A New Natural Language Processing-Inspired Methodology (Detection, Initial Characterization, and Semantic Characterization) to Investigate Temporal Shifts (Drifts) in Health Care Data: Quantitative Study.

BACKGROUND: Proper analysis and interpretation of health care data can significantly improve patient outcomes by enhancing services and revealing the impacts of new technologies and treatments. Understanding the substantial impact of temporal shifts in these data is crucial. For example, COVID-19 vaccination initially lowered the mean age of at-risk patients and later changed the characteristics of those who died. This highlights the importance of understanding these shifts for assessing factors that affect patient outcomes. OBJECTIVE: This study aims to propose detection, initial characterization, and semantic characterization (DIS), a new methodology for analyzing changes in health outcomes and variables over time while discovering contextual changes for outcomes in large volumes of data. METHODS: The DIS methodology involves 3 steps: detection, initial characterization, and semantic characterization. Detection uses metrics such as Jensen-Shannon divergence to identify significant data drifts. Initial characterization offers a global analysis of changes in data distribution and predictive feature significance over time. Semantic characterization uses natural language processing-inspired techniques to understand the local context of these changes, helping identify factors driving changes in patient outcomes. By integrating the outcomes from these 3 steps, our results can identify specific factors (eg, interventions and modifications in health care practices) that drive changes in patient outcomes. DIS was applied to the Brazilian COVID-19 Registry and the Medical Information Mart for Intensive Care, version IV (MIMIC-IV) data sets. RESULTS: Our approach allowed us to (1) identify drifts effectively, especially using metrics such as the Jensen-Shannon divergence, and (2) uncover reasons for the decline in overall mortality in both the COVID-19 and MIMIC-IV data sets, as well as changes in the cooccurrence between different diseases and this particular outcome. Factors such as vaccination during the COVID-19 pandemic and reduced iatrogenic events and cancer-related deaths in MIMIC-IV were highlighted. The methodology also pinpointed shifts in patient demographics and disease patterns, providing insights into the evolving health care landscape during the study period. CONCLUSIONS: We developed a novel methodology combining machine learning and natural language processing techniques to detect, characterize, and understand temporal shifts in health care data. This understanding can enhance predictive algorithms, improve patient outcomes, and optimize health care resource allocation, ultimately improving the effectiveness of machine learning predictive algorithms applied to health care data. Our methodology can be applied to a variety of scenarios beyond those discussed in this paper.

Comprehensive statistical analysis reveals significant benefits of COVID-19 vaccination in hospitalized patients: propensity score, covariate adjustment, and feature importance by permutation.

BACKGROUND: COVID-19 vaccines effectively prevent infection and hospitalization. However, few population-based studies have compared the clinical characteristics and outcomes of patients hospitalized for COVID-19 using advanced statistical methods. Our objective is to address this evidence gap by comparing vaccinated and unvaccinated patients hospitalized for COVID-19. METHODS: This retrospective cohort included adult COVID-19 patients admitted from March 2021 to August 2022 from 27 hospitals. Clinical characteristics, vaccination status, and outcomes were extracted from medical records. Vaccinated and unvaccinated patients were compared using propensity score analyses, calculated based on variables associated with vaccination status and/or outcomes, including waves. The vaccination effect was also assessed by covariate adjustment and feature importance by permutation. RESULTS: From the 3,188 patients, 1,963 (61.6%) were unvaccinated and 1,225 (38.4%) were fully vaccinated. Among these, 558 vaccinated individuals were matched with 558 unvaccinated ones. Vaccinated patients had lower rates of mortality (19.4% vs. 33.3%), invasive mechanical ventilation (IMV-18.3% vs. 34.6%), noninvasive mechanical ventilation (NIMV-10.6% vs. 22.0%), intensive care unit admission (ICU-32.0% vs. 44.1%) vasoactive drug use (21.1% vs. 32.6%), dialysis (8.2% vs. 14.7%) hospital length of stay (7.0 vs. 9.0 days), and thromboembolic events (3.9% vs.7.7%), p < 0.05 for all. Risk-adjusted multivariate analysis demonstrated a significant inverse association between vaccination and in-hospital mortality (adjusted odds ratio [aOR] = 0.42, 95% confidence interval [CI]: 0.31-0.56; p < 0.001) as well as IMV (aOR = 0.40, 95% CI: 0.30-0.53; p < 0.001). These results were consistent in all analyses, including feature importance by permutation. CONCLUSION: Vaccinated patients admitted to hospital with COVID-19 had significantly lower mortality and other severe outcomes than unvaccinated ones during the Delta and Omicron waves. These findings have important implications for public health strategies and support the critical importance of vaccination efforts, particularly in low-income countries, where vaccination coverage remains suboptimal.

