Cost-effectiveness of transcatheter aortic valve implantation in patients with severe symptomatic aortic stenosis of intermediate surgical risk in Singapore.

OBJECTIVE: The objective was to assess the cost-effectiveness of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis with intermediate surgical risk in Singapore. METHODS: A de novo Markov model with three health states - stroke with long-term sequelae, no stroke, and death - was developed and simulated using Monte Carlo simulations with 10,000 iterations over a five-year time horizon from the Singapore healthcare system perspective. A 3% annual discount rate for costs and outcomes and monthly cycle lengths were used. By applying the longest available published clinical evidence, simulated patients received either TAVI or surgical aortic valve replacement (SAVR) and were at risk of adverse events (AEs) such as moderate-to-severe paravalvular aortic regurgitation (PAR). RESULTS: When five-year PARTNER 2A data was applied, base-case analyses showed that the incremental cost-effectiveness ratio (ICER) for TAVI compared to SAVR was US$315,760 per quality-adjusted life year (QALY) gained. The high ICER was due to high incremental implantation and procedure costs of TAVI compared to SAVR, and marginal improvement of 0.10 QALYs as simulated mortality of TAVI exceeded SAVR at 3.75 years post-implantation. One-way sensitivity analysis showed that the ICERs were most sensitive to cost of PAR, utility values of SAVR patients, and cost of TAVI and SAVR implants and procedures. When disutilities for AEs were additionally applied, the ICER decreased to US$300,070 per QALY gained. TAVI was dominated by SAVR when the time horizon increased to 20 years. Clinical outcomes projected from one-year PARTNER S3i data further reduced the ICER to US$86,337 per QALY gained for TAVI, assuming early all-cause mortality benefits from TAVI continued to persist. This assumption was undermined when longer term data showed that TAVI's early mortality benefits diminished at five years. LIMITATIONS AND CONCLUSION: TAVI is unlikely to be cost-effective in intermediate surgical-risk patients compared to SAVR in Singapore.

Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms.

Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases.