Identifying chronic thromboembolic pulmonary hypertension through the French national hospital discharge database.

Chronic thromboembolic pulmonary hypertension (CTEPH), a rare pulmonary vascular disease, is often misdiagnosed due to nonspecific symptoms. The objective of the study was to develop, refine and validate a case ascertainment algorithm to identify CTEPH patients within the French exhaustive hospital discharge database (PMSI), and to use it to estimate the annual number of hospitalized patients with CTEPH in France in 2015, as a proxy for disease prevalence. As ICD-10 coding specifically for CTEPH was not available at the time of the study, a case ascertainment algorithm was developed in close collaboration with an expert committee, using a two-step process (refinement and validation), based on matched data from PMSI and hospital medical records from 2 centres. The best-performing algorithm (specificity 95%, sensitivity 70%) consisted of ≥1 pulmonary hypertension (PH) diagnosis during 2015 and any of the following criteria over 2009-2015: (i) CTEPH interventional procedure, (ii) admission for PH and pulmonary embolism (PE), (iii) PE followed by hospitalization in competence centre then in reference centre, (iv) history of PE and right heart catheterization. Patients with conditions suggestive of pulmonary arterial hypertension were excluded. A total of 3,138 patients hospitalized for CTEPH was estimated for 2015 (47 cases/million, range 43 to 50 cases/million). Assuming that patients are hospitalized at least once a year, the present study provides an estimate of the minimal prevalence of CTEPH and confirms the heavy burden of this disease.

Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq.

A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the space flight environment has never been accomplished because of significant technological and logistical hurdles. Moreover, the effects of space flight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared with identical ground control cultures. Global microarray and proteomic analyses revealed that 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground-based microgravity culture model. Space flight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during space flight missions and provide novel therapeutic options on Earth.