Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction.

OBJECTIVE: Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. METHODS: A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%-94% in the UK, 84% in Denmark and 95% in Colombia. CONCLUSIONS: Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF

A protein methylation pathway in Chlamydomonas flagella is active during flagellar resorption

Author Posting. © American Society for Cell Biology, 2008. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 19 (2008): 4319-4327, doi:10.1091/mbc.E08-05-0470.During intraflagellar transport (IFT), the regulation of motor proteins, the loading and unloading of cargo and the turnover of flagellar proteins all occur at the flagellar tip. To begin an analysis of the protein composition of the flagellar tip, we used difference gel electrophoresis to compare long versus short (i.e., regenerating) flagella. The concentration of tip proteins should be higher relative to that of tubulin (which is constant per unit length of the flagellum) in short compared with long flagella. One protein we have identified is the cobalamin-independent form of methionine synthase (MetE). Antibodies to MetE label flagella in a punctate pattern reminiscent of IFT particle staining, and immunoblot analysis reveals that the amount of MetE in flagella is low in full-length flagella, increased in regenerating flagella, and highest in resorbing flagella. Four methylated proteins have been identified in resorbing flagella, using antibodies specific for asymmetrically dimethylated arginine residues. These proteins are found almost exclusively in the axonemal fraction, and the methylated forms of these proteins are essentially absent in full-length and regenerating flagella. Because most cells resorb cilia/flagella before cell division, these data indicate a link between flagellar protein methylation and progression through the cell cycle.This work was supported by National Institutes of Health Grant DK071720 (R.D.S.) and National Science Foundation Grant MCB 0418877 (R.D.S.)

Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction

Objective Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. Methods A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). Results In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%–94% in the UK, 84% in Denmark and 95% in Colombia. Conclusions Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF

A new cost-effectiveness modelling approach in chronic heart failure with reduced ejection fraction - PCV118

Objectives: As new therapies for chronic heart failure with reduced ejection fraction (HFrEF) emerge, health technology assessments (HTAs) will require cost-effectiveness analyses to inform decision making. The objective was to develop a model framework for evaluating the cost-effectiveness of LCZ696, a novel oral therapy proposed for the treatment of HFrEF. Methods: A systematic literature review was performed. Searches were conducted in MEDLINE, EMBASE, EconLit, and Cochrane Library databases, with supplementary hand searching of conferences and HTA websites. Of 63 distinct analyses identified, 33 used decision-analytic models. Structures were most commonly described as Markov models (n=27