Real-Life Data on Hydroxychloroquine or Chloroquine with or Without Azithromycin in COVID-19 Patients: A Retrospective Analysis in Brazil. / Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil.

BACKGROUND: Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. OBJECTIVES: To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. METHODS: A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. RESULTS: From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). CONCLUSION: COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.

FUNDAMENTO: Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. OBJETIVOS: Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. MÉTODOS: Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. RESULTADOS: Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). CONCLUSÃO: Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.

Temporal validation of the MMCD score to predict kidney replacement therapy and in-hospital mortality in COVID-19 patients.

BACKGROUND: Acute kidney injury has been described as a common complication in patients hospitalized with COVID-19, which may lead to the need for kidney replacement therapy (KRT) in its most severe forms. Our group developed and validated the MMCD score in Brazilian COVID-19 patients to predict KRT, which showed excellent performance using data from 2020. This study aimed to validate the MMCD score in a large cohort of patients hospitalized with COVID-19 in a different pandemic phase and assess its performance to predict in-hospital mortality. METHODS: This study is part of the "Brazilian COVID-19 Registry", a retrospective observational cohort of consecutive patients hospitalized for laboratory-confirmed COVID-19 in 25 Brazilian hospitals between March 2021 and August 2022. The primary outcome was KRT during hospitalization and the secondary was in-hospital mortality. We also searched literature for other prediction models for KRT, to assess the results in our database. Performance was assessed using area under the receiving operator characteristic curve (AUROC) and the Brier score. RESULTS: A total of 9422 patients were included, 53.8% were men, with a median age of 59 (IQR 48-70) years old. The incidence of KRT was 8.8% and in-hospital mortality was 18.1%. The MMCD score had excellent discrimination and overall performance to predict KRT (AUROC: 0.916 [95% CI 0.909-0.924]; Brier score = 0.057). Despite the excellent discrimination and overall performance (AUROC: 0.922 [95% CI 0.914-0.929]; Brier score = 0.100), the calibration was not satisfactory concerning in-hospital mortality. A random forest model was applied in the database, with inferior performance to predict KRT requirement (AUROC: 0.71 [95% CI 0.69-0.73]). CONCLUSION: The MMCD score is not appropriate for in-hospital mortality but demonstrates an excellent predictive ability to predict KRT in COVID-19 patients. The instrument is low cost, objective, fast and accurate, and can contribute to supporting clinical decisions in the efficient allocation of assistance resources in patients with COVID-19.

Potential and limitations of machine meta-learning (ensemble) methods for predicting COVID-19 mortality in a large inhospital Brazilian dataset.

The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48-71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.

Clinical characteristics and outcomes of hospital-manifested COVID-19 among Brazilians.

OBJECTIVES: To analyze the clinical characteristics and outcomes of admitted patients with the hospital- versus community-manifested COVID-19 and to evaluate the risk factors related to mortality in the first population. METHODS: This retrospective cohort included consecutive adult patients with COVID-19, hospitalized between March and September 2020. The demographic data, clinical characteristics, and outcomes were extracted from medical records. Patients with hospital-manifested COVID-19 (study group) and those with community-manifested COVID-19 (control group) were matched by the propensity score model. Logistic regression models were used to verify the risk factors for mortality in the study group. RESULTS: Among 7,710 hospitalized patients who had COVID-19, 7.2% developed symptoms while admitted for other reasons. Patients with hospital-manifested COVID-19 had a higher prevalence of cancer (19.2% vs 10.8%) and alcoholism (8.8% vs 2.8%) than patients with community-manifested COVID-19 and also had a higher rate of intensive care unit requirement (45.1% vs 35.2%), sepsis (23.8% vs 14.5%), and death (35.8% vs 22.5%) (P <0.05 for all). The factors independently associated with increased mortality in the study group were increasing age, male sex, number of comorbidities, and cancer. CONCLUSION: Hospital-manifested COVID-19 was associated with increased mortality. Increasing age, male sex, number of comorbidities, and cancer were independent predictors of mortality among those with hospital-manifested COVID-19 disease.

Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil / Real-Life Data on Hydroxychloroquine or Chloroquine with or Without Azithromycin in COVID-19 Patients: A Retrospective Analysis in Brazil

Resumo Fundamento Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. Objetivos Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. Métodos Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). Conclusão Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.

Abstract Background Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. Objectives To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. Methods A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. Results From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). Conclusion COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.

Frequency and burden of neurological manifestations upon hospital presentation in COVID-19 patients: Findings from a large Brazilian cohort.

