Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

Transglutaminase Type II Is Involved in the Pathogenesis of Endotoxic Shock

Abstract The pathogenesis of sepsis is characterized by the inability of the host to regulate the inflammatory response, and as a consequence, dysregulated inflammatory processes induce organ dysfunctions and death. Altered transglutaminase type II (TG2) expression is associated with the development of many inflammatory diseases. Therefore, in this study, we questioned whether TG2 could also contribute to the pathological inflammatory dysregulation occurring in septic shock in vivo. To this aim, we used as an experimental model the TG2 knockout mice, in which the process of septic shock was elicited by treatment with LPS. Interestingly, our results demonstrated that TG2 ablation leads to partial resistance to experimental sepsis. The increased survival of TG2−/− mice was reflected in a drastic reduction of organ injury, highlighted by a limited infiltration of neutrophils in kidney and peritoneum and by a better homeostasis of the proinflammatory mediators as well as mitochondrial function. We also showed that in wild-type mice, the TG2 expression is increased during endotoxemia and, being directly involved in the mechanisms of NF-κB activation, it may cause a continuous activation cycle in the inflammatory process, thus contributing to development of sepsis pathogenesis. We propose that the inhibition of TG2 could represent a novel approach in the treatment of inflammatory processes associated with sepsis

Clinical pathway for LNG-IUS and usual medical treatment.

<p>Clinical pathway for LNG-IUS and usual medical treatment.</p

Results of the probabilistic sensitivity analysis (SF-6D).

<p>Results of the probabilistic sensitivity analysis (SF-6D).</p

Results of the probabilistic sensitivity analysis (EQ-5D).

<p>Results of the probabilistic sensitivity analysis (EQ-5D).</p

Base case and deterministic sensitivity analysis results using EQ-5D.

<p>Cost are rounded to nearest 10. QALYs are rounded to 3 decimal places QALYS; quality adjusted life year, LNG-IUS; levonorgestrel-releasing intrauterine system, ICER; incremental cost-effectiveness ratio.</p><p><b>^*</b>Deterministic sensitivity analysis 1 =  Use median utility values.</p>#<p>Deterministic sensitivity analysis 2 =  Use NICE assumptions.</p><p><b>°</b>Deterministic sensitivity analysis 3 =  Assigning EQ-5D completion date utility for change treatment, if change treatment date is the same as EQ-5D completion date.</p

Probability parameters used in the analysis.

<p>α and β values for the PSA distribution are rounded to the nearest whole number. LNG-IUS; levonorgestrel-releasing intrauterine system, PSA; probabilistic sensitivity analysis.</p

Cost-effectiveness acceptability curves for usual medical treatment and LNG-IUS using EQ-5D.

<p>Cost-effectiveness acceptability curves for usual medical treatment and LNG-IUS using EQ-5D.</p