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3.
Crit Care ; 28(1): 63, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414082

RESUMO

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Pneumonia Bacteriana , Síndrome do Desconforto Respiratório , Humanos , COVID-19/complicações , Influenza Humana/complicações , Influenza Humana/terapia , Espectrometria de Massas em Tandem , Cromatografia Líquida , Lisina , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/terapia , Piruvatos
4.
BMC Proc ; 18(Suppl 2): 1, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38233894

RESUMO

Randomized controlled trials (RCTs) have traditionally been considered the gold standard for medical evidence. However, in light of emerging methodologies in data science, many experts question the role of RCTs. Within this context, experts in the USA and Canada came together to debate whether the primacy of RCTs as the gold standard for medical evidence, still holds in light of recent methodological advances in data science and in the era of big data. The purpose of this manuscript, aims to raise awareness of the pros and cons of RCTs and observational studies in order to help guide clinicians, researchers, students, and decision-makers in making informed decisions on the quality of medical evidence to support their work. In particular, new and underappreciated advantages and disadvantages of both designs are contrasted. Innovations taking place in both of these research methodologies, which can blur the lines between the two, are also discussed. Finally, practical guidance for clinicians and future directions in assessing the quality of evidence is offered.

5.
J Proteome Res ; 23(1): 52-70, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38048423

RESUMO

Many COVID-19 survivors have post-COVID-19 conditions, and females are at a higher risk. We sought to determine (1) how protein levels change from acute to post-COVID-19 conditions, (2) whether females have a plasma protein signature different from that of males, and (3) which biological pathways are associated with COVID-19 when compared to restrictive lung disease. We measured protein levels in 74 patients on the day of admission and at 3 and 6 months after diagnosis. We determined protein concentrations by multiple reaction monitoring (MRM) using a panel of 269 heavy-labeled peptides. The predicted forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were measured by routine pulmonary function testing. Proteins associated with six key lipid-related pathways increased from admission to 3 and 6 months; conversely, proteins related to innate immune responses and vasoconstriction-related proteins decreased. Multiple biological functions were regulated differentially between females and males. Concentrations of eight proteins were associated with FVC, %, and they together had c-statistics of 0.751 (CI:0.732-0.779); similarly, concentrations of five proteins had c-statistics of 0.707 (CI:0.676-0.737) for DLCO, %. Lipid biology may drive evolution from acute to post-COVID-19 conditions, while activation of innate immunity and vascular regulation pathways decreased over that period. (ProteomeXchange identifiers: PXD041762, PXD029437).


Assuntos
COVID-19 , Proteômica , Masculino , Feminino , Humanos , Pulmão , Capacidade Vital , Doença Crônica , Lipídeos
6.
Am J Respir Crit Care Med ; 209(1): 24-36, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38032683

RESUMO

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.


Assuntos
Bloqueadores Neuromusculares , Síndrome do Desconforto Respiratório , Adulto , Humanos , Corticosteroides/uso terapêutico , Pulmão , Bloqueadores Neuromusculares/uso terapêutico , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/tratamento farmacológico
7.
J Am Med Inform Assoc ; 31(3): 651-665, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38128123

RESUMO

OBJECTIVES: Distributed computations facilitate multi-institutional data analysis while avoiding the costs and complexity of data pooling. Existing approaches lack crucial features, such as built-in medical standards and terminologies, no-code data visualizations, explicit disclosure control mechanisms, and support for basic statistical computations, in addition to gradient-based optimization capabilities. MATERIALS AND METHODS: We describe the development of the Collaborative Data Analysis (CODA) platform, and the design choices undertaken to address the key needs identified during our survey of stakeholders. We use a public dataset (MIMIC-IV) to demonstrate end-to-end multi-modal FL using CODA. We assessed the technical feasibility of deploying the CODA platform at 9 hospitals in Canada, describe implementation challenges, and evaluate its scalability on large patient populations. RESULTS: The CODA platform was designed, developed, and deployed between January 2020 and January 2023. Software code, documentation, and technical documents were released under an open-source license. Multi-modal federated averaging is illustrated using the MIMIC-IV and MIMIC-CXR datasets. To date, 8 out of the 9 participating sites have successfully deployed the platform, with a total enrolment of >1M patients. Mapping data from legacy systems to FHIR was the biggest barrier to implementation. DISCUSSION AND CONCLUSION: The CODA platform was developed and successfully deployed in a public healthcare setting in Canada, with heterogeneous information technology systems and capabilities. Ongoing efforts will use the platform to develop and prospectively validate models for risk assessment, proactive monitoring, and resource usage. Further work will also make tools available to facilitate migration from legacy formats to FHIR and DICOM.