BACKGROUND: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection and outcomes in the Brazilian population. METHODS: This study is part of the Brazilian COVID-19 Registry, a multicentric cohort, including data from 37 hospitals. For the present analysis, patients were grouped according to the presence of reported symptoms (i.e., headache; anosmia and ageusia; syncope and dizziness) vs. clinically-diagnosed neurological manifestations (clinically-defined neurological syndrome: neurological signs or diagnoses captured by clinical evaluation) and matched with patients without neurological manifestations by age, sex, number of comorbidities, hospital of admission, and whether or not patients had underlying neurological disease. RESULTS: From 6,635 hospitalized patients with COVID-19, 30.8% presented reported neurological manifestations, 10.3% were diagnosed with a neurological syndrome and 60.1% did not show any neurological manifestations. In patients with reported symptoms, the most common ones were headache (20.7%), ageusia (11.1%) and anosmia (8.0%). In patients with neurological syndromes, acute encephalopathy was the most common diagnosis (9.7%). In the matched analysis, patients with neurological syndromes presented more cases of septic shock (17.0 vs. 13.0%, p = 0.045), intensive care unit admission (45.3 vs. 38.9%, p = 0.023), and mortality (38.7 vs. 32.6%, p = 0.026; and 39.2 vs. 30.3%, p < 0.001) when compared to controls. CONCLUSION: COVID-19 in-hospital patients with clinically defined neurological syndromes presented a higher incidence of septic shock, ICU admission and death when compared to controls.

Hospital characteristics associated with COVID-19 mortality: data from the multicenter cohort Brazilian Registry.

The COVID-19 pandemic caused unprecedented pressure over health care systems worldwide. Hospital-level data that may influence the prognosis in COVID-19 patients still needs to be better investigated. Therefore, this study analyzed regional socioeconomic, hospital, and intensive care units (ICU) characteristics associated with in-hospital mortality in COVID-19 patients admitted to Brazilian institutions. This multicenter retrospective cohort study is part of the Brazilian COVID-19 Registry. We enrolled patients ≥ 18 years old with laboratory-confirmed COVID-19 admitted to the participating hospitals from March to September 2020. Patients' data were obtained through hospital records. Hospitals' data were collected through forms filled in loco and through open national databases. Generalized linear mixed models with logit link function were used for pooling mortality and to assess the association between hospital characteristics and mortality estimates. We built two models, one tested general hospital characteristics while the other tested ICU characteristics. All analyses were adjusted for the proportion of high-risk patients at admission. Thirty-one hospitals were included. The mean number of beds was 320.4 ± 186.6. These hospitals had eligible 6556 COVID-19 admissions during the study period. Estimated in-hospital mortality ranged from 9.0 to 48.0%. The first model included all 31 hospitals and showed that a private source of funding (ß = - 0.37; 95% CI - 0.71 to - 0.04; p = 0.029) and location in areas with a high gross domestic product (GDP) per capita (ß = - 0.40; 95% CI - 0.72 to - 0.08; p = 0.014) were independently associated with a lower mortality. The second model included 23 hospitals and showed that hospitals with an ICU work shift composed of more than 50% of intensivists (ß = - 0.59; 95% CI - 0.98 to - 0.20; p = 0.003) had lower mortality while hospitals with a higher proportion of less experienced medical professionals had higher mortality (ß = 0.40; 95% CI 0.11-0.68; p = 0.006). The impact of those association increased according to the proportion of high-risk patients at admission. In-hospital mortality varied significantly among Brazilian hospitals. Private-funded hospitals and those located in municipalities with a high GDP had a lower mortality. When analyzing ICU-specific characteristics, hospitals with more experienced ICU teams had a reduced mortality.

Predictors of venous thromboembolism in COVID-19 patients: results of the COVID-19 Brazilian Registry.

Previous studies that assessed risk factors for venous thromboembolism (VTE) in COVID-19 patients have shown inconsistent results. Our aim was to investigate VTE predictors by both logistic regression (LR) and machine learning (ML) approaches, due to their potential complementarity. This cohort study of a large Brazilian COVID-19 Registry included 4120 COVID-19 adult patients from 16 hospitals. Symptomatic VTE was confirmed by objective imaging. LR analysis, tree-based boosting, and bagging were used to investigate the association of variables upon hospital presentation with VTE. Among 4,120 patients (55.5% men, 39.3% critical patients), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95% CI 1.11-2.02); being an ex-smoker (OR 1.44, 95% CI 1.03-2.01); surgery ≤ 90 days (OR 2.20, 95% CI 1.14-4.23); axillary temperature (OR 1.41, 95% CI 1.22-1.63); D-dimer ≥ 4 times above the upper limit of reference value (OR 2.16, 95% CI 1.26-3.67), lactate (OR 1.10, 95% CI 1.02-1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01-1.18); and neutrophil count (OR 1.04, 95% CI 1.005-1.075) were independent predictors of VTE. Atrial fibrillation, peripheral oxygen saturation/inspired oxygen fraction (SF) ratio and prophylactic use of anticoagulants were protective. Temperature at admission, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. By using ML and LR analyses, we showed that D-dimer, axillary temperature, neutrophil count, CRP and lactate levels are risk factors for VTE in COVID-19 patients.

