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1.
Curr Opin Crit Care ; 30(5): 427-438, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39150040

RESUMO

PURPOSE OF REVIEW: To date, most randomized clinical trials in critical care report neutral overall results. However, research as to whether heterogenous responses underlie these results and give opportunity for personalized care is gaining momentum but has yet to inform clinical practice guidance. Thus, we aim to provide an overview of methodological approaches to estimating heterogeneity of treatment effects in randomized trials and conjecture about future paths to application in patient care. RECENT FINDINGS: Despite their limitations, traditional subgroup analyses are still the most reported approach. More recent methods based on subphenotyping, risk modeling and effect modeling are still uncommonly embedded in primary reports of clinical trials but have provided useful insights in secondary analyses. However, further simulation studies and subsequent guidelines are needed to ascertain the most efficient and robust manner to validate these results for eventual use in practice. SUMMARY: There is an increasing interest in approaches that can identify heterogeneity in treatment effects from randomized clinical trials, extending beyond traditional subgroup analyses. While prospective validation in further studies is still needed, these approaches are promising tools for design, interpretation, and implementation of clinical trial results.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Humanos , Cuidados Críticos , Interpretação Estatística de Dados , Resultado do Tratamento , Heterogeneidade da Eficácia do Tratamento
2.
Eur J Nutr ; 63(7): 2391-2405, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38967674

RESUMO

PURPOSE: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events. METHODS: Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence's certainty. RESULTS: From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events. CONCLUSIONS: Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting.


Assuntos
Aterosclerose , Biomarcadores , Inflamação , Lipídeos , Nozes , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Biomarcadores/sangue , Aterosclerose/sangue , Aterosclerose/prevenção & controle , Lipídeos/sangue , Inflamação/sangue , Dieta/métodos , Doenças Cardiovasculares/prevenção & controle
3.
J Thromb Thrombolysis ; 57(6): 1031-1039, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38762708

RESUMO

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.


Assuntos
COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio , Hemorragia , Trombose , Humanos , COVID-19/sangue , COVID-19/complicações , COVID-19/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/induzido quimicamente , Masculino , Feminino , Trombose/sangue , Trombose/etiologia , Trombose/diagnóstico , Idoso , Pessoa de Meia-Idade , Hospitalização , Fatores de Risco , SARS-CoV-2 , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos
4.
JAMA ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382244

RESUMO

Importance: Despite its implementation in several countries, there has not been a randomized clinical trial to assess whether telemedicine in intensive care units (ICUs) could improve clinical outcomes of critically ill patients. Objective: To determine whether an intervention comprising daily multidisciplinary rounds and monthly audit and feedback meetings performed by a remote board-certified intensivist reduces ICU length of stay (LOS) compared with usual care. Design, Setting, and Participants: A parallel cluster randomized clinical trial with a baseline period in 30 general ICUs in Brazil in which daily multidisciplinary rounds performed by board-certified intensivists were not routinely available. All consecutive adult patients (aged ≥18 years) admitted to the participating ICUs, excluding those admitted due to justice-related issues, were enrolled between June 1, 2019, and April 7, 2021, with last follow-up on July 6, 2021. Intervention: Remote daily multidisciplinary rounds led by a board-certified intensivist through telemedicine, monthly audit and feedback meetings for discussion of ICU performance indicators, and provision of evidence-based clinical protocols. Main Outcomes and Measures: The primary outcome was ICU LOS at the patient level. Secondary outcomes included ICU efficiency, in-hospital mortality, incidence of central line-associated bloodstream infections, ventilator-associated events, catheter-associated urinary tract infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation, and rate of patients with oxygen saturation values under that of normoxemia, assessed using generalized linear mixed models. Results: Among 17 024 patients (1794 in the baseline period and 15 230 in the intervention period), the mean (SD) age was 61 (18) years, 44.7% were female, the median (IQR) Sequential Organ Failure Assessment score was 6 (2-9), and 45.5% were invasively mechanically ventilated at admission. The median (IQR) time under intervention was 20 (16-21) months. Mean (SD) ICU LOS, adjusted for baseline assessment, did not differ significantly between the tele-critical care and usual care groups (8.1 [10.0] and 7.1 [9.0] days; percentage change, 8.2% [95% CI, -5.4% to 23.8%]; P = .24). Results were similar in sensitivity analyses and prespecified subgroups. There were no statistically significant differences in any other secondary or exploratory outcomes. Conclusions and Relevance: Daily multidisciplinary rounds conducted by a board-certified intensivist through telemedicine did not reduce ICU LOS in critically ill adult patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03920501.

