Chagas disease.

Chagas disease persists as a global public health problem due to the high morbidity and mortality burden. Despite the possibility of a cure and advances in transmission control, epidemiological transformations, such as urbanisation and globalisation, and the emerging importance of oral and vertical transmission mean that Chagas disease should be considered an emerging disease, with new cases occurring worldwide. Important barriers to diagnosis, treatment, and care remain, resulting in repressed numbers of reported cases, which in turn leads to inadequate public policies. The validation of new diagnostic tools and treatment options is needed, as existing tools pose serious limitations to access to health care. Integrated models of surveillance, with community and intersectional participation, embedded in the concept of One Health, are essential for control. In addition, mitigation strategies for the main social determinants of health, including difficulties imposed by migration, are important to improve access to comprehensive health care in a globalised scenario.

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

Hospital case fatality and mortality related to Chagas disease in Brazil over two decades.

OBJECTIVE: To analyse hospital case fatality and mortality related to Chagas disease (CD) in Brazil, 2000-2019. METHOD: This is a mixed ecological study with spatial and temporal trends, based on national population data from the Brazilian Ministry of Health - hospital admissions (HA) and death certificates (DC). Records with CD as a primary or secondary cause of death in HA and/or as an underlying or associated cause of death in DC were evaluated. Temporal trends were analysed by Joinpoint regression and the spatial distribution of age- and gender-adjusted rates, spatial moving averages, and standardized morbidity ratios. RESULTS: There were a total of 4,376 HA due to CD resulting in death in Brazil, with a hospital case fatality rate of 0.11/100,000 inhabitants. The Southeast region had the highest rate (63.9%, n = 2,796; 0.17/100,000 inhabitants). The general trend for this indicator in Brazil is upwards (average annual percentage change [AAPC] 7.5; 95% confidence interval [CI] 5.3 to 9.9), with increases in the North, Northeast and Southeast regions. During the same period 122,275 deaths from CD were registered in DC, with a mortality rate of 3.14/100,000 inhabitants. The highest risk of CD-related death was found among men (relative risk [RR] 1.27) and Afro-Brazilians (RR 1.63). There was a downward trend in CD mortality in the country (AAPC - 0.7%, 95%CI -0.9 to -0.5), with an increase in the Northeast region (AAPC 1.1%, 95%CI 0.6 to 1.6). Municipalities with a very high Brazilian Deprivation Index tended to show an increase in mortality (AAPC 2.1%, 95%CI 1.6 to 2.7), while the others showed a decrease. CONCLUSION: Hospital case fatality and mortality due to CD are a relevant public health problem in Brazil. Differences related to gender, ethnicity, and social vulnerability reinforce the need for comprehensive care, and to ensure equity in access to health in the country. Municipalities, states, and regions with indicators that reveal higher morbidity and mortality need to be prioritized.

Cardiac and Liver Fibrosis Assessed by Multiparametric MRI in Patients with Fontan Circulation.

The abnormal hemodynamics in Fontan circulation due to persistently increased systemic venous pressure results in hepatic venous congestion and Fontan-associated liver disease. Combined assessment of cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in this context have not been fully explored. To evaluate cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in patients who have undergone Fontan procedures. Thirty-eight patients and 23 controls underwent cardiac and liver MRI examinations in a 3.0-T scanner. Mann-Whitney, Fisher exact test, and Spearman's correlation were applied to evaluate myocardial volumes, function, native cardiac and liver T1 mapping, ECVs and liver stiffness. The mean native cardiac T1 value (p = 0.018), cardiac ECV (p < 0.001), liver native T1 (p < 0.001), liver ECV (p < 0.001), and liver stiffness (p < 0.001) were higher in patients than controls. The indexed end-diastolic volume (EDVi) correlated with the myocardial ECV (r = 0.356; p = 0.033), native liver T1 (r = 0.571; p < 0.001), and with liver stiffness (r = 0.391; p = 0.015). In addition, liver stiffness correlated with liver ECV (r = 0.361; p = 0.031) and native liver T1 (r = 0.458; p = 0.004). An association between cardiac remodeling and cardiac and liver fibrosis were found in this population. The usefulness of MRI to follow cardiac and liver involvement in these patients is critical to improve treatment strategies and to prevent the need for combined liver and heart transplantation.

Use of PET/CT to detect myocardial inflammation and the risk of malignant arrhythmia in chronic Chagas disease.

