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Background: The response of Canada's research community to the COVID-19 pandemic provides a unique opportunity to examine the country's clinical health research ecosystem. We sought to describe patterns of enrolment across Canadian Institutes of Health Research (CIHR)-funded studies on COVID-19., Methods: We identified COVID-19 studies funded by the CIHR and that enrolled participants from Canadian acute care hospitals between January 2020 and April 2023. We collected information on study-and site-level variables from study leads, site investigators, and public domain sources. We described and evaluated factors associated with cumulative enrolment., Results: We obtained information for 23 out of 26 (88%) eligible CIHR-funded studies (16 randomized controlled trials [RCTs] and 7 cohort studies). The 23 studies were managed by 12 Canadian and 3 international coordinating centres. Of 419 Canadian hospitals, 97 (23%) enrolled a total of 28 973 participants - 3876 in RCTs across 78 hospitals (median cumulative enrolment per hospital 30, interquartile range [IQR] 10-61), and 25 097 in cohort studies across 62 hospitals (median cumulative enrolment per hospital 158, IQR 6-348). Of 78 hospitals recruiting participants in RCTs, 13 (17%) enrolled 50% of all RCT participants, whereas 6 of 62 hospitals (9.7%) recruited 54% of participants in cohort studies., Interpretation: A minority of Canadian hospitals enrolled the majority of participants in CIHR-funded studies on COVID-19. This analysis sheds light on the Canadian health research ecosystem and provides information for multiple key partners to consider ways to realize the full research potential of Canada's health systems., Competing Interests: Competing interests:: Christopher Yarnell reports receiving a Vanier Scholarship from the Canadian Institutes of Health Research (CIHR), outside the submitted work. Kathryn Rowan reports holding the role of programme director, Health & Social Care Delivery Research Programme, UK National Institute for Health and Care Research (NIHR), a part-time, paid secondment from the Intensive Care National Audit and Research Centre. Kusum Menon reports receiving salary support from a CHEO Foundation Research Chair in Pediatric Intensive Care Medicine. Dr. Menon has also received a CIHR grant for researching stress hydrocortisone in pediatric septic shock. Dr. Menon is the chair of the Canadian Critical Care Trials Group. Robert Fowler reports receiving a grant from CIHR in support of the COVID-19 Network of Clinical Trials Networks. Alison Fox-Robichaud is the nominated principal applicant and holder of the CIHR Sepsis Canada network grant. As scientific director of Sepsis Canada, Dr. Fox-Robichaud also reports receiving additional support from McMaster University and Hamilton Health Sciences. John Marshall reports receiving support from CIHR in support of the current manuscript. Dr. Marshall has also participated on a data safety monitoring or advisory board for the AM Pharma REVIVAL Trial and the SHIPSS Trial, and is the chair of the International Forum for Acute Care Trialists. Michelle Kho reports receiving support as the Canada Research Chair in Critical Care Rehabilitation and Knowledge Translation and from Sepsis Canada and the COVID-19 Network of Clinical Trials Networks, in support of the current manuscript. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: There have been multiple waves in the COVID-19 pandemic in many countries. We sought to compare mortality and respiratory, cardiovascular and renal dysfunction between waves in 3 Canadian provinces., Methods: We conducted a substudy of the ARBs CORONA I study, a multicentre Canadian pragmatic observational cohort study that examined the association of pre-existing use of angiotensin receptor blockers with outcomes in adults admitted to hospital with acute COVID-19 up to April 2021 from 9 community and teaching hospitals in 3 Canadian provinces (British Columbia, Ontario and Quebec). We excluded emergency department admissions without hospital admission, readmissions and admissions for another reason. We used logistic and 0-1-inflated β regression models to compare 28-day and in-hospital mortality, and the use of invasive mechanical ventilation, vasopressors and renal replacement therapy (RRT) between the first 3 waves of the COVID-19 pandemic in these provinces., Results: A total of 520, 572 and 245 patients in waves 1, 2 and 3, respectively, were included. Patients in wave 3 were on average younger and had fewer comorbidities than those in waves 1 and 2. The unadjusted 28-day mortality rate was significantly lower in wave 3 (7.8%) than in wave 1 (18.3%) (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.24-0.78) and wave 2 (16.3%) (OR 0.46, 95% CI 0.27-0.79). After adjustment for differences in baseline characteristics, the difference in 28-day mortality remained significant (adjusted OR wave 3 v. wave 1: 0.46, 95% CI 0.26-0.81; wave 3 v. wave 2: 0.52, 95% CI 0.29-0.91). In-hospital mortality findings were similar. Use of invasive mechanical ventilation or vasopressors was less common in waves 2 and 3 than in wave 1, and use of RRT was less common in wave 3 than in wave 1., Interpretation: Severity of illness decreased (lower mortality and less use of organ support) across waves among patients admitted to hospital with acute COVID-19, possibly owing to changes in patient demographic characteristics and management, such as increased use of dexamethasone. Continued application of proven therapies may further improve outcomes., Study Registration: ClinicalTrials.gov, no. NCT04510623., Competing Interests: Competing interests: James Russell reports an investigator-initiated grant from Grifols that was provided to and administered by the University of British Columbia (UBC). He reports patents owned by UBC that are related to the use of PCSK9 inhibitor(s) in sepsis and the use of vasopressin in septic shock, and a patent owned by Ferring Pharmaceuticals for use of selepressin in septic shock. He is an inventor on these patents. He was a founder, director and shareholder in Cyon Therapeutics and is a shareholder in Molecular You. He reports consulting fees from SIB Therapeutics (developing a sepsis drug) and Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin). He is no longer actively consulting for any industry. He was a nonfunded science advisor and member of the Government of Canada COVID-19 Therapeutics Task Force (June 2020–December 2021) and a nonfunded member of the data and safety monitoring board of a trial of plasma in COVID-19 (PassITON) (2020–2021) sponsored by the National Institutes of Health. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Competing Interests: Intérêts concurrents: François Lamontagne a été rémunéré par les Instituts de recherche en santé du Canada, le Fonds de recherche du Québec – Santé, le National Institute for Health Research (NIHR) et la Fondation Lotte & John Hecht pour avoir fait des évaluations par les pairs. Il a codirigé l’essai « 65 Trial », un projet financé par le programme d’évaluation des technologies en santé du NIHR (PMID : 32049269) et coordonné par l’unité des essais cliniques de l’Intensive Care National Audit and Research Centre (ICNARC). Il est également codirecteur scientifique du Réseau Sepsis Canada, qui reçoit des fonds des IRSC, et codirecteur du Réseau québécois COVID — Pandémie, qui lui est financé par le Fonds de recherche du Québec – Santé. Kathryn Rowan est directrice de l’ICNARC et de son unité d’essais cliniques, et également professeure honoraire à la London School of Hygiene and Tropical Medicine. Elle déclare avoir reçu des subventions des programmes de financement de la recherche du NIHR. Aucun autre intérêt concurrent n’a été déclaré.

