Association between immigration status and total knee arthroplasty outcomes in Ontario, Canada: a population-based matched cohort study.

BACKGROUND: Immigrants and refugees face unique challenges navigating the health care system to manage severe arthritis, because of unfamiliarity, lack of awareness of surgical options, or access. The purpose of this study was to assess total knee arthroplasty (TKA) uptake, surgical outcomes, and hospital utilization among immigrants and refugees compared with Canadian-born patients. METHODS: We included all adults undergoing primary TKA from January 2011 to December 2020 in Ontario. Cohorts were defined as Canadian-born or immigrants and refugees. We assessed change in yearly TKA utilization for trend. We compared differences in 1-year revision, infection rates, 30-day venous thromboembolism (VTE), presentation to emergency department, and hospital readmission between matched Canadian-born and immigrant and refugee groups. RESULTS: We included 158 031 TKA procedures. A total of 11 973 (7.6%) patients were in the immigrant and refugee group, and 146 058 (92.4%) patients were in the Canadian-born group. The proportion of TKAs in Ontario performed among immigrants and refugees nearly doubled over the 10-year study period (p < 0.001). After matching, immigrants were at relatively lower risk of 1-year revision (0.9% v. 1.6%, p < 0.001), infection (p < 0.001), death (p = 0.004), and surgical complications (p < 0.001). No differences were observed in rates of 30-day VTE or length of hospital stay. Immigrants were more likely to be discharged to rehabilitation (p < 0.001) and less likely to present to the emergency department (p < 0.001) than Canadian-born patients. CONCLUSION: Compared with Canadian-born patients, immigrants and refugees have favourable surgical outcomes and similar rates of resource utilization after TKA. We observed an underutilization of these procedures in Ontario relative to their proportion of the population. This may reflect differences in perceptions of chronic pain or barriers accessing arthroplasty.

Beliefs of physician directors on the management of devastating brain injuries at the Canadian emergency department and intensive care unit interface: a national site-level survey.

PURPOSE: Insufficient evidence-based recommendations to guide care for patients with devastating brain injuries (DBIs) leave patients vulnerable to inconsistent practice at the emergency department (ED) and intensive care unit (ICU) interface. We sought to characterize the beliefs of Canadian emergency medicine (EM) and critical care medicine (CCM) physician site directors regarding current management practices for patients with DBI. METHODS: We conducted a cross-sectional survey of EM and CCM physician directors of adult EDs and ICUs across Canada (December 2022 to March 2023). Our primary outcome was the proportion of respondents who manage (or consult on) patients with DBI in the ED. We conducted subgroup analyses to compare beliefs of EM and CCM physicians. RESULTS: Of 303 eligible respondents, we received 98 (32%) completed surveys (EM physician directors, 46; CCM physician directors, 52). Most physician directors reported participating in the decision to withdraw life-sustaining measures (WLSM) for patients with DBI in the ED (80%, n = 78), but 63% of these (n = 62) said this was infrequent. Physician directors reported that existing neuroprognostication methods are rarely sufficient to support WLSM in the ED (49%, n = 48) and believed that an ICU stay is required to improve confidence (99%, n = 97). Most (96%, n = 94) felt that providing caregiver visitation time prior to WLSM was a valid reason for ICU admission. CONCLUSION: In our survey of Canadian EM and CCM physician directors, 80% participated in WLSM in the ED for patients with DBI. Despite this, most supported ICU admission to optimize neuroprognostication and patient-centred end-of-life care, including organ donation.

