; for the COALITION COVID-19 Brazil III Investigators IMPORTANCE Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. OBJECTIVE To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. INTERVENTIONS Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). MAIN OUTCOMES AND MEASURES The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. RESULTS A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, −1.16; 95% CI, −1.94 to −0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days.

OBJECTIVES: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV2 infection (Coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop Acute Respiratory Distress Syndrome (ARDS). Several clinical trials evaluated the role of corticosteroids in non-COVID-19 ARDS with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe ARDS due to confirmed or probable COVID-19. METHODS: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48h before randomization) moderate or severe ARDS, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (intervention group) or standard treatment without dexamethasone (control group). Patients in the intervention group will receive dexamethasone 20mg IV once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until Intensive Care Unit (ICU) discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment (SOFA) Score evaluation at 48h, 72h and 7 days and ICU-free days within 28. ETHICS AND DISSEMINATION: This trial was approved by the Brazilian National Committee of Ethics in Research (Comissão Nacional de Ética em Pesquisa - CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete.

Introduction. Class 3 obesity (BMI≥40 kg/m2) is a growing health problem worldwide associated with considerable comorbidity including Type 2 diabetes mellitus (T2DM). The multidisciplinary medical management of obesity can be difficult in T2DM due to potential weight gain from medications including sulphonylureas and insulin. However, newer weight-neutral/losing diabetes medications can aid additional weight loss. The aim of this study was to compare weight loss outcomes of patients with and without T2DM, and in patients with T2DM, to compare diabetes outcomes and change in medications at 6 months. Methods. All patients entering a multidisciplinary weight management metabolic program in a publicly funded hospital clinic in Sydney between March 2018 and March 2019, with BMI≥40 kg/m2 and aged ≥18 years were included. Data was collected from patient clinical and electronic notes at baseline and 6 months. Results. Of the 180 patients who entered the program, 53.3% had T2DM at baseline. There was no difference in percentage weight loss in those with or without T2DM (4.2±4.9% vs. 3.6±4.7%, p=0.35). Additionally, T2DM patients benefited from a 0.47% reduction in HbA1c (p<0.01) and a reduction in the number of medications from baseline to 6 months (1.8±1.0/patient vs. 1.0±1.2/patient, p<0.001). T2DM patients who started on weigh-neutral/losing medications in the program lost more weight than those started on weight-gaining medications (7.7±5.3% vs. 2.4±3.8%, p=0.015). Conclusions. Patients with class 3 obesity had significant weight loss at 6 months in this program. Patients with T2DM at baseline had comparable weight loss at 6 months, a significant improvement in glycaemic control, and a reduction in diabetes medication load. Additionally, patients with T2DM who were started on weight-neutral/losing medications lost significantly more weight than those started on weight-gaining medications, and these medications should be preferentially used in class 3 obesity and comorbid T2DM.

Objective The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV-2 infection (coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop acute respiratory distress syndrome. Several clinical trials evaluated the role of corticosteroids in non-COVID-19 acute respiratory distress syndrome with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe acute respiratory distress syndrome due to confirmed or probable COVID-19. Methods This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48 hours before randomization) moderate or severe acute respiratory distress syndrome, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (Intervention Group) or standard treatment without dexamethasone (Control Group). Patients in the intervention group will receive dexamethasone 20mg intravenous once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until intensive care unit discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment Score evaluation at 48 hours, 72 hours and 7 days and intensive care unit -free days within 28.

O objetivo deste estudo foi avaliar as correlações existentes entre o Nível de Atividade Física Habitual (NAFH) mensurado por acelerometria, a distância percorrida no Teste de Caminhada de Seis Minutos (DTC6) e o escore obtido por meio de um questionário de NAFH. Trinta e três adultos (23 mulheres; 64±7 anos) foram avaliados. Os participantes responderam ao Questionário Internacional de Atividade Física (IPAQ) e foram submetidos a dois Testes de Caminhada de Seis Minutos (TC6). A média do número de passos diários (NPM) de cinco dias foi analisada por um acelerômetro uniaxial. As correlações entre as variáveis estudadas foram avaliadas e dois modelos de regressão múltipla foram desenvolvidos para comparar a influência das variáveis estudadas no NPM. No primeiro modelo, foram considerados a DTC6 e o escore total do IPAQ como variáveis independentes. No segundo modelo, a DTC6 e variáveis demográficas e antropométricas foram incluídas (por exemplo, idade, estatura, peso e gênero). O NPM correlacionou-se significativamente (p<0,05) com a DTC6 (r=0,51) e com o escore total do IPAQ (r=0,47). Após análise de regressão, apenas a DTC6 foi selecionada como determinante de 26,5% da variabilidade total do NPM. Podemos concluir que o TC6 correlacionou-se apenas moderadamente com o NAFH. Entretanto, associado ao sexo, a DTC6 foi capaz de explicar 36,6% da variabilidade total do NPM.