Background: Clinical data on patients admitted to hospital with coronavirus disease 2019 (COVID-19) provide clinicians and public health officials with information to guide practice and policy. The aims of this study were to describe patients with COVID-19 admitted to hospital and intensive care, and to investigate predictors of outcome to characterize severe acute respiratory infection., Methods: This observational cohort study used Canadian data from 32 selected hospitals included in a global multisite cohort between Jan. 24 and July 7, 2020. Adult and pediatric patients with a confirmed diagnosis of COVID-19 who received care in an intensive care unit (ICU) and a sampling of up to the first 60 patients receiving care on hospital wards were included. We performed descriptive analyses of characteristics, interventions and outcomes. The primary analyses examined in-hospital mortality, with secondary analyses of the length of hospital and ICU stay., Results: Between January and July 2020, among 811 patients admitted to hospital with a diagnosis of COVID-19, the median age was 64 (interquartile range [IQR] 53-75) years, 495 (61.0%) were men, 46 (5.7%) were health care workers, 9 (1.1%) were pregnant, 26 (3.2%) were younger than 18 years and 9 (1.1%) were younger than 5 years. The median time from symptom onset to hospital admission was 7 (IQR 3-10) days. The most common symptoms on admission were fever, shortness of breath, cough and malaise. Diabetes, hypertension and cardiac, kidney and respiratory disease were the most common comorbidities. Among all patients, 328 received care in an ICU, admitted a median of 0 (IQR 0-1) days after hospital admission. Critically ill patients received treatment with invasive mechanical ventilation (88.8%), renal replacement therapy (14.9%) and extracorporeal membrane oxygenation (4.0%); 26.2% died. Among those receiving mechanical ventilation, 31.2% died. Age was an influential predictor of mortality (odds ratio per additional year of life 1.06, 95% confidence interval 1.03-1.09)., Interpretation: Patients admitted to hospital with COVID-19 commonly had fever, respiratory symptoms and comorbid conditions. Increasing age was associated with the development of critical illness and death; however, most critically ill patients in Canada, including those requiring mechanical ventilation, survived and were discharged from hospital., Competing Interests: Competing interests: See the end of the article. Competing interests: Todd Lee reports salary support from Fonds de recherche du Québec – Santé. Deepali Kumar reports grants and personal fees from Roche. Michelle Kho reports grants from Canada Research Chairs. Matthew Cheng reports grants from the McGill Interdisciplinary Initiative in Infection and Immunity and personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and personal fees from nplex biosciences (as a member of the scientific advisory board). Philippe Jouvet reports consulting for Mallinckrodt Pharmaceuticals and grants to his institution from VitalTracer and Evolucare. Patrick Archambault is a co-investigator in the Canadian Institutes of Health Research (CIHR)–funded Canadian COVID-19 Emergency Department Rapid Response Network (https://canadiancovid19ednetwork.org). No other competing interests were declared., (© 2021 Joule Inc. or its licensors.)

