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Objectives: To assess the burden of hospitalizations due to cannabis harms in Ontario, Canada before Canada's legalization of nonmedical cannabis., Methods: We conducted a retrospective population-level study that included all individuals living in Ontario between 2003 and 2017. We described patterns of hospitalizations due to cannabis harms in men and women by demographics, socioeconomic factors, and mental health comorbidities. We calculated annual crude rates of hospitalizations due to cannabis harms and assessed time trends using Poisson regression models., Results: There were 39,092 hospitalizations due to cannabis harms among 32,811 unique individuals. Annual hospitalizations due to a cannabis harm increased by 176% between 2003 and 2017 (1712 vs 4730), with increases noted for all age groups and sexes. Rates of hospitalizations due to cannabis harms were greater in young adults, low-income individuals, and those with mental health comorbidities. Overall, the rate of hospitalizations due to cannabis harms increased on average by 7.8% per year (95% CI 7.5-8.0). Women aged 15 to 24 experienced the largest average annual increase (12.2% per year, 95% CI 11.5 to 12.8)., Conclusions: There are distinct patterns of hospitalizations due to cannabis harms in different priority populations. Young women aged 15 to 24 are a key demographic that is disproportionately burdened with a rapid increase in hospitalizations due to cannabis harms. Jurisdictions considering new approaches to cannabis control policy and addiction services should consider the rising burden of harms faced by youth and young adults when planning interventions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Introduction: The use of contralateral prophylactic mastectomy (CPM) continues to grow despite the absence of evidence supporting a survival benefit. This study's objectives were to (1) describe the trends in the rates of unilateral and bilateral mastectomy (BM) in women diagnosed with unilateral breast cancer (UBC) in Ontario, Canada from 1991 to 2013, and (2) identify factors associated with BM to treat UBC., Methods: This retrospective cohort analysis included all women aged 18 and older diagnosed with UBC between January 1991 and December 2013. Health administrative data from the Institute for Clinical Evaluative Sciences, the Ontario Cancer Registry, and the Discharge Abstract Database were used to identify all breast cancer and mastectomy cases. Age-adjusted mastectomy rates were plotted over time. Univariable and multivariable analyses included clinically significant covariates., Results: From 1991 to 2013 there were 172,165 cases of UBC and 64,886 mastectomies (37.7%) performed in Ontario. 13.6% of the mastectomies were bilateral. BM rates increased over sixfold (from 4 to 25%) across all age groups under age 70 over a 23-year period. On multivariable analysis, younger age, higher income, rural community, earlier breast cancer stage, lobular histology, availability of reconstruction and teaching hospitals were associated with increased odds of BM., Conclusions: This is the largest population study of breast cancer patients in Canada and shows an increasing rate of BM for UBC. The results are similar to those already described in the US and highlight the importance of continued efforts to promote efficient communication and evidence-based decision-making prior to breast surgery.

Background: Adjuvant trastuzumab for early-stage (I-III) HER2-positive breast cancer (BC) has led to statistically significant improvement in cancer outcomes but carries a risk of cardiotoxicity. Trastuzumab is discontinued early in many patients for asymptomatic changes in left ventricular ejection fraction. We evaluated the impact of early discontinuation of trastuzumab on cancer outcomes., Methods: We conducted a retrospective population-based cohort study of early BC patients treated with adjuvant trastuzumab in Ontario, Canada, 2007-2016. Four groups were analyzed: group A was full treatment, 17-18 cycles trastuzumab; group B was cardiac event (CE) within treatment period; group C was ≤16 cycles, no CEs, stopped within 30 days from last cardiac imaging; and group D was ≤16 cycles, no CEs, stopped more than 30 days from cardiac imaging. Primary outcome was disease-free survival (DFS); secondary outcomes were: overall survival, cancer-specific mortality, and cardiovascular mortality. Sensitivity analyses were performed 14 months after cycle 1 trastuzumab to control for early relapse., Results: A total of 5547 patients met the inclusion criteria: group A = 3921, group B = 309, group C = 362, and group D = 955. The 5-year DFS was 94.1% in group A, 80.1% in group B, 81.4% in group C, and 82.4% in group D. Using a Cox model, the hazard ratio for 5-year DFS was 3.15 (95% confidence interval [CI] = 2.13 to 4.65) for group B, 1.94 (95% CI = 1.30 to 2.89) for group C, and 1.92 (95% CI = 1.46 to 2.53) for group D. Overall, 26 patients (0.5%) died of cardiac causes., Conclusions: BC patients in Ontario who did not complete adjuvant trastuzumab had a statistically significantly higher risk of BC relapse and death and low incidence of cardiac death. These findings support 1 year of adjuvant trastuzumab in early-stage BC., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Invasive lobular carcinoma (ILC) is less common that invasive ductal carcinoma (IDC), and more challenging to diagnose by examination and screening mammography. This study evaluated current trends in ILC incidence, and described the 5-, 10-, and 15-year survival probabilities for women diagnosed with ILC in Ontario, Canada., Methods: This retrospective cohort analysis included all women aged 18 years and older diagnosed with breast cancer between 1991 and 2015. Health administrative data from the Institute of Clinical Evaluative Sciences and the Ontario Cancer Registry were used to identify breast cancer cases. Age-adjusted incidence was plotted by year. Crude proportions were plotted by year of diagnosis for stage and hormone receptor status. Kaplan-Meier curves were generated to determine the 5-, 10-, and 15-year survival probabilities for ILC and IDC., Results: From 1991 to 2015, there were 194,065 cases of breast cancer in Ontario, 14.7% of which were ILC. The age-adjusted incidence of breast cancer increased 1.04-fold, while ILC rates increased 1.53-fold. All bilateral breast cancers were of lobular origin. The proportion of stage 1 ILC decreased, while the proportion of stage 2-4 ILC increased. The 5-, 10-, and 15-year overall survival probabilities for women diagnosed with ILC were 82.7%, 65.3%, and 50.2%, respectively., Conclusions: This study contains the largest population dataset of ILC evaluated to date. While total breast cancer incidence rates in Ontario are largely unchanged, ILC incidence rates are steadily increasing and there is a trend towards diagnosis of ILC at a later stage. These trends highlight the ongoing diagnostic and treatment challenge ILC presents for patients and clinicians.

Avoidable mortality (AM) is a health indicator used to examine trends in avoidable deaths amenable to public health and medical interventions. AM is more likely amongst marginalized populations. Our objective was to examine trends in AM rates by level of neighborhood marginalization. Decedents under age 75 years in Ontario from 1993 to 2014 (n = 691,453) were assigned to a quintile-level of each Ontario Marginalization (ON-Marg) Index dimension: material deprivation, residential instability, dependency, and ethnic concentration. We calculated ON-Marg Index dimension and quintile specific age- and sex-standardized AM incidence rates. We then calculated annual AM rate ratios between the most (Q5) and least (Q1) marginalized quintiles for each ON-Marg dimension. To describe the inequity gap in AM over time we calculated the absolute difference in the Q5/Q1 rate ratio between 2014 and 1993 for each dimension. AM rates in Ontario were almost halved (48.6%) from 1993 to 2014 (216 vs. 111 per 100,000 population). This decline was greater for treatable AM (75 vs. 36 per 100,000 population) than preventable AM (128 vs. 88 per 100,000 population). The inequity gap in AM Q5/Q1 rate ratios (RR) between 1993 and 2014 widened for all marginalization dimensions: dependency (RR 2.11-2.58), ethnic concentration (RR 0.59-0.48), material deprivation (RR 1.63-2.23), and residential instability (RR 2.01-2.43). To attain further declines in AM, policymakers and governments must address AM due to preventable deaths in neighborhoods highly marginalized by dependency, material deprivation, and residential instability.

