Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network)

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines

Serum biomarkers associated with SARS-CoV-2 severity

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity

Confiabilidade e validade das Declarações de Óbito por câncer de boca no Município de Teresina, Piauí, Brasil, no período de 2004 e 2005 Reliability and validity of death certificates specifying oral cancer as cause of death in Teresina, Piauí State, Brazil, 2004-2005

A política de saúde brasileira depende da precisão dos dados contidos no sistema de informação em saúde. Com objetivo de avaliar a confiabilidade e validade da causa básica de morte por uma neoplasia específica, no Município de Teresina, Piauí, Brasil, foram utilizadas todas as Declarações de Óbito (DO) que possuíam como causa básica de morte o câncer de boca nos anos de 2004 e 2005, contabilizando um total de 23 DO. Elas foram submetidas à nova codificação da causa básica mediante utilização de formulário direcionado à coleta de dados clínicos e de exames complementares para a confirmação do diagnóstico nos prontuários médicos. O diagnóstico foi confirmado pelo exame histopatológico e história clínica. Observou-se uma concordância simples de 91,3% e coeficiente kappa de 0,84. O valor preditivo positivo correspondeu a 90,9%. Assim, pode-se afirmar que as referidas estatísticas de mortalidade são válidas e confiáveis. Este estudo teve como limitação possíveis sub-registros de casos que tiveram como causa básica de morte a referida patologia, visto que tais dados não constam no sistema de informação em mortalidade de Teresina.<br>Brazilian health policy depends on the accuracy of data in the health information system. This study aimed to assess the reliability and validity of data on underlying cause of death due to a specific neoplasm in the Municipality of Teresina, Piauí State, Brazil, based on all the death certificates from 2004 and 2005 that reported oral cancer as the underlying cause of death (total of 23 death certificates). The death certificates were recoded for underlying cause of death by using a form targeted at collecting clinical and laboratory data to confirm the medical diagnosis on patient charts. Diagnosis was confirmed by histopathologic examination and clinical history. Simple agreement was 91.3%, kappa coefficient 0.84, and positive predictive value 90.9%. Based on the findings, the mortality statistics were valid and reliable. One limitation to this study was the possible underreporting of cases with oral cancer as the underlying cause of death, given that such data are not included in the mortality information system in Teresina