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Background There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. Methods A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. Results 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). Conclusions Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. Trial registration ClinicalTrials.gov NCT01310738, Author summary Visceral leishmaniasis remains a worldwide public health concern with high mortality even when proper treatment is instituted. There is a need to develop efficacious, safer and shorter treatment alternatives as the current options suffer from high toxicity and long treatment duration. Combination therapies emerge as an alternative, and WHO has encouraged the conduct of studies to evaluate drug combinations where evidence for current treatment regimens is not available. In Brazil, there is no local evidence to support the current treatment recommendations. Therefore, a clinical trial was conducted in five hospitals in Brazil to evaluate the efficacy and safety of the current available treatments—meglumine antimoniate, amphotericin B deoxycholate and liposomal amphotericin B—and of a combination of liposomal amphotericin B, single dose, and meglumine antimoniate, in a shorter administration regimen. Preliminary safety results led to the discontinuation of the amphotericin B deoxycholate treatment arm and a planned interim analysis resulted in the trial interruption. The final results, comparing liposomal amphotericin B and liposomal amphotericin B plus meglumine antimoniate to the standard meglumine antimoniate treatment, did not show a statistically significant difference in cure rates, though cure rate was higher in the liposomal amphotericin B group. Liposomal amphotericin B treatment showed a better safety profile compared to meglumine antimoniate. These results will support future changes in treatment protocols in Brazil and potentially in Latin America.

OBJETIVO: Avaliar o tratamento das cardiopatias congênitas realizadas de 2000 a 2009. MÉTODOS: A amostra constituiu-se de todos os pacientes submetidos a correção cirúrgica para cardiopatias congênitas por dez anos em Sergipe, Brasil. Os pacientes foram operados em três hospitais localizados na cidade de Aracaju (SE, Brasil), capital do estado de Sergipe. O estudo foi dividido em dois períodos, definidos pela data do início da centralização das cirurgias. As variáveis coletadas foram: faixa etária, gênero, diagnóstico pós-operatório, destino, tipo de cirurgia e hospital em que foi realizado o procedimento e a classificação RACHS -1. RESULTADOS: No período I, a estimativa do déficit de cirurgia foi de 69%, ocorrendo decréscimo no período II para 55,3%. O diagnóstico pós-operatório mais frequente foi de fechamento de comunicação interventricular (20,5%), fechamento de canal arterial (20,2%) e da comunicação interatrial (19%). Houve correlação estatisticamente significativa entre mortalidade esperada pelo RACHS-1 e a observada na amostra. A avaliação do RACHS-1 como fator preditor da mortalidade hospitalar por meio da curva ROC demonstrou área de 0,860 IC 95% 0,818 a 0,902, com P < 0,0001. CONCLUSÃO: Os resultados deste estudo indicam que a centralização e a organização dos recursos existentes são necessárias para melhora no desempenho das correções cirúrgicas das cardiopatias congênitas.OBJECTIVE: This study aims evaluate the treatment of congenital heart disease conducted from 2000 to 2009. METHODS: The sample consisted of all patients undergoing surgical correction for congenital heart disease for ten years in Sergipe, Brazil. The patients were operated in three hospitals located in the city of Aracaju, capital of the state of Sergipe (Brazil). The study was divided into two periods defined by the start date of centralization of surgery. The variables collected were: age, sex, postoperative diagnosis, destination, type of surgery and hospital where the procedure was performed and the classification RACHS -1. RESULTS: In the period I, the estimate deficit of surgery was 69% decrease occurring in the period II to 55.3%. The postoperative diagnosis was more frequent closure of the interventricular communication (20.5%), closure of patent ductus arteriosus (20.2%) and atrial septal defect (19%). There was a statistically significant correlation between the expected mortality RACHS-1 and observed in the sample. The evaluation of RACHS-1 as a predictor of hospital mortality by ROC curve showed area of 0.860 95% CI 0.818 to 0.902 with P

As cardiopatias congenitas sao a malformacao congenita mais frequente, estando presente em oito de cada 1000 nascidos vivos e apresentando necessidade cirurgica em 80% dos casos. O objetivo deste estudo foi analisar o tratamento cirurgico das cardiopatias congenitas de Sergipe em dez anos. Foram coletados dados dos registros de circulacao extra-corporea comum a todos os Hospitais de Sergipe, no periodo de 1o de janeiro de 2000 a 31 de dezembro de 2009, com as seguintes variaveis: faixa etaria, genero, procedencia, destino, diagnostico pos-operatorio, tipo de cirurgia, hospital onde foi realizado o procedimento, tipo de assistencia medica, categoria de risco cirurgico RACHS -1. Foram registrados os dados das declaracoes de nascidos vivos e obitos por cardiopatia congenita nos anos do estudo. O estudo foi dividido em dois periodos em funcao da centralizacao dos recursos em um unico hospital a partir de 2007. Foram realizadas 932 cirurgias nos dez anos. Houve reducao do deficit de cirurgias de 69% no periodo pre-contrato para 55,3% no pos-contrato; quanto a faixa etaria, 62,8% dos pacientes tinham entre 1 a 12 anos. Em relacao ao genero, o sexo feminino foi o mais frequente com 55% dos casos. A assistencia medica mais frequente foi o Sistema Unico de Saude e os diagnosticos mais frequentes foram CIV (20,5%), PCA (20,2%) e CIA (19%). Os fatores preditores de mortalidade hospitalar foram faixa etaria, categoria RACHS -1 e Hospital onde foi realizado o procedimento. Os resultados deste estudo indicam que a centralizacao dos recursos humanos e materiais e importante para cirurgia cardiaca das cardiopatias congenitas. Houve reducao na mortalidade hospitalar, no pre-contrato de 9,8% para 5,4% no pos- contrato.