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Indices of aggressive or supportive end-of-life (EOL) care are used to evaluate health services quality. Disparities according to sex were previously described, with studies showing that male sex is associated with aggressive EOL care. This is a secondary analysis of 69,983 patients who died of a GI malignancy in Ontario between 2006 and 2018. Quality indices from the last 14–30 days of life and aggregate measures for aggressive and supportive EOL care were derived from administrative data. Hospitalizations, emergency department use, intensive care unit admissions, and receipt of chemotherapy were considered indices of aggressive care, while physician house call and palliative home care were considered indices of supportive care. Overall, a smaller proportion of females experienced aggressive care at EOL (14.3% vs. 19.0%, standardized difference = 0.13, where ≥0.1 is a meaningful difference). Over time, rates of aggressive care were stable, while rates of supportive care increased for both sexes. Logistic regression showed that younger females (ages 18–39) had increased odds of experiencing aggressive EOL care (OR 1.71, 95% CI 1.30–2.25), but there was no such association for males. Quality of EOL care varies according to sex, with a smaller proportion of females experiencing aggressive EOL care. [ABSTRACT FROM AUTHOR]

Aim: To assess this risk of SARS-CoV-2 infection among Ontario physicians by specialty and in comparison with nonphysician controls during the COVID-19 pandemic. Methods: In this retrospective cohort study, the primary outcome was incident SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR). Secondary outcomes were hospitalization, use of critical care, and mortality. Results: From March 1, 2020 to December 31, 2022, 6172/30 617 (20%) active Ontario physicians tested positive for SARS-CoV-2. Infection was less likely if physicians were older (OR 0.78 [0.76-0.81] per 10 years), rural residents (OR 0.70 [0.59-0.83]), and lived in more marginalized neighborhoods (OR 0.74 [0.62-0.89]), but more likely if they were female (OR 1.14 [1.07-1.22]), worked in long-term care settings (OR 1.16 [1.02-1.32]), had higher patient volumes (OR 2.05 [1.82-2.30] for highest vs lowest), and were pediatricians (OR 1.25 [1.09-1.44]). Compared with communitymatched controls (n = 29 763), physicians had a higher risk of infection during the first two waves of the pandemic (OR 1.38 [1.20-1.59]) but by wave 3 the risk was no longer significantly different (OR 0.93 [0.83-1.05]). Physicians were less likely to be hospitalized within 14 days of their first positive PCR test than non-physicians (P < 0.0001), but there was no difference in the use of critical care (P = 0.48) or mortality (P = 0.15). Conclusion: Physicians had higher rates of infection than community-matched controls during the first two waves of the pandemic in Ontario, but not from wave 3 onward. Physicians practicing in long-term care facilities and pediatricians were more likely to test positive for SARS-CoV-2 than other physicians. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV). Observational cohort studies or single arms of clinical trials were eligible. MEDLINE, EMBASE and CENTRAL were systematically searched from their respective dates of inception to January 2023. No exclusions were made based on date of publication, study outcomes, or study language. The study populations composed of adult patients (≥18 years old) with amyloid cardiomyopathy. All studies included the use of CMR with and without intravenous gadolinium contrast administration to assess myocardial native T1 mapping, T2 mapping, and ECV in association with the pre-specified primary outcome of all-cause mortality. Data were extracted from eligible primary studies by two independent reviewers and pooled via the inverse variance method using random effects models for meta-analysis. A total of 3852 citations were reviewed. A final nine studies including a total of 955 patients (mean age 65 ± 10 years old, 32% female, mean left ventricular ejection fraction (LVEF) 59 ± 12% and 24% had NYHA class III or IV symptoms) with cardiac amyloidosis [light chain amyloidosis (AL) 50%, transthyretin amyloidosis (ATTR) 49%, other 1%] were eligible for inclusion and suitable for data extraction. All included studies were single centered (seven with 1.5 T MRI scanners, two with 3.0 T MRI scanners) and non-randomized in design, with follow-up spanning from 8 to 64 months (median follow-up = 25 months); 320 patients died during follow-up, rendering a weighted mortality rate of 33% across studies. Compared with patients with AL amyloid, patients with ATTR amyloid had significantly higher mean left ventricular mass index (LVMi) (102 ± 34 g/m2 vs 127 ± 37 g/m2, p = 0.02). N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T levels, mean native T1 values, ECV and T2 values did not differ between patients with ATTR amyloid and AL amyloid (all p > 0.25). Overall, the hazard ratios for mortality were 1.33 (95% CI = [1.10, 1.60]; p = 0.003; I 2 = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], p < 0.0001; I 2 = 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; I 2 = 0%) for myocardial-to-skeletal T2 ratio below the mean (vs above the mean). Higher native T1 time and ECV, and lower myocardial to skeletal T2 ratio, on CMR are associated with worse mortality in patients with cardiac amyloidosis. Therefore, tissue mapping using CMR may offer a useful non-invasive technique to monitor disease progression and determine prognosis in patients with cardiac amyloidosis. • In this meta-analysis of nine studies of cardiac MRI (CMR) in cardiac amyloidosis, patients with cardiac amyloidosis have high mortality rate. • Every 3% increase in myocardial extracellular volume on CMR corresponds to 16% relative increase in mortality risk. • Every 60 ms increase in myocardial T1 time on CMR corresponds to 33% relative increase in mortality risk. • Lower myocardial to skeletal T2 ratio is associated with a higher mortality rate. • Therefore, CMR is a useful tool for prognostication in patients with cardiac amyloidosis. [ABSTRACT FROM AUTHOR]