BACKGROUND: Chagas heart disease (CHD) is characterized by progressive myocardial inflammation associated with myocardial fibrosis and segmental abnormalities that may lead to malignant ventricular arrhythmia and sudden cardiac death. This arrhythmia might be related to the persistence of parasitemia or inflammation in the myocardium in late-stage CHD. Positron emission tomography/computed tomography (PET/CT) has been used to detect myocardial inflammation in non-ischemic cardiomyopathies, such as sarcoidosis, and might be useful for risk prediction in patients with CHD. METHODS AND RESULTS: Twenty-four outpatients with chronic CHD were enrolled in this prospective cross-sectional study between May 2019 and March 2022. The patients were divided into two groups: those with sustained ventricular tachycardia and/or aborted sudden cardiac death who required implantable cardioverter-defibrillators, and those with the same stages of CHD and no complex ventricular arrhythmia. Patients underwent 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATOC PET/CT, and blood samples were collected for qualitative parasite assessment by polymerase chain reaction. Although similar proportions of patients with and without complex ventricular arrhythmia showed 18F-FDG and 68Ga-DOTATOC uptake, 68Ga-DOTATOC corrected SUVmax was higher in patients with complex arrhythmia (3.4 vs 1.7; P = .046), suggesting that inflammation could be associated with the presence of malignant arrhythmia in the late stages of CHD. We also detected Trypanosoma cruzi in both groups, with a nonsignificant trend of increased parasitemia in the group with malignant arrhythmia (66.7% vs 33.3%). CONCLUSION: 18F-FDG and 68Ga-DOTATOC uptake on PET/CT may be useful for the detection of myocardial inflammation in patients with Chagas cardiomyopathy, and 68Ga-DOTATOC uptake may be associated with the presence of malignant arrhythmia, with potential therapeutic implications.

Autonomic denervation, myocardial hypoperfusion and fibrosis may predict ventricular arrhythmia in the early stages of Chagas cardiomyopathy.

BACKGROUND: Sudden cardiac death (SCD) can be the first clinical event of Chagas heart disease (CHD). However, current guidelines contain no clear recommendation for early cardioverter-defibrillator implantation. Using imaging modalities, we evaluated associations among autonomic denervation, myocardial hypoperfusion, fibrosis and ventricular arrhythmia in CHD. METHODS AND RESULTS: Twenty-nine patients with CHD and preserved left ventricular function underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy, 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion and cardiac magnetic resonance imaging (MRI). They were divided into arrhythmic (≥ 6 ventricular premature complexes/h and/or non-sustained ventricular tachycardia on 24-hour Holter, n = 15) and non-arrhythmic (< 6 ventricular premature complexes/h and no ventricular tachycardia; n = 14) groups. The arrhythmic group had higher denervation scores from MIBG imaging (23.2 ± 18.7 vs 5.6 ± 4.9; P < .01), hypoperfusion scores from MIBI SPECT (4.7 ± 6.8 vs 0.29 ± 0.6: P = .02), innervation/perfusion mismatch scores (18.5 ± 17.5 vs 5.4 ± 4.8; P = .01) and fibrosis by late gadolinium enhancement on MRI (14.3% ± 13.5% vs 4.0% ± 2.9%; P = .04) than the non-arrhythmic group. CONCLUSION: These imaging parameters were associated with ventricular arrhythmia in early CHD and may enable risk stratification and the implementation of primary preventive strategies for SCD.

Imaging Features and Complications of Facial Cosmetic Procedures.

Facial aesthetic procedures have become increasingly popular and complex, making knowledge of facial anatomy crucial for achieving desired outcomes without complications. Some of the most common procedures include blepharoplasty, bichectomy, face-lifts, facial implants, thread lifting, and fillers. Blepharoplasty and bichectomy are surgical procedures that respectively aim to restore youthful contours to the periorbita and create a slimmer lower face by removing Bichat fat from the maxillofacial region. Facial implants are used for aesthetic augmentation of the skeletal structure and restoration of facial contour by using biomaterials or autogenous bone grafts. Face-lift surgeries involve incisions and removal of excess skin, and thread lifts involve less invasive procedures performed by inserting threads beneath the skin, with the aim to lift the skin and thus reduce wrinkles and sagging. Fillers improve wrinkles and loss of facial volume, with biologic types made from animal, human, or bacterial sources (such as hyaluronic acid), while synthetic fillers include substances such as paraffin, silicone, calcium hydroxyapatite, polymethylmethacrylate microspheres, polyacrylamide hydrogel, hydroxyethyl-ethyl methacrylate, and poly-l-lactic acid. Synthetic fillers can be classified as rapidly resorbable (<12 months), slowly resorbable (<24 months), or permanent. Imaging modalities such as US, CT, and MRI can help identify and analyze each type of facial aesthetic procedure or filler, as well as their possible complications such as foreign-body granuloma, noninflammatory nodule, late intermittent persistent edema, filler migration, infection, or complications after removal of the buccal fat pad. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center The online slide presentation from the RSNA Annual Meeting is available for this article.

