Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society (ERS) and the European Society of Intensive Care Medicine (ESICM). Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society and the European Society of Intensive Care Medicine. Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

The trajectory of very old critically ill patients.

The demographic shift, together with financial constraint, justify a re-evaluation of the trajectory of care of very old critically ill patients (VIP), defined as older than 80 years. We must avoid over- as well as under-utilisation of critical care interventions in this patient group and ensure the inclusion of health care professionals, the patient and their caregivers in the decision process. This new integrative approach mobilises expertise at each step of the process beginning prior to intensive care unit (ICU) admission and extending to long-term follow-up. In this review, several international experts have contributed to provide recommendations that can be universally applied. Our aim is to define a minimum core dataset of information to be shared and discussed prior to ICU admission and to facilitate the shared-decision-making process with the patient and their caregivers, throughout the patient journey. Documentation of uncertainty may contribute to a tailored level of care and ultimately to discussions around possible limitations of life sustaining treatments. The goal of ICU care is not only to avoid death, but more importantly to maintain an acceptable quality of life and functional autonomy after hospital discharge. Societal consideration is important to highlight, together with alternatives to ICU admission. We discuss challenges for the future and potential areas of research. In summary, this review provides a state-of-the-art current overview and aims to outline future directions to address the challenges in the treatment of VIP.

A New Global Definition of Acute Respiratory Distress Syndrome.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Clinical phenotypes of cardiogenic shock survivors: insights into late host responses and long-term outcomes.

AIMS: An elevated risk of adverse events persists for years in cardiogenic shock (CS) survivors with high mortality rate and physical/mental disability. This study aims to link clinical CS-survivor phenotypes with distinct late host-response patterns at intensive care unit (ICU) discharge and long-term outcomes using model-based clustering. METHODS AND RESULTS: In the original prospective, observational, international French and European Outcome Registry in Intensive Care Units (FROG-ICU) study, ICU patients with CS on admission were identified (N = 228). Among them, 173 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct CS-survivor phenotypes at ICU discharge using 15 readily available clinical and laboratory variables. The primary endpoint was 1 year of mortality after ICU discharge. Secondary endpoints were readmission and physical/mental disability [short form-36 questionnaire (SF-36) score] within 1 year after ICU discharge. Two distinct phenotypes at ICU discharge were identified (A and B). Patients in Phenotype B (38%) were more anaemic and had higher circulating levels of lactate, sustained kidney injury, and persistent elevation in plasma markers of inflammation, myocardial fibrosis, and endothelial dysfunction compared with Phenotype A. They had also a higher rate of non-ischaemic origin of CS and right ventricular dysfunction on admission. CS survivors in Phenotype B had higher 1 year of mortality compared with Phenotype A (P = 0.045, Kaplan-Meier analysis). When adjusted for traditional risk factors (i.e. age, severity of illness, and duration of ICU stay), Phenotype B was independently associated with 1 year of mortality [adjusted hazard ratio = 2.83 (95% confidence interval 1.21-6.60); P = 0.016]. There was a significantly lower physical quality of life in Phenotype B patients at 3 months (i.e. SF-36 physical component score). CONCLUSIONS: A phenotype with sustained inflammation, myocardial fibrosis, and endothelial dysfunction at ICU discharge was identified from readily available data and was independently associated with poor long-term outcomes in CS survivors.

Sex and gender differences in intensive care medicine.

Despite significant advancements in critical care medicine, limited attention has been given to sex and gender disparities in management and outcomes of patients admitted to the intensive care unit (ICU). While "sex" pertains to biological and physiological characteristics, such as reproductive organs, chromosomes and sex hormones, "gender" refers more to sociocultural roles and human behavior. Unfortunately, data on gender-related topics in the ICU are lacking. Consequently, data on sex and gender-related differences in admission to the ICU, clinical course, length of stay, mortality, and post-ICU burdens, are often inconsistent. Moreover, when examining specific diagnoses in the ICU, variations can be observed in epidemiology, pathophysiology, presentation, severity, and treatment response due to the distinct impact of sex hormones on the immune and cardiovascular systems. In this narrative review, we highlight the influence of sex and gender on the clinical course, management, and outcomes of the most encountered intensive care conditions, in addition to the potential co-existence of unconscious biases which may also impact critical illness. Diagnoses with a known sex predilection will be discussed within the context of underlying sex differences in physiology, anatomy, and pharmacology with the goal of identifying areas where clinical improvement is needed. To optimize patient care and outcomes, it is crucial to comprehend and address sex and gender differences in the ICU setting and personalize management accordingly to ensure equitable, patient-centered care. Future research should focus on elucidating the underlying mechanisms driving sex and gender disparities, as well as exploring targeted interventions to mitigate these disparities and improve outcomes for all critically ill patients.

Long-Term Outcomes of Cardiogenic Shock Complicating Myocardial Infarction.

BACKGROUND: Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short-term mortality; however, there are limited data on long-term outcomes and trends. OBJECTIVES: This study sought to examine long-term outcomes of AMI-CS patients. METHODS: This was a population-based, retrospective cohort study in Ontario, Canada of critically ill adult patients with AMI-CS who were admitted to hospitals between April 1, 2009 and March 31, 2019. Outcome data were captured using linked health administrative databases. RESULTS: A total of 9,789 consecutive patients with AMI-CS from 135 centers were included. The mean age was 70.5 ± 12.3 years, and 67.7% were male. The incidence of AMI-CS was 8.2 per 100,000 person-years, and it increased over the study period. Critical care interventions were common, with 5,422 (55.4%) undergoing invasive mechanical ventilation, 1,425 (14.6%) undergoing renal replacement therapy, and 1,484 (15.2%) receiving mechanical circulatory support. A total of 2,961 patients (30.2%) died in the hospital, and 4,004 (40.9%) died by 1 year. Mortality at 5 years was 58.9%. Small improvements in short- and long-term mortality were seen over the study period. Among survivors to discharge, 2,870 (42.0%) required increased support in care from their preadmission baseline, 3,244 (47.5%) were readmitted to the hospital within 1 year, and 1,047 (15.3%) died within 1 year. The mean number of days at home in the year following discharge was 307.9 ± 109.6. CONCLUSIONS: Short- and long-term mortality among patients with AMI-CS is high, with minimal improvement over time. AMI-CS survivors experience significant morbidity, with high risks of readmission and death. Future studies should evaluate interventions to minimize postdischarge morbidity and mortality among AMI-CS survivors.

Understanding How Post-COVID-19 Condition Affects Adults and Health Care Systems.

Importance: Post-COVID-19 condition (PCC), also known as long COVID, encompasses the range of symptoms and sequelae that affect many people with prior SARS-CoV-2 infection. Understanding the functional, health, and economic effects of PCC is important in determining how health care systems may optimally deliver care to individuals with PCC. Observations: A rapid review of the literature showed that PCC and the effects of hospitalization for severe and critical illness may limit a person's ability to perform day-to-day activities and employment, increase their risk of incident health conditions and use of primary and short-term health care services, and have a negative association with household financial stability. Care pathways that integrate primary care, rehabilitation services, and specialized assessment clinics are being developed to support the health care needs of people with PCC. However, comparative studies to determine optimal care models based on their effectiveness and costs remain limited. The effects of PCC are likely to have large-scale associations with health systems and economies and will require substantial investment in research, clinical care, and health policy to mitigate these effects. Conclusions and Relevance: An accurate understanding of additional health care and economic needs at the individual and health system levels is critical to informing health care resource and policy planning, including identification of optimal care pathways to support people affected by PCC.

Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations.

Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after the acute phase, lasting for weeks or months after the initial acute illness. The post-acute sequelae of COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID or post-COVID-19 condition. The substantial burden of this multisystem condition is felt at individual, health-care system, and socioeconomic levels, on an unprecedented scale. Survivors of COVID-19-related critical illness are at risk of the well known sequelae of acute respiratory distress syndrome, sepsis, and chronic critical illness, and these multidimensional morbidities might be difficult to differentiate from the specific effects of SARS-CoV-2 and COVID-19. We provide an overview of the manifestations of post-COVID-19 condition after critical illness in adults. We explore the effects on various organ systems, describe potential pathophysiological mechanisms, and consider the challenges of providing clinical care and support for survivors of critical illness with multisystem manifestations. Research is needed to reduce the incidence of post-acute sequelae of COVID-19-related critical illness and to optimise therapeutic and rehabilitative care and support for patients.

Outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation: a prospective observational study.

PURPOSE: Descriptive information on referral patterns and short-term outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation (ECMO) is lacking. METHODS: We conducted a prospective single-centre observational cohort study of ECMO referrals to Toronto General Hospital (receiving hospital) for severe respiratory failure (COVID-19 and non-COVID-19), between 1 December 2019 and 30 November 2020. Data related to the referral, the referral decision, and reasons for refusal were collected. Reasons for refusal were grouped into three mutually exclusive categories selected a priori: "too sick now," "too sick before," and "not sick enough." In declined referrals, referring physicians were surveyed to collect patient outcome on day 7 after the referral. The primary study endpoints were referral outcome (accepted/declined) and patient outcome (alive/deceased). RESULTS: A total of 193 referrals were included; 73% were declined for transfer. Referral outcome was influenced by age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95 to 0.96; P < 0.01) and involvement of other members of the ECMO team in the discussion (OR, 4.42; 95% CI, 1.28 to 15.2; P < 0.01). Patient outcomes were missing in 46 (24%) referrals (inability to locate the referring physician or the referring physician being unable to recall the outcome). Using available data (95 declined and 52 accepted referrals; n = 147), survival to day 7 was 49% for declined referrals (35% for patients deemed "too sick now," 53% for "too sick before," 100% for "not sick enough," and 50% for reason for refusal not reported) and 98% for transferred patients. Sensitivity analysis setting missing outcomes to directional extreme values retained robustness of survival probabilities. CONCLUSION: Nearly half of the patients declined for ECMO consideration were alive on day 7. More information on patient trajectory and long-term outcomes in declined referrals is needed to refine selection criteria.

RéSUMé: OBJECTIF: On manque d'informations descriptives sur les schémas de références et les devenirs à court terme des patient·es atteint·es d'insuffisance respiratoire n'ayant pas pu recevoir une oxygénation par membrane extracorporelle (ECMO). MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective monocentrique sur les références vers l'ECMO à l'Hôpital général de Toronto (hôpital d'accueil) pour insuffisance respiratoire grave (COVID-19 et non-COVID-19), entre le 1er décembre 2019 et le 30 novembre 2020. Les données relatives à la référence, à la décision de référence et aux motifs du refus ont été recueillies. Les motifs de refus ont été regroupés en trois catégories mutuellement exclusives sélectionnées a priori : « Trop malade maintenant ¼, « Trop malade avant ¼ et « Pas assez malade ¼. En ce qui concerne les références refusées, un sondage envoyé aux médecins traitant·es avait pour objectif de recueillir les devenirs des patient·es le jour 7 suivant la référence. Les critères d'évaluation principaux de l'étude étaient le résultat de la référence (accepté/refusé) et le devenir des patient·es (vivant·e/décédé·e). RéSULTATS: Au total, 193 références ont été incluses; le transfert a été refusé dans 73 % des cas. L'acceptation ou le refus de la référence était influencé par l'âge (rapport de cotes [RC], 0,97; intervalle de confiance [IC] à 95 %, 0,95 à 0,96; P < 0,01) et la participation d'autres membres de l'équipe ECMO à la discussion (RC, 4,42; IC 95 %, 1,28 à 15,2; P < 0,01). Les devenirs des patient·es étaient manquants pour 46 (24 %) des personnes référées (incapacité de localiser les médecins traitant·es ou incapacité des médecins de se souvenir du devenir). À l'aide des données disponibles (95 références refusées et 52 références acceptées; n = 147), la survie jusqu'au jour 7 était de 49 % pour les références refusées (35 % pour la patientèle jugée « trop malade maintenant ¼, 53 % pour celle « trop malade avant ¼, 100 % pour celle « pas assez malade ¼ et 50 % pour les cas où la raison du refus n'était pas déclarée) et 98 % pour les patient·es transféré·es. L'analyse de sensibilité établissant les résultats manquants à des valeurs extrêmes directionnelles a conservé la robustesse des probabilités de survie. CONCLUSION: Près de la moitié des patient·es pour lesquel·les un traitement sous ECMO a été refusé étaient en vie au jour 7. Davantage d'informations concernant la trajectoire et les devenirs à long terme des patient·es refusé·es sont nécessaires pour parfaire les critères de sélection.

ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies.

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

Comparison of Medical and Mental Health Sequelae Following Hospitalization for COVID-19, Influenza, and Sepsis.

Importance: People who survive hospitalization for COVID-19 are at risk for developing new cardiovascular, neurological, mental health, and inflammatory autoimmune conditions. It is unclear how posthospitalization risks for COVID-19 compare with those for other serious infectious illnesses. Objective: To compare risks of incident cardiovascular, neurological, and mental health conditions and rheumatoid arthritis in 1 year following COVID-19 hospitalization against 3 comparator groups: prepandemic hospitalization for influenza and hospitalization for sepsis before and during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study included all adults hospitalized for COVID-19 between April 1, 2020, and October 31, 2021, historical comparator groups of people hospitalized for influenza or sepsis, and a contemporary comparator group of people hospitalized for sepsis in Ontario, Canada. Exposure: Hospitalization for COVID-19, influenza, or sepsis. Main Outcome and Measures: New occurrence of 13 prespecified conditions, including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis, within 1 year of hospitalization. Results: Of 379 366 included adults (median [IQR] age, 75 [63-85] years; 54% female), there were 26 499 people who survived hospitalization for COVID-19, 299 989 historical controls (17 516 for influenza and 282 473 for sepsis), and 52 878 contemporary controls hospitalized for sepsis. Hospitalization for COVID-19 was associated with an increased 1-year risk of venous thromboembolic disease compared with influenza (adjusted hazard ratio, 1.77; 95% CI, 1.36-2.31) but with no increased risks of developing selected ischemic and nonischemic cerebrovascular and cardiovascular disorders, neurological disorders, rheumatoid arthritis, or mental health conditions compared with influenza or sepsis cohorts. Conclusions and Relevance: In this cohort study, apart from an elevated risk of venous thromboembolism within 1 year, the burden of postacute medical and mental health conditions among those who survived hospitalization for COVID-19 was comparable with other acute infectious illnesses. This suggests that many of the postacute consequences of COVID-19 may be related to the severity of infectious illness necessitating hospitalization rather than being direct consequences of infection with SARS-CoV-2.

Critical Care Cycling to Improve Lower Extremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients.

INTRODUCTION: In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. METHODS AND ANALYSIS: We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups. ETHICS AND DISSEMINATION: Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

Sex and age affect acute and persisting COVID-19 illness.

Long COVID is associated with neurological and neuropsychiatric manifestations. We conducted an observational study on 97 patients with prior SARS-CoV-2 infection and persisting cognitive complaints that presented to the University Health Network Memory Clinic between October 2020 and December 2021. We assessed the main effects of sex, age, and their interaction on COVID-19 symptoms and outcomes. We also examined the relative contribution of demographics and acute COVID-19 presentation (assessed retrospectively) on persistent neurological symptoms and cognition. Among our cohort, males had higher hospitalization rates than females during the acute COVID-19 illness (18/35 (51%) vs. 15/62 (24%); P = .009). Abnormal scores on cognitive assessments post-COVID were associated with older age (AOR = 0.84; 95% CI 0.74-0.93) and brain fog during initial illness (AOR = 8.80; 95% CI 1.76-65.13). Female sex (ARR = 1.42; 95% CI 1.09-1.87) and acute shortness of breath (ARR = 1.41; 95% CI 1.09-1.84) were associated with a higher risk of experiencing more persistent short-term memory symptoms. Female sex was the only predictor associated with persistent executive dysfunction (ARR = 1.39; 95% CI 1.12-1.76) and neurological symptoms (ARR = 1.66; 95% CI 1.19-2.36). Sex differences were evident in presentations and cognitive outcomes in patients with long COVID.

Association of Days Alive and at Home at Day 90 After Intensive Care Unit Admission With Long-term Survival and Functional Status Among Mechanically Ventilated Patients.

Importance: Many conventional end points in randomized clinical trials of interventions for critically ill patients do not account for patient-centered concerns such as time at home, physical function, and quality of life after critical illness. Objective: To establish whether days alive and at home at day 90 (DAAH90) is associated with long-term survival and functional outcomes in mechanically ventilated patients. Design, Setting, and Participants: The RECOVER prospective cohort study was conducted from February 2007 to March 2014, using data from 10 intensive care units (ICUs) in Canada. Patients were included in the baseline cohort if they were aged 16 years or older and underwent invasive mechanical ventilation for 7 or more days. The follow-up cohort analyzed here comprised RECOVER patients who were alive and had functional outcomes ascertained at 3, 6, and 12 months. Secondary data analysis occurred from July 2021 to August 2022. Exposures: Composite of survival and days alive and at home at day 90 after ICU admission (DAAH90). Main Outcomes and Measures: Functional outcomes at 3, 6, and 12 months were evaluated with the Functional Independence Measure (FIM), the 6-Minute Walk Test (6MWT), the Medical Research Council (MRC) Scale for Muscle Strength, and the 36-Item Short Form Health Survey physical component summary (SF-36 PCS). Mortality was evaluated at 1 year from ICU admission. Ordinal logistic regression was used to describe the association between DAAH90 tertiles and outcomes. Cox proportional hazards regression models were used to examine the independent association of DAAH90 tertiles with mortality. Results: The baseline cohort comprised 463 patients. Their median age was 58 years (IQR, 47-68 years), and 278 patients (60.0%) were men. In these patients, Charlson Comorbidity Index score, Acute Physiology and Chronic Health Evaluation II score, ICU intervention (eg, kidney replacement therapy or tracheostomy), and ICU length of stay were independently associated with lower DAAH90. The follow-up cohort comprised 292 patients. Their median age was 57 years (IQR, 46-65 years), and 169 patients (57.9%) were men. Among patients who survived to day 90, lower DAAH90 was associated with higher mortality at 1 year after ICU admission (tertile 1 vs tertile 3: adjusted hazard ratio [HR], 0.18 [95% CI, 0.07-0.43]; P < .001). At 3 months of follow-up, lower DAAH90 was independently associated with lower median scores on the FIM (tertile 1 vs tertile 3, 76 [IQR, 46.2-101] vs 121 [IQR, 112-124.2]; P = .04), 6MWT (tertile 1 vs tertile 3, 98 [IQR, 0-239] vs 402 [IQR, 300-494]; P < .001), MRC (tertile 1 vs tertile 3, 48 [IQR, 32-54] vs 58 [IQR, 51-60]; P < .001), and SF-36 PCS (tertile 1 vs tertile 3, 30 [IQR, 22-38] vs 37 [IQR, 31-47]; P = .001) measures. Among patients who survived to 12 months, being in tertile 3 vs tertile 1 for DAAH90 was associated with higher FIM score at 12 months (estimate, 22.4 [95% CI, 14.8-30.0]; P < .001), but this association was not present for ventilator-free days (estimate, 6.0 [95% CI, -2.2 to 14.1]; P = .15) or ICU-free days (estimate, 5.9 [95% CI, -2.1 to 13.8]; P = .15) at day 28. Conclusions and Relevance: In this study, lower DAAH90 was associated with greater long-term mortality risk and worse functional outcomes among patients who survived to day 90. These findings suggest that the DAAH90 end point reflects long-term functional status better than standard clinical end points in ICU studies and may serve as a patient-centered end point in future clinical trials.