Publications by authors named "Michael Paterson"

233 Publications

Effects of hospital funding reform on wait times for hip fracture surgery: a population-based interrupted time-series analysis.

BMC Health Serv Res 2021 Jun 13;21(1):576. Epub 2021 Jun 13.

ICES, Toronto, Canada.

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.
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http://dx.doi.org/10.1186/s12913-021-06601-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201723PMC
June 2021

Risk of Total Hip Arthroplasty After Acetabular Fracture Fixation: The Importance of Age.

J Arthroplasty 2021 Apr 24. Epub 2021 Apr 24.

Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Orthopaedic Surgery, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada.

Background: Geriatric patients are the most rapidly growing cohort of patients sustaining acetabular fractures (AFs). The purpose of this study was to examine the risk of a secondary total hip arthroplasty (THA) in older patients (>60 year old) with a prior AF open reduction internal fixation (ORIF) compared with younger patients (<60 year old) with an AF ORIF on a large population level.

Methods: Using administrative health care data from 1996 to 2010 inclusive of all 202 hospitals in Ontario, Canada, all adult patients with an AF ORIF and a minimum of two year follow-up were identified and included. The risk of THA was examined using a Cox proportional hazards model adjusting for patient risk factors. Secondary outcomes included surgical complications and all-cause mortality.

Results: A total of 1725 patients had an AF ORIF; 1452 (84.2%, mean age of 38.3 ± 12.1 years) aged <60 years ("younger") and 273 (15.8%, mean age of 69.9 ± 7.8 years) > 60 years ("older"). The mean (SD) follow-up time for all patients was 6.9 (4.2) years. In older patients, 19.4% (53 of 273) went on to receive a secondary THA with a median time to event of 3.9 years, compared with 12.9% (187 of 1452) in the younger patient cohort with a median time of 6.9 years (HR 1.7, 95% CI: 1.2-2.3). As expected, older patients had a higher 90-day mortality rate compared with younger patients (7.7% vs. 0.7%, respectively; HR 9.2, 95% CI: 4.3-19.9; P < .001).

Conclusion: Older patients with an AF ORIF are at a significantly higher risk for a secondary THA than younger patients with an AF ORIF.
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http://dx.doi.org/10.1016/j.arth.2021.04.025DOI Listing
April 2021

Inequities in access to primary care among opioid recipients in Ontario, Canada: A population-based cohort study.

PLoS Med 2021 Jun 1;18(6):e1003631. Epub 2021 Jun 1.

Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada.

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.
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http://dx.doi.org/10.1371/journal.pmed.1003631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168863PMC
June 2021

Trends in Postpartum Opioid Prescribing: A Time Series Analysis.

Clin Pharmacol Ther 2021 May 25. Epub 2021 May 25.

Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Opioids are commonly prescribed following childbirth, but data are lacking on trends in postpartum opioid prescribing over time. We examined whether a highly publicized 2006 case report questioning the safety of codeine during lactation was associated with changes in postpartum opioid prescribing. We conducted a cross-sectional time series analysis of all publicly funded prescriptions for opioids to postpartum women in Ontario, Canada, from April 1, 2000, to March 31, 2017. The intervention was the publication of a case report in 2006 attributing the death of a breastfeeding neonate to maternal codeine use. The primary outcome was the rate of opioid prescribing to postpartum women. Among postpartum women eligible for prescription drug coverage, 17.5% filled an opioid prescription in the third quarter of 2006 (immediately prior to the intervention), with codeine representing 89.8% of all prescriptions. By the fourth quarter of 2010, only 12.2% of postpartum women filled an opioid prescription, representing a decline of 30% (P < 0.01), with codeine representing 71.9% of all prescriptions. During this period, we observed sizeable relative increases in the proportion of opioid prescriptions filled for morphine, hydromorphone, and oxycodone. By 2017, among women prescribed opioids post partum, 39.0% filled a prescription for codeine, while the remainder filled prescriptions for oxycodone (18.6%), morphine (25.5%), and hydromorphone (16.9%). A highly publicized case report questioning the safety of maternal codeine use during breastfeeding was associated with significant changes in opioid prescribing to postpartum women, including a decline in overall opioid prescribing and a shift from codeine to stronger opioids.
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http://dx.doi.org/10.1002/cpt.2307DOI Listing
May 2021

Using zooplankton metabarcoding to assess the efficacy of different techniques to clean-up an oil-spill in a boreal lake.

Aquat Toxicol 2021 Jul 1;236:105847. Epub 2021 May 1.

International Institute for Sustainable Development - Experimental Lakes Area, Kenora, ON, Canada.

Regulators require adequate information to select best practices with less ecosystem impacts for remediation of freshwater ecosystems after oil spills. Zooplankton are valuable indicators of aquatic ecosystem health as they play pivotal roles in biochemical cycles while stabilizing food webs. Compared with morphological identification, metabarcoding holds promise for cost-effective, high-throughput, and benchmarkable biomonitoring of zooplankton communities. The objective of this study was to apply DNA and RNA metabarcoding of zooplankton for ecotoxicological assessment and compare it with traditional morphological identification in experimental shoreline enclosures in a boreal lake. These identification methods were also applied in context of assessing response of the zooplankton community exposed to simulated spills of diluted bitumen (dilbit), with experimental remediation practices (enhanced monitored natural recovery and shoreline cleaner application). Metabarcoding detected boreal zooplankton taxa up to the genus level, with a total of 24 shared genera, and while metabarcoding-based relative abundance served as an acceptable proxy for biomass inferred by morphological identification (ρ ≥ 0.52). Morphological identification determined zooplankton community composition changes due to treatments at 11 days post-spill (PERMANOVA, p = 0.0143) while metabarcoding methods indicated changes in zooplankton richness and communities at 38 days post-spill (T-test, p < 0.05; PERMANOVA, p ≤ 0.0429). Shoreline cleaner application overall seemed to have the largest impact on zooplankton communities relative to enhanced monitored natural recovery, regardless of zooplankton identification method. Both metabarcoding and morphological identification were able to discern the differences between the two experimental remediation practices. Metabarcoding of zooplankton could provide informative results for ecotoxicological assessment of the remediation practices of dilbit, advancing our knowledge of best practices for remediating oil-impacted aquatic ecosystems while serving to accelerate the assessment of at-risk freshwater ecosystems.
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http://dx.doi.org/10.1016/j.aquatox.2021.105847DOI Listing
July 2021

Off-label postpartum use of domperidone in Canada: a multidatabase cohort study.

CMAJ Open 2021 Apr-Jun;9(2):E500-E509. Epub 2021 May 14.

Centre for Clinical Epidemiology (Moriello, Reynier, Aibibula, Filion), Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Que; ICES (Paterson); Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Manitoba Centre for Health Policy, Department of Community Health Sciences (Dahl, Kuo), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Department of Anesthesiology, Pharmacology and Therapeutics (Fisher), University of British Columbia, Vancouver BC; School of Pharmacy (Gamble), University of Waterloo, Kitchener, Ont.; Department of Community Health Sciences (Ronksley), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Saskatchewan Health Quality Council (Winquist); Department of Community Health and Epidemiology (Winquist), College of Medicine, University of Saskatchewan, Saskatoon Sask.; Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health (Filion), McGill University, Montréal, Que.

Background: Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients.

Methods: We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death.

Results: We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41).

Interpretation: Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865.
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http://dx.doi.org/10.9778/cmajo.20200084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157989PMC
May 2021

Prevalence of winter migration to warmer destinations among Ontarians ("snowbirds") and patterns of their use of health care services: a population-based analysis.

CMAJ Open 2021 Apr-Jun;9(2):E491-E499. Epub 2021 May 14.

ICES Western (Shariff, Dixon, Garg, Clemens); Arthur Labatt Family School of Nursing (Shariff), Western University; Lawson Health Research Institute (Shariff, Garg, Clemens), London, Ont.; ICES Central (Paterson), Toronto, Ont.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Department of Epidemiology and Biostatistics (Dixon, Garg), Western University, London, Ont.; Department of Mathematics and Statistics (Dixon), University of Guelph, Guelph, Ont.; Department of Medicine (Garg, Clemens), Western University; St. Joseph's Health Care London (Clemens), London, Ont.

Background: Older Canadians frequently migrate to warmer destinations for the winter season (snowbirds). Our aim was to examine the prevalence of migration to warmer destinations among Ontarians, and to compare the characteristics and use of health care services of snowbirds to those of older Ontarians who did not migrate for the winter.

Methods: We conducted a population-based analysis using health administrative databases from Ontario. We compiled 10 seasonal cohorts (2009/10 to 2018/19) of adults aged 65 or more who filled a travel supply of medications under the Ontario Drug Benefits program (snowbirds) between September and January (snowbird season). We calculated the seasonal prevalence of snowbirds per 100 Ontarians aged 65 or more. We matched each snowbird in the 2018/19 season to 2 nonsnowbirds on age and sex, and compared their characteristics and patterns of use of government-funded health care services.

Results: Over the 10-year period, 53 431 to 70 863 Ontarians aged 65 or more were identified as snowbirds (seasonal prevalence 2.6%-3.3%). Compared to nonsnowbirds, snowbirds were more likely to be recent migrants, live in higher-income neighbourhoods, have fewer comorbidities and make more visits to primary care physicians. From January to March 2019, snowbirds accessed government-funded health care services for a median of 0 days (interquartile range [IQR] 0-1 d), compared to 4 days (IQR 2-8 d) among nonsnowbirds.

Interpretation: About 3% of older Ontarians migrate to warmer destinations for the winter each season. Since few access health care services in Ontario from January to March, researchers are encouraged to consider the snowbird population and the impact of their absence on evaluations that assume continuous observation.
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http://dx.doi.org/10.9778/cmajo.20200270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157986PMC
May 2021

Health care costs of rheumatoid arthritis: A longitudinal population study.

PLoS One 2021 6;16(5):e0251334. Epub 2021 May 6.

University of Toronto, Toronto, Ontario, Canada.

Quantifying the contribution of rheumatoid arthritis to the acquisition of subsequent health care costs is an emerging focus of the rheumatologic community and payers of health care. Our objective was to determine the healthcare costs before and after diagnosis of rheumatoid arthritis (RA) from the public payer's perspective. The study design was a longitudinal observational administrative data-based cohort with RA cases from Ontario Canada (n = 104,933) and two control groups, matched 1:1 on year of cohort entry from 2001 to 2016. The first control group was matched on age, sex and calendar year of cohort entry (diagnosis year for those with RA); the second group added medical history to the match before RA diagnosis year. The main exposure was new onset RA. The secondary exposure was calendar year of RA diagnosis to compare attributable costs over the study observation window. Main outcomes were health care costs in 2015 Canadian dollars, overall and by cost category. We used attribution methods to classify costs into those associated with RA, those associated with comorbidities, and age/sex-related underlying costs. Health care costs associated with RA increased up to the year of diagnosis, where they reached $8,591: $4,142 in RA associated costs; $1,242 in RA comorbidity associated costs; and $3,207 in underlying costs. In the eighth-year post diagnosis, the RA costs declined to $2,567 while the RA comorbidity associated costs remained relatively constant at $1,142, and the underlying age/sex related cost increased to $4,426. RA patients had lower costs when diagnosed in later calendar years. Our results suggest a large proportion of disease related health care costs are a result of costs associated with RA comorbidities, which may appear many years before diagnosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251334PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101709PMC
May 2021

Association Between Bariatric Surgery and Major Adverse Diabetes Outcomes in Patients With Diabetes and Obesity.

JAMA Netw Open 2021 Apr 1;4(4):e216820. Epub 2021 Apr 1.

Division of General Surgery, McMaster University, Hamilton, Canada.

Importance: There are high-quality randomized clinical trial data demonstrating the effect of bariatric surgery on type 2 diabetes remission, but these studies are not powered to study mortality in this patient group. Large observational studies are warranted to study the association of bariatric surgery with mortality in patients with type 2 diabetes.

Objective: To determine the association between bariatric surgery and all-cause mortality among patients with type 2 diabetes and severe obesity.

Design, Setting, And Participants: This retrospective, population-based matched cohort study included patients with type 2 diabetes and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) 35 or greater who underwent bariatric surgery from January 2010 to December 2016 in Ontario, Canada. Multiple linked administrative databases were used to define confounders, including age, baseline BMI, sex, comorbidities, duration of diabetes diagnosis, health care utilization, socioeconomic status, smoking status, substance abuse, cancer screening, and psychiatric history. Potential controls were identified from a primary care electronic medical record database. Data were analyzed in 2020.

Exposure: Bariatric surgery (gastric bypass and sleeve gastrectomy) and nonsurgical management of obesity provided by the primary care physician.

Main Outcomes And Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality and nonfatal morbidities. Groups were compared through a multivariable Cox proportional Hazards model.