Discontinuing vs continuing ACEIs and ARBs in hospitalized patients with COVID-19 according to disease severity: Insights from the BRACE CORONA trial.

BACKGROUND: We explored the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with COVID-19 according to baseline disease severity. METHODS: We randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity. RESULTS: At presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 [SD 6.3] days) and continuation (mean 23.8 [SD 6.5] days), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 [SD 9.5] days) than continuation (mean 21.6 [SD 7.6] days), with a mean ratio of 0.90 (95% CI 0.81-1.00; P-interaction = .01). The impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity. CONCLUSIONS: Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04364893).

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.

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.

Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. Design, Setting, and Participants: A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Interventions: Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. Results: Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). Conclusions and Relevance: Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04364893.

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.

A cardiac rehabilitation exercise program potentially inhibits progressive inflammation in patients with severe Chagas cardiomyopathy: A pilot single-arm clinical trial.

BACKGROUND: Cardiac rehabilitation exerts anti-inflammatory effect on several cardiovascular diseases; however, these effects were not described for Chagas cardiomyopathy, which is associated with pro-inflammatory imbalance. MATERIALS AND METHODS: Ten patients with severe Chagas cardiomyopathy performed 8 months of exercise training in a cardiac rehabilitation program. Interleukin-1 beta (IL-1ß), IL-8, IL-10, interferon gamma (IF-γ), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) serum levels were measured using enzyme-linked immunosorbent assay at baseline, 4, and 8 months. The influence of exercise on cytokine levels was evaluated using the one-way analysis of variance for repeated measurements, with Bonferroni posttest for multiple comparisons. RESULTS: Levels of pro-inflammatory (TNF-α, IL-1ß, IL-8, IF-γ, and (MCP-1) and anti-inflammatory (IL-10) cytokines did not vary significantly during the observation period. CONCLUSION: Exercise may benefit patients with severe Chagas cardiomyopathy by curbing the production of pro-inflammatory cytokines in this disease characterized by a continuous state of inflammation.

Benznidazole treatment safety: the Médecins Sans Frontières experience in a large cohort of Bolivian patients with Chagas' disease.

Background: Up to half of patients with Chagas' disease under benznidazole treatment present adverse drug reactions (ADRs) and up to one-third do not complete standard treatment. Objectives: To verify the incidence and possible factors associated with the suspension of benznidazole treatment in a large cohort of patients. Methods: We included 2075 patients treated with benznidazole during the projects managed by the medical humanitarian organization Doctors Without Borders (Médecins Sans Frontières) in Bolivia from 2009 to 2013. Benznidazole treatment was provided two or three times per day for ∼60 days at 5-7.5 mg/kg/day. A multiple logistic regression model was developed to evaluate the factors associated with permanent suspension of benznidazole treatment. Results: Permanent benznidazole treatment suspension occurred in 211 patients (10.2%) and the average time until permanent treatment suspension was 23 days. Multifactorial analysis revealed that female sex (adjusted OR = 1.70), moderate ADRs (adjusted OR = 10.57), mild ADRs (adjusted OR = 1.69) and skin disorders (adjusted OR = 4.18) were significantly associated with the permanent suspension of benznidazole treatment. Women with mild or moderate skin ADRs presented a probability of treatment interruption of 18.6% and 59.0%, respectively. Conclusions: Benznidazole treatment was safe and a large proportion of patients were able to complete a full course of benznidazole treatment under close treatment surveillance. Female sex, skin disorders and mild and moderate ADRs were independently associated with the permanent suspension of benznidazole treatment. In particular, women with moderate skin ADRs had the highest risk of benznidazole treatment interruption.

A clinical adverse drug reaction prediction model for patients with chagas disease treated with benznidazole.

Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease, and the evidence supporting the benefits of BZN use during the chronic phase of the disease will favor its use in millions of individuals. However, more than 30% of patients treated with BZN may suffer adverse drug reactions (ADRs), and the development of tools to identify those patients at risk is highly desirable. In the present study, we aimed to identify predictive factors for ADRs in Chagas disease patients treated with BZN. Among 195 patients included in the study, 48.7% experienced ADRs and 31.3% had ADRs that caused BZN treatment discontinuation. Overall ADRs and ADRs that caused BZN treatment discontinuation were more common among women and in those who graduated from elementary school. Overall ADRs were also less frequent among black individuals. Based on logistic regression analysis, female sex (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.5 to 5.4), graduation from elementary school (OR, 2.0; 95% CI, 1.1 to 3.8), and white (OR, 5.0; 95% CI, 1.0 to 24.1) and mulatto (OR, 5.6; 95% CI, 1.1 to 28.7) races were considered to predict overall ADRs, and female sex (OR, 2.3; 95% CI, 1.2 to 4.3) was considered to predict ADRs that caused BZN treatment discontinuation. Graduation from elementary school also presented a tendency to predict ADRs that caused BZN treatment discontinuation (OR, 1.8; 95% CI, 0.9 to 3.6). The logistic regression (LR) models to predict ADRs to BZN described in this study may become important tools to minimize ADRs and improve patients' compliance and thus assist physicians treating patients with Chagas disease with BZN.

