Epidemiology and Outcomes of AKI Treated With Continuous Kidney Replacement Therapy: The Multicenter CRRTnet Study.

Rationale & Objective: Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney replacement therapy used for critically ill adult patients with acute kidney injury (AKI). Given the variability in CKRT practice, a contemporary understanding of its epidemiology is necessary to improve care delivery. Study Design: Multicenter, prospective living registry. Setting & Population: 1,106 critically ill adults with AKI requiring CKRT from December 2013 to January 2021 across 5 academic centers and 6 intensive care units. Patients with pre-existing kidney failure and those with coronavirus 2 infection were excluded. Exposure: CKRT for more than 24 hours. Outcomes: Hospital mortality, kidney recovery, and health care resource utilization. Analytical Approach: Data were collected according to preselected timepoints at intensive care unit admission and CKRT initiation and analyzed descriptively. Results: Patients' characteristics, contributors to AKI, and CKRT indications differed among centers. Mean (standard deviation) age was 59.3 (13.9) years, 39.7% of patients were women, and median [IQR] APACHE-II (acute physiologic assessment and chronic health evaluation) score was 30 [25-34]. Overall, 41.1% of patients survived to hospital discharge. Patients that died were older (mean age 61 vs. 56.8, P < 0.001), had greater comorbidity (median Charlson score 3 [1-4] vs. 2 [1-3], P < 0.001), and higher acuity of illness (median APACHE-II score 30 [25-35] vs. 29 [24-33], P = 0.003). The most common condition predisposing to AKI was sepsis (42.6%), and the most common CKRT indications were oliguria/anuria (56.2%) and fluid overload (53.9%). Standardized mortality ratios were similar among centers. Limitations: The generalizability of these results to CKRT practices in nonacademic centers or low-and middle-income countries is limited. Conclusions: In this registry, sepsis was the major contributor to AKI and fluid management was collectively the most common CKRT indication. Significant heterogeneity in patient- and CKRT-specific characteristics was found in current practice. These data highlight the need for establishing benchmarks of CKRT delivery, performance, and patient outcomes. Data from this registry could assist with the design of such studies.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Coronavirus disease 2019 (COVID-19) excess mortality outcomes associated with pandemic effects study (COPES): A systematic review and meta-analysis.

Background and aim: With the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times. Methods: We searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Of 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons (n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06-0.06% p < 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38-1.70, p < 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07-1.30, p < 0.00001). There was "very low" certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain. Interpretation: The COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain. Systematic review registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256].

Evidence-informed consensus statements to guide COVID-19 patient visitation policies: results from a national stakeholder meeting.

PURPOSE: Hospital policies forbidding or limiting families from visiting relatives on the intensive care unit (ICU) has affected patients, families, healthcare professionals, and patient- and family-centered care (PFCC). We sought to refine evidence-informed consensus statements to guide the creation of ICU visitation policies during the current COVID-19 pandemic and future pandemics and to identify barriers and facilitators to their implementation and sustained uptake in Canadian ICUs. METHODS: We created consensus statements from 36 evidence-informed experiences (i.e., impacts on patients, families, healthcare professionals, and PFCC) and 63 evidence-informed strategies (i.e., ways to improve restricted visitation) identified during a modified Delphi process (described elsewhere). Over two half-day virtual meetings on 7 and 8 April 2021, 45 stakeholders (patients, families, researchers, clinicians, decision-makers) discussed and refined these consensus statements. Through qualitative descriptive content analysis, we evaluated the following points for 99 consensus statements: 1) their importance for improving restricted visitation policies; 2) suggested modifications to make them more applicable; and 3) facilitators and barriers to implementing these statements when creating ICU visitation policies. RESULTS: Through discussion, participants identified three areas for improvement: 1) clarity, 2) accessibility, and 3) feasibility. Stakeholders identified several implementation facilitators (clear, flexible, succinct, and prioritized statements available in multiple modes), barriers (perceived lack of flexibility, lack of partnership between government and hospital, change fatigue), and ways to measure and monitor their use (e.g., family satisfaction, qualitative interviews). CONCLUSIONS: Existing guidance on policies that disallowed or restricted visitation in intensive care units were confusing, hard to operationalize, and often lacked supporting evidence. Prioritized, succinct, and clear consensus statements allowing for local adaptability are necessary to guide the creation of ICU visitation policies and to optimize PFCC.

