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OBJECTIVE: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. STUDY DESIGN: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. RESULTS: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled

BACKGROUND: Characterizing the multiorgan manifestations and outcomes of patients hospitalized with COVID-19 will inform resource requirements to address the long-term burden of this disease. We conducted a descriptive analysis using prospectively collected data to describe the clinical characteristics and spectrum of organ dysfunction, and in-hospital and longer-term clinical outcomes of patients hospitalized with COVID-19 during the first wave of the pandemic at a Canadian centre. METHODS: We conducted a prospective case series involving adult patients (aged ≥ 18 yr) with COVID-19 admitted to 1 of 2 hospitals in London, Ontario, from Mar. 17 to June 18, 2020, during the first wave of the pandemic. We recorded patients' baseline characteristics, physiologic parameters, measures of organ function and therapies administered during hospitalization among patients in the intensive care unit (ICU) and in non-ICU settings, and compared the characteristics of hospital survivors and nonsurvivors. Finally, we recorded follow-up thoracic computed tomography (CT) and echocardiographic findings after hospital discharge. RESULTS: We enrolled 100 consecutive patients (47 women) hospitalized with COVID-19, including 32 patients who received ICU care and 68 who received treatment in non-ICU settings. Respiratory sequelae were common: 23.0% received high-flow oxygen by nasal cannula, 9.0% received noninvasive ventilation, 24.0% received invasive mechanical ventilation and 2.0% received venovenous extracorporeal membrane oxygenation. Overall, 9.0% of patients had cerebrovascular events (3.0% ischemic stroke, 6.0% intracranial hemorrhage), and 6.0% had pulmonary embolism. After discharge, 11 of 19 patients had persistent abnormalities on CT thorax, and 6 of 15 had persistent cardiac dysfunction on echocardiography. INTERPRETATION: This study provides further evidence that COVID-19 is a multisystem disease involving neurologic, cardiac and thrombotic dysfunction, without evidence of hepatic dysfunction. Patients have persistent organ dysfunction after hospital discharge, underscoring the need for research on long-term outcomes of COVID-19 survivors.

Providing optimal care to patients with acute respiratory illness while preventing hospital transmission of COVID-19 is of paramount importance during the pandemic; the challenge lies in achieving both goals simultaneously. Controversy exists regarding the role of early intubation versus use of non-invasive respiratory support measures to avoid intubation. This review summarizes available evidence and provides a clinical decision algorithm with risk mitigation techniques to guide clinicians in care of the hypoxemic, non-intubated, patient during the COVID-19 pandemic. Although aerosolization of droplets may occur with aerosol-generating medical procedures (AGMP), including high flow nasal oxygen and non-invasive ventilation, the risk of using these AGMP is outweighed by the benefit in carefully selected patients, particularly if care is taken to mitigate risk of viral transmission. Non-invasive support measures should not be denied for conditions where previously proven effective and may be used even while there is suspicion of COVID-19 infection. Patients with de novo acute respiratory illness with suspected/confirmed COVID-19 may also benefit. These techniques may improve oxygenation sufficiently to allow some patients to avoid intubation; however, patients must be carefully monitored for signs of increased work of breathing. Patients showing signs of clinical deterioration or high work of breathing not alleviated by non-invasive support should proceed promptly to intubation and invasive lung protective ventilation strategy. With adherence to these principles, risk of viral spread can be minimized.

Purpose: The 3 Wishes Project (3WP) promotes holistic end-of-life care in the intensive care unit (ICU) to honor dying patients, support families, and encourage clinician compassion. Organ donation is a wish that is sometimes made by, or on behalf of, critically ill patients. Our objective was to describe the interface between the 3WP and organ donation as experienced by families, clinicians, and organ donation coordinators. Methods: In a multicenter evaluation of the 3WP in 4 Canadian ICUs, we conducted a thematic analysis of transcripts from interviews and focus groups with clinicians, organ donation coordinators, and families of dying or died patients for whom donation was considered. Results: We analyzed transcripts from 26 interviews and 2 focus groups with 18 family members, 17 clinicians, and 6 organ donation coordinators. The central theme describes the mutual goals of the 3WP and organ donation—emphasizing personhood and agency across the temporal continuum of care. During family decision-making, conversations encouraged by the 3WP can facilitate preliminary discussions about donation. During preparation for donation, memory-making activities supported by the 3WP redirect focus toward personhood. During postmortem family care, the 3WP supports families, including when donation is unsuccessful, and highlights aspirational pursuits of donation while encouraging reflections on other fulfilled wishes. Conclusions: Organ donation and the 3WP provide complementary opportunities to engage in value-based conversations during the dying process. The shared values of these programs may help to incorporate organ donation and death into a person’s life narrative and incorporate new life into a person’s death narrative.

Hemodynamic management of adults with distributive shock often includes the use of catecholamine-based vasoconstricting medications. It is unclear whether adding vasopressin or vasopressin analogues to catecholamine therapy is beneficial in the management of patients with distributive shock. The purpose of this guideline was to develop an evidence-based recommendation regarding the addition of vasopressin to catecholamine vasopressors in the management of adults with distributive shock. We summarized the evidence informing this recommendation by updating a recently published meta-analysis. Then, a multidisciplinary panel from the Canadian Critical Care Society developed the recommendation using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The updated systematic review identified 25 randomized controlled trials including a total of 3,737 patients with distributive shock. Compared with catecholamine therapy alone, the addition of vasopressin or its analogues was associated with a reduced risk of mortality (relative risk [RR], 0.91; 95% confidence interval [CI], 0.85 to 0.99; low certainty), reduced risk of atrial fibrillation (RR, 0.77; 95% CI, 0.67 to 0.88; high certainty), and increased risk of digital ischemia (RR, 2.56; 95% CI, 1.24 to 5.25; moderate certainty). After considering certainty in the evidence, values and preferences, cost, and other factors, the expert guideline panel suggests using vasopressin or vasopressin analogues in addition to catecholamines over catecholamine vasopressors alone for the management of distributive shock (conditional recommendation, low certainty evidence).