RéSUMé: OBJECTIF: L'insuffisance des recommandations fondées sur des données probantes pour guider les soins aux individus atteints de lésions cérébrales dévastatrices rend ces personnes vulnérables à des pratiques incohérentes à la jonction entre le service des urgences et de l'unité de soins intensifs (USI). Nous avons cherché à caractériser les croyances des directeurs médicaux canadiens en médecine d'urgence et médecine de soins intensifs concernant les pratiques de prise en charge actuelles des personnes ayant subi une lésion cérébrale dévastatrice. MéTHODE: Nous avons réalisé un sondage transversal auprès des directeurs médicaux des urgences et des unités de soins intensifs pour adultes du Canada (décembre 2022 à mars 2023). Notre critère d'évaluation principal était la proportion de répondant·es qui prennent en charge (ou jouent un rôle de consultation auprès) des personnes atteintes de lésions cérébrales dévastatrices à l'urgence. Nous avons effectué des analyses en sous-groupes pour comparer les croyances des médecins des urgences et des soins intensifs. RéSULTATS: Sur les 303 personnes répondantes admissibles, 98 (32 %) ont répondu aux sondages (directions médicales des urgences, 46; directions médicales d'USI, 52). La plupart des directeurs médicaux ont déclaré avoir participé à la décision de retirer des traitements de maintien des fonctions vitales (TFMV) pour des patient·es atteint·es de lésions cérébrales dévastatrices à l'urgence (80 %, n = 78), mais 63 % (n = 62) ont déclaré que c'était peu fréquent. Les directions médicales ont indiqué que les méthodes de neuropronostic existantes sont rarement suffisantes pour appuyer le retrait des TMFV à l'urgence (49 %, n = 48) et croyaient qu'un séjour aux soins intensifs était nécessaire pour améliorer leur confiance en ces méthodes (99 %, n = 97). La plupart (96 %, n = 94) estimaient que le fait d'offrir du temps de visite aux personnes soignantes avant le retrait des TMFV était un motif valable d'admission aux soins intensifs. CONCLUSION: Dans le cadre de notre sondage mené auprès des directions médicales des services d'urgence et des USI au Canada, 80 % d'entre elles ont participé au retrait de TMFV à l'urgence pour des patient·es souffrant de lésions cérébrales dévastatrices. Malgré cela, la plupart d'entre elles étaient en faveur d'une admission aux soins intensifs afin d'optimiser le neuropronostic et les soins de fin de vie axés sur les patient·es, y compris le don d'organes.

Addressing health care inequities in Canadian critical care through inclusive science: a pilot tool for standardized data collection.

PURPOSE: Sociodemographic risks contributing to health inequities are often inadequately captured and reported in critical care studies. To address the lack of standardized terms and definitions, we sought to develop a practical and convenient resource of questions and response options for collecting sociodemographic variables for critical care research. SOURCE: To identify domains and variables that impact health equity, we searched: 1) PubMed for critical care randomized trials (2010 to 2021); 2) high-impact critical care and general medicine journals for special issues relating to equity; and 3) governmental and nongovernmental resources. PRINCIPAL FINDINGS: We identified 23 domains associated with health equity, including pronouns, age, sex, gender identity, sexual orientation, race and ethnicity, visible minorities, language, household income, marital/relationship status, education, disabilities, immigrant and refugee status, employment, primary care access, expanded health insurance, internet access, housing security, food security, dependents, religion, and postal code. For each domain we provided standardized questions and response options; for 13/23 domains, we included more than one version of the question and response categories. CONCLUSION: We developed a standardized, practical, and convenient demographic data collection tool for critical care research studies. Questions and response options can be adapted by researchers for inclusion in individual study questionnaires or case report forms.