Corrigendum: Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit.

[This corrects the article DOI: 10.3389/fmed.2023.1130218.].

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.

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.

Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit.

Objectives: To assess the ABC2-SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score). Materials and methods: Consecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC2-SPH was used as the reference score, and comparisons between ABC2-SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality. Results: ABC2-SPH had an area under the curve of 0.716 (95% CI 0.693-0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC2-SPH and SAPS-3, 4C Mortality Score, and the novel severity score. Conclusion: ABC2-SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients.

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.

Myocardial Injury and Prognosis in Hospitalized COVID-19 Patients in Brazil: Results From The Brazilian COVID-19 Registry. / Lesão Miocárdica e Prognóstico em Pacientes Hospitalizados com COVID-19 no Brasil: Resultados do Registro Nacional de COVID-19.

BACKGROUND: Cardiovascular complications of COVID-19 are important aspects of the disease's pathogenesis and prognosis. Evidence on the prognostic role of troponin and myocardial injury in Latin American hospitalized COVID-19 patients is still scarce. OBJECTIVES: To evaluate myocardial injury as independent predictor of in-hospital mortality and invasive mechanical ventilation support in hospitalized patients, from the Brazilian COVID-19 Registry. METHODS: This cohort study is a substudy of the Brazilian COVID-19 Registry, conducted in 31 Brazilian hospitals of 17 cities, March-September 2020. Primary outcomes included in-hospital mortality and invasive mechanical ventilation support. Models for the primary outcomes were estimated by Poisson regression with robust variance, with statistical significance of p<0.05. RESULTS: Of 2,925 patients (median age of 60 years [48-71], 57.1% men), 27.3% presented myocardial injury. The proportion of patients with comorbidities was higher among patients with cardiac injury (median 2 [1-2] vs. 1 [0-2]). Patients with myocardial injury had higher median levels of brain natriuretic peptide, lactate dehydrogenase, creatine phosphokinase, N-terminal pro-brain natriuretic peptide, and C-reactive protein than patients without myocardial injury. As independent predictors, C-reactive protein and platelet counts were related to the risk of death, and neutrophils and platelet counts were related to the risk of invasive mechanical ventilation support. Patients with high troponin levels presented a higher risk of death (RR 2.03, 95% CI 1.60-2.58) and invasive mechanical ventilation support (RR 1.87, 95% CI 1.57-2.23), when compared to those with normal troponin levels. CONCLUSION: Cardiac injury was an independent predictor of in-hospital mortality and the need for invasive mechanical ventilation support in hospitalized COVID-19 patients.