Key Points Question Do clinical practice guidelines (CPGs) that report on pharmacologic treatments of hospitalized patients with COVID-19 meet the National Academy of Medicine standards for trustworthiness? Findings In this systematic review of 32 CPGs of predominantly low quality, few reported funding sources or conflicts of interest, included a methodologist, described a search strategy or study selection process, or synthesized evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated the confidence in the quality of the evidence (6 [18.8%]), described potential benefits and harms (6 [18.8%]), or graded the strength of recommendations (5 [15.6%]). Meaning The findings of this study suggest that few COVID-19 CPGs meet National Academy of Medicine standards for trustworthy guidelines., This systematic review evaluates the quality and trustworthiness of clinical practice guidelines for pharmacologic treatment of hospitalized patients with COVID-19 using the National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards instrument., Importance The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission. Objective To appraise the quality of clinical practice guidelines (CPGs) using the National Academy of Medicine (NAM) criteria. Evidence Review A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument. Findings Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 [18.8%]), described potential benefits and harms (6 of 32 [18.8%]), or graded the strength of the recommendations (5 of 32 [15.6%]). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions. Conclusions and Relevance In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges. Trial Registration PROSPERO Identifier: CRD42021245239

Objective: Concerns that medical assistance in dying (MAiD) may harm vulnerable groups unable to access medical treatments and social supports have arisen since the legalization of MAiD on June 17, 2016; however, there is little research on the topic. The purpose of this study is to investigate the socioeconomic status (SES) of patients who request MAiD at the London Health Sciences Centre (LHSC). Methods: A retrospective analysis of patients from the LHSC MAiD database between June 6, 2016 and December 20, 2019 was conducted. Patients were linked to income data from the 2016 Canadian Census, and their corresponding income quintile was a proxy for SES. Geographic information system (GIS) mapping software was used to visualize the distribution of income and MAiD requests. Results: 39.4% of the LHSC catchment area was classified as low SES. Two hundred thirty-seven (58.1%) MAiD requests came from low SES patients and 171 (41.9%) requests came from high SES patients. Two hundred fifty-nine (63.5%) patients who requested a MAiD assessment did not receive MAiD following their request. Of the 237 lower SES patients, 150 (63.3% [95% CI 57.2-69.3]) did not receive MAiD. Of the 171 higher SES patients, 109 (63.7% [95% CI 56.5-70.9]) did not receive MAiD. Conclusion: A disproportionate number of requests for a MAiD assessment at LHSC came from lower SES patients; however, similar proportions of patients who requested MAiD from each SES group received aid in dying. Future research should explore why a disproportionately high number of low SES patients request MAiD at LHSC.

Digital, Background: The coronavirus disease 19 (covid-19) pandemic has underscored the need to expedite clinical research, which may lead investigators to shift away from measuring patient-important outcomes (PIO), limiting research applicability. We aim to investigate if randomized controlled trials (RCTs) of covid-19 pharmacological thera‑ pies include PIOs. Methods: We will perform a meta-epidemiological study of RCTs that included people at risk for, or with suspected, probable, or confrmed covid-19, examining any pharmacological treatment or blood product aimed at prophylaxis or treatment. We will obtain data from all RCTs identifed in a living network metanalysis (NMA). The main data sources are the living WHO covid-19 database up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Two reviewers independently will review each citation, full-text article, and abstract data. To categorize the out‑ comes according to their importance to patients, we will adapt a previously defned hierarchy: a) mortality, b) quality of life/ functional status/symptoms, c) morbidity, and d) surrogate outcomes. Outcomes within the category a) and b) will be considered critically important to patients, and outcomes within the category c) will be regarded as important. We will use descriptive statistics to assess the proportion of studies that report each category of outcomes. We will perform univariable and multivariable analysis to explore associations between trial characteristics and the likelihood of reporting PIOs. Discussion: The fndings from this meta-epidemiological study will help health care professionals and researchers understand if the current covid-19 trials are efectively assessing and reporting the outcomes that are important to patients. If a defciency in capturing PIOs is identifed, this information may help inform the development of future RCTs in covid-19. Systematic review registrations: Open Science Framework registration: osf.io/6xgjz., Ciencias Médicas y de la Salud

BACKGROUND Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature. OBJECTIVE We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19. METHODS We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available. RESULTS Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses. CONCLUSIONS The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review. CLINICALTRIAL PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209187 INTERNATIONAL REGISTERED REPORT RR1-10.2196/33989