5.
N Engl J Med ; 383(21): 2041-2052, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32706953

RESUMO

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).


Assuntos
Antivirais/administração & dosagem , Azitromicina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Brasil , COVID-19 , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Gravidade do Paciente , SARS-CoV-2 , Falha de Tratamento , Tratamento Farmacológico da COVID-19
6.
N Engl J Med ; 383(22): 2117-2126, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33196155

RESUMO

BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Bioprótese , Valva Mitral , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Doenças Cardiovasculares/epidemiologia , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Método Simples-Cego , Acidente Vascular Cerebral/prevenção & controle , Varfarina/efeitos adversos
7.
Am J Respir Crit Care Med ; 205(12): 1419-1428, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35349397

RESUMO

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).


Assuntos
Estado Terminal , Sepse , Adulto , Teorema de Bayes , Estado Terminal/terapia , Soluções Cristaloides/uso terapêutico , Hidratação/métodos , Humanos , Solução Salina
8.
Lancet ; 397(10291): 2253-2263, 2021 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-34097856

RESUMO

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.


Assuntos
Anticoagulantes/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/sangue , Enoxaparina/uso terapêutico , Heparina/uso terapêutico , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Adulto , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Brasil/epidemiologia , Determinação de Ponto Final , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , SARS-CoV-2 , Resultado do Tratamento
9.
Am J Respir Crit Care Med ; 204(3): 303-311, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33784486

RESUMO

Rationale: Mortality in acute respiratory distress syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower Vt, lower driving pressure (ΔP), lower respiratory rates (RR), and higher end-expiratory pressure have all been suggested as key components of lung protection strategies. A unifying theoretical explanation has been proposed that attributes lung injury to the energy transfer rate (mechanical power) from the ventilator to the patient, calculated from a combination of several ventilator variables.Objectives: To assess the impact of mechanical power on mortality in patients with ARDS as compared with that of primary ventilator variables such as the ΔP, Vt, and RR.Methods: We obtained data on ventilatory variables and mechanical power from a pooled database of patients with ARDS who had participated in six randomized clinical trials of protective mechanical ventilation and one large observational cohort of patients with ARDS. The primary outcome was mortality at 28 days or 60 days.Measurements and Main Results: We included 4,549 patients (38% women; mean age, 55 ± 23 yr). The average mechanical power was 0.32 ± 0.14 J · min-1 · kg-1 of predicted body weight, the ΔP was 15.0 ± 5.8 cm H2O, and the RR was 25.7 ± 7.4 breaths/min. The driving pressure, RR, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of the ΔP on mortality was four times as large as that of the RR.Conclusions: Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS, but a simpler model using only the ΔP and RR was equivalent.


Assuntos
Mortalidade , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Adulto , Idoso , Transferência de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Taxa Respiratória , Lesão Pulmonar Induzida por Ventilação Mecânica
10.
Lancet ; 396(10256): 959-967, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-32896292

RESUMO

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus , Brasil/epidemiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Terapia Respiratória , SARS-CoV-2 , Padrão de Cuidado , Resultado do Tratamento
11.
Am Heart J ; 238: 1-11, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33891907

