Cost-effectiveness analysis of 3D versus 2D transesophageal echocardiography for the evaluation of patients with primary mitral regurgitation with indication of surgical treatment

OBJECTIVES: To perform the cost-effectiveness analysis of three-dimensional transesophageal echocardiography (3DTEE) in comparison to two-dimensional transesophageal echocardiography (2DTEE) for the anatomic-functional evaluation and surgical planning of severe primary mitral regurgitation. METHODS: a complete economic study was based on a systematic review of 3DTEE and 2DTEE accuracy and private health system costs of two different surgical interventions: mitral valve plasty and mitral valve replacement. The prevalence of common postoperative complications was also predicted for elective procedures: atrial fibrillation (8.6%); acute myocardial infarction (1.4%); thrombosis (3.5%); bleeding (1.5%); endocarditis (6.3%). The decision tree method was adopted as a data analysis model. The Bayes" theorem was used based on sensitivity and specificity measurements. The costs, considering literature and professional tables, were: 3DTEE = US$ 349; 2DTEE = US$ 204; diagnostic evaluation = US$ 597; surgical procedure = US$ 3,643; surgical treatment = US$ 374. RESULTS: The deterministic analysis of the diagnostic test shows that 3DTEE (non-dominated) is superior to 2DTEE (absolutely dominated). The 3DTEE presents a cost reduction of US$ 1,147 and incremental effectiveness (true identification) of 22% when compared to 2DTEE. The multivariate probabilistic sensitivity analysis showed that after 100,000 iterations, the diagnosis based on the 3DTEE becomes the first choice regardless of the willingness to pay threshold. CONCLUSIONS: 3DTEE was cost-effective compared to 2DTEE. Thus, 3DTEE is a potential device to promote health compared to 2DTEE for surgical planning of severe primary mitral regurgitation. (AU)

Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism.

Progesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As ß-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves ß-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 µM), in the presence or absence of α-tocopherol (40 µM). After 24 or 48 h, membrane integrity and DNA fragmentation were analyzed by flow cytometry. Caspase activity was used to identify the mode of cell death. The involvement of endoplasmic reticulum stress in the action of progesterone was investigated by western blotting. Oxidative stress was measured by 2',7'-dichlorofluorescein diacetate (DCFDA) oxidation. Isolated rat islets were used in similar experiments in order to confirm the effect of progesterone in primary ß-cells. Incubation of RINm5F cells with progesterone increased the number of cells with loss of membrane integrity and DNA fragmentation. Progesterone induced generation of reactive species. Pre-incubation with α-tocopherol attenuated progesterone-induced apoptosis. Western blot analyses revealed increased expression of CREB2 and CHOP in progesterone-treated cells. Progesterone caused apoptotic death of rat islet cells and enhanced generation of reactive species. Our results show that progesterone can be toxic to pancreatic ß-cells through an oxidative-stress-dependent mechanism that induces apoptosis. This effect may contribute to the development of GD during pregnancy, particularly under conditions that require administration of pharmacological doses of this hormone.