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Background: Preventive measures and treatments for psychiatric disorders are limited. Circulating metabolites are potential candidates for biomarker and therapeutic target identification, given their measurability and essential roles in biological processes., Methods: Leveraging large-scale genome-wide association studies, we conducted Mendelian randomization analyses to assess the associations between circulating metabolite abundances and the risks of bipolar disorder, schizophrenia, and depression. Genetic instruments were selected for 94 metabolites measured in the Canadian Longitudinal Study on Aging cohort (N = 8299). We repeated Mendelian randomization analyses based on the UK Biobank, INTERVAL, and EPIC (European Prospective Investigation into Cancer)-Norfolk studies., Results: After validating Mendelian randomization assumptions and colocalization evidence, we found that a 1 SD increase in genetically predicted circulating abundances of eicosapentaenoate and docosapentaenoate was associated with odds ratios of 0.72 (95% CI, 0.65-0.79) and 0.63 (95% CI, 0.55-0.72), respectively, for bipolar disorder. Genetically increased Ω-3 unsaturated fatty acids abundance and Ω-3-to-total fatty acids ratio, as well as genetically decreased Ω-6-to-Ω-3 ratio, were negatively associated with the risk of bipolar disorder in the UK Biobank. Genetically increased circulating abundances of 3 N-acetyl-amino acids were associated with an increased risk of schizophrenia with a maximum odds ratio of 1.31 (95% CI, 1.18-1.44) per 1 SD increase. Furthermore, a 1 SD increase in genetically predicted circulating abundance of hypotaurine was associated with an odds ratio of 0.85 (95% CI, 0.78-0.93) for depression., Conclusions: The biological mechanisms that underlie Ω-3 unsaturated fatty acids, NAT8-catalyzed N-acetyl-amino acids, and hypotaurine warrant exploration to identify new biomarkers and potential therapeutic targets., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Injectable extended-release buprenorphine (BUP-ER) (Sublocade®) is a newer form of opioid agonist therapy (OAT) administered monthly. It was listed on formularies across Canada in February 2020, expanding the options for OAT across the country. This study describes rates of injectable BUP-ER uptake in five provinces to compare access to this novel medication across Canada., Methods: We conducted a retrospective time-series analysis among individuals who received injectable BUP-ER in British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario from February 1, 2020, to March 31, 2022. The primary outcome was the population-adjusted rate of injectable BUP-ER in each province, with secondary analyses exploring rates by urban/rural location, and the number of prescribers of injectable BUP-ER per 100,000 population., Results: In total, 6528 individuals were treated with injectable BUP-ER, with the majority in British Columbia (29.0 %) and Ontario (47.0 %). By March 2022, the rate of BUP-ER use was highest in British Columbia (16.6 per 100,000), and lowest in Ontario (9.1 per 100,000). The rate of BUP-ER use was higher in rural areas (15.5 per 100,000) compared to urban centres (10.6 per 100,000), and British Columbia had the highest rate of prescribers per 100,000 population (5.9) compared to Ontario (2.2), Alberta (2.3), Saskatchewan (3.4) and Manitoba (3.5) by the end of Q1-2022., Conclusion: Uptake of BUP-ER varied geographically since being approved by Health Canada. More rapid uptake in rural areas is reassuring and suggests that this form of OAT may be supporting treatment access to those with barriers to more traditional treatment formulations., Competing Interests: Declaration of Competing Interest Dr. Gomes reports consulting fees from Canada’s Drugs Agency, honoraria from Indigenous Services Canada, and contracts with the Ontario College of Pharmacists and the Auditor General of British Columbia unrelated to this work. She has also been paid for expert testimony in an inquest led by the Ontario Office of the Chief Coroner. No authors have any other disclosures., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Although a "multisite" definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein, we sought to generate that evidence., Methods: We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively diagnosed patients with tuberculosis (TB) in Canada. Definitions were combined in a multi-variable logistic regression to determine the risk factors for TB-related death in DTB., Results: We applied two mutually exclusive definitions of DTB to our data set: 1. "strict" - TB disease associated with a positive TB culture in blood/bone marrow or TB disease associated with a miliary pattern on chest imaging and a positive TB culture or, 2. multisite - TB disease in two or more non-contiguous sites. Among 2877 notified patients with TB, 110 (3.8%) met the strict definition, whereas 168 (5.8%) met the multisite definition. Of all 278 patients with DTB, only 135 (48.6%) were notified as DTB using International Classification of Disease codes and only 66 (23.7%) were classified as DTB by Canada's Public Health Agency. Patients with DTB by either definition were less likely to achieve cure/treatment completion and more likely to die. The risk factors for a fatal outcome included extremes of age, Canadian birth, central nervous system involvement, and HIV co-infection., Conclusion: Our findings support the combination of a strict and multisite definition of DTB for purposes of reporting consistency and investigational comparability., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Targeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts., Methods: In this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up., Results: We included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant., Conclusion: Diet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function., Competing Interests: Conflict of interest The authors report that there are no disclosures relevant to this publication., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The second-to-fourth digit ratio (2D:4D) is thought to reflect prenatal exposure to sex steroids. We investigated the relationship between 2D:4D and odds of prostate cancer., Method: Data were collected in PROtEuS, a population-based case-control study conducted in Montréal, Canada (2005-2012), including 1931 incident prostate cancer cases aged < 76 years and 1994 population controls. In-person interviews elicited information on potential risk factors. Digit lengths were measured by interviewers applying a standard protocol. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders., Results: The OR of prostate cancer for a standard deviation increase in 2D:4D was 0.91 (95 % CI: 0.85-0.98). For less and more aggressive cancers, ORs were 0.93 (95 % CI: 0.87-1.00) and 0.85 (95 % CI: 0.77-0.93), respectively. There was an interaction with ancestry (p=0.04), whereas the OR among men of African descent was 1.23 (95 % CI: 0.96-1.57, based on 128 cases)., Conclusion: Findings suggest an inverse association between 2D:4D and odds of overall prostate cancer, more pronounced for aggressive cancers. This supports the notion that high levels of testosterone in utero, estimated by a low 2D:4D ratio, are associated with a higher risk of prostate cancer. Contrastingly, a high digit ratio was associated with greater cancer odds among participants of African descent. Upon replication, 2D:4D could prove to be an easily measured marker of prostate cancer risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Biomarkers of glucose metabolism may reflect insulin resistance, a risk factor for diabetes and cardiovascular disease (CVD). Neighborhoods conducive to a physically active lifestyle have the potential to improve these biomarkers. We examined cross-sectional associations between walkability and blood biomarkers of glucose metabolism in 29,649 Canadian Health Measures Survey (CHMS) participants. We used generalized linear mixed models with sampling weights adjusted for province, participants' age, sex, annual household income and educational attainment, cigarette smoking, environmental tobacco smoke, alcohol consumption, and exposure to ambient fine particulate air pollution (PM 2.5 ). A higher value of the Canadian Active Living Environments Index, a measure of neighborhood walkability, equivalent to the magnitude of its interquartile range (IQR) of 2.4 was significantly associated with percentage differences of -0.48 (95% confidence interval (CI): 0.63, -0.32), -3.17 (95%CI: 5.27, -1.08), -3.88 (95%CI: 6.38, -1.38), and -3.36 (95%CI: 5.25, -1.47) in HbA1C, fasting insulin, HOMA-IR, and HOMA-β, respectively, for all CHMS participants. No significant effects were observed in those ≤16 years old. Canadians living in neighborhoods that facilitate active living have more favorable biomarkers of glucose metabolism, suggesting that the built environment has the potential to improve risk factors for diabetes and CVD in adults., 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 © 2024. Published by Elsevier Inc. All rights reserved.)