To evaluate the impact of the COVID-19 pandemic on Canadian intensive care unit (ICU) workers.Between June and August 2020, we distributed a cross-sectional online survey of ICU workers evaluating the impact of the pandemic, coping strategies, symptoms of post-traumatic stress disorder (PTSD; Impact of Events Scale-Revised), and psychological distress, anxiety, and depression (Kessler Psychological Distress Scale). We performed regression analyses to determine the predictors of psychological symptoms.We analyzed responses from 455 ICU workers (80% women; 67% from Ontario; 279 nurses, 69 physicians, and 107 other healthcare professionals). Respondents felt that their job put them at great risk of exposure (60%), were concerned about transmitting COVID-19 to family members (76%), felt more stressed at work (67%), and considered leaving their job (37%). Overall, 25% had probable PTSD and 18% had minimal or greater psychological distress. Nurses were more likely to report PTSD symptoms (33%) and psychological distress (23%) than physicians (5% for both) and other health disciplines professionals (19% and 14%). Variables associated with PTSD and psychological distress included female sex (beta-coefficient [B], 1.59; 95% confidence interval [CI], 1.20 to 2.10 and B, 3.79; 95% CI, 1.79 to 5.78, respectively; P0.001 for differences in scores across groups) and perceived increased risk due to PPE shortage or inadequate PPE training (B, 1.87; 95% CI, 1.51 to 2.31 and B, 4.88; 95% CI, 3.34 to 6.43, respectively). Coping strategies included talking to friends/family/colleagues (80%), learning about COVID-19 (78%), and physical exercise (68%). Over half endorsed the following workplace strategies as valuable: hospital-provided scrubs, clear communication and protocols by hospitals, knowing their voice is heard, subsidized parking, and gestures of appreciation from leadership.This survey study shows that ICU workers have been impacted by the COVID-19 pandemic with high levels of stress and psychological burden. Respondents endorsed communication, protocols, and appreciation from leadership as helpful mitigating strategies.RéSUMé: OBJECTIF: Évaluer l’impact de la pandémie de COVID-19 sur les travailleurs canadiens des unités de soins intensifs (USI). MéTHODE: Entre juin et août 2020, nous avons fait parvenir un sondage transversal en ligne aux travailleurs des soins intensifs pour évaluer l’impact de la pandémie, les stratégies d’adaptation et les symptômes de stress post-traumatique (SPT; Échelle révisée de l’impact de l’événement - IES-R), ainsi que la détresse psychologique, l’anxiété et la dépression (Échelle de détresse psychologique de Kessler). Nous avons réalisé des analyses de régression pour déterminer les prédicteurs de symptômes psychologiques. RéSULTATS: Nous avons analysé les réponses de 455 travailleurs des soins intensifs (80 % de femmes; 67 % de l’Ontario; 279 infirmières/infirmiers, 69 médecins et 107 autres professionnels de la santé). Les répondants ont estimé que leur emploi les plaçait face à un risque élevé d’exposition (60 %), craignaient de transmettre la COVID-19 aux membres de leur famille (76 %), se sentaient plus stressés au travail (67 %) et avaient envisagé de quitter leur emploi (37 %). Dans l’ensemble, 25 % souffraient probablement d’un SPT et 18 % présentaient une détresse psychologique minimale ou supérieure. Les infirmières et infirmiers étaient plus susceptibles de rapporter des symptômes de SPT (33 %) et de détresse psychologique (23 %) que les médecins (5 % pour les deux) et les professionnels de la santé des autres disciplines (19 % et 14 %). Les variables associées à un SPT et à la détresse psychologique comprenaient le sexe féminin (coefficient bêta [B], 1,59; intervalle de confiance [IC] à 95 %, 1,20 à 2,10 et B, 3,79; IC 95 %, 1,79 à 5,78, respectivement; P0,001 pour les différences de scores entre les groupes) et la perception d’un risque accru en raison des pénuries d’EPI ou d’une formation inadéquate en EPI (B, 1,87; IC 95 %, 1,51 à 2,31 et B, 4,88; IC 95 %, 3,34 à 6,43, respectivement). Les stratégies d’adaptation comprenaient le fait de parler aux amis, à la famille ou aux collègues (80 %), l’acquisition de connaissances concernant la COVID-19 (78 %) et l’exercice physique (68 %). Plus de la moitié ont estimé que les stratégies de travail suivantes étaient utiles : des uniformes fournis par les hôpitaux, une communication et des protocoles clairs de la part des hôpitaux, le fait de savoir que leur voix est entendue, un stationnement subventionné et des gestes d’appréciation de la part des dirigeants. CONCLUSION: Cette étude montre que les travailleurs des soins intensifs ont été touchés par la pandémie de COVID-19 avec des niveaux élevés de stress et de fardeau psychologique. Les répondants ont déclaré que la communication, les protocoles et les gestes d’appréciation de la direction constituaient des stratégies d’atténuation utiles.

Elevated cardiac troponin concentrations in people with critical illness are associated with an increased risk of death. We aimed to assess the feasibility of a larger study to ascertain the utility of cardiac troponin as a prognostic tool for mortality in critically ill patients. Patients admitted to participating intensive care units during the one-month enrolment period were eligible. We excluded cardiac surgical patients and patients who were admitted and either died or were discharged within 12 hr. In enrolled patients, we measured high-sensitivity cardiac troponin I (hs-cTnI) and obtained electrocardiograms to ascertain the incidence of myocardial infarction (MI) and isolated troponin elevation. Our feasibility objectives were to measure recruitment rate, the proportion of patients who consented under a deferred consent model, and time required for data collection and study procedures. Over a four-week enrolment period, 280 patients were enrolled using a deferred consent model. We obtained subsequent consent from 81% of patients. Study procedures and data collection required 1.7 hr per participant. Overall, 86 (38%) suffered a MI, 23 (10%) had an isolated hs-cTnI elevation, and 117 (52%) had no hs-cTnI elevation. The crude hospital mortality rate was 10% without an hs-cTnI elevation, 29% with an isolated hs-cTnl elevation (relative risk [RR]) 2.2; 95% confidence interval [CI], 1.0 to 6.0) and 29% with an MI (RR, 2.6; 95% CI, 1.4 to 5.1). Myocardial injury with elevated hs-cTnI concentrations and MIs occur frequently during critical illness. This pilot study has established the feasibility of conducting a large-scale investigation addressing this issue.

