Cost-effectiveness of TAS-102 plus bevacizumab versus TAS-102 monotherapy in patients with metastatic colorectal cancer.

BACKGROUND: TAS-102 plus bevacizumab is an anticipated combination regimen for patients who have metastatic colorectal cancer. However, evidence supporting its use for this indication is limited. We compared the cost-effectiveness of TAS-102 plus bevacizumab combination therapy with TAS-102 monotherapy for patients with chemorefractory metastatic colorectal cancer. METHOD: Markov decision modeling using treatment costs, disease-free survival, and overall survival was performed to examine the cost-effectiveness of TAS-102 plus bevacizumab combination therapy and TAS-102 monotherapy. The Japanese health care payer's perspective was adopted. The outcomes were modeled on the basis of published literature. The incremental cost-effectiveness ratio (ICER) between the two treatment regimens was the primary outcome. Sensitivity analysis was performed and the effect of uncertainty on the model parameters were investigated. RESULTS: TAS-102 plus bevacizumab had an ICER of $21,534 per quality-adjusted life-year (QALY) gained compared with TAS-102 monotherapy. Sensitivity analysis demonstrated that TAS-102 monotherapy was more cost-effective than TAS-102 and bevacizumab combination therapy at a willingness-to-pay of under $50,000 per QALY gained. CONCLUSIONS: TAS-102 and bevacizumab combination therapy is a cost-effective option for patients who have metastatic colorectal cancer in the Japanese health care system.

Quantitative determination of ion distributions in bacterial lipopolysaccharide membranes by grazing-incidence X-ray fluorescence.

A model of the outer membrane of Gram-negative bacteria was created by the deposition of a monolayer of purified rough mutant lipopolysaccharides at an air/water interface. The density profiles of monovalent (K(+)) and divalent (Ca(2+)) cations normal to the lipopolysaccharides (LPS) monolayers were investigated using grazing-incidence X-ray fluorescence. In the absence of Ca(2+), a K(+) concentration peak was found in the negatively charged LPS headgroup region. With the addition of CaCl(2), Ca(2+) ions almost completely displaced K(+) ions from the headgroup region. By integrating the experimentally reconstructed excess ion density profiles, we obtained an accurate measurement of the effective charge density of LPS monolayers. The experimental findings were compared to the results of Monte Carlo simulations based on a coarse-grained minimal model of LPS molecules and showed excellent agreement.

Crucial roles of charged saccharide moieties in survival of gram negative bacteria against protamine revealed by combination of grazing incidence x-ray structural characterizations and Monte Carlo simulations.

Grazing incidence x-ray scattering techniques and Monte Carlo (MC) simulations are combined to reveal the influence of molecular structure (genetic mutation) and divalent cations on the survival of gram negative bacteria against cationic peptides such as protamine. The former yields detailed structures of bacterial lipopolysaccharide (LPS) membranes with minimized radiation damages, while the minimal computer model based on the linearized Poisson-Boltzmann theory allows for the simulation of conformational changes of macromolecules (LPSs and peptides) that occur in the time scale of ms. The complementary combination of the structural characterizations and MC simulation demonstrates that the condensations of divalent ions (Ca2+ or Mg2+) in the negatively charged core saccharides are crucial for bacterial survival.