the validity of diagnoses for SARS-CoV-2 infection recorded in different health care settings, geographic areas and over time. Our multiprovince validation study provides evidence about the potential use of inpatient and emergency department records as an alternative to population-based laboratory data for identification of patients with SARS-CoV-2 infection, but does not support the use of outpatient claims for this purpose., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined whether initiation of oxycodone after delivery was associated with an increased risk of persistent opioid use relative to initiation of codeine., Methods: We conducted a population-based cohort study of people who filled a prescription for either codeine or oxycodone within 7 days of discharge from hospital after delivery between Sept. 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, defined as 1 or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and 1 or more additional prescriptions in the 91 to 365 days thereafter. We used inverse probability of treatment weighting to assess the risk of persistent postpartum opioid use, comparing people who initiated oxycodone with those who initiated codeine., Results: Over the 8-year study period, we identified 70 607 people who filled an opioid prescription within 7 days of discharge from hospital: 21 308 (30.2%) received codeine and 49 299 (69.8%) oxycodone. Compared with people who filled a prescription for codeine, receipt of oxycodone was not associated with persistent opioid use (relative risk [RR] 1.04, 95% confidence interval [CI] 0.91-1.20). We found an association between a prescription for oxycodone and persistent use after vaginal delivery (RR 1.63, 95% CI 1.31-2.03), but not after cesarean delivery (RR 0.85, 95% CI 0.73-1.00)., Interpretation: Initiation of oxycodone (v. codeine) was not associated with an increased risk of persistent opioid use, except after vaginal delivery., Competing Interests: Competing interests: Jonathan Zipursky has received payments from private law firms for medicolegal opinions on the safety and effectiveness of analgesics, including opioids. Dr. Zipursky is supported by the University of Toronto Department of Medicine Clinician Scientist Training Program and a Canadian Institutes of Health Research (CIHR) Banting and Best Doctoral Award. David Juurlink reports receiving payment for expert testimony from multiple law firms related to analgesics, including opioids; an honorarium for a lecture on pain management from Texas Tech University Health Sciences Center; and reimbursement for travel costs for presentations and scientific meetings from CIHR, Stanford University and Texas Tech University Health Sciences Center. Dr. Juurlink is an unpaid member of Physicians for Responsible Opioid Prescribing (PROP), a nongovernmental organization with the goal of promoting opioid stewardship. Tara Gomes reports receiving grant and contract funding from the Ontario Ministry of Health, the Public Health Agency of Canada, the Ontario College of Pharmacists and the Government of Canada (paid to institution in support of Dr. Gomes’ research program). A Tier 2 Canada Research Chair supports Dr. Gomes’ salary. Dr. Gomes has also received payment for travel and a stipend for participating in the Drugs and Therapeutics Advisory Committee from Indigenous Services Canada. Muhammad Mamdani reports receiving grant funding from Roche, examining drug use for multiple sclerosis. Dr. Mamdani has also received honoraria as a member of the scientific advisory board of SaNotize. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Importance: Opioid-related harms constitute a major public health crisis in the US, and this crisis has worsened during the COVID-19 pandemic., Objectives: To characterize the societal burden of unintentional opioid-related deaths in the US and describe changing mortality patterns during the COVID-19 pandemic., Design, Setting, and Participants: A serial cross-sectional study examined all unintentional opioid-related deaths in the US, evaluated annually from calendar years 2011 to 2021., Main Outcomes and Measures: The public health burden of opioid toxicity-related deaths was estimated in 2 ways. First, the proportion of all deaths that were attributable to unintentional opioid toxicity by year (2011, 2013, 2015, 2017, 2019, and 2021) and age group (15-19, 20-29, 30-39, 40-49, 50-59, and 60-74 years) were calculated, using age-specific estimates of all-cause mortality as the denominator. Second, the total years of life lost (YLL) due to unintentional opioid toxicity was estimated, overall and by sex and age group, for each year studied., Results: Among the 422 605 unintentional deaths due to opioid toxicity between 2011 and 2021, the median age of the individuals was 39 (IQR, 30-51) years, and 69.7% were male. The number of unintentional deaths due to opioid toxicity increased 289% over the study period, from 19 395 (2011) to 75 477 (2021). Similarly, the percentage of all deaths that were attributed to opioid toxicity increased from 1.8% in 2011 to 4.5% in 2021. By 2021, opioid toxicity was responsible for 10.2% of all deaths among those aged 15 to 19 years, 21.7% of deaths among those aged 20 to 29 years, and 21.0% of deaths among those aged 30 to 39 years. The YLL due to opioid toxicity increased 276% over the study period, from 777 597 in 2011 to 2 922 497 in 2021. While YLL plateaued between 2017 (7.0 YLL per 1000) and 2019 (7.2 YLL per 1000), it increased by 62.9% between 2019 and 2021 coincident with the COVID-19 pandemic, reaching 11.7 YLL per 1000 population. This relative increase was similar across all age groups and sexes with the exception of those aged 15 to 19 years, in whom the YLL nearly tripled, from 1.5 to 3.9 YLL per 1000 population., Conclusions and Relevance: In this cross-sectional study, deaths due to opioid toxicity increased substantially during the COVID-19 pandemic. By 2021, 1 of every 22 deaths in the US was attributable to unintentional opioid toxicity, underscoring the urgent need to support people at risk of substance-related harm, particularly men, younger adults, and adolescents.

