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Objectives: The objective of this study was to evaluate the utility of circumferential casting in the emergency department (ED), orthopedic follow-up visits, and radiographic follow-up in the management of children with wrist buckle fractures.Methods: We performed a retrospective medical record review of all children < 18 years of age who presented to our tertiary care children's hospital between July 1, 2000, and June 30, 2001, and were diagnosed with a fracture of the wrist, radius or ulna. Based on the radiology reports, we identified buckle fractures of the distal radius, the distal ulna, or both bones. We excluded children who had other types of fractures.Results: We identified 840 children with fractures of the wrist, radius, or ulna. Of these, 309 met our inclusion criteria. The median age of our study cohort was 9.2 years. Emergency physicians immobilized 269 of these fractures in circumferential casts; of these, 30 (11%) had cast complications. Of the 276 subjects who had orthopedic follow-up visits and radiographs, 184 (67%) had multiple visits and 127 (46%) had multiple radiographs performed. No subjects had fracture displacement identified on follow-up.Conclusions: Orthopedic follow-up visits and radiographic follow-up may have minimal utility in the treatment of pediatric wrist buckle fractures. ED casting may pose more risk than benefit for these children. Splinting in the ED with primary care follow-up appears to be a reasonable management strategy for these fractures. A prospective study comparing ED splinting and casting for pediatric wrist buckle fractures is needed. [ABSTRACT FROM AUTHOR]

Background: In Canada, academic hospitals are the principal drivers of research and medical education, while community hospitals provide patient care to a majority of the population. Benefits of increasing community hospital research include improved patient outcomes and access to research, enhanced staff satisfaction and retention and increased research efficiency and generalizability. While the resources required to build Canadian community hospital research capacity have been identified, strategies for strengthening organizational research culture in these settings are not well defined. This study aimed to understand how research culture is experienced and shaped in Canadian community hospitals to provide strategies for strengthening research culture in these settings., Methods: This qualitative descriptive study, as part of a larger study, explored the underlying dimensions of research culture. Participants were purposefully sampled and included healthcare providers, research staff or hospital administrators from community hospitals across Canada, with non-existent, emerging or established research programs. Data were collected via virtual semi-structured interviews and a demographic questionnaire. Interview transcripts were analyzed using reflexive thematic analysis and Schein's Model of Organizational Culture as a sensitizing framework. Demographic data were analyzed using descriptive statistics., Results: A total of 38 participants from 20 Canadian community hospitals described their experiences of research culture illustrating three key themes. As community hospital research programs matured, participants described a shift in research culture whereby research became more embedded in "the way things are done" within the community hospital. Recommended strategies to achieve an embedded culture of research involve: communications; relationship building; mentorship, training and education opportunities; selecting locally relevant studies; and systems-level support. A top-down approach to embedding research culture was contrasted with a bottom-up approach., Conclusions: This study described the underlying dimensions of community hospital research culture and targeted strategies for strengthening research culture at different levels of research program maturity. Community hospitals without pre-existing research infrastructure were able to foster a culture of research from the bottom-up by emphasizing the value of embedding research in clinical practice. Although challenging, fostering a culture of research from the bottom-up may be necessary to propel research forward and initiate the process to build research capacity within a community hospital., Competing Interests: Declarations. Ethics approval and consent to participate: This study received approval from the Hamilton Integrated Research Ethics Board (Study 14222). Informed written consent for participation was obtained for all participants prior to each interview. Participants were informed that they were free to withdraw from the study at any time and up to 2 weeks after the interview. Participant confidentiality was maintained by de-identifying the data. Consent for publication: Not applicable. Competing interests: J.T. and A.B. are clinician–scientists and clinical research program leads working in Canadian community hospitals with established research programs. J.T. is the Executive Director and Chief Scientist of a community hospital-based research institute. A.B. leads the Critical Care Research Program at a community hospital. Both A.B. and J.T. are co-founders and co-chair of the Canadian Community ICU Research Network. K.R. is a research coordinator, and E.O. and R.M. are research managers working in Canadian community hospitals with established research programs., (© 2024. The Author(s).)

Aims: To describe intensive care unit nurses' experiences of moral distress during the COVID-19 pandemic, and their recommendations for mitigative interventions., Design: Interpretive description., Methods: Data were collected with a purposeful sample of 40 Canadian intensive care unit nurses between May and September 2021. Nurses completed a demographic questionnaire, the Measure of Moral Distress-Healthcare Professionals survey and in-depth interviews. Quantitative data were analysed using descriptive statistics. Qualitative data were categorized and synthesized using reflexive thematic analysis and rapid qualitative analysis., Results: Half of the nurses in this sample reported moderate levels of moral distress. In response to moral distress, nurses experienced immediate and long-term effects across multiple health domains. To cope, nurses discussed varied reactions, including action, avoidance and acquiescence. Nurses provided recommendations for interventions across multiple organizations to mitigate moral distress and negative health outcomes., Conclusion: Nurses reported that moral distress drove negative health outcomes and attrition in response to moral events in practice. To change these conditions of moral distress, nurses require organizational investments in interventions and cultures that prioritize the inclusion of nursing perspectives and voices., Implications for the Profession: Nurses engage in a variety of responses to cope with moral distress. They possess valuable insights into the practice issues central to moral distress that have significant implications for all members of the healthcare teams, patients and systems. It is essential that nurses' voices be included in the development of future interventions central to the responses to moral distress., Reporting Method: This study adheres to COREQ guidelines., Impact: What Problem did the Study Address? Given the known structural, systemic and environmental factors that contribute to intensive care unit nurses' experiences of moral distress, and ultimately burnout and attrition, it was important to learn about their experiences of moral distress and their recommendations for organizational mitigative interventions. Documentation of these experiences and recommendations took on a greater urgency during the context of a global health emergency, the COVID-19 pandemic, where such contextual influences on moral distress were less understood. What Were the Main Findings? Over half of the nurses reported a moderate level of moral distress. Nurses who were considering leaving nursing practice reported higher moral distress scores than those who were not considering leaving. In response to moral distress, nurses experienced a variety of outcomes across several health domains. To cope with moral distress, nurses engaged in patterns of action, avoidance and acquiescence. To change the conditions of moral distress, nurses desire organizational interventions, practices and culture changes situated in the amplification of their voices. Where and on Whom Will the Research Have an Impact on? These findings will be of interest to: (1) researchers developing and evaluating interventions that address the complex phenomenon of moral distress, (2) leaders and administrators in hospitals, and relevant healthcare and nursing organizations, and (3) nurses interested in leveraging evidence-informed recommendations to advocate for interventions to address moral distress. What Does this Paper Contribute to the Wider Global Community? This paper advances the body of scientific work on nurses' experiences of moral distress, capturing this phenomenon within the unique context of a global health emergency. Nurses' levels of moral distress using Measure of Moral Distress-Healthcare Professional survey were reported, serving as a comparator for future studies seeking to measure and evaluate intensive care unit nurses' levels of moral distress. Nurses' recommendations for mitigative interventions for moral distress have been reported, which can help inform future interventional studies., Patient or Public Contribution: No patient or public contribution., (© 2024 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Purpose: Community hospitals account for 90% of hospitals in Canada, but clinical research is mainly conducted in academic hospitals. Increasing community hospital research participation can improve generalizability of study results, while also accelerating study recruitment and increasing staff engagement. We aimed to identify and describe the factors that influence community intensive care unit (ICU) research participation and the development, implementation, and sustainability of a community ICU research program., Methods: We conducted a qualitative descriptive study using semistructured interviews. Between April 2022 and May 2023, we interviewed a purposeful sample of individuals interested or involved in community hospital research in Canadian community ICUs. We analyzed qualitative data using both conventional content analysis and rapid qualitative analysis. Findings were deductively mapped out using the Ecological Model of Health Behavior. Quantitative survey data were analyzed using descriptive statistics., Results: Participants included 23 health care workers, ten research staff, and five hospital administrators (n = 38) from 20 community hospitals across six provinces in Canada. The main factors associated with community ICU research participation were 1) infrastructure, 2) personnel characteristics, 3) key relationships and connections, and 4) the COVID-19 pandemic., Conclusion: In this qualitative descriptive study, participants identified the physical resources, skills, and relationships required to start and sustain a clinical research program in a Canadian community ICU. Our findings suggest that all levels of the Canadian health care system need to invest in strengthening community hospital research capacity to increase research participation., (© 2024. The Author(s).)

Background: Most Canadians receive their care in community hospitals, yet most clinical research is conducted in academic hospitals. This study aims to compare patients with community acquired pneumonia (CAP) treated in academic and community hospitals with respect to their demographics, clinical characteristics, treatments and outcomes., Methods: This nested observational cohort substudy of the Community Acquired Pneumonia: Toward InnoVAtive Treatment (CAPTIVATE) trial included 1,329 hospitalized adults with CAP recruited between March 1st, 2018 and September 31st, 2023 from 15 Canadian hospitals. Unadjusted and adjusted analyses for age, sex and co-morbidities using logistic, Cox and censored quantile regressions were conducted., Results: Patients in community hospitals were older (mean [SD] 75.0 [15.7] years vs. 68.3 [16.2] years; p < 0.001), were more likely to be female (49.7% vs. 41.0%, p = 0.002), and had more comorbidities (75.9% vs. 64.8%, p < 0.001). More patients in community hospitals received corticosteroids (49.2% vs. 37.4%, p < 0.001). Community hospital patients had a higher likelihood of developing acute respiratory distress syndrome (OR 3.13, 95% CI: 1.87, 5.24, p = < 0.001), and acute cardiac injury (OR 2.53, 95% CI: 1.33, 4.83, p = 0.005). In unadjusted and adjusted analyses, 28-day mortality difference did not meet statistical significance (OR 1.43, 95% CI: 0.98, 20.7, p = 0.062 and OR 1.23, 95% CI: 0.81, 1.87, p = 0.332, respective)., Conclusion: Patients with CAP in Canadian community and academic hospitals differed with respect to their age, clinical characteristics, treatments and outcomes, emphasizing the importance of including more community hospitals in clinical research studies to ensure the generalizability of results., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was received from the University of British Columbia Providence Health Care Research Ethics Board (REB Number: H20-00600) and by each of the participating sites. Consent for publication: Not applicable. Competing interests: Support for CAPTIVATE was obtained from grants to J.A.R. from the Canadian Institutes of Health Research (grant number: 439993) and St. Paul’s Hospital Foundation. J.B. is a recipient of a Providence Health Care Research Scholarship. K.W. is supported by Canadian Institutes of Health Research (CIHR) Foundation Grant (FDN 154311). A.F.T. is the chairholder of the Canada Research Chair in Critical care neurology and trauma. D.C.V. is supported by the Fonds de recherche du Québec – Santé (FRQS) clinician-scientist Senior scholar award. D.C.V. has received funding support from the Jeffrey Modell Foundation, FRQS, and Canadian Institutes of Health Research. D.C.V. has served on advisory boards for: Astra Zeneca; CSL Behring; Novartis Canada; Moderna; Takeda. D.C.V. has received speaker honoraria from: CSL Behring; Merck Canada. DCV has a patent application pending (Electronic Filing System ID: 40101099) unrelated to this work. M.C. reports grants from the Canadian Institutes of Health Research during the conduct of the study and is supported by the Fonds de Recherche du Québec – Santé. M.C. reports personal fees from GEn1E Lifesciences and from nomic bio as a member of the scientific advisory board, as well as honoraria from AstraZeneca, Takeda, Merck, and Pfizer. M.C. reports research support from Cidara therapeutics, from Scynexis, Inc., and from Amplyx Pharmaceutics during the conduct of the study but outside the submitted work. M.C. is the co-founder of Kanvas Biosciences, Inc. and owns equity in the company. M.C. has pending patents, including: i) Methods for detecting tissue damage, graft versus host disease, and infections using cell-free DNA profiling, ii) Methods for assessing the severity and progression of SARS-CoV-2 infections using cell-free DNA pending., (© 2024. The Author(s).)