RéSUMé: OBJECTIF: Les risques sociodémographiques qui contribuent aux inégalités en matière de santé sont souvent mal saisis et rapportés dans les études de soins intensifs. Pour remédier au manque de termes et de définitions normalisés, nous avons cherché à élaborer une ressource à la fois pratique et utile de questions et d'options de réponse pour le recueil des variables sociodémographiques pour la recherche en soins intensifs. SOURCES: Pour identifier les domaines et les variables qui ont une incidence sur l'équité en santé, nous avons effectué des recherches dans : 1) PubMed, pour en extraire les études randomisées en soins intensifs (2010 à 2021); 2) des revues de soins intensifs et de médecine générale à impact élevé pour identifier les numéros spéciaux liés à l'équité; et 3) les ressources gouvernementales et non gouvernementales. CONSTATATIONS PRINCIPALES: Nous avons identifié 23 domaines associés à l'équité en santé, y compris les pronoms, l'âge, le sexe, l'identité de genre, l'orientation sexuelle, la race et l'origine ethnique, les minorités visibles, la langue, le revenu du ménage, l'état matrimonial / relationnel, l'éducation, les handicaps, le statut d'immigrant·e et de réfugié·e, l'emploi, l'accès aux soins primaires, l'assurance maladie élargie, l'accès à l'internet, la sécurité du logement, la sécurité alimentaire, les personnes à charge, la religion et le code postal. Pour chaque domaine, nous avons fourni des questions et des options de réponse normalisées; pour 13/23 domaines, nous avons inclus plus d'une version des catégories de questions et réponses. CONCLUSION: Nous avons mis au point un outil de collecte de données démographiques normalisé, pratique et utile pour la recherche en soins intensifs. Les options de questions et de réponses peuvent être adaptées par les chercheuses et chercheurs pour être incluses dans des questionnaires d'étude individuels ou des formulaires de présentation de cas.

Definitions, rates and associated mortality of ICU-acquired pneumonia: A multicenter cohort study.

INTRODUCTION: We aimed to analyze intensive care unit (ICU)-acquired pneumonia according to 7 definitions, estimating associated hospital mortality. METHODS: This cohort study was nested within an international randomized trial, evaluating the effect of probiotics on ICU-acquired pneumonia in 2650 mechanically ventilated adults. Each clinically suspected pneumonia was adjudicated by two physicians blinded to allocation and center. The primary outcome was ventilator-associated pneumonia (VAP) informed by ventilation for ≥2 days, new, progressive or persistent infiltrate plus 2 of: temperature > 38 °C or < 36 °C; leukopenia (<3 × 10(Fernando et al., 20206)/L) or leukocytosis (>10 × 10(Fernando et al., 20206)/L); and purulent sputum. We also used 6 other definitions estimating the risk of hospital mortality. RESULTS: The frequency of ICU-acquired pneumonia varied by definition: the trial primary outcome VAP (21.6%), Clinical Pulmonary Infection Score (CPIS) (24.9%), American College Chest Physicians (ACCP) (25.0%), International Sepsis Forum (ISF) (24.4%), Reducing Oxidative Stress Study (REDOXS) (17.6%), Centers for Disease Control (CDC) (7.8%), and invasively microbiologically confirmed (1.9%). The trial primary outcome VAP (HR 1.31 [1.08, 1.60]), ISF (HR 1.32 [1.09,1.60]), CPIS (HR 1.30 [1.08,1.58]) and ACCP definitions (HR 1.22 [1.00,1.47]) were associated with hospital mortality. CONCLUSIONS: Rates of ICU-acquired pneumonia vary by definition and are associated with differential increased risk of death.

The effect of duration of antimicrobial treatment for bacteremia in critically ill patients on in-hospital mortality - Retrospective double center analysis.

