Background: There are few contemporary cohorts of Trypanosoma cruzi -seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. Methods: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi -seropositive blood donors. T. cruzi -seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, electrocardiogram, and echocardiogram at enrollment (2008 to 2010) and at follow-up (2018 to 2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% and/or QRS complex duration ≥ 120 ms. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. Results: We enrolled 499 T. cruzi -seropositive donors (age 48 ± 10 years, 52% male), 488 T. cruzi -seronegative donors (age 49 ± 10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48 ± 8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000py (17/114, 15%) in T. cruzi -seropositives with cardiomyopathy at baseline. Among T. cruzi -seropositive donors without cardiomyopathy at baseline mortality was 3.7 events/1000py (15/385, 4%), which was no different from T. cruzi -seronegative donors with 3.6 deaths/1000py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi -seropositive donors was 13.8 (95% CI 9.5-19.6) events/1000py (32/262, 12%) compared with 4.6 (95% CI 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI 3.6 - 15.0) events/1000py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted OR of 1.4, 95% CI 1.1-1.8). Conclusions: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti- T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.
Background: The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. We therefore sought to evaluate the effectiveness of a C-reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients. Methods: A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to (i) intervention to receive antibiotics guided by daily monitoring of CRP levels and (ii) control to receive antibiotics according to the best practices for rational use of antibiotics. Results: One hundred thirty patients were included in the CRP (n = 64) and control (n = 66) groups. In the intention-to-treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0-8.8) days in the CRP and 7.0 (7.0-11.3) days in the control (p = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group only for the index infection episode (p = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0-8.0) days for the CRP and 7.0 (7.0-10.0) days for the control (p = 0.011) groups. There was no between-group difference regarding the total days of antibiotic exposure and antibiotic-free days.
Background Left ventricular systolic dysfunction (LVSD) in Chagas disease (ChD) is relatively common and its treatment using low-cost drugs can improve symptoms and reduce mortality. Recently, an artificial intelligence (AI)-enabled ECG algorithm showed excellent accuracy to detect LVSD in a general population, but its accuracy in ChD has not been tested. Objective To analyze the ability of AI to recognize LVSD in patients with ChD, defined as a left ventricular ejection fraction determined by the Echocardiogram ≤ 40%. Methodology/principal findings This is a cross-sectional study of ECG obtained from a large cohort of patients with ChD named São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) Study. The digital ECGs of the participants were submitted to the analysis of the trained machine to detect LVSD. The diagnostic performance of the AI-enabled ECG to detect LVSD was tested using an echocardiogram as the gold standard to detect LVSD, defined as an ejection fraction <40%. The model was enriched with NT-proBNP plasma levels, male sex, and QRS ≥ 120ms. Among the 1,304 participants of this study, 67% were women, median age of 60; there were 93 (7.1%) individuals with LVSD. Most patients had major ECG abnormalities (59.5%). The AI algorithm identified LVSD among ChD patients with an odds ratio of 63.3 (95% CI 32.3–128.9), a sensitivity of 73%, a specificity of 83%, an overall accuracy of 83%, and a negative predictive value of 97%; the AUC was 0.839. The model adjusted for the male sex and QRS ≥ 120ms improved the AUC to 0.859. The model adjusted for the male sex and elevated NT-proBNP had a higher accuracy of 0.89 and an AUC of 0.874. Conclusion The AI analysis of the ECG of Chagas disease patients can be transformed into a powerful tool for the recognition of LVSD.
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