Introduction: Colorectal cancer (CRC) incidence among adults younger than 50 years has increased in recent decades, leading to some advocating for lowering the age to start CRC screening. Here, we estimate age-specific trends in CRC incidence in Canada and changes in risk by birth cohort., Methods: CRC incidence data from 1971 to 2021 by province, sex, and five-year age group (35-64) were obtained from the National Cancer Incidence Reporting System and the Canadian Cancer Registry. Annual percent changes in age-specific or age-adjusted incidence rates were analyzed with joinpoint regression. Birth cohort effect was estimated with age-period-cohort models and reported as cohort incidence rate ratios (IRRs) with respect to the 1947-51 cohort., Results: CRC incidence has increased among all age groups under 50 years, with the largest relative increases occurring in the youngest age group (35-39 years). Males and females had similar incidence trends, though males under age 50 had larger increases than females. The birth cohort analysis showed that males born since 1966 have a significantly higher risk than those born at any other time., Conclusions: These results up to 2021 confirm and update reports that CRC incidence is increasing among adults under age 50 in Canada and that the youngest birth cohorts carry the highest risk. Future studies should assess the effectiveness of CRC screening in younger populations., Competing Interests: Declaration of Competing Interest The authors declare they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the success of diagnostic genetic testing in inherited retinal dystrophy (IRD) patients in the clinical setting., Design: Retrospective cohort analysis., Participants: A total of 446 consecutive participants from diverse ethnic backgrounds living in western Canada., Methods: Clinical information was collected from participants, including family history, and they underwent a full ophthalmic examination with chart review. Those with a suspected IRD were offered panel-based genetic testing of 351 genes between March 1, 2019, and February 28, 2022. The main outcome measure was effect of the genetic testing results on clinical diagnosis., Results: Genetic testing established a conclusive molecular diagnosis in 249 of 446 cases (55.8%), a clearly negative result in 90 of 446 cases (20.1%), and an inconclusive diagnosis in 108 of 446 cases (24.2%). Conclusive disease-causing variants were identified in 69 genes, and the most commonly affected genes were ABCA4 (31 variants), USH2A (25 variants), and RPGR (19 variants). The inconclusive group included likely novel autosomal dominant variants or a pathogenic variant with a variant of uncertain significance in the same gene for a recessive phenotype. Notably, an inconclusive molecular genetic diagnosis was seen in as many as 47.3% of East Asian participants with an outer retinal dystrophy., Conclusions: This study represents the largest review of molecular genetic testing in IRDs in Canada. That negative or inconclusive results obtained in approximately 45% of cases demonstrates that there is an important need for new research into molecular genetic causes of IRDs. This is particularly true in addressing the problem of interpreting a variant of uncertain significance in ethnic minorities., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Abdominal Radical hysterectomy (ARH) with pelvic lymph node assessment is considered the standard treatment for early-stage cervical cancer. Accepted routes have previously included laparoscopic or robotic approaches (LRH). Laparoscopy-assisted vaginal or vaginal radical hysterectomy (LVRH) are performed in some centers. The objective of this study is to compare surgical and oncological outcomes of LVRH, to laparoscopic and abdominal approaches., Design Patients Setting: A retrospective multicenter analysis of consecutive cervical cancer cases who underwent a radical hysterectomy between 2007 and 2017 in eleven regional cancer centers across Canada., Measurements: A comparison of patients stratified by surgical technique was undertaken. T-test, Wilcoxon rank-sum and chi-square were used to compare patient characteristics. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across surgical groups., Main Results: A total of 1071 patients with cervical cancer stage IA1 with lymphovascular invasion to stage IIIC (FIGO 2018) <4 cm were identified. Postoperative complication rate was lowest for women undergoing LVRH (9.1 %, vs 18.3 % and 22.1 % for minimally invasive and open respectively). During follow up, 114 women recurred, and 70 women died. 5-year recurrence-free survival was 85.4 % for LRH, 89.4 % for ARH and 92.2 % for LVRH. LVRH was not found to be associated with a higher risk of recurrence or death than ARH on multivariable analysis (aHR for recurrence 0.62, CI 0.21-1.77; aHR for death 0.63, CI 0.14-2.77) CONCLUSION: In this retrospective study, vaginal or laparoscopy-assisted vaginal radical hysterectomy for cervical cancer was associated with favorable perioperative and oncological outcomes., Competing Interests: Declaration of competing interest The authors do not have financial interest with commercial entities that are marketing or developing products (drugs, devices, diagnostic tools, etc.) related to the subject matter of the manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To assess the outcomes and failure risk factors for Kahook Dual Blade (KDB) excisional goniotomy with cataract surgery (phaco-KDB) in eyes with various glaucoma subtypes and severities., Methods: This multisurgeon consecutive case series included glaucomatous eyes with cataract that underwent phaco-KDB and had a minimum follow-up of 12 months postoperatively. Efficacy was assessed by absolute and qualified surgical success (defined by different criteria) and changes in intraocular pressure (IOP) and antiglaucoma medication (AGM) at the last postoperative follow-up. Safety included best-corrected visual acuity, cup-to-disc ratio, visual field mean deviation, retinal nerve fibre layer thickness, and adverse events., Results: A total of 108 eyes of 89 patients with a median follow-up of 18 months (range, 12-47 months) were included. IOP decreased by 26% from 19.1 ± 5.0 mm Hg to 14.1 ± 3.5 mm Hg (p < 0.001), AGM use decreased by 29% from 2.4 ± 1.3 medications to 1.7 ± 1.3 (p < 0.001), and 25% of eyes became free of AGMs (vs 3% at baseline). Qualified success rates achieved for IOP cutoffs of 18, 15, and 12 mm Hg were 87%, 68%, and 46%, respectively. Higher baseline IOP and postoperative incidence of IOP spikes were associated with a higher risk of surgical failure. Best-corrected visual acuity improved postoperatively (p < 0.001), and visual field mean deviation, cup-to-disc ratio, and retinal nerve fibre layer thickness remained stable. Overall, safety was favourable, and adverse events were transient and not sight threatening., Conclusion: This multicentre Canadian study provides real-world data that support the safety and efficacy of phaco-KDB in reducing IOP and AGM use with no evidence of disease progression during the follow-up period., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD)., Research Question: Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD?, Study Design and Methods: Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS score 1-3), vulnerable (CFS score 4), and frail (CFS score 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort was used to establish prognostic performance. Trajectories of functional tests were compared using joint models., Results: Of the 1,587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) were vulnerable, and 329 (21%) were frail. Frailty was a risk factor for early mortality (hazard ratio, 5.58; 95% CI, 3.64-5.76, P < .001) in the entire cohort, in individual ILD diagnoses, and after adjustment for potential confounders. Adding frailty to established risk prediction parameters improved the prognostic performance in derivation and validation cohorts. Patients in the frail subgroup had larger annual declines in FVC % predicted than patients in the fit subgroup (-2.32; 95% CI, -3.39 to -1.17 vs -1.55; 95% CI, -2.04 to -1.15, respectively; P = .02)., Interpretation: The simple and practical CFS is associated with pulmonary and physical function decline in patients with fibrotic ILD and provides additional prognostic accuracy in clinical practice., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Describe the rate of death over 4 consecutive quarters and determine optimal categorization of residents into risk-of-death categories, expanding the Changes in Health, Endstage Disease, Signs and Symptoms (CHESS) scale., Design: Using secondary analysis design with Minimum Data Set (MDS) data, the CHESS scale provided the base upon which the DeathRisk-NH scale was developed., Setting and Participants: Baseline and 4 quarterly follow-up analyses of Canadian (n = 109,145) and US (n = 1,075,611) nursing home resident data were completed., Methods: Logistic regression analyses identified predictors of death, additive to CHESS, to form the DeathRisk-NH scale. The independent variable set used MDS items, focusing on clinical complexity indicators, diagnostic conditions, and measures of severe clinical distress., Results: Country cohorts had similar percentages of residents with mean activities of daily living hierarchy scores, dependence in mobility, continence, memory, and overall CHESS scores. The percentage of individuals who died increased from 10.5% (3 months) to 30.7% (12 months). The average annual death rate for this cohort was 5.5 times higher than the national annual death rate of approximately 5.6%., Conclusions and