RESUMO

BACKGROUND: Observational studies have suggested a higher risk of thrombotic events in patients with coronavirus disease 2019 (COVID-19). Moreover, elevated D-dimer levels have been identified as an important prognostic marker in COVID-19 directly associated with disease severity and progression. Prophylactic anticoagulation for hospitalized COVID-19 patients might not be enough to prevent thrombotic events; therefore, therapeutic anticoagulation regimens deserve clinical investigation. DESIGN: ACTION is an academic-led, pragmatic, multicenter, open-label, randomized, phase IV clinical trial that aims to enroll around 600 patients at 40 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with symptoms up to 14 days and elevated D-dimer levels will be randomized to a strategy of full-dose anticoagulation for 30 days with rivaroxaban 20 mg once daily (or full-dose heparin if oral administration is not feasible) vs standard of care with any approved venous thromboembolism prophylaxis regimen during hospitalization. A confirmation of COVID-19 was mandatory for study entry, based on specific tests used in clinical practice (RT-PCR, antigen test, IgM test) collected before randomization, regardless of in the outpatient setting or not. Randomization will be stratified by clinical stability at presentation. The primary outcome is a hierarchical analysis of mortality, length of hospital stay, or duration of oxygen therapy at the end of 30 days. Secondary outcomes include the World Health Organization's 8-point ordinal scale at 30 days and the following efficacy outcomes: incidence of venous thromboembolism , acute myocardial infarction, stroke, systemic embolism, major adverse limb events, duration of oxygen therapy, disease progression, and biomarkers. The primary safety outcomes are major or clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria. SUMMARY: The ACTION trial will evaluate whether in-hospital therapeutic anticoagulation with rivaroxaban for stable patients, or enoxaparin for unstable patients, followed by rivaroxaban through 30 days compared with standard prophylactic anticoagulation improves clinical outcomes in hospitalized patients with COVID-19 and elevated D-dimer levels.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/complicações , Enoxaparina/uso terapêutico , Rivaroxabana/uso terapêutico , Trombose/prevenção & controle , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Brasil , COVID-19/sangue , COVID-19/mortalidade , Esquema de Medicação , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Oxigenoterapia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Trombose/etiologia , Fatores de Tempo
12.
Am Heart J ; 231: 128-136, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045224

RESUMO

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.


Assuntos
Fibrilação Atrial/complicações , Flutter Atrial/complicações , Bioprótese , Inibidores do Fator Xa/uso terapêutico , Próteses Valvulares Cardíacas , Valva Mitral , Rivaroxabana/uso terapêutico , Trombose/prevenção & controle , Administração Oral , Aspirina/administração & dosagem , Bioprótese/efeitos adversos , Brasil , Causas de Morte , Creatinina/metabolismo , Embolia , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Próteses Valvulares Cardíacas/efeitos adversos , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Ataque Isquêmico Transitório , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Tamanho da Amostra , Acidente Vascular Cerebral , Procedimentos Cirúrgicos Operatórios , Trombose/etiologia , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Varfarina/uso terapêutico
13.
Int J Obes (Lond) ; 45(4): 914-917, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33589771

RESUMO

BACKGROUND: Most of the evidence on bariatric surgery on obstructive sleep apnea (OSA) is based on observational studies and/or short-term follow-up in patients with obesity grade 3. SUBJECTS/METHODS: This randomized study compared the effects of roux-en-Y gastric bypass (RYGB) or usual care (UC) on OSA severity in patients with obesity grade 1-2. Mild, moderate, and severe OSA was defined by the apnea-hypopnoea index (AHI): 5-14.9; 15-29.9, and ≥30 events/h, respectively. OSA remission was defined by converting any form of OSA into normal AHI (<5 events/h). RESULTS: After 3-year of follow-up, the body-mass index increased in the UC while decreased in the RYGB group: +1.7 (-1.9; 2.7) versus -10.6 (-12.7; -9.2) kg/m2, respectively. The AHI increased by 5 (-4.2; 12.7) in the UC group while reduced in the RYGB group to -13.2 (-22.7; -7) events/h. UC significantly increase the frequency of moderate OSA (from 15.4 to 46.2%). In contrast, RYGB had a huge impact on reaching no OSA status (from 4.2 to 70.8%) in parallel to a decrease of moderate (from 41.7 to 8.3%) and severe OSA (from 20.8 to 0%). CONCLUSIONS: RYGB is an attractive strategy for mid-term OSA remission or decrease moderate-to-severe forms of OSA in patients with obesity grade 1-2.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida/cirurgia , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Índice de Massa Corporal , Brasil , Feminino , Derivação Gástrica , Humanos , Masculino , Pessoa de Meia-Idade
14.
Am J Respir Crit Care Med ; 201(4): 423-429, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31574228