Background: Walk-in clinics are common in North America and are designed to provide acute episodic care without an appointment. We sought to describe a sample of walk-in clinic patients in Ontario, Canada, which is a setting with high levels of primary care attachment., Methods: We performed a cross-sectional study using health administrative data from 2019. We compared the sociodemographic characteristics and health care utilization patterns of patients attending 1 of 72 walk-in clinics with those of the general Ontario population. We examined the subset of patients who were enrolled with a family physician and compared walk-in clinic visits to family physician visits., Results: Our study found that 562 781 patients made 1 148 151 visits to the included walk-in clinics. Most (70%) patients who attended a walk-in clinic had an enrolling family physician. Walk-in clinic patients were younger (mean age 36 yr v. 41 yr, standardized mean difference [SMD] 0.24), yet had greater health care utilization (moderate and high use group 74% v. 65%, SMD 0.20) than the general Ontario population. Among enrolled Ontarians, walk-in patients had more comorbidities (moderate and high count 50% v. 45%, SMD 0.10), lived farther from their enrolling physician (median 8 km v. 6 km, SMD 0.21) and saw their enrolling physician less in the previous year (any visit 67% v. 80%, SMD 0.30). Walk-in encounters happened more often after hours (16% v. 9%, SMD 0.20) and on weekends (18% v. 5%, SMD 0.45). Walk-in clinics were more often within 3 km of patients' homes than enrolling physicians' offices (0 to < 3 km: 32% v. 22%, SMD 0.21)., Interpretation: Our findings suggest that proximity of walk-in clinics and after-hours access may be contributing to walk-in clinic use among patients enrolled with a family physician. These findings have implications for policy development to improve the integration of walk-in clinics and longitudinal primary care., Competing Interests: Competing interests: Lauren Lapointe-Shaw is supported by the University of Toronto Department of Medicine, the Toronto General Hospital Research Institute, the Women’s College Institute for Health System Solutions and Virtual Care and the Peter Gilgan Centre for Women’s Cancers at the Women’s College Hospital, in partnership with the Canadian Cancer Society. Tara Kiran is the Fidani Chair of Improvement and Innovation at the University of Toronto and is supported as a clinician scientist by the Department of Family and Community Medicine at St. Michael’s Hospital and the University of Toronto. Noah M. Ivers is supported by a Canada Research Chair in Implementation of Evidence-based Practice and a clinician scholar award from the Department of Family and Community Medicine at the Women’s College Hospital and the University of Toronto., (© 2023 CMA Impact Inc. or its licensors.)