Implications: The DeathRisk-NH is an effective prediction model to identify residents at risk of death within the first 12 months after admission to the nursing home. The tool may be helpful in patient care planning, resource allocation, and excess death monitoring., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Coping strategies used in response to stress have the potential to influence the development of mental health disorders, including alcohol use disorders. The current study investigated whether coping strategies placed an individual at greater likelihood for developing a future alcohol use disorder., Methods: This study used data from the Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey; a nationally representative 16-year follow-up survey, with initial data collected in the 2002 Canadian Community Health Survey - Canadian Forces Supplement. The total sample from the two datasets included 2941 individuals who were Regular Force members in 2002. Coping styles included problem-focused, avoidant, and self-medication. Adjusted logistic regression analyses examined relationships between coping style (in 2002) and alcohol use disorders (developed between 2002 and 2018)., Results: Self-medication coping in 2002 was associated with any alcohol disorder since last interview (i.e., 2002-2018) (AOR 1.26; 95 % CI, 1.02-1.57) and during the past year (adjusted odds ratios [AOR 1.26; 95 % CI, 1.08-1.47]), as well as past-year binge drinking (AOR 1.19; 95 % CI, 1.09-1.29). Problem-focused coping was protective against past-year alcohol abuse (AOR 0.84; 95 % CI, 0.71-1.00) and any alcohol use disorder (AOR 0.87; 95 % CI 0.76-1.00)., Conclusion: Coping styles were strongly associated with future alcohol use disorders. Notably, results show the risk extended over a 16-year period. Findings suggest the use of self-medicating coping strategies places an individual at increased risk of developing alcohol use disorders, while problem-focused coping may decrease future risk of alcohol use disorders., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The database autopsy method was developed to determine probable causes of maternal deaths in the Canadian Institute for Health Information's hospital discharge abstract database; however, the method has yet to be validated. Using immediate cause of death information from Québec's hospitalization database as the gold standard, this study assessed the validity and reliability of the database autopsy method for pregnancy-associated deaths. The method had high sensitivity and specificity for identifying the most common causes of these deaths, as well as high interobserver agreement. We conclude that the database autopsy method is valid and reliable overall., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Considerable evidence has been accumulated on serious acute health outcomes associated with short-term exposure to ambient fine particulate matter (PM 2.5 ). Modifying factors of those associations, however, have been less explored and need further analyses. In this national study, we investigated whether short-term effects of PM 2.5 are modified according to region, cause of mortality/hospitalization, season, age, and sex. PM 2.5 -related adverse health effects were estimated by an ecological time-series study, covering about 80 % of the Canadian population for 18 years (2001-2018). We estimated city-specific associations using daily averages of PM 2.5 and temperature, and daily counts of hospitalizations and mortality (non-accidental all-cause, circulatory, and respiratory). National and regional associations were then estimated with a 2-stage model. We considered potential modifying factors of PM 2.5 -related adverse health effects, and examined linear trends in the annual associations. Nationally, PM 2.5 exposure was associated with both hospitalizations and mortality, and there was evidence of differences by the modifying factors. Of the various causes, circulatory mortality and respiratory hospitalization were more attributable to PM 2.5 exposure. We found regional differences for both all-cause hospitalization and all-cause mortality, and seasonal differences for respiratory hospitalization (warm season) and circulatory hospitalization (cold season). Circulatory mortality risk was significant for seniors and females. All-cause hospitalizations appeared to gradually decrease over time, but annual all-cause mortality remained constant at 0.6 % of the population. Adverse health effects of PM 2.5 exposures may depend on not only PM 2.5 concentration, but also other factors (region, cause, season, age, sex). National estimates for the baseline (age ≥ 1 year, both sexes) risk cannot be interpreted without consideration of the differences by modifying factors. Study findings can be used by seniors, women, and those who have pre-existing health conditions to make informed decisions regarding their health risks from daily exposure to ambient PM 2.5 ., Competing Interests: Declaration of competing interest The study sponsor (Health Canada) had no role in study design, collection, analysis, interpretation of data, or writing of the manuscript. The authors also declare that they have no actual or potential competing financial interests, and that this study did not have any relationships or support that might be perceived as constituting a conflict of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Purpose: In adults, intimate partner violence victimization and traumatic brain injuries, including concussion, are strongly connected. However, no prior research has explored this association among youth. This study explores the association between teen dating violence (TDV) and concussion to inform clinical care for these at-risk groups., Methods: We used data from ninth and 10th grade youth in the 2017/18 Health Behavior in School-Aged Children nationally representative Canadian dataset (N = 2,926). TDV in the past 12 months was measured using three items for victimization and three for perpetration. Youth were asked if they had been told by a doctor or nurse that they had had a concussion in the past 12 months and where they were and what they were doing when they had the concussion. We used coarsened exact matching to create equivalent groups of TDV victims and nonvictims, and then explored the association between TDV and concussion using doubly robust logistic regression models. We also explored effect modification by gender., Results: TDV was related to higher odds of concussion, both overall and when restricted to nonsport settings. In nonsport settings, youth who reported mutual TDV reported the highest odds of past-year concussion (adjusted odds ratio = 2.14, 95% confidence interval: 1.07, 4.28, p = .032). We also found that girls and nonbinary youth reported elevated risk of concussion in the context of TDV., Discussion: We found that TDV was associated with increased risk for concussion. Findings can be used to inform future research and may assist adolescent health providers who treat youth with concussion., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Atherosclerotic cardiovascular disease (ASCVD) is a significant health challenge, and apolipoprotein B (ApoB)-containing lipoproteins are increasingly recognized as central to its progression. Initially labelled as the "low-density lipoprotein hypothesis," our understanding of the etiology of ASCVD has evolved into the "ApoB principle," which highlights the causal and consistent role of all ApoB lipoproteins in ASCVD development. We review the large body of data from genetic studies, to epidemiologic studies, to clinical trials that support this foundational principle. We also provide an overview of the recommendations from guideline committees across the globe on dyslipidemia management and compare these with recent Canadian guidelines. With a few key differences, recent guidelines worldwide provide largely concordant recommendations for diagnosing and managing dyslipidemia with general consensus regarding the need for optimal control of low-density lipoprotein cholesterol and ApoB-containing lipoproteins to prevent cardiovascular events and improve patient care., (Copyright © 2024. Published by Elsevier Inc.)

