Biomarker signatures of sickle cell disease severity.

Identifying sickle cell disease patients at high risk of complications could lead to personalized treatment and better prognosis but despite many advances prediction of the clinical course of these patients remains elusive. We propose a system-type approach to discover profiles of multiple, common biomarkers that correlate with morbidity and mortality in sickle cell disease. We used cluster analysis to discover 17 signatures of 17 common circulating biomarkers in 2320 participants of the Cooperative Study of Sickle Cell Disease, and evaluated the association of these signatures with risk for stroke, pain, leg ulceration, acute chest syndrome, avascular necrosis, seizure, death, and trend of fetal hemoglobin and hemolysis using longitudinally collected data. The analysis shows that some of the signatures are associated with reduced risk for complications, while others are associated with increased risk for complications. We also show that these signatures repeat in two more contemporary studies of sickle cell disease and correlate with recently discovered biomarkers of pulmonary vascular disease. With replication and further study, these biomarker signatures could become an important and affordable precision medicine tool to aid treatment and management of the disease.

Predictors of delayed care seeking for tuberculosis in southern India: an observational study.

BACKGROUND: Reducing delay to accessing care is necessary to reduce the Tuberculosis (TB) burden in high incidence countries such as India. This study aimed to identify factors associated with delays in seeking care for TB in Southern India. METHODS: We analyzed data from newly diagnosed, smear-positive, culture-confirmed, pulmonary TB patients in the Regional Prospective Observational Research for TB (RePORT) cohort in Puducherry and Tamil Nadu, India. Data were collected on demographic characteristics, symptom duration, and TB knowledge, among other factors. Delay was defined as cough ≥4 weeks before treatment initiation. Risky alcohol use was defined by the AUDIT-C score which incorporates information about regular alcohol use and binge drinking. TB knowledge was assessed by knowing transmission mode or potential curability. RESULTS: Of 501 TB patients, 369 (73.7%) subjects delayed seeking care. In multivariable analysis, risky alcohol use was significantly associated with delay (aOR 2.20, 95% CI: 1.31, 3.68). Delay was less likely in lower versus higher income groups (<3000 versus >10,000 rupees/month, aOR 0.31, 95% CI: 0.12, 0.78). TB knowledge was not significantly associated with delay. CONCLUSIONS: Local TB programs should consider that risky alcohol users may delay seeking care for TB. Further studies will be needed to determine why patients with higher income delay in seeking care.