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2.
BMJ Open ; 11(6): e042302, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: covidwho-1282095

RESUMO

INTRODUCTION: Daily multidisciplinary rounds (DMRs) consist of systematic patient-centred discussions aiming to establish joint therapeutic goals for the next 24 hours of intensive care unit (ICU) care. The aim of the present study protocol is to evaluate whether an intervention consisting of guided DMRs, supported by a remote specialist and audit/feedback on care performance will reduce ICU length of stay compared with a control group. METHODS AND ANALYSIS: A multicentre, controlled, cluster-randomised superiority trial including 30 ICUs in Brazil (15 intervention and 15 control), from August 2019 to June 2021. In a parallel assignment, ICUs are randomised to a complex-intervention composed by daily rounds carried out through Tele-ICU by a remote ICU physician; development of local quality indicators dashboards coupled with monthly meetings with local leadership; and dissemination of evidence-based clinical protocols versus usual care. Primary outcome is ICU length of stay. Secondary outcomes include classification of the unit according to the profiles defined by the standardised resource use and the standardised mortality rate, hospital mortality, incidence of healthcare-associated infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation or alert and calm, rate of patients under normoxaemia. All adult patients admitted after the beginning of the study in each participant ICU will be enrolled. Inclusion criteria (clusters): public Brazilian ICUs with a minimum of 8 ICU beds interested/committed to participating in the study. Exclusion criteria (clusters): units with fully established DMRs by an intensivist, specialised or step-down units. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board (IRB) of the coordinator centre, and by IRBs of each enrolled hospital/ICU. Statistical analysis protocol is being prepared for submission before the end of patient's enrolment. Results will be disseminated through conferences, peer-reviewed journals and to each participating unit. TRIAL REGISTRATION NUMBER: NCT03920501; Pre-results.


Assuntos
COVID-19 , Telescópios , Adulto , Brasil , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Lancet ; 397(10291): 2253-2263, 2021 06 12.
Artigo em Inglês | MEDLINE | ID: covidwho-1253771

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 , COVID-19/sangue , COVID-19/tratamento farmacológico , 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
4.
N Engl J Med ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: covidwho-1270703

RESUMO

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

5.
BMJ Open ; 11(6): e042302, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155070

RESUMO

INTRODUCTION: Daily multidisciplinary rounds (DMRs) consist of systematic patient-centred discussions aiming to establish joint therapeutic goals for the next 24 hours of intensive care unit (ICU) care. The aim of the present study protocol is to evaluate whether an intervention consisting of guided DMRs, supported by a remote specialist and audit/feedback on care performance will reduce ICU length of stay compared with a control group. METHODS AND ANALYSIS: A multicentre, controlled, cluster-randomised superiority trial including 30 ICUs in Brazil (15 intervention and 15 control), from August 2019 to June 2021. In a parallel assignment, ICUs are randomised to a complex-intervention composed by daily rounds carried out through Tele-ICU by a remote ICU physician; development of local quality indicators dashboards coupled with monthly meetings with local leadership; and dissemination of evidence-based clinical protocols versus usual care. Primary outcome is ICU length of stay. Secondary outcomes include classification of the unit according to the profiles defined by the standardised resource use and the standardised mortality rate, hospital mortality, incidence of healthcare-associated infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation or alert and calm, rate of patients under normoxaemia. All adult patients admitted after the beginning of the study in each participant ICU will be enrolled. Inclusion criteria (clusters): public Brazilian ICUs with a minimum of 8 ICU beds interested/committed to participating in the study. Exclusion criteria (clusters): units with fully established DMRs by an intensivist, specialised or step-down units. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board (IRB) of the coordinator centre, and by IRBs of each enrolled hospital/ICU. Statistical analysis protocol is being prepared for submission before the end of patient's enrolment. Results will be disseminated through conferences, peer-reviewed journals and to each participating unit. TRIAL REGISTRATION NUMBER: NCT03920501; Pre-results.


Assuntos
COVID-19 , Telescópios , Adulto , Brasil , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
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 , COVID-19/sangue , COVID-19/tratamento farmacológico , 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
7.
N Engl J Med ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133856

RESUMO

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

8.
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
9.
Am Heart J ; 238: 1-11, 2021 08.
Artigo em Inglês | MEDLINE | ID: covidwho-1193194

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
10.
Rev Bras Ter Intensiva ; 33(1): 31-37, 2021.
Artigo em Português, Inglês | MEDLINE | ID: mdl-33886851

RESUMO

INTRODUCTION: The long-term effects caused by COVID-19 are unknown. The present study aims to assess factors associated with health-related quality of life and long-term outcomes among survivors of hospitalization for COVID-19 in Brazil. METHODS: This is a multicenter prospective cohort study nested in five randomized clinical trials designed to assess the effects of specific COVID-19 treatments in over 50 centers in Brazil. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed-up for a period of 1 year by means of structured telephone interviews. The primary outcome is the 1-year utility score of health-related quality of life assessed by the EuroQol-5D3L. Secondary outcomes include all-cause mortality, major cardiovascular events, rehospitalizations, return to work or study, physical functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living, dyspnea assessed by the modified Medical Research Council dyspnea scale, need for long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-Revised, and self-rated health assessed by the EuroQol-5D3L Visual Analog Scale. Generalized estimated equations will be performed to test the association between five sets of variables (1- demographic characteristics, 2- premorbid state of health, 3- characteristics of acute illness, 4- specific COVID-19 treatments received, and 5- time-updated postdischarge variables) and outcomes. ETHICS AND DISSEMINATION: The study protocol was approved by the Research Ethics Committee of all participant institutions. The results will be disseminated through conferences and peer-reviewed journals.


