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

Aleitamento materno exclusivo e anemia ferropriva nos seis primeiros meses de vida.

Objective The objective was to determine the prevalence of iron deficiency and iron deficiency anemia among exclusively breastfed infants from one to six months of life and to identify associated risk factors. Methods This is a cohort study of the hemoglobin and serum ferritin levels of 102 healthy full-term infants, weighing more than 2500 grams (5.5 pounds) at birth, evaluated for growth development and supported to promote exclusive breastfeeding. Hemoglobin and ferritin levels were measured in the first, fourth, and sixth months of life. The hemoglobin and ferritin levels of the mothers were also measured in the first month postpartum. Results At four months, 5.7% presented iron deficiency and 3.4% had iron deficiency anemia. At six months, the percentage of children with iron deficiency increased more than four times, reaching 26.1%, while iron deficiency anemia was present in 23.9% of the infants studied. Iron deficiency at six months of age was significantly correlated to growth velocity. Conclusion According to the results of this study, exclusive breastfeeding protects infants from iron deficiency and iron deficiency anemia for the first four months of life. After this age, in accordance with the literature, the findings of this study demonstrated an increase in anemia and iron deficiency rates, adding to evidence that supports the monitoring of iron levels in exclusively breastfed children presenting higher weight gains beginning at four months of age.Objetivo Determinar a prevalência da deficiência de ferro e anemia ferropriva em crianças, de um aos seis meses de vida, alimentadas exclusivamente ao seio materno e identificar os fatores de risco associados. Métodos Estudo de coorte dos valores de hemoglobina e ferritina sérica de 102 lactentes a termo, saudáveis, nascidos com peso maior que 2500 g, acompanhados quanto ao crescimento e desenvolvimento e com apoio à promoção do aleitamento materno exclusivo. Hemoglobina e ferritina sérica foram dosadas no primeiro, quarto e sexto mês de vida. Hemoglobina e ferritina sérica também foram dosadas nas mães no primeiro mês pós-parto. Resultados Aos quatro meses, 5,7% dos lactentes apresentaram deficiência de ferro e 3,4%, anemia ferropriva. Aos seis meses, o percentual de crianças com deficiência de ferro aumentou mais de quatro vezes, atingindo a proporção de 26,1%, enquanto a anemia ferropriva esteve presente em 23,9% dos lactentes da amostra. A deficiência de ferro aos seis meses foi associada significativamente com maior ganho ponderal. Conclusão Neste estudo, o aleitamento materno exclusivo protegeu as crianças da deficiência de ferro e da anemia ferropriva nos primeiros quatro meses de vida. Após essa idade, concordando com dados da literatura, esse estudou mostrou aumento na taxa de anemia e da deficiência de ferro, o que fornece mais uma evidência para apoiar a vigilância do estado do ferro, a partir dos quatro meses, para crianças em aleitamento materno exclusivo e que apresentem ganho de peso acima da média.State University of Pará Department of Integral Health ProfessorUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Department of PediatricsUNIFESP, EPM, Department of PediatricsSciEL

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

Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study

Background Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. Methods PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [VT] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Findings Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27\u201333), representing 0\ub714 cases per ICU bed over a 1-week period. VT was similar for patients at risk and not at risk of ARDS (median 7\ub76 mL/kg PBW [IQR 6\ub77\u20139\ub71] vs 7\ub79 mL/kg PBW [6\ub78\u20139\ub71]; p=0\ub7346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6\ub70 cm H2O [IQR 5\ub70\u20138\ub70] vs 5\ub70 cm H2O [5\ub70\u20137\ub70]; p&lt;0\ub70001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556 [3%]; p=0\ub7004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%]; p&lt;0\ub70001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p&lt;0\ub70001), and 90-day mortality (109/653 [17%] vs 88/282 [31%]; p&lt;0\ub70001). VT did not differ between patients who did and did not develop ARDS (p=0\ub7471 for those at risk of ARDS; p=0\ub7323 for those not at risk). Interpretation Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS

Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study

Background Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. Methods PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [VT] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Findings Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27–33), representing 0·14 cases per ICU bed over a 1-week period. VT was similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW [IQR 6·7–9·1] vs 7·9 mL/kg PBW [6·8–9·1]; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H2O [IQR 5·0–8·0] vs 5·0 cm H2O [5·0–7·0]; p&lt;0·0001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556 [3%]; p=0·004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%]; p&lt;0·0001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p&lt;0·0001), and 90-day mortality (109/653 [17%] vs 88/282 [31%]; p&lt;0·0001). VT did not differ between patients who did and did not develop ARDS (p=0·471 for those at risk of ARDS; p=0·323 for those not at risk). Interpretation Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population