Results: A total of 6910 patients (mean [SD] age at baseline, 52.04 [9.45] years; 4950 [71.6%] women) were included, with 3455 patients who underwent bariatric surgery and 3455 match controls and a median (interquartile range) follow-up time of 4.6 (3.22-6.35) years. In the surgery group, 83 patients (2.4%) died, compared with 178 individuals (5.2%) in the control group (hazard ratio [HR] 0.53 [95% CI, 0.41-0.69]; P < .001). Bariatric surgery was associated with a 68% lower cardiovascular mortality (HR, 0.32 [95% CI, 0.15-0.66]; P = .002) and a 34% lower rate of composite cardiac events (HR, 0.68 [95% CI, 0.55-0.85]; P < .001). Risk of nonfatal renal events was also 42% lower in the surgical group compared with the control group (HR, 0.58 [95% CI, 0.35-0.95], P = .03). Of the groups that had the highest absolute benefit associated with bariatric surgery, men had an absolute risk reduction (ARR) of 3.7% (95% CI, 1.7%-5.7%), individuals with more than 15 years of diabetes had an ARR of 4.3% (95% CI, 0.8%-7.8%), and individuals aged 55 years or older had an ARR of 4.7% (95% CI, 3.0%-6.4%).

Conclusions And Relevance: These findings suggest that bariatric surgery was associated with reduced all-cause mortality and diabetes-specific cardiac and renal outcomes in patients with type 2 diabetes and severe obesity.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.6820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076963PMC
April 2021

Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort.

JAMA Netw Open 2021 Apr 1;4(4):e215329. Epub 2021 Apr 1.

ICES, Toronto, Ontario, Canada.

Importance: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes.

Objective: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations.

Design, Setting, And Participants: This is a cohort study conducted in 3 countries, with a meta-analysis. Participants included women and girls aged 12 to 55 years who experienced spontaneous abortion, induced abortion, stillbirth, or live birth between April 2002 and March 2016, as recorded in administrative data from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario), the US IBM MarketScan Research Databases, and the UK Clinical Practice Research Datalink. The statistical analysis was completed in October 2020.

Exposures: Exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication.

Main Outcomes And Measures: The primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. Secondary outcomes were the 2 components of the primary outcome and major congenital malformations identified during the year after a live birth. Adjusted hazard ratios were estimated using Cox proportional hazards models with time-dependent drug exposures and were adjusted using high-dimensional propensity scores. For major congenital malformations, adjusted odds ratios were estimated from logistic models. Site-level results were pooled using random-effects meta-analysis. Sensitivity analyses considered second-line antiemetic exposure and exposure specifically during 4 to 10 weeks of gestation.

Results: Data from 456 963 pregnancies were included in this study of fetal death (249 787 [54.7%] in Canada, 197 913 [43.3%] in the US, and 9263 [2.0%] in the UK; maternal age, ≤24 years, 93 201 patients [20.4%]; 25-29 years, 149 117 patients [32.6%]; 30-34 years, 142 442 patients [31.2%]; and ≥35 years, 72 203 patients [15.8%]). Fetal death occurred in 12 907 (7.9%) of 163 810 pregnancies exposed to ondansetron, and 17 476 (5.7%) of 306 766 pregnancies exposed to other antiemetics. The adjusted hazard ratios were 0.91 (95% CI, 0.67-1.23) for fetal death with time-dependent ondansetron exposure during pregnancy, 0.82 (95% CI, 0.64-1.04) for spontaneous abortion, and 0.97 (95% CI, 0.79-1.20) for stillbirth. For major congenital malformations, the estimated odds ratio was 1.06 (95% CI, 0.91-1.22). Results of sensitivity analyses were generally consistent with those of the primary analyses.

Conclusions And Relevance: In this large, multicenter cohort study, there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.5329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065380PMC
April 2021

Adverse event rates associated with oral anticoagulant treatment early versus later after hospital discharge in older adults: a retrospective population-based cohort study.

CMAJ Open 2021 Apr-Jun;9(2):E364-E375. Epub 2021 Apr 16.

Division of Clinical Pharmacology & Toxicology (Holbrook), Department of Medicine and Department of Health Research Methods, Evidence, and Impact (Holbrook, Benipal, Greaves), McMaster University, Hamilton, Ont.; ICES (Paterson, Gomes); Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Schulich School of Medicine and Dentistry (Lee), Western University, London, Ont.; Li Ka Shing Knowledge Institute (Martins, Gomes), St. Michael's Hospital, Toronto, Ont.

Background: Oral anticoagulants are commonly used high-risk medications, but little is known about their safety in transition from hospital to home. Our objective was to measure the rates of hemorrhage and thromboembolic events among older adults receiving oral anticoagulant treatment early after hospital discharge compared to later.

Methods: We conducted a retrospective population-based cohort study among Ontario residents aged 66 years or more who started, continued or resumed oral anticoagulant therapy at hospital discharge between September 2010 and March 2015. We calculated the rates of hemorrhage and thromboembolic events requiring hospital admission or an emergency department visit over a 1-year follow-up period, stratified by the first 30 days after discharge and the remainder of the year. We used multivariable regression models, adjusting for covariates, to estimate the effect of sex, prevalent versus incident use, and switching anticoagulants on events.

Results: A total of 123 139 patients (68 408 women [55.6%]; mean age 78.2 yr) were included. About one-quarter (32 563 [26.4%]) had a Charlson Comorbidity Index score of 2 or higher. The rates of hemorrhage and thromboembolic events per 100 person-years were highest during the first 30 days after hospital discharge (25.8, 95% CI 24.8-26.8 and 19.3, 95% CI 18.4-20.2, respectively), falling to 15.7 (95% CI 15.3-16.1) and 6.9 (95% CI 6.6-7.1), respectively, during the subsequent 11 months. Multivariable analysis showed that patients whose anticoagulant was switched in hospital and men had more hemorrhages and thromboembolic events in follow-up.

Interpretation: The first few weeks following hospital discharge represent a very high-risk period for adverse events related to oral anticoagulant treatment among older adults. The results support an intervention trial addressing anticoagulation management in the early postdischarge period.
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http://dx.doi.org/10.9778/cmajo.20200138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084547PMC
April 2021

Bariatric Surgery and Cardiovascular Outcomes in Patients With Obesity and Cardiovascular Disease:: A Population-Based Retrospective Cohort Study.

Circulation 2021 Apr 5;143(15):1468-1480. Epub 2021 Apr 5.

Division of General Surgery (A.G.D., Y.L., D.H., M.A.), McMaster University, Hamilton, Ontario, Canada.

Background: Bariatric surgery has been shown to significantly reduce cardiovascular risk factors. However, whether surgery can reduce major adverse cardiovascular events (MACE), especially in patients with established cardiovascular disease, remains poorly understood. The present study aims to determine the association between bariatric surgery and MACE among patients with cardiovascular disease and severe obesity.