Background: Biosampling studies in critically ill patients traditionally involve bedside collection of samples followed by local processing (ie. centrifugation, aliquotting, and freezing) and storage. However, community hospitals, which care for the majority of Canadian patients, often lack the infrastructure for local processing and storage of specimens. A potential solution is a "simplified" biosampling protocol whereby blood samples are collected at the bedside and then shipped to a central site for processing and storage. One potential limitation of this approach is that delayed processing may alter sample characteristics., Objective: To determine whether delays in blood sample processing affect the stability of cytokines (IL-6, TNF, IL-10, IFN-γ), chemokines (IL-8, IP-10, MCP-1, MCP-4, MIP-1α, MIP-1β), cell-free DNA (cfDNA) (released by dying cells), and blood clotting potential in human blood samples., Methods: Venous blood was collected into EDTA and citrate sample tubes and stored at room temperature (RT) or 4°C for progressive intervals up to 72 hours, prior to processing. Plasma cytokines and chemokines were quantified using single or multiplex immunoassays. cfDNA was measured using Picogreen DNA Quantification. Blood clotting potential was measured using a thrombin generation assay., Results: Blood samples were collected from 9 intensive care unit (ICU) patients and 7 healthy volunteers. Admission diagnoses for the ICU patients included sepsis, trauma, ruptured abdominal aortic aneurysm, intracranial hemorrhage, gastrointestinal bleed, and hyperkalemia. After pre-processing delays of up to 72 hours at RT or 4°C, no significant changes were observed in plasma cytokines, chemokines, cfDNA, or thrombin formation., Conclusions: Delayed sample processing for up to 72 hours at either RT or 4°C did not significantly affect cytokines, chemokines, cfDNA, or blood clotting potential in plasma samples from healthy volunteers and ICU patients. A "simplified" biosampling protocol is a feasible solution for conducting biosampling research at hospitals without local processing capacity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gyorffy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear., Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding., Results: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups., Conclusions: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Objective: Collection of biosamples for translational research studies is vital for understanding biological pathways, discovering disease-related biomarkers, and identifying novel therapeutic targets. However, a lack of infrastructure for sample procurement, processing, storage, and shipping may hinder the ability of clinical research units to effectively engage in translational research. The purpose of this study was to identify the barriers to biosampling-based translational research in the critical care setting in Canada., Methods: We administered an online survey to members of the Canadian Critical Care Trials Group (CCCTG), the Canadian Critical Care Translational Biology Group (CCCTBG), and the Canadian Critical Care Research Coordinators Group (CCCRCG). The survey focused on participants' personal experience of biosampling research, research infrastructure, motivating factors, and perceived barriers., Results: We received 59 responses from 31 sites, including 6 community intensive care unit (ICU) sites. The overall response rate was 11.3%. The majority of respondents were research coordinators (44%), followed by clinician-investigators (33.8%), graduate students (10.2%), and PhD-investigators (8.5%). Although most (63.8%) respondents reported an interest in participating in translational research, they also reported that their ICUs were currently contributing to a third of the number of translational studies compared to clinical studies. For respondents with experience in participating in translational research studies, the most common barriers were lack of funding, lack of time, and insufficient research staff. For respondents without previous experience, the perceived facilitators were more interest from their research group, improved training/mentorship, increased funding, and better access to laboratory equipment., Conclusions: Our survey found that the majority of participants were interested in and recognize the value of participating in biosampling-based translational research but lacked funding, time, and research personnel trained in biosampling protocols. Our survey also identified factors that might encourage participation at new sites. Addressing these barriers will be a key step towards increasing translational research capacity across Canada., Competing Interests: No authors have competing interests., (Copyright: © 2024 Cani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Intensive care unit healthcare workers (ICU HCW) are at risk of mental health disorders during emerging disease outbreaks. Numerous cross-sectional studies have reported psychological distress, anxiety, and depression amongst ICU HCW during the COVID-19 pandemic. However, few studies have followed HCW longitudinally, and none of these have examined the association between COVID-19 workload and mental health. We conducted a longitudinal cohort study of 309 Canadian ICU HCW from April 2020 to August 2020, during the 1st wave of the COVID-19 pandemic. Psychological distress was assessed using the General Health Questionnaire 12-item scale (GHQ-12) at 3 timepoints: during the acceleration phase of the 1st wave (T1), the deceleration phase of the 1st wave (T2), and after the 1st wave had passed (T3). Clinically relevant psychological distress, defined as a GHQ-12 score ≥ 3, was identified in 64.7% of participants at T1, 41.0% at T2, and 34.6% at T3. Psychological distress was not associated with COVID-19 workload at T1. At T2, psychological distress was associated with the number of COVID-19 patients in the ICU (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.00, 1.13) while at T3, when COVID-19 patient numbers were low, it was associated with the number of weekly hospital shifts with COVID-19 exposure (OR: 1.33, 95% CI: 1.09, 1.64). When analyzed longitudinally in a mixed effects model, pandemic timepoint was a stronger predictor of psychological distress (OR: 0.24, 95% CI: 0.15, 0.40 for T2 and OR: 0.16, 95% CI: 0.09, 0.27 for T3) than COVID-19 workload. Participants who showed persistent psychological distress at T3 were compared with those who showed recovery at T3. Persistent psychological distress was associated with a higher number of weekly shifts with COVID-19 exposure (OR: 1.97, 95% CI:1.33, 3.09) but not with a higher number of COVID-19 patients in the ICU (OR: 0.86, 95% CI: 0.76, 0.95). In summary, clinically relevant psychological distress was observed in a majority of ICU HCW during the acceleration phase of the 1st wave of the COVID-19 pandemic but decreased rapidly as the 1st wave progressed. Persistent psychological distress was associated with working more weekly shifts with COVID-19 exposure but not with higher numbers of COVID-19 patients in the ICU. In future emerging disease outbreaks, minimizing shifts with direct disease exposure may help alleviate symptoms for individuals with persistent psychological distress., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pestana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties., Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia., Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization., Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events., Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612., Competing Interests: Potential conflicts of interest. M.L. reports funding support from the Canadian Institutes of Health Research (CIHR) Vanier Doctoral Scholarship. M.P.C. 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). J.L.Y.T. reports a Physicians” Services Incorporated Foundation grant to her institution, outside the submitted work. She is cochair of the Canadian Community ICU Research Network (CCIRNet) and vice chair of the Quest Community Health Centre board of directors. S.M. reports a grant from the Health Research Foundation, Innovative Medicines Canada. M.B.S. reports salary support from Fonds de recherche du Québec—Santé and is part of the advisory Board or equivalent of: Bausch, Stallergenes, Novartis, & Sanofi. Participating or participated in a clinical trial: Novartis, Aimmune, & Sanofi. T.C.L. reports salary support from Fonds de recherche du Québec—Santé. E.N. has been an Advisory Board/Speaker/Consultant and/or received Investigator Initiated Educational and/or Research funding from AbbVie Inc., Bausch Health, Beiersdorf, Boehringer Ingelheim International, Bristol Myers Squibb, Eli Lilly, Galderma SA., Janssen Inc., LEO Pharma, Medexus, Novartis Pharmaceuticals, Pfizer Inc., Sanofi Genzyme, Sun Pharmaceuticals, and UCB. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Blood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded., Objective: To determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures., Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 25 adult medical-surgical ICUs in Canada (February 5, 2019 to January 21, 2021)., Interventions: ICUs were randomized to transition from standard-volume (n = 10 940) to small-volume tubes (n = 10 261) for laboratory testing., Main Outcomes and Measures: The primary outcome was RBC transfusion (units per patient per ICU stay). Secondary outcomes were patients receiving at least 1 RBC transfusion, hemoglobin decrease during ICU stay (adjusted for RBC transfusion), specimens with insufficient volume for testing, length of stay in the ICU and hospital, and mortality in the ICU and hospital. The primary analysis included patients admitted for 48 hours or more, excluding those admitted during a 5.5-month COVID-19-related trial hiatus., Results: In the primary analysis of 21 201 patients (mean age, 63.5 years; 39.9% female), which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference in RBC units per patient per ICU stay (relative risk [RR], 0.91 [95% CI, 0.79 to 1.05]; P = .19; absolute reduction of 7.24 RBC units/100 patients per ICU stay [95% CI, -3.28 to 19.44]). In a prespecified secondary analysis (n = 27 411 patients), RBC units per patient per ICU stay decreased after transition from standard-volume to small-volume tubes (RR, 0.88 [95% CI, 0.77 to 1.00]; P = .04; absolute reduction of 9.84 RBC units/100 patients per ICU stay [95% CI, 0.24 to 20.76]). Median decrease in transfusion-adjusted hemoglobin was not statistically different in the primary population (mean difference, 0.10 g/dL [95% CI, -0.04 to 0.23]) and lower in the secondary population (mean difference, 0.17 g/dL [95% CI, 0.05 to 0.29]). Specimens with insufficient quantity for analysis were rare (≤0.03%) before and after transition., Conclusions and Relevance: Use of small-volume blood collection tubes in the ICU may decrease RBC transfusions without affecting laboratory analysis., Trial Registration: ClinicalTrials.gov Identifier: NCT03578419.