Assuntos
Instalações de Saúde , Software , Humanos , Atenção à Saúde , Aprendizado de Máquina , Canadá
8.
Indian J Crit Care Med ; 27(12): 910-916, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38074959

RESUMO

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes. Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India. Adult patients (≥18 years) with proven or suspected infection as the main diagnosis and needing a continuous intravenous vasopressor infusion were randomized to intravenous vitamin C (50 mg/kg every 6 hours for a maximum of 16 doses) or matching placebo. Primary outcomes were related to protocol adherence and feasibility (enrollment per month). The key secondary outcome was the composite of mortality or persistent organ dysfunction (POD) at day 28 after randomization. Results: 60 patients were screened, 51 were eligible, 32 were randomized, and 30 were included in the analysis (randomized/eligible ratio: 0.63). The overall rate of enrollment was 1.5 patients per month. The median (IQR) age was 63.5 (51.0, 70.0) and 70.0% of the patients were male. In both arms, all patients received ≥90% of scheduled doses of the study drug. No patient received open-label vitamin C and there were no deviations from the glucose monitoring protocol. The composite outcome of mortality or POD at day 28 occurred in 56.3% (9/16) in the vitamin C arm as compared to 42.9% (6/14) in the placebo arm [RR: 1.31 (95% CI: 0.62, 2.76), p = 0.47]. Conclusion: In this pilot feasibility randomized controlled trial of vitamin C for adult patients with sepsis, protocol adherence was excellent and feasibility endpoints were met. Trial registration: CTRI/2020/03/024371. How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramanathan Y, Margabandhu S, Jayakumar D, Ramachandran P, et al. A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial. Indian J Crit Care Med 2023;27(12):910-916.

9.
JAMA Netw Open ; 6(12): e2346502, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38147336

RESUMO

Importance: Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. Objectives: To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. Design, Setting, and Participants: This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Exposure: Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Main Outcomes and Measures: Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Results: Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). Conclusions and Relevance: The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation.


Assuntos
COVID-19 , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos de Coortes , Estudos Prospectivos , Corticosteroides/uso terapêutico , África
11.
Crit Care Med ; 51(12): e283-e284, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37971352
12.
N Engl J Med ; 389(25): 2341-2354, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-37888913

RESUMO

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2). RESULTS: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control. CONCLUSIONS: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).


Assuntos
COVID-19 , Estado Terminal , Inibidores de Hidroximetilglutaril-CoA Redutases , Sinvastatina , Humanos , Teorema de Bayes , COVID-19/mortalidade , COVID-19/terapia , Tratamento Farmacológico da COVID-19 , Estado Terminal/mortalidade , Estado Terminal/terapia , Mortalidade Hospitalar , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Sinvastatina/uso terapêutico , Resultado do Tratamento
13.
Intensive Care Med ; 49(11): 1305-1316, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37815560

RESUMO

BACKGROUND: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). METHODS: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. RESULTS: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). CONCLUSIONS: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Humanos , Injúria Renal Aguda/terapia , Estado Terminal/terapia , Diálise Renal , Terapia de Substituição Renal
14.
CMAJ Open ; 11(4): E672-E683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37527902

RESUMO

BACKGROUND: Omicron is the current predominant variant of concern of SARS-CoV-2. We hypothesized that vaccination alters outcomes of patients hospitalized with COVID-19 during the Omicron wave and that these patients have different characteristics and outcomes than in previous waves. METHODS: This is a substudy of the Host Response Mediators in Coronavirus (COVID-19) Infection (ARBs CORONA I) trial, which included adults admitted to hospital with acute COVID-19 up to July 2022 from 9 hospitals in British Columbia, Ontario and Quebec. We excluded emergency department visits without hospital admission, readmissions and admissions for another reason. Using adjusted regression analysis, we compared mortality and organ dysfunction between vaccinated (≥ 2 doses) and unvaccinated patients during the Omicron wave, as well as between all patients in the Omicron and first 3 waves of the COVID-19 pandemic. RESULTS: During the Omicron wave, 28-day mortality was significantly lower in vaccinated (n = 19/237) than unvaccinated hospitalized patients (n = 12/127) (adjusted odds ratio [OR] 0.36, 95% confidence interval [CI] 0.15-0.89); vaccinated patients had lower risk of admission to the intensive care unit, invasive ventilation and acute respiratory distress syndrome and shorter hospital length of stay. Patients hospitalized during the Omicron wave had more comorbidities than in previous waves, and lower 28-day mortality than in waves 1 and 2 (adjusted OR 0.38, 95% CI 0.24-0.59; and 0.42, 95% CI 0.26-0.65) but not wave 3 (adjusted OR 0.81, 95% CI 0.43-1.51) and had less organ dysfunction than in the first 2 waves. INTERPRETATION: Patients who were at least double vaccinated had lower mortality than unvaccinated patients hospitalized during the Omicron wave. Patients hospitalized during the Omicron wave had more chronic disease and lower mortality than in the first 2 waves, but not wave 3. Changes in vaccination, treatments and predominant SARS-CoV-2 variant may have decreased mortality in patients hospitalized during the Omicron wave.