Introduction: The recent publication of a national guideline and quality standards in Canada have provided clinicians with new, evidence-based recommendations on safe, appropriate opioid use. We sought to characterize how well opioid initiation practices aligned with these recommendations before and following their release., Methods: We conducted a population-based study among people initiating opioids prior to the release of national guidelines (April 2015-March 2016; fiscal year [FY] 2015) and in the most recent year available (January-December 2019) in Ontario, Canada. We used linked administrative claims data to ascertain the apparent indication for opioid therapy, and characterized the initial daily dose (milligrams morphine or equivalent; MME) and prescription duration for each indication., Results: In FY2015, 653,885 individuals commenced opioids, compared to 571,652 in 2019. Over time, there were small overall reductions in the prevalence of initial daily doses exceeding 50MME (23.9% vs. 20.1%) and durations exceeding 7 days (17.4% vs. 14.8%); but the magnitude of the reductions varied widely by indication. The prevalence of high dose (>50MME) initial prescriptions reduced significantly across all indications, with the exception of dentist-prescribed opioids (13.6% vs. 12.1% above 50MME). In contrast, there was little change in initial durations exceeding 7 days across most indications, with the exception of some surgical indications (e.g. common excision; 9.3% vs. 6.2%) and among those in palliative care (35.2% vs. 29.2%)., Conclusion: Despite some modest reductions in initiation of high dose and long duration prescription opioids between 2015 and 2019, clinical practice is highly variable, with opioid prescribing practices influenced by clinical indication. These findings may help identify medical specialties well-suited to targeted interventions to promote safer opioid prescribing., Competing Interests: Dr. Muhammad Mamdani has received honoraria from Boehringer Ingelheim, Pfizer, Mristol-Myers Squibb, and Bayer. Dr. David Juurlink has received payment for lectures and medicolegal opinions regarding the safety and effectiveness of analgesics, including opioids. He is a member of Physicians for Responsible Opioid Prescribing, a volunteer organization that seeks to reduce opioid-related harm through more cautious prescribing practices. Dr. Gomes has received grant funding from the Ontario Ministry of Health. No other authors have any conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Gomes 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.)

Objective: To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014., Methods: We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion. We determined maternal use of antiemetics from pharmacy claims in Canada and the United States and from prescriptions in the United Kingdom., Results: The most common outcome of 3 848 734 included pregnancies (started 2002-2014) was live birth (66.7% of all pregnancies) followed by spontaneous abortion (20.2%). Use of antiemetics during pregnancy increased over time in all three countries. Canada had the highest prevalence of use of prescription antiemetics during pregnancy (17.7% of pregnancies overall, 13.2% of pregnancies in 2002, and 18.9% in 2014), followed by the United States (14.0% overall, 8.9% in 2007, and 18.1% in 2014), and the United Kingdom (5.0% overall, 4.2% in 2002, and 6.5% in 2014). Besides use of antiemetic drugs being considerably lower in the United Kingdom, the increase in its use over time was more modest. The most commonly used antiemetic was combination doxylamine/pyridoxine in Canada (95.2% of pregnancies treated with antiemetics), ondansetron in the United States (72.2%), and prochlorperazine in the United Kingdom (63.5%)., Conclusions: In this large cohort study, we observed an overall increase in antiemetic use during pregnancy, and patterns of use varied across jurisdictions. Continued monitoring of antiemetic use and further research are warranted to better understand the reasons for differences in use of these medications and to assess their benefit-risk profile in this population., Competing Interests: : SS reported receiving personal fees from Atara, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Novartis, Pfizer, and Seqirus outside the submitted work. KBF is supported by a salary support award from the Fonds de recherche du Québec – santé (FRQS; Quebec Foundation for Research – Health) and a William Dawson Scholar award from McGill University. RWP holds the Albert Boehringer I Chair in Pharmacoepidemiology at McGill University. RWP reported receiving personal fees from Amgen, Biogen, Merck, and Pfizer outside the submitted work. MP reported grants from Canadian Institutes of Health Research during the conduct of the study. No other disclosures were reported. No endorsement by the funders, data providers, data stewards, CIHI, or Health Canada is intended or should be inferred. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Fisher 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: Anecdotally there are reports of newly diagnosed SARS-CoV-2 infection shortly after vaccination. This has led some to speculate that vaccination itself might inadvertently increase the short-term risk of COVID potentially due to airborne spread at mass vaccination clinics or relaxation of precautions following vaccination. We explored whether receipt of vaccination was associated with a short-term increase in the risk of being diagnosed with COVID-19 and if differences exist between vaccination settings., Methods: We conducted a cohort study in Ontario, Canada to compare the risk of SARS-CoV-2 infection within 21 days of receiving a first vaccination, according to the setting in which vaccines were administered between March 1, 2021 and May 6, 2021. We used linked population-wide vaccination, laboratory testing, and health administrative databases. We created a 1:1 matched comparison group of unexposed individuals. We reported the overall risk of infection calculated at 3, 7, 10, 14, 18, and 21 days. This was completed overall and by setting of vaccine receipt., Results: We identified 4,798,430 Ontario residents who received their first dose of a COVID-19 vaccine. In the primary analysis, the rate of SARS-CoV-2 infection was significantly lower among vaccine recipients vs non-recipients at all the post-vaccination time points. Analysis stratified by vaccination setting found that mass vaccination clinics, pharmacies, and physician offices were consistent with the main findings. Individuals who received their first vaccine dose in congregate residential settings had a higher rate of SARS-CoV-2 infection at 7 days (HR 1.35, 95% CI 1.00-1.83) and 10 days (HR 1.49, 95% CI 1.03-2.15)., Conclusion: In this population-based cohort study, we found that there was no increased risk of SARS-CoV2 infection after vaccination suggesting no broad transmission of disease at time of vaccination. Some evidence of increased risk among those vaccinated in congregate settings, highlighting the need to consider opportunities for supporting safe vaccine administration in these settings. Given ongoing and future immunization programs, the results support the need for continued vigilance during any mass vaccination processes and education regarding the delayed nature of protection following vaccination., Competing Interests: The authors do not report any relevant conflicts of interest.

Background: There are limited published data on population estimates of survival after spinal surgery for metastatic disease. We performed a population-based study to evaluate survival and complications among patients with cancer who underwent surgery for spinal metastases in Ontario, Canada, between 2006 and 2016., Methods: We used health administrative databases to identify all patients who underwent surgery for spinal metastases in Ontario between Jan. 1, 2006, and Dec. 31, 2016. We assessed overall survival, mortality rates according to primary cancer lesion and complications after surgery. We contrast the results to those for a comparable cohort from 1991 to 1998., Results: A total of 2646 patients (1194 women [45.1%]; mean age 62.5 yr [standard deviation 12.2 yr]) were identified. The median survival time was 236 (interquartile range 84-740) days. Mortality was highest for patients with melanoma, upper gastrointestinal cancer and lung cancer, with 50% dying within 90 days of surgery. The longest median survival times were observed for primary cancers of the thyroid (906 d) and breast (644 d), and myeloma (830 d). Overall 90-day and 1-year mortality rates were 29% and 59%, respectively., Conclusion: We identified differential survivorship based on primary tumour type and a shift in the distribution of operations performed for specific primary cancers over the past 2 decades in Ontario. Overall reductions in mortality associated with this shift in treatment may reflect the use of adjuvant therapies and more personalized treatment approaches., Competing Interests: Competing interests: Joel Finkelstein receives consultant fees from Zimmer Biomet Institutional Educational Support. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Computational biology provides software tools for testing and making inferences about biological data. In the face of increasing volumes of data, heuristic methods that trade software speed for accuracy may be employed. We have studied these trade-offs using the results of a large number of independent software benchmarks, and evaluated whether external factors, including speed, author reputation, journal impact, recency and developer efforts, are indicative of accurate software., Results: We find that software speed, author reputation, journal impact, number of citations and age are unreliable predictors of software accuracy. This is unfortunate because these are frequently cited reasons for selecting software tools. However, GitHub-derived statistics and high version numbers show that accurate bioinformatic software tools are generally the product of many improvements over time. We also find an excess of slow and inaccurate bioinformatic software tools, and this is consistent across many sub-disciplines. There are few tools that are middle-of-road in terms of accuracy and speed trade-offs., Conclusions: Our findings indicate that accurate bioinformatic software is primarily the product of long-term commitments to software development. In addition, we hypothesise that bioinformatics software suffers from publication bias. Software that is intermediate in terms of both speed and accuracy may be difficult to publish-possibly due to author, editor and reviewer practises. This leaves an unfortunate hole in the literature, as ideal tools may fall into this gap. High accuracy tools are not always useful if they are slow, while high speed is not useful if the results are also inaccurate., (© 2022. The Author(s).)