Background: This update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial-North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units., Methods/design: Protocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials ( https://doi.org/10.4172/2167-0870.1000284 ) and Trials (https://doi: 10.1186/s13063-019-3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis., Trial Registration: Clinical Trials.gov NCT02399267., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Randomized controlled trials (RCTs) provide essential evidence to inform practice, but the many necessary steps result in lengthy times to initiation, which is problematic in the case of rapidly emerging infections such as COVID-19. This study aimed to describe the start-up timelines for the Canadian Treatments for COVID-19 (CATCO) RCT., Methods: We surveyed hospitals participating in CATCO and ethics submission sites using a structured data abstraction form. We measured durations from protocol receipt to site activation and to first patient enrolment, as well as durations of administrative processes, including research ethics board (REB) approval, contract execution and lead times between approvals to site activation., Results: All 48 hospitals (26 academic, 22 community) and 4 ethics submission sites responded. The median time from protocol receipt to trial initiation was 111 days (interquartile range [IQR] 39-189 d, range 15-412 d). The median time between protocol receipt and REB submission was 41 days (IQR 10-56 d, range 4-195 d), from REB submission to approval, 4.5 days (IQR 1-12 d, range 0-169 d), from REB approval to site activation, 35 days (IQR 22-103 d, range 0-169 d), from protocol receipt to contract submission, 42 days (IQR 20-51 d, range 4-237 d), from contract submission to full contract execution, 24 days (IQR 15-58 d, range 5-164 d) and from contract execution to site activation, 10 days (IQR 6-27 d, range 0-216 d). Processes took longer in community hospitals than in academic hospitals., Interpretation: The time required to initiate RCTs in Canada was lengthy and varied among sites. Adoption of template clinical trial agreements, greater harmonization or central coordination of ethics submissions, and long-term funding of platform trials that engage academic and community hospitals are potential solutions to improve trial start-up efficiency., Competing Interests: Competing interests: Jennifer Tsang reports a Physicians’ Services Incorporated Foundation grant to her institution, outside the submitted work. She is cochair of the Canadian Community ICU Research Network (CCIRNet) and vice-chair of the Quest Community Health Centre board of directors. Alexandra Binnie reports a Physicians’ Services Incorporated Foundation grant and a Mohawk Medbuy grant to her institution, outside the submitted work. She is cochair of CCIRNet. Srinivas Murthy reports a grant from the Health Research Foundation, Innovative Medicines Canada, outside the submitted work. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Introduction: In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults., Methods and Analysis: We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups., Ethics and Dissemination: C ritical Care C yc ling to improve L ower E xtremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations., Trial Registration Number: NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot)., Competing Interests: Competing interests: MEK received an equipment loan of 4 RT300 supine cycles from Restorative Therapies, Baltimore, Maryland, USA for this study. On behalf of the remaining authors, the corresponding author states there is no conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic., Design: Cross-sectional survey using four validated instruments., Setting: Sixty-two sites in Canada and the United States., Subjects: Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs., Intervention: None., Measurements and Main Results: We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and self-reported moral distress (240 [56.9%]) and burnout (259 [63.8%]). Of the 10 top-ranked items that incited moral distress, most pertained to regulatory/organizational ( n = 6) or local/institutional ( n = 2) issues or both ( n = 2). Average moral distress (95.6 ± 66.9), professional fulfilment (6.5 ± 2.1), and burnout scores (3.6 ± 2.0) were moderate with 227 physicians (54.6%) meeting burnout criteria. A significant dose-response existed between COVID-19 patient volume and moral distress scores. Physicians who worked more days/mo and more scheduled in-house nightshifts, especially combined with more unscheduled in-house nightshifts, experienced significantly more moral distress. One in five physicians used at least one maladaptive coping strategy. We identified four coping profiles (active/social, avoidant, mixed/ambivalent, infrequent) that were associated with significant differences across all wellness measures., Conclusions: Despite moderate intrapandemic moral distress and burnout, physicians experienced moderate professional fulfilment. However, one in five physicians used at least one maladaptive coping strategy. We highlight potentially modifiable factors at individual, institutional, and regulatory levels to enhance physician wellness., Competing Interests: Dr. Burns disclosed that the Canadian Critical Care Society (CCSS) paid for the statistical analyses. Dr. Lorens received funding from the CCCS. Drs. Lorens and Kerlin disclosed work for hire. Drs. Viglianti, Kohn, Peltan, and Schnapp received support for article research from the National Institutes of Health (NIH). Dr. Fox-Robichaud’s institution received funding from the Canadian Institutes of Health Research and Hamilton Academic Hospitals. Dr. Mathews’ institution received funding from the National Heart, Lung, and Blood Institute (NHLBI); he received funding from Roivant/Kinevant Sciences. Dr. Jain is supported by the National Institute on Aging (NIA) T32AG019134, the Pepper Scholar Award from Yale Claude D. Pepper Older American Independence Center (P30AG021342), NIA of the NIH GEMSSTAR Award (R03AG078942), Parker B. Francis Fellowship Award, and Yale Physician-Scientist Development Award. Drs. Akgun and Crothers disclosed government work. Dr. Gershengorn received funding from the American Thoracic Society (ATS), Gilead Sciences, and Southeastern Critical Care Summit. Dr. Martin’s institution received funding from BARDA; he received funding from Genetech. Dr. Stapleton disclosed that she is chair of DSMB for Altimmune and a member of the ATS Board of Directors 2019–2021 (elected to Chair the Critical Care Assembly which includes a position on the Board). Dr. Attia’s institution received funding from the NHBLI (NHLBI K23 HL129888 and R03 [pending]), the Centers for Aids Research, and Pediatric HIV/AIDS Cohort Study. Dr. Maddux’s institution received funding from the National Institute of Child Health and Human Development (K23HD096018) and the Francis Family Foundation. Dr. Bagshaw received funding from Baxter and Bioporto. Dr. Crothers’ institution received funding from the NIH and Veteran’s Affairs. Dr. Peltan’s institution received funding from Regeneron and Asahi Kasei Pharma; he received funding from the NIH (K23GM129661) and Janssen. Dr. Schnapp received funding from UptoDate and Elsevier. Dr. Kraft’s institution received funding from the NIH, the American Lung Association, Sanofi, and AstraZeneca Consulting; she received funding from Sanofi, Astra-Zeneca, Chiesi Speaking, and UptoDate; she disclosed she is a cofounder and Chief Medical Officer of RaeSedo LLC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Clinical research in Canada is conducted primarily in "academic" hospitals, whereas most clinical care is provided in "community" hospitals. The objective of this nested observational study was to compare patient characteristics, outcomes, process-of-care variables, and trial metrics for patients enrolled in a large randomized controlled trial who were admitted to academic and community hospitals in Canada., Design: We conducted a preplanned observational study nested within the Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT, a randomized controlled trial comparing probiotics to placebo in mechanically ventilated patients) Research Program., Setting: ICUs., Patients: Mechanically ventilated patients., Measurements: We compared patient characteristics, interventions, outcomes, and trial metrics between patients enrolled in PROSPECT from academic and community hospitals., Main Results: Participating centers included 34 (82.9%) academic and seven (17.1%) community hospitals, which enrolled 2,203 (86.2%) and 352 (13.8%) patients, respectively. Compared with academic hospitals, patients enrolled in community hospitals were older (mean [sd] 62.7 yr [14.9 yr] vs 59.5 yr [16.4 yr]; p = 0.044), had longer ICU stays (median [interquartile range {IQR}], 13 d [8-23 d] vs 11 d [7-8 d]; p = 0.012) and higher mortality (percentage, [95% CI] in the ICU, 30.4% [25.8-35.4%]vs 20.5% [18.9-11.3%]; p = 0.002) and hospital (40.6% [35.6-45.8%] vs 26.1% [24.3-27.9%]; p < 0.001). Trial metrics, including informed consent rate (85.9% vs 76.3%; p = 0.149), mean (sd) monthly enrolment rate (2.1 [1.4] vs 1.1 [0.7]; p = 0.119), and protocol adherence (90.6% vs 91.6%; p = 0.207), were similar between community and academic ICUs., Conclusions: Community hospitals can conduct high-quality research, with similar trial metrics to academic hospitals. Patient characteristics differed between community and academic hospitals, highlighting the need for broader engagement of community hospitals in clinical research to ensure generalizability of study results., Competing Interests: The Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial Trial was funded by the Canadian Institutes of Health Research Research Grant. Dr. Tsang is supported by a Mid-Career Research Award of the McMaster University Department of Medicine. Dr. Cook is supported by a Canada Research Chair of the Canadian Institutes for Health Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir., Methods: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed., Results: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation., Interpretation: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation., Study Registration: ClinicalTrials. gov, no. NCT04330690., Competing Interests: Competing interests: Robert Fowler is the H. Barrie Fairley Professor of Critical Care Medicine at the University Health Network and the University of Toronto Interdepartmental Division of Critical Care Medicine. Robert Fowler declares a Canadian Institutes of Health Research (CIHR) operating grant. John Conly declares grants from the CIHR, Pfizer and the World Health Organization (WHO). He declares a peer-reviewed research grant on acute and primary care preparedness for COVID-19 in Alberta, Canada; he was a primary local investigator for the STRIVE Staphylococcus aureus vaccine randomized controlled trial in vertebral spinal surgery with instrumentation for which all funding was provided only to the University of Calgary; he was a co-investigator on a WHO-funded study using integrated human factors and ethnography approaches to identify and scale innovative infection prevention and control (IPC) guidance implementation supports in primary care with a focus on low-resource settings and using drone aerial systems to deliver medical supplies and personal protective equipment to remote First Nations communities during the COVID-19 pandemic. John Conly also reports receiving accommodations and airfare from the Centers for Disease Control and Prevention to attend a meeting in 2019. He is a member and chair of the WHO Infection Prevention and Control Research and Development Expert Group for COVID-19 and a member of the WHO Health Emergencies Programme Ad-hoc COVID-19 IPC Guidance Development Group, both of which provide multidisciplinary advice to the WHO, for which no funding is received and from which no funding recommendations are made for any WHO contracts or grants. He is also a member of the Cochrane Acute Respiratory Infections Group. Darrell Tan is supported by a Tier 2 Canada Research Chair in HIV Prevention and STI Research. Ryan Zarychanski reports grants from the CIHR, the Peter Munk Cardiac Centre, the Thistledown Foundation and the National Institutes of Health. He is a WHO thrombostasis technical advisory member. Ryan Zarychanski is the recipient of the Lyonel G. Israels Research Chair in Hematology at the University of Manitoba. Todd Lee reports a CATCO operating grant from the CIHR as a co–principal investigator and a co-investigator. He reports various operating grants from the CIHR, a technical development grant from the Centre for Aging + Brain Health Innovation and research salary support from the Fonds de recherche du Québec — Santé. He is the co-owner of a company that is bringing Med-Safer to market. Srinivas Murthy is the Innovative Medicines Canada and Health Research Foundation Chair in Pandemic Preparedness Research. Srinivas Murthy reports a grants from the CIHR and Health Research Foundation and Innovative Medicines Canada., (© 2022 CMA Impact Inc. or its licensors.)

