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Summary: Background: Liver disease is an increasing burden on population health globally. Aims: To characterise burden of liver disease among general internal medicine inpatients at seven Toronto‐area hospitals and compare it to other common medical conditions. Methods: Data from April 2010 to October 2017 were obtained from hospitals participating in the GEMINI collaborative. Using these cohort data from hospital information systems linked to administrative data, we defined liver disease admissions using most responsible discharge diagnoses categorised according to international classification of diseases, 10th Revision—enhanced Canadian version (ICD‐10‐CA). We identified admissions for heart failure, chronic obstructive pulmonary disease (COPD) and pneumonia as comparators. We calculated standardised mortality ratios (SMRs) as the ratio of observed to expected deaths. Results: Among 239 018 discharges, liver disease accounted for 1.7% of most responsible discharge diagnoses. Liver disease was associated with marked premature mortality, with SMR of 8.84 (95% CI 8.06‐9.67) compared to 1.06 (95% CI 0.99‐1.12) for heart failure, 1.05 (95% CI 0.96‐1.15) for COPD and 1.28 (95% CI 1.20‐1.37) for pneumonia. The majority of deaths were among patients younger than 65 years (57.7%) compared to 3.3% in heart failure, 5.6% in COPD and 10.7% in pneumonia. Liver disease patients presented with worse Laboratory‐Based Acute Physiology Scores, were more frequently admitted to the intensive care unit (14.4%), incurred higher average total costs (median $6723 CAD), had higher in‐hospital mortality (11.4%), and were more likely to be a readmission from 30 days prior (19.8%). Non‐alcoholic fatty liver disease admissions increased from 120 in 2011‐2012 to 215 in 2016‐2017 (P < 0.01). Conclusion: In Canada's largest urban centre, liver disease admissions resulted in premature morbidity and mortality with higher resource use compared to common cardio‐respiratory conditions. Re‐evaluation of approaches to caring for inpatients with liver disease is timely and justified. [ABSTRACT FROM AUTHOR]

Background: Multi-disciplinary heart failure (HF) clinics have been shown to improve outcomes for HF patients in randomized clinical trials. However, it is unclear how widely available specialized HF clinics are in Ontario. Also, the service models of current clinics have not been described. It is therefore uncertain whether the efficacy of HF clinics in trials is generalizable to the HF clinics currently operating in the province. Methods: As part of a comprehensive evaluation of HF clinics in Ontario, we performed an environmental scan to identify all HF clinics operating in 2010. A semi-structured interview was conducted to understand the scope of practice. The intensity and complexity of care offered were quantified through the use of a validated instrument, and clinics were categorized as high, medium or low intensity clinics. Results: We identified 34 clinics with 143 HF physicians. We found substantial regional disparity in access to care across the province. The majority of HF physicians were cardiologists (81%), with 81% of the clinics physically based in hospitals, of which 26% were academic centers. There was a substantial range in the complexity of services offered, most notably in the intensity of education and medication management services offered. All the clinics focused on ambulatory care, with only one having an in-patient focus. None of the HF clinics had a home-based component to care. Conclusions: Multiple HF clinics are currently operating in Ontario with a wide spectrum of care models. Further work is necessary to understand which components lead to improved patient outcomes. [ABSTRACT FROM AUTHOR]

The prevalence of anxiety disorders continues to increase in Canada. The study aimed to evaluate sex differences in the prevalence of anxiety disorders, associated identity factors and social determinants, and their interactions among the Canadian population. We used data from the 2017–2018 Canadian Community Health Survey (CCHS), a nationally representative survey. We evaluated associations between sex, other identity characteristics and social determinants, and anxiety disorders using multivariable logistic regression. To account for the complex sampling design, we applied sampling and bootstrap weights. The CCHS included 113,290 respondents, representative of 98% of the Canadian population over 12 years old. The prevalence of self-reported anxiety disorders was higher among females than males (11.6% vs 6.3%, p < 0.001). Adjusted regression analysis revealed higher odds of having mood disorders for those who were female, non-White, non-immigrant, homosexual or bisexual, unemployed, had lower income or food insecurity, had a disability and a weak sense of community belonging. Younger age was associated with higher odds of anxiety disorders among females (aOR: 1.50, 95%CI: 1.10–2.05) but not among males (aOR: 0.99, 95%CI: 0.64–1.56). An association between employment and higher income with lower odds of anxiety disorders, and bisexuality with higher odds of anxiety disorders, was stronger among males compared with females. Anxiety disorders are more prevalent among females than males in Canada. Age, employment, income, and sexual orientation have varying associations with anxiety disorders among the sexes. Strategies for improving mental health must recognize the complex links between sex and intersecting factors. • The prevalence of anxiety disorders in Canada is significantly higher among females. • The association of younger age with anxiety disorders is stronger among females. • Bisexuality has a stronger association with anxiety disorders among males. • Income is more strongly associated with anxiety disorders in males. [ABSTRACT FROM AUTHOR]

