Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy.

BACKGROUND: The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven. METHODS: We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event. RESULTS: The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P=0.16 for interaction). CONCLUSIONS: Trypanocidal therapy with benznidazole in patients with established Chagas' cardiomyopathy significantly reduced serum parasite detection but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up. (Funded by the Population Health Research Institute and others; ClinicalTrials.gov number, NCT00123916; Current Controlled Trials number, ISRCTN13967269.).

The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease.

Among the pathophysiological derangements operating in the chronic phase of Chagas disease, parasite persistence is likely to constitute the main mechanism of myocardial injury in patients with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless, inflammatory process and induces myocardial autoimmune injury. These facts suggest that trypanocidal therapy may positively impact the clinical course of patients with chronic Chagas heart disease. However, the experimental and clinical evidence currently available is insufficient to support the routine use of etiologic treatment in these patients. The BENEFIT project--Benznidazole Evaluation for Interrupting Trypanosomiasis--is an international, multicenter, double-blind, placebo-controlled trial of trypanocidal treatment with benznidazole in patients with chronic Chagas heart disease. This project is actually comprised of two studies. The pilot study investigates whether etiologic treatment significantly reduces parasite burden, as assessed by polymerase chain reaction-based techniques and also determines the safety and tolerability profile of the trypanocidal drug in this type of chagasic population. The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease.

Effects of Trypanocidal Treatment on Echocardiographic Parameters in Chagas Cardiomyopathy and Prognostic Value of Wall Motion Score Index: A BENEFIT Trial Echocardiographic Substudy.

BACKGROUND: Serial echocardiographic studies in chronic Chagas cardiomyopathy are scarce. The aims of this study were to evaluate whether therapy with benznidazole modifies the progression of cardiac impairment and to identify baseline echocardiographic parameters related to prognosis. METHODS: A prospective substudy was conducted in 1,508 patients with chronic Chagas cardiomyopathy randomized to benznidazole or placebo, who underwent two-dimensional echocardiography at enrollment, 2 years, and final follow-up (5.4 years). Left ventricular (LV) ejection fraction, LV wall motion score index (WMSI), indexed left atrial volume, and chamber dimensions were collected and correlated to all-cause death and a composite hard outcome using univariate and multivariate analyses. RESULTS: At enrollment, most patients had normal chamber dimensions, and 70.5% had preserved LV ejection fractions. During follow-up, all chamber dimensions increased similarly in both treatment arms. LV ejection fraction was comparably reduced (55.7 ± 12.7% to 52.1 ± 14.6% vs 56.3 ± 12.7% to 52.8 ± 14.1%) and LV WMSI similarly increased (1.31 ± 0.41 to 1.49 ± 0.03 and 1.27 ± 0.38 to 1.51 ± 0.03) for the benznidazole and placebo groups, respectively (P > .05). A higher baseline LV WMSI was identified in subjects who died compared with those alive at final echocardiography (1.76 ± 0.517 vs 1.271 ± 0.393, P < .0001). There was a significant (P < .0001) graded increase in the risk for the composite outcome with worsening LV WMSI (hazard ratios, 2.27 [95% CI, 1.69-3.06] and 6.42 [95% CI, 4.94-8.33]) and also of death (hazard ratios, 2.45 [95% CI, 1.62-3.71] and 8.99 [95% CI, 6.3-12.82]) for 1 < LV WMSI < 1.5 and LV WMSI > 1.5, respectively. Both LV WMSI and indexed left atrial volume remained independent predictors in multivariate analysis. CONCLUSIONS: Trypanocidal treatment had no effect on echocardiographic progression of chronic Chagas cardiomyopathy over 5.4 years. Despite normal global LV systolic function, regional wall motion abnormalities and indexed left atrial volume identified patients at higher risk for hard adverse clinical outcomes.

Prevalence, awareness, treatment and control of hypertension in rural and urban communities in Latin American countries.

OBJECTIVES: The objective is to describe hypertension (HTN) prevalence, awareness, treatment and control in urban and rural communities in Latin America to inform public and policy-makers. METHODS: Cross-sectional analysis from urban (n = 111) and rural (n = 93) communities including 33 276 participants from six Latin American countries (Argentina, Brazil, Chile, Colombia, Peru and Uruguay) were included. HTN was defined as self-reported HTN on blood pressure (BP) medication or average BP over 140/90 mmHg, awareness as self-reported HTN, and controlled as those with BP under 140/90 mmHg. RESULTS: Mean age was 52 years, 60% were Female and 32% belonged to rural communities. HTN prevalence was 44.0%, with the lowest rates in Peru (17.7%) and the highest rates in Brazil (52.5%). 58.9% were aware of HTN diagnosis and 53.3% were receiving treatment. Prevalence of HTN were higher in urban (44.8%) than rural (42.1%) communities in all countries. Most participants who were aware of HTN were receiving medical treatment (90.5%), but only 37.6% of patients receiving medical treatment had their BP controlled (<140/<90 mmHg), with the rates being higher in urban (39.6%) than in rural (32.4%) communities. The rate of use of two or more drugs was low [36.4%, lowest in Argentina (29.6%) and highest in Brazil (44.6%)]. Statin use was low (12.3%), especially in rural areas (7.0%). Most modifiable risk factors were higher in people with HTN than people without HTN. CONCLUSION: HTN prevalence is high but BP control is low in Latin America, with marked differences between countries and between urban and rural settings. There is an urgent need for systematic approaches for better detection, treatment optimization and risk factor modification among those with HTN in Latin America.