FUNDAMENTO: As complicações cardiovasculares da COVID-19 são aspectos importantes da patogênese e do prognóstico da doença. Evidências do papel prognóstico da troponina e da lesão miocárdica em pacientes hospitalizados com COVID-19 na América Latina são ainda escassos. OBJETIVOS: Avaliar a lesão miocárdica como preditor independente de mortalidade hospitalar e suporte ventilatório mecânico em pacientes hospitalizados, do registro brasileiro de COVID-19. MÉTODOS: Este estudo coorte é um subestudo do registro brasileiro de COVID-19, conduzido em 31 hospitais brasileiros de 17 cidades, de março a setembro de 2020. Os desfechos primários incluíram mortalidade hospitalar e suporte ventilatório mecânico invasivo. Os modelos para os desfechos primários foram estimados por regressão de Poisson com variância robusta, com significância estatística de p<0,05. RESULTADOS: Dos 2925 pacientes [idade mediana de 60 anos (48-71), 57,1%], 27,3% apresentaram lesão miocárdica. A proporção de pacientes com comorbidades foi maior nos pacientes com lesão miocárdica [mediana 2 (1-2) vs. 1 (0-20)]. Os pacientes com lesão miocárdica apresentaram maiores valores medianos de peptídeo natriurético cerebral, lactato desidrogenase, creatina fosfoquinase, N-terminal do pró-peptídeo natriurético tipo B e proteína C reativa em comparação a pacientes sem lesão miocárdica. Como fatores independentes, proteína C reativa e contagem de plaquetas foram relacionados com o risco de morte, e neutrófilos e contagem de plaquetas foram relacionados ao risco de suporte ventilatório mecânico invasivo. Os pacientes com níveis elevados de troponina apresentaram um maior risco de morte (RR 2,03, IC95% 1,60-2,58) e suporte ventilatório mecânico (RR 1,87;IC95% 1,57-2,23), em comparação àqueles com níveis de troponina normais. CONCLUSÃO: Lesão cardíaca foi um preditor independente de mortalidade hospitalar e necessidade de suporte ventilatório mecânico em pacientes hospitalizados com COVID-19.

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.

Lesão Miocárdica e Prognóstico em Pacientes Hospitalizados com COVID-19 no Brasil: Resultados do Registro Nacional de COVID-19 / Myocardial Injury and Prognosis in Hospitalized COVID-19 Patients in Brazil: Results From The Brazilian COVID-19 Registry

Resumo Fundamento As complicações cardiovasculares da COVID-19 são aspectos importantes da patogênese e do prognóstico da doença. Evidências do papel prognóstico da troponina e da lesão miocárdica em pacientes hospitalizados com COVID-19 na América Latina são ainda escassos. Objetivos Avaliar a lesão miocárdica como preditor independente de mortalidade hospitalar e suporte ventilatório mecânico em pacientes hospitalizados, do registro brasileiro de COVID-19. Métodos Este estudo coorte é um subestudo do registro brasileiro de COVID-19, conduzido em 31 hospitais brasileiros de 17 cidades, de março a setembro de 2020. Os desfechos primários incluíram mortalidade hospitalar e suporte ventilatório mecânico invasivo. Os modelos para os desfechos primários foram estimados por regressão de Poisson com variância robusta, com significância estatística de p<0,05. Resultados Dos 2925 pacientes [idade mediana de 60 anos (48-71), 57,1%], 27,3% apresentaram lesão miocárdica. A proporção de pacientes com comorbidades foi maior nos pacientes com lesão miocárdica [mediana 2 (1-2) vs. 1 (0-20)]. Os pacientes com lesão miocárdica apresentaram maiores valores medianos de peptídeo natriurético cerebral, lactato desidrogenase, creatina fosfoquinase, N-terminal do pró-peptídeo natriurético tipo B e proteína C reativa em comparação a pacientes sem lesão miocárdica. Como fatores independentes, proteína C reativa e contagem de plaquetas foram relacionados com o risco de morte, e neutrófilos e contagem de plaquetas foram relacionados ao risco de suporte ventilatório mecânico invasivo. Os pacientes com níveis elevados de troponina apresentaram um maior risco de morte (RR 2,03, IC95% 1,60-2,58) e suporte ventilatório mecânico (RR 1,87;IC95% 1,57-2,23), em comparação àqueles com níveis de troponina normais. Conclusão Lesão cardíaca foi um preditor independente de mortalidade hospitalar e necessidade de suporte ventilatório mecânico em pacientes hospitalizados com COVID-19.