Methods: This was a propensity score-matched cohort study using province-wide multiple-linked administrative databases in Ontario, Canada. Patients with previous ischemic heart disease or heart failure who received bariatric surgery were matched on age, sex, heart failure history, and a propensity score to similar controls from a primary care medical record database in a 1:1 ratio. The primary outcome was the incidence of extended MACE (first occurrence of all-cause mortality, myocardial infarction, coronary revascularization, cerebrovascular events, and heart failure hospitalization). Secondary outcome included 3-component MACE (myocardial infarction, ischemic stroke, and all-cause mortality). Outcomes were evaluated through a combination of matching via propensity score and subsequent multivariable adjustment.

Results: A total of 2638 patients (n=1319 in each group) were included, with a median follow-up time of 4.6 years. The primary outcome occurred in 11.5% (151/1319) of the surgery group and 19.6% (259/1319) of the controls (adjusted hazard ratio [HR], 0.58 [95% CI, 0.48-0.71]; <0.001). The association was notable for those with heart failure (HR, 0.44 [95% CI, 0.31-0.62]; <0.001; absolute risk difference, 19.3% [95% CI, 12.0%-26.7%]) and in those with ischemic heart disease (HR, 0.60 [95% CI, 0.48-0.74]; <0.001; absolute risk difference, 7.5% [95% CI, 4.7%-10.5%]). Surgery was also associated with a lower incidence of the secondary outcome (HR, 0.66 [95% CI, 0.52-0.84]; =0.001) and cardiovascular mortality (HR, 0.35 [95% CI, 0.15-0.80]; =0.001).

Conclusions: Bariatric surgery was associated with a lower incidence of MACE in patients with cardiovascular disease and obesity. These findings require confirmation by a large-scale randomized trial.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052386DOI Listing
April 2021

Basketball vs. Hockey-The Changing Face of Sport-Related Injuries in Canada.

Clin J Sport Med 2021 Mar 24. Epub 2021 Mar 24.

Department of Orthopedic Surgery, McMaster University, Hamilton, ON, Canada; University of Toronto, Faculty of MedicineToronto, ON, Canada; Sunnybrook Health Sciences Centre & Sunnybrook Research Institute, Toronto, ON, Canada; and Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Objective: To characterize and compare the incidence of basketball-related, soccer-related, and hockey-related injuries over a 10-year period.

Design: Cohort analysis of sport-related injuries using multiple Ontario healthcare databases.

Setting: Emergency department visits in Ontario, Canada.

Patients: Any patient who sustained musculoskeletal injuries sustained while playing basketball, soccer, or hockey between 2006 and 2017 were identified.

Assessment Of Risk Factors: Sport of injury, age, sex, rurality index, marginalization status, and comorbidity score.

Main Outcome Measures: Annual Incidence Density Rates of injury were calculated for each sport, and significance of trends was analyzed by assessing overlap of 95% confidence intervals.

Results: One lakhs eighty five thousand eighty hundred sixty-eight patients (median age: 16 years, interquartile range 13-26) received treatment for sport-related injuries (basketball = 55 468; soccer = 67 021; and hockey = 63 379). The incidence of basketball-related and soccer-related injuries increased from 3.4 (3.3-3.5) to 5.6 (5.5-5.7) and 4.4 (4.3-4.5) to 4.9 (4.8-5) per 10 000 person years, respectively, whereas the incidence of hockey-related injuries decreased from 4.7 (4.6-4.8) to 3.7 (3.6-3.8). Patients with basketball injuries were more marginalized (3.01 ± 0.74) compared with patients with soccer and hockey injuries (2.90 ± 0.75 and 2.72 ± 0.69, respectively).

Conclusions: Accurate regional epidemiologic information regarding sports injuries can be used to guide policy development for municipal planning and sport program development. The trends and demographic patterns described highlight general and sport-specific injury patterns in Ontario. Populations with the highest incidence of injury, most notably adolescents and men older than 50, may represent an appropriate population for injury risk prevention.
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http://dx.doi.org/10.1097/JSM.0000000000000908DOI Listing
March 2021

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

Am J Prev Med 2021 06 17;60(6):831-839. Epub 2021 Mar 17.

ICES, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Unity Health Toronto, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Introduction: Dentists are a common source of opioid exposure. This study investigates the association between initial dental opioid prescription characteristics and subsequent persistent use and examines the rate of opioid overdose after initiation.

Methods: A retrospective cohort study was conducted among Ontario residents who were dispensed an initial opioid prescription originating from a dentist between October 2014 and September 2018 (data were analyzed in October 2019-May 2020). Exposures were characterized on the basis of the average daily dose in milligram morphine equivalents and the duration and formulation (long versus short acting) of the initial prescription. New, persistent use was defined as ≥1 opioid prescription within 90 days and another within 91-365 days after the initial prescription. The rate of an opioid overdose within 90 days after initiation was examined.

Results: Among 786,125 Ontarians who initiated a dentist-prescribed opioid, 34,880 (4.4%) developed persistent use, whereas 140 (0.72 per 1,000 person-years) had evidence of an overdose within 90 days. People dispensed an initial daily dose >90 milligram morphine equivalents (n=5,644, 0.7%) had significantly greater odds of persistence (AOR=1.20, 95% CI=1.07, 1.34) than those dispensed ≤20 milligram morphine equivalents (n=179,884, 22.9%). Persistence was also significantly associated with receiving longer prescription durations and a long-acting opioid on initiation.

Conclusions: Among people who initiated a dentist-prescribed opioid, 1 in 23 experienced persistent use, and persistence was associated with the characteristics of the prescription. Prescribing lower doses, prescribing for shorter durations, and avoiding long-acting formulations may be an opportunity to lessen the risk of persistent opioid use.
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http://dx.doi.org/10.1016/j.amepre.2021.01.016DOI Listing
June 2021

Evaluation of Rheumatology Workforce Supply Changes in Ontario, Canada, from 2000 to 2030.

Healthc Policy 2021 Feb;16(3):119-134

Rheumatologist, Southlake Regional Health Centre, Newmarket, ON; Assistant Professor of Medicine, University of Toronto, Toronto, ON.

Rheumatology workforces are increasingly challenged by too few physicians in face of the growing burden of rheumatic and musculoskeletal diseases (RMDs). Rheumatology is one of the most frequent non-surgical specialty referrals and has the longest wait times for subspecialists. We used a population-based approach to describe changes in the rheumatology workforce, patient volumes and geographic variation in the supply of and access to rheumatologists, in Ontario, Canada, between 2000 and 2019, and projected changes in supply by 2030. Over time, we observed greater feminization of the workforce and increasing age of workforce members. We identified a large regional variation in rheumatology supply. Fewer new patients are seen annually, which likely contributes to increasing wait times and reduced access to care. Strategies and policies to raise the critical mass and improve regional distribution of supply to effectively provide rheumatology care and support the healthcare delivery of patients with RMDs are needed.
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http://dx.doi.org/10.12927/hcpol.2021.26428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957360PMC
February 2021

Rates of rebleeding, thrombosis and mortality associated with resumption of anticoagulant therapy after anticoagulant-related bleeding.