In response to the rapid spread of SARS-CoV-2, hospitals in Canada enacted temporary visitor restrictions to limit the spread of COVID-19 and preserve personal protective equipment supplies. This study describes the extent, variation, and fluctuation of Canadian adult intensive care unit (ICU) visitation policies before and during the first wave of the COVID-19 pandemic.We conducted an environmental scan of Canadian hospital visitation policies throughout the first wave of the pandemic. We conducted a two-phased study analyzing both quantitative and qualitative data.We collected 257 documents with reference to visitation policies (preCOVID, 101 [39%]; midCOVID, 71 [28%]; and lateCOVID, 85 [33%]). Of these 257 documents, 38 (15%) were ICU-specific and 70 (27%) referenced the ICU. Most policies during the midCOVID/lateCOVID pandemic period allowed no visitors with specific exceptions (e.g., end-of-life). Framework analysis revealed five overarching themes: 1) reasons for restricted visitation policies; 2) visitation policies and expectations; 3) exceptions to visitation policy; 4) patient and family-centred care; and 5) communication and transparency.During the first wave of the COVID-19 pandemic, most Canadian hospitals had public-facing visitor restriction policies with specific exception categories, most commonly for patients at end-of-life, patients requiring assistance, or COVID-19 positive patients (varying from not allowed to case-by-case). Further studies are needed to understand the consistency with which visitation policies were operationalized and how they may have impacted patient- and family-centred care.RéSUMé: OBJECTIF: En réponse à la propagation rapide du SRAS-CoV-2, les hôpitaux du Canada ont adopté des restrictions temporaires pour les visites afin de limiter la propagation de la COVID-19 et de préserver les stocks d’équipements de protection individuelle. Cette étude décrit l’ampleur, les variations et fluctuations des politiques canadiennes concernant les visites aux unités de soins intensifs (USI) pour adultes avant et pendant la première vague de la pandémie de COVID-19. MéTHODE: Nous avons réalisé une étude de milieu des politiques hospitalières canadiennes concernant les visites tout au long de la première vague de la pandémie. Nous avons mené une étude en deux phases analysant des données quantitatives et qualitatives. RéSULTATS: Nous avons recueilli 257 documents faisant référence aux politiques de visites (pré-COVID, 101 [39 %]; mid-COVID, 71 [28 %]; et COVID-tardif, 85 [33 %]). Sur ces 257 documents, 38 (15 %) étaient spécifiques aux USI et 70 (27 %) faisaient référence aux USI. La plupart des politiques au cours de la période pandémique mid-COVID/COVID-tardif ne permettaient aucune visite sauf exception spécifique (p. ex., fin de vie). L’analyse du cadre a révélé cinq thèmes généraux : 1) les raisons des restrictions des politiques de visites; 2) les politiques et attentes en matière de visites; 3) les exceptions aux politiques de visites; 4) les soins aux patients et centrés sur la famille; et 5) la communication et la transparence. CONCLUSION: Au cours de la première vague de la pandémie de COVID-19, la plupart des hôpitaux canadiens avaient des politiques de restriction des visites s’appliquant au public avec des catégories d’exception spécifiques, le plus souvent pour les patients en fin de vie, les patients nécessitant de l’aide ou les patients COVID-positifs (variant d’une interdiction au cas par cas). D’autres études sont nécessaires pour comprendre l’uniformité avec laquelle les politiques de visites ont été mises en œuvre et comment elles ont pu avoir une incidence sur les soins centrés sur le patient et la famille.

Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%-100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.

ObjectivesSARS-CoV-2-related disease, referred to as COVID-19, has emerged as a global pandemic since December 2019. While there is growing recognition regarding possible airborne transmission, particularly in the setting of aerosol-generating procedures and treatments, whether nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 generate aerosols remains unclear.DesignSystematic review.Data sourcesWe searched Ovid MEDLINE and EMBASE up to 3 November 2020. We also searched the China National Knowledge Infrastructure, Chinese Medical Journal Network, medRxiv and ClinicalTrials.gov up to 29 March 2020.Eligibility criteriaAll comparative and non-comparative studies that evaluated dispersion or aerosolisation of viable airborne organisms, or transmission of infection associated with nasopharyngeal or oropharyngeal swab testing.ResultsOf 7702 citations, only one study was deemed eligible. Using a dedicated sampling room with negative pressure isolation room, personal protective equipment including N95 or higher masks, strict sterilisation protocols, structured training with standardised collection methods and a structured collection and delivery system, a tertiary care hospital proved a 0% healthcare worker infection rate among eight nurses conducting over 11 000 nasopharyngeal swabs. No studies examining transmissibility with other safety protocols, nor any studies quantifying the risk of aerosol generation with nasopharyngeal or oropharyngeal swabs for detection of SARS-CoV-2, were identified.ConclusionsThere is limited to no published data regarding aerosol generation and risk of transmission with nasopharyngeal and oropharyngeal swabs for the detection of SARS-CoV-2. Field experiments to quantify this risk are warranted. Vigilance in adhering to current standards for infection control is suggested.

ObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 19 January 2021, and six additional Chinese databases to 20 January 2021.Study selectionRandomized trials in which people at risk of covid-19 were randomized to drug prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsThe first iteration of this living network meta-analysis includes nine randomized trials – six addressing hydroxychloroquine (6,059 participants), one addressing ivermectin combined with iota-carrageenan (234 participants) and two addressing ivermectin alone (540 participants), all compared to standard care or placebo. Hydroxychloroquine has no important effect on admission to hospital (risk difference (RD) 1 fewer per 1,000, 95% credible interval (CrI) 3 fewer to 4 more, high certainty) or mortality (RD 1 fewer per 1,000, 95% CrI 2 fewer to 3 more, high certainty). Hydroxychloroquine probably has no important effect on laboratory-confirmed infection (RD 2 more per 1,000, 95% CrI 18 fewer to 28 more, moderate certainty), probably increases adverse effects leading to drug discontinuation (RD 19 more per 1,000, 95% CrI 1 fewer to 70 more, moderate certainty) and may have no important effect on suspected, probable or laboratory-confirmed infection (RD 15 fewer per 1,000, 95% CrI 64 fewer to 41 more, low certainty). Due to serious risk of bias and very serious imprecision – and thus very low certainty evidence, the effects of ivermectin combined with iota-carrageenan on laboratory-confirmed infection (RD 52 fewer per 1,000, 95% CrI 58 fewer to 37 fewer), and ivermectin alone on laboratory-confirmed infection (RD 50 fewer per 1,000, 95% CrI 59 fewer to 16 fewer) and suspected, probable or laboratory-confirmed infection (RD 159 fewer per 1,000, 95% CrI 165 fewer to 144 fewer) remain uncertain.ConclusionHydroxychloroquine prophylaxis does not have an important effect on hospital admission and mortality, probably increases adverse effects, and probably does not have an important effect on laboratory-confirmed SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, we are highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Additional file 1. Recommendations for Clinical Practice and Future Research.

BackgroundThe coronavirus disease (Covid-19) pandemic has produced a large number of clinical trial reports with unprecedented rapidity, raising concerns about methodological quality and potential for research waste.ObjectivesTo describe the characteristics of randomized clinical trials (RCTs) investigating prophylaxis or treatment of Covid-19 infection and examine the effect of trial characteristics on whether the study reported a statistically significant effect on the primary outcome(s).Study DesignMeta-epidemiological study of Covid-19 treatment and prophylaxis RCTs.Eligibility criteriaEnglish-language RCTs (peer-reviewed or preprint) that evaluated pharmacologic agents or blood products compared to standard care, placebo, or an active comparator among participants with suspected or confirmed Covid-19 or at risk for Covid-19. We excluded trials of vaccines or traditional herbal medicines.Information sourcesWe searched 25 databases in the US Centre for Disease Control Downloadable Database from January 1 to October 21, 2020.Trial appraisal and synthesis methodsWe extracted trial characteristics including number of centres, funding sources (industry versus non-industry), and sample size. We assessed risk of bias (RoB) using the modified Cochrane RoB 2.0 Tool. We used descriptive statistics to summarize trial characteristics and logistic regression to evaluate the association between RoB due to the randomization process, centre status (single vs. multicentre), funding source, and sample size, and statistically significant effect in the primary outcome.ResultsWe included 91 RCTs (46,802 participants) evaluating Covid-19 therapeutic drugs (n = 76), blood products (n = 9) or prophylactic drugs (n = 6). Of these, 40 (44%) were single-centre, 23 (25.3%) enrolled < 50 patients, and 28 (30.8%) received industry funding. RoB varied across trials, with high or probably high overall RoB in 75 (82.4%) trials, most frequently due to deviations from the intended protocol (including blinding) and randomization processes. Thirty-eight trials (41.8%) found a statistically significant effect in the primary outcome. RoB due randomization (odds ratio [OR] 3.77, 95% confidence interval [CI], 1.47 to 9.72) and single centre trials (OR 3.15, 95% CI, 1.25 to 7.97) were associated with higher likelihood of finding a statistically significant effect.ConclusionsThere was high variability in RoB amongst Covid-19 trials. RoB attributed to the randomization process and single centre status were associated with a three-fold increase in the odds of finding a statistically significant effect. Researchers, funders, and knowledge users should remain cognizant of the impact of study characteristics, including RoB, on trial results when designing, conducting, and appraising Covid-19 trials.

Background: The coronavirus disease 19 (covid-19) pandemic has underscored the need to expedite clinical research, which may lead investigators to shift away from measuring patient-important outcomes (PIOs), limiting research applicability. We aim to describe the extent to which randomized controlled trials (RCTs) of covid-19 therapies will determine PIOs. Methods: We will perform a meta-epidemiological study of RCTs that included people at risk for, or with suspected, probable, or confirmed covid-19, examining any pharmacological treatment or blood product aimed at prophylaxis or treatment. We will obtain data from all RCTs identified in a recent published network metanalysis (NMA). To categorize the outcomes according to their importance to patients, we will adapt a previously defined hierarchy: a) mortality, b) quality of life/ functional status/symptoms, c) morbidity, and d) surrogate outcomes. Outcomes within the category a) and b) will be considered critically important to patients, and outcomes within the category c) will be regarded as important. We will use descriptive statistics to assess the proportion of studies that report each category of outcomes. We will perform univariable and multivariable analysis to explore associations between trial characteristics and the likelihood of reporting PIOs. Discussion: The findings from this meta-epidemiological study will help health care professionals and researchers understand if the current covid-19 trials are effectively assessing and reporting the outcomes that are important to patients. If a deficiency in capturing PIOs is identified, this information may help inform the development of future RCTs in covid-19.Systematic Review registrations: Open Science Framework registration: osf.io/6xgjz

Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is publicly available in the supplementary material. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Objectives Numerous risk factors for sleep disruption in critically ill adults have been described. We performed a systematic review of all risk factors associated with sleep disruption in the ICU setting. Data sources PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central Register for Controlled Trials, and Cochrane Database of Systematic Reviews. Study selection English-language studies of any design published between 1990 and April 2018 that evaluated sleep in greater than or equal to 10 critically ill adults (> 18 yr old) and investigated greater than or equal to 1 potential risk factor for sleep disruption during ICU stay. We assessed study quality using Newcastle-Ottawa Scale or Cochrane Risk of Bias tool. Data extraction We abstracted all data independently and in duplicate. Potential ICU sleep disruption risk factors were categorized into three categories based on how data were reported: 1) patient-reported reasons for sleep disruption, 2) patient-reported ratings of potential factors affecting sleep quality, and 3) studies reporting a statistical or temporal association between potential risk factors and disrupted sleep. Data synthesis Of 5,148 citations, we included 62 studies. Pain, discomfort, anxiety/fear, noise, light, and ICU care-related activities are the most common and widely studied patient-reported factors causing sleep disruption. Patients rated noise and light as the most sleep-disruptive factors. Higher number of comorbidities, poor home sleep quality, home sleep aid use, and delirium were factors associated with sleep disruption identified in available studies. Conclusions This systematic review summarizes all premorbid, illness-related, and ICU-related factors associated with sleep disruption in the ICU. These findings will inform sleep promotion efforts in the ICU and guide further research in this field.

We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products.Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology.No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density.High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.RéSUMé: OBJECTIF: Nous avons réalisé deux comptes rendus sur commande de l’Organisation mondiale de la santé pour guider l’utilisation de canules nasales à haut débit (CNHD) chez les patients ayant contracté le coronavirus (COVID-19). Nous avons synthétisé les données probantes concernant leur efficacité et leur innocuité (compte rendu 1), ainsi que les risques de dispersion des gouttelettes, de génération d’aérosols, et de transmission associée d’éléments viraux (compte rendu 2).Des recherches de littérature ont été réalisées dans les bases de données Ovid MEDLINE, Embase, Web of Science, ainsi que dans les bases de données chinoises et medRxiv. Compte rendu 1 : nous avons synthétisé les résultats d’études randomisées contrôlées (ERC) comparant les CNHD à une oxygénothérapie conventionnelle chez des patients en état critique atteints d’insuffisance respiratoire hypoxémique aiguë. Compte rendu 2 : nous avons résumé sous forme narrative les constatations d’études évaluant la dispersion de gouttelettes, la génération d’aérosols ou la transmission infectieuse associées aux CNHD. Pour les deux comptes rendus, des réviseurs appariés ont réalisé la sélection des études, l’extraction des données et l’évaluation du risque de biais de manière indépendante. Nous avons évalué la certitude des données probantes en nous fondant sur la méthodologie GRADE.Aucune étude éligible n’incluait de patients atteints de COVID-19. Compte rendu 1 : 12 ERC (n = 1989 patients) ont fourni des données probantes de certitude faible selon lesquelles les CNHD réduiraient la ventilation invasive (risque relatif [RR], 0,85; intervalle de confiance [IC] 95 %, 0,74 à 0,99) et l’intensification de l’oxygénothérapie (RR, 0,71; IC 95 %, 0,51 à 0,98) chez les patients atteints d’insuffisance respiratoire. Les résultats n’ont pas démontré de différences en matière de mortalité (certitude modérée), ni de durée du séjour hospitalier ou à l’unité des soins intensifs (certitude modérée et faible, respectivement). Compte rendu 2 : quatre études évaluant la dispersion de gouttelettes et trois évaluant la génération et la dispersion d’aérosols ont fourni des données probantes de très faible certitude. Deux études de simulation et une étude croisée ont donné des résultats mitigés quant à l’effet des CNHD sur la dispersion des gouttelettes. Bien que deux études de simulation n’aient rapporté aucune augmentation associée concernant la dispersion d’aérosols, l’une a rapporté que des taux de débit plus élevés étaient associés à des régions à densité d’aérosols élevée plus grandes.Les canules nasales à haut débit pourraient réduire la nécessité de recourir à la ventilation invasive et l’escalade des traitements par rapport à l’oxygénothérapie conventionnelle chez les patients atteints de COVID-19 souffrant d’insuffisance respiratoire hypoxémique aiguë. Cet avantage doit être soupesé contre le risque inconnu de transmission atmosphérique.

Long-term cognitive impairment is common among ICU survivors, but its natural history remains unclear. In this systematic review, we report the frequency of cognitive impairment in ICU survivors across various time points after ICU discharge that were extracted from 46 of the 3,350 screened records. Prior studies used a range of cognitive instruments, including subjective assessments (10 studies), single or screening cognitive test such as Mini-Mental State Examination or Trail Making Tests A and B (23 studies), and comprehensive cognitive batteries (26 studies). The mean prevalence of cognitive impairment was higher with objective rather than subjective assessments (54% [95% confidence interval (CI), 51 57%] vs. 35% [95% CI, 29 41%] at 3 months after ICU discharge) and when comprehensive cognitive batteries rather than Mini-Mental State Examination were used (ICU discharge: 61% [95% CI, 38 100%] vs. 36% [95% CI, 15 63%]; 12 months after ICU discharge: 43% [95% CI, 10 78%] vs. 18% [95% CI, 10 20%]). Patients with acute respiratory distress syndrome had higher prevalence of cognitive impairment than mixed ICU patients at ICU discharge (82% [95% CI, 78 86%] vs. 48% [95% CI, 44 52%]). Although some studies repeated tests at more than one time point, the time intervals between tests were arbitrary and dictated by operational limitations of individual studies or chosen cognitive instruments. In summary, the prevalence and temporal trajectory of ICU-related cognitive impairment varies depending on the type of cognitive instrument used and the etiology of critical illness. Future studies should use modern comprehensive batteries to better delineate the natural history of cognitive recovery across ICU patient subgroups and determine which acute illness and treatment factors are associated with better recovery trajectories.