Competing Interests: Competing interests: François Lamontagne has received peer-reviewed funds from the Canadian Institutes of Health Research, the Fonds de Recherche du Québec – Santé, the National Institute for Health Research (NIHR), and the Lotte & John Hecht Memorial Foundation. Dr. Lamontagne co-led the 65 Trial funded by the NIHR Health Technology Assessment Programme (PMID 32049269) and coordinated by the Intensive Care National Audit & Research Centre (ICNARC) Clinical Trials Unit. He is the co-scientific director of the CIHR-funded Canadian Sepsis Network, and co-director of the Réseau Québécois COVID-19 et Pandémies, funded by the Fonds de recherche du Québec – Santé. Kathryn Rowan is the director/clinical trials unit director at ICNARC and honourary professor at the London School of Hygiene & Tropical Medicine. Dr. Rowan reports receiving research grants from NIHR Research Funding Programmes. No other competing interests were declared.

Competing Interests: Intérêts concurrents: Younsuck Koh, Bin Du et Yaseen Arab déclarent être les auteurs de Surviving Sepsis Campaign : Guidelines on the Management of Critically Ill Adults With Coronavirus Disease 2019, qui formule une recommandation en lien avec cette ligne directrice au sujet des corticostéroïdes dans le syndrome de détresse respiratoire aiguë. Bin Du déclare être l’investigateur principal d’un essai randomisé et contrôlé (ERC) prospectif en cours sur l’efficacité des corticostéroïdes chez les patients atteints de maladie à coronavirus 2019 (COVID-19) dans sa forme de modérée à grave, soutenu par la subvention de recherche n° 2020YFC0841300 du ministère des Sciences et de la Technologie de la République populaire de Chine. Srinivas Murthy et Robert Fowler déclarent être les investigateurs d’un essai bénéficiant d’une subvention des Instituts de recherche en santé du Canada (IRSC), pour évaluer l’effet des corticostéroïdes et des antiviraux (hydroxychloroquine et lopinavir-ritonavir) chez des patients atteints de COVID-19. Ning Shen déclare être investigateur pour un essai qui mesure l’effet de l’hydroxychloroquine chez des patients atteints de COVID-19, subventionné par le Centre des sciences de la santé de l’Université de Pékin. Neill Adhikari déclare être co-investigateur d’un projet subventionné par les IRSC sur les antiviraux chez les patients hospitalisés pour COVID-19 et d’un second projet subventionné par les IRSC sur divers traitements, y compris les corticostéroïdes, dans des cas critiques de COVID-19. Mark Loeb déclare avoir reçu une subvention et des honoraires personnels de l’Organisation mondiale de la santé (OMS) pour des travaux contractuels sur la grippe et la résistance aux antibiotiques, des honoraires de consultation et une subvention de Seqirus pour un ERC sur la grippe, des honoraires personnels à titre de membre du comité consultatif et un soutien non financier de Sanofi sous forme de don de vaccins en vue d’un ERC sur la grippe, et des honoraires à titre de consultant pour Pfizer et Medicago. Le Dr Loeb déclare aussi être investigateur pour un essai sur l’effet de la chloroquine-azithromycine chez les patients atteints de COVID-19, subventionné par le ministère de la Santé de l’Ontario, Bayer et Abbott. François Lamontagne et Bram Rochwerg déclarent être investigateurs d’un essai subventionné par les IRSC sur l’effet des corticostéroïdes et des antiviraux (hydroxychloroquine et lopinavir-ritonavir) chez des patients atteints de COVID-19. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Younsuck Koh, Bin Du and Yaseen Arabi report being authors of Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults With Coronavirus Disease 2019, which made 1 recommendation relevant to this guideline regarding corticosteroids in acute respiratory distress syndrome. Bin Du reports being the principal investigator of an ongoing prospective randomized controlled trial (RCT) examining the efficacy of corticosteroids in patients with moderate-to-severe coronavirus disease 2019 (COVID-19), which is funded by the research grant 2020YFC0841300 from the Ministry of Science and Technology of the People’s Republic of China. Srinivas Murthy and Robert Fowler report being investigators in a trial, supported by a Canadian Institutes of Health Research (CIHR) grant, evaluating the effect of corticosteroids and antiviral drugs (hydroxychloroquine and lopinavir-ritonavir) in patients with COVID-19. Ning Shen reports being an investigator in a trial evaluating the effect of hydroxychloroquine in patients with COVID-19, funded by Peking University Health Science Center. Neill Adhikari reports being a co-investigator of a CIHR-funded grant of antivirals in hospitalized patients with COVID-19 and of a second CIHR-funded grant of a variety of treatments, including corticosteroids, in critically ill patients with COVID-19. Mark Loeb reports receiving a grant and personal fees from the World Health Organization (WHO) for contract work on influenza and antibiotic resistance; consulting fees and a grant from Seqirus for an RCT on influenza; personal fees as a member of the advisory board and non-financial support from Sanofi, for an in-kind vaccine for the influenza RCT; and consulting fees from Pfizer and Medicago. Dr. Loeb also reports being an investigator in a trial evaluating the effect of chloroquine-azithromycin in patients with COVID-19, funded by Ontario Ministry of Health, Bayer and Abbott. François Lamontagne and Bram Rochwerg report being investigators in a trial, supported by a CIHR grant, evaluating the effect of corticosteroids and antiviral drugs (hydroxychloroquine and lopinavir-ritonavir) in patients with COVID-19. No other competing interests were declared.