Rationale: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches., Methods: On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy) and collect the primary outcome (physical function 3-days post-ICU discharge) and 90-day outcomes. We advised sites to prioritize data for the study's primary outcome. We sought feedback on pandemic barriers related to trial procedures., Results: Our main Methods Centre mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, developing standardized internal tools focused on high-risk points in the protocol for monitoring patient progress, data entry, and validation, and providing guidance to conduct some research activities remotely. For study sites, our strategies included determining how institutional pandemic research policies applied to CYCLE, communicating with the Methods Centre about capacity to continue any part of the research, and developing contingency plans to ensure the protocol was delivered as intended. From 15 active sites (12 Canada, 2 US, 1 Australia), 5 patients were still receiving the study intervention in ICUs, 6 required primary outcomes, and 17 required 90-day assessments. With these mitigation strategies, we attempted 100% of ICU interventions, 83% of primary outcomes, and 100% of 90-day assessments per our protocol., Conclusions: We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that it also provides a helpful framework for reporting mitigation strategies with the goal of improving research transparency and trial management., Trial Registration: NCT03471247. Registered on March 20, 2018., (© 2022. The Author(s).)

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19., Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19., Design, Setting, and Participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021., Intervention: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195)., Main Outcomes and Measures: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events., Results: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group., Conclusions and Relevance: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit., Trial Registration: ClinicalTrials.gov Identifier: NCT04350723.

Only a small proportion of COVID-19 patients in Canada have been recruited into clinical research studies. One reason is that few community intensive care units (ICUs) in Canada participate in research. The objective of this study was to examine the motivating factors, barriers and facilitators to research participation amongst Canadian community ICU stakeholders. A cross-sectional online survey was distributed between May and November 2020. The survey focused on 6 domains: participant demographics, ICU characteristics, ICU research infrastructure, motivating factors, perceived barriers, and perceived facilitators. Responses were received from 73 community ICU stakeholders, representing 18 ICUs. 7/18 ICUs had a clinical research program. Participants rated their interest in pandemic research at a mean of 5.2 (Standard Deviation [SD] = 1.9) on a 7-point Likert scale from 'not interested' to 'very interested'. The strongest motivating factor for research participation was the belief that research improves clinical care and outcomes. The most significant facilitators of research involvement were the availability of an experienced research coordinator and dedicated external funding to cover start-up costs, while the most significant barriers to research involvement were a lack of start-up funding for a research coordinator and a lack of ICU research experience. Canadian Community ICU stakeholders are interested in participating in pandemic research but lack basic infrastructure, research personnel, research experience and start-up funding. Evolution of a research support model at community hospitals, where most patients receive acute care, may increase research participation and improve the generalizability of funded research in Canada., Competing Interests: The authors have declared that no competing interests exist.

