Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Gravidade do déficit neurológico e incidência de infecções hospitalares em pacientes idosos com acidente vascular cerebral agudo

Aims: To evaluate the association between severity of neurological deficit/degree of functional disability and incidence of nosocomial infections, length of hospital stay, and mortality, in elderly patients with acute stroke.Methods: A prospective cohort study evaluated elderly patients with acute stroke, hospitalized at the Hospital of the Marilia Medical School, in Marilia, SP, Brazil. Inclusion criteria were patients aged 60 years or more and diagnosed with acute stroke. Patients were stratified according to the severity of the stroke by the National Institutes of Health Stroke Scale and the degree of dependence by the modified Rankin scale. All patients were followed from the time of admission to discharge or death.Results: We studied 113 patients with a mean age of 70.8 years, 63 (55.7%) men. The main underlying diseases were hypertension (77.9%) and type 2 diabetes mellitus (30.1%). Seventy-eight (69%) patients were affected for the first time and 86 (76.1%) had ischemic stroke. Nosocomial infection occurred in 24 patients (21.2%) and pneumonia was the most frequent (13.5%). The average length of hospital stay among patients with nosocomial infection was higher when compared to those without nosocomial infection (16.2±16.2 days and 33.2±22.9 days, p<0.001). There was association between score 16-42 points on the National Institute of Health Stroke Scale and the occurrence of nosocomial infection (risk ratio 4.4; 95% confidence interval 1.8 to 11.0). In-hospital mortality was 15.9%, higher among patients considered severe at admission compared to those with moderate to mild severity by the National Institute of Health Stroke Scale (34.6% and 1.6% respectively, p<0.001) and also among those who developed nosocomial infection when compared to those without this complication (37.5% and 10.1% respectively, p=0.003).Conclusions: Nosocomial infections were major complications among elderly patients with acute stroke and were associated with severity of neurological deficit, higher degree of dependence, longer hospital stay and higher mortality rate.Objetivos: Avaliar a associação entre gravidade do déficit neurológico/grau de incapacidade funcional e incidência de infecções hospitalares, tempo de permanência hospitalar e mortalidade, em pacientes idosos com acidente vascular cerebral agudo.Métodos: Um estudo de coorte prospectivo avaliou pacientes idosos com diagnóstico de acidente vascular cerebral agudo, internados no Hospital de Clínicas da Faculdade de Medicina de Marília, em Marília, SP. Os critérios de inclusão foram idade igual ou superior a 60 anos e diagnóstico de acidente vascular cerebral agudo. Os pacientes foram agrupados de acordo com a gravidade do acidente vascular cerebral pela National Institute of Health Stroke Scale e o grau de dependência pela escala modificada de Rankin. Todos os pacientes foram acompanhados desde o momento da internação até a alta hospitalar ou óbito.Resultados: Foram estudados 113 pacientes com média de idade de 70,8 anos, sendo 63 (55,7%) homens. As principais doenças de base relacionadas foram hipertensão arterial (77,9%) e diabetes mellitus tipo 2 (30,1%). Setenta e oito (69%) pacientes foram acometidos pela primeira vez e 86 (76,1%) apresentaram acidente vascular cerebral isquêmico. Tiveram infecção hospitalar 24 pacientes (21,2%) sendo pneumonia a mais frequente (13,5%). O tempo médio de permanência hospitalar dos pacientes com infecção hospitalar foi maior, quando comparados àqueles sem infecção hospitalar (16,2±16,2 dias e 33,2±22,9 dias, p<0,001). Observou-se relação entre escore de 16 a 42 pontos, na National Institute of Health Stroke Scale, e a ocorrência de infecção hospitalar (rico relativo 4,4; intervalo de confiança 95% 1,8 a 11,0). A mortalidade intra-hospitalar foi de 15,9%, sendo maior entre pacientes considerados muito graves à admissão, quando comparados com aqueles com gravidade moderada a leve pela National Institute of Health Stroke Scale, (34,6% e 1,6% respectivamente, p<0,001) e também entre aqueles que desenvolveram infecção hospitalar quando comparados aos que não apresentaram esta complicação (37,5% e 10,1% respectivamente, p=0,003).Conclusões: As infecções hospitalares foram complicações importantes entre os pacientes idosos com acidente vascular cerebral agudo e estiveram associadas com maior gravidade do déficit neurológico, maior grau de dependência, tempo de hospitalização mais prolongado e taxa de mortalidade mais alta