Introduction: Health care systems have faced unprecedented challenges due to the COVID-19 pandemic. Access to timely population-based data has been vital to informing public health policy and practice., Methods: We describe how ICES, an independent not-for-profit research and analytic institute in Ontario, Canada, pivoted existing research infrastructure and engaged health system stakeholders to provide near real-time population-based data and analytics to support Ontario's COVID-19 pandemic response., Results: Since April 2020, ICES provided the Ontario COVID-19 Provincial Command Table and public health partners with regular and ad hoc reports on SARS-CoV-2 testing and COVID-19 vaccine coverage. These reports: 1) helped identify congregate care/shared living settings that needed testing and prevention efforts early in the pandemic; 2) provided early indications of inequities in testing and infection in marginalized neighbourhoods, including areas with higher proportions of immigrants and visible minorities; 3) identified areas with high test positivity, which helped Public Health Units target and evaluate prevention efforts; and 4) contributed to altering the province's COVID-19 vaccine roll-out strategy to target high-risk neighbourhoods and helping Public Health Units and community organizations plan local vaccination programs. In addition, ICES is a key component of the Ontario Health Data Platform, which provides scientists with data access to conduct COVID-19 research and analyses., Discussion and Conclusion: ICES was well-positioned to provide rapid analyses for decision-makers to respond to the evolving public health emergency, and continues to contribute to Ontario's pandemic response by providing timely, relevant reports to health system stakeholders and facilitating data access for externally-funded COVID-19 research., Competing Interests: Declaration of conflicts of interest (COI): All authors are employees of ICES, which is funded by the Ontario Ministries of Health and Long-Term Care.

Importance: Little is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients., Objective: To estimate the CDI incidence and outcomes in SOT recipients., Design, Setting, and Participants: A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period., Main Outcomes and Measures: The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis., Results: Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality., Conclusions and Relevance: In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

Background: Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada., Methods: We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine., Results: In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab)., Interpretation: Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients., Competing Interests: Competing interests: Muhammad Mamdani reports receiving honoraria from Neurocrine Biosciences, and reports being a one-time advisory board member for Roche. Laurie Proulx reports membershp of the executive of the Canadian Arthritis Patient Alliance. Tara Gomes reports receiving a grant from the Ontario Ministry of Health. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

ICES upholds a strong reputation for generating high-quality evidence to inform policy and practice through its collaborations with a broad range of health system stakeholders including government policymakers and healthcare providers including clinicians. Supported by the Ontario Ministry of Health and Ministry of Long-Term Care, the ICES Applied Health Research Question (AHRQ) Program leverages the data holdings and, scientific and clinical expertise to generate evidence tailored to the information needs of requestors. This paper outlines the approach, process, strengths, challenges and the resulting influence and impact to the healthcare landscape in Ontario., Competing Interests: Declaration of conflicts of interest (COI): All authors are employees of ICES, which is funded by the Ontario Ministries of Health and Long-Term Care.

Competing Interests: Competing interests: None declared.

Importance: Data on the long-term health care expenditures associated with bariatric surgery consisting of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy are lacking., Objective: To compare 4-year health care expenditures after RYGB vs sleeve gastrectomy, identify factors independently associated with 4-year health care expenditures, and compare the procedures in terms of subsequent hospitalizations, bariatric procedures, and all-cause mortality., Design, Setting, and Participants: In this propensity score-matched cohort study, all residents of Ontario, Canada, who underwent publicly funded surgery with RYGB (n = 6301) or sleeve gastrectomy (n = 926) from March 1, 2010, to March 31, 2015, and consented to participate in the Ontario Bariatric Registry were eligible for the study. Follow-up was completed on March 31, 2019, and data were analyzed from May 5, 2020, to May 20, 2021., Interventions: RYGB and sleeve gastrectomy., Main Outcomes and Measures: Publicly funded health care expenditures, subsequent hospitalizations, bariatric procedures, and mortality during the 4 years after RYGB or sleeve gastrectomy., Results: The 1:1 matched study cohorts consisted of 1624 patients (812 per cohort) with a mean (SD) age of 48.0 (10.6) years, and 1242 women (76.5%). The mean body mass index (calculated as weight in kilograms divided by height in square meters) was 51.9 (8.3) for the RYGB cohort and 51.9 (8.9) for the sleeve gastrectomy cohort. The 4-year cumulative costs were not statistically significantly different between RYGB and sleeve gastrectomy (mean [SD], $33 682 [$31 169] vs $33 948 [$32 633], respectively; P = .86). Having a history of coronary artery disease was associated with a 35% increase in overall health care expenditures; chronic kidney disease, a 54% increase; and mental health admissions, a 67% increase. There were no statistically significant differences in all-cause mortality between RYGB and sleeve gastrectomy (1.5% vs 2.2%, respectively; P = .26) or the total number of hospitalizations (754 vs 669, respectively; P = .11) during the 4-year follow-up period. However, nonelective hospitalizations occurred more frequently with RYGB vs sleeve gastrectomy (472 vs 339, respectively; P = .002). Roux-en-Y gastric bypass was associated with relatively fewer subsequent bariatric procedures during the 4-year follow-up period (9 vs 40, respectively; P < .001)., Conclusions and Relevance: In this Canadian population-based study, key results indicated that 4-year health care expenditures, all-cause mortality, and number of hospital admissions associated with RYGB did not significantly differ from those for sleeve gastrectomy. The rate of subsequent bariatric surgery was lower with RYGB. This study identified important patient-level drivers of health care expenditures that need to be further investigated.

