Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BACKGROUND: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. RESULTS: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. CONCLUSIONS: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. CLINICAL TRIALS REGISTRATION: NCT04343729.

Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial.

Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days. Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical-radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit. Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission. Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis. Trial Registration: ClinicalTrials.gov, Identifier: NCT04343729.

Hemorrhagic and thrombotic manifestations in the central nervous system in COVID-19: A large observational study in the Brazilian Amazon with a complete autopsy series.

SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.

Special education of students with Down Syndrome for self-care / Educación especial de estudiantes con Síndrome de Down para el autocuidado / Educação especial de estudantes com Síndrome de Down para o autocuidado

ABSTRACT Objective: to analyze the care taught by teachers and parents and learned by students with Down Syndrome. Method: descriptive study with qualitative approach carried out in a special education school, based in the city of Manaus. Eleven students with Down Syndrome, 11 parents of students and 11 teachers from the school participated in the study. Data were collected from November 2017 to February 2018, through a semi-structured interview, and analyzed by the content analysis technique. The theoretical framework regarded Down Syndrome. Results: three thematic categories emerged: the care learned by the student; the care taught by the teacher and; the care taught by the parents. Conclusion and implications for practice: family and teachers play a facilitating role in the learning to care for themselves and in the socio-cognitive and affective development of the person with Down Syndrome. The care learned by the student involved dialogic communication for care through learning of good habits, autonomy, independence and healthy eating. The study shows that nursing has the role of teaching the family how to help the child's progress, which results in significant future changes.

RESUMEN Objetivo: analizar la enseñanza del cuidado realizado por profesores y padres y el aprendizaje de estudiantes con Síndrome de Down. Método: Estudio descriptivo con enfoque cualitativo, realizado en una escuela de educación especial, con sede en la ciudad de Manaos. Once estudiantes con Síndrome de Down, 11 padres y 11 profesores de la escuela participaron del estudio. Los datos se recopilaron de noviembre de 2017 a febrero de 2018, a través de entrevista semiestructurada, y se analizaron mediante la técnica de análisis de contenido. El marco teórico abordó el Síndrome de Down. Resultados: surgieron tres categorías temáticas: el cuidado aprendido por el estudiante; el cuidado enseñado por el profesor y; el cuidado enseñado por los padres. Conclusión e implicaciones para la práctica: familiares y profesores desempeñan un papel facilitador en el aprendizaje para el autocuidado y en el desarrollo sociocognitivo y afectivo de la persona con Síndrome de Down. El aprendizaje del estudiante involucró la comunicación dialógica para el cuidado a través del aprendizaje de buenos hábitos, autonomía, independencia y alimentación saludable. El estudio evidencia que la enfermería tiene el papel de enseñar la familia y ayudar el progreso del hijo, lo que resulta en cambios significativos futuros.

RESUMO Objetivo: analisar o cuidado ensinado por professores e pais e aprendido por estudantes com Síndrome de Down. Método: estudo descritivo de abordagem qualitativa, realizado em uma escola de educação especial, sediada na cidade de Manaus. Participaram do estudo 11 estudantes com Síndrome de Down, 11 pais dos estudantes e 11 professores da escola. Os dados foram coletados no período de novembro de 2017 a fevereiro de 2018, por meio de entrevista semiestruturada, e analisados pela técnica de análise de conteúdo. O embasamento teórico versou sobre a doença Síndrome de Down. Resultados: emergiram três categorias temáticas: o cuidado aprendido pelo aluno; o cuidado ensinado pelo professor e; o cuidado ensinado pelos pais. Conclusão e implicações para a prática: a família e os professores exercem um papel de facilitadores do aprendizado para o cuidado de si e no desenvolvimento sócio-cognitivo e afetivo da pessoa com Síndrome de Down. O cuidado aprendido pelo estudante envolveu comunicação dialógica para o cuidado por meio de aprendizagem de bons hábitos, autonomia, independência e alimentação saudável. O estudo evidencia que a enfermagem tem o papel de ensinar a família como ajudar no progresso do filho, o que resulta em mudanças significativas futuras.

Aspergilose Pulmonar em diagnóstico postmortem de pacientes Infectados pelo vírus da Síndrome Respiratória Aguda Grave Coronavírus 2 (SARS-CoV-2)

Infecções secundárias em quadros respiratórios agudos graves em pacientes infectados por coronavírus 2 (SARS-CoV-2), como foram bem documentados em pacientes com gripe, nos quais levam à deterioração clínica e mortalidade, e requerem cuidados intensivos. No entanto, há incerteza na literatura sobre se o COVID-19 predispõe a doenças fúngicas invasivas. Entre abril e julho de 2020, antes da ampla recomendação de corticosteroides para COVID-19 grave, um total de 50 autópsias foram realizadas em Manaus. As amostras de tecido pulmonar foram preparadas e analisadas por dois patologistas diferentes. Detecção de galactomanana sérica, reação de cadeia polimerase e sequenciamento da amostra foram realizados para confirmar doença fúngica associada à COVID-19. A incidência de CAPA foi calculada, sendo considerada a razão entre o número de pacientes com Aspergilose e o total de pacientes autopsiados. Confirmamos dois casos de Aspergilose Invasiva por meio de análise histopatológica e sequenciamento de genes (4%) em nossa série de autópsias. A incidência de Aspergilose confirmada parece muito menor do que o esperado nas definições 'provável e possível', e uma abordagem individualizada deve ser considerada para cada cenário de país. Curiosamente, o tempo prolongado de internação na UTI não foi observado em nenhum dos casos. O diagnóstico e tratamento oportunos da infecção fúngica podem reduzir as taxas de mortalidade.