We assessed the sex-differences in the prevalence and associated factors of mood disorders in Canada using a nationally representative survey, focusing on identity characteristics and socioeconomic factors. A secondary analysis of the 2017–2018 Canadian Community Health Survey (CCHS) - Annual Component was conducted using Gender-Based Analysis Plus, which is an analytical process for incorporating various intersecting identity factors into research, programs, and policies. The presence of mood disorders was assessed through self-reporting. Factors associated with mood disorders were evaluated using multivariable logistic regression analysis after the application of sampling and bootstrap weights. The CCHS was completed by 113,290 Canadians, representative of 98 % of the population over the age of 12. Self-reported mood disorders were more prevalent among females than males (11.0 % vs 6.4 %, p < 0.001). Adjusted regression analysis revealed higher odds of reporting mood disorders for those who were female, unemployed, non-immigrant, non-White, smokers, homosexual or bisexual, had lower income, suffered from food insecurity, had a disability and weak sense of community belonging. Employment and higher income were more protective against mood disorders among males than females, and the association of older age with mood disorders was stronger in males than in females. Mood disorders were assessed through self-reporting, and certain population groups were excluded from the survey. Females in Canada are affected by mood disorders at higher rates than males and certain factors have differential associations with mood disorders among the sexes. Strategies targeting mental disorders must be tailored towards the needs of specific groups. • Mood disorders affect females in Canada at significantly higher rates than males. • Older age is more strongly associated with mood disorders among males. • Employment and higher income are more protective against mood disorders among males. [ABSTRACT FROM AUTHOR]

Purpose: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer., Methods: The economic evaluation, conducted from societal and health care payer perspectives, used a 12-month time horizon. The Canadian 5C study randomly assigned patients to receive GAM or UC. Quality-adjusted life-years (QALYs) were measured using the EuroQol five dimension-5L questionnaire and health care utilization using cost diaries and chart reviews. We evaluated the incremental net monetary benefit (INMB) for the full sample and preselected subgroups., Results: A total of 350 patients were included, of whom 173 received GAM and 177 UC. At 12 months, the average QALYs per patient were 0.728 and 0.751 for GAM and UC, respectively (ΔQALY, -0.023 [95% CI, -0.076 to 0.028]). Considering a societal perspective, the total average costs (in 2021 Canadian dollars) per patient were $46,739 and $45,177 for GAM and UC, respectively (ΔCost, $1,563 [95% CI, -$6,583 to $10,403]). At a cost-effectiveness threshold of $50,000/QALY, GAM was not cost-effective compared with UC (INMB, -$2,713 [95% CI, -$11,767 to $5,801]). The INMB was positive ($2,984 [95% CI, -$7,050 to $14,179]; probability of being cost-effective, 72%) for patients treated with curative intent, but remained negative for patients treated with palliative intent (INMB, -$9,909 [95% CI, -$24,436 to $4,153]). Findings were similar considering a health care payer perspective., Conclusion: To our knowledge, this is the first cost-utility analysis of GAM in cancer. GAM was cost-effective for patients with cancer treated with curative but not with palliative intent. The study provides further considerations for future adoption of GAM in practice.