Tendência temporal das internações por condições sensíveis à atenção primária em idosos no Brasil / Temporal trend of hospitalization for ambulatory care sensitive conditions in the elderly in Brazil / Tendencia temporal de las hospitalizaciones por condiciones sensibles de la atención primaria en mayores de Brasil

Objetivo: Avaliar a tendência temporal das Internações por Condições Sensíveis à Atenção Primária (ICSAP), em idosos, segundo sua estrutura, magnitude e causas, no Brasil, entre 2000 e 2018. Métodos: Estudo ecológico realizado com base em dados do Sistema de Informação Hospitalar do Sistema Único de Saúde (SUS) e Sistema de Informação da Atenção Básica (SIAB), entre 2000 e 2018, referentes a indivíduos com 60 anos ou mais, sendo incluídas 20.695.407 internações. Calcularam-se os coeficientes brutos e específicos de hospitalizações segundo sexo, faixa etária e região e estimaram-se a cobertura da Estratégia de Saúde da Família e o número de consultas médicas na atenção primária. Para análise da série temporal utilizou-se o método de regressão linear simples, sendo testada a correlação pelo Coeficiente de Correlação de Pearson (p<0,05). Resultados: Observou-se tendência de redução nas taxas de ICSAP em idosos no Brasil, de 2000 a 2018, para ambos os sexos, todas as faixas etárias e regiões (p<0,001). As principais causas de ICSAP concentraram-se nas doenças do aparelho circulatório (14,42%); respiratório (11,52%); e endócrinas, metabólicas e nutricionais (4,42%). Ocorreu diminuição de 61,50% de internações por insuficiência cardíaca e um aumento de 27,29% nas internações por pneumonia. Constatou-se tendência de aumento da cobertura da Estratégia de Saúde da Família (ESF) e do número médio de consultas (p<0,001), em idosos, no Brasil, de 2000 a 2015. Houve correlação negativa entre internações e indicadores de acesso à atenção primária (p<0,001). Conclusão: Há tendência de redução nas taxas gerais de ICSAP em idosos no Brasil, em função de melhorias na cobertura da atenção primária.

Objective: To evaluate the temporal trend of hospitalizations for Ambulatory Care Sensitive Conditions (ACSC) in the elderly, according to their structure, magnitude, and causes, in Brazil, between 2000 and 2018. Methods: An ecological study based on data from the Hospital Information System of the Unified Health System (Sistema Único de Saúde - SUS) and the Primary Care Information System (Sistema de Informações sobr à Atenção Básica - SIAB), between 2000 and 2018, referring to individualsaged 60 years or older, including 20,695,407 hospitalizations. Gross and specific coefficients of hospitalizations were calculated according to sex, age group, and region, and the coverage of the Family Health Strategy (Estratégia Saúde da Família ­ ESF), and the number of medical consultations in primary care were estimated. For the time series analysis, the simple linear regression method was used, and the correlation was tested by Pearson's Correlation Coefficient (p<0.05). Results: There was a trend of reduction in the rates of hospitalizations for ACSC in the elderly in Brazil, from 2000 to 2018, for both sexes, all age groups, and regions (p<0.001). The main causes of ACSC were concentrated in diseases of the circulatory system (14.42%), respiratory (11.52%), and endocrine, metabolic and nutritional (4.42%). There was a 61.50% decrease in hospitalizations for heart failure and a 27.29% increase in hospitalizations for pneumonia. There was a tendency to increase the coverage of the ESF and the average number of consultations (p<0.001) in the elderly in Brazil from 2000 to 2015. There was a negative correlation between hospitalizations and indicators of access to primary care (p<0.001). Conclusion: There is a trend of a reduction in the general rates of hospitalizations for ACSC in the elderly in Brazil due to improvements in primary care coverage.

Objetivo: Evaluar la tendencia temporal de las Hospitalizaciones por Condiciones Sensible de la Atención Primaria (HCSAP), de mayores, según la estructura, la magnitud y sus causas, en Brasil, entre 2000 y 2018. Métodos: Estudio ecológico realizado en la base de datos del Sistema de Información Hospitalaria del Sistema Único de Salud (SUS) y del Sistema de Información de la Atención Básica (SIAB), entre 2000 y 2018, referentes a los individuos de 60 años o más, con la inclusión de 20.695.407 hospitalizaciones. Se ha calculado los coeficientes brutos y específicos de las hospitalizaciones según el sexo, la franja de edad y la región y se ha estimado la cobertura de la Estrategia Salud de la Familia y el número de citas médicas de la atención primaria. Para el análisis de la serie temporal se ha utilizado el método de regresión linear simple y se ha testada la correlación por el Coeficiente de Correlación de Pearson (p<0,05). Resultados: Se observó la tendencia para la reducción de las tasas de HCSAP de mayores en Brasil entre 2000 y 2018, para ambos sexos, todas las franjas de edad y regiones (p<0,001). Las principales causas de HCSAP se han concentrado en las enfermedades del aparato circulatorio (14,42%); del respiratorio (11,52%); y las endocrinas, las metabólicas y las nutricionales (4,42%). Hubo una disminución del 61,50% de ingresos por insuficiencia cardiaca y el aumento del 27,29% de los ingresos por neumonía. Se ha constatado la tendencia de aumento de la cobertura de la Estrategia Salud de la Familia (ESF) y del número medio de citas (p<0,001) de mayores en Brasil entre 2000 y 2015. Hubo correlación negativa entre los ingresos y los indicadores de acceso a la atención primaria (p<0,001). Conclusión: Hay una tendencia para la reducción de las tasas generales de HCSAP de mayores en Brasil debido las mejorías de la cobertura de la atención primaria.