Abstract Background Cardiovascular complications of COVID-19 are important aspects of the disease's pathogenesis and prognosis. Evidence on the prognostic role of troponin and myocardial injury in Latin American hospitalized COVID-19 patients is still scarce. Objectives To evaluate myocardial injury as independent predictor of in-hospital mortality and invasive mechanical ventilation support in hospitalized patients, from the Brazilian COVID-19 Registry. Methods This cohort study is a substudy of the Brazilian COVID-19 Registry, conducted in 31 Brazilian hospitals of 17 cities, March-September 2020. Primary outcomes included in-hospital mortality and invasive mechanical ventilation support. Models for the primary outcomes were estimated by Poisson regression with robust variance, with statistical significance of p<0.05. Results Of 2,925 patients (median age of 60 years [48-71], 57.1% men), 27.3% presented myocardial injury. The proportion of patients with comorbidities was higher among patients with cardiac injury (median 2 [1-2] vs. 1 [0-2]). Patients with myocardial injury had higher median levels of brain natriuretic peptide, lactate dehydrogenase, creatine phosphokinase, N-terminal pro-brain natriuretic peptide, and C-reactive protein than patients without myocardial injury. As independent predictors, C-reactive protein and platelet counts were related to the risk of death, and neutrophils and platelet counts were related to the risk of invasive mechanical ventilation support. Patients with high troponin levels presented a higher risk of death (RR 2.03, 95% CI 1.60-2.58) and invasive mechanical ventilation support (RR 1.87, 95% CI 1.57-2.23), when compared to those with normal troponin levels. Conclusion Cardiac injury was an independent predictor of in-hospital mortality and the need for invasive mechanical ventilation support in hospitalized COVID-19 patients.

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.

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

BACKGROUND: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. METHODS: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). CONCLUSIONS: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

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.

Neurological manifestations by sex and age group in COVID-19 inhospital patients.

Introduction: Neurological manifestations have been associated with a poorer prognosis in COVID-19. However, data regarding their incidence according to sex and age groups is still lacking. Methods: This retrospective multicentric cohort collected data from 39 Brazilian hospitals from 17 cities, from adult COVID-19 admitted from March 2020 to January 2022. Neurological manifestations presented at hospital admission were assessed according to incidence by sex and age group. Results: From 13,603 COVID-19 patients, median age was 60 years old and 53.0% were men. Women were more likely to present with headaches (22.4% vs. 17.7%, p < 0.001; OR 1.36, 95% confidence interval [CI] 1.22-1.52) than men and also presented a lower risk of having seizures (OR 0.43, 95% CI 0.20-0.94). Although delirium was more frequent in women (6.6% vs. 5.7%, p = 0.020), sex was not associated with delirium in the multivariable logistc regresssion analysis. Delirium, syncope and coma increased with age (1.5% [18-39 years] vs. 22.4% [80 years or over], p < 0.001, OR 1.07, 95% CI 1.06-1.07; 0.7% vs. 1.7%, p = 0.002, OR 1.01, 95% CI 1.00-1.02; 0.2% vs. 1.3% p < 0.001, OR 1.04, 95% CI 1.02-1.06), while, headache (26.5% vs. 7.1%, OR 0.98, 95% CI 0.98-0.99), anosmia (11.4% vs. 3.3%, OR 0.99, 95% CI] 0.98-0.99 and ageusia (13.1% vs. 3.5%, OR 0.99, CI 0.98-0.99) decreased (p < 0.001 for all). Conclusion: Older COVID-19 patients were more likely to present delirium, syncope and coma, while the incidence of anosmia, ageusia and headaches decreased with age. Women were more likely to present headache, and less likely to present seizures.

Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry.