RéSUMé: OBJECTIF: Les politiques hospitalières interdisant ou limitant les visites des familles à des proches à l'unité de soins intensifs (USI) ont affecté les patients, les familles, les professionnels de la santé et les soins centrés sur le patient et la famille (SCPF). Nous avons cherché à affiner les déclarations de consensus fondées sur des données probantes afin de guider la création de politiques de visite aux soins intensifs pendant la pandémie actuelle de COVID-19 et les pandémies futures, et dans le but d'identifier les obstacles et les critères facilitants à leur mise en œuvre et à leur adoption répandue dans les unités de soins intensifs canadiennes. MéTHODE: Nous avons créé des déclarations de consensus à partir de 36 expériences fondées sur des données probantes (c.-à-d. impacts sur les patients, les familles, les professionnels de la santé et les SCPF) et 63 stratégies fondées sur des données probantes (c.-à-d. moyens d'améliorer les restrictions des visites) identifiées au cours d'un processus Delphi modifié (décrit ailleurs). Au cours de deux réunions virtuelles d'une demi-journée tenues les 7 et 8 avril 2021, 45 intervenants (patients, familles, chercheurs, cliniciens, décideurs) ont discuté et affiné ces déclarations de consensus. Grâce à une analyse descriptive qualitative du contenu, nous avons évalué les points suivants pour 99 déclarations de consensus : 1) leur importance pour l'amélioration des politiques de restriction des visites; 2) les modifications suggérées pour les rendre plus applicables; et 3) les critères facilitants et les obstacles à la mise en œuvre de ces déclarations lors de la création de politiques de visite aux soins intensifs. RéSULTATS: En discutant, les participants ont identifié trois domaines à améliorer : 1) la clarté, 2) l'accessibilité et 3) la faisabilité. Les intervenants ont identifié plusieurs critères facilitants à la mise en œuvre (énoncés clairs, flexibles, succincts et hiérarchisés disponibles dans plusieurs modes), des obstacles (manque perçu de flexibilité, manque de partenariat entre le gouvernement et l'hôpital, fatigue du changement) et des moyens de mesurer et de surveiller leur utilisation (p. ex., satisfaction des familles, entrevues qualitatives). CONCLUSION: Les directives existantes sur les politiques qui interdisaient ou limitaient les visites dans les unités de soins intensifs étaient déroutantes, difficiles à mettre en oeuvre et manquaient souvent de données probantes à l'appui. Des déclarations de consensus hiérarchisées, succinctes et claires permettant une adaptabilité locale sont nécessaires pour guider la création de politiques de visite en soins intensifs et pour optimiser les soins centrés sur le patient et la famille.

Non-COVID outcomes associated with the coronavirus disease-2019 (COVID-19) pandemic effects study (COPES): A systematic review and meta-analysis.

BACKGROUND: As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs. METHODS: We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology. RESULTS: Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28-1.50; absolute risk difference: 5% [95% CI: 4-6%], p<0.00001, very low certainty evidence). Twenty-eight studies (17%) reported significant changes in morbidity (where 93% reported increases), while 30 studies (18%) reported no significant change (very low certainty). Thirty-nine studies (23%) reported significant changes in hospitalizations (97% reporting decreases), while 111 studies (66%) reported no significant change (very low certainty). Sixty-two studies (37%) reported significant disruptions in standards-to-care (73% reporting increases), while 62 studies (37%) reported no significant change (very low certainty). CONCLUSIONS: There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020201256 (Sept 2, 2020).

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit.

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

BACKGROUND: The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. OBJECTIVE: We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database. METHODS: The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses. RESULTS: The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. CONCLUSIONS: We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36261.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study.

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.