ABC2-SPH risk score for in-hospital mortality in COVID-19 patients: development, external validation and comparison with other available scores.

OBJECTIVES: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. METHODS: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients. RESULTS: Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). CONCLUSIONS: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.

The Economic Impact of COVID-19 Treatment at a Hospital-level: Investment and Financial Registers of Brazilian Hospitals.

Background: The economic impact associated with the treatment strategies of coronavirus disease-2019 (COVID-19) patients by hospitals and health-care systems in Brazil is unknown and difficult to estimate. This research describes the investments made to absorb the demand for treatment and the changes in occupation rates and billing in Brazilian hospitals. Methods: This research covers the initial findings of "COVID-19 hospital costs and the proposition of a bundled reimbursement strategy for the health-care system," which includes 10 hospitals. The chief financial officer, the chief medical officer, and hospital executives of each participating hospital provided information regarding investments attributed to COVID-19 patient treatment. The analysis included variations in occupation rates and billing from 2019 to 2020 observed in each institution, and the investments for medical equipment, individual protection materials and building construction per patient treated. Results: The majority of hospitals registered a decrease in hospitalization rates and revenue from 2019 to 2020. For intensive care units (ICUs), the mean occupancy rate ranged from 88% to 83%, and for wards, it ranged from 85% to 73%. Monthly average revenue decreased by 10%. The mean hospital investment per COVID-19 inpatient was I$6800 (standard deviation 7664), with the purchase of ventilators as the most common investment. For this item, the mean, highest and lowest acquisition cost per ventilator were, respectively, I$31 468, I$48 881 and I$17 777. Conclusion: There was significant variability in acquisition costs and investments by institution for responding to the COVID-19 pandemic. These findings highlight the importance of continuing microeconomic studies for a comprehensive assessment of hospital costs. Only with more detailed analyses, will it be possible to define and drive sustainable strategies to manage and reimburse COVID-19 treatment in health-care systems.

Risco de Fibrilação Atrial após Ablação de Flutter Dependente de Istmo Cavo-Tricuspídeo: Vale a Pena Fazer a Ablação da FA Simultaneamente? / Risk of Atrial Fibrillation after Ablation of Cavotricuspid Isthmus-Dependent Atrial Flutter: Is Combined Ablation of Atrial Fibrillation Worthwhile?