15.
Intensive Care Med ; 49(9): 1103-1106, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37505257

Assuntos
COVID-19 , Humanos , SARS-CoV-2
16.
Acta Anaesthesiol Scand ; 67(10): 1423-1431, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37500083

RESUMO

BACKGROUND: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? METHODS: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. RESULTS: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis. CONCLUSIONS: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged.

17.
BMJ Open ; 13(6): e075685, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37355270

RESUMO

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).


Assuntos
Estado Terminal , Respiração Artificial , Adulto , Humanos , Adolescente , Estado Terminal/terapia , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Extremidade Inferior , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
18.
Am J Epidemiol ; 192(10): 1678-1687, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37254775

RESUMO

We aimed to assess the impact of allocation concealment and blinding on the results of coronavirus disease 2019 (COVID-19) trials, using the World Health Organization COVID-19 database (to February 2022). We identified 488 randomized trials comparing drug therapeutics with placebo or standard care in patients with COVID-19. We performed random-effects meta-regressions comparing the results of trials with and without allocation concealment and blinding of health-care providers and patients. We found that, compared with trials with allocation concealment, trials without allocation concealment may estimate treatments to be more beneficial for mortality, mechanical ventilation, hospital admission, duration of hospitalization, and duration of mechanical ventilation, but results were imprecise. We did not find compelling evidence that, compared with trials with blinding, trials without blinding produce consistently different results for mortality, mechanical ventilation, and duration of hospitalization. We found that trials without blinding may estimate treatments to be more beneficial for hospitalizations and duration of mechanical ventilation. We did not find compelling evidence that COVID-19 trials in which health-care providers and patients are blinded produce different results from trials without blinding, but trials without allocation concealment estimate treatments to be more beneficial compared with trials with allocation concealment. Our study suggests that lack of blinding may not always bias results but that evidence users should remain skeptical of trials without allocation concealment.


Assuntos
COVID-19 , Humanos , Viés , Hospitalização
19.
Crit Care Med ; 51(8): e152-e156, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37026849

RESUMO

OBJECTIVES: The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis. DESIGN: Bayesian reanalysis of a randomized placebo-controlled trial. SETTING: Thirty-five ICUs. PATIENTS: Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission. INTERVENTIONS: Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04-1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00-1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97-1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98-1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94-1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92-1.19; probability of harm, 76%) priors. CONCLUSIONS: The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.


Assuntos
Sepse , Vitaminas , Humanos , Adulto , Ácido Ascórbico/uso terapêutico , Insuficiência de Múltiplos Órgãos/complicações , Teorema de Bayes , Sepse/tratamento farmacológico , Sepse/complicações
20.
J Clin Monit Comput ; 37(4): 1023-1033, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37074523

RESUMO

The integration of illness severity and organ dysfunction scores into clinical practice, including the APACHE II and SOFA scores, has been challenging due to constraints associated to manual score calculation. With electronic medical records (EMR), score calculation automation using data extraction scripts has emerged as a solution. We aimed to demonstrate that APACHE II and SOFA scores calculated with an automated EMR-based data extraction script predict important clinical endpoints. In this retrospective cohort study, every adult patient admitted to one of our three ICUs, between July 1, 2019, and December 31, 2020, were enrolled. For every patient, an automated ICU admission APACHE II score was calculated using EMR data and minimal clinician input. Fully automated daily SOFA scores were calculated for every patient. 4 794 ICU admissions met our selection criteria. Of these ICU admissions, 522 deaths were recorded (10.9% in-hospital mortality rate). The automated APACHE II was discriminant for in-hospital mortality (AU-ROC = 0.83 (95% CI 0.81-0.85)). We observed an association between the APACHE II score and ICU LOS, with a statistically significant mean increase of 1.1 days of ICU LOS (1.1 [1-1.2]; p = < .0001) for each 10 units increase in APACHE score. SOFA score curves did not discrimate significantly between survivors and non-survivors. A partially automated APACHE II score, calculated with real-world EMR data using an extraction script, is associated with in-hospital mortality risk. The automated APACHE II score could potentially constitute an acceptable surrogate of ICU acuity to be used in resource allocation and triaging, especially in time of high demand for ICU beds.


Assuntos
Registros Eletrônicos de Saúde , Escores de Disfunção Orgânica , Adulto , Humanos , APACHE , Índice de Gravidade de Doença , Estudos Retrospectivos , Unidades de Terapia Intensiva , Prognóstico , Curva ROC
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