Background: Studies have reported increasing incidence rates of paediatric diabetes, especially among those aged 0-5 years. Epidemiological evidence linking ambient air pollution to paediatric diabetes remains mixed., Objective: This study investigated the association between maternal and early-life exposures to common air pollutants (NO 2 , PM 2.5 , O 3 , and oxidant capacity [Ox; the redox-weighted average of O 3 and NO 2 ]) and the incidence of paediatric diabetes in children up to 6 years of age., Methods: All registered singleton births in Ontario, Ca nada occurring between April 1st , 2006 and March 31st , 2012 were included through linkage from health administrative data. Monthly exposures to NO 2 , PM 2.5 , O 3 , and O x were estimated across trimesters, the entire pregnancy period and during childhood. Random effects Cox proportional hazards models were used to assess the relationships with paediatric diabetes incidence while controlling for important covariates. We also modelled the shape of concentration-response (CR) relationships., Results: There were 1094 children out of a cohort of 754,698 diagnosed with diabetes before the age of six. O 3 exposures during the first trimester of pregnancy were associated with paediatric diabetes incidence (hazard ratio (HR) per interquartile (IQR) increase = 2.00, 95% CI: 1.04-3.86). The CR relationship between O 3 during the first trimester and paediatric diabetes incidence appeared to have a risk threshold, in which there was little-to-no risk below 25 ppb of O 3 , while above this level risk increased sigmoidally. No other associations were observed., Conclusion: O 3 exposures during a critical period of development were associated with an increased risk of paediatric diabetes incidence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the impact of neighbourhood marginalization on avoidable mortality (AM) from preventable and treatable causes of death., Methods: All premature deaths between 1993 and 2014 (N = 691,453) in Ontario, Canada, were assigned to quintiles of neighbourhood marginalization using the four dimensions of the Ontario Marginalization Index: dependency, ethnic concentration, material deprivation, and residential instability. We conducted two multivariate logistic regressions to examine the association between neighbourhood marginalization, first with AM compared with non-AM as the outcome, and second with AM from preventable causes compared with treatable causes as the outcome. All models were adjusted for decedent age, sex, urban/rural location, and level of comorbidity., Results: A total of 463,015 deaths were classified as AM and 228,438 deaths were classified as non-AM. Persons living in the most materially deprived (OR, 1.24; 95% CI, 1.22 to 1.27) and residentially unstable neighbourhoods (OR, 1.13; 95% CI, 1.11 to 1.15) had greater odds of AM, particularly from preventable causes. Those living in the most dependent (OR, 0.91; 95% CI, 0.89 to 0.93) and ethnically concentrated neighbourhoods (OR, 0.93; 95% CI, 0.91 to 0.93) had lower odds of AM, although when AM occurred, it was more likely to arise from treatable causes., Conclusion: Different marginalization dimensions have unique associations with AM. By identifying how different aspects of neighbourhood marginalization influence AM, these results may have important implications for future public health efforts to reduce inequities in avoidable deaths.

Objectives: Biliary atresia (BA) is the most common reason for liver transplant in childhood, and outcomes worsen with older age at hepatoportoenterostomy (HPE). We determined direct health care costs in children with BA, compared to controls in a population-based cohort of children in Ontario, Canada., Methods: We used health administrative data to identify all children diagnosed with BA between 2002 and 2016 (n = 121) and matched controls (n = 602). We determined annual direct healthcare costs, and rates of health services utilization, liver transplantation, death, portal hypertension, cirrhosis, esophageal varices, and major upper gastrointestinal bleeding requiring hospitalization. Multivariable regression models determined the association between age at HPE, risk of liver transplant, and direct costs., Results: Incidence of BA was 6.07 (4.99-7.15) per 100,000 live births. The annual median (interquartile range) direct health care costs were higher in BA cases ($4210; interquartile range $1091-$16,765) compared to controls ($283; $112-$634). Compared to age at HPE <45 days, there was no significant association between direct costs and HPE ≥90 days (rate ratio 1.24, 95% confidence interval [CI] 0.78-1.97) or 45 to 90 days (rate ratio 1.05, 95% CI 0.73-1.50). Age at HPE ≥90 days was significantly associated with risk of undergoing liver transplant compared to age <45 days (hazard ratio 5.27, 95% CI 2.45-11.34). Direct costs were higher in patients with BA who underwent liver transplantation compared to those who did not ($39,476±$84,367 vs $22,579 ± $67,913)., Conclusions: Direct ealth care costs were high in patients with BA, especially in those who underwent liver transplantation. Age at HPE was associated with risk of liver transplantation, but not direct health care costs, utilization, or other risk outcomes.