Background: Most deaths in critically ill patients with severe traumatic brain injury are associated with a decision to withdraw life-sustaining treatments. We aimed to identify the behavioural determinants that influence recommendations by critical care physicians to consider the withdrawal of life-sustaining treatments in this population., Methods: We conducted a descriptive qualitative study based on the Theoretical Domains Framework of critical care physicians caring for patients with severe traumatic brain injury across Canada. We stratified critical care physicians by regions and used a purposive sampling strategy. We conducted semistructured phone interviews using a piloted and pretested interview guide. We transcribed the interviews verbatim and verified the content for accuracy. We performed the analysis using a 3-step approach: coding, generation of specific beliefs and generation of specific themes., Results: We recruited 20 critical care physicians across 4 geographic regions. After reaching saturation, we identified 7 core themes across 4 Theoretical Domains Framework domains for factors relevant to the decision to withdraw life-sustaining treatments. Four factors (i.e., clinical triggers, social triggers, interaction with families and intentions with medical decisions) were identified before the decision is made and 3 were identified during the decision-making process (i.e., considerations, priorities and knowledge needs). We identified multiple themes reflecting internal ( n = 18, 8 Theoretical Domains Framework domains) and external ( n = 15, 6 Theoretical Domains Framework domains) influences on the decision to withdraw life-sustaining treatments., Interpretation: We identified several core themes and domains considered by critical care physicians in Canada in the decision to withdraw life-sustaining treatments in critically ill patients with severe traumatic brain injury. Future research should aim at identifying the factors influencing surrogate decision-makers in the decision to withdraw life-sustaining treatments in these patients., Competing Interests: Competing interests: None declared., (© 2019 Joule Inc. or its licensors or its licensors.)