A health technology assessment (HTA) does not systematically account for the circumstances and needs of children and youth. To supplement HTA processes, we aimed to develop a child-tailored value assessment framework using a multicriteria decision analysis approach. We constructed a multicriteria-decision-analysis-based model in multiple phases to create the Comprehensive Assessment of Technologies for Child Health (CATCH) framework. Using a modified Delphi process with stakeholders having broad disciplinary and geographic variation (N = 23), we refined previously generated criteria and developed rank-based weights. We established a criterion-pertinent scoring rubric for assessing incremental benefits of new drugs. Three clinicians independently assessed comprehension by pilotscoring 9 drugs. We then validated CATCH for 2 childhood cancer therapies through structured deliberation with an expert panel (N = 10), obtaining individual scores, consensus scores, and verbal feedback. Analyses included descriptive statistics, thematic analysis, exploratory disagreement indices, and sensitivity analysis. The modified Delphi process yielded 10 criteria, based on absolute importance/relevance and agreed importance (median disagreement indices = 0.34): Effectiveness, Child-specific Health-related Quality of Life, Disease Severity, Unmet Need, Therapeutic Safety, Equity, Family Impacts, Life-course Development, Rarity, and Fair Share of Life. Pilot scoring resulted in adjusted criteria definitions and more precise score-scaling guidelines. Validation panelists endorsed the framework's key modifiers of value. Modes of their individual prescores aligned closely with deliberative consensus scores. We iteratively developed a value assessment framework that captures dimensions of child-specific health and nonhealth gains. CATCH could improve the richness and relevance of HTA decision making for children in Canada and comparable health systems. • Health technology assessment (HTA) methods for child health technologies are challenged by evidentiary limitations and incomplete consideration of the unique biological and social circumstances and needs of children and youth. Multicriteria decision analysis has emerged as an HTA tool for explicitly considering nonconventional values. • This article presents novel child-specific value assessment criteria based in societal preferences, which reflect the importance of family impacts and long-term flourishing of children beyond immediate health gains obtained through treatment. • A child-tailored multicriteria decision analysis approach facilitating HTA deliberations may broaden the normative lens through which child health technologies are evaluated, contributing to more comprehensive and relevant decision making. [ABSTRACT FROM AUTHOR]

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug's safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11–16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3–15.4%), neutropenia was 7.1% (95% CI, 4.6–10.4%), and anemia was 11.3% (95% CI, 8.0–15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the impact of marginalization on DLBCL overall survival (OS) within the Canadian setting. We conducted a population-based retrospective cohort study of adult patients with newly diagnosed DLBCL in Ontario between 1 January 2005 and 31 December 2017 receiving a rituximab-containing chemotherapy regimen with curative intent followed until 1 March 2020. Our primary exposure of interest was the Ontario Marginalization Index (ON-Marg). The primary outcome was 2-year OS, accounting for patient age, sex, cancer characteristics, comorbidity burden, and rural dwelling status. While two-year overall survival was inferior for individuals in the most deprived marginalization quintile (70.4% Q5 vs. 76.0% Q1), after adjustment for relevant covariates neither the composite ON-Marg nor any of its dimensions had a significant effect. Within the Canadian context, among patients who receive chemotherapy, marginalization may not have a significant association with overall survival when accounting for key patient covariates, lending support for preserved outcomes. [ABSTRACT FROM AUTHOR]