CMAJ 2021 Mar;193(9):E304-E309

Department of Medicine (Little, Douketis, Holbrook) and ICES McMaster (Cerasuolo, Perez), Faculty of Health Sciences, McMaster University, Hamilton, Ont.; ICES Central (Sutradhar, Paterson), Toronto, Ont.; Department of Medicine (Little); Division of Biostatistics (Sutradhar), Dalla Lana School of Public Health; Institute of Health Policy, Management and Evaluation (Paterson); Leslie Dan Faculty of Pharmacy (Gomes), University of Toronto; Unity Health Toronto (Gomes), Toronto, Ont.; Department of Medicine (Siegal), University of Ottawa, Ottawa, Ont.

Background: Data on resuming oral anticoagulants (OACs) after bleeding are primarily from studies involving patients given warfarin, with few data on direct OACs (DOACs). We aimed to characterize prescribing patterns for OACs after OAC-related bleeding and compare the rates of bleeding, thrombosis and mortality in patients who resumed either type of OAC with those who did not.

Methods: We conducted a population-based cohort study of adults aged 66 years or older who were admitted to hospital for bleeding while receiving OACs from Apr. 1, 2012, to Mar. 31, 2017, using linked administrative health databases from Ontario. We used competing risk methods to calculate cause-specific adjusted hazard ratios (HRs) for thrombosis, bleeding and mortality with resumption of OACs adjusted as a time-varying covariate. We determined time to OAC resumption using the Kaplan-Meier method.

Results: We included 6793 patients with gastrointestinal ( = 4297, 63.3%), intracranial ( = 805, 11.9%) or other bleeding ( = 1691, 25.0%). At cohort entry, 3874 patients (57.0%) were prescribed warfarin and 2919 patients (43.0%) were prescribed a DOAC. The most common indication for OAC was atrial fibrillation ( = 5557, 81.8%), followed by venous thromboembolism ( = 1367, 20.1%). Oral anticoagulants were resumed in 4792 patients (70.5%) within 365 days of the index bleed. The median time to resumption was 46 (interquartile range 6-550) days. We found that resuming OAC was associated with reduced rates of thrombosis (adjusted HR 0.60, 95% confidence interval [CI] 0.50-0.72) and mortality (adjusted HR 0.54, 95% CI 0.48-0.60), and an increased rate of rebleeding (adjusted HR 1.88, 95% CI 1.64-2.17).

Interpretation: We found that resuming OAC is associated with a reduction in thrombosis and mortality but an increase in bleeding. Randomized controlled trials that evaluate the net benefit of strategies for resumption of OAC after a bleeding event are warranted.
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http://dx.doi.org/10.1503/cmaj.201433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034308PMC
March 2021

The Subgingival Plaque Microbiome, Systemic Antibodies Against Bacteria and Citrullinated Proteins Following Periodontal Therapy.

Pathogens 2021 Feb 10;10(2). Epub 2021 Feb 10.

Oral Sciences, College of Medical, Veterinary and Life Sciences, Dental School, University of Glasgow, Glasgow G12 8QQ, UK.

Periodontitis (PD) shows an association with rheumatoid arthritis (RA) and systemic inflammation. Periodontal pathogens, namely and , are proposed to be capable of inducing citrullination of peptides in the gingiva, inducing the formation of anti-citrullinated protein antibodies (ACPAs) within susceptible hosts. Here, we sought to investigate whether periodontal treatment influenced systemic inflammation and antibody titres to , , and ACPA in 42 systemically health patients with periodontal disease. Subgingival plaque and serum samples were collected from study participants before (baseline) and 90 days after treatment to analyse the abundance of specific bacteria and evaluate anti-bacterial antibodies, C-reactive protein (CRP), tumour necrosis factor α (TNF-α), interleukin 6 (IL-6) and ACPA in serum. Following treatment, all patients showed reduced periodontal inflammation. Despite observing a weak positive correlation between CRP and IL-6 with periodontal inflammation at baseline, we observed no significant reductions in any indicators of systemic inflammation 90 days after treatment. In contrast, anti- IgG significantly reduced post-treatment ( < 0.001, Wilcoxon signed rank test), although no changes were observed for other antibody titres. Patients who had detectable in subgingival plaques had significantly higher anti- IgG and ACPA titres, suggesting a potential association between colonisation and systemic antibody titres.
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http://dx.doi.org/10.3390/pathogens10020193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916579PMC
February 2021

Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study.

J Neuromuscul Dis 2021 Feb 4. Epub 2021 Feb 4.

Department of Medicine, Division of Neurology, The Ottawa Hospital, and Ottawa Hospital Research Institute, Ottawa, Canada.

Background: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy.

Objective: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients.

Methods: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression.

Results: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63-0.88).

Conclusions: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.
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http://dx.doi.org/10.3233/JND-200612DOI Listing
February 2021

Impact of preoperative echocardiography on surgical delays and outcomes among adults with hip fracture.

Bone Joint J 2021 Feb;103-B(2):271-278

Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Canada.

Aims: Echocardiography is commonly used in hip fracture patients to evaluate perioperative cardiac risk. However, echocardiography that delays surgical repair may be harmful. The objective of this study was to compare surgical wait times, mortality, length of stay (LOS), and healthcare costs for similar hip fracture patients evaluated with and without preoperative echocardiograms.

Methods: A population-based, matched cohort study of all hip fracture patients (aged over 45 years) in Ontario, Canada between 2009 and 2014 was conducted. The primary exposure was preoperative echocardiography (occurring between hospital admission and surgery). Mortality rates, surgical wait times, postoperative LOS, and medical costs (expressed as 2013$ CAN) up to one year postoperatively were assessed after propensity-score matching.

Results: A total of 2,354 of 42,230 (5.6%) eligible hip fracture patients received a preoperative echocardiogram during the study period. Echocardiography ordering practices varied among hospitals, ranging from 0% to 23.0% of hip fracture patients at different hospital sites. After successfully matching 2,298 (97.6%) patients, echocardiography was associated with significantly increased risks of mortality at 90 days (20.1% vs 16.8%; p = 0.004) and one year (32.9% vs 27.8%; p < 0.001), but not at 30 days (11.4% vs 9.8%; p = 0.084). Patients with echocardiography also had a mean increased delay from presentation to surgery (68.80 hours (SD 44.23) vs 39.69 hours (SD 27.09); p < 0.001), total LOS (19.49 days (SD 25.39) vs 15.94 days (SD 22.48); p < 0.001), and total healthcare costs at one year ($51,714.69 (SD 54,675.28) vs $41,861.47 (SD 50,854.12); p < 0.001).