RESUMO

Rationale: A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared with lactate-guided resuscitation strategy in patients with septic shock, but the difference in the primary outcome, 28-day mortality, did not reach the proposed statistical significance threshold (P = 0.06). We tested different analytic methods to aid in the interpretation of these results.Objectives: To reassess the results of the ANDROMEDA-SHOCK trial using both Bayesian and frequentist frameworks.Methods: All patients recruited in ANDROMEDA-SHOCK were included. Both a post hoc Bayesian analysis and a mixed logistic regression analysis were performed. The Bayesian analysis included four different priors (optimistic, neutral, null, and pessimistic) for mortality endpoints. The probability of having a Sequential Organ Failure Assessment in the lowest quartile at 72 hours was assessed using Bayesian networks.Measurements and Main Results: In the Bayesian analysis, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28 days was above 90% for all priors; the probability of benefit at 90 days was above 90% for all but the pessimistic prior. Using an optimistic prior, posterior median odds ratios were 0.61 (95% credible interval, 0.41-0.90) and 0.68 (95% credible interval, 0.47-1.01) for 28-day and 90-day mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were 0.61 (95% confidence interval [CI], 0.38-0.92) and 0.70 (95% CI, 0.45-1.08), respectively. The odds that that patients in the peripheral perfusion-targeted resuscitation arm had Sequential Organ Failure Assessment scores in the lower quartile at 72 hours was 1.55 (95% CI, 1.02-2.37).Conclusions: Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared with a lactate-targeted resuscitation strategy.


Assuntos
Hidratação/métodos , Hidratação/estatística & dados numéricos , Ácido Láctico/sangue , Ressuscitação/métodos , Ressuscitação/estatística & dados numéricos , Choque Séptico/mortalidade , Choque Séptico/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Índice de Perfusão
15.
Am J Respir Crit Care Med ; 201(7): 789-798, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31910037

RESUMO

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).


Assuntos
Escores de Disfunção Orgânica , Sepse/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo
16.
Ann Intern Med ; 173(9): 685-693, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-32805133

RESUMO

BACKGROUND: Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain. OBJECTIVE: To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone. DESIGN: Randomized clinical trial. (ClinicalTrials.gov: NCT01784848). SETTING: Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil. PARTICIPANTS: Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m2 were randomly assigned (1:1 ratio). INTERVENTION: RYGB plus MT or MT alone. MEASUREMENTS: The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg). RESULTS: Among 100 patients (76% female; mean BMI, 36.9 kg/m2 [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03]; P < 0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (P < 0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B12 and 2 patients required reoperation. LIMITATION: Single-center, nonblinded trial. CONCLUSION: RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity. PRIMARY FUNDING SOURCE: Ethicon, represented in Brazil by Johnson & Johnson do Brasil.


Assuntos
Anti-Hipertensivos/uso terapêutico , Cirurgia Bariátrica , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Obesidade/complicações , Obesidade/cirurgia , Adolescente , Adulto , Idoso , Anemia/etiologia , Cirurgia Bariátrica/efeitos adversos , Pressão Sanguínea , Índice de Massa Corporal , Aconselhamento , Feminino , Derivação Gástrica , Humanos , Hiperparatireoidismo/etiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Complicações Pós-Operatórias , Indução de Remissão , Deficiência de Vitamina B 12/etiologia , Redução de Peso , Adulto Jovem
17.
JAMA ; 326(21): 2161-2171, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34874419

RESUMO

IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.


Assuntos
COVID-19/complicações , Intubação Intratraqueal/estatística & dados numéricos , Oxigenoterapia/métodos , Oxigênio/uso terapêutico , Insuficiência Respiratória/terapia , Idoso , Idoso de 80 Anos ou mais , COVID-19/terapia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/instrumentação , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , SARS-CoV-2 , Fatores de Tempo , Resultado do Tratamento
18.
JAMA ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34375394

RESUMO

IMPORTANCE: Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. OBJECTIVE: To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). INTERVENTIONS: Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day survival. RESULTS: Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed; P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05]; P = .47). There were no unexpected treatment-related severe adverse events in either group. CONCLUSION AND RELEVANCE: Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02875873.

19.
JAMA ; 326(9): 830-838, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34547081

RESUMO

Importance: Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective: To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants: Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions: Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures: The primary end point was 90-day survival. Results: Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11; P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance: Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02875873.


Assuntos
Estado Terminal/mortalidade , Estado Terminal/terapia , Hidratação/métodos , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
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