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020–2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers. [ABSTRACT FROM AUTHOR]

Background: Ontario publicly funds reference trastuzumab (Herceptin) and four biosimilar trastuzumab products for adjuvant treatment of HER2+ breast cancer. We assessed the real-world safety and effectiveness of biosimilar trastuzumab compared to Herceptin for adjuvant treatment of patients with HER2+ breast cancer. Methods: This was a population-based, retrospective study comparing the safety and effectiveness of biosimilar trastuzumab and Herceptin for neoadjuvant/adjuvant treatment of HER2+ breast cancer from 2016 to 2021. Treatment patients started biosimilar trastuzumab from November 2019 to June 2021; historical comparator patients started Herceptin from June 2016 to October 2019. Safety outcomes death within 30 days of last dose of trastuzumab, direct hospitalization, emergency department visit leading to hospitalization, early treatment discontinuation, and in-patient admission for congestive heart failure were measured using logistic/negative binomial regression. Overall survival (OS) was measured using Kaplan–Meier methods and Cox proportional hazards regression. Propensity score matching was applied. Results: From June 2016 to 2021, 5071 patients with breast cancer were treated with neoadjuvant/adjuvant trastuzumab. The rate of direct hospitalization (RR: 0.85, 95% CI: 0.74–0.98, p-value: 0.032) was significantly lower in biosimilar compared to Herceptin patients. OS (log-rank test p = 0.98) and risk of mortality (HR: 1.29, 95% CI: 0.72–2.30, p-value = 0.39) did not significantly differ between treatment groups. Conclusions: Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars and demonstrate the value of real-world evidence generation for supporting biosimilar implementations and reassessments. [ABSTRACT FROM AUTHOR]

Aim: This pilot study examined the feasibility, safety, and effects of a Nintendo Ring Fit Adventure™‐based exercise program to enhance balance and lower limb muscle strength in community‐dwelling older adults with a history of falls. Methods: In total, 42 older adults who experienced at least one fall in the past year were randomly assigned to an experimental or control group. Participants in the experimental group performed 60‐min sessions of the exercise program twice per week for 8 weeks. The control group received usual care. We assessed the feasibility (retention and adherence to the exercise program), safety (number of adverse events), and clinical outcomes: (1) balance (Mini‐BESTest); (2) functional lower limb muscle strength (Five‐Time Sit‐to‐Stand test); (3) mobility (Timed‐Up and Go test); (4) dual‐task ability (Timed‐Up and Go test – Dual Task); (5) fear of falling (Icon‐FES); and (6) executive function (Color Trails Test). Results: Thirty‐one participants (74%) completed the 8‐week assessment. No adverse event associated with the exercise program was reported. There was a significant interaction in the anticipatory domain score of the Mini‐BESTest between the experimental and control groups over the 8 weeks (P = 0.019). Conclusions: The Nintendo Ring Fit Adventure™‐based exercise program was feasible, safe, and potentially effective in improving anticipatory balance in community‐dwelling older fallers. Geriatr Gerontol Int 2024; 24: 334–341. [ABSTRACT FROM AUTHOR]

Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease therapy. Here, we present two cases of fetal hyperthyroidism with maternal hypothyroidism and review the assessment and intrauterine therapy for fetal hyperthyroidism. Both women were referred at 22+ and 23+ weeks of gestation with abnormal ultrasound findings, including fetal heart enlargement, pericardial effusion, and fetal tachycardia. Both women had a history of Graves disease while in a state of hypothyroidism with a high titer of TRAb. A sonographic examination showed a diffusely enlarged fetal thyroid with abundant blood flow. Invasive prenatal testing revealed no significant chromosomal aberration. Low fetal serum TSH and high TRAb levels were detected in the cord blood. Fetal hyperthyroidism was considered, and maternal oral methimazole (MMI) was administered as intrauterine therapy, with the slowing of fetal tachycardia, a reduction in fetal heart enlargement, and thyroid hyperemia. During therapy, maternal thyroid function was monitored, and the dosage of maternal levothyroxine was adjusted accordingly. Both women delivered spontaneously at 36+ weeks of gestation, and neonatal hyperthyroidism was confirmed in both newborns. After methimazole and propranolol drug treatment with levothyroxine for 8 and 12 months, both babies became euthyroid with normal growth and development. [ABSTRACT FROM AUTHOR]