Conclusion: Preoperative echocardiography for hip fracture patients is associated with increased postoperative mortality at 90 days and one year but not at 30 days. Preoperative echocardiography is also associated with increased surgical delay, postoperative LOS, and total healthcare costs at one year. Echocardiography should be considered an urgent test when ordered to prevent additional surgical delay. Cite this article: 2021;103-B(2):271-278.
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http://dx.doi.org/10.1302/0301-620X.103B2.BJJ-2020-1011.R1DOI Listing
February 2021

Medication use and its impact on high-cost health care users among older adults: protocol for the population-based matched cohort HiCOSTT study.

CMAJ Open 2021 Jan-Mar;9(1):E44-E52. Epub 2021 Jan 11.

Division of Geriatric Medicine (Lee), Department of Medicine, and Department of Health Research Methods, Evidence, and Impact (Lee, Muratov, Tarride, Mbuagbaw, Seow, Thabane, Holbrook), and Centre for Health Economics and Policy Analysis (CHEPA) (Tarride), McMaster University, Hamilton, Ont.; ICES (Paterson, Gomes, Khuu, Seow, Thavorn); Institute of Health Policy, Management and Evaluation (Paterson, Thavorn), University of Toronto, Toronto, Ont.; Ottawa Hospital Research Institute (Thavorn), The Ottawa Hospital, Ottawa, Ont.; Li Ka Shing Knowledge Institute (Gomes), St. Michael's Hospital, Toronto, Ont.; Department of Oncology (Seow), Faculty of Health Sciences, and Division of Clinical Pharmacology and Toxicology (Holbrook), Department of Medicine, McMaster University, Hamilton, Ont.

Background: Health interventions and policies for high-cost health care users (HCUs) who are older adults need to be informed by a better understanding of their multimorbidity and medication use. This study aims to determine the financial contribution of medications to HCU expenditures and explore whether potentially inappropriate prescribing is associated with incident HCU development.

Methods: This is a protocol for a retrospective population-based matched cohort analysis of incident older adult HCUs (those with the highest 5% of costs and 66 years of age or older) in Ontario during fiscal year 2013. We will obtain person-level data for the index year and year before HCU status from health administrative databases and match each HCU to 3 non-HCUs based on age, sex and geographic location. Average annual medication costs (per patient) and the ratio of medication to total health care costs (at population level) will be examined over the HCU transition period and compared with non-HCUs. We will explore potential quality improvement areas for prescribing by analyzing chronic conditions and the use of medications with a strong evidence base for either clinical benefit or risk of harms outweighing benefits in older adults with these diagnoses. The relation between these medication classes and incident HCU status will be explored using logistic regression.

Interpretation: Using a matched cohort design and focusing on incident rather than prevalent HCUs, this protocol will explore our hypotheses that medications and the quality of their prescribing may be important triggers of HCU status and facilitate the identification of potential preventive clinical interventions or policies. Dissemination of results will occur via publications in peer-reviewed journals, presentations at conferences and academic settings, and knowledge translation activities with relevant health system and patient stakeholder groups.

Study Registration: Clinicaltrials.gov, no. NCT02815930.
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http://dx.doi.org/10.9778/cmajo.20190196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843076PMC
July 2021

Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study.

CMAJ Open 2020 Oct-Dec;8(4):E877-E886. Epub 2020 Dec 18.

Internal Medicine Service (Durand), Centre hospitalier de l'Université de Montréal (CHUM) and CHUM Research Centre (Durand); Faculty of Pharmacy (Schnitzer) and Department of Social and Preventive Medicine (Schnitzer), Université de Montréal; Departments of Epidemiology, Biostatistics and Occupational Health (Schnitzer, Pang, Filion, Renoux), Medicine (Filion) and Neurology and Neurosurgery (Renoux), McGill University, Montréal, Que.; Departments of Anesthesiology, Pharmacology and Therapeutics (Carney, Fisher), Faculty of Medicine, University of British Columbia, Vancouver, BC; College of Pharmacy (Eltonsy, Kuo), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Clinical Epidemiology (Filion, Renoux), Lady Davis Institute, Jewish General Hospital, Montréal, Que.; The George Institute for Global Health (Jun), University of New South Wales, Sydney, Australia; ICES Central (Paterson); Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Health Quality Council (Quail) and Department of Community Health and Epidemiology (Quail), University of Saskatchewan, Saskatoon, Sask.; Cardiology Service (Matteau), CHUM and CHUM Research Centre, Montréal, Que.

Background: Direct oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.

Methods: We conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009-2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses.

Results: We included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85).

Interpretation: In this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation.

Trial Registration: ClinicalTrials.gov, no. NCT03596502.
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http://dx.doi.org/10.9778/cmajo.20200055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759115PMC
May 2021

Initial opioid prescription patterns and the risk of ongoing use and adverse outcomes.

Pharmacoepidemiol Drug Saf 2021 03 18;30(3):379-389. Epub 2020 Dec 18.

ICES, Toronto, Ontario, Canada.

Purpose: As clinical practice moves towards more judicious opioid prescribing, physicians require information on how to safely initiate opioids. The objective of this study was to examine the association between initial opioid prescription characteristics and risks of harm and long-term use.

Methods: We conducted a population-based retrospective cohort study among Ontario residents newly dispensed an opioid for pain between July 2013 and March 2016. The primary exposure was the average daily opioid dose dispensed at initiation (in milligram morphine equivalents; MME), with secondary exposures including the initial prescription's duration and formulation. The primary outcome was fatal or non-fatal opioid overdose. A secondary analysis studied continued opioid use for at least 1 year.

Results: Among the 2 021 371 individuals meeting our inclusion criteria, 1121 (0.56 per 1000 person-years) experienced an opioid overdose within 1 year and 64 013 (3.17%) continued treatment for at least 1 year. Higher initial daily dose, longer prescription duration, and receipt of a long-acting formulation at initiation were significantly associated with higher hazard of overdose. Compared to daily doses of 20 MME or lower, initial doses exceeding 200 MME daily were associated with a particularly high hazard of overdose (aHR 2.97, 95% confidence interval [CI] 1.62 to 5.44). In the secondary analysis, there were similar associations between initial dose, duration, and formulation and long-term use.

Conclusions: Although the absolute risk of an opioid overdose within the first year of prescription opioid use is low, better alignment of opioid initiation practices with guidelines may reduce opioid-related harm.
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http://dx.doi.org/10.1002/pds.5180DOI Listing
March 2021

Feminization of the Rheumatology Workforce: A Longitudinal Evaluation of Patient Volumes, Practice Sizes, and Physician Remuneration.