Resumo Fundamento A ablação da fibrilação atrial (FA) e do flutter atrial dependente de istmo cavo-tricuspídeo (FLA-ICT) pode ser realizada simultaneamente quando as duas arritmias tenham sido registradas antes do procedimento. Entretanto, a melhor abordagem não é clara quando pacientes com FLA-ICT são encaminhados para ablação sem o registro prévio de FA. Objetivos Avaliar a prevalência e identificar os preditores de ocorrência do primeiro episódio de FA após ablação de FLA-ICT em pacientes sem o registro prévio de FA. Métodos Coorte retrospectiva de pacientes submetidos exclusivamente a ablação por cateter para FLA-ICT, sem registro prévio de FA. As características clínicas foram comparadas entre os grupos em que houve ocorrência de FA pós-ablação de FLA-ICT vs. sem ocorrência de FA. O nível de significância estatística adotado foi de 5%. Na análise de preditores, o desfecho primário avaliado foi ocorrência de FA após ablação de FLA-ICT. Resultados De um total de 227 pacientes submetidos a ablação de FLA-ICT (110 com registro de FA e 33 sem seguimento adequado), 84 pacientes foram incluídos, dos quais 45 (53,6%) apresentaram FA pós-ablação. Não houve variáveis preditoras de ocorrência de FA. Os escores HATCH e CHA2DS2-VASC foram semelhantes nos dois grupos. As taxas de recorrência de FLA-ICT e complicações após a ablação foram de 11,5% e 1,2%, respectivamente. Conclusões A ablação de FLA-ICT é eficaz e segura, mas 50% dos pacientes desenvolvem FA após ablação. Entretanto, ainda é incerto o papel da ablação combinada (FLA-ICT e FA) visando prevenção da ocorrência de FA. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Simultaneous ablation of atrial fibrillation (AF) and cavotricuspid isthmus (CTI)-dependent atrial flutter can be performed when both arrythmias had been recorded before the procedure. However, the best approach has not been defined in case of patients referred for ablation with CTI-dependent atrial flutter, without history of AF. Objectives To assess the prevalence and to identify predictors of the first episode of AF after ablation of CTI-dependent atrial flutter in patients without history of AF. Methods Retrospective cohort of patients with CTI-dependent atrial flutter without history of AF undergoing catheter ablation. Clinical characteristics were compared between patients who developed AF and those who did not have AF after the procedure. Significance level was set at 5%. In the analysis of predicting factors, the primary outcome was occurrence of AF after CTI-dependent atrial flutter ablation. Results Of a total of 227 patients undergoing ablation of CTI-dependent atrial flutter (110 with history of AF and 33 without adequate follow-up), 84 were included, and 45 (53.6%) developed post-ablation AF. The HATCH and CHA2DS2-VASC scores were not different between the groups. Recurrence rate of CTI-dependent atrial flutter and complication rate were 11.5% and 1.2%, respectively, after ablation. Conclusions Although ablation of CTI-dependent atrial flutter is a safe and effective procedure, 50% of the patients developed AF after the procedure. However, the role of combined ablation (CTI-dependent atrial flutter plus AF) aiming at preventing AF is still uncertain. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Risk of Atrial Fibrillation after Ablation of Cavotricuspid Isthmus-Dependent Atrial Flutter: Is Combined Ablation of Atrial Fibrillation Worthwhile? / Risco de Fibrilação Atrial após Ablação de Flutter Dependente de Istmo Cavo-Tricuspídeo: Vale a Pena Fazer a Ablação da FA Simultaneamente?

BACKGROUND: Simultaneous ablation of atrial fibrillation (AF) and cavotricuspid isthmus (CTI)-dependent atrial flutter can be performed when both arrythmias had been recorded before the procedure. However, the best approach has not been defined in case of patients referred for ablation with CTI-dependent atrial flutter, without history of AF. OBJECTIVES: To assess the prevalence and to identify predictors of the first episode of AF after ablation of CTI-dependent atrial flutter in patients without history of AF. METHODS: Retrospective cohort of patients with CTI-dependent atrial flutter without history of AF undergoing catheter ablation. Clinical characteristics were compared between patients who developed AF and those who did not have AF after the procedure. Significance level was set at 5%. In the analysis of predicting factors, the primary outcome was occurrence of AF after CTI-dependent atrial flutter ablation. RESULTS: Of a total of 227 patients undergoing ablation of CTI-dependent atrial flutter (110 with history of AF and 33 without adequate follow-up), 84 were included, and 45 (53.6%) developed post-ablation AF. The HATCH and CHA2DS2-VASC scores were not different between the groups. Recurrence rate of CTI-dependent atrial flutter and complication rate were 11.5% and 1.2%, respectively, after ablation. CONCLUSIONS: Although ablation of CTI-dependent atrial flutter is a safe and effective procedure, 50% of the patients developed AF after the procedure. However, the role of combined ablation (CTI-dependent atrial flutter plus AF) aiming at preventing AF is still uncertain. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: A ablação da fibrilação atrial (FA) e do flutter atrial dependente de istmo cavo-tricuspídeo (FLA-ICT) pode ser realizada simultaneamente quando as duas arritmias tenham sido registradas antes do procedimento. Entretanto, a melhor abordagem não é clara quando pacientes com FLA-ICT são encaminhados para ablação sem o registro prévio de FA. OBJETIVOS: Avaliar a prevalência e identificar os preditores de ocorrência do primeiro episódio de FA após ablação de FLA-ICT em pacientes sem o registro prévio de FA. MÉTODOS: Coorte retrospectiva de pacientes submetidos exclusivamente a ablação por cateter para FLA-ICT, sem registro prévio de FA. As características clínicas foram comparadas entre os grupos em que houve ocorrência de FA pós-ablação de FLA-ICT vs. sem ocorrência de FA. O nível de significância estatística adotado foi de 5%. Na análise de preditores, o desfecho primário avaliado foi ocorrência de FA após ablação de FLA-ICT. RESULTADOS: De um total de 227 pacientes submetidos a ablação de FLA-ICT (110 com registro de FA e 33 sem seguimento adequado), 84 pacientes foram incluídos, dos quais 45 (53,6%) apresentaram FA pós-ablação. Não houve variáveis preditoras de ocorrência de FA. Os escores HATCH e CHA2DS2-VASC foram semelhantes nos dois grupos. As taxas de recorrência de FLA-ICT e complicações após a ablação foram de 11,5% e 1,2%, respectivamente. CONCLUSÕES: A ablação de FLA-ICT é eficaz e segura, mas 50% dos pacientes desenvolvem FA após ablação. Entretanto, ainda é incerto o papel da ablação combinada (FLA-ICT e FA) visando prevenção da ocorrência de FA. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Impacto do conhecimento nas atitudes, no sofrimento e qualidade de vida do paciente diabético / Impact of knowledge attitudes, without suffering and quality of life of the diabetic patient