PURPOSE: Excessive duration of antibiotic treatment is a major factor for inappropriate antibiotic consumption. Although in some instances shorter antibiotic courses are as efficient as longer ones, no specific recommendations as to the duration of antimicrobial treatment for bloodstream infections currently exist. In the present study, we investigated the effect of antibiotic treatment duration on in-hospital mortality using retrospective data from two cohorts that included patients with bacteremia at two Swiss tertiary Intensive Care Units (ICUs). MATERIALS AND METHODS: Overall 8227 consecutive patients requiring ICU admission were screened for bacteremia between 01/2012-12/2013 in Lausanne and between 07/2016-05/2017 in Bern. Patients with an infection known to require prolonged treatment or having single positive blood culture with common contaminant pathogens were excluded. The primary outcome of interest was the time from start of antimicrobial treatment to in-hospital death or hospital discharge, whichever comes first. The predictor of interest was adequate antimicrobial treatment duration, further divided into shorter (≤10 days) and longer (>10 days) durations. A time-dependent Cox model and a cloning approach were used to address immortality bias. The secondary outcomes were the median duration of antimicrobial treatment for patients with bacteremia overall and stratified by underlying infectious syndrome and pathogens in the case of secondary bacteremia. RESULTS: Out of the 707 patients with positive blood cultures, 382 were included into the primary analysis. Median duration of antibiotic therapy was 14 days (IQR, 7-20). Most bacteremia (84%) were monomicrobial; 18% of all episodes were primary bacteremia. Respiratory (28%), intra-abdominal (23%) and catheter infections (17%) were the most common sources of secondary bacteremia. Using methods to mitigate the risk of confounding associated with antibiotic treatment durations, shorter versus longer treatment groups showed no differences in in-hospital survival (time-dependent Cox-model: HR 1.5, 95% CI (0.8, 2.7), p = 0.20; Cloning approach: HR 1.0, 95% CI (0.7,1.5) p = 0.83). Sensitivity analyses showed that the interpretation did not change when using a 7 days cut-off. CONCLUSIONS: In this restrospective study, we found no evidence for a survival benefit of longer (>10 days) versus shorter treatment course in ICU patients with bacteremia. TRIAL REGISTRATION: The study was retrospectively registered on clinicatrials.gov (NCT05236283), 11 February 2022. The respective cantonal ethics commission (KEK Bern # 2021-02302) has approved the study.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.

Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE).

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen. RESULTS: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care. CONCLUSION: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. STUDY REGISTRATION: ClinicalTrials.gov NCT04383613.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Epidemiology of intravenous immune globulin in septic shock: a retrospective cohort analysis of the Premier Healthcare Database.

PURPOSE: Intravenous immune globulin (IVIG) may improve survival in people with septic shock. Current utilization patterns of IVIG are unknown. We sought to characterize adult patients with septic shock requiring vasopressors who received IVIG, describes IVIG regimens, and evaluate determinants of IVIG use in patients with septic shock. METHODS: We conducted a retrospective database study of adult patients with septic shock admitted to US hospitals in the Premier Healthcare Database (from July 2010 to June 2013). We described the proportion of patients with septic shock receiving IVIG, examined IVIG regimens across sites and employed random-effects multivariable regression techniques to identify predictors of IVIG use. RESULTS: Intravenous immune globulin was administered to 0.3% (n = 685) of patients with septic shock; with a median [interquartile range (IQR)] dose of 1 [0.5-1.8] g·kg-1 for a median [IQR] of 1 [1-2] day. Receipt of IVIG was less likely for Black patients (odds ratio [OR], 0.54; 95% confidence interval [CI] 0.41 to 0.72) and patients without private insurance (Medicare OR, 0.73; 95% CI 0.59 to 0.90; Medicaid OR, 0.41; 95% CI 0.30 to 0.57) and more likely for patients with immunocompromise (OR, 6.83; 95% CI 5.47 to 8.53), necrotizing fasciitis (OR, 9.78; 95% CI 6.97 to 13.72), and toxic shock (OR, 56.9; 95% CI 38.7 to 83.7). CONCLUSIONS: Intravenous immune globulin is used infrequently across the US in patients with septic shock. Regimens of IVIG in septic shock may be less intensive than those associated with a survival benefit in meta-analyses. Observed infrequent use supports apparent clinical equipoise, perhaps secondary to limitations of the primary literature. A clinical trial evaluating the role of IVIG in septic shock is needed.

