SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study

BACKGROUND: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. METHODS: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. RESULTS: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). CONCLUSIONS: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. FUNDING: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem

Construction and validation of indicators and respective definitions for the nursing outcome Swallowing Status

;;OBJETIVO:;; construir e validar por especialistas e clinicamente os indicadores para o resultado de enfermagem Estado da deglutição e suas definições conceituais e operacionais em pacientes após acidente vascular cerebral.;;;;MÉTODO:;; estudo metodológico, com análise de conceito e validações de conteúdo e clínica. Verificou-se o Índice de Validade de Conteúdo para as notas atribuídas por 11 especialistas aos indicadores revisados. Na validação clínica, examinaram-se 81 pacientes por duas duplas de enfermeiros, uma usando instrumento com as definições construídas e outra com instrumento sem definições. As avaliações foram comparadas pelo Coeficiente de Correlação Intraclasse, teste de Friedman e Diferença Mínima Significante.;;;;RESULTADOS:;; exceto o indicador Captura do alimento, todos apresentaram Índice de Validade de Conteúdo superior a 0,80. A dupla de enfermeiros com instrumento contendo as definições construídas apresentou Coeficiente de Correlação Intraclasse superior a 0,80 para todos os indicadores e pelo cálculo da Diferença Mínima Significante houve similaridade entre todas as avaliações. Na dupla que estava sem as definições elaboradas, o coeficiente foi baixo (ρ;;;;CONCLUSÃO:;; os dados evidenciaram aumento na uniformidade e acurácia entre as avaliações dos enfermeiros ao utilizar as definições conceituais e operacionais para os indicadores do resultado de enfermagem Estado da deglutição.;;;;OBJECTIVE:;; to develop indicators for the nursing outcome Swallowing Status and the respective conceptual and operational definitions validated by experts and in a clinical setting among patients after having experienced a stroke.;;;;METHOD:;; methodological study with concept analysis and content and clinical validations. The Content Validation Index was verified for the scores assigned by 11 experts to indicators. Two pairs of nurses assessed 81 patients during the clinical validation: one pair used an instrument with definitions and the other used an instrument without definitions. The resulting assessments were compared using Intraclass Correlation Coefficient, Friedman's test, and Minimal Important Difference calculation.;;;;RESULTS:;; All the indicators, with the exception of the indicator Ability to bring food to mouth, presented Content Validation Index above 0.80. The pair using the instrument with definitions presented an Intraclass Correlation Coefficient above 0.80 for all the indicators and similarity was found in all the assessments, according to the Minimal Important Difference calculation. The pair using the instrument without definitions presented a low coefficient (ρ;;OBJETIVO:;; construir y validar por especialistas y clínicamente los indicadores para el resultado de enfermería Estado de la deglución y sus definiciones conceptuales y operacionales en pacientes después de accidente vascular cerebral.;;;;MÉTODO:;; estudio metodológico, con análisis de concepto y validaciones de contenido y clínicas. Se verificó el Índice de Validez de Contenido para las notas atribuidas por 11 especialistas a los indicadores revisados. En la validación clínica, fueron examinados 81 pacientes por dos parejas de enfermeros, una usando instrumento con las definiciones construidas y la otra con instrumento sin definiciones. Las evaluaciones fueron comparadas por el Coeficiente de Correlación Intraclase, test de Friedman y Diferencia Mínima Significativa.;;;;RESULTADOS:;; exceptuando el indicador Captura del alimento, todos presentaron Índice de Validez de Contenido superior a 0,80. La pareja de enfermeros con instrumento conteniendo las definiciones construidas presentó Coeficiente de Correlación Intraclase superior a 0,80 para todos los indicadores y por el cálculo de la Diferencia Mínima Significativa hubo semejanza entre todas las evaluaciones. En la pareja que estaba sin las definiciones elaboradas, el coeficiente fue bajo (

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management