Outcomes of critically ill COVID-19 survivors and caregivers: a case study-centred narrative review Devenir des survivants et des soignants gravement atteints par la COVID-19 : une revue narrative centrée sur une étude de cas

Purpose Critical illness is a transformative experience for both patients and their family members. For COVID-19 patients admitted to the intensive care unit (ICU), survival may be the start of a long road to recovery. Our knowledge of the post-ICU long-term sequelae of acute respiratory distress syndrome (ARDS) and severe acute respiratory syndrome (SARS) may inform our understanding and management of the long-term effects of COVID-19. Source We identified international and Canadian epidemiologic data on ICU admissions for COVID-19, COVID-19 pathophysiology, emerging ICU practice patterns, early reports of long-term outcomes, and federal support programs for survivors and their families. Centred around an illustrating case study, we applied relevant literature from ARDS and SARS to contextualize knowledge within emerging COVID-19 research and extrapolate findings to future long-term outcomes. Principal findings COVID-19 is a multisystem disease with unknown long-term morbidity and mortality. Its pathophysiology is distinct and unique from ARDS, SARS, and critical illness. Nevertheless, based on initial reports of critical care management for COVID-19 and the varied injurious supportive practices employed in the ICU, patients and families are at risk for post-intensive care syndrome. The distinct incremental risk of COVID-19 multiple organ dysfunction is unknown. The risk of mood disorders in family members may be further exacerbated by imposed isolation and stigma. Conclusion Emerging literature on COVID-19 outcomes suggests some similarities with those of ARDS/SARS and prolonged mechanical ventilation. The pathophysiology of COVID-19 is presented here in the context of early outcome data and to inform an agenda for longitudinal research for patients and families.

Outcomes of critically ill COVID-19 survivors and caregivers: a case study-centred narrative review.

PURPOSE: Critical illness is a transformative experience for both patients and their family members. For COVID-19 patients admitted to the intensive care unit (ICU), survival may be the start of a long road to recovery. Our knowledge of the post-ICU long-term sequelae of acute respiratory distress syndrome (ARDS) and severe acute respiratory syndrome (SARS) may inform our understanding and management of the long-term effects of COVID-19. SOURCE: We identified international and Canadian epidemiologic data on ICU admissions for COVID-19, COVID-19 pathophysiology, emerging ICU practice patterns, early reports of long-term outcomes, and federal support programs for survivors and their families. Centred around an illustrating case study, we applied relevant literature from ARDS and SARS to contextualize knowledge within emerging COVID-19 research and extrapolate findings to future long-term outcomes. PRINCIPAL FINDINGS: COVID-19 is a multisystem disease with unknown long-term morbidity and mortality. Its pathophysiology is distinct and unique from ARDS, SARS, and critical illness. Nevertheless, based on initial reports of critical care management for COVID-19 and the varied injurious supportive practices employed in the ICU, patients and families are at risk for post-intensive care syndrome. The distinct incremental risk of COVID-19 multiple organ dysfunction is unknown. The risk of mood disorders in family members may be further exacerbated by imposed isolation and stigma. CONCLUSION: Emerging literature on COVID-19 outcomes suggests some similarities with those of ARDS/SARS and prolonged mechanical ventilation. The pathophysiology of COVID-19 is presented here in the context of early outcome data and to inform an agenda for longitudinal research for patients and families.

RéSUMé: OBJECTIF: Les maladies au stade critique constituent une expérience bouleversante tant pour les patients que pour leurs proches. Pour les patients atteints de la COVID-19 admis aux soins intensifs (USI), la survie peut être le début d'un long parcours vers la guérison. Notre connaissance des séquelles à long terme post-USI d'un syndrome de détresse respiratoire aiguë (SDRA) ou d'un syndrome respiratoire aigu sévère (SRAS) pourrait éclairer notre compréhension et notre prise en charge des effets à long terme de la COVID-19. SOURCES: Nous avons identifié des données épidémiologiques internationales et canadiennes sur les admissions aux soins intensifs pour la COVID-19, la physiopathologie de la COVID-19, les schémas de pratique émergents en soins intensifs, les premiers rapports sur les issues à long terme et les programmes de soutien fédéraux pour les survivants et leurs familles. En nous centrant autour d'une étude de cas pour illustrer notre propos, nous avons appliqué la littérature pertinente à propos du SDRA et du SRAS afin de contextualiser les connaissances de la recherche émergente sur la COVID-19 et extrapoler les conclusions aux futures issues à long terme. CONSTATATIONS PRINCIPALES: La COVID-19 est une maladie multisystémique dont la morbidité et la mortalité à long terme sont inconnues. Sa physiopathologie est unique et distincte du SDRA, du SRAS et des maladies graves. Néanmoins, en nous fondant sur les rapports initiaux de prise en charge aux soins intensifs de la COVID-19 et sur les diverses pratiques de support préjudiciables utilisées aux soins intensifs, les patients et les familles sont à risque de syndrome post-soins intensifs. Le risque distinct supplémentaire de dysfonctionnement multiviscéral de la COVID-19 est inconnu. Le risque de troubles de l'humeur chez les proches peut être encore exacerbé par l'isolement imposé et la stigmatisation. CONCLUSION: La littérature émergente sur les issues de la COVID-19 suggère certaines similitudes avec celles du SDRA/SRAS et de la ventilation mécanique prolongée. La physiopathologie de la COVID-19 est présentée ici dans le contexte des premières données sur les issues et pour éclairer un programme de recherche longitudinale pour les patients et leurs familles.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the ISARIC WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe COVID-19, many were treated outside of the traditional walls of the ICU, and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside of the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the ISARIC WHO COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or non-invasive mechanical ventilation, high-flow nasal cannula, inotropes, and vasopressors. A logistic Generalised Additive Model was used to compare clinical outcomes among patients admitted and not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median [IQR], 67 years [55, 78]), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 days (5–19) and was longer in patients admitted to an ICU than in those that were cared for outside of ICU (12 [6–23] versus 8 [4–15] days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% [5797/18831] versus 39.0% [7532/19295], p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR:0.70, 95%CI: 0.65-0.75, p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside of an ICU.

