Effect of an exercise-based cardiac rehabilitation program on quality of life of patients with chronic Chagas cardiomyopathy: results from the PEACH randomized clinical trial.

To investigate the effect of an exercise-based cardiac rehabilitation program on the quality of life (QoL) of patients with chronic Chagas cardiomyopathy (CCC). PEACH study was a single-center, superiority randomized clinical trial of exercise training versus no exercise (control). The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction < 45%, without or with HF symptoms (CCC stages B2 or C, respectively). QoL was assessed at baseline, after three months, and at the end of six months of follow-up using the SF-36 questionnaire. Patients randomized for the exercise group (n = 15) performed exercise training (aerobic, strength and stretching exercises) for 60 min, three times a week, during six months. Patients in the control group (n = 15) were not provided with a formal exercise prescription. Both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of exercise training on QoL, considering the interaction term (group × time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using linear mixed models. Models were fitted adjusting for each respective baseline QoL value. There were significant improvements in physical functioning (ß = + 10.7; p = 0.02), role limitations due to physical problems (ß = + 25.0; p = 0.01), and social functioning (ß = + 19.2; p < 0.01) scales during the first three months in the exercise compared to the control group. No significant differences were observed between groups after six months. Exercise-based cardiac rehabilitation provided short-term improvements in the physical and mental aspects of QoL of patients with CCC.Trial registration: ClinicalTrials.gov Identifier: NCT02517632; August 7, 2015.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

The association between variables of cardiopulmonary exercise test and quality of life in patients with chronic Chagas cardiomyopathy (Insights from the PEACH STUDY).

Studies investigating the association between functional capacity and quality of life (QoL) in individuals with chronic Chagas cardiomyopathy (CCC) usually do not include a gold-standard evaluation of functional capacity, limiting the validity and the interpretation of the results. The present study is a cross-section analysis aiming to evaluate the association between functional capacity (quantified by cardiopulmonary exercise test [CPET]) and QoL in individuals with CCC. QoL was assessed using the SF-36 questionnaire. Sociodemographic, anthropometric, clinical, cardiac function and maximal progressive CPET variables were obtained from PEACH study. Generalized linear models adjusted for age, sex, and left ventricular ejection fraction were performed to evaluate the association between CPET variables and QoL. After adjustments, VO2 peak and VO2 AT were both associated with physical functioning (ß = +0.05 and ß = +0.05, respectively) and physical component summary (ß = +0.03 and ß = +0.03, respectively). Double product was associated with physical functioning (ß = +0.003), general health perceptions (ß = +0.003), physical component summary (ß = +0.002), and vitality (ß = +0.004). HRR≤12bpm was associated with physical functioning (ß = -0.32), role limitations due to physical problems (ß = -0.87), bodily pain (ß = -0.26), physical component summary (ß = -0.21), vitality (ß = -0.38), and mental health (ß = -0.19). VE/VCO2 slope presented association with all mental scales of SF-36: vitality (ß = -0.028), social functioning (ß = -0.024), role limitations due to emotional problems (ß = -0.06), mental health (ß = -0.04), and mental component summary (ß = -0.02). The associations between CPET variables and QoL demonstrate the importance of CPET inclusion for a more comprehensive evaluation of individuals with CCC. In this setting, intervention strategies aiming to improve functional capacity may also promote additional benefits on QoL and should be incorporated as a treatment strategy for patients with CCC.

Cost-effectiveness of an exercise-based cardiovascular rehabilitation program in patients with chronic Chagas cardiomyopathy in Brazil: An analysis from the PEACH study.

OBJECTIVES: The present study aimed to perform a cost-effectiveness analysis of an exercise-based cardiovascular rehabilitation (CR) program in patients with chronic Chagas cardiomyopathy (CCC). METHODS: Cost-effectiveness analysis alongside a randomised clinical trial evaluating the effects of a 6-month exercise-based CR program. The intervention group underwent 3 weekly exercise sessions. The variation of peak oxygen consumption (VO2peak ) was used as a measurement of clinical outcome. Cost information from all healthcare expenses (examinations, healthcare visits, medication and hospitalisation) were obtained from the medical records in Brazilian reais (R$) and transformed into dollars using the purchasing power parity ($PPP). The longitudinal costs variation was evaluated through linear mixed models, represented by ß coefficient, adjusted for the baseline values of the dependent variable. The cost-effectiveness evaluation was determined through an incremental cost-effectiveness ratio using the HEABS package (Stata 15.0). RESULTS: The intervention group presented higher costs with healthcare visits (ß = +3317.3; p < 0.001), hospitalisation (ß = +2810.4; p = 0.02) and total cost (ß = +6407.9; p < 0.001) after 3 months of follow-up. Costs related to healthcare visits (ß = +2455.8; p < 0.001) and total cost (ß = +4711.4; p < 0.001) remained higher in the intervention group after 6 months. The CR program showed an incremental cost-effectiveness ratio (ICER) of $PPP 1874.3 for each increase of 1.0 ml kg-1  min-1 of VO2peak . CONCLUSIONS: The CR program can be considered a cost-effective alternative and should be included as an intervention strategy in the care of patients with CCC.

