Factors associated with unfavourable treatment outcomes among persons with Pulmonary Tuberculosis: a multicentric prospective cohort study from India.

In this prospective cohort of 2,006 individuals with non-MDR tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes.

Comparison of gene set scoring methods for reproducible evaluation of tuberculosis gene signatures.

BACKGROUND: Blood-based transcriptional gene signatures for tuberculosis (TB) have been developed with potential use to diagnose disease. However, an unresolved issue is whether gene set enrichment analysis of the signature transcripts alone is sufficient for prediction and differentiation or whether it is necessary to use the original model created when the signature was derived. Intra-method comparison is complicated by the unavailability of original training data and missing details about the original trained model. To facilitate the utilization of these signatures in TB research, comparisons between gene set scoring methods cross-data validation of original model implementations are needed. METHODS: We compared the performance of 19 TB gene signatures across 24 transcriptomic datasets using both rrebuilt original models and gene set scoring methods. Existing gene set scoring methods, including ssGSEA, GSVA, PLAGE, Singscore, and Zscore, were used as alternative approaches to obtain the profile scores. The area under the ROC curve (AUC) value was computed to measure performance. Correlation analysis and Wilcoxon paired tests were used to compare the performance of enrichment methods with the original models. RESULTS: For many signatures, the predictions from gene set scoring methods were highly correlated and statistically equivalent to the results given by the original models. In some cases, PLAGE outperformed the original models when considering signatures' weighted mean AUC values and the AUC results within individual studies. CONCLUSION: Gene set enrichment scoring of existing gene sets can distinguish patients with active TB disease from other clinical conditions with equivalent or improved accuracy compared to the original methods and models. These data justify using gene set scoring methods of published TB gene signatures for predicting TB risk and treatment outcomes, especially when original models are difficult to apply or implement.

Improving Clinician Awareness of and Screening for Chagas Disease with an Educational Intervention.

Chagas disease is an underrecognized, chronic, and potentially life-threatening disease caused by the parasite Trypanosoma cruzi. We aimed to improve awareness and screening for Chagas disease among patients from endemic areas using a large safety-net academic hospital system in the United States. We developed an educational intervention consisting of a case-based didactic session presented to physicians, trainees, and other healthcare providers at conferences across different departments. Performance on a knowledge assessment administered before and after the presentation was analyzed with paired Student's t-test for within-subject difference testing. Institutional testing rates for T. cruzi were evaluated for an equal time period (29 months) before and after the start of the intervention. Testing rates were compared by a Welch's unequal variances t-test and by interrupted time series based on multivariate linear regression. Eleven educational sessions were held over the intervention period, and 103 participants completed the pre- and post-presentation surveys. The mean survey scores were 59.2% before the presentation and 96.6% after presentation (P <0.001). Trypanosoma cruzi testing during the postintervention period was significantly higher than testing during the pre-intervention period (171 patients pre-intervention versus 378 patients postintervention [P = 0.015]). Notable increases in testing from the pre-intervention to postintervention periods occurred among midwives (1-68 patients tested) and trainees (57-133 patients tested). Overall, 56/537 (10.4%) nonduplicate T. cruzi commercial screening tests were positive. Testing increased over time, both at an institutional level and within targeted departments. In addition to the educational program, other factors likely influenced expanded testing.

Chagas cardiomyopathy in Boston, Massachusetts: Identifying disease and improving management after community and hospital-based screening.

BACKGROUND: Limited data exist regarding cardiac manifestations of Chagas disease in migrants living in non-endemic regions. METHODS: A retrospective cohort analysis of 109 patients with Chagas disease seen at Boston Medical Center (BMC) between January 2016 and January 2023 was performed. Patients were identified by screening and testing migrants from endemic regions at a community health center and BMC. Demographic, laboratory, and cardiac evaluation data were collected. RESULTS: Mean age of the 109 patients was 43 years (range 19-76); 61% were female. 79% (86/109) were diagnosed with Chagas disease via screening and 21% (23/109) were tested given symptoms or electrocardiogram abnormalities. Common symptoms included palpitations (25%, 27/109) and chest pain (17%, 18/109); 52% (57/109) were asymptomatic. Right bundle branch block (19%, 19/102), T-wave changes (18%, 18/102), and left anterior fascicular block (11%, 11/102) were the most common electrocardiogram abnormalities; 51% (52/102) had normal electrocardiograms. Cardiomyopathy stage was ascertained in 94 of 109 patients: 51% (48/94) were indeterminate stage A and 49% (46/94) had cardiac structural disease (stages B1-D). Clinical findings that required clinical intervention or change in management were found in 23% (25/109), and included cardiomyopathy, apical hypokinesis/aneurysm, stroke, atrial or ventricular arrhythmias, and apical thrombus. CONCLUSIONS: These data show high rates of cardiac complications in a cohort of migrants living with Chagas disease in a non-endemic setting. We demonstrate that Chagas disease diagnosis prompts cardiac evaluation which often identifies actionable cardiac disease and provides opportunities for prevention and treatment.