Rationale: The end of life (EOL) experience in the intensive care unit (ICU) can be psychologically distressing for patients, families, and clinicians. The 3 Wishes Project (3WP) personalizes the EOL experience by carrying out wishes for dying patients and their families. While the 3WP has been integrated in academic, tertiary care ICUs, implementing this project in a community ICU has yet to be described., Objectives: To examine facilitators of, and barriers to, implementing the 3WP in a community ICU from the clinician and implementation team perspective., Methods: This qualitative descriptive study evaluated the implementation of the 3WP in a 20-bed community ICU in Southern Ontario, Canada. Patients were considered for the 3WP if they had a high likelihood of imminent death or planned withdrawal of life-sustaining therapy. Following the qualitative descriptive approach, semi-structured interviews were conducted with purposively sampled clinicians and implementation team. Data from transcribed interviews were analyzed in triplicate through qualitative content analysis., Results: Interviews with 12 participants indicated that the 3WP personalized and enriched the EOL experience. Interviewees indicated higher intensity education strategies were needed to enable spread as the project grew. Clinicians described many physical resources for the project but suggested more non-clinical project support for orientation, continuing education, and data collection. A majority of wishes focused on physical resources including keepsakes, which helped facilitate project spread when clinician capacity was attenuated by competing duties., Conclusions: In this community hospital, ICU clinicians and implementation team members report perceived improved EOL care for patients, families, and clinicians following 3WP initiation and integration. Implementing individualized and meaningful wishes at EOL for dying patients in a community ICU requires adequate planning and time dedicated to optimizing clinician education. Adapting key features of an intervention to local expertise and capacity may facilitate spread during project initiation and integration., (© 2021 John Wiley & Sons, Ltd.)

Risk prediction scores are important tools to support clinical decision-making for patients with coronavirus disease (COVID-19). The objective of this paper was to validate the 4C mortality score, originally developed in the United Kingdom, for a Canadian population, and to examine its performance over time. We conducted an external validation study within a registry of COVID-19 positive hospital admissions in the Kitchener-Waterloo and Hamilton regions of southern Ontario between March 4, 2020 and June 13, 2021. We examined the validity of the 4C score to prognosticate in-hospital mortality using the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals calculated via bootstrapping. The study included 959 individuals, of whom 224 (23.4%) died in-hospital. Median age was 72 years and 524 individuals (55%) were male. The AUC of the 4C score was 0.77, 95% confidence interval 0.79-0.87. Overall mortality rates across the pre-defined risk groups were 0% (Low), 8.0% (Intermediate), 27.2% (High), and 54.2% (Very High). Wave 1, 2 and 3 values of the AUC were 0.81 (0.76, 0.86), 0.74 (0.69, 0.80), and 0.76 (0.69, 0.83) respectively. The 4C score is a valid tool to prognosticate mortality from COVID-19 in Canadian hospitals and can be used to prioritize care and resources for patients at greatest risk of death., (© 2021. The Author(s).)

Intensive care unit healthcare workers (ICU HCW) are at risk of mental health issues during emerging disease outbreaks. A study of ICU HCW from France revealed symptoms of anxiety and depression in 50.4% and 30.4% of workers at the peak of the first wave of the pandemic. The level of COVID-19 exposure of these ICU HCW was very high. In Canada, ICU HCW experienced variable exposure to COVID-19 during the first wave of the pandemic, with some hospitals seeing large numbers of patients while others saw few or none. In this study we examined the relationship between COVID-19 exposure and mental health in Canadian ICU HCW. We conducted a cross-sectional cohort study of Canadian ICU HCW in April 2020, during the acceleration phase of the first wave of the pandemic. Psychosocial distress was assessed using the 12-item General Health Questionnaire (GHQ-12). Participants were asked about sources of stress as well as about exposure to COVID-19 patients and availability of personal protective equipment (PPE). Factors associated with clinically-relevant psychosocial distress were identified. Responses were received from 310 Canadian ICU HCW affiliated with more than 30 institutions. Of these, 64.5% scored ≥ 3 points on the GHQ-12 questionnaire, indicating clinically-relevant psychosocial distress. The frequency of psychosocial distress was highest amongst registered nurses (75.7%) and lowest amongst physicians (49.4%). It was also higher amongst females (64.9%) than males (47.6%). Although PPE availability was good (> 80% of participants reported adequate availability), there was significant anxiety with respect to PPE availability, with respect to the risk of being infected with COVID-19, and with respect to the risk of transmitting COVID-19 to others. In multivariable regression analysis, Anxiety with respect to being infected with COVID-19 (OR 1.53, CI 1.31-1.81) was the strongest positive predictor of clinically-relevant psychosocial distress while the Number of shifts with COVID-19 exposure (OR 0.86, CI 0.75-0.95) was the strongest negative predictor. In summary, clinically-relevant psychosocial distress was identified amongst a majority of ICU HCW during the acceleration phase of the first wave of the COVID-19 pandemic, including those with minimal or no exposure to COVID-19. Strategies to support mental health amongst ICU HCW are required across the entire healthcare system., Competing Interests: The authors declare that no competing interests exist.

Background: The incidence of acute kidney injury (AKI) in patients with COVID-19 and its association with mortality and disease severity is understudied in the Canadian population., Objective: To determine the incidence of AKI in a cohort of patients with COVID-19 admitted to medicine and intensive care unit (ICU) wards, its association with in-hospital mortality, and disease severity. Our aim was to stratify these outcomes by out-of-hospital AKI and in-hospital AKI., Design: Retrospective cohort study from a registry of patients with COVID-19., Setting: Three community and 3 academic hospitals., Patients: A total of 815 patients admitted to hospital with COVID-19 between March 4, 2020, and April 23, 2021., Measurements: Stage of AKI, ICU admission, mechanical ventilation, and in-hospital mortality., Methods: We classified AKI by comparing highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We calculated the unadjusted and adjusted odds ratio for the stage of AKI and the outcomes of ICU admission, mechanical ventilation, and in-hospital mortality., Results: Of the 815 patients registered, 439 (53.9%) developed AKI, 253 (57.6%) presented with AKI, and 186 (42.4%) developed AKI in-hospital. The odds of ICU admission, mechanical ventilation, and death increased as the AKI stage worsened. Stage 3 AKI that occurred during hospitalization increased the odds of death (odds ratio [OR] = 7.87 [4.35, 14.23]). Stage 3 AKI that occurred prior to hospitalization carried an increased odds of death (OR = 5.28 [2.60, 10.73])., Limitations: Observational study with small sample size limits precision of estimates. Lack of nonhospitalized patients with COVID-19 and hospitalized patients without COVID-19 as controls limits causal inferences., Conclusions: Acute kidney injury, whether it occurs prior to or after hospitalization, is associated with a high risk of poor outcomes in patients with COVID-19. Routine assessment of kidney function in patients with COVID-19 may improve risk stratification., Trial Registration: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

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.)