Ischemic heart disease and stroke are the leading causes of death worldwide. Herein we review the burden, epidemiology, and risk factors for atherosclerotic cardiovascular disease (ASCVD). The focus of this review is on the current state of ASCVD in Canada, however, the findings regarding epidemiological trends are likely to be reflective of global trends, particularly in high-income countries, and the discussion regarding risk factors and lipid lowering is universally applicable. In Canada, the burden of death from ASCVD is second only to cancer deaths. There are major differences in disease burden related to sex, geography, and socioeconomic status. The major risk factors for ASCVD have been identified, although new and emerging risk factors are an active area of research. Recent developments such as polygenic risk scores provide potential to identify individuals at risk for ASCVD earlier in life and institute preventative measures. Dyslipidemia, and in particular elevated concentrations of low-density lipoprotein cholesterol and apolipoprotein B are a major cause of ASCVD. Therapies to lower low-density lipoprotein/apolipoprotein B levels are key components to treating and preventing ASCVD. Addressing the causal risk factors for ASCVD in a manner that comprehensively considers the clinical, social, and economic implications of prevention strategies will be essential to reduce the burden of ASCVD and improve outcomes for patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The incidence of early-onset (<50 years of age) colorectal cancer (eoCRC) has been steadily increasing in high-income countries including Canada. Despite this increase in incidence, the etiology of eoCRC remains unclear and prospective cohort studies of potential risk factors are limited., Methods: We examined two prospective cohorts of healthy individuals (<50 years of age) who completed baseline questionnaires in the Ontario Health Study and Alberta's Tomorrow Project. We examined the associations between demographic characteristics, chronic health conditions, and lifestyle behaviours with the development of eoCRC using Cox proportional hazard models. Cohorts were analyzed separately and hazard ratios for each risk factor were pooled with random effects meta-analyses., Results: During an average follow-up of 6.63 years, 98 eoCRC cases occurred among study participants (n=127,852). A family history of CRC alone or with a history of other cancer types was associated with an increased risk of developing eoCRC (HR: 2.76, 95% CI: 1.43-5.32), but a family history of a non-CRC cancer only was not (HR: 1.18, 95% CI: 0.61-2.30). Heavy smokers (≥ 10 pack-years) at baseline had a higher risk of eoCRC compared to non-smokers (HR: 1.87, 95% CI: 1.00-3.52). Sex, socioeconomic factors, diabetes, alcohol consumption, among other factors were not significantly associated with the risk of eoCRC., Conclusion: Our findings indicate that specific CRC risk factors are also associated with developing eoCRC. The data in the study offers valuable insights that could be integrated in future meta-analyses. Additional prospective cohort studies are required to understand the etiology of eoCRC., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: The Eye Institute of Alberta Emergency Eye Clinic (EIA EEC) is a tertiary eye care centre that provides emergency eye services to a population of more than 1 million. The purpose of this study was to describe the epidemiology of ocular emergencies at the EIA EEC., Design: Prospective epidemiologic study based on secondary use of patient data., Participants: All patients seen in the EIA EEC on weekdays between July 2020 and June 2021., Methods: Charts were reviewed to obtain patient demographics, referral details, final diagnoses, need for imaging, emergency procedures, or further referrals. SPSS Statistics was used for data analysis., Results: A total of 2586 patients were seen over the study period. Most of the referrals (58%) were from emergency physicians. Optometrists and general physicians contributed 14% and 11% of referrals, respectively. Most referral diagnoses were related to inflammation (32%), and trauma (22%). Of all the cases of inflammation, 41% involved infection of the eye and 8% involved infection of ocular adnexa. In addition, 44% and 7% of cases involved noninfectious inflammation of the eye and adnexa, respectively. Frequently preformed emergency procedures were corneal or conjunctival foreign-body removal (39%) and corneal scraping (14%)., Conclusions: Continuing education related to emergency eye care may be most beneficial to emergency physicians, general practitioners, and optometrists. Educational opportunities could focus on most frequently seen diagnostic categories such as inflammation and trauma. Targeted public education aimed at preventing ocular trauma and infection, such as promoting wearing eye protection and practicing contact lens hygiene, may be beneficial., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Borrelia burgdorferi sensu lato (Bb) are a complex of bacteria genospecies that can cause Lyme disease (LD) in humans after the bite of an infected Ixodes spp. vector tick. In Canada, incidence of LD is increasing in part due to the rapid geographic expansion of Ixodes scapularis across the southcentral and eastern provinces. To better understand temporal and spatial (provincial) prevalence of Bb infection of I. scapularis and how tick surveillance is utilized in Canada to assess LD risk, a literature review was conducted. Tick surveillance studies published between January 1975 to November 2023, that measured the prevalence of Bb in I. scapularis via "passive surveillance" from the public citizenry or "active surveillance" by drag or flag sampling of host-seeking ticks in Canada were included for review. Meta-analyses were conducted via random effects modeling. Forty-seven articles, yielding 26 passive and 28 active surveillance studies, met inclusion criteria. Mean durations of collection for I. scapularis were 2.1 years in active surveillance studies (1999-2020) and 5.5 years by passive surveillance studies (1990-2020). Collectively, data were extracted on 99,528 I. scapularis nymphs and adults collected between 1990-2020 across nine provinces, including Newfoundland & Labrador (33 ticks) and Alberta (208 ticks). More studies were conducted in Ontario (36) than any other province. Across nine provinces, the prevalence of Bb infection in I. scapularis collected by passive surveillance was 14.6% with the highest prevalence in Nova Scotia at 20.5% (minimum studies >1). Among host-seeking I. scapularis collected via active surveillance, Bb infection prevalence was 10.5% in nymphs, 31.9% in adults, and 23.8% across both life stages. Host-seeking I. scapularis nymphs and adults from Ontario had the highest Bb prevalence at 13.6% and 34.8%, respectively. Between 2007-2019, Bb infection prevalence in host-seeking I. scapularis was positively associated over time (p<0.001) which is concurrent with a ∼25-fold increase in the number of annually reported LD cases in Canada over the same period. The prevalence of Bb-infection in I. scapularis has rapidly increased over three decades as reported by tick surveillance studies in Canada which coincides with increasing human incidence for LD. The wide-ranging distribution and variable prevalence of Bb-infected I. scapularis ticks across provinces demonstrates the growing need for long-term standardized tick surveillance to monitor the changing trends in I. scapularis populations and best define LD risk areas in Canada., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PHK, YT, QY, MS, AD, MM, AG, KH, FJA, JM and JHS are employees of Pfizer and may hold shares and/or stock options in the company. The other authors have no potential conflict of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To investigate the association between the neighborhood built environment and trajectories of body mass index (BMI) in youth., Methods: Data were collected in a prospective study of 1293 adolescents in Montreal. Built environment variables were obtained from public databases for road networks, land use, and the Canadian Census. Anthropometric data were collected when participants were ages 12.5, 15 and 17 years. We undertook hierarchical cluster analysis to identify contrasting neighborhood types based on features of the built environment (e.g., vegetation, population density, walkability). Associations between neighborhood type and trajectories of BMI z-score (BMIz) were estimated using multivariable linear mixed regression analyses, stratified by sex., Results: We identified three neighborhood types: Urban, Suburban, and Village. In contrast to the Urban type, the Suburban type was characterized by more vegetation, few services and low population density. Village and Suburban types were similar, but the former had greater land use diversity, population density with more parks and a denser food environment. Among girls, living in Urban types was associated with decreasing BMIz trajectories. Living in Village types was associated with increasing BMIz trajectories. No associations were observed among boys., Conclusions: Neighborhoods characterized by greater opportunities for active living appear to be less obesogenic, particularly among girls., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To examine the impact of two key choices when conducting a network analysis (clustering methods and measure of association) on the number and type of multimorbidity clusters., Study Design and Setting: Using cross-sectional self-reported data on 24 diseases from 30,097 community-living adults aged 45-85 from the Canadian Longitudinal Study on Aging, we conducted network analyses using 5 clustering methods and 11 association measures commonly used in multimorbidity studies. We compared the similarity among clusters using the adjusted Rand index (ARI); an ARI of 0 is equivalent to the diseases being randomly assigned to clusters, and 1 indicates perfect agreement. We compared the network analysis results to disease clusters independently identified by two clinicians., Results: Results differed greatly across combinations of association measures and cluster algorithms. The number of clusters identified ranged from 1 to 24, with a low similarity of conditions within clusters. Compared to clinician-derived clusters, ARIs ranged from -0.02 to 0.24, indicating little similarity., Conclusion: These analyses demonstrate the need for a systematic evaluation of the performance of network analysis methods on binary clustered data like diseases. Moreover, in individual older adults, diseases