Background: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery., Methods: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients ( n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 μmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery., Results: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease., Interpretation: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388., Competing Interests: Competing interests: P.J. Devereaux has received grants from Abbott Diagnostics, Boehringer Ingelheim, Covidien, Octapharma, Philips Healthcare, Roche Diagnostics and Stryker for projects outside the work reported here. Chirag Parikh reports personal fees from AbbVie Pharmaceutical Research and Development and GENFIT Biopharmaceutical Company; funding from Renalytix AI; and grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung and Blood Institute. Vlado Perkovic reports receiving personal fees for advisory boards or scientific presentations from Retrophin, Janssen, Merck and Servier. Vlado Perkovic was a member of the SONAR Steering Committee; has served on steering committees for trials funded by AbbVie, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Novo Nordisk, Retrophin and Tricida; and has participated in scientific presentations and advisory boards with AbbVie, Astellas, Astra-Zeneca, Bayer, Baxter, Bristol-Myers Squibb, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Mitsubishi Tanabe, Novartis, Novo Nordisk, Pfizer, PharmaLink, Relypsa, Retrophin, Sanofi, Servier, Vifor and Tricida. Richard Whitlock reports grants and personal fees from Boehringer Ingelheim. No other competing interests were declared., (© 2019 Joule Inc. or its licensors.)

Background: We performed a directed environmental scan to identify and categorize quality indicators unique to critical care that are reported by key stakeholder organizations., Methods: We convened a panel of experts ( n = 9) to identify key organizations that are focused on quality improvement or critical care, and reviewed their online publications and website content for quality indicators. We identified quality indicators specific to the care of critically ill adult patients and then categorized them according to the Donabedian and the Institute of Medicine frameworks. We also noted the organizations' rationale for selecting these indicators and their reported evidence base., Results: From 28 targeted organizations, we identified 222 quality indicators, 127 of which were unique. Of the 127 indicators, 63 (32.5%) were safety indicators and 61 (31.4%) were effectiveness indicators. The rationale for selecting quality indicators was supported by consensus for 58 (26.1%) of the 222 indicators and by published research evidence for 45 (20.3%); for 119 indicators (53.6%), the rationale was not reported or the reader was referred to other organizations' reports. Of the 127 unique quality indicators, 27 (21.2%) were accompanied by a formal grading of evidence, whereas for 52 (40.9%), no reference to evidence was provided., Interpretation: There are many quality indicators related to critical care that are available in the public domain. However, owing to a paucity of rationale for selection, supporting evidence and results of implementation, it is not clear which indicators should be adopted for use., Competing Interests: Competing interests: None declared., (Copyright 2017, Joule Inc. or its licensors.)

Background: Surveillance of antimicrobial resistance is vital to guiding empirical treatment of infections. Collating and reporting routine data on clinical isolate testing may offer more timely information about resistance patterns than traditional surveillance network methods., Methods: Using routine microbiology testing data collected from the Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness retrospective cohort study, we conducted a descriptive secondary analysis among critically ill patients in whom bloodstream infections had been diagnosed in 14 intensive care units (ICUs) in Canada. The participating sites were located within tertiary care teaching hospitals and represented 6 provinces and 10 cities. More than 80% of the study population was accrued from 2011-2013. We assessed the epidemiologic features of the infections and corresponding antimicrobial susceptibility profiles. Susceptibility testing was done according to Clinical Laboratory Standards Institute guidelines at accredited laboratories., Results: A total of 1416 pathogens were isolated from 1202 patients. The most common organisms were Escherichia coli (217 isolates [15.3%]), Staphylococcus aureus (175 [12.4%]), coagulase-negative staphylococci (117 [8.3%]), Klebsiella pneumoniae (86 [6.1%]) and Streptococcus pneumoniae (85 [6.0%]). The contribution of individual pathogens varied by site. For 13 ICUs, gram-negative susceptibility rates were high for carbapenems (95.4%), tobramycin (91.2%) and piperacillin - tazobactam (90.0%); however, the proportion of specimens susceptible to these agents ranged from 75.0%-100%, 66.7%-100% and 75.0%-100%, respectively, across sites. Fewer gram-negative bacteria were susceptible to fluoroquinolones (84.5% [range 64.1%-97.2%]). A total of 145 patients (12.1%) had infections caused by highly resistant microorganisms, with significant intersite variation (range 2.6%-24.0%, χ2 = 57.50, p < 0.001)., Interpretation: We assessed the epidemiologic features of bloodstream infections in a geographically diverse cohort of critically ill Canadian patients using routine pathogen and susceptibility data extracted from readily available microbiology testing databases. Expanding data sharing across more ICUs, with serial measurement and prompt reporting, could provide much-needed guidance for empiric treatment for patients as well as system-wide prevention methods to limit antimicrobial resistance., Competing Interests: Conflicts of Interest: None declared.