BACKGROUND: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. METHODS: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis from 37 hospitals. Matching for age, sex, number of comorbidities, and hospital was performed for the paired analysis. RESULTS: Of 7,762 patients with COVID-19, 526 had previously diagnosed hypothyroidism and 526 were matched controls. The median age was 70 years, and 68.3% were females. The prevalence of comorbidities was similar, except for coronary and chronic kidney diseases that were higher in the hypothyroidism group (p=0.015 and p=0.001). D-dimer levels were lower in patients with hypothyroid (p=0.037). In-hospital management was similar, but hospital length-of-stay (p=0.029) and mechanical ventilation requirement (p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs 27.0%; p=0.062). CONCLUSION: Patients with hypothyroidism had a lower requirement of mechanical ventilation and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis.

Validação do Escore TIMI de Risco para Infarto Agudo com Supradesnivelamento do Segmento ST / Validation of TIMI Risk Score for STEMI

Fundamento:O escore TIMI de risco para infarto agudo do miocárdio com supradesnivelamento de ST (IAM CSST) é uma ferramenta importante para estratificar o risco de morte no IAM, porém, ainda não está validado em nosso meio. Objetivos: Validar o escore TIMI de risco para pacientes com IAM CSST como preditor de óbito intra-hospitalar e identificar outros preditores independentes de mortalidade intra-hospitalar não descritos neste escore. Métodos: Coorte retrospectiva com 938 pacientes com diagnóstico de IAM CSST pertencentes ao banco de dados de duas instituições de atendimento cardiológico de referência no Rio Grande do Sul. As variáveis clínicas foram testadas por análise univariada e análise multivariada por regressão logística. A área sob a curva (ASC) foi aplicada para definir sensibilidade, especificidade e poder discriminatório do escore. Um escore de risco, intitulado "Escore TIMI de Risco Modificado", foi criado na tentativa de aumentar o poder discriminatório. Resultados: A mortalidade intra-hospitalar foi de 8,6%. O escore TIMI de risco para IAM CSST demonstrou poder discriminatório de 0,82, sem identificar novos preditores de mortalidade. Peso < 67 Kg, infarto anterior, bloqueio de ramo esquerdo e hipertensão não apresentaram significância estatística na análise multivariada. Um escore TIMI modificado que excluiu essas variáveis teve poder discriminatório de 0,84. Conclusão: O escore TIMI de risco para IAM CSST apresentou bom poder discriminatório como preditor de óbito intra-hospitalar. Não foram encontrados novos preditores de mortalidade hospitalar. O escore TIMI modificado não apresentou um poder discriminatório superior ao do escore TIMI

Background: TIMI risk score for ST elevation myocardial infarction (STEMI) is an important tool to assess mortality risk; however, it has not yet been validated in Brazil. Objectives: To validate the TIMI risk score for STEMI patients as a predictor of in-hospital mortality and to identify new independent predictors of in-hospital mortality not described by this score. A new risk score called "Modified TIMI Risk Score" was created in an attempt to increase its discriminatory power. Methods: Retrospective cohort study evaluating 983 patients with STEMI, obtained from a database of two leading cardiology institutions in Rio Grande do Sul. Clinical variables described for the TIMI risk score were tested using univariate analysis and multivariate analysis by logistic regression. Area under curve (AUC) was used to define sensitivity, specificity and discriminatory power of the score. Non-significant variables on multivariate analysis were excluded, and the discriminatory power of the modified TIMI risk score was calculated. Results: In-hospital mortality was 8.6%. The TIMI risk score for STEMI showed a discriminatory power of 0.82, with no identification of new predictors of mortality. In the multivariate analysis, weight < 67 Kg, previous infarction, left bundle branch block and hypertension did not show statistical significance. A modified TIMI score that excluded these variables had discriminatory power of 0.84. Conclusion: TIMI risk score for STEMI presented good discriminatory power as a predictor of in-hospital mortality. No new predictors of in-hospital mortality were found. The modified TIMI score did not present a discriminatory power that was superior to the TIMI score