may not cluster predictably, highlighting the need for a personalized approach to their care., Competing Interests: Declaration of competing interest The authors declare no financial conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH., Methods: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis., Results: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival., Conclusion: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose., Impact and Implications: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This article examines the care gaps in lipid-lowering therapy for atherosclerotic cardiovascular disease (ASCVD), primarily focusing on discrepancies between recommended practices and actual clinical implementation. It provides an overview of the different challenges in lipid management following percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS). Studies reveal gaps in lipid testing and treatment adequacy post-PCI and ACS, as well as knowledge and practice gaps among primary care practitioners, particularly in adhering to the latest lipid guidelines. Initiatives such as the Guidelines Oriented Approach to Lipid-Lowering (GOAL) Canada program and the North American ACS Reflective III Pilot demonstrate improvements in the uptake of nonstatin therapies and achievement of low-density lipoprotein cholesterol targets through targeted educational and feedback interventions. Nonetheless, systemic challenges in the drug approval and reimbursement process persist and affect the accessibility of newer lipid-lowering agents. The most notable contribution of the reviewed studies is the demonstration of improved lipid management outcomes in high-risk ASCVD populations through targeted educational interventions, highlighting their potential value to change clinical practice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The COVID-19 pandemic prompted the scientific community to collaborate in an unprecedented way, with the rapid and urgent generation and translation of new knowledge about the disease and its causative agent. Iteratively, and at different levels of government and globally, population-level guidance was created and updated, resulting in the need for a living catalog of guidelines, the eCOVID-19 Recommendations Map and Gateway to Contextualization (RecMap). This article focuses on the approach that was used to analyze barriers and opportunities associated with using the RecMap in public health in Canada., Study Design and Setting: A mixed qualitative and quantitative approach data were used to inform this knowledge mobilization project and inform feedback on implementation of the eCOVID-19 RecMap. This approach involved surveying 110 attendees from a public health webinar. Following this webinar, an evidence brief and series of case studies were created and disseminated to 24 Canadian public health practitioners who attended a virtual workshop. This workshop identified barriers and opportunities to improve RecMap use., Results: This study helped to shed light on the needs that public health practitioners have when finding, using, and disseminating public health guidelines. Through the workshop that was conducted, opportunities for public health guidelines can be categorized into 4 categories: 1) information access, 2) awareness, 3) public health development, and 4) usability. Barriers that were identified can also be categorized into 4 categories: 1) usability, 2) information maintenance, 3) public health guidance, 4) awareness., Conclusion: This work will help to inform the development and organization of future public health guidelines, and the needs that public health practitioners have when engaging with them., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Wastewater-based surveillance (WBS) has shown to be an effective tool in monitoring the spread of SARS-CoV-2 and has helped guide public health actions. Consequently, WBS has expanded to now include the monitoring of mpox virus (MPXV) to contribute to its mitigation efforts. In this study, we demonstrate a unique sample processing and a molecular diagnostic strategy for MPXV detection that can inform on the epidemiological situation of mpox outbreaks through WBS. We conducted WBS for MPXV in 22 Canadian wastewater treatment plants (WWTPs) for 14 weeks. Three MPXV qPCR assays were assessed in this study for the detection of MPXV which include the G2R assays (G2R&#95;WA and G2R&#95;G) developed by the Centers for Disease Control and Prevention (CDC) in 2010, and an in-house-developed assay that we have termed G2R&#95;NML. The G2R&#95;NML assay was designed using reference genomes from the 2022 MPXV outbreak and provides a larger qPCR amplicon size to facilitate Sanger sequencing. Results show that all three assays have similar limits of detection and are able to detect the presence of MPXV in wastewater. The G2R&#95;NML assay produced a significantly greater number of Sanger sequence-confirmed MPXV results compared to the CDC G2R assays. Detection of MPXV was possible where provincial surveillance indicated overall low caseloads, and in some sites forewarning of up to several weeks was observed. Overall, this study proposes that WBS of MPXV provides additional information to help fill knowledge gaps in clinical case-surveillance and is potentially an essential component to the management of mpox., 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 © 2024. Published by Elsevier B.V. All rights reserved.)

Plant-based meat alternatives (PBMAs) are highly processed food products that typically replace meat in the diet. In Canada, the growing demand for PBMAs coincides with public health recommendations to reduce ultra-processed food consumption, which prompts the need to investigate the long-term health implications of PBMAs. This review assesses the available literature on PBMAs and cardiovascular disease (CVD), including an evaluation of their nutritional profile and impact on CVD risk factors. Overall, the nutritional profiles of PBMAs vary considerably but generally align with recommendations for improving cardiovascular health; compared with meat, PBMAs are usually lower in saturated fat and higher in polyunsaturated fat and dietary fibre. Some dietary trials that have replaced meat with PBMAs have reported improvements in CVD risk factors, including total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B-100, and body weight. No currently available evidence suggests that the concerning aspects of PMBAs (eg, food processing and high sodium content) negate the potential cardiovascular benefits. We conclude that replacing meat with PBMAs may be cardioprotective; however, long-term randomised controlled trials and prospective cohort studies that evaluate CVD events (eg, myocardial infarction, stroke) are essential to draw more definitive conclusions., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Limited data are available on complex high-risk percutaneous coronary intervention (CHiP) trends and outcomes in nonsurgical centres (NSCs), particularly in health care systems where most centres are NSCs., Methods: Using data from a national registry, we studied the characteristics and outcomes of CHiP procedures performed for stable angina from 2006 to 2017 according to the presence or absence of on-site surgical cover. Multivariate regression analyses and propensity score matching were used to determine risks for in-hospital death, major bleeding, and major cardiovascular or cerebral events (MACCE)., Results: Out of 134,730 CHiP procedures, 42,433 (31.5%) were performed in NSCs, increasing from 12.5% in 2006 to 42% in 2017. Compared with surgical centres (SCs), patients who had a CHiP procedure undertaken in NSCs were, on average, 2.4 years older and had a greater prevalence of cardiovascular risks. Common CHiP procedures performed in NSCs included poor left ventricular function (41.6%), chronic renal failure (38.8%), and chronic total occlusion percutaneous coronary intervention (31.1%). NSC-based CHiP is associated with lower odds of mortality (adjusted odds ratio [aOR] 0.7, 95% confidence interval [CI] 0.5-0.8) and major bleeding (aOR 0.7, 95% CI 0.6-0.8). In both groups, MACCE odds were similar (aOR 1.0, 95% CI 0.9-1.1)., Conclusions: CHiP numbers have steadily increased in NSCs. NSC patients were older and had a higher prevalence of cardiovascular risks than SC patients. Mortality and major bleeding odds were significantly lower in those cases undertaken in NSCs, although MACCE odds were not different between the groups., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by bi-allelic pathogenic variants in the microsomal triglyceride transfer protein (MTTP) gene. This disease is characterized by a deficiency in the secretion of apolipoprotein B-containing lipoproteins. Patients with ABL present with neurological, hematological, and gastrointestinal symptoms due to fat malabsorption and a deficiency in liposoluble vitamins. In this report, we present a total of four ABL cases, including three new cases, all originating from the same French-Canadian founder population in Saguenay-Lac-Saint-Jean, Québec, Canada. These individuals are homozygous for the same pathogenic variant in the MTTP gene (c.419dup, p.Asn140Lysfs*2). We found that this variant is more common than anticipated in this population, with an estimated carrier frequency of 1:203. Early diagnosis is essential to initiate treatment known to prevent