Assuntos
COVID-19/complicações , Qualidade de Vida , Adulto , Brasil , COVID-19/mortalidade , Doenças Cardiovasculares/etiologia , Causas de Morte , Seguimentos , Humanos , Readmissão do Paciente , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Retorno ao Trabalho , Tamanho da Amostra , Sobreviventes , Telefone
13.
Int J Obes (Lond) ; 45(4): 914-917, 2021 Apr.
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.

15.
BMJ ; 372: n84, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: covidwho-1039870

RESUMO

OBJECTIVE: To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). DESIGN: Randomised, open label trial. SETTING: Nine hospitals in Brazil, 8 May to 17 July 2020. PARTICIPANTS: Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. INTERVENTIONS: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). MAIN OUTCOME MEASURE: The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. RESULTS: A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. CONCLUSIONS: In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403685.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/terapia , Estado Terminal , Feminino , Seguimentos , Hospitalização , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
16.
Am. heart j ; (231): 128-136, Jan. 2021. tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1145450

RESUMO

Background 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 , Rivaroxabana , Bioprótese , Valva Mitral , Anticoagulantes
17.
Circulation ; 143(12): 1215-1223, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33461308

RESUMO

BACKGROUND: In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. METHODS: In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial. RESULTS: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min-1·1.73 m-2, respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min-1·1.73 m-2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min-1·1.73 m-2: 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively. CONCLUSIONS: The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

18.
BMJ ; 372: n84, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472855

RESUMO

OBJECTIVE: To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). DESIGN: Randomised, open label trial. SETTING: Nine hospitals in Brazil, 8 May to 17 July 2020. PARTICIPANTS: Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. INTERVENTIONS: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). MAIN OUTCOME MEASURE: The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. RESULTS: A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. CONCLUSIONS: In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403685.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/terapia , Estado Terminal , Feminino , Seguimentos , Hospitalização , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
19.
Arq. bras. cardiol ; 116(1): 108-116, Jan. 2021. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1152964

RESUMO

Resumo Fundamento Na prática clínica, há evidências de falhas na prescrição de terapias baseadas em evidências para pacientes de alto risco cardiovascular. Entretanto, no Brasil, ainda são insuficientes os dados sobre a evolução ao longo de 1 ano desses pacientes. Objetivos Descrição no acompanhamento de 12 meses da utilização de terapias baseadas em evidência e da ocorrência de desfechos cardiovasculares maiores e seus principais preditores em um registro brasileiro multicêntrico de pacientes de alto risco cardiovascular. Métodos Estudo observacional prospectivo que documentou a prática clínica ambulatorial de indivíduos acima de 45 anos e de alto risco cardiovascular tanto em prevenção primária como secundária. Os pacientes foram seguidos por 1 ano e avaliou-se a prescrição de terapias baseadas em evidência e a ocorrência de eventos cardiovasculares maiores (infarto agudo do miocárdio [IAM], acidente vascular cerebral [AVC], parada cardíaca e mortalidade por causa cardiovascular). Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados De julho de 2010 até agosto de 2014, 5.076 indivíduos foram incluídos em 48 centros, sendo 91% dos 4.975 pacientes elegíveis acompanhados em centros de cardiologia e 68,6% em prevenção secundária. Em 1 ano, o uso concomitante de antiplaquetários, estatinas e inibidores da enzima conversora de angiotensina (IECA) reduziu de 28,3% para 24,2% (valor de p < 0,001). A taxa de eventos cardiovasculares maiores foi de 5,46%, e os preditores identificados foram: idade, pacientes em prevenção secundária e nefropatia diabética. Conclusões Neste grande registro nacional de pacientes de alto risco cardiovascular, foram identificados preditores de risco semelhantes aos registros internacionais, porém a adesão da prescrição médica a terapias baseadas em evidência esteve abaixo dos dados da literatura internacional e apresentou piora significativa em 1 ano. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)


Abstract Background In clinical practice, there is evidence of failure to prescribe evidence-based therapies for patients at high cardiovascular risk. However, in Brazil, data on 1-year outcomes of these patients remain insufficient. Objectives To describe the use of evidence-based therapies and the occurrence of major cardiovascular outcomes and their major predictors in a 12-month follow-up of a Brazilian multicenter registry of patients at high cardiovascular risk. Methods This prospective observational study documented the outpatient clinical practice of managing patients over 45 years of age and of high cardiovascular risk in both primary and secondary prevention. Patients were followed-up for 1 year, and the prescription of evidence-based therapies and the occurrence of major cardiovascular events (myocardial infarction, stroke, cardiac arrest, and cardiovascular death) were assessed. P-values < 0.05 were considered statistically significant. Results From July 2010 to August 2014, a total of 5076 individuals were enrolled in 48 centers, 91% of the 4975 eligible patients were followed-up in cardiology centers, and 68.6% were in secondary prevention. At 1 year, the concomitant use of antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors reduced from 28.3% to 24.2% (p < 0.001). Major cardiovascular event rate was 5.46%, and the identified predictors were age, patients in secondary prevention, and diabetic nephropathy. Conclusions In this large national registry of patients at high cardiovascular risk, risk predictors similar to those of international registries were identified, but medical prescription adherence to evidence-based therapies was inferior and significantly worsened at 1 year. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

20.
Acta Diabetol ; 58(2): 215-220, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33047257

RESUMO

AIMS: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. METHODS: In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. RESULTS: Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. CONCLUSIONS: Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. TRIAL REGISTRATION: Clinical trials registration number: NCT00971165.


Assuntos
Amilorida/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Clortalidona/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertensão/tratamento farmacológico , Losartan/administração & dosagem , Adulto , Idoso , Amilorida/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Brasil , Clortalidona/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/complicações , Hipertensão/patologia , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
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