Finite element analysis of stability and functional stress with implant-supported maxillary obturator prostheses.

STATEMENT OF PROBLEM: Maxillary resections jeopardize the stability and functional stress generated by implanted-supported prostheses. PURPOSE: The purpose of this study was to evaluate the stability and functional stress caused by implanted-supported obturator prostheses in simulated maxillary resections of an edentulous maxilla corresponding to Okay Classes Ib, II, and III, with no surgical reconstruction. MATERIAL AND METHODS: Implants were positioned in the residual maxilla, and bar-clip retention systems were designed for each experimental model. The 3-dimensional models of the maxillary resection and corresponding implanted-supported obturator prosthesis, constructed from a computed tomography scan, were used to develop a finite element mesh. Loads were simultaneously applied to the occlusal (80 N) and anterior (35 N) platforms corresponding to the prosthetic teeth. Qualitative analysis was based on the scale of maximum principal stress; values obtained by means of quantitative analysis were expressed in MPa. RESULTS: The implant-supported obturator prostheses tended to rotate toward the surgical resection, the region with no osseous support. Tensile and compressive stresses in the gingival mucosa and in the cortical bone increased as the osseous support and the numbers of implants and clips diminished. CONCLUSIONS: All evaluated bar-clip retention systems displayed a tendency toward dislodgment of the obturator prosthesis, increasing as the osseous resection area amplified. The osseous tensile and compressive stresses resulting from the bar-clip retention system for Okay Classes Ib, II, and III maxillectomy may not be favorable to the survival rate of implants.

Patient and Family Preferences About Place of End-of-Life Care and Death: An Umbrella Review.

CONTEXT: The place where people are cared towards the end of their life and die is a complex phenomenon, requiring a deeper understanding. Honoring preferences is critical for the delivery of high-quality care. OBJECTIVES: In this umbrella review we examine and synthesize the evidence regarding preferences about place of end-of-life care and death of patients with life-threatening illnesses and their families. METHODS: Following the Joanna Briggs Institute methodology, we conducted a comprehensive search for systematic reviews in PsycINFO, MEDLINE, EMBASE, CINAHL, Epistemonikos, and PROSPERO without language restrictions. RESULTS: The search identified 15 reviews (10 high-quality, three with meta-analysis), covering 229 nonoverlapping primary studies. Home is the most preferred place of end-of-life care for both patients (11%-89%) and family members (23%-84%). It is also the most preferred place of death (patient estimates from two meta-analyses: 51%-55%). Hospitals and hospice/palliative care facilities are preferred by substantial minorities. Reasons and factors affecting preferences include illness-related, individual, and environmental. Differences between preferred places of care and death are underexplored and the evidence remains inconclusive about changes over time. Congruence between preferred and actual place of death ranges 21%-100%, is higher in studies since 2004 and a meta-analysis shows noncancer patients are at higher risk of incongruence than cancer patients (OR 1.23, 95% CI: 1.01-1.49, I2 = 62%). CONCLUSION: These findings are a crucial starting point to address gaps and enhance strategies to align care with patient and family preferences. To accurately identify patient and family preferences is an important opportunity to change their lives positively.

The use of rapid diagnostic tests for chronic Chagas disease: An expert meeting report.

Chagas disease, caused by Trypanosoma cruzi, affects millions of people globally and is associated with significant underdiagnosis and undertreatment. Current diagnostic algorithms face challenges in remote regions. We aimed to review the potential of rapid diagnostic tests (RDTs) for screening or diagnosing chronic Chagas disease in endemic areas. An expert panel representing scientific and academic institutions from the Americas convened with the aim of discussing the use of RDTs. The study employed the nominal group technique, gathering insights from diverse experts during a 3-day meeting. Panel discussions covered RDT application, research protocols, and regulatory mechanisms. The results indicate that RDTs play a crucial role in surveillance and screening, although limitations in sensitivity and specificity exist. The expert group recommends standardized protocols, emphasizes the importance of cost-effectiveness assessments, and highlights the need to consider geographic validation. Despite these challenges, RDTs present a promising avenue for improving Chagas disease diagnosis in resource-limited settings. Future research and a collaborative approach are deemed essential for effective implementation.