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Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population.

Accurate estimates of gestational age (GA) at birth are important for preterm birth surveillance but can be challenging to obtain in low income countries. Our objective was to develop machine learning models to accurately estimate GA shortly after birth using clinical and metabolomic data. We derived three GA estimation models using ELASTIC NET multivariable linear regression using metabolomic markers from heel-prick blood samples and clinical data from a retrospective cohort of newborns from Ontario, Canada. We conducted internal model validation in an independent cohort of Ontario newborns, and external validation in heel prick and cord blood sample data collected from newborns from prospective birth cohorts in Lusaka, Zambia and Matlab, Bangladesh. Model performance was measured by comparing model-derived estimates of GA to reference estimates from early pregnancy ultrasound. Samples were collected from 311 newborns from Zambia and 1176 from Bangladesh. The best-performing model accurately estimated GA within about 6 days of ultrasound estimates in both cohorts when applied to heel prick data (MAE 0.79 weeks (95% CI 0.69, 0.90) for Zambia; 0.81 weeks (0.75, 0.86) for Bangladesh), and within about 7 days when applied to cord blood data (1.02 weeks (0.90, 1.15) for Zambia; 0.95 weeks (0.90, 0.99) for Bangladesh). Algorithms developed in Canada provided accurate estimates of GA when applied to external cohorts from Zambia and Bangladesh. Model performance was superior in heel prick data as compared to cord blood data.

Since Canadian Blood Services (CBS) developed policy guidance in 2019 for organ and tissue donation after medical assistance in dying (MAiD), the federal government has made changes to legislation related to MAiD. This document provides updated guidance for clinicians, organ donation organizations, end-of-life care experts, MAiD providers and policy-makers on the impact of these changes. Canadian Blood Services assembled a group of 63 experts from critical care, organ and tissue donation, health care administration, MAiD, bioethics, law and research to review the legislative changes in the Organ and Tissue Donation After Medical Assistance in Dying – Guidance for Policy forum. Two patients who had requested and been found eligible for MAiD and 2 family members of patients who had donated organs after MAiD were also included as participants. In a series of 3 online meetings from June 2021 to April 2022, forum participants addressed a variety of topics in small and large groups. These discussions were informed by a comprehensive scoping review using JBI methodology. We used an adapted form of nominal group technique to develop the recommendations, which were approved by consensus of the participants. Management of competing interests was in accordance with Guideline International Network principles. Although many of the recommendations from the guidance developed in 2019 are still relevant, this guidance provides 2 updated recommendations and 8 new recommendations in the following areas: referral to an organ donation organization, consent, directed and conditional donation, MAiD procedures, determination of death, health care professionals and reporting. Policies and practices for organ and tissue donation after MAiD in Canada should align with current Canadian legislation. This updated guidance will help clinicians navigate the medical, legal and ethical challenges that arise when they support patients pursuing donation after MAiD.

The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Recommandations: Meme si bon nombre des recommandations du document d'orientation de 2019 demeurent pertinentes, la presente mise a jour a permis d'en actualiser 2 et d'en formuler 8 nouvelles dans les domaines suivants: aiguillage vers un organisme de don d'organes, consentement, dons diriges et conditionnels, procedure d'AMM, determination du deces, equipes soignantes et preparation de rapports.

In Canada, vaccine safety studies are often conducted at the provincial/territorial level where the primary data on vaccination reside. Combining health services data from multiple jurisdictions using a pooled data analytic approach would reduce the amount of time needed to detect vaccine safety signals. To determine the difference in the time it would take to identify safety signals using different proportions of the Canadian population, we conducted power and sample size calculations for a hypothetical self-controlled case series-based surveillance analysis. We used scenarios modeled after the real-world examples of myocarditis and vaccine-induced immune thrombotic thrombocytopenia (VITT) following COVID-19 vaccination as our base cases. Our calculations demonstrated that in the case of a myocarditis-type event, a pooled analysis would reduce the time needed to detect a safety signal by over 60% compared to using Ontario data alone. In the case of a VITT-type event, a pooled analysis could detect a safety signal 49 days sooner than using Ontario data alone, potentially averting as many as 30 events. Our analysis demonstrates that there is substantial value in using pan-Canadian health services data to evaluate the safety of vaccines. Efforts should be made to develop a pan-Canadian vaccine data source to allow for an earlier evaluation of suspected adverse events following immunization.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists’ Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

In Canada, organ donation from deceased donors is a common practice that saves or improves the lives of more than nearly 2000 Canadians every year, accounting for more than 3 of 4 of all transplanted organs. Deceased donation is permitted after either neurologic or circulatory determination of death, with the latter accounting for 25% of all organs donated in Canada in 2017.1 The current Canadian guideline recommendations for donation after circulatory determination of death, published in 2006, address the conventional scenario of an unconscious, incapable, critically ill patient not expected to survive the withdrawal of life-sustaining measures. The target audience of this guidance consists of clinicians, organ donation organizations, end-of-life care experts, medical assistance in dying providers and policy-makers. This document is intended to inform policies related to offering organ and tissue donation to patients who have made a decision that will lead to imminent death.

Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle. Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. Regeneration occurs through robust proliferation of cardiomyocytes localized at the leading epicardial edge of the new myocardium. The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Thus, injury-induced cardio-myocyte proliferation in zebrafish can overcome scar formation, allowing cardiac muscle regeneration. These findings indicate that zebrafish will be useful for genetically dissecting the molecular mechanisms of cardiac regeneration.

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa.