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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 40â440 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)â 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 18â831) versus 39.0% (7532 out of 19â295), 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.
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INTRODUCTION: Very little is known about possible clinical sequelae that may persist after resolution of acute COVID-19. A recent longitudinal cohort from Italy including 143 patients followed up after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60-day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical intensive care unit patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. The primary aim of this study is to characterise physical and psychosocial sequelae in patients post-COVID-19 hospital discharge. METHODS AND ANALYSIS: This is an international open-access prospective, observational multisite study. This protocol is linked with the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) and the WHO's Clinical Characterisation Protocol, which includes patients with suspected or confirmed COVID-19 during hospitalisation. This protocol will follow-up a subset of patients with confirmed COVID-19 using standardised surveys to measure longer term physical and psychosocial sequelae. The data will be linked with the acute phase data. Statistical analyses will be undertaken to characterise groups most likely to be affected by sequelae of COVID-19. The open-access follow-up survey can be used as a data collection tool by other follow-up studies, to facilitate data harmonisation and to identify subsets of patients for further in-depth follow-up. The outcomes of this study will inform strategies to prevent long-term consequences; inform clinical management, interventional studies, rehabilitation and public health management to reduce overall morbidity; and improve long-term outcomes of COVID-19. ETHICS AND DISSEMINATION: The protocol and survey are open access to enable low-resourced sites to join the study to facilitate global standardised, longitudinal data collection. Ethical approval has been given by sites in Colombia, Ghana, Italy, Norway, Russia, the UK and South Africa. New sites are welcome to join this collaborative study at any time. Sites interested in adopting the protocol as it is or in an adapted version are responsible for ensuring that local sponsorship and ethical approvals in place as appropriate. The tools are available on the ISARIC website (www.isaric.org). PROTOCOL REGISTRATION NUMBER: osf.io/c5rw3/ PROTOCOL VERSION: 3 August 2020 EUROQOL ID: 37035.
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COVID-19/diagnóstico , COVID-19/psicologia , Colômbia , Gana , Humanos , Itália , Estudos Longitudinais , Noruega , Estudos Prospectivos , Fatores de Risco , Federação Russa , África do Sul , Reino UnidoRESUMO
OBJECTIVES: The 2009-2010 influenza A (H1N1pdm09) pandemic caused substantial morbidity and mortality among young patients; however, mortality estimates have been confounded by regional differences in eligibility criteria and inclusion of selected populations. In 2013-2014, H1N1pdm09 became North America's dominant seasonal influenza strain. Our objective was to compare the baseline characteristics, resources, and treatments with outcomes among critically ill patients with influenza A (H1N1pdm09) in Mexican and Canadian hospitals in 2014 using consistent eligibility criteria. DESIGN: Observational study and a survey of available healthcare setting resources. SETTING: Twenty-one hospitals, 13 in Mexico and eight in Canada. PATIENTS: Critically ill patients with confirmed H1N1pdm09 during 2013-2014 influenza season. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were 90-day mortality and independent predictors of mortality. Among 165 adult patients with H1N1pdm09-related critical illness between September 2013 and March 2014, mean age was 48.3 years, 64% were males, and nearly all influenza was community acquired. Patients were severely hypoxic (median PaO2-to-FIO2 ratio, 83 mm Hg), 97% received mechanical ventilation, with mean positive end-expiratory pressure of 14 cm H2O at the onset of critical illness and 26.7% received rescue oxygenation therapy with prone ventilation, extracorporeal life support, high-frequency oscillatory ventilation, or inhaled nitric oxide. At 90 days, mortality was 34.6% (13.9% in Canada vs 50.5% in Mexico, p < 0.0001). Independent predictors of mortality included lower presenting PaO2-to-FIO2 ratio (odds ratio, 0.89 per 10-point increase [95% CI, 0.80-0.99]), age (odds ratio, 1.49 per 10 yr increment [95% CI, 1.10-2.02]), and requiring critical care in Mexico (odds ratio, 7.76 [95% CI, 2.02-27.35]). ICUs in Canada generally had more beds, ventilators, healthcare personnel, and rescue oxygenation therapies. CONCLUSIONS: Influenza A (H1N1pdm09)-related critical illness still predominantly affects relatively young to middle-aged patients and is associated with severe hypoxemic respiratory failure. The local critical care system and available resources may be influential determinants of patient outcome.
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Estado Terminal/terapia , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/fisiopatologia , Influenza Humana/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Corticosteroides/economia , Corticosteroides/uso terapêutico , Adulto , Idoso , Antivirais/economia , Antivirais/uso terapêutico , Canadá/epidemiologia , Estado Terminal/epidemiologia , Oxigenação por Membrana Extracorpórea/economia , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Gastos em Saúde , Humanos , Influenza Humana/economia , Influenza Humana/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Respiração Artificial/economia , Respiração Artificial/métodos , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapiaRESUMO
BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.
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Anticoagulantes/administração & dosagem , Anticoagulantes/economia , Dalteparina/administração & dosagem , Dalteparina/economia , Custos de Medicamentos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/economia , Heparina/administração & dosagem , Heparina/economia , Custos Hospitalares , Tromboembolia Venosa/economia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Austrália , Brasil , Protocolos Clínicos , Redução de Custos , Análise Custo-Benefício , Cuidados Críticos , Dalteparina/efeitos adversos , Fibrinolíticos/efeitos adversos , Heparina/efeitos adversos , Humanos , Modelos Econômicos , América do Norte , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Projetos de Pesquisa , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Cardiac surgery has been shown to result in a significant decrease of the antioxidant selenium, which is associated with the development of multiorgan dysfunction and increased mortality. Thus, a large-scale study is needed to investigate the effect of perioperative selenium supplementation on the occurrence of postoperative organ dysfunction. METHODS/DESIGN: We plan a prospective, randomized double-blind, multicenter controlled trial, which will be conducted in North and South America and in Europe. In this trial we will include 1,400 high-risk patients, who are most likely to benefit from selenium supplementation. This includes patients scheduled for non-emergent combined and/or complex procedures, or with a predicted operative mortality of ≥ 5% according to the EuroSCORE II. Eligible patients will be randomly assigned to either the treatment group (bolus infusion of 2,000 µg sodium selenite immediately prior to surgery, followed by an additional dosage of 2,000 µg at ICU admission, and a further daily supplementation of 1,000 µg up to 10 days or ICU discharge) or to the control group (placebo administration at the same time points).The primary endpoint of this study is a composite of 'persistent organ dysfunction' (POD) and/or death within 30 days from surgery (POD + death). POD is defined as any need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or new intermittent hemodialysis) at any time within 30 days from surgery. DISCUSSION: The SUSTAIN-CSX™ study is a multicenter trial to investigate the effect of a perioperative high dosage sodium selenite supplementation in high-risk cardiac surgical patients. TRIAL REGISTRATION: This trial was registered at Clinicaltrials.gov (identifier: NCT02002247) on 28 November 2013.
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Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Insuficiência de Múltiplos Órgãos/prevenção & controle , Projetos de Pesquisa , Selenito de Sódio/administração & dosagem , Síndrome de Resposta Inflamatória Sistêmica/prevenção & controle , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Protocolos Clínicos , Método Duplo-Cego , Esquema de Medicação , Europa (Continente) , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , América do Norte , Assistência Perioperatória , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Selenito de Sódio/efeitos adversos , América do Sul , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
Every country has finite resources that are expended to provide citizens with social "goods," including education, protection, infrastructure, and health care. Rationing-of any resource-refers to distribution of an allotted amount and may involve withholding some goods that would benefit some citizens. Health-care rationing is controversial because good health complements so many human endeavors. We explored (perceptions regarding) critical care rationing in seven industrialized countries. Academic physicians from England, Spain, Italy, France, Argentina, Canada, and the United States wrote essays that addressed specific questions including: (1) What historical, cultural, and medical institutional features inform my country's approach to rationing of health care? (2) What is known about formal rationing, especially in critical care, in my country? (3) How does rationing occur in my ICU? Responses suggest that critical care is rationed, by varying mechanisms, in all seven countries. We speculate that while no single "best" method of rationing is likely to be acceptable or optimal for all countries, professional societies could serve international health by developing evidence-based guidelines for just and effective rationing of critical care.
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Cuidados Críticos/economia , Alocação de Recursos para a Atenção à Saúde/economia , Alocação de Recursos para a Atenção à Saúde/legislação & jurisprudência , Argentina , Canadá , Inglaterra , França , Gastos em Saúde/tendências , Humanos , Unidades de Terapia Intensiva/economia , Itália , Espanha , Estados UnidosRESUMO
BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901.
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Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/tratamento farmacológico , Pirimidinas/uso terapêutico , Projetos de Pesquisa , Sulfonamidas/uso terapêutico , Doença Aguda , Argentina , Austrália , Canadá , Comportamento Cooperativo , Cuidados Críticos , Estado Terminal , Quimioterapia Combinada , Estudos de Viabilidade , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Consentimento Livre e Esclarecido , México , Nova Zelândia , Seleção de Pacientes , Projetos Piloto , Respiração Artificial , Rosuvastatina Cálcica , Arábia Saudita , Resultado do TratamentoRESUMO
CONTEXT: In March 2009, novel 2009 influenza A(H1N1) was first reported in the southwestern United States and Mexico. The population and health care system in Mexico City experienced the first and greatest early burden of critical illness. OBJECTIVE: To describe baseline characteristics, treatment, and outcomes of consecutive critically ill patients in Mexico hospitals that treated the majority of such patients with confirmed, probable, or suspected 2009 influenza A(H1N1). DESIGN, SETTING, AND PATIENTS: Observational study of 58 critically ill patients with 2009 influenza A(H1N1) at 6 hospitals between March 24 and June 1, 2009. Demographic data, symptoms, comorbid conditions, illness progression, treatments, and clinical outcomes were collected using a piloted case report form. MAIN OUTCOME MEASURES: The primary outcome measure was mortality. Secondary outcomes included rate of 2009 influenza (A)H1N1-related critical illness and mechanical ventilation as well as intensive care unit (ICU) and hospital length of stay. RESULTS: Critical illness occurred in 58 of 899 patients (6.5%) admitted to the hospital with confirmed, probable, or suspected 2009 influenza (A)H1N1. Patients were young (median, 44.0 [range, 10-83] years); all presented with fever and all but 1 with respiratory symptoms. Few patients had comorbid respiratory disorders, but 21 (36%) were obese. Time from hospital to ICU admission was short (median, 1 day [interquartile range {IQR}, 0-3 days]), and all patients but 2 received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia (median day 1 ratio of Pao(2) to fraction of inspired oxygen, 83 [IQR, 59-145] mm Hg). By 60 days, 24 patients had died (41.4%; 95% confidence interval, 28.9%-55.0%). Patients who died had greater initial severity of illness, worse hypoxemia, higher creatine kinase levels, higher creatinine levels, and ongoing organ dysfunction. After adjusting for a reduced opportunity of patients dying early to receive neuraminidase inhibitors, neuraminidase inhibitor treatment (vs no treatment) was associated with improved survival (odds ratio, 8.5; 95% confidence interval, 1.2-62.8). CONCLUSION: Critical illness from 2009 influenza A(H1N1) in Mexico occurred in young individuals, was associated with severe acute respiratory distress syndrome and shock, and had a high case-fatality rate.