RéSUMé: OBJECTIF: L'immunoglobuline intraveineuse (IGIV) peut améliorer la survie chez les personnes atteintes de choc septique. Les pratiques actuelles d'utilisation de l'IGIV sont inconnues. Nous avons cherché à caractériser les patients adultes en état de choc septique et nécessitant des vasopresseurs qui ont reçu de l'IGIV, à décrire les dosages administrés d'IGIV, et à évaluer les causes déterminantes d'une utilisation d'IGIV chez ces patients. MéTHODE: Nous avons réalisé une étude rétrospective de base de données portant sur des patients adultes atteints de choc septique admis dans des hôpitaux américains et inclus dans la base de données Premier Healthcare (de juillet 2010 à juin 2013). Nous avons décrit la proportion de patients en choc septique recevant de l'IGIV, examiné les posologies utilisées d'IGIV à travers les sites et employé des techniques de régression multivariable à effets aléatoires pour identifier les prédicteurs de l'utilisation d'IGIV. RéSULTATS: L'IGIV a été administrée à 0,3 % (n = 685) des patients présentant un choc septique, avec une dose médiane [écart interquartile (ÉIQ)] de 1 [0,5­1,8] g·kg-1 pour une médiane [ÉIQ] de 1 [1­2] jour. L'administration d'IGIV était moins probable chez les patients noirs (rapport de cotes [RC], 0,54; intervalle de confiance [IC] à 95 %, 0,41 à 0,72) et les patients sans assurance privée (RC Medicare, 0,73; IC 95 %, 0,59 à 0,90; RC Medicaid, 0,41; IC 95 %, 0,30 à 0,57) et plus probable chez les patients immunodéprimés (RC, 6,83; IC 95 %, 5,47 à 8,53), atteints de fasciite nécrosante (RC, 9,78; IC 95 %, 6,97 à 13,72), et en choc toxique (RC, 56,9; IC 95 %, 38,7 à 83,7). CONCLUSION: L'IGIV est rarement utilisée aux États-Unis chez les patients en choc septique. Les dosages d'IGIV utilisés en cas de choc septique pourraient être moins intensifs que ceux associés à un effet bénéfique en matière de survie dans les méta-analyses. L'utilisation peu fréquente observée appuie une équivalence clinique apparente, peut-être secondaire aux limites de la littérature princeps. Une étude clinique évaluant le rôle de l'IGIV dans le choc septique est nécessaire.

Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.

PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

The association between varying levels of palliative care involvement on costs during terminal hospitalizations in Canada from 2012 to 2015.

BACKGROUND: Inpatient palliative care is associated with lower inpatient costs; however, this has yet to be studied using a more nuanced, multi-tiered measure of inpatient palliative care and a national population-representative dataset. Using a population-based cohort of Canadians who died in hospital, our objectives were to: describe patients' receipt of palliative care and active interventions in their terminal hospitalization; and examine the relationship between inpatient palliative care and hospitalization costs. METHODS: Retrospective cohort study using data from the Discharge Abstract Database in Canada between fiscal years 2012 and 2015. The cohort were Canadian adults (age ≥ 18 years) who died in hospital between April 1st, 2012 and March 31st, 2015 (N = 250,640). The exposure was level of palliative care involvement defined as: medium-high, low, or no palliative care. The main measure was acute care costs calculated using resource intensity weights multiplied by the cost of standard hospital stay, represented in 2014 Canadian dollars (CAD). Descriptive statistics were represented as median (IQR), and n(%). We modelled cost as a function of palliative care using a gamma generalized estimating equation (GEE) model, accounting for clustering by hospital. RESULTS: There were 250,640 adults who died in hospital. Mean age was 76 (SD 14), 47% were female. The most common comorbidities were: metastatic cancer (21%), heart failure (21%), and chronic obstructive pulmonary disease (16%). Of the decedents, 95,450 (38%) had no palliative care involvement, 98,849 (38%) received low involvement, and 60,341 (24%) received medium to high involvement. Controlling for age, sex, province and predicted hospital mortality risk at admission, the cost per day of a terminal hospitalization was: $1359 (95% CI 1323: 1397) (no involvement), $1175 (95% CI 1146: 1206) (low involvement), and $744 (95% CI 728: 760) (medium-high involvement). CONCLUSIONS: Increased involvement of palliative care was associated with lower costs. Future research should explore whether this relationship holds for non-terminal hospitalizations, and whether palliative care in other settings impacts inpatient costs.

Post-exposure prophylaxis against SARS-CoV-2 in close contacts of confirmed COVID-19 cases (CORIPREV): study protocol for a cluster-randomized trial.