Importance: Severe obesity is a risk factor for major early complications after total hip arthroplasty (THA)., Objective: To determine the association between surgeon experience with THA in patients with severe obesity and risk of complications., Design, Setting, and Participants: This retrospective population-based cohort study was performed in Ontario, Canada, from April 1, 2007, to March 31, 2017, with data analysis performed from March 2020 to January 2021. A cohort of patients who received a primary THA for osteoarthritis and who also had severe obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] ≥40) at the time of surgery was defined. These patients were identified using the Canadian Institute for Health Information Discharge Abstract Database and physician claims from the Ontario Health Insurance Plan. Generalized estimating equations were used to determine the association between overall THA and severe obesity-specific THA surgeon volume and the occurrence of complications after controlling for potential confounders. The study hypothesized that surgeon experience specific to patients with severe obesity could further reduce the risk of complications., Exposures: Primary THA., Main Outcomes and Measures: Complications were considered as a composite outcome (revision, infection requiring surgery, or dislocation requiring reduction), within 1 year of surgery. This was defined before the study, as was the study hypothesis., Results: A total of 4781 eligible patients was identified. The median age was 63 (interquartile range [IQR], 56-69) years, and 3050 patients (63.8%) were women. Overall, 186 patients (3.9%) experienced a surgical complication within 1 year of surgery. The median overall THA surgeon volume was 70 (IQR, 46-106) cases/y, whereas the median obesity-specific surgeon volume was 5 (IQR, 2-9) cases/y. After controlling for patient and hospital factors, greater obesity-specific THA surgeon volume (adjusted odds ratio per additional 10 cases, 0.65 [95% CI, 0.47-0.89]; P = .007), but not greater overall THA surgeon volume (adjusted odds ratio per 10 additional cases, 0.97 [95% CI, 0.93-1.02]; P = .24), was associated with a reduced risk of complication., Conclusions and Relevance: Increased surgeon experience performing THA in patients with severe obesity was associated with fewer major surgical complications. These findings suggest that surgeon experience is required to mitigate the unique anatomical challenges posed by surgery in patients with severe obesity. Referral pathways for patients with severe obesity to surgeons with high obesity-specific THA volume should be considered.

This cross-sectional study compares rates of emergency department visits and hospitalizations for assault and maltreatment by age category and sex in Ontario, Canada, before vs during the COVID-10 pandemic., Competing Interests: Conflict of Interest Disclosures: Dr Saunders reported receiving grants from the Ontario Ministry of Health during the conduct of the study and receiving honorarium from the Archives of Diseases in Childhood, The BMJ Group outside the submitted work. Dr Plumptre reported receiving grants from the Ontario Ministry of Health through the Applied Health Research Question program during the conduct of the study. No other disclosures were reported., (Copyright 2021 Saunders N et al. JAMA Health Forum.)