Objectives: Recent evidence from the fields of microbiology and immunology, as well as a small number of human sepsis studies, suggest that epigenetic regulation may play a central role in the pathogenesis of sepsis. The term "epigenetics" refers to regulatory mechanisms that control gene expression but are not related to changes in DNA sequence. These include DNA methylation, histone modifications, and regulation of transcription via non-coding RNAs. Epigenetic modifications, occurring in response to external stressors, lead to changes in gene expression, and thus lie at the intersection between genetics and the environment. In this review, we examine data from in vitro studies, animal studies, and the existing human sepsis studies in epigenetics to demonstrate that epigenetic mechanisms are likely central to the pathogenesis of sepsis and that epigenetic therapies may have potential in the treatment of sepsis and its associated organ failures., Data Sources: Online search of published scientific literature via Pubmed using the term "epigenetics" in combination with the terms "sepsis", "infection", "bacterial infection", "viral infection", "critical illness", "acute respiratory distress syndrome", and "acute lung injury"., Study Selection: Articles were chosen for inclusion based on their relevance to sepsis, acute inflammation, sepsis-related immune suppression, and sepsis-related organ failure. Reference lists were reviewed to identify additional relevant articles., Data Extraction: Relevant data was extracted and synthesized for narrative review., Data Synthesis: Epigenetic regulation is a key determinant of gene expression in sepsis. At the onset of infection, host-pathogen interactions often result in epigenetic alterations to host cells that favor pathogen survival. In parallel, the host inflammatory response is characterized by epigenetic modifications in key regulatory genes, including tumor necrosis factor and interleukin-1β. In human sepsis patients, multiple epigenetic modifying enzymes show differential expression in early sepsis, suggesting a role for epigenetics in coordinating the response to infection. In the later stages of sepsis, epigenetic modifications accompany endotoxin tolerance and the immune-suppressed state. In animal models, treatment with epigenetic modifiers can mitigate the effects of sepsis and improve survival as well as reverse sepsis-associated organ injury., Conclusions: Epigenetic modifications are associated with key phases of sepsis, from the host-pathogen interaction, to acute inflammation, to immune suppression. Epigenetic markers show promise in the diagnosis and prognosis of sepsis and epigenetic modifying agents show promise as therapeutic tools in animal models of sepsis. Human studies in the area of epigenetics are sorely lacking and should be a priority for sepsis researchers.

Background: Sepsis is a life-threatening syndrome and a leading cause of morbidity and mortality representing significant financial burden on the health-care system. Early identification and intervention is crucial to maximizing positive outcomes. We studied a quality improvement initiative with the aim of reviewing the initial management of patients with sepsis in Canadian community emergency departments, to identify areas for improving the delivery of sepsis care. We present a retrospective, multicenter, observational study during 2011 to 2015 in the community setting., Methods: We collected data on baseline characteristics, clinical management metrics (triage-to-physician-assessment time, triage-to-lactate-drawn time, triage-to-antibiotic time, and volume of fluids administered within the first 6 hours of triage), and outcomes (intensive care unit [ICU] admission, in-hospital mortality) from a regional database., Results: A total of 2056 patients were analyzed. The median triage-to-physician-assessment time was 50 minutes (interquartile range [IQR]: 25-104), triage-to-lactate-drawn time was 50 minutes (IQR: 63-94), and triage-to-antibiotics time was 129 minutes (IQR: 70-221). The median total amount of fluid administered within 6 hours of triage was 2.0 L (IQR: 1.5-3.0). The ICU admission rate was 36% and in-hospital mortality was 25%. We also observed a higher ICU admission rate (51% vs 24%) and in-hospital mortality (44% vs 14%) in those with higher lactate concentration (≥4 vs ≤2 mmol/L), independent of other sepsis-related parameters., Conclusion: Time-to-physician-assessment, time-to-lactate-drawn, time-to-antibiotics, and fluid resuscitation in community emergency departments could be improved. Future quality improvement interventions are required to optimize management of patients with sepsis. Elevated lactate concentration was also independently associated with ICU admission rate and in-hospital mortality rate., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: Epigenetic alterations are an important regulator of gene expression in health and disease; however, epigenetic data in sepsis are lacking. To demonstrate proof of concept and estimate effect size, we performed the first epigenome-wide methylation analysis of whole blood DNA samples from a cohort of septic and nonseptic critically ill patients., Design: A nested case-control study using genomic DNA isolated from whole blood from septic (n = 66) and nonseptic (n = 68) critically ill patients on "Day 1" of ICU admission. Methylation patterns were identified using Illumina 450K arrays with percent methylation expressed as β values. After quality control, 134 participants and 414,818 autosomal cytosine-phosphate-guanine sites were used for epigenome-wide methylation analyses., Setting: Tertiary care hospitals., Subjects: Critically ill septic and nonseptic patients., Interventions: Observational study., Measurements and Main Results: A total of 668 differentially methylated regions corresponding to 443 genes were identified. Known sepsis-associated genes included complement component 3; angiopoietin 2; myeloperoxidase; lactoperoxidase; major histocompatibility complex, class I, A; major histocompatibility complex, class II, isotype DR β I; major histocompatibility complex, class I, C; and major histocompatibility complex, class II, isotype DQ β I. When compared with whole blood gene expression data from seven external datasets containing septic and nonseptic patients, 81% of the differentially methylated region-associated genes were differentially expressed in one or more datasets and 31% in three or more datasets. Functional analysis showed enrichment for antigen processing and presentation, methyltransferase activity, cell adhesion, and cell junctions. Analysis by weighted gene coexpression network analysis revealed DNA comethylation modules that were associated with clinical traits including severity of illness, need for vasopressors, and length of stay., Conclusions: DNA methylation marks may provide important causal and potentially biomarker information in critically ill patients with sepsis.

Competing Interests: Competing interests: Oleksa Rewa has received consultant fees from Baxter, outside the submitted work. No other competing interests were declared.

Introduction: Diarrhoea is a frequent concern in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, increased length of ICU stay, skin breakdown and renal dysfunction. However, its prevalence, aetiology and prognosis in the critically ill have been poorly studied. The primary objectives of this study are to determine the incidence, risk factors and consequences of diarrhoea in critically ill adults. The secondary objectives are to estimate the incidence of Clostridium difficile- associated diarrhoea (CDAD) in ICU patients and to validate the Bristol Stool Chart and Bliss Stool Classification System characterising bowel movements in the ICU. Our primary outcome is the incidence of diarrhoea . Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay., Methods and Analysis: This international prospective cohort study will enrol patients over 10 weeks in 12 ICUs in Canada, the USA, Poland and Saudi Arabia. We will include all patients 18 years of age and older who are admitted to the ICU for at least 24 hours and follow them daily until ICU discharge. Our primary outcome is the incidence of diarrhoea based on the WHO definition, during the ICU stay. Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay. We will use logistic regression to identify factors associated with diarrhoea (as defined using WHO criteria) and the kappa statistic to measure agreement on diarrhoea rates between the WHO definition and the Bristol Stool Chart and Bliss Stool Classification System., Ethics and Dissemination: The protocol has been approved by the research ethics board of all participating centres. The diarrhoea interventions, consequences and epidemiology in the intensive care unit (DICE-ICU) study will generate evidence about diarrhoea and its frequency, predisposing factors and consequences, to inform critical care practice and future research., Lay Summary: Diarrhoea is a frequent clinical problem for hospitalised patients including those who are critically ill in the ICU. Diarrhoea can cause complications such as skin damage, dehydration and kidney problems. It is not clear how common diarrhoea is in the ICU, the factors that cause it or the best way for clinicians to assess it. The DICE-ICU study is an international prospective observational study to examine the frequency, risk factors and outcomes of diarrhoea during critical illness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pain and agitation are closely linked to the development of delirium, which affects 60%-87% of critically ill patients. Delirium is associated with increased mortality and morbidity. Clinical guidelines that suggest routine assessment, treatment and prevention of pain, agitation and delirium (PAD) is crucial to improving patient outcomes. However, the adoption of and adherence to PAD guidelines remain suboptimal, especially in community hospitals. The aim of this quality improvement study is to evaluate the impact of a multifaceted and multidisciplinary intervention on PAD management in a Canadian community intensive care unit (ICU)., Methods: This is a quality improvement, uncontrolled, before-and-after study of a multifaceted and multidisciplinary intervention targeting nurses (educational modules, visual reminders), family members (interviews, educational pamphlets and an educational video), physicians (multidisciplinary round script) and the multidisciplinary team as a whole (delirium poster). We will collect data every day for 6 weeks before implementing the intervention. Data collection will include clinical information and information on process of care. We will then implement the intervention. Four weeks after, we will collect data daily for 6 weeks to evaluate the effect of the intervention. On the basis of the volume of the ICU, we expect to enroll approximately 280 patients. We have obtained local ethics approval from the Hamilton Integrated Research Ethics Board (HiREB 18-040-C)., Interpretation: The results of this quality improvement study will provide information on adherence to PAD guidelines in a Canadian community ICU setting. They will also supply information on the feasibility of implementing multifaceted and multidisciplinary PAD interventions in community ICUs., Competing Interests: Competing interests: None declared., (Copyright 2019, Joule Inc. or its licensors.)