BACKGROUND: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. METHODS: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment. DISCUSSION: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. TRIAL REGISTRATION: This trial was registered at www.ClinicalTrials.gov ( NCT04321174 ) on March 25, 2020.

Association between high cost user status and end-of-life care in hospitalized patients: A national cohort study of patients who die in hospital.

BACKGROUND: Studies comparing end-of-life care between patients who are high cost users of the healthcare system compared to those who are not are lacking. AIM: The objective of this study was to describe and measure the association between high cost user status and several health services outcomes for all adults in Canada who died in acute care, compared to non-high cost users and those without prior healthcare use. SETTINGS AND PARTICIPANTS: We used administrative data for all adults who died in hospital in Canada between 2011 and 2015 to measure the odds of admission to the intensive care unit (ICU), receipt of invasive interventions, major surgery, and receipt of palliative care during the hospitalization in which the patient died. High cost users were defined as those in the top 10% of acute healthcare costs in the year prior to a person's hospitalization in which they died. RESULTS: Among 252,648 people who died in hospital, 25,264 were high cost users (10%), 112,506 were non-high cost users (44.5%) and 114,878 had no prior acute care use (45.5%). After adjustment for age and sex, high cost user status was associated with a 14% increased odds of receiving an invasive intervention, a 15% increased odds of having major surgery, and an 8% lower odds of receiving palliative care compared to non-high cost users, but opposite when compared to patients without prior healthcare use. CONCLUSIONS: Many patients receive aggressive elements of end-of-life care during the hospitalization in which they die and a substantial number do not receive palliative care. Understanding how this care differs between those who were previously high- and non-high cost users may provide an opportunity to improve end of life care for whom better care planning and provision ought to be an equal priority.

Observational study of agreement between attending and trainee physicians on the surprise question: "Would you be surprised if this patient died in the next 12 months?"

BACKGROUND: Optimal end-of-life care requires identifying patients that are near the end of life. The extent to which attending physicians and trainee physicians agree on the prognoses of their patients is unknown. We investigated agreement between attending and trainee physician on the surprise question: "Would you be surprised if this patient died in the next 12 months?", a question intended to assess mortality risk and unmet palliative care needs. METHODS: This was a multicentre prospective cohort study of general internal medicine patients at 7 tertiary academic hospitals in Ontario, Canada. General internal medicine attending and senior trainee physician dyads were asked the surprise question for each of the patients for whom they were responsible. Surprise question response agreement was quantified by Cohen's kappa using Bayesian multilevel modeling to account for clustering by physician dyad. Mortality was recorded at 12 months. RESULTS: Surprise question responses encompassed 546 patients from 30 attending-trainee physician dyads on academic general internal medicine teams at 7 tertiary academic hospitals in Ontario, Canada. Patients had median age 75 years (IQR 60-85), 260 (48%) were female, and 138 (25%) were dependent for some or all activities of daily living. Trainee and attending physician responses agreed in 406 (75%) patients with adjusted Cohen's kappa of 0.54 (95% credible interval 0.41 to 0.66). Vital status was confirmed for 417 (76%) patients of whom 160 (38% of 417) had died. Using a response of "No" to predict 12-month mortality had positive likelihood ratios of 1.84 (95% CrI 1.55 to 2.22, trainee physicians) and 1.51 (95% CrI 1.30 to 1.72, attending physicians), and negative likelihood ratios of 0.31 (95% CrI 0.17 to 0.48, trainee physicians) and 0.25 (95% CrI 0.10 to 0.46, attending physicians). CONCLUSION: Trainee and attending physician responses to the surprise question agreed in 54% of cases after correcting for chance agreement. Physicians had similar discriminative accuracy; both groups had better accuracy predicting which patients would survive as opposed to which patients would die. Different opinions of a patient's prognosis may contribute to confusion for patients and missed opportunities for engagement with palliative care services.

How the COVID-19 pandemic will change the future of critical care.

Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.

Intravenous immune globulin in septic shock: a Canadian national survey of critical care medicine and infectious disease specialist physicians.