Background: Health care funding reforms are being used worldwide to improve system performance but may invoke unintended consequences. We assessed the effects of introducing a targeted hospital funding model, based on fixed price and volume, for hip fractures. We hypothesized the policy change was associated with reduction in wait times for hip fracture surgery, increase in wait times for non-hip fracture surgery, and increase in the incidence of after-hours hip fracture surgery., Methods: This was a population-based, interrupted time series analysis of 49,097 surgeries for hip fractures, 10,474 for ankle fractures, 1,594 for tibial plateau fractures, and 40,898 for appendectomy at all hospitals in Ontario, Canada between April 2012 and March 2017. We used segmented regression analysis of interrupted monthly time series data to evaluate the impact of funding reform enacted April 1, 2014 on wait time for hip fracture repair (from hospital presentation to surgery) and after-hours provision of surgery (occurring between 1700 and 0700 h). To assess potential adverse consequences of the reform, we also evaluated two control procedures, ankle and tibial plateau fracture surgery. Appendectomy served as a non-orthopedic tracer for assessment of secular trends., Results: The difference (95 % confidence interval) between the actual mean wait time and the predicted rate had the policy change not occurred was - 0.46 h (-3.94 h, 3.03 h) for hip fractures, 1.46 h (-3.58 h, 6.50 h) for ankle fractures, -3.22 h (-39.39 h, 32.95 h) for tibial plateau fractures, and 0.33 h (-0.57 h, 1.24 h) for appendectomy (Figure 1; Table 3). The difference (95 % confidence interval) between the actual and predicted percentage of surgeries performed after-hours - 0.90 % (-3.91 %, 2.11 %) for hip fractures, -3.54 % (-11.25 %, 4.16 %) for ankle fractures, 7.09 % (-7.97 %, 22.14 %) for tibial plateau fractures, and 1.07 % (-2.45 %, 4.59 %) for appendectomy., Conclusions: We found no significant effects of a targeted hospital funding model based on fixed price and volume on wait times or the provision of after-hours surgery. Other approaches for improving hip fracture wait times may be worth pursuing instead of funding reform.

Background: Stigma and high-care needs can present barriers to the provision of high-quality primary care for people with opioid use disorder (OUD) and those prescribed opioids for chronic pain. We explored the likelihood of securing a new primary care provider (PCP) among people with varying histories of opioid use who had recently lost access to their PCP., Methods and Findings: We conducted a retrospective cohort study using linked administrative data among residents of Ontario, Canada whose enrolment with a physician practicing in a primary care enrolment model (PEM) was terminated between January 2016 and December 2017. We assigned individuals to 3 groups based upon their opioid use on the date enrolment ended: long-term opioid pain therapy (OPT), opioid agonist therapy (OAT), or no opioid. We fit multivariable models assessing the primary outcome of primary care reattachment within 1 year, adjusting for demographic characteristics, clinical comorbidities, and health services utilization. Secondary outcomes included rates of emergency department (ED) visits and opioid toxicity events. Among 154,970 Ontarians who lost their PCP, 1,727 (1.1%) were OAT recipients, 3,644 (2.4%) were receiving long-term OPT, and 149,599 (96.5%) had no recent prescription opioid exposure. In general, OAT recipients were younger (median age 36) than those receiving long-term OPT (59 years) and those with no recent prescription opioid exposure (44 years). In all exposure groups, the majority of individuals had their enrolment terminated by their physician (range 78.1% to 88.8%). In the primary analysis, as compared to those not receiving opioids, OAT recipients were significantly less likely to find a PCP within 1 year (adjusted hazard ratio [aHR] 0.55, 95% confidence interval [CI] 0.50 to 0.61, p < 0.0001). We observed no significant difference between long-term OPT and opioid unexposed individuals (aHR 0.96; 95% CI 0.92 to 1.01, p = 0.12). In our secondary analysis comparing the period of PCP loss to the year prior, we found that rates of ED visits were elevated among people not receiving opioids (adjusted rate ratio (aRR) 1.20, 95% CI 1.18 to 1.22, p < 0.0001) and people receiving long-term OPT (aRR 1.37, 95% CI 1.28 to 1.48, p < 0.0001). We found no such increase among OAT recipients, and no significant increase in opioid toxicity events in the period following provider loss for any exposure group. The main limitation of our findings relates to their generalizability outside of PEMs and in jurisdictions with different financial incentives incorporated into primary care provision., Conclusions: In this study, we observed gaps in access to primary care among people who receive prescription opioids, particularly among OAT recipients. Ongoing efforts are needed to address the stigma, discrimination, and financial disincentives that may introduce barriers to the healthcare system, and to facilitate access to high-quality, consistent primary care services for chronic pain patients and those with OUD., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests to report: TG and RG have received grant funding from the Ontario Ministry of Health and CIHR. RG serves as a CIHR Scientific Director. DNJ is an unpaid member of Physicians for Responsible Opioid Prescribing (PROP). He is also a member of the American College of Medical Toxicology. Both groups have publicly available positions on this issue. He has received payment for lectures and medicolegal opinions regarding the safety and effectiveness of analgesics, including opioids. MMM has received honoraria for attending Advisory Board meetings for NovoNordisk and Neurocrine Biosciences.