Background: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies show variable efficacy for patients with CF. Patient-derived predictive tools may identify individuals likely to respond to CFTRs, but are not in routine use. We aimed to determine the cost-utility of predictive tool-guided treatment with CFTRs as add-on to standard of care (SoC) for individuals with CF., Methods: This economic evaluation compared two strategies using an individual level simulation: (i) Treat All, where all patients received CFTRs plus SoC and (ii) Test→Treat, where patients who tested positive on predictive tools received CFTRs plus SoC and those who tested negative received SoC only. We simulated 50,000 individuals over their lifetime, and estimated costs (2020 CAD) per quality-adjusted life year (QALY) from the healthcare payer's perspective, discounted at 1.5% annually. The model was populated using Canadian CF registry data and published literature. Probabilistic and deterministic sensitivity were conducted., Results: The Treat All and Test→Treat and strategies yielded 22.41 and 21.36 QALYs, and cost $4.21 M and $3.15 M respectively. Results of probabilistic sensitivity analysis showed that Test→Treat was highly cost-effective compared to Treat All in 100% of simulations at cost-effectiveness thresholds as high as $500,000 per QALY. Test→Treat may save between $931 K to $1.1 M per QALY lost, depending on sensitivity and specificity of predictive tools., Conclusion: The use of predictive tools could optimize the health benefits of CFTR modulators while reducing costs. Our findings support the use of pre-treatment predictive testing and may help inform coverage and reimbursement policies for individuals with CF., Competing Interests: Declaration of Competing Interests Felix Ratjen acts as an advisor to Vertex Pharmaceuticals; Drs. Sahakyan Y, Abrahamyan L, Bear C, Strug L, Eckford P, Peel J, Krahn M, Sander B: no conflicts, (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background and Aims: We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC)., Approach and Results: Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event-free and liver transplantation-free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed-effects regression. Health-related quality of life was assessed using the Short Form 36, the PBC-40 questionnaire, and the 5-D Itch scale and analyzed using mixed-effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant-free and event-free survival compared to White patients (HR, 3.66; 95% CI, 2.23-6.01; HR, 3.09; 95% CI, 1.94-4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow-up., Conclusions: Indigenous Canadians with PBC present with advanced disease and have worse long-term outcomes compared to White patients., (© 2022 American Association for the Study of Liver Diseases.)

Purpose: To evaluate the perceptions and practices of Canadian cardiovascular anesthesiologists and intensivists towards intravenous albumin as a resuscitation fluid in patients undergoing cardiac surgery., Methods: We conducted a cross-sectional survey of cardiac anesthesiologists and intensivists involved in the care of cardiac surgical patients. The 22-item survey included seven open-ended questions and assessed practice patterns and attitudes towards albumin. Descriptive statistics were analyzed using counts and proportions. Qualitative data were analyzed to identify themes describing albumin use patterns in Canada., Results: A total of 133 respondents from seven provinces participated, with 83 (62%) using albumin perioperatively. The majority of respondents (77%) felt a low fluid balance in cardiac surgical patients was important, and that supplementing crystalloids with albumin was helpful for this objective (67%). There was poor agreement among survey respondents regarding the role of albumin for faster vasopressor weaning or intensive care discharge, and ≥ 90% did not feel albumin reduced mortality, renal injury, or coagulopathy. Nevertheless, cardiac surgical patients were identified as a distinct population where albumin may help to minimize fluid balance. There was an acknowledged paucity of formal evidence supporting possible benefits. Fewer than 10% of respondents could identify institutional or national guidelines for albumin use. A lack of evidence supporting albumin use in cardiac surgical patients, especially those at highest risk of complications, was a frequently identified concern., Conclusions: The majority of Canadian anesthesiologists and intensivists (62%) use albumin in cardiac surgical patients. There is clinical equipoise regarding its utility, and an acknowledged need for higher quality evidence to guide practice., (© 2022. Canadian Anesthesiologists' Society.)

Background: Hemophilia A is a rare, sex-linked genetic disorder treated with intravenous administration of factor VIII (FVIII) to prevent bleeding; however, approaches vary across and within countries. Value-of-information (VOI) methods identify situations in which the cost-benefit evidence is sufficient to adopt one treatment strategy over another; when the evidence is insufficient, VOI methods provide the optimal sample size for additional research., Objective: The objective of the study was to use VOI methods in a cost-benefit decision context to evaluate the current evidence in support of using (1) alternate day prophylaxis (AP), (2) tailored prophylaxis (TP) or (3) on-demand treatment (OD) with FVIII to prevent arthropathy in children with severe hemophilia A., Methods: To apply VOI methods, several parameters such as incidence, time horizon for the decision, costs, and threshold values to avoid MRI-detected joint damage or arthropathy were defined. Two baseline threshold values of willingness to pay for avoiding arthropathy--$200,000 and $400,000--were selected for comparing the treatment strategies., Results: For threshold values < $200,000, OD had a higher expected net benefit than either prophylaxis strategy, and the evidence was sufficient for its adoption. For threshold values > $400,000 prophylaxis strategies had higher expected net benefit; however, a new trial with 38 patients per arm was needed to compare AP and TP, yielding an expected net gain of over $17 million. In sensitivity analyses, the results were robust to assumptions regarding discount rate, trial fixed and variable costs, enrollment fraction, and the time horizon., Conclusions: In rare diseases, evidence is often scarce and insufficient for decision making. In considering the funding of new research and patient reimbursement in rare diseases, VOI methodology may provide more relevant determinations of the value and costs of additional research, compared to standard frequentist methods.