A Modified Delphi Process to Prioritize Experiences and Guidance Related to ICU Restricted Visitation Policies During the Coronavirus Disease 2019 Pandemic.

To create evidence-based consensus statements for restricted ICU visitation policies to support critically ill patients, families, and healthcare professionals during current and future pandemics. DESIGN: Three rounds of a remote modified Delphi consensus process. SETTING: Online survey and virtual polling from February 2, 2021, to April 8, 2021. SUBJECTS: Stakeholders (patients, families, clinicians, researchers, allied health professionals, decision-makers) admitted to or working in Canadian ICUs during the coronavirus disease 2019 pandemic. MEASUREMENTS AND MAIN RESULTS: During Round 1, key stakeholders used a 9-point Likert scale to rate experiences (1-not significant, 9-significant impact on patients, families, healthcare professionals, or patient- and family-centered care) and strategies (1-not essential, 9-essential recommendation for inclusion in the development of restricted visitation policies) and used a free-text box to capture experiences/strategies we may have missed. Consensus was achieved if the median score was 7-9 or 1-3. During Round 2, participants used a 9-point Likert scale to re-rate experiences/strategies that did not meet consensus during Round 1 (median score of 4-6) and rate new items identified in Round 1. During Rounds 2 and 3, participants ranked items that reached consensus by order of importance (relative to other related items and experiences) using a weighted ranking system (0-100 points). Participants prioritized 11 experiences (e.g., variability of family's comfort with technology, healthcare professional moral distress) and developed 21 consensus statements (e.g., communicate policy changes to the hospital staff before the public, permit visitors at end-of-life regardless of coronavirus disease 2019 status, creating a clear definition for end-of-life) regarding restricted visitation policies. CONCLUSIONS: We have formulated evidence-informed consensus statements regarding restricted visitation policies informed by diverse stakeholders, which could enhance patient- and family-centered care during a pandemic.

Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review.

BACKGROUND: Restricted visitation policies in acute care settings because of the COVID-19 pandemic have negative consequences. The objective of this scoping review is to identify impacts of restricted visitation policies in acute care settings, and describe perspectives and mitigation approaches among patients, families, and healthcare professionals. METHODS: We searched Medline, Embase, PsycINFO, Healthstar, CINAHL, Cochrane Central Register of Controlled Trials on January 01/2021, unrestricted, for published primary research records reporting any study design. We included secondary (e.g., reviews) and non-research records (e.g., commentaries), and performed manual searches in web-based resources. We excluded records that did not report primary data. Two reviewers independently abstracted data in duplicate. RESULTS: Of 7810 citations, we included 155 records. Sixty-six records (43%) were primary research; 29 (44%) case reports or case series, and 26 (39%) cohort studies; 21 (14%) were literature reviews and 8 (5%) were expert recommendations; 54 (35%) were commentary, editorial, or opinion pieces. Restricted visitation policies impacted coping and daily function (n = 31, 20%) and mental health outcomes (n = 29, 19%) of patients, families, and healthcare professionals. Participants described a need for coping and support (n = 107, 69%), connection and communication (n = 107, 69%), and awareness of state of well-being (n = 101, 65%). Eighty-seven approaches to mitigate impact of restricted visitation were identified, targeting families (n = 61, 70%), patients (n = 51, 59%), and healthcare professionals (n = 40, 46%). CONCLUSIONS: Patients, families, and healthcare professionals were impacted by restricted visitation polices in acute care settings during COVID-19. The consequences of this approach on patients and families are understudied and warrant evaluation of approaches to mitigate their impact. Future pandemic policy development should include the perspectives of patients, families, and healthcare professionals. TRIAL REGISTRATION: The review was registered on PROSPERO (CRD42020221662) and a protocol peer-reviewed prior to data extraction.