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience.

BACKGROUND: We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. METHODS: This was an observational retrospective study with clinical data retrieved from medical records. RESULTS: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. CONCLUSIONS: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Gene expression profile of Mycobacterium leprae contribution in the pathology of leprosy neuropathy

Peripheral neuropathy is the main cause of physical disability in leprosy patients.Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience

ABSTRACT Background We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. Methods: This was an observational retrospective study with clinical data retrieved from medical records. Results: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. Conclusions: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges.

Covid-19 is a novel infectious disease whose spectrum of presentation ranges from absence of symptoms to widespread interstitial pneumonia associated with severe acute respiratory syndrome (SARS), leading to significant mortality. Given the systemic pattern of Covid-19, there are many factors that can influence patient's functional capacity after acute infection and the identification of such factors can contribute to the development of specific rehabilitation strategies. Pulmonary impairment is the primary cause of hospitalization due to Covid-19, and can progress to SARS as well as increase length of hospitalization. Moreover, cardiac involvement is observed in approximately 30% of hospitalized patients, with an increased risk of acute myocarditis, myocardial injury, and heart failure, which may compromise functional capacity in the long-term. Thromboembolic complications have also been reported in some patients with Covid-19 and are associated with a poor prognosis. Musculoskeletal complications may result from long periods of hospitalization and immobility, and can include fatigue, muscle weakness and polyneuropathy. Studies that address the functional capacity of patients after Covid-19 infection are still scarce. However, based on knowledge from the multiple systemic complications associated with Covid-19, it is reasonable to suggest that most patients, especially those who underwent prolonged hospitalization, will need a multiprofessional rehabilitation program. Further studies are needed to evaluate the functional impact and the rehabilitation strategies for patients affected by Covid-19.

Exercise training improves microvascular function in patients with Chagas heart disease: Data from the PEACH study.

BACKGROUND: Chagas heart disease (CHD) impairs the systemic microvascular function. We investigated the effects of exercise training on cutaneous microvascular function among patients with CHD. METHODS: Patients from the PEACH study were randomly assigned to a supervised exercise training 3 times/week for 6 months (Trained; n = 10) or a control group (Untrained; n = 8). Both groups underwent evaluation of microvascular function before, and at 3- and 6-months of follow-up. Cutaneous vascular conductance (CVC) was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh), sodium nitroprusside (SNP) and during post-occlusive reactive hyperemia (PORH). RESULTS: At 3-months of follow-up, no difference was detected between groups in CVC responses to ACh (p = 0.50), SNP (p = 0.26) and HRPO (p = 0.65). However, at 6-months of follow-up, trained vs. untrained patients improved CVC induced by SNP-iontophoresis (0.19 ± 0.10 vs. 0.14 ± 0.15 APU.mmHg-1; p = 0.05) and PORH (0.63 ± 0.15 vs. 0.48 ± 0.18 APU.mmHg-1; p = 0.05). CVC response to ACh-iontophoresis was similar between groups (0.19 ± 0.11 vs. 0.22 ± 0.17 APU.mmHg-1; p = 0.38). CONCLUSION: Exercise training performed during 6 months improved the cutaneous microvascular function of CHD patients. Further studies evaluating the mechanism involved in this response are warranted.

Factors related to the discontinuation and mortality rates of a cardiac rehabilitation programme in patients with Chagas disease: a 6-year experience in a Brazilian tertiary centre.