J Rheumatol 2021 Jul 1;48(7):1090-1097. Epub 2020 Dec 1.

S. Bernatsky, MD, PhD, Department of Epidemiology, McGill University, and Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.

Objective: To compare differences in clinical activity and remuneration between male and female rheumatologists and to evaluate associations between physician gender and practice sizes and patient volume, accounting for rheumatologists' age, and calendar year effects.

Methods: We conducted a population-based study in Ontario, Canada, between 2000 to 2015 identifying all rheumatologists practicing as full-time equivalents (FTEs) or above and assessed differences in practice sizes (number of unique patients), practice volumes (number of patient visits), and remuneration (total fee-for-service billings) between male and female rheumatologists. Multivariable linear regression was used to evaluate the effects of gender on practice size and volume separately, accounting for age and year.

Results: The number of rheumatologists practicing at ≥ 1 FTE increased from 89 to 120 from 2000 to 2015, with the percentage of females increasing from 27.0% to 41.7%. Males had larger practice sizes and practice volumes. Remuneration was consistently higher for males (median difference of CAD $46,000-102,000 annually). Our adjusted analyses estimated that in a given year, males saw a mean of 606 (95% CI 107-1105) more patients than females did, and had 1059 (95% CI 345-1773) more patient visits. Among males and females combined, there was a small but statistically significant reduction in mean annual number of patient visits, and middle-aged rheumatologists had greater practice sizes and volumes than their younger/older counterparts.

Conclusion: On average, female rheumatologists saw fewer patients and had fewer patient visits annually relative to males, resulting in lower earnings. Increasing feminization necessitates workforce planning to ensure that populations' needs are met.
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http://dx.doi.org/10.3899/jrheum.201166DOI Listing
July 2021

Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi-database cohort study with meta-analysis.

Br J Clin Pharmacol 2021 Jun 16;87(6):2589-2601. Epub 2020 Dec 16.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.

Aims: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF).

Methods: We conducted multicentre matched cohort studies with secondary meta-analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across 9 administrative healthcare databases. We included adults with NVAF initiating anticoagulation therapy (dabigatran, rivaroxaban or apixaban), and constructed 3 cohorts to compare DOACs pairwise. The primary outcome was pooled hazard ratio (pHR) of ischaemic stroke or systemic thromboembolism. Secondary outcomes included pHR of major bleeding, and a composite of stroke, major bleeding, or all-cause mortality. We used proportional hazard Cox regressions models, and pooled estimates were obtained with random effect meta-analyses.

Results: The cohorts included 73 414 new users of dabigatran, 92 881 of rivaroxaban, and 61 284 of apixaban. After matching, the pHRs (95% confidence intervals) comparing rivaroxaban initiation to dabigatran were: 1.11 (0.93, 1.32) for ischaemic stroke or systemic thromboembolism, 1.26 (1.09, 1.46) for major bleeding, and 1.17 (1.05, 1.30) for the composite endpoint. For apixaban vs dabigatran, they were: 0.91 (0.74, 1.12) for ischaemic stroke or systemic thromboembolism, 0.89 (0.75, 1.05) for major bleeding, and 0.94 (0.78 to 1.14) for the composite endpoint. For apixaban vs rivaroxaban, they were: 0.85 (0.74, 0.99) for ischaemic stroke or systemic thromboembolism, 0.61 (0.53, 0.70) for major bleeding, and 0.82 (0.76, 0.88) for the composite endpoint.

Conclusion: We found that apixaban use is associated with lower risks of stroke and bleeding compared with rivaroxaban, and similar risks compared with dabigatran.
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http://dx.doi.org/10.1111/bcp.14669DOI Listing
June 2021

Utilisation and outcomes of allogeneic hematopoietic cell transplantation in Ontario, Canada, and New York State, USA: a population-based retrospective cohort study.

BMJ Open 2020 10 31;10(10):e039293. Epub 2020 Oct 31.

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Objective: Allogeneic haematopoietic cell transplantation (HCT) is a potentially curative treatment for haematologic and oncologic diseases. There is a perception that the United States of America (USA) offers greater access to expensive therapies such as HCT. Alternatively, Canada is thought to suffer from protracted wait times, but lower spending. Our objective was to compare HCT utilisation and short-term outcomes in Ontario (ON), Canada, and New York State (NY), USA.

Design, Setting And Participants: We conducted a population-based cohort study using administrative health data to identify all residents of ON and NY who underwent allogeneic HCT between 2012 and 2015.

Primary And Secondary Outcome Measures: The primary outcome measures were age and sex standardised HCT utilisation rates, in-hospital mortality, hospital length of stay (LOS) and readmission rates in ON and NY. Secondary outcomes included comparing ON and NY HCT recipients with respect to demographic characteristics and patient wealth (using neighbourhood income quintile).

Results: We identified 547 HCT procedures in ON and 1361 HCT procedures performed in NY. HCT recipients in ON were younger than NY (mean age 49.0 vs 51.6 years; p<0.001) and a lower percentage of ON recipients resided in affluent neighbourhoods compared with NY (47.2% vs 52.6%; p=0.026). Utilisation of HCT was 14.4 per 1 million population per year in ON and 26.7 per 1 million per year in NY (p<0.001). The magnitude of the ON-NY difference in utilisation was larger for older patients. In-hospital mortality, LOS and readmission rates were lower in ON than NY in both unadjusted and adjusted analyses.

Conclusions: We found significantly lower utilisation of HCT in ON compared with NY, particularly among older patients. Higher in-hospital mortality in NY relative to ON requires further study. These differences are thought provoking for patients, healthcare providers and policy-makers in both jurisdictions.
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http://dx.doi.org/10.1136/bmjopen-2020-039293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783612PMC
October 2020

Comorbidities Before and After the Diagnosis of Rheumatoid Arthritis: A Matched Longitudinal Study.

ACR Open Rheumatol 2020 Nov 26;2(11):648-656. Epub 2020 Oct 26.

University of Toronto and the Toronto General Research Institute, Toronto, Ontario, Canada.

Objective: To determine the contribution of rheumatoid arthritis (RA) to conditions and medical events. A secondary objective is to quantify this association before and after the introduction of biologic medications.

Methods: All data were collected as health administrative data in Ontario, Canada. Patients with RA (n = 136 678) matched 1:1 to a pool of possible controls without RA from 1995 to 2016. The study was a retrospective longitudinal observational administrative data-based cohort study with cases (RA) and controls (two non-RA comparator groups). The main exposure was new-onset RA identified by a validated diagnosis algorithm. The secondary exposure was the calendar year, which provided a natural experiment to compare years in which biologics were unavailable (pre-2001) to increasing utilization over time. The main outcomes were counts of 27 Johns Hopkins Expanded Diagnostic Cluster Comorbid Conditions. Outcomes were reported as counts and percentage differences between cases and matched controls.