complications associated with ABL. Population carrier screening or newborn screening for ABL should be considered in this French-Canadian founder population., Competing Interests: Declaration of competing interest AB received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst, and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Ionis Pharmaceuticals, Inc., ISIS Pharmaceuticals, The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen, and Sanofi. SPG, MP, LG, GG, VD, VP, and LB have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Data regarding coronavirus disease 2019 (COVID-19) outcomes in solid organ transplant recipients (SOTr) across severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) waves, including the impact of different measures, are lacking. This cohort study, conducted from March 2020 to May 2023 in Toronto, Canada, aimed to analyze COVID-19 outcomes in 1975 SOTr across various SARS-CoV-2 waves and assess the impact of preventive and treatment measures. The primary outcome was severe COVID-19, defined as requiring supplemental oxygen, with secondary outcomes including hospitalization, length of stay, intensive care unit (ICU) admission, and 30-day and 1-year all-cause mortality. SARS-CoV-2 waves were categorized as Wildtype/Alpha/Delta (318 cases, 16.1%), Omicron BA.1 (268, 26.2%), Omicron BA.2 (268, 13.6%), Omicron BA.5 (561, 28.4%), Omicron BQ.1.1 (188, 9.5%), and Omicron XBB.1.5 (123, 6.2%). Severe COVID-19 rate was highest during the Wildtype/Alpha/Delta wave (44.6%), and lower in Omicron waves (5.7%-16.1%). Lung transplantation was associated with severe COVID-19 (OR: 4.62, 95% CI: 2.71-7.89), along with rituximab treatment (OR: 4.24, 95% CI: 1.04-17.3), long-term corticosteroid use (OR: 3.11, 95% CI: 1.46-6.62), older age (OR: 1.51, 95% CI: 1.30-1.76), chronic lung disease (OR: 2.11, 95% CI: 1.36-3.30), chronic kidney disease (OR: 2.18, 95% CI: 1.17-4.07), and diabetes (OR: 1.97, 95% CI: 1.37-2.83). Early treatment and ≥3 vaccine doses were associated with reduced severity (OR: 0.29, 95% CI: 0.19-0.46, and 0.35, 95% CI: 0.21-0.60, respectively). Tixagevimab/cilgavimab and bivalent boosters did not show a significant impact. The study concludes that COVID-19 severity decreased across different variants in SOTr. Lung transplantation was associated with worse outcomes and may benefit more from preventive and early therapeutic interventions., Competing Interests: Declaration of competing interest Deepali Kumar has received clinical trial grants from GSK, Roche, and consultancy fees from GSK, Roche, Merck, Takeda, Exevir, and Allovir. Atul Humar has received clinical trial grants from Merck and consultancy fees from Merck and Takeda. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Accurate benchmarking of outcomes after elective open total arch replacement is important for surgical decision making and for comparisons with emerging endovascular technologies., Methods: A multicentre registry of consecutive aortic arch procedures in 9 centres across Canada contained 250 elective total arch replacements from 2010 to 2021. A total of 728 patients undergoing elective hemiarch replacement over the same time period was used as a comparator group. Propensity score matching was used to construct 202 well matched pairs., Results: Patients undergoing total arch replacement were 63.2 ± 13.6 years old, and 34% were female. These patients were more likely to have connective tissue disorders compared with patients undergoing hemiarch replacement. When under hypothermic circulatory arrest, the total arch group uniformly used antegrade cerebral perfusion with median nadir temperature of 24°C (interquartile range [IQR] 21-25°C), and median duration 33 minutes (IQR 23-51 minutes). Before matching, in-hospital mortality and stroke rates were 5.2% and 10%, respectively, for the total arch group. After matching, the total arch group had in-hospital mortality similar to the hemiarch group (P = 0.58). Rates of stroke were also not statistically different (P = 0.11). The total arch group was more likely to experience delirium, prolonged intubation, increased intensive care unit length of stay, and transfusions., Conclusions: Elective total arch replacement is performed with good in-hospital mortality rates that are similar to rates after elective hemiarch repairs. However, total arch replacement was associated with significantly higher rates of other morbidities, including delirium and prolonged intubation., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Myocardial infarction with no obstructive coronary artery disease (MINOCA) represents 6%-15% of all acute coronary syndromes, and women are disproportionately represented. MINOCA is an encompassing preliminary diagnosis, and emerging evidence supports a more expansive comprehensive diagnostic and therapeutic clinical approach. The current clinical practice update summarizes the latest evidence regarding the epidemiology, clinical presentation, and diagnostic evaluation of MINOCA. A cascaded approach to diagnostic workup is outlined for clinicians, for noninvasive and invasive diagnostic pathways, depending on clinical setting and local availability of diagnostic modalities. Evidence concerning the nonpharmacological and pharmacological treatment of MINOCA are presented and summarized according to underlying cause of MINOCA, with practical tips on the basis of expert opinion, outlining a real-life, evidence-based, comprehensive approach to management of this challenging condition., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: During the COVID-19 pandemic, public health measures were used to reduce the spread of COVID-19; it is unknown whether people with chronic conditions differentially adhered to public health measures. The objectives of this study were to evaluate the association between chronic conditions and adherence and to explore effect modification by sex, age, and income., Study Design: An analysis of data from the Canadian Longitudinal Study on Aging COVID-19 Questionnaires (from April to September 2020) was conducted among middle-aged and older adults aged 50-96 years (n = 28,086)., Methods: Self-reported chronic conditions included lung disease, diabetes, heart disease, cancer, obesity, anxiety, and depression. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic conditions and low, medium, and high levels of adherence. Effect modification was evaluated using statistical interaction and stratification., Results: Most people (n = 17,435; 62%) had at least one chronic condition, and 2866 (10%) had three to seven chronic conditions. Among those with high adherence to public health measures, 69% had one or more chronic condition (n = 2266). Having three to seven chronic conditions, compared with none, was associated with higher adherence to public health measures (OR: 2.14; 95% CI: 1.12-1.42). Higher adherence was also noted across chronic conditions, for example, those with diabetes had higher adherence (OR: 1.72; 95% CI: 1.53-1.93). There was limited evidence of effect modification by sex, age, or income., Conclusions: Canadians with chronic conditions were more likely to adhere to public health measures; however, future research is needed to understand whether adherence helped to prevent adverse COVID-19 outcomes and if adherence had unintended consequences., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Unlike other developed countries that hold national burn registries to monitor burn injury and care, Canada relies on single-centre secondary datasets and administrative databases as surveillance mechanisms. The objective of this study was to determine the knowledge gap faced in Canada for not having a dedicated burn registry. A comprehensive scoping review was conducted to identify the burn literature that has arisen from secondary datasets in Canada. Literature of all study designs was included with the exception of case reports and cases series. Once data extraction was concluded, a thematic framework was constructed based on the information that arose from nations that hold national burn registries. Eighty-eight studies were included. Twelve studies arose from national datasets, and 18 from provincial databases, most of which were from Ontario and British Columbia. Only seven studies were conducted using a combination of Canadian units' single-centre datasets. The majority of included studies (58%) resulted from non-collaborative use of single-centre secondary datasets. Research efforts were predominantly conducted by burn units in Ontario, British Columbia, Manitoba and Alberta. A significant number of the included studies were outdated and several provinces/territories had no published burn data whatsoever. Efforts should be made towards the development of systems to surveil burn injury and care in Canada. This study supports the development of a nation-wide burn registry to bridge this knowledge gap., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Despite decades of social epidemiologic research, health inequities remain pervasive and ubiquitous in Canada and elsewhere. One reason may be our use of socioeconomic measurement, which has often relied on single point-in-time exposures. To explore the extent to which researchers have incorporated dynamic socioeconomic measurement into cardiovascular health outcome evaluations, we performed a narrative review. We estimated the prevalence of socioeconomic longitudinal