Background: Self-harm is increasing among adolescents, and because of changing behaviours, current data are needed on the consequences of self-harm. We sought to investigate the trends related to hospital presentation, readmission, patient outcome and medical costs in adolescents who presented with self-harm to the emergency department., Methods: We used administrative data on 403 805 adolescents aged 13-17 years presenting to Ontario emergency departments in 2011-2013. Adolescents with self-harm visits were 1:2 propensity matched to controls with visits without self-harm, using demographic, mental health and other clinical variables. Five years after the index presentation, hospital or emergency department admission rates for self-harm, overall mortality, suicides and conservative cost estimates were compared between the 2 groups., Results: Of 5832 adolescents who visited Ontario emergency departments in 2011-2013 after self-harm (1.4% of visits), 5661 were matched to 10 731 adolescents who presented for reasons other than self-harm. Adolescents who presented with self-harm had a shorter time to a repeat emergency department or hospital admission for self-harm (hazard ratio [HR] 4.84, 95% confidence interval [CI] 4.44-5.27), more suicides (HR 7.96, 95% CI 4.00-15.86), and higher overall mortality (HR 3.23, 95% CI 2.12-4.93; p < 0.001). The positive predictive value of self-harm-related emergency department visits for suicide was 0.7%. Adolescents with self-harm visits had mean 5-year estimates of health care costs of $30 388 compared with $19 055 for controls ( p < 0.001)., Interpretation: Adolescents with emergency department visits for self-harm have higher rates of mortality, suicide and recurrent self-harm, as well as higher health care costs, than matched controls. Development of algorithms and interventions that can identify and help adolescents at highest risk of recurrent self-harm is warranted., Competing Interests: Competing interests: William Gardner reports receiving grants from the Canadian Institutes of Health Research and research contracts from the Public Health Agency of Canada and the US Centers for Disease Control. Dr. Gardner is also the CHEO and University of Ottawa Senior Research Chair in Child and Adolescent Psychiatry. Ian Colman is a Canada Research Chair in mental health epidemiology. Roger Zemek reports receiving competitively funded research grants from the Canadian Institutes of Health Research, Ontario Neurotrauma Foundation, Physician Services Incorporated Foundation, CHEO Foundation, Ontario Brain Institute, the Ontario SPOR Support Unit and the National Football League. Dr. Zemek is also the Clinical Research Chair in Pediatric Concussion at University of Ottawa. No other competing interests were declared., (© 2019 Joule Inc. or its licensors.)

Objective: To document the rates of intentional self-harm and mental disorders among youths aged 13 to 17 years visiting Ontario emergency departments (EDs) from 2003-2017., Methods: This was a repeated cross-sectional observational design. Outcomes were rates of adolescents with (1) at least 1 self-harm ED visit and (2) a visit with a mental disorder code., Results: Rates of youths with self-harm visits fell 32% from 2.6/1000 in 2003 to 1.8 in 2009 but rose 135% to 4.2 by 2017. The slope of the trend in self-harm visits changed from -0.18 youths/1000/year (confidence interval [CI], -0.24 to -0.13) during 2003 to 2009 to 0.31 youths/1000/year (CI, 0.27 to 0.35) during 2009 to 2017 ( P < 0.001). Rates of youths with mental health visits rose from 11.7/1000 in 2003 to 13.5 in 2009 (15%) and to 24.1 (78%) by 2017. The slope of mental health visits changed from 0.22 youths/1000/year (CI, 0.02 to 0.42) during 2003 to 2009 to 1.84 youths/1000/year (CI, 1.38 to 2.30) in 2009 to 2017 ( P < 0.001). Females were more likely to have self-harm ( P < 0.001) and mental health visits ( P < 0.001). Rates of increase after 2009 were greater for females for both self-harm ( P < 0.001) and mental health ( P < 0.001)., Conclusions: Rates of adolescents with self-harm and mental health ED visits have increased since 2009, with greater increases among females. Research is required on the determinants of adolescents' self-harm and mental health ED visits and how they can be addressed in that setting. Sufficient treatment resources must be supplied to address increased demands for services.