PURPOSE: This national survey evaluated the perceived efficacy and safety of intravenous immune globulin (IVIG) in septic shock, self-reported utilization patterns, barriers to use, the population of interest for further trials and willingness to participate in future research of IVIG in septic shock. METHODS: We conducted a cross-sectional survey of critical care and infectious diseases physicians across Canada. We summarized categorical item responses as counts and proportions. We developed a multivariable logistic regression model to identify physician-level predictors of IVIG use in septic shock. RESULTS: Our survey was disseminated to 674 eligible respondents with a final response rate of 60%. Most (91%) respondents reported having prescribed IVIG to patients with septic shock at least once, 86% for septic shock due to necrotizing fasciitis, 52% for other bacterial toxin-mediated causes of septic shock, and 5% for undifferentiated septic shock. The majority of respondents expressed uncertainty regarding the impact of IVIG on mortality (97%) and safety (95%) in septic shock. Respondents were willing to participate in further IVIG research with 98% stating they would consider enrolling their patients into a trial of IVIG in septic shock. Familiarity with published evidence was the single greatest predictor of IVIG use in septic shock (odds ratio, 10.2; 95% confidence interval, 3.4 to 30.5; P < 0.001). CONCLUSIONS: Most Canadian critical care and infectious diseases specialist physicians reported previous experience using IVIG in septic shock. Respondents identified inadequacy of existing research as the greatest barrier to routine use of IVIG in septic shock. Most respondents support the need for further studies on IVIG in septic shock, and would consider enrolling their own patients into a trial of IVIG in septic shock.

RéSUMé: OBJECTIF : Cette enquête nationale a évalué l'efficacité et l'innocuité perçues des immunoglobulines intraveineuses (IgIV) dans le contexte du choc septique, les habitudes d'utilisation autodéclarées, les obstacles à l'utilisation de cette modalité, les populations à explorer pour des études futures et la volonté de participer aux recherches futures sur les IgIV et le choc septique. MéTHODE : Nous avons mené une enquête transversale auprès de médecins intensivistes et spécialistes des maladies infectieuses au Canada. Nous avons résumé les réponses de chaque point catégorique en tant que dénombrement et proportions. Nous avons mis au point un modèle de régression logistique multivariée afin d'identifier les prédicteurs, au niveau des médecins, d'une utilisation des IgIV en cas de choc septique. RéSULTATS : Notre sondage a été acheminé à 674 médecins admissibles et nous avons obtenu un taux de réponse final de 60 %. La plupart (91%) des répondants ont indiqué avoir prescrit des IgIV aux patients en choc septique au moins une fois, 86 % pour un choc septique dû à une fasciite nécrosante, 52 % pour des chocs septiques d'autres étiologies médiées par des toxines bactériennes, et 5 % dans des cas de choc septique non différencié. La majorité des répondants ont exprimé de l'incertitude quant à l'incidence des IgIV sur la mortalité (97 %) et l'innocuité (95 %) lors de choc septique. Les répondants étaient disposés à participer à d'autres recherches sur les IgIV, 98 % déclarant qu'ils envisageraient d'inscrire leurs patients à une étude sur les IgIV et le choc septique. La familiarité avec les données probantes publiées était le plus grand prédicteur d'utilisation d'IgIV dans un contexte de choc septique (rapport de cotes, 10,2; intervalle de confiance à 95 %, 3,4 à 30,5; P < 0,001). CONCLUSION : La plupart des médecins intensivistes et spécialistes des maladies infectieuses canadiens ont rapporté avoir une expérience antérieure d'utilisation d'IgIV en cas de choc septique. Les répondants ont identifié l'insuffisance de la recherche existante comme le plus grand obstacle à l'utilisation systématique d'IgIV dans les cas de choc septique. La plupart des répondants appuient la nécessité d'études plus approfondies sur les IgIV et le choc septique et envisageraient d'inscrire leurs propres patients à une étude sur les IgIV dans un contexte de choc septique.