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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.

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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.

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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 0·3­0·7 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 0·59­1·22], 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 1·61­8·27], 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.

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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.

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The aims of this paper were to evaluate the nutritional status of children orphaned by aids or homicides in the city of São Paulo and to estimate the association of nutritional indexes with orphanhood-related variables. The study was a household survey carried out between 2006 and 2007. We sampled 484 children representative of São Paulo, 5-14 years old who lost either or both of their parents from aids or homicides between 2000 and 2004. We selected body-mass-index-for-age (BMI) and height-for-age (height) as outcomes for analysis. Multiple linear regression in the light of a conceptual hierarchical approach was used for estimating BMI-for-age and height-for-age associated factors. Children from aids and homicides groups differed in terms of orphanhood-related variables and age. Economic, household, health and nutritional conditions were similar between groups. Underweight accounted for 1.3% and 2.1% of children under the age of 10 and adolescents, respectively. Stunting accounted for 0.7% and 4.0% of children and adolescents, respectively. Overweight accounted for 19% and 20% of children and adolescents, respectively. BMI and height were unaffected by orphanhood-related variables after adjusting for selected classical determinants of nutritional status in the hierarchical model. Economic status was the main determinant of the nutritional profile. Nutritional status of children orphaned by aids or homicides in São Paulo was similar and mainly influenced by economic status. The nutritional profile, characterized by being overweight, suggests that these orphans have not shown additional risks due to those orphanhood-related variables.

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O artigo tem como objetivos avaliar o estado nutricional de órfãos por aids ou homicídios residentes em São Paulo e estimar a associação de índices nutricionais com variáveis relacionadas à orfandade. Trata-se de estudo transversal de base domiciliar que utilizou amostra representativa de 484 indivíduos de 5 a 14 anos que perderam um ou ambos os pais durante os anos de 2000 e 2004 devido à aids ou a homicídio no município de São Paulo. A avaliação nutricional foi feita com o índice de massa corporal-para-idade (IMC) e da altura-para-idade (altura). A associação entre os índices nutricionais e as variáveis relacionadas à orfandade foi estimada em análise hierárquica, com uso de modelo de regressão linear múltiplo. Órfãos por aids ou homicídios diferiram quanto às características da orfandade e à idade média. As condições econômicas, domiciliares, o estado de saúde e o estado nutricional foram semelhantes entre os grupos. O déficit de IMC ocorreu em 1,3% das crianças abaixo de 10 anos e em 2,1% dos adolescentes. O déficit de altura ocorreu em 0,7% das crianças e em 4,0% dos adolescentes. O excesso de peso ocorreu em 19% e 20% das crianças e adolescentes, respectivamente. A análise hierárquica indicou ausência de efeito das variáveis relacionadas à orfandade sobre o IMC ou a altura; o principal determinante do estado nutricional foi de natureza econômica. Os órfãos por aids ou homicídio de São Paulo apresentaram estado nutricional semelhante e majoritariamente influenciado pela situação econômica. O perfil nutricional identificado no grupo, caracterizado pelo excesso de peso, sugere que os órfãos de São Paulo não apresentam riscos adicionais decorrentes da orfandade.

The aims of this paper were to evaluate the nutritional status of children orphaned by aids or homicides in the city of São Paulo and to estimate the association of nutritional indexes with orphanhood-related variables. The study was a household survey carried out between 2006 and 2007. We sampled 484 children representative of São Paulo, 5-14 years old who lost either or both of their parents from aids or homicides between 2000 and 2004. We selected body-mass-index-for-age (BMI) and height-for-age (height) as outcomes for analysis. Multiple linear regression in the light of a conceptual hierarchical approach was used for estimating BMI-for-age and height-for-age associated factors. Children from aids and homicides groups differed in terms of orphanhood-related variables and age. Economic, household, health and nutritional conditions were similar between groups. Underweight accounted for 1.3% and 2.1% of children under the age of 10 and adolescents, respectively. Stunting accounted for 0.7% and 4.0% of children and adolescents, respectively. Overweight accounted for 19% and 20% of children and adolescents, respectively. BMI and height were unaffected by orphanhood-related variables after adjusting for selected classical determinants of nutritional status in the hierarchical model. Economic status was the main determinant of the nutritional profile. Nutritional status of children orphaned by aids or homicides in São Paulo was similar and mainly influenced by economic status. The nutritional profile, characterized by being overweight, suggests that these orphans have not shown additional risks due to those orphanhood-related variables.