Organ Donation after Euthanasia Medical assistance in dying followed by organ donation is new to North America. If chosen, this path offers potential donors the opportunity to fulfill their last re...

PURPOSE/OBJECTIVE(S) Medical assistance in dying (MAID) was legislatively enacted in Canada in June 2016. MAID is performed most frequently for oncology patients. The aim of this study is to describe the patient, disease and process characteristics in this population. MATERIALS/METHODS We performed a single-institution review of all oncology patients who requested MAID at a tertiary care hospital between June 2016 and June 2020. A prospective database including patient demographics, terminal illness type, dates of assessment, cause of death, and date of death was used. Additional data such as demographic, oncologic, treatment-related, and symptom-related details were retrospectively collected. Descriptive statistics were reported. Our primary hypothesis is that performance status is one of the important factors associated with MAID provision. RESULTS Between June 2016 and June 2020, 346 oncology patients requested and 103 received MAID. Identifiers were available and data were retrospectively collected for 92/103 patients. Median age was 72 (range 25-97) and 54% were female. The most common primary malignancies were lung (15/92, 16%), pancreaticobiliary (14/92, 16%), colorectal (13/92, 14%), and hematologic malignancy (11/92, 12%). Performance status was documented for 60 patients within 1 week of MAID provision; 90% of patients (54/60) had ECOG performance status of 3 or 4, and 42% patients (25/60) had ECOG performance status of 4. At the time of initial MAID request, 65% of patients (60/92) had metastatic disease, among which 52% of patients (31/60) received palliative-intent systemic therapy. Sixteen percent of patients with metastases (10/60) received at least 3 lines of palliative-intent systemic therapy. Median number of days from first MAID assessment to MAID provision was 7 days (range 0 to 349 days). Sixty-seven percent of patients (60/89) received MAID within 10 days of first MAID assessment and 87% (77/89) within 30 days. The most common debilitating symptoms were uncontrolled pain (53%, 49/92), fatigue (37%, 34/92), and dyspnea (27%, 25/92). CONCLUSION Ninety percent of oncology patients who received MAID had ECOG performance status of 3 or 4, which is reflective of patients' poor prognosis and limited ability to perform daily activity. The median time interval between first MAID assessment to MAID received was 7 days and most patients received MAID within 30 days.

Roux-en-Y gastric bypass (RYGB) is associated with the remission of type 2 diabetes mellitus (DM). There are a number of scoring systems available that help predict type 2 diabetes remission rates after bariatric surgery; however, relatively few have been validated externally. The DiaRem score, comprised of four preoperative variables (age, haemoglobin A1c [HbA1c], sulfonylurea and insulin-sensitizing agent use and insulin use), allows for the identification of patients who are most likely to have DM remission following RYGB. Our primary objective was to determine the variables predictive of DM remission 1 year post-RYGB, determine how well the DiaRem score predicts DM remission 1 year post-RYGB and identify the optimal cut-off DiaRem score. The study is based on results of RYGB performed across multiple centres in Ontario, Canada, overseen by the Centre for Surgical Invention and Innovation in Hamilton, with direction from the Ontario Bariatric Network. Regression analysis was used to determine the predictive value of demographic and clinical variables and that of the DiaRem score. The optimal DiaRem cut-off score was determined using sensitivity and specificity analysis. Of 3874 patients in the Ontario Bariatric Registry between January 2010 and February 2015, 915 had complete 1-year follow-up data. Among these, 15 were not classified as having DM at baseline and were excluded. Of the remaining 900 patients with type 2 diabetes and who underwent RYGB surgery, 333 (37.0%) had DM remission at 1-year follow-up. Three of four DiaRem variables (age, HbA1c, insulin use), in addition to use of any hypoglycaemic agent, were associated with DM remission. DiaRem score had moderate predictive value. A DiaRem score cut-off of

Background: Informed consent is a hallmark of ethical clinical research. An inherent challenge in critical care research is obtaining consent when patients lack decision-making capacity. One solution is deferred consent, which is often used for studies that are low risk or involve emergency interventions. Our objective was to describe a deferred consent model in a low-risk critical care study. Methods: Prognostic Value of Elevated Troponins in Critical Illness Study was a prospective, pilot observational study of critically ill patients in 3 intensive care units, involving serial electrocardiograms and cardiac biomarkers. Newly admitted patients were enrolled over 1 month. When possible, informed consent was obtained a priori from the patient or substitute decision maker (SDM); otherwise, consent was deferred until the patient regained consent capacity or until their SDM was available. Logistic regression analysis was used to determine the association between patient’s sex, Acute Physiology and Chronic Health Evaluation II score, study center, person providing consent (patient vs SDM), method of consent (telephone vs in person), and the provision or not of informed consent. Results: The overall consent rate was 80.1% (213 of 266 persons approached). Of the 53 persons declining consent, 37 (69.8%) agreed to the use of data collected up until that point. Over half of all consent encounters were with patients rather than SDMs. Median interval delay between enrollment and the consent encounter was 1 day. On multivariate analysis, the only variable associated with consent was male sex of the patient (odds ratio for males 2.59, confidence interval: 1.19-5.63). Conclusion: Deferred consent facilitates implementation of time-sensitive research protocols until a consent encounter is possible. As a feasible alternative to exclusive a priori consent, the deferred consent model can be useful in low-risk studies in critically ill patients.

Cardiac transplantation is a definitive therapy for end-stage heart failure, but demand exceeds supply. Cardiac donation after circulatory determination of death (cardiac DCDD) can be performed using direct procurement and perfusion (DPP), where cardiac activity is restored after heart recovery, or (NRP), where brain blood supply is surgically interrupted, circulation to the thoraco-abdominal organs is restored within the donor’s body, followed by heart recovery. While cardiac DCDD would increase the number of heart donors, uptake of programs has been slowed in part because of ethical concerns within the medical community. These debates have been largely devoid of discussion regarding public perceptions. We conducted a national survey of public perceptions regarding cardiac DCDD. We surveyed 1,001 Canadians about their attitudes towards cardiac DCDD using a rigorously designed and pre-tested survey. We found that 843 of 1,001 respondents (84.2%; 95% confidence interval [CI], 81.8 to 86.3) accepted the DPP approach, 642 (64.1%; 95% CI, 61.1 to 67.0) would agree to donate their heart using DPP, and 696 (69.5%; 95% CI, 66.6 to 72.3) would consent to the same for a family member. We found that 779 respondents of 1,001 respondents (77.8%; 95% CI, 75.1 to 80.3) accepted the NRP approach, 587 (58.6%; 95% CI, 55.5 to 61.6) would agree to donate their heart using NRP, and 636 (63.5%; 95% CI, 60.5 to 66.4) would consent to the same for a family member. Most respondents supported the implementation of DPP (738 respondents or 73.7%; 95% CI, 70.9 to 76.3) and NRP (655 respondents or 65.4%; 95% CI, 62.4 to 68.3) in Canada. The results of this national survey of public attitudes towards cardiac DCDD will inform the implementation of cardiac DCDD programs in a manner that is consistent with public values.

The number of patients on cardiac transplant waitlists exceeds the number of available donor organs. Cardiac donation is currently limited to those declared dead by neurologic criteria in all but three countries. Cardiac donation after circulatory determination of death (cardiac DCDD) can be conducted using direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP). Implementation of cardiac DCDD in many countries has been slowed by ethical debates within the donation and transplantation community. We conducted a national survey to determine the perceptions of healthcare providers regarding cardiac DCDD. We conducted an electronic survey of 398 healthcare providers who are involved in the management of heart donors and/or heart transplant recipients in Canada (226 nurses, 82 critical care physicians, 31 donation specialists, and 59 transplant specialists). Our primary outcomes were their attitudes towards and concerns regarding cardiac DCDD protocols and their implementation in Canada. We distributed the survey electronically through several Canadian donation and transplantation organizations. We identified that 361 of 391 respondents (92.3%; 95% confidence interval [CI], 89.6 to 95.1) believed that DPP is acceptable, and 329 of 377 respondents (87.3%; 95% CI, 83.9 to 90.7) supported its implementation in Canada. We found that 301 of 384 respondents (78.4%; 95% CI, 74.2 to 82.6) believed that NRP is acceptable and 266 of 377 respondents (70.6%; 95% CI, 66.0 to 75.2) supported its implementation in Canada. This is the first survey describing the attitudes of healthcare providers towards cardiac DCDD. We identified widespread support for cardiac DCDD and its implementation in Canada among Canadian healthcare providers within the organ donation and transplantation community in Canada.

Objective To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. Design Living systematic review and network meta-analysis. Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. Study selection Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. Methods Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Results The first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. Conclusions Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. Systematic review registration This review was not registered. The protocol established a priori is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Identifying modifiable factors associated with survival following in-hospital cardiac arrest is crucial. The purpose of this study was to determine the extent to which adherence to the 2010 American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) guidelines in their entirety affects patient outcomes. In addition, we explored the role of code leader training level on patient outcomes.We conducted a retrospective review of records for cardiac arrests that occurred on hospital wards and were run by the hospital code team, at three tertiary care centres over 2 to 4 years. Deviations from the ACLS guidelines were quantified using a standardized checklist. Primary outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge.Of 160 resuscitation events, ROSC was achieved in 75 events (46.9%) and survival to hospital discharge in 20 patients (13.1%). On average, there were 2.3 deviations from ACLS guidelines during events that led to ROSC and 3.9 deviations during events that did not lead to ROSC (p 0.0001). There were fewer deviations during events that led to survival to hospital discharge (2.1) compared to those where the patient did not survive to hospital discharge (3.1; p = 0.016). Code leader training level was not associated with patient outcomes. Multivariable logistic regression analysis confirmed an association between deviations from ACLS guidelines and ROSC, but not for survival to hospital discharge. The latter finding may reflect a very low survival rate.We found that higher numbers of deviations from ACLS guidelines were associated with a lower likelihood of ROSC and survival to hospital discharge. These findings emphasize the importance of adherence to ACLS guidelines and the need for training healthcare personnel in resuscitation guidelines in order to improve outcomes for victims of in-hospital cardiac arrest.