Objectives: The purpose of this study was to explore the experiences, beliefs and perceptions of intensive care unit (ICU) nurses on the management of pain, agitation and delirium (PAD) in critically ill patients., Design: A qualitative descriptive study., Setting: This study took place in a community hospital ICU located in a medium size Canadian city., Participants: Purposeful sampling was conducted. Participants included full-time nurses working in the ICU. Forty-six ICU nurses participated., Methods: A total of five focus group sessions were held to collect data. There were one to three separate groups in each focus group session, with no more than seven participants in each group. There were 10 separate groups in total. A semistructured question guide was used. Thematic analysis method was adopted to analyse the data, and to search for emergent themes and patterns., Results: Three main themes emerged: (1) the professional perspectives on patient wakefulness state, (2) the professional perspectives on PAD management of critically ill patients and (3) the factors impacting PAD management. Nurses have different opinions on the optimal level of patient sedation and felt that many factors, including environmental, healthcare teams, patients and family members, can influence PAD management. This potentially leads to inconsistent PAD management in critically ill patients. The nurses also believed that PAD management requires a multidisciplinary approach including healthcare teams and patients' families., Conclusions: Many external and internal factors contribute to the complexity of PAD management including the attitudes of nursing staff towards PAD. The themes emerged from this study suggested the need of a multifaceted and multidisciplinary quality improvement programme to optimise the management of PAD in the ICU., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Delirium is a common manifestation in the intensive care unit (ICU) that is associated with increased mortality and morbidity. Guidelines suggested appropriate management of pain, agitation and delirium (PAD) is crucial in improving patient outcomes. However, the practice of PAD assessment and management in community hospitals is unclear and the mechanisms contributing to the potential care gap are unknown., Objectives: This quality improvement initiative aimed to review the practice of PAD assessment and management in a community medical-surgical ICU (MSICU) and to explore the community MSICU nurses' perceived comfort and satisfaction with PAD management in order to understand the mechanisms of the observed care gap and to inform subsequent quality improvement interventions., Methods: We prospectively collected basic demographic data, clinical information and daily data on PAD process measures including PAD assessment and target Richmond Agitation-Sedation Scale (RASS) score ordered by intensivists on all patients admitted to a community MSICU for >24 hours over a 20-week period. All ICU nurses in the same community MSICU were invited to participate in an anonymous survey., Results: We collected data on a total of 1101 patient-days (PD). 653 PD (59%), 861 PD (78%) and 439 PD (39%) had PAD assessment performed, respectively. Target RASS was ordered by the intensivists on 515 PD (47%). Our nurse survey revealed that 88%, 85% and 41% of nurses were comfortable with PAD assessment, respectively., Conclusions: Delirium assessment was not routinely performed. This is partly explained by the discomfort nurses felt towards conducting delirium assessment. Our results suggested that improvement in nurse comfort with delirium assessment and management is needed in the community MSICU setting., Competing Interests: Competing interests: None declared.

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS systems was not officially launched for diagnostic use in clinical microbiology laboratories in China until 2012. Here, we report the findings from the first large-scale evaluation study of VITEK MS for routine bacterial identification in two major diagnostic centres in Beijing and Hong Kong. A total of 2266 unique isolates representing 56 genera and 127 species were analysed, and results were compared to those obtained by VITEK 2. Any discrepancies were resolved by 16S rRNA sequencing. Overall, VITEK MS provided correct identification for 2246 (99.1%) isolates, including 2193 (96.8 %) with correct species-level identifications and 53 (2.3 %) matched at the genus level only. VITEK MS surpassed VITEK 2 consistently in species-level identification of important pathogens, including non-Enterobacteriaceae Gram-negative bacilli (94.7 versus 92 %), staphylococci (99.7 versus 92.4 %), streptococci (92.6 versus 79.4 %), enterococci (98.8 versus 92.6 %) and Clostridium spp. (97.3 versus 55.5 %). The findings demonstrated that VITEK MS is highly accurate and reliable for routine bacterial identification in clinical settings in China., (© 2015 The Authors.)

Activated neutrophils can injure host cells through direct effects of oxidants on membrane phospholipids, but an ability to induce apoptotic cell death has not previously been reported. We show that neutrophils activated in vivo in patients who have sustained multiple trauma or in vitro by exposure to bacterial lipopolysaccharide promote epithelial cell apoptosis through SHP-1-mediated dephosphorylation of epithelial cell caspase-8. Epithelial cell apoptosis induced by circulating neutrophils from patients who had sustained serious injury depended on the generation of neutrophil-derived reactive oxygen intermediates and was blocked by inhibition of NADPH oxidase or restoration of intracellular glutathione. Caspase-8 was constitutively tyrosine phosphorylated in a panel of resting epithelial cells, but underwent SHP-1-dependent dephosphorylation in response to hydrogen peroxide, activated neutrophils, or inhibition of Src kinases. Cells transfected with a mutant caspase-8 in which tyrosine residues at Tyr397 or Tyr465 are replaced by nonphosphorylatable phenylalanine underwent accelerated apoptosis, whereas either mutation of these residues to phosphomimetic glutamic acid or transfection with the Src kinases Lyn or c-Src inhibited hydrogen peroxide-induced apoptosis. Exposure to either hydrogen peroxide or lipopolysaccharide-stimulated neutrophils increased phosphorylation and activity of the phosphatase SHP-1, increased activity of caspases 8 and 3, and accelerated epithelial cell apoptosis. These observations reveal a novel mechanism for neutrophil-mediated tissue injury through oxidant-dependent, SHP-1-mediated dephosphorylation of caspase-8 resulting in enhanced epithelial cell apoptosis., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Innate-like lymphocytes are a recently described subset of the immune response with known antibacterial properties. This human trial in critically ill patients provides the first evidence of the drop in MAIT cells during bacterial sepsis, which compounds the already known immune defects. The persistent depletion and potential for nosocomial infections is an interesting finding and one likely to provide fertile grounds for future studies.