Propionic Acid Promotes the Virulent Phenotype of Crohn's Disease-Associated Adherent-Invasive Escherichia coli.

Propionic acid (PA) is a bacterium-derived intestinal antimicrobial and immune modulator used widely in food production and agriculture. Passage of Crohn's disease-associated adherent-invasive Escherichia coli (AIEC) through a murine model, in which intestinal PA levels are increased to mimic the human intestine, leads to the recovery of AIEC with significantly increased virulence. Similar phenotypic changes are observed outside the murine model when AIEC is grown in culture with PA as the sole carbon source; such PA exposure also results in AIEC that persists at 20-fold higher levels in vivo. RNA sequencing identifies an upregulation of genes involved in biofilm formation, stress response, metabolism, membrane integrity, and alternative carbon source utilization. PA exposure also increases virulence in a number of E. coli isolates from Crohn's disease patients. Removal of PA is sufficient to reverse these phenotypic changes. Our data indicate that exposure to PA results in AIEC resistance and increased virulence in its presence.

Evaluating the cost-effectiveness of afatinib after platinum-based therapy for the treatment of squamous non-small-cell lung cancer in France.

BACKGROUND AND AIMS: Lung cancer has the highest mortality rate of all cancers worldwide. Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers and has an extremely poor prognosis. Afatinib is an irreversible ErbB family blocker designed to suppress cellular signaling and inhibit cellular growth and is approved in Europe after platinum-based therapy for squamous NSCLC. The objective of the present analysis was to evaluate the cost-effectiveness of afatinib after platinum-based therapy for squamous NSCLC in France. METHODS: The study population was based on the LUX-Lung 8 trial that compared afatinib with erlotinib in patients with squamous NSCLC. The analysis was performed from the perspective of all health care funders and affected patients. A partitioned survival model was developed to evaluate cost-effectiveness based on progression-free survival and overall survival in the trial. Life expectancy, quality-adjusted life expectancy and direct costs were evaluated over a 10-year time horizon. Future costs and clinical benefits were discounted at 4% annually. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Model projections indicated that afatinib was associated with greater life expectancy (0.16 years) and quality-adjusted life expectancy (0.094 quality-adjusted life years [QALYs]) than that projected for erlotinib. The total cost of treatment over a 10-year time horizon was higher for afatinib than erlotinib, EUR12,364 versus EUR9,510, leading to an incremental cost-effectiveness ratio of EUR30,277 per QALY gained for afatinib versus erlotinib. Sensitivity analyses showed that the base case findings were stable under variation of a range of model inputs. CONCLUSION: Based on data from the LUX-Lung 8 trial, afatinib was projected to improve clinical outcomes versus erlotinib, with a 97% probability of being cost-effective assuming a willingness to pay of EUR70,000 per QALY gained, after platinum-based therapy in patients with squamous NSCLC in France.

Long-term Cost-effectiveness of Two GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus in the Italian Setting: Liraglutide Versus Lixisenatide.

PURPOSE: Maintaining glycemic control is the key treatment target for patients with type 2 diabetes mellitus. In addition, the glucagon-like peptide-1 (GLP-1) receptor agonists may be associated with other favorable treatment characteristics, such as reduction in body weight and reduced risk of hypoglycemia compared with traditional diabetes interventions. The aim of the present analysis was to compare the long-term cost-effectiveness of 2 GLP-1 receptor agonists, liraglutide 1.8 mg and lixisenatide 20 µg (both administered once daily), in the treatment of patients with type 2 diabetes failing to achieve glycemic control with metformin monotherapy in the Italian setting. METHODS: The IMS CORE Diabetes Model was used to project long-term clinical outcomes and subsequent costs (in 2015 Euros [€]) associated with liraglutide 1.8 mg versus lixisenatide 20 µg treatment in a cohort with baseline characteristics derived from the open-label LIRA-LIXI trial (Efficacy and Safety of Liraglutide Versus Lixisenatide as Add-on to Metformin in Subjects With Type 2 Diabetes; NCT01973231) over patient lifetimes from the perspective of a health care payer. Efficacy data were taken from the 26-week end points of the same trial, including changes in glycated hemoglobin, body mass index, serum lipid levels, and hypoglycemic event rates. Outcomes projected included life expectancy, quality-adjusted life expectancy, cumulative incidence and time to onset of diabetes-related complications, and direct medical costs. Outcomes were discounted at 3% annually, and sensitivity analyses were performed. FINDINGS: Liraglutide 1.8 mg was associated with improved discounted life expectancy (14.07 vs 13.96 years) and quality-adjusted life expectancy (9.18 vs 9.06 quality-adjusted life years [QALYs]) compared with lixisenatide 20 µg. These improvements were mostly attributable to a greater reduction in glycated hemoglobin level with liraglutide 1.8 mg versus lixisenatide 20 µg, leading to reduced incidence and increased time to onset of diabetes-related complications. Compared with lixisenatide 20 µg, liraglutide 1.8 mg was associated with increased total costs over patient lifetimes (€41,623 vs €41,380), but this was offset by lower costs of treating diabetes-related complications (€26,682 vs €27,476). Liraglutide 1.8 mg was associated with an incremental cost-effectiveness ratio of €2001 per QALY gained versus lixisenatide 20 µg. At a willingness-to-pay threshold of €30,000 per QALY gained, liraglutide 1.8 mg had a probability of 77.2% of being cost-effective. IMPLICATIONS: Based on long-term projections, liraglutide 1.8 mg is likely to be considered cost-effective compared with lixisenatide 20 µg for the treatment of patients with type 2 diabetes in Italy.