O Diabetes Mellitus é uma doença crônica não transmissível com alta prevalência global. Para evitar complicações e tratar corretamente, é necessário que os pacientes tenham o conhecimento sobre sua doença e atitudes positivas, para que seja possível a prevenção do sofrimento e uma melhor qualidade de vida. O presente estudo objetivou avaliar conhecimento, atitude, sofrimento e qualidade de vida de indivíduos diabéticos de uma Unidade Básica de Saúde (UBS) de Palhoça, Santa Catarina, Brasil. Trata-se de um estudo transversal realizado com 80 pacientes diabéticos. Foram avaliadas variáveis sociodemográficas, clínicas, conhecimento (DKN-A), atitude (ATT-19), nível de sofrimento emocional (PAID) e qualidade de vida (SF-36). Os dados foram descritos na forma de frequências (absoluta/relativa), média e desvio padrão. A diferença entre médias foi estabelecida pelo teste T de student para amostras independentes (p≤0,05), a partir do SPSS 18.0. Observou-se 81,3% da população com baixo conhecimento sobre a doença, 97,5% com atitudes negativas e 32,5% com alto nível de sofrimento emocional. Em relação à qualidade de vida, os menores escores foram observados no sumário mental, com diferenças estatisticamente significativas nos domínios vitalidade, limitação por aspectos emocionais e saúde mental (p<0,05). Assim, o estudo demonstrou que os pacientes diabéticos apresentaram baixo conhecimento, atitudes negativas frente a doença, alto nível de sofrimento emocional e baixa qualidade de vida.

Diabetes Mellitus is a chronic, non-communicable disease with high global prevalence. To avoid complications and treat correctly, patients need to be knowledgeable about their illness and positive attitudes, so that suffering can be prevented and a better quality of life is possible. The present study aimed to evaluate the knowledge, attitude, suffering and quality of life of diabetic individuals of a Basic Health Unit (BHU) in Palhoça, Santa Catarina, Brazil. It is a cross-sectional study with 80 diabetic patients. Sociodemographic, clinical, knowledge (DKN-A), attitude (ATT-19), emotional distress level (PAID) and quality of life (SF-36) were evaluated. Data were described in the form of frequencies (absolute / relative), mean and standard deviation. The difference between means was established by the student T test for independent samples (p≤0.05), from SPSS 18.0. It was observed 81.3% of the population with low knowledge about the disease, 97.5% with negative attitudes and 32.5% with high level of emotional suffering. Regarding quality of life, the lowest scores were observed in the mental summary, with statistically significant differences in the domains of vitality, limitation by emotional aspects and mental health (p <0.05). Thus, the study demonstrated that diabetic patients presented low knowledge, negative attitudes towards the disease, high level of emotional suffering and low quality of life.

Imunização contra papilomavirus humano em escolas municipais / Immunization against human papilomavirus in municipal schools

Objetivo: descrever a experiência da realização de atividades educativas, análise do estado vacinal e imunização contra o papilomavírus humano (HPV) em estudantes da rede municipal da região norte de Palmas - TO. Método: tratase de um estudo descritivo, do tipo relato de experiência, desenvolvido a partir de ações do projeto de extensão universitária "Imuniza Escola" do Curso de Enfermagem da Universidade Federal do Tocantins em parceria com quatro escolas municipais e Centros de Saúde da Comunidade de Palmas ­ TO. Formaram-se grupos de educação em saúde alertando sobre a importância da vacinação contra o HPV e foram solicitados os cartões de vacina para análise e imunização. Resultados: organizaram-se grupos educativos com 1756 estudantes, sendo que, destes, 440 apresentaram os cartões de vacina para análise e 237 estavam com estado vacinal contra o HPV em atraso. Imunizaram-se 161 estudantes com a primeira dose e 73 com a segunda dose da vacina contra o HPV. Conclusão: observou-se que a experiência proporcionou, aos extensionistas, a oportunidade de vivenciar, na prática, os conteúdos ministrados na academia, além de contribuir para o aumento da cobertura vacinal e, consequentemente, a diminuição do número de casos de câncer evitados pela imunização contra o HPV.(AU)

Objective: to describe the experience of conducting educational activities, analysis of vaccination status and immunization against human papillomavirus (HPV) in students from the municipal system of northern Palmas-TO. Method: this is a descriptive study, of the experience report type, developed from actions of the university extension project "Immuniza Escola" of the Nursing Course of the Federal University of Tocantins in partnership with four municipal schools and Health Centers of the Palms Community-TO. Health education groups were formed warning about the importance of HPV vaccination and vaccination cards for analysis and immunization were requested. Results: educational groups were organized with 1756 students, of which 440 presented the vaccination cards for analysis and 237 were in delayed HPV vaccination status. 161 students with the first dose and 73 students with the second dose of the HPV vaccine were immunized. Conclusion: it was observed that the experience provided, to extensionists, the opportunity to experience, in practice, the contents taught in the academy, besides contributing to the increase of the vaccination coverage and, consequently, the decrease of the number of cancer cases avoided by the HPV immunization.(AU)

Objetivo: describir la experiencia de realizar actividades educativas, análisis del estado de vacunación e inmunización contra el virus del papiloma humano (VPH) en estudiantes del sistema municipal, en el norte de Palmas-TO. Método: este es un estudio descriptivo, del tipo de informe de experiencia, desarrollado a partir de acciones del proyecto de extensión universitaria "Immuniza Escola" del Curso de Enfermería de la Universidad Federal de Tocantins en colaboración con cuatro escuelas municipales y Centros de Salud de la Comunidad de Palmas-TO. Los grupos de educación sanitaria se hicieron advertir sobre la importancia de la vacunación contra el VPH y se solicitaron tarjetas de vacunación para su análisis e inmunización. Resultados: se organizaron grupos educativos con 1756 estudiantes, de los cuales 440 presentaron las tarjetas de vacunación para su análisis y 237 tenían el estado de la vacuna contra el VPH en mora. Se inmunizaron 161 estudiantes con la primera dosis y 73 con la segunda dosis de la vacuna contra el VPH. Conclusión: se observó que la experiencia brindó a los extensionistas la oportunidad de experimentar en la práctica los contenidos enseñados en la academia, además de contribuir al aumento de la cobertura de vacunación y, en consecuencia, a la reducción del número de casos de cáncer prevenidos por la inmunización contra el VPH.(AU)

Low-anxiety rat phenotypes can be further reduced through genetic intervention.

BACKGROUND: A previous study using an intercross between the inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) identified a locus on chromosome 4, named Anxrr16, influencing an experimental index of anxiety and showing a transgressive effect, with alleles from the LEW strain (more anxious) decreasing rather than increasing anxiety. OBJECTIVE: To confirm the location and isolate the effect of a rat genome region named Anxrr16 through a planned genomic recombination strategy, where the target locus in SHR rats was replaced with LEW genetic material. METHODS: A new congenic strain, named SHR.LEW-Anxrr16 (SLA16), was developed from a cross between LEW (donor) and SHR (receptor) rats and then evaluated in several anxiety-related tests. The activity and attention levels of the new strain were also evaluated, since hyperactivity was observed during its construction and because SHR is a model of attention deficit hyperactivity disorder. RESULTS: Significant effects of Anxrr16 were found for open field central locomotion, as well as for other indices of anxiety from the light/dark box, triple test and T-maze. In all cases, the low-anxiety levels of SHR rats were further reduced by the insertion of LEW alleles. Differences in locomotor activity were found only in unfamiliar (hence stressful) environments and no genetic effects were observed in indices of attention. CONCLUSION: The SLA16 strain can help in the identification of the molecular pathways involved in experimental anxiety and it demonstrates how apparently extreme phenotypes sometimes hide major opposite-acting genes.

The influence of sex and estrous cycle on QTL for emotionality and ethanol consumption.

The inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) differ with respect to several emotionality- and ethanol intake-related behaviors, one of which (inner locomotion in the open field; OF) is strongly influenced by a locus (Anxrr16) on chromosome (Chr) 4. We aimed to further investigate the influence of Chr 4 on these behaviors and to evaluate the role of the estrous cycle in QTL expression. LEW females and SHR males were intercrossed to produce F1 and F2 rats (96-97/sex), which were then tested in the OF, light-dark box (LDB), forced swimming test (FST), and an ethanol consumption procedure (ECP). In addition, another group of 96 F2 females were tested in the OF and LDB according to their estrous cycle phase. All animals were genotyped for microsatellite markers located on Chr 4 and two QTL analyses were performed. A factor analysis of the F2 population produced five factors reflecting different behavioral dimensions. QTL analysis revealed five significant loci in males, some of which with pleiotropic effects on behaviors measured in the OF, LDB, and ECP. The second QTL analysis revealed two significant loci in females in diestrous-proestrous and one in females in estrous-metestrous that influence behaviors in the OF and LDB. Results revealed that Anxrr16 and four other new QTL influence emotionality- and ethanol-related behaviors in male rats, whereas Anxrr16 attained suggestive levels only in females in diestrous-proestrous, which raises the need for taking into account factors related to the sex and estrous cycle in behavioral QTL analysis.