Background: The promotion of early mobilization following critical illness is tempered by national reports of patient and institutional barriers to this approach. We carried out a survey to assess current knowledge, perceptions and practices of Canadian physicians and physiotherapists with respect to acquired weakness and early mobilization in adults in the intensive care unit (ICU)., Methods: We conducted a cross-sectional, self-administered postal survey among critical care physicians and physiotherapists in all 46 academic ICUs in Canada in 2011-2012. To identify all physicians and physiotherapists working in the ICUs, we contacted division heads and senior physiotherapists by telephone or email. We designed, tested and administered a questionnaire with the following domains: knowledge of ICU-acquired weakness and early mobilization; personal views of, perceived barriers to and adequacy of technical skills for early mobilization; assessments for initiation of early mobilization and permissible activity levels by patient physiologic characteristics, diagnoses and therapies; staffing issues; and sedation practices., Results: The overall response rate was 71.3% (311/436); it was 64.2% (194/302) among physicians and 87.3% (117/134) among physiotherapists. A total of 214 respondents (68.8%) underestimated the incidence of ICU-acquired weakness in the general medical-surgical ICU population, and 186 (59.8%) stated they had insufficient knowledge or skills to mobilize patients receiving mechanical ventilation. Excessive sedation, medical instability, limited staffing, safety concerns, insufficient guidelines and insufficient equipment were common perceived barriers to early mobilization., Interpretation: Physicians and physiotherapists in the ICU underestimated the incidence of ICU-acquired weakness and felt inadequately trained to mobilize patients receiving mechanical ventilation. We identified multiple modifiable barriers to early mobilization at the institutional, health care provider and patient levels that need to be addressed when designing mobilization programs for critically ill adults., Competing Interests: Conflicts of Interest: None declared.

Background: Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury., Methods: We searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses., Results: We screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I 2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I 2 = 82%). We were unable to determine a clinical threshold value using the available patient data., Interpretation: In patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available., Competing Interests: See end of article.

Background: Without robust clinical evidence to guide titration of vasopressors in septic shock, it is unclear how dosing of these potent medications occurs. We sought to measure the proportion of vasopressor prescriptions for septic shock that were missing explicit targets and to describe the targets that we identified., Methods: We conducted a multicentre, retrospective cohort study involving 9 intensive care units (ICUs) located at 3 academic hospitals in Canada and Australia. We reviewed charts of consecutive patients aged 18 years or older who were admitted to the ICU for a presumptive diagnosis of sepsis. Other inclusion criteria were hypotension (systolic arterial pressure ≤ 90 mm Hg or mean arterial pressure [MAP] ≤ 65 mm Hg) and continuous infusion of vasopressors for at least 1 hour within the initial 48 hours of ICU stay, the period of observation for this study., Results: We included data from 369 patient charts. At least 1 target was specified in 99% of charts. The most common targets were MAP measurements (73%). The median initial MAP target was 65 (range 55-90) mm Hg. In multivariable regression models, hospital site and older age of the patient, but not comorbidities of the patient, were associated with MAP targets. In 40% of patients, the treating team modified the initial target at least once., Interpretation: This study suggests that an explicit blood pressure target accompanies nearly every vasopressor prescription and that patient characteristics have little influence on its value. Identification of a titration strategy that will maximize benefit and minimize harm constitutes a research priority.

Background: Based on promising results from laboratory studies, we hypothesized that pneumococcal vaccination would protect patients from myocardial infarction., Methods: We conducted a hospital-based case-control study that included patients considered to be at risk of myocardial infarction. We used health databases to obtain hospital diagnoses and vaccination status. We compared patients who had been admitted for treatment of myocardial infarction with patients admitted to a surgical department in the same hospital for a reason other than myocardial infarction between 1997 and 2003., Results: We found a total of 43 209 patients who were at risk; of these, we matched 999 cases and 3996 controls according to age, sex and year of hospital admission. Cases were less likely than controls to have been vaccinated (adjusted odds ratio [OR] 0.53, 95% confidence interval [CI] 0.40-0.70). This putative protective role of the vaccine was not observed for patients who had received the vaccine up to 1 year before myocardial infarction (adjusted OR 0.85, 95% CI 0.54-1.33). In contrast, if vaccination had occurred 2 years or more before the hospital admission, the association was stronger (adjusted OR 0.33, 95% CI 0.20-0.46)., Interpretation: Pneumococcal vaccination was associated with a decrease of more than 50% in the rate myocardial infarction 2 years after exposure. If confirmed, this association should generate interest in exploring the putative mechanisms and may offer another reason to promote pneumococcal vaccination.