An environmental scan of visitation policies in Canadian intensive care units during the first wave of the COVID-19 pandemic.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19: Meta-analysis/Meta-regression Adjusted for Confounding Factors.

BACKGROUND: Angiotensin receptor blockers (ARBs) and/or angiotensin-converting enzyme (ACE) inhibitors could alter mortality from coronavirus disease 2019 (COVID-19), but existing meta-analyses that combined crude and adjusted results may be confounded by the fact that comorbidities are more common in ARB/ACE inhibitor users. METHODS: We searched PubMed/MEDLINE/Embase for cohort studies and meta-analyses reporting mortality by preexisting ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex, and prevalence of cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease between users and nonusers of ARBs/ACE inhibitors at the study level during data synthesis. RESULTS: In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease. ARB/ACE inhibitor use was associated with significantly lower mortality after controlling for potential confounding factors (odds ratio 0.77 [95% confidence interval: 0.62, 0.96]). In contrast, meta-analysis of ARB/ACE inhibitor use was not significantly associated with mortality when all studies were combined with no adjustment made for confounders (0.87 [95% confidence interval: 0.71, 1.08]). CONCLUSIONS: ARB/ACE inhibitor use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes, and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality from COVID-19 because of indication bias.

INTRODUCTION: Les antagonistes des récepteurs de l'angiotensine (ARA) et/ou les inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) feraient varier la mortalité liée à la COVID-19, mais il est possible que les méta-analyses actuelles qui combinaient les résultats bruts et ajustés soient invalidées du fait que les comorbidités sont plus fréquentes chez les utilisateurs d'ARA/IECA. MÉTHODES: Nous avons effectué des recherches dans les bases de données PubMed/MEDLINE/Embase pour trouver des études de cohorte et des méta-analyses qui portent sur la mortalité associée à un traitement préexistant par ARA/IECA chez les patients hospitalisés atteints de la COVID-19. Nous avons utilisé la métarégression à effets aléatoires pour calculer les rapports de cotes regroupés de mortalité ajustés en fonction du déséquilibre de l'âge, du sexe, et de la prévalence des maladies cardiovasculaires, de l'hypertension, du diabète sucré et de l'insuffisance rénale chronique entre les utilisateurs et les non-utilisateurs d'ARA/IECA dans le cadre de l'étude durant la synthèse des données. RÉSULTATS: Dans les 30 études portant sur 17 281 patients, 22 %, 68 %, 25 % et 11 % avaient respectivement une maladie cardiovasculaire, de l'hypertension, le diabète sucré et de l'insuffisance rénale chronique. L'utilisation des ARA/IECA a été associée à une mortalité significativement plus faible après avoir tenu compte des facteurs confusionnels potentiels (rapport de cotes 0,77 [intervalle de confiance à 95 % : 0,62, 0,96]). En revanche, la méta-analyse sur l'utilisation des ARA/IECA n'a pas été associée de façon significative à la mortalité lorsque toutes les études ont été combinées sans ajustement sur les facteurs confusionnels (0,87 [intervalle de confiance à 95 % : 0,71, 1,08]). CONCLUSIONS: L'utilisation des ARA/IECA a été associée à la diminution de la mortalité au sein des cohortes de patients atteints de la COVID-19 après l'ajustement en fonction de l'âge, du sexe, des maladies cardiovasculaires, de l'hypertension, du diabète et de l'insuffisance rénale chronique. Les méta-analyses non ajustées peuvent ne pas permettre de déterminer si les ARA/IECA sont associés à la mortalité liée à la COVID-19 en raison du biais d'indication.