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BACKGROUNDS & AIMS: The boundaries between the categories of body composition provided by vectorial analysis of bioimpedance are not well defined. In this paper, fuzzy sets theory was used for modeling such uncertainty. METHODS: An Italian database with 179 cases 18-70 years was divided randomly into developing (n = 20) and testing samples (n = 159). From the 159 registries of the testing sample, 99 contributed with unequivocal diagnosis. Resistance/height and reactance/height were the input variables in the model. Output variables were the seven categories of body composition of vectorial analysis. For each case the linguistic model estimated the membership degree of each impedance category. To compare such results to the previously established diagnoses Kappa statistics was used. This demanded singling out one among the output set of seven categories of membership degrees. This procedure (defuzzification rule) established that the category with the highest membership degree should be the most likely category for the case. RESULTS: The fuzzy model showed a good fit to the development sample. Excellent agreement was achieved between the defuzzified impedance diagnoses and the clinical diagnoses in the testing sample (Kappa = 0.85, p < 0.001). CONCLUSIONS: fuzzy linguistic model was found in good agreement with clinical diagnoses. If the whole model output is considered, information on to which extent each BIVA category is present does better advise clinical practice with an enlarged nosological framework and diverse therapeutic strategies.

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OBJETIVO: Estimar valores de referência e função de hierarquia de docentes em Saúde Coletiva do Brasil por meio de análise da distribuição do índice h. MÉTODOS: A partir do portal da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, 934 docentes foram identificados em 2008, dos quais 819 foram analisados. O índice h de cada docente foi obtido na Web of Science mediante algoritmos de busca com controle para homonímias e alternativas de grafia de nome. Para cada região e para o Brasil como um todo ajustou-se função densidade de probabilidade exponencial aos parâmetros média e taxa de decréscimo por região. Foram identificadas medidas de posição e, com o complemento da função probabilidade acumulada, função de hierarquia entre autores conforme o índice h por região. RESULTADOS: Dos docentes, 29,8 por cento não tinham qualquer registro de citação (h = 0). A média de h para o País foi 3,1, com maior média na região Sul (4,7). A mediana de h para o País foi 2,1, também com maior mediana na Sul (3,2). Para uma padronização de população de autores em cem, os primeiros colocados para o País devem ter h = 16; na estratificação por região, a primeira posição demanda valores mais altos no Nordeste, Sudeste e Sul, sendo nesta última h = 24. CONCLUSÕES: Avaliados pelos índices h da Web of Science, a maioria dos autores em Saúde Coletiva não supera h = 5. Há diferenças entres as regiões, com melhor desempenho para a Sul e valores semelhantes entre Sudeste e Nordeste.

OBJECTIVE: To estimate reference values and the hierarchy function of professors engaged in Collective Health in Brazil by analyzing the distribution of the h-index. METHODS: From the Portal da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Portal of Coordination for the Improvement of Higher Education Personnel ), 934 authors were identified in 2008, of whom 819 were analyzed. The h-index of each professor was obtained through the Web of Science using search algorithms controlling for namesakes and alternative spellings of their names. For each Brazilian region and for the country as a whole, we adjusted an exponential probability density function to provide the population parameters and rate of decline by region. Ranking measures were identified using the complement of the cumulative probability function and the hierarchy function among authors according to the h-index by region. RESULTS: Among the professors analyzed, 29.8 percent had no citation record in Web of Science (h=0). The mean h for the country was 3.1, and the region with greatest mean was the southern region (h=4.7). The median h for the country was 3.1, and the greatest median was for the southern region (3.2). Standardizing populations to one hundred, the first rank in the country was h=16, but stratification by region shows that, within the northeastern, southeastern and southern regions, a greater value is necessary for achieving the first rank. In the southern region, the index needed to achieve the first rank was h=24. CONCLUSIONS: Most of the Brazilian Collective Health authors, if assessed on the basis of the Web of Science h-index, did not exceed h=5. Regional differences exist, with the southeastern and northeastern regions being similar and the southern region being outstanding.

OBJETIVO: Estimar valores de referencia y función de jerarquía de docentes en Salud Colectiva de Brasil por medio de análisis de distribución del índice h. MÉTODOS: A partir del Portal de la Coordinación de Perfeccionamiento de Personal de Nivel Superior 934 docentes fueron identificados en 2008, de los cuales 819 fueron analizados. El índice h de cada docente fue obtenido en la Web of Science mediante algoritmos de búsqueda con control para homonimias y alternativas de grafía de nombre. Para cada región y para Brasil como un todo se ajustó función de densidad de probabilidad exponencial a los parámetros promedio y tasa de decrecimiento por región. Fueron identificadas medidas de posición y, con el complemento de la función probabilidad acumulada, función de jerarquía entre autores conforme el índice h por región. RESULTADOS: De los docentes, 29,8 por ciento no tenían registro alguno de citación (h=0). El promedio de h para Brasil fue 3,1, con mayor promedio en la región Sur (4,7). La mediana de h para el país fue 2,1, también con mayor mediana en el Sur (3,2). Para una estandarización de población de autores en cien, los primeros colocados para el país deben tener h=16; en la estratificación por región, la primera posición demanda valores más altos en el Noreste, Sureste y Sur, siendo en ésta última h=24. CONCLUSIONES: Evaluados por los índices h de la Web of Science, la mayoría de los autores en Salud Colectiva no supera h=5. Hay diferencias entre las regiones, con mejor desempeño para el Sur y valores semejantes entre Sureste y Noreste.

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OBJECTIVE: To estimate reference values and the hierarchy function of professors engaged in Collective Health in Brazil by analyzing the distribution of the h-index. METHODS: From the Portal da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Portal of Coordination for the Improvement of Higher Education Personnel ), 934 authors were identified in 2008, of whom 819 were analyzed. The h-index of each professor was obtained through the Web of Science using search algorithms controlling for namesakes and alternative spellings of their names. For each Brazilian region and for the country as a whole, we adjusted an exponential probability density function to provide the population parameters and rate of decline by region. Ranking measures were identified using the complement of the cumulative probability function and the hierarchy function among authors according to the h-index by region. RESULTS: Among the professors analyzed, 29.8% had no citation record in Web of Science (h=0). The mean h for the country was 3.1, and the region with greatest mean was the southern region (h=4.7). The median h for the country was 3.1, and the greatest median was for the southern region (3.2). Standardizing populations to one hundred, the first rank in the country was h=16, but stratification by region shows that, within the northeastern, southeastern and southern regions, a greater value is necessary for achieving the first rank. In the southern region, the index needed to achieve the first rank was h=24. CONCLUSIONS: Most of the Brazilian Collective Health authors, if assessed on the basis of the Web of Science h-index, did not exceed h=5. Regional differences exist, with the southeastern and northeastern regions being similar and the southern region being outstanding.

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O objetivo deste artigo é estimar a sensibilidade e a especificidade de três critérios para triagem do excesso de peso em adolescentes pós-menarca. Trata-se de estudo transversal que utilizou dados de 78 adolescentes, entre 14 e 19 anos, estudantes da rede pública de ensino do município de Alfenas (MG). Utilizaram-se as medidas de peso, altura e pregas cutâneas triciptal, biciptal, subescapular e suprailíaca. Todas as medidas foram obtidas de forma padronizada.Calculou-se o Índice de Massa Corporal (IMC) e o excesso de peso foi classificado segundo IMC para idade com uso de critérios norte americano, internacional e brasileiro. A variável de referência gordura corporal foi expressa como o resíduo padronizado da prega cutânea triciptal. Estimaram-se sensibilidade, especificidade e áreas ROC de cada classificação. Os resultados mostraram baixa sensibilidade e elevada especificidade para os três critérios de classificação do excesso de peso e pior desempenho para classificação norte americana Must. Concluiu-se que o uso de critérios com dados nacionais parece minimizar erros no diagnóstico de excesso de peso em adolescentes do sexo feminino.

The aim of this study is to estimate the sensitivity and specificity of three criteria for overweight screening in post menarche adolescents. It is a cross-sectional study that used data from 78 adolescents aged 14-19 years old, students in public school in the municipality of Alfenas (MG). Weight, height and triciptal, biciptal, subescapular and suprailiac skinfold thickness measures were used. All measures were obtained by standardized procedures. Body Mass Index (BMI) was calculated and overweight were classified according to BMIto- age, using North-American, International and Brazilian criteria. The reference variable body fatness was expressed as the standardized residual of triciptal skin fold thickness. It was estimated the sensitivity, specificity and ROC curves for each classification.The results showed that all three criteria had low sensibility and high specificity and North- American classification showed the lowest performance. Criteria containing national data may minimize miss-classification in overweight screening in female adolescents.

El objetivo de este trabajo es estimar la sensibilidad y la especificidad de três criterios para la detección de adolescentes con sobrepeso en la post-menarquia. Se trata de un estudio de tipo transversal que utilizó datos de 78 adolescentes entre 14 y 19 años, estudiantes de la enseñanza pública del municipio de Alfenas (MG). Se utilizaron las medidas de peso, talla y el pliegue cutáneo del tríceps, bíceps, subescapular y suprailíaco. Todas lãs mediciones estuvieron de acuerdo a los patrones. Se calculó el Índice de Masa Corporal (IMC) y el sobrepeso se clasificó de acuerdo con el IMC para la edad mediante el uso de critérios Internacionales, de Brasil y de EE.UU. La variable de referencia de materia grasa corporalse expresó como residual estandarizado del pliegue del tríceps. Se estimó la sensibilidad, especificidad, y las áreas ROC para cada clasificación. Los resultados mostraron baja sensibilidad y especificidad alta para los tres criterios de clasificación del sobrepeso y la peor clasificación de desempeño fue la de los EE.UU, Must. Se concluyó que el uso de criterios con datos nacionales parece minimizar los errores en el diagnóstico de sobrepeso en las mujeres adolescentes.

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