OBJECTIVES: To describe the clinical and sociodemographic characteristics of participants as well as discontinuation and mortality rates in a cardiac rehabilitation programme (CRP) tailored to Chagas disease (CD). METHODS: Participants underwent functional capacity, anthropometry and cardiac function evaluations before beginning a CRP. Univariate and multivariate Cox proportional hazards models were performed to investigate the associations between clinical and sociodemographic characteristics at baseline with discontinuation rates and deaths. RESULTS: Forty-two patients were enrolled in the CRP (61.9% men, mean age of 58.1 ± 11.8 years). During a median follow-up period of 10.8 months, 74% discontinued and 14% died while enrolled in CRP. 34% of the patients who discontinued CRP died during follow-up. White race (HR = 0.09; 95% CI 0.01-1.00), right ventricular systolic dysfunction (HR = 10.54; 95% CI 1.24-89.50) and oxygen pulse (HR = 0.69; 95% CI 0.48-0.99) were independently associated with death while enrolled in CRP. Married status (HR = 0.44; 95% CI 0.21-0.95) was independently associated with discontinuation rates from CRP. VO2 peak (HR = 0.85; 95% CI 0.74-0.98) and CRP discontinuation due to CD-related reasons (HR = 8.33; 95% CI 1.91-36.27) were the variables independently associated with death after discontinuation of CRP. CONCLUSION: In this population, sociodemographic aspects and severity of CD were important determinants of CRP discontinuation and mortality.

OBJECTIFS: Décrire les caractéristiques cliniques et sociodémographiques des participants ainsi que les taux d'abandon et de décès dans un programme de réadaptation cardiaque (PRC) adapté à la maladie de Chagas (MC). MÉTHODES: Les participants ont subi des évaluations de la capacité fonctionnelle, de l'anthropométrie et de la fonction cardiaque avant de commencer un PRC. Des modèles de risques proportionnels de Cox univariés et multivariés ont été appliqués pour étudier les associations entre les caractéristiques cliniques et sociodémographiques au départ avec les taux d'abandon et les décès. RÉSULTATS: 42 patients ont été enrôlés dans le PRC (61,9% d'hommes, âge moyen de 58,1 ± 11,8 ans). Au cours d'une période médiane de suivi de 10,8 mois, 74% ont abandonné et 14% sont décédés durant leur enrôlement au PRC. 34% des patients qui ont arrêté le PRC sont décédés au cours du suivi. La race blanche (HR = 0,09; IC95%: 0,01-1,00), le dysfonctionnement systolique ventriculaire droite (HR = 10,54; IC95%: 1,24-89,50) et le pouls d'oxygène (HR = 0,69; IC95%: 0,48-0,99) étaient indépendamment associés avec le décès lors de l'enrôlement au PRC. Le statut marié (HR = 0,44; IC95%: 0,21-0,95) était indépendamment associé aux taux d'abandon de la CRP. Le pic de VO2 (HR = 0,85; IC95%: 0,74-0,98) et l'arrêt du PRC pour des raisons liées à la MC (HR = 8,33; IC95%: 1,91 à 36,27) étaient les variables indépendamment associées au décès après l'arrêt du PRC. CONCLUSION: Dans cette population, les aspects sociodémographiques et la sévérité de la MC étaient des déterminants importants de l'arrêt du PRC et du décès.

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges

Abstract Covid-19 is a novel infectious disease whose spectrum of presentation ranges from absence of symptoms to widespread interstitial pneumonia associated with severe acute respiratory syndrome (SARS), leading to significant mortality. Given the systemic pattern of Covid-19, there are many factors that can influence patient's functional capacity after acute infection and the identification of such factors can contribute to the development of specific rehabilitation strategies. Pulmonary impairment is the primary cause of hospitalization due to Covid-19, and can progress to SARS as well as increase length of hospitalization. Moreover, cardiac involvement is observed in approximately 30% of hospitalized patients, with an increased risk of acute myocarditis, myocardial injury, and heart failure, which may compromise functional capacity in the long-term. Thromboembolic complications have also been reported in some patients with Covid-19 and are associated with a poor prognosis. Musculoskeletal complications may result from long periods of hospitalization and immobility, and can include fatigue, muscle weakness and polyneuropathy. Studies that address the functional capacity of patients after Covid-19 infection are still scarce. However, based on knowledge from the multiple systemic complications associated with Covid-19, it is reasonable to suggest that most patients, especially those who underwent prolonged hospitalization, will need a multiprofessional rehabilitation program. Further studies are needed to evaluate the functional impact and the rehabilitation strategies for patients affected by Covid-19.

Progression Rate from the Indeterminate Form to the Cardiac Form in Patients with Chronic Chagas Disease: Twenty-Two-Year Follow-Up in a Brazilian Urban Cohort.

Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. METHODS: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. RESULTS: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 4 8 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). CONCLUSION: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.

Adverse drug events and the associated factors in patients with chronic Chagas disease.

INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.