Impact of pharmaceutical care on the quality of life of patients with heart failure due to chronic Chagas disease: Randomized clinical trial.

AIMS: Chronic Chagas disease (ChD) has high morbimortality and loss in quality of life due to heart failure (HF). Pharmaceutical care (PC) optimizes clinical treatment and can improve quality of life in HF. We evaluated if PC improves quality of life of patients with ChD and HF. METHODS: Single-blinded, randomized, controlled trial that assigned adult patients with ChD and HF (81 patients; 61 ± 11 years; 48% male) to PC (n = 40) or standard care (n = 41). Quality of life according to SF-36 and Minnesota living with HF questionnaires, incidence of drug-related problems (DRPs), and adherence to medical treatment were determined at baseline and at every 3 months for 1 year. Intention-to-treat analyses were performed by mixed linear model to verify the treatment effect on the changes of these variables throughout the intervention period. RESULTS: Relative changes from baseline to 1 year of follow-up of the domains physical functioning (+16.6 vs -8.5; P < .001), role-physical (+34.0 vs +5.2; P = .01), general health (+19.4 vs -6.1; P < .001), vitality (+11.5 vs. -5.8; P = .003), social functioning (+7.5 vs -13.3; P = .002), and mental health (+9.0 vs -3.7; P = .006) of the SF-36 questionnaire and the Minnesota living with HF questionnaire score (-12.7 vs +4.8; P < .001) were superior in the PC group than in the standard care group. Adherence to medical treatment increased as early as after 3 months of follow-up and DRPs incidence decreased after 6 months of follow-up only in the PC group. CONCLUSIONS: Patients with ChD and HF who received PC presented improved quality of life, decrease in DRP frequency, and increase in medication adherence.

TGF-ß Polymorphisms Are a Risk Factor for Chagas Disease.

Transforming growth factor ß1 (TGF-ß1) is an important mediator in Chagas disease. Furthermore, patients with higher TGF-ß1 serum levels show a worse clinical outcome. Gene polymorphism may account for differences in cytokine production during infectious diseases. We tested whether TGFB1 polymorphisms could be associated with Chagas disease susceptibility and severity in a Brazilian population. We investigated five single-nucleotide polymorphisms (-800 G>A, -509 C>T, +10 T>C, +25 G>C, and +263 C>T). 152 patients with Chagas disease (53 with the indeterminate form and 99 with the cardiac form) and 48 noninfected subjects were included. Genotypes CT and TT at position -509 of the TGFB1 gene were more frequent in Chagas disease patients than in noninfected subjects. Genotypes TC and CC at codon +10 of the TGFB1 gene were also more frequent in Chagas disease patients than in noninfected subjects. We found no significant differences in the distribution of the studied TGFB1 polymorphisms between patients with the indeterminate or cardiac form of Chagas disease. Therefore, -509 C>T and +10 T>C TGFB1 polymorphisms are associated with Chagas disease susceptibility in a Brazilian population.

Itraconazole vs. trimethoprim-sulfamethoxazole: A comparative cohort study of 200 patients with paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Brazil accounts for approximately 80% of cases, where it represents a major public health issue due to its disabling impact and the number of premature deaths it causes. We present a retrospective cohort study that was conducted in order to better understand factors that relate to cure of the infection in the treatment of 200 patients with PCM. We evaluated the influence of sociodemographic and clinical factors as well as therapeutic regimen (trimethoprim-sulfamethoxazole [TMP-SMX] and itraconazole) on the progress of PCM (cure and noncure). There was a higher incidence of cure (83%) among patients who regularly received treatment for their infections and completed the treatment protocol. Moreover, itraconazole (86.4%) was significantly superior to TMP-SMX (51.3%) in terms of cure rate and had a median treatment period that was significantly shorter (12 months) than that for TMP-SMX (23 months). A Cox proportional hazard regression model showed that use of itraconazole increased the hazard of cure, regardless of sex, age, education, clinical form, completion of treatment, and regularity. Although the results of this study show that itraconazole was the best treatment option for PCM patients, a double-blind, randomized, controlled trial is necessary to confirm this conclusion.

Matrix metalloproteinases 2 and 9 are differentially expressed in patients with indeterminate and cardiac clinical forms of Chagas disease.

Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8(+) T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.

Avaliação das concentrações de citocinas séricas de pacientes em diferentes estágios da doença de Chagas / Assessment of concentrations of serum cytokines of patients at different stages of Chagas disease

A resposta imune é muito importante para a proteção contra doenças. Estudos têm avaliado a resposta imunológica de pacientes com doença de Chagas na tentativa de explicar a fisiopatologia da doença. O objetivo deste trabalho foi avaliar as concentrações das citocinas séricas IL-4, IL- 10, IL-12, TNF- e IFN- em pacientes nas diferentes formas clínicas da doença de Chagas. Foi realizado um estudo caso-controle de 115 indivíduos. Os indivíduos infectados foram divididos em estágios conforme o consenso brasileiro de doença de Chagas: indeterminados ou sem cardiopatia aparente (eletrocardiograma e ecocardiograma normais); cardíacos A (eletrocardiograma alterado e ecocardiograma normal); cardíacos C (eletrocardiograma e ecocardiograma alterados com ICC compensável) e cardíacos D (eletrocardiograma e ecocardiograma alterados com ICC refratária). Também foram incluídos indivíduos não infectados pelo T. cruzi. Foram incluídos 30 pacientes indeterminados; 31 cardíacos A; 14 cardíacos C, 11 cardíacos D e 29 indivíduos não infectados...

Entre as citocinas pró-inflamatórias, o IFN- apresentou maior concentração sérica em relação às citocinas IL-12 e TNF- . Os cardíacos no estágio A apresentaram maiores concentrações de TNF- , entretanto houve uma queda significativa nas concentrações desta citocina à medida que observamos os estágios mais avançados da CCC. Tanto os indeterminados quanto os cardíacos apresentaram altos níveis de TFN- e IFN- e baixos níveis de IL-4 e IL-10, demonstrando um perfil predominante de Th1, com uma resposta imune não balanceada. Este estudo demonstrou uma proporcionalidade direta nas concentrações das citocinas pró-inflamatórias e antiinflamatórias em relação à FEVE, em todos os grupos de pacientes estudados, sugerindo que essa correlação poderia ser utilizada como um possível marcador de evolução para a CCC...