Characteristics and outcomes of patients with COVID-19 admitted to hospital and intensive care in the first phase of the pandemic in Canada: a national cohort study.

BACKGROUND: Clinical data on patients admitted to hospital with coronavirus disease 2019 (COVID-19) provide clinicians and public health officials with information to guide practice and policy. The aims of this study were to describe patients with COVID-19 admitted to hospital and intensive care, and to investigate predictors of outcome to characterize severe acute respiratory infection. METHODS: This observational cohort study used Canadian data from 32 selected hospitals included in a global multisite cohort between Jan. 24 and July 7, 2020. Adult and pediatric patients with a confirmed diagnosis of COVID-19 who received care in an intensive care unit (ICU) and a sampling of up to the first 60 patients receiving care on hospital wards were included. We performed descriptive analyses of characteristics, interventions and outcomes. The primary analyses examined in-hospital mortality, with secondary analyses of the length of hospital and ICU stay. RESULTS: Between January and July 2020, among 811 patients admitted to hospital with a diagnosis of COVID-19, the median age was 64 (interquartile range [IQR] 53-75) years, 495 (61.0%) were men, 46 (5.7%) were health care workers, 9 (1.1%) were pregnant, 26 (3.2%) were younger than 18 years and 9 (1.1%) were younger than 5 years. The median time from symptom onset to hospital admission was 7 (IQR 3-10) days. The most common symptoms on admission were fever, shortness of breath, cough and malaise. Diabetes, hypertension and cardiac, kidney and respiratory disease were the most common comorbidities. Among all patients, 328 received care in an ICU, admitted a median of 0 (IQR 0-1) days after hospital admission. Critically ill patients received treatment with invasive mechanical ventilation (88.8%), renal replacement therapy (14.9%) and extracorporeal membrane oxygenation (4.0%); 26.2% died. Among those receiving mechanical ventilation, 31.2% died. Age was an influential predictor of mortality (odds ratio per additional year of life 1.06, 95% confidence interval 1.03-1.09). INTERPRETATION: Patients admitted to hospital with COVID-19 commonly had fever, respiratory symptoms and comorbid conditions. Increasing age was associated with the development of critical illness and death; however, most critically ill patients in Canada, including those requiring mechanical ventilation, survived and were discharged from hospital.

Epidemiology, clinical characteristics and treatment of critically ill patients with COVID-19): a protocol for a living systematic review.

INTRODUCTION: In December 2019, the first cases of COVID-19 associated with SARS-CoV-2 viral infection were described in Wuhan, Hubei Province, China. Since then, it has spread rapidly affecting 188 countries and was declared a pandemic by the WHO on 11 March 2020. Preliminary reports suggest up to 30% of patients require intensive care unit (ICU) admission and case fatality rate estimate is 2.3%-7.2%. The primary reason for ICU admission is hypoxaemic respiratory failure, while factors associated with ICU admission include increased age, presence of comorbidities and cytokine storm. Case series and retrospective trials initially assessed proposed treatments with randomised controlled trials now reporting early outcomes. We conduct a systematic review and meta-analysis to identify epidemiological factors, treatments and complications that predict mortality among critically ill patients with COVID-19. METHODS AND ANALYSIS: Our comprehensive search strategy was developed in consultation with a research librarian. We will search electronic databases: Ovid Medline, Ovid Embase, Ovid Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Wiley Cochrane Library. The search strategy combines concepts from COVID-19, validated COVID-19 search filters and geographical locations of large outbreaks. Citation screening, selection, quality assessment and data abstraction will be performed in duplicate. Clinically homogenous epidemiological characteristics, interventions and complications will be pooled in statistical meta-analysis. Within the framework of a living systematic review, the search and data analysis will be updated every 6 months. ETHICS AND DISSEMINATION: Our systematic review will synthesise literature on risk factors and interventions associated with mortality in critically ill patients with COVID-19. Results will be presented at national and international conferences and submitted for peer-reviewed publication. The pooled analysis can provide guidance to inform clinical guidelines for care of critically ill patients with COVID-19. Iterative updates will be made public through open access. Research ethics approval is not required. PROSPERO REGISTRATION NUMBER: CRD42020176672.