cardiovascular research studies that identified socioeconomic exposures at 2 or more points in time between the years of 2019 and 2023. We defined cardiovascular outcome studies as those that examined coronary artery disease, myocardial infarction, acute coronary syndrome, stroke, heart failure, cardiac arrhythmias, cardiac death, cardiometabolic factors, transient ischemic attacks, peripheral artery disease, or hypertension. Socioeconomic exposures included individual income, neighbourhood income, intergenerational social mobility, education, occupation, insurance status, and economic security. Seven percent of socioeconomic cardiovascular outcome studies have measured socioeconomic status at 2 or more points in time throughout the follow-up period, hypothesized mechanisms by which dynamic socioeconomic measures affected outcome focused on social mobility, accumulation, and critical period theories. Insights, implications, and future directions are discussed, in which we highlight ways in which postal code data can be better used methodologically as a dynamic socioeconomic measure. Future research must incorporate dynamic socioeconomic measurement to better inform root causes, interventions, and health-system designs if health equity is to be improved., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: The high output cardiac state (HOCS) [cardiac index (CI) >4 L/min/m2 ], primarily driven by abnormally low systemic vascular resistance (SVR), is a relatively under-recognized condition. Although, majority of these patients meet criteria for heart failure (HF), their treatment should be aimed at the primary pathology, as the majority of guideline directed HF therapies can reduce SVR further., Objectives: To characterize patients with HOCS and provide valuable insight into the condition., Methods: Patients investigated by right heart catheterization (RHC) at the St. Boniface Hospital, Winnipeg, Canada between January 2009 and November 2021 were reviewed. Two groups of patients were included: 1) HOCS [CI >4 L/min/m 2 ], and 2) pre-HOCS [CI between 3.8-4.0 L/min/m 2 ]. Their medical records were reviewed to identify plausible etiologies, relevant investigations, and outcomes., Results: 177/2950 (6 %) patients met criteria for inclusion: 144/177 (81 %) with HOCS [mean age 51 years (range 19 - 82); 67/144 (47 %) female] and 33/177 (19 %) with pre-HOCS [mean age 55 years (range 30 - 83); 6/33 (18 %) female]. The most common plausible etiologies for the HOCS included anemia (36 %), obesity (34 %), cirrhosis (17 %), and lung disease (32 %). Trans-thoracic echocardiography and magnetic resonance imaging findings were non-specific and predominantly described preserved left ventricular ejection fraction, and pulmonary hypertension. The population experienced high rates of hospitalization, and significantly high mortality [36/144 (25 %) of HOCS at a median follow-up of 31.5 months, and 13/33 (39 %) of pre-HOCS at a median follow-up of 17 months]., Conclusions: HOCS is not an uncommon condition and is associated with high mortality. Current HF guideline should incorporate such evaluation into the diagnostic criteria., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Immigration policies shape the composition, socioeconomic characteristics, and health of migrant populations. The health of migrants is also influenced by a confluence of social, economic, environmental, and political factors. Immigrants and refugees often face various barriers to accessing health care because of factors such as lack of familiarity with navigating the health care system, language barriers, systemic racism, and gaps in health insurance. Social determinants of health and access to primary care health services likely influence the burden of cardiovascular risk factors among immigrants. The relatively low burden of many cardiovascular risk factors in many immigrant populations likely contributes to the generally lower incidence rates of acute myocardial infarction, heart failure, and stroke in immigrants compared with nonimmigrants, although cardiovascular disease incidence rates vary substantially by country of origin. The "healthy immigrant effect" is the hypothesis that immigrants to high-income countries, such as Canada, are healthier than nonimmigrants in the host population. However, this effect may not apply universally across all immigrants, including recent refugees, immigrants without formal education, and unmarried immigrants. As unfolding sociopolitical events generate new waves of global migration, policymakers and health care providers need to focus on addressing social and structural determinants of health to better manage cardiovascular risk factors and prevent cardiovascular disease, especially among the most marginalized immigrants and refugees., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease has been the leading cause of death in the United States and Canada for decades. Although it affects millions of people across a multitude of backgrounds, notable disparities in cardiovascular health are observed among women and become more apparent when accounting for race and socioeconomic status. Although intrinsic sex-specific physiologic differences predispose women to poorer outcomes, social determinants of health (SDOH) and biases at both the individual provider and the larger health care system levels play an equal, if not greater, role. This review examines socioeconomic disparities in women compared with men regarding cardiovascular risk factors, treatments, and outcomes. Although various at-risk subpopulations exist, we highlight the impact of SDOH in specific populations, including patients with disabilities, transgender persons, and South Asian and Indigenous populations. These groups are underrepresented in studies and experience poorer health outcomes owing to structural barriers to care. These findings emphasise the significance of understanding the interplay of different socioeconomic factors and how their stacking can negatively affect women's cardiovascular health. To address these disparities, we propose a multipronged approach to augment culturally sensitive and patient-centred care. This includes increased cardiovascular workforce diversity, inclusion of underrepresented populations into analyses of cardiovascular metrics, and greater utilisation of technology and telemedicine to improve access to health care. Achieving this goal will necessitate active participation from patients, health care administrators, physicians, and policy makers, and is imperative in closing the cardiovascular health gap for women over the coming decades., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients with fibrotic hypersensitivity pneumonitis (fHP) are frequently treated with immunosuppression to slow lung function decline; however, the impact of this treatment has not been studied across different types of antigen exposure., Research Question: In patients with fHP, do disease outcomes and response to treatment vary by antigen type?, Study Design and Methods: A multicenter interstitial lung disease database (Canadian Registry for Pulmonary Fibrosis) was used to identify patients with fHP. The causative antigen was categorized as avian, mold, unknown, or other. Treatment was defined as mycophenolate ≥ 1,000 mg/d or azathioprine ≥ 75 mg/d for ≥ 30 days. Statistical analysis included t tests, χ 2 tests, and one-way analysis of variance. Unadjusted and adjusted competing risks and Cox proportional hazards models were used to assess survival., Results: A total of 344 patients were identified with the following causative antigens: avian (n = 93; 27%), mold (n = 88; 26%), other (n = 15; 4%), and unknown (n = 148; 43%). Patient characteristics and lung function were similar among antigen groups with a mean FVC % predicted of 75 ± 20. The percent of patients treated with immunosuppression was similar between antigens with 58% of patients treated. There was no change in lung function or symptom scores with the initiation of immunosuppression in the full cohort. Immunosuppression was not associated with a change in survival for patients with avian or mold antigen (avian: hazard ratio, 0.41; 95% CI, 0.11-1.59; P = .20; mold: hazard ratio, 1.13; 95% CI, 0.26-4.97; P = .88). For patients with unknown causative antigen, survival was worse when treated with immunosuppression (hazard ratio, 2.65; 95% CI, 1.01-6.92; P = .047)., Interpretation: Response to immunosuppression varies by antigen type in patients with fHP. Additional studies are needed to test the role of immunosuppression in fHP, and particularly in those with an unknown antigen., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. W. W. reports personal fees from Boehringer Ingelheim and Astra Zeneca, outside the submitted work. V. M. reports personal fees from Boehringer Ingelheim Canada, Hoffman-La Roche Ltd, and Astra Zeneca; and reports grants from the University of Saskatchewan, Royal University Hospital Foundation, Boehringer Ingelheim, Astra Zeneca, and Hoffman-La Roche. D.