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.).

Psychological stress and cardiovascular risk among women in Brazilian communities: a cross-sectional study.

Psychosocial evaluations are rarely conducted with community-dwelling individuals, especially those with higher risk of cardiovascular disease. This study aims to evaluate the perceptual stress and cardiovascular risk among women in a large cross-sectional study performed in Brazilian communities. Subjects aged over 18 years were included out of 500 public basic health units (BHU) in Brazil. All subjects were subjected to a clinical consultation and questionnaires application. Data were used to identify healthy lifestyle, smoking status, and self-perception of psychological stress. The National Health and Nutrition Examination Survey (NHANES) risk score (NRS) was used to estimate cardiovascular risk. Ethnicity information was self-reported, considering white versus non-white (black, brown, and mixed-race) women. A total of 93,605 patients were recruited from a primary care setting, of which 62,200 (66.4%) were women. Intense and severe auto-perception of stress was higher within non-white women at home (p < 0.001), at work (p = 0.008), socially (p < 0.001), and financially (p < 0.001) compared to white women. Therefore, the NRS indicates that non-white women had higher cardiovascular risk, lower physical activity, and lower daily vegetables/fruits consumption compared to white women (p < 0.001). Non-white women in Brazilian communities are susceptible to increased stress and cardiovascular disease risk, which adds up to disparities in access to the public health system.

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.

Psychological stress and cardiovascular risk among women in Brazilian communities: a cross-sectional study / Estresse psicológico e risco cardiovascular de mulheres em comunidades brasileiras: um estudo transversal / Estrés psicológico y riesgo cardiovascular entre mujeres en comunidades brasileñas: un estudio transversal

Abstract: Psychosocial evaluations are rarely conducted with community-dwelling individuals, especially those with higher risk of cardiovascular disease. This study aims to evaluate the perceptual stress and cardiovascular risk among women in a large cross-sectional study performed in Brazilian communities. Subjects aged over 18 years were included out of 500 public basic health units (BHU) in Brazil. All subjects were subjected to a clinical consultation and questionnaires application. Data were used to identify healthy lifestyle, smoking status, and self-perception of psychological stress. The National Health and Nutrition Examination Survey (NHANES) risk score (NRS) was used to estimate cardiovascular risk. Ethnicity information was self-reported, considering white versus non-white (black, brown, and mixed-race) women. A total of 93,605 patients were recruited from a primary care setting, of which 62,200 (66.4%) were women. Intense and severe auto-perception of stress was higher within non-white women at home (p < 0.001), at work (p = 0.008), socially (p < 0.001), and financially (p < 0.001) compared to white women. Therefore, the NRS indicates that non-white women had higher cardiovascular risk, lower physical activity, and lower daily vegetables/fruits consumption compared to white women (p < 0.001). Non-white women in Brazilian communities are susceptible to increased stress and cardiovascular disease risk, which adds up to disparities in access to the public health system.

Resumo: Avaliações psicossociais raramente são realizadas com indivíduos residentes na comunidade, especialmente aqueles com maior risco de doença cardiovascular. Este estudo tem como objetivo avaliar o estresse perceptivo e o risco cardiovascular entre mulheres em um grande estudo transversal realizado em comunidades brasileiras. Foram incluídas mulheres com idade superior a 18 anos de 500 unidades básicas de saúde (UBS) públicas do Brasil. Todas as participantes foram submetidas a consulta clínica e aplicação de questionários. Os dados foram utilizados para identificar estilo de vida saudável, tabagismo e autopercepção de estresse psicológico. O índice de risco (NRS) do National Health and Nutrition Examination Survey (NHANES) foi utilizado para estimar o risco cardiovascular. As informações de etnia foram autorreferidas, considerando mulheres brancas versus não brancas (negras, pardas e pardas). Um total de 93.605 pacientes foram recrutados em um ambiente de atenção primária, dos quais 62.200 (66,4%) eram mulheres. A autopercepção intensa e grave de estresse foi maior em mulheres não brancas em casa (p < 0,001), no trabalho (p = 0,008), socialmente (p < 0,001) e financeiramente (p < 0,001) em comparação com mulheres brancas. Portanto, a NRS indica que as mulheres não brancas apresentaram maior risco cardiovascular, menor atividade física e menor consumo diário de vegetais/frutas em comparação às mulheres brancas (p < 0,001). As mulheres não brancas nas comunidades brasileiras são suscetíveis ao aumento do estresse e do risco de doenças cardiovasculares, o que aumenta as disparidades no acesso ao sistema público de saúde.

Resumen: Raramente se realizan evaluaciones psicosociales con personas que viven en la comunidad, especialmente aquellas con mayor riesgo de enfermedad cardiovascular. Este estudio tiene como objetivo evaluar el estrés perceptivo y el riesgo cardiovascular entre las mujeres en un gran estudio transversal realizado en comunidades brasileñas. Se incluyeron mujeres mayores de 18 años de 500 unidades básicas de salud (UBS) públicas de Brasil. Todas las participantes fueron sometidas a una consulta clínica y aplicación de cuestionarios. Los datos se utilizaron para identificar el estilo de vida saludable, el tabaquismo y la autopercepción del estrés psicológico. Se utilizó la puntuación de riesgo (NRS) de la Encuesta Nacional de Examen de Salud y Nutrición (NHANES) para estimar el riesgo cardiovascular. La información étnica fue autoinformada, considerando mujeres blancas versus no blancas (negras, marrones y mestizas). Se reclutó a un total de 93.605 pacientes en un entorno de atención primaria, de los cuales 62.200 (66,4%) eran mujeres. La autopercepción intensa y severa del estrés fue mayor entre las mujeres no blancas en el hogar (p < 0,001), en el trabajo (p = 0,008), socialmente (p < 0,001) y financieramente (p < 0,001) en comparación con las mujeres blancas. Por lo tanto, el NRS indica que las mujeres no blancas tenían mayor riesgo cardiovascular, menor actividad física y menor consumo diario de verduras y frutas en comparación con las mujeres blancas (p < 0,001). Las mujeres no blancas en las comunidades brasileñas son susceptibles a un mayor estrés y riesgo de enfermedades cardiovasculares, lo que se suma a las disparidades en el acceso al sistema de salud pública.

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.

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.

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.

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

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.