Gravidade do déficit neurológico e incidência de infecções hospitalares em pacientes idosos com acidente vascular cerebral agudo = Severity of neurological deficit and incidence of nosocomial infections in elderly patients with acute stroke

Objetivos: Avaliar a associação entre gravidade do déficit neurológico/grau de incapacidade funcional e incidência de infecções hospitalares, tempo de permanência hospitalar e mortalidade, em pacientes idosos com acidente vascular cerebral agudo. Métodos: Um estudo de coorte prospectivo avaliou pacientes idosos com diagnóstico de acidente vascular cerebral agudo, internados no Hospital de Clínicas da Faculdade de Medicina de Marília, em Marília, SP. Os critérios de inclusão foram idade igual ou superior a 60 anos e diagnóstico de acidente vascular cerebral agudo. Os pacientes foram agrupados de acordo com a gravidade do acidente vascular cerebral pela National Institute of Health Stroke Scale e o grau de dependência pela escala modificada de Rankin. Todos os pacientes foram acompanhados desde o momento da internação até a alta hospitalar ou óbito. Resultados: Foram estudados 113 pacientes com média de idade de 70,8 anos, sendo 63 (55,7%) homens. As principais doenças de base relacionadas foram hipertensão arterial (77,9%) e diabetes mellitus tipo 2 (30,1%). Setenta e oito (69%) pacientes foram acometidos pela primeira vez e 86 (76,1%) apresentaram acidente vascular cerebral isquêmico. Tiveram infecção hospitalar 24 pacientes (21,2%) sendo pneumonia a mais frequente (13,5%). O tempo médio de permanência hospitalar dos pacientes com infecção hospitalar foi maior, quando comparados àqueles sem infecção hospitalar (16,2±16,2 dias e 33,2±22,9 dias, p<0,001). Observou-se relação entre escore de 16 a 42 pontos, na National Institute of Health Stroke Scale, e a ocorrência de infecção hospitalar (rico relativo 4,4; intervalo de confiança 95% 1,8 a 11,0) A mortalidade intra-hospitalar foi de 15,9%, sendo maior entre pacientes considerados muito graves à admissão, quando comparados com aqueles com gravidade moderada a leve pela National Institute of Health Stroke Scale, (34,6% e 1,6% respectivamente, p<0,001) e também entre aqueles que desenvolveram infecção hospitalar quando comparados aos que não apresentaram esta complicação (37,5% e 10,1% respectivamente, p=0,003). Conclusões: As infecções hospitalares foram complicações importantes entre os pacientes idosos com acidente vascular cerebral agudo e estiveram associadas com maior gravidade do déficit neurológico, maior grau de dependência, tempo de hospitalização mais prolongado e taxa de mortalidade mais alt

Effect of short-term nutritional supplementation of green microalgae on some reproductive indicators of Anglo-Nubian crossbred goats

Background and Aim: Despite the wide spectrum of uses, one of the chief drawbacks to expanding microalgae as a food supplement in livestock is the lack of a regimen protocol with established dosage and time length of supplementation. Therefore, this study aimed to investigate the effect of short-term supplementation with increasing doses of microalgae on ovarian response in goats reared in northeast Brazil. Materials and Methods: Twenty-eight goats had their follicular waves synchronized using three injections of a prostaglandin analog at 7-day intervals. Goats were allocated to groups that received daily oral Chlorella supplementation for 7 days, respectively: 5 g, GMA5 group (n = 7), 10 g (GMA10; n = 7), and 20 g (GMA20; n = 7). The control group (GMA 0; n = 7) received a drench of water. Results: The groups showed a quadratic increase (p = 0.0156) in kidney fat thickness but there was a significant reduction in dry matter intake in the GMA20 group. The GMA20 group showed higher glucose levels and glutathione peroxidase (p 3 mm in the GMA10 group, which also showed a greater (p < 0.05) area of intraovarian blood perfusion and pulsatility index of the ovarian artery. Conclusion: We conclude that for 7 days of supplementation, the administration of 10 g of microalgae appears to be the most efficient dosage for stimulating the ovarian response in tropical goats

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt