Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Aim: Previous studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy. Methods: Patients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6-12 months after treatment, and intention-to-treat analysis was used. Results: We screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60-0.97) vs. 66% (95% CI 0.40-0.86), p = 0.47, at 6 months and 68% (95% CI 0.43-0.87) vs. 72% (95% CI 0.46-0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group. Conclusion: G-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02154269].

Avaliaçäo da atençäo à saúde através da investigaçäo de óbitos infantis / Evaluation of health care by means of infant death investigation

Foram investigados todos os óbitos de crianças menores de um ano residentes no Distrito Sanitário de Pau da Lima, Município de Salvador, Brasil, no ano de 1991, através de consultas aos respectivos prontuários hospitalares e visitas domiciliares. O estudo visava a aferir a efetividade dos serviços de saúde por meio da verificaçäo de óbitos potencialmente evitáveis e o grau de adequaçäo dos cuidados médicos prestados às crianças. De um total de 47 óbitos, observou-se que mais da metade dos mesmos ocorreu por causas vulneráveis à açäo oportuna dos serviços de saúde, e que 21,3 por cento dos óbitos ocorreram em via pública e domicílios. Houve 76,6 por cento de perdas de informaçäo nas entrevistas com as mäes, atribuídas a problemas de preenchimento incompleto ou incorreto da Declaraçäo de Obito, e por mudanças de endereço. A pesquisa dos prontuários nas unidades de saúde registrou perda de 58,3 por cento, revelando o baixo grau de organizaçäo das estatísticas hospitalares; prevaleceram atendimentos classificados como pouco adequados e inadequados, principalmente nos itens exame físico e tratamento. Apesar das limitaçöes operacionais do estudo, os resultados apontam problemas de acesso, efetividade e adequaçäo do processo de assistência à saúde.