Absence of repeated-trial tolerance to the anxiolytic-like effects of chlordiazepoxide in the rat triple test.

The triple test, recently developed to assess anxiety-related behaviors in rodents, combines three widely used behavioral tests: the open field (OF), elevated plus maze (EPM) and light/dark box (LDB). The EPM and LDB, individually, are normally sensitive to the anxiolytic effects of benzodiazepines only in the first trial, due to the phenomenon of one-trial tolerance, which limits their use in longitudinal studies. The main objective of the present investigation was to verify whether the anxiolytic-like effects of chlordiazepoxide (CDZ), previously observed in naive animals submitted to the triple test, would persist after repeated testing. To this end, three experiments were carried out where male Wistar rats received CDZ (10mg/kg) 30min before the triple test for 2, 3 or 20 consecutive days. Except for the first day of drug treatment following a previous test experience in an undrugged state, CDZ had enduring anxiolytic-like effects under all schedules, promoting an increase in the exploration of the EPM open arms (and in some cases of the white compartment of the LDB), without affecting the number of closed-arm entries. The finding that rats did not develop tolerance to CDZ even with chronic treatment and repeated exposures to the triple test suggests that this new device is a promising tool to be used in longitudinal studies involving pharmacological manipulations of anxiety-related behaviors.

Integrating the open field, elevated plus maze and light/dark box to assess different types of emotional behaviors in one single trial.

Current anxiety tests do not provide, individually, a pure and complete picture of an animal's emotional profile. Therefore, many authors test their experimental hypotheses using a series of anxiety-related tests, which are thought to reflect different facets of emotionality. The objective of this study was to investigate the potential usefulness of integrating three widely used behavioral tests, the open field (OF), elevated plus maze (EPM), and light/dark box (LDB), to assess a wider range of emotional and non-emotional behaviors within one single trial. A protocol was developed where rats could freely explore an OF that was physically connected to an EPM and a LDB during 15min. Classical anxiety- and locomotion-related behaviors from each test were measured. Lewis and spontaneously hypertensive rats (SHR) inbred strains, known to present genetic differences in each of the individual tests, differed for all anxiety-related behaviors from the combined apparatus. Factor analyses revealed that similar anxiety- and locomotion-related factors were produced by the three tests applied either separately or in combination. Under both conditions, each test produced its own anxiety-related factor. Two benzodiazepines, chlordiazepoxide (at 5 and 10mg/kg) and midazolam (at 0.75mg/kg), facilitated the approach towards the EPM open arms, whereas pentylenetetrazole (10mg/kg) specifically inhibited exploration of the three aversive areas (OF center, EPM open arms, LDB light compartment). Together, these results suggest that the new integrated apparatus may contribute to the study of anxiety, by providing a rapid, comprehensive and reliable method of assessing emotionality-related behaviors and its underlying components.

Immunosuppressive therapy modulates T lymphocyte gene expression in patients with systemic lupus erythematosus.

To evaluate the T-cell large-scale differential gene expression in systemic lupus erythematosus (SLE) patients presenting with glomerulonephritis we studied SLE patients before and after immunosuppressive treatment. Large-scale gene expression of peripheral blood mononuclear T cells was evaluated using cDNA microarray nylon membranes containing 5184 cDNAs. Data were analysed using the SAM and Cluster and Treeview software. When untreated patients were compared to healthy individuals, 38 genes, most of them located on chromosomes 1, 3, 6, 17 and 19, were repressed, and when untreated patients were compared to treated ones, 154 genes, located on chromosomes 1, 6, 7, 12 and 17, were induced. In terms of biological function of coded proteins, the differentially expressed genes were associated with apoptosis, cell cycle, chromosomal scaffold, cytokine/chemokine, DNA repair/replication, Golgi/mitochondrial proteins, mRNA processing, signalling molecules and tumour suppressors. Two autoantigen genes related to RNA splicing (small nuclear riboprotein 70,000 MW-U1 SNR, and splicing factor 3a, 60,000 MW), and the tetranectin-plasminogen-binding protein were repressed. The Fc fragment of immunoglobulin G low affinity IIb, apoptotic protease activating factor-1, two subunits of cytochrome c, caspase 8, complement C5a, HLA-DRA, HLA-DQB1, transforming growth factor-beta receptor II, small nuclear ribonucleoprotein polypeptide N (Sm protein N) genes, heterogeneous nuclear riboprotein-C, and argininosuccinate lyase genes, among others, were induced. A total of 10 genes were repressed in untreated patients and induced in treated ones, among them tumour necrosis factor (ligand) superfamily member 9, tumour protein p53, mannosidase alpha class IA, and CD22. Although some of these differentially expressed genes are typically expressed in B cells, CD22 and CD32 have also been reported in T cells and may provide regulatory signals to B cells. Assessment of differential gene expression may provide hybridization signatures that may identify susceptibility, diagnostic and prognostic markers of SLE.