Results: Patients experienced increases in conditions and medical events up to 5 years before RA disease incidence-4.9 conditions per patient-year compared with 4.6 conditions per patient-year in matched controls. Comorbidities increased to 8.7 conditions per patient-year in the year of RA incidence but were lower in the years after diagnosis-6.9 conditions per patient-year at 5 years postdiagnosis.

Conclusion: This study reframes the clinical manifestations of RA with detailed data on the marginal contribution of RA to conditions and medical events. These results show that a large portion of disease burden is due to the indirect effects of RA.
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http://dx.doi.org/10.1002/acr2.11182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672304PMC
November 2020

Trends in mortality and cause-specific mortality among patients with psoriasis and psoriatic arthritis in Ontario, Canada.

J Am Acad Dermatol 2021 May 21;84(5):1302-1309. Epub 2020 Oct 21.

Women's College Hospital, Toronto, Canada; University of Toronto, Toronto, Canada. Electronic address:

Background: There is limited information about mortality rates among patients with psoriasis and psoriatic arthritis (PsA) in North America and their change over the past 2 decades.

Objective: To compare all-cause and cause-specific mortality rates in patients with psoriasis to the general population in Ontario, Canada, from 1996 to 2016.

Methods: We conducted a population-based, retrospective cohort study of adult residents using administrative health data. All-cause and cause-specific standardized mortality rates, standardized mortality ratios, and excess mortality rates were calculated.

Results: 176,858 (2,524 deaths) patients with psoriasis and 15,430 (221 deaths) patients with PsA were identified in 2016. Patients with psoriasis and PsA had standardized excess mortality rates of 1.44 and 2.43 per 1000 population, respectively. Standardized mortality rates decreased by approximately 30% over the study period in both disease groups but remained significantly elevated compared to the general population. The leading causes of death in psoriasis and PsA patients were cancer, circulatory disease, and respiratory conditions.

Limitations: We were unable to classify patients according to disease severity.

Conclusions: Despite improvements in psoriasis treatment, the relative excess mortality, which may be related to risk factors for psoriatic disease, remained unchanged, with an average of approximately 1 to 2 extra deaths per 1,000 patients in 2016.
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http://dx.doi.org/10.1016/j.jaad.2020.10.031DOI Listing
May 2021

Predictors of oral anticoagulant-associated adverse events in seniors transitioning from hospital to home: a retrospective cohort study protocol.

BMJ Open 2020 09 22;10(9):e036537. Epub 2020 Sep 22.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Introduction: Oral anticoagulants (OACs) are widely prescribed in older adults. High OAC-related adverse event rates in the early period following hospital discharge argue for an analysis to identify predictors. Our objective is to identify and validate clinical and continuity of care variables among seniors discharged from hospital on an OAC, which are independently associated with OAC-related adverse events within 30 days.

Methods And Analysis: We propose a population-based retrospective cohort study of all adults aged 66 years or older who were discharged from hospital on an OAC from September 2010 to March 2015 in Ontario, Canada. The primary outcome is a composite of the first hospitalisation or emergency department visit for a haemorrhage or thromboembolic event or mortality within 30 days of hospital discharge. A Cox proportional hazards model will be used to determine the association between the composite outcome and a set of prespecified covariates. A split sample method will be adopted to validate the variables associated with OAC-related adverse events.

Ethics And Dissemination: The use of data in this project was authorised under section 45 of Ontario's Personal Health Information Protection Act, which does not require review by a research ethics board. Results will be disseminated via peer-reviewed publications and presentations at conferences and will determine intervention targets to improve OAC management in upcoming randomised trials.

Trial Registration Number: ClinicalTrials.gov Identifier: NCT02777047; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-036537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509956PMC
September 2020

Estimated surge in hospital and intensive care admission because of the coronavirus disease 2019 pandemic in the Greater Toronto Area, Canada: a mathematical modelling study.

CMAJ Open 2020 Jul-Sep;8(3):E593-E604. Epub 2020 Sep 22.

Division of Infectious Diseases, Department of Medicine (Mishra, Coomes, Chan, Muller); MAP Centre for Urban Health Solutions (Mishra, Wang, Ma, Yiu, Landsman), Li Ka Shing Knowledge Institute, St. Michael's Hospital; Institute of Health Policy, Management and Evaluation (Paterson, Schull), University of Toronto; ICES (Paterson, Kim, Schull, Ishiguro); Decision Support (Pequegnat, Lee), Unity Health Toronto; Division of Infectious Diseases (Chan), Sunnybrook Health Sciences, University of Toronto; Infection Prevention and Control (Downing), St. Joseph's Health Centre, Unity Health Toronto; Department of Medicine (Straus), St. Michael's Hospital, University of Toronto; Infection Prevention and Control (Muller), St. Michael's Hospital, Unity Health Toronto, Toronto, Ont.

Background: In pandemics, local hospitals need to anticipate a surge in health care needs. We examined the modelled surge because of the coronavirus disease 2019 (COVID-19) pandemic that was used to inform the early hospital-level response against cases as they transpired.

Methods: To estimate hospital-level surge in March and April 2020, we simulated a range of scenarios of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread in the Greater Toronto Area (GTA), Canada, using the best available data at the time. We applied outputs to hospital-specific data to estimate surge over 6 weeks at 2 hospitals (St. Michael's Hospital and St. Joseph's Health Centre). We examined multiple scenarios, wherein the default (R = 2.4) resembled the early trajectory (to Mar. 25, 2020), and compared the default model projections with observed COVID-19 admissions in each hospital from Mar. 25 to May 6, 2020.

Results: For the hospitals to remain below non-ICU bed capacity, the default pessimistic scenario required a reduction in non-COVID-19 inpatient care by 38% and 28%, respectively, with St. Michael's Hospital requiring 40 new ICU beds and St. Joseph's Health Centre reducing its ICU beds for non-COVID-19 care by 6%. The absolute difference between default-projected and observed census of inpatients with COVID-19 at each hospital was less than 20 from Mar. 25 to Apr. 11; projected and observed cases diverged widely thereafter. Uncertainty in local epidemiological features was more influential than uncertainty in clinical severity.

Interpretation: Scenario-based analyses were reliable in estimating short-term cases, but would require frequent re-analyses. Distribution of the city's surge was expected to vary across hospitals, and community-level strategies were key to mitigating each hospital's surge.
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http://dx.doi.org/10.9778/cmajo.20200093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641231PMC
January 2021