-C. M. reports consultancy and speaking fees from Boehringer Ingelheim. B. Z. reports speaking fees from Boehringer Ingelheim and Abbvie. D. A. is supported by the Fonds de Recherche du Quebec en Santé, reports personal fees and grants from Boehringer Ingelheim, reports personal fees from Hoffmann-La Roche, and reports grants from the Canadian Institute for Health Research. K. A. J. reports grants from Boehringer Ingelheim, Pulmonary Fibrosis Society of Calgary, and University of Calgary School of Medicine; and reports personal fees from Boehringer Ingelheim, Roche, Three Lakes Foundation, Pliant Therapeutics, Theravance, and Blade Therapeutics. M. K. reports grants from the Canadian Institute for Health Research, Roche, Boehringer Ingelheim, Pieris, and Prometic; and reports personal fees from Boehringer Ingelheim, Roche, European Respiratory Journal, Belerophon, United Therapeutics, Nitto Denko, MitoImmune, Pieris, Abbvie, DevPro Biopharma, Horizon, Algernon, and CSL Behring. H. M. reports grants from Boehringer Ingelheim and Gilead. J. M. reports personal fees from Boehringer Ingelheim and Roche. C. J. R. reports grants from Boehringer Ingelheim; and reports personal fees from Astra Zeneca, Boehringer Ingelheim, Roche, Pliant Therapeutics, Cipla, and Veracyte. None declared (M. L. M., G. F., J. H. F., N. K., B. M., E. F.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the perception of immediately sequential bilateral cataract surgery (ISBCS) among Canadian ophthalmologists., Design: An anonymous survey was sent to all active members of the Canadian Ophthalmological Society., Methods: Basic demographic information, cataract surgery practice patterns, and perceived advantages, disadvantages, and concerns regarding ISBCS were collected from respondents., Results: A total of 352 ophthalmologists answered the survey. Among these, 94 respondents (27%) practice ISBCS routinely, 123 (35%) practice ISBCS in exceptional cases, and 131 (37%) do not practice ISBCS. ISBCS practitioners were significantly younger than nonpractitioners (p < 0.001) and had a shorter duration of practice (p < 0.001). The prevalence of ISBCS practitioners also varied significantly by province (p < 0.001): most practitioners who routinely practice ISBCS were from Quebec (n = 44; 48%), where financial disincentives are lowest in the country. The main work setting of ISBCS practitioners was academic centres (n = 39; 42%) as opposed to private or community settings (p < 0.001). The main reason for performing ISBCS was more efficient operating theatre use (n = 142; 65%). The main concerns regarding ISBCS were the risk of bilateral complications (n = 193; 57%) and the lack of refractive outcomes for second-eye surgery (n = 184; 52%). The COVID-19 pandemic positively influenced the view of 152 respondents (43%), but this was mostly among practitioners who already performed ISBCS routinely (n = 77; 84%)., Conclusions: ISBCS practitioners are more likely younger ophthalmologists working in academic centres. Quebec has the highest prevalence of ISBCS practitioners. ISBCS practitioners were positively influenced by the COVID-19 pandemic to offer ISBCS more often compared with non-ISBCS practitioners., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Formerly incarcerated people have exceptionally poor health profiles and are at increased risk of preventable mortality when compared with their general population peers. However, not enough is known about the epidemiology of mortality in this population-specifically the rates, causes, and timing of death in specific subgroups and regions-to inform the development of targeted, evidence-based responses. We aimed to document the incidence, timing, causes, and risk factors for mortality after release from incarceration., Methods: We analysed linked administrative data from the multi-national Mortality After Release from Incarceration Consortium (MARIC) study. We examined mortality outcomes for 1 471 526 people released from incarceration in eight countries (Australia, Brazil, Canada, New Zealand, Norway, Scotland, Sweden, and the USA) from 1980 to 2018, across 10 534 441 person-years of follow-up (range 0-24 years per person). We combined data from 18 cohort studies using two-step individual participant data meta-analyses to estimate pooled all-cause and cause-specific crude mortality rates (CMRs) per 100 000 person-years, for specific time periods (first, daily from days 1-14; second, weekly from weeks 3-12; third, weeks 13-52 combined; fourth, weeks 53 and over combined; and fifth, total follow-up) after release, overall and stratified by age, sex, and region., Findings: 75 427 deaths were recorded. The all-cause CMR during the first week following release (1612 [95% CI 1048-2287]) was higher than during all other time periods (incidence rate ratio [IRR] compared with week 2: 1·5 [95% CI 1·2-1·8], I 2 =26·0%, weeks 3-4: 2·0 [1·5-2·6], I 2 =53·0%, and weeks 9-12: 2·2 [1·6-3·0], I 2 =70·5%). The highest cause-specific mortality rates during the first week were due to alcohol and other drug poisoning (CMR 657 [95% CI 332-1076]), suicide (135 [36-277]), and cardiovascular disease (71 [16-153]). We observed considerable variation in cause-specific CMRs over time since release and across regions. Pooled all-cause CMRs were similar between males (731 [95% CI 630-839]) and females (660 [560-767]) and were higher in older age groups., Interpretation: The markedly elevated rate of death in the first week post-release underscores an urgent need for investment in evidence-based, coordinated transitional healthcare, including treatment for mental illness and substance use disorders to prevent post-release deaths due to suicide and overdose. Temporal variations in rates and causes of death highlight the need for routine monitoring of post-release mortality., Funding: Australia's National Health and Medical Research Council., Competing Interests: Declaration of interests RB declares salary and research support from an NHMRC Emerging Leadership-2 Investigator Grant (EL2; GNT2008073). MJS is a recipient of an Australian Research Council Future Fellowship (project number FT180100075) funded by the Australian Government. SLa is supported by a research scholar award from Fonds de recherche du Québec–Santé. JRA is supported by the US National Institutes of Health (R01 AI130058). RC, PK, and KT wish to acknowledge funding from a University of Otago research grant. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Pediatric pulmonary embolism (PE) is a rare event associated with significant morbidity and mortality. Awareness of clinical presentation and practices unique to children may aid clinicians in prompt identification and treatment., Objectives: To describe the incidence, risk factors, clinical presentation, diagnostic and therapeutic practices, and short-term outcomes of pediatric PE., Methods: We conducted a 3-year national surveillance study through the Canadian Pediatric Surveillance Program. Over 2800 pediatric specialists and subspecialists were contacted monthly from 2020 to 2022 and requested to report all new cases of PE in patients up to 18 years of age. Case-specific data were obtained through voluntary completion of a detailed questionnaire., Results: Fifty-eight cases (78% female, n = 45) were reported (2.4 cases per million children), with rates highest in adolescents 15 to 18 years (6.6 cases per million). Detailed information, available for 31 (53%) cases, documented at least 1 risk factor in 28 (90%) cases; 24 (77%) patients presented with 2 or more symptoms. Computed tomography pulmonary angiography was used for diagnostic confirmation in 25 (81%) cases. Anticoagulation was initiated in 24 (77%) of 31 cases; fewer than 5 patients underwent thrombolysis or surgical interventions. Of 28 patients who received therapeutic interventions, 8 (29%) experienced treatment-related complications. Fewer than 5 mortalities were reported., Conclusion: Pediatric PE is a rare event, with female adolescents at the highest risk. Although the presentation is often nonspecific, clinicians should maintain a high index of suspicion, particularly in patients with risk factors and when other diagnoses that may explain symptoms have been excluded., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is evidence that women with congenital anomalies are at risk of having an infant with the same defect. However, the risk of having an infant with a different type of defect is less well described., Aims: We evaluated the extent to which offspring of women with congenital anomalies were at risk of having a birth defect, including defects that were similar to or different from their mother's., Methods: We analyzed a retrospective cohort of 1,311,532 infants born in Canada between 2006 and 2022. The exposure was a maternal congenital anomaly, and the outcome included birth defects in the newborn. We estimated risk ratios (RR) and confidence intervals (CI) for the association of specific maternal anomalies with the risk of having an infant with a similar or different defect using log-binomial regression models adjusted for patient characteristics., Results: While mothers with anomalies were at risk of having an infant with the same defect, associations with other types of defects were not as strong. For example, compared with no maternal anomaly, maternal urogenital defects were associated with up to 45 times the risk of having an infant with a similar urogenital defect (RR 45.33, 95 % CI 31.92-64.36), but <2 times the risk of having an infant with orofacial clefts (RR 1.89, 95 % CI 1.07-3.34) and clubfoot (RR 1.36, 95 % CI 1.02-1.81)., Conclusion: The findings suggest that maternal congenital anomalies are only weakly associated with occurrence of a different type of defect in offspring., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)