Independent predictors of effective blood pressure control in patients with hypertension on drug treatment in Brazil.

Population assessment of effective blood pressure (BP) control is fundamental for reducing the global burden of hypertension, especially in low- and middle-income countries. The authors evaluated the effectiveness of BP control and determined independent predictors associated with effective control among patients with hypertension on drug treatment in a large cross-sectional study performed in two metropolitan areas in Brazil's southeast region. A total of 43 647 patients taking antihypertensive treatment were identified. Less than half of the patients (40.9%) had controlled BP (systolic BP <140 mm Hg and diastolic BP <90 mm Hg). Independent predictors of BP control were age, eating fruit daily, physical activity, previous cardiovascular disease, male sex, diabetes mellitus, ethnicity, and obesity. Simple variables associated with BP control may be utilized for knowledge translation strategies aiming to reduce the burden of hypertension.

Langerhans' cell histiocytosis with neurological injuries diagnosed from a single cutaneous lesion.

Histiocytoses are rare diseases caused by the proliferation of histiocytes. The pathogenesis remains unknown and the highest incidence occurs in pediatric patients. The clinical presentations can be varied, in multiple organs and systems, and the skin lesions are not always present. Evolution is unpredictable and treatment depends on the extent and severity of the disease. It is described the case of a patient with various neurological symptoms, extensively investigated, who had its was diagnosed with histiocytosis from a single skin lesion. This report highlights the importance of Dermatology in assisting the investigation of difficult cases in medical practice.

Paracoccidioidomycosis with sarcoid-like lesions:a diagnostic challenge.

Clinical presentation of paracoccidioidomycosis (PCM) can be diverse. Morphology and quantity of skin lesions depends on interactions between host immunity and fungus virulence. Diagnosis can be a challenge considering that this fungus has low virulence and some individuals have immunity to microorganism, which results in well-marked granulomas without visible microorganisms. We report herein a clinical presentation of sarcoid-like PCM, initially diagnosed as tuberculoid leprosy. This rare type of PCM is often mistaken for other types of chronic granulomatous diseases. Diagnosis was confirmed after 4 years when a special stain analysis helped in the identification of the specific etiologic agent.

Secondary CV Prevention in South America in a Community Setting: The PURE Study.

BACKGROUND: Despite the availability of evidence-based therapies, there is no information on the use of medications for the secondary prevention of cardiovascular disease in urban and rural community settings in South America. OBJECTIVES: This study sought to assess the use, and its predictors, of effective secondary prevention therapies in individuals with a history of coronary heart disease (CHD) or stroke. METHODS: In the PURE (Prospective Urban Rural Epidemiological) study, we enrolled 24,713 individuals from South America ages 35 to 70 years from 97 rural and urban communities in Argentina, Brazil, Chile, and Colombia. We assessed the use of proven therapies with standardized questionnaires. We report estimates of drug use at national, community, and individual levels and the independent predictors of their utilization through a multivariable analysis model. RESULTS: Of 24,713 individuals, 910 had a self-reported CHD event (at a median of 5 years earlier) and 407 had stroke (6 years earlier). The proportions of individuals with CHD who received antiplatelet medications (30.1%), beta-blockers (34.2%), angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers (36.0%), or statins (18.0%) were low; with even lower proportions among stroke patients (antiplatelets 24.3%, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers 37.6%, statins 9.8%). A substantial proportion of patients did not receive any proven therapy (CHD 31%, stroke 54%). A minority of patients received either all 4 (4.1%) or 3 proven therapies (3.3%). Male sex, age >60 years, better education, more wealth, urban location, diabetes, and obesity were associated with higher rates of medication use. In a multivariable model, markers of wealth had the largest impact in secondary prevention. CONCLUSIONS: There are large gaps in the use of proven medications for secondary prevention of cardiovascular disease in South America. Strategies to improve the sustained use of these medications will likely reduce cardiovascular disease burden substantially.

Importance of multidisciplinary approach in diagnosis of histoplasmosis.

A patient with systemic involvement, initially treated as tuberculosis, is presented in this report. There were only two painful subcutaneous nodules, from which we arrived at the correct diagnosis of histoplasmosis. The patient was attended by several experts in the fields of infectious diseases, nephrology and internal medicine, but the diagnosis was only possible after dermatological examination and skin biopsy. This case values multidisciplinary interaction between dermatologists and other medical areas for diagnosis of cases with atypical manifestations.

Paracoccidioidomycosis with sarcoid-like lesions: a diagnostic challenge

Abstract Clinical presentation of paracoccidioidomycosis (PCM) can be diverse. Morphology and quantity of skin lesions depends on interactions between host immunity and fungus virulence. Diagnosis can be a challenge considering that this fungus has low virulence and some individuals have immunity to microorganism, which results in well-marked granulomas without visible microorganisms. We report herein a clinical presentation of sarcoid-like PCM, initially diagnosed as tuberculoid leprosy. This rare type of PCM is often mistaken for other types of chronic granulomatous diseases. Diagnosis was confirmed after 4 years when a special stain analysis helped in the identification of the specific etiologic agent.

Langerhans' cell histiocytosis with neurological injuries diagnosed from a single cutaneous lesion

Abstract: Histiocytoses are rare diseases caused by the proliferation of histiocytes. The pathogenesis remains unknown and the highest incidence occurs in pediatric patients. The clinical presentations can be varied, in multiple organs and systems, and the skin lesions are not always present. Evolution is unpredictable and treatment depends on the extent and severity of the disease. It is described the case of a patient with various neurological symptoms, extensively investigated, who had its was diagnosed with histiocytosis from a single skin lesion. This report highlights the importance of Dermatology in assisting the investigation of difficult cases in medical practice.

Importance of multidisciplinary approach in diagnosis of histoplasmosis

Abstract: A patient with systemic involvement, initially treated as tuberculosis, is presented in this report. There were only two painful subcutaneous nodules, from which we arrived at the correct diagnosis of histoplasmosis. The patient was attended by several experts in the fields of infectious diseases, nephrology and internal medicine, but the diagnosis was only possible after dermatological examination and skin biopsy. This case values multidisciplinary interaction between dermatologists and other medical areas for diagnosis of cases with atypical manifestations.

Padrões de atividade física e dislipidemia entre moradores de áreas urbana e rural no Brasil / Patterns of physical activity and dyslipidemia among residents of urban and rural areas in Brazil

Introdução São escassas as evidências do impacto dos padrões de atividade física (AF) e local de residência (rural e urbano) para a dislipidemia e ao perfil lipídio. Objetivos Avaliar a associação dos padrões de atividade física e local de residência (urbano e rural) com dislipidemia. Associar a correlação do gasto energético estimado em Mets e valores e frações de colesterol e triglicérides. Metodologia Estudo Transversal em coorte prospectiva, com 4551 indivíduos com idade entre 35 e 70 anos de áreas urbana e rural. A AF foi avaliada utilizando o Questionário Internacional de Atividade Física (IPAQ). Foi realizada regressão múltipla para a associação de AF e local de residência com o tipo de dislipidemia. A regressão linear foi realizada para avaliar o efeito da AF e local de residência nos valores e frações de colesterol e triglicérides. Resultados A prevalência de baixa AF no rural foi de 5,1 por cento (mulheres 4,3 por cento e homens 6,0 por cento ), urbano 11,2 por cento (7,9 por cento mulheres e 5,5 por cento homens), p

Introduction There is scarce evidence about the impact of physical activity (PA) and residence area (rural and urban) on dyslipidemia and lipid profile. Objectives To assess the association between patterns of physical activity, residence area (rural or urban) and dyslipidemia. To assess the correlation between energy expenditure in estimated Mets and total cholesterol, HDL, LDL and l triglycerides levels. Methodology A cross sectional evaluation in a prospective cohort with 4551 individuals aged between 35 and 70 years from rural and urban areas. The PA was assessed using the International Physical Activity Questionnaire (IPAQ). Multiple logistic regression was performed to determine the association between PA and residence area and the type of dyslipidemia. Linear regression was used to determine the effect of PA on the cholesterol, HDL, LDL and triglycerides levels. Results The prevalence of low PA in rural individuals was 5.1 per cent (4.3 per cent women and 6.0 per cent men), urban 11.2 per cent (7.9 per cent women and 5.5 per cent men), p

Osteoartopatia hipertrófica pulmonar e mesotelioma pleural maligno / Pulmonary hypertrophic osteoarthropathy and malignant pleural mesothelioma

Apresenta-se um caso raro de osteoartropatia hipertrófica secundária a um mesotelioma pleural maligno difuso tipo misto, com diagnóstico clínico-radiológico inicial de abscesso pulmonar, em uma jovem de 17 anos de idade

Cistos do ducto do tiroglosso com carcinoma papilífero numa índia Txukahamäe / Thyroglossal duct cyst with papillary carcinoma in a Txukahamae indian

Relatamos a ocorrência de cistos do ducto do tiroglosso com carcinoma papilífero numa india Txukahamäe do Parque Nacional do Xingu. A punçäo aspirativa com agulha fina do cisto do ducto do tiroglosso possibilitou o diagnóstico pré-cirúrgico do carcinoma. O exame anatomopatológico do conjunto extraído confirmou cistos do ducto do tiroglosso e carcinoma papilífero.