Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Avaliação da eficácia da gestão de pesquisa nos Parques Estaduais de São Paulo

Protected areas are considered one of the most important elements for biodiversity conservation. One of the pillars that sustain the management of these areas is scientific research, which provides the knowledge necessary for the conservation of environmental and historical-cultural heritage. The general objective of the present study was to evaluate the current state and propose improvements in the management of research of the State Parks of São Paulo in light of already existing practices of Knowledge Management. By the analysis of Research Programs present in the Management Plans of the Units, we identify the main aspects that underpin the research management and evaluate their effectiveness within the current context of each Park and for all the system (set of Parks). The main challenges pointed out in the evaluation were related to the lack of assurance regarding the return of the results of the surveys for management of the areas; the insufficiency of human resources directed to the execution of the activities foreseen in the Research Programs and the monitoring process carried out without periodicity and systematization. We could also observe the low correlation between well-managed Management Plans and Research Programs and the satisfactory performance of the actions foreseen in these documents, suggesting that the process of research management in these areas is not necessarily being directed by some planning instrument.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)As Unidades de Conservação (UC) são considerados os elementos mais importantes para conservação da biodiversidade. Um dos pilares que sustentam a gestão dessas áreas é a pesquisa científica, que proporciona a obtenção de conhecimentos indispensáveis à conservação do patrimônio ambiental e histórico-cultural. O objetivo geral do presente trabalho foi avaliar o estado atual e propor melhorias na gestão de pesquisa dos Parques Estaduais de São Paulo à luz de boas práticas da Gestão do Conhecimento já existentes. Por meio da análise dos Programas de Pesquisa presentes nos Planos de Manejo das Unidades, identificamos os principais aspectos que alicerçam a gestão de pesquisa e avaliamos sua eficácia dentro do contexto atual de cada Parque e para o sistema (conjunto de Parques). Os principais desafios apontados na avaliação estiveram relacionados à falta de garantia quanto ao retorno dos resultados das pesquisas para gestão das áreas; a insuficiência de recursos humanos direcionados à execução das atividades previstas nos Programas de Pesquisa e o processo de monitoramento realizado sem periodicidade e sistematização. Pudemos observar ainda a baixa correlação entre Planos de Manejo e Programas de Pesquisa bem estruturados e desempenho satisfatório das ações previstas nesses documentos, sugerindo que o processo de gestão da pesquisa nessas áreas não necessariamente está sendo direcionado por algum instrumento de planejamento

AVALIAÇÃO DA GESTÃO DE PESQUISA EM ÁREAS PROTEGIDAS – UM ESTUDO DE CASO NOS PARQUES ESTADUAIS DE SÃO PAULO

Protected areas have been the central strategy for biodiversity conservation, in accordance with the objectives of the Convention on Biological Diversity (CBD). The goals of Aichi for the Conservation of Biodiversity also require that they be effectively managed. Despite scientific research is extremely important to protected areas as they are able to assist management actions and decision making, the gap betweenresearch and practice continues to limit the success of conservation. We designed a methodological proposal, based on the adaptation of the method of Cifuentes, Izurieta and Faria (2000), to assist managers of protected areas in the identification of deficient points in research management. We tested the proposal at the São Paulo State Parks and discussed its implications. We conclude, based on the case study, that the proposal is efficient in understanding how research unfolds in contributions and directions to the management of protected areas and is flexible because it allows the evaluation of different research management structures.As áreas protegidas têm representado a estratégia central para conservação da biodiversidade, de acordo com os objetivos da Convenção sobre Diversidade Biológica (CDB). As metas de Aichi para a Conservação da Biodiversidade exigem, também, que sejam efetivamente gerenciadas. Apesar das pesquisas científicas mostrarem-se de extrema importância às áreas protegidas por serem capazes de auxiliar ações de manejo e tomadas de decisão, a lacuna entre pesquisa e prática continua a limitar o sucesso da conservação. Desenhamos uma propostametodológica, com base na adaptação do método de Cifuentes, Izurieta e Faria (2000), para auxiliar os gerentes das áreas protegidas na identificação de pontos deficientes na gestão de pesquisa. Testamos a proposta nos Parques Estaduais de São Paulo e discutimos suas implicações. Concluímos, com base no estudo de caso, que a proposta se mostra eficiente também na compreensão de como as pesquisas se desdobram em contribuições e direcionamentos ao gerenciamento das áreasprotegidas e flexível na medida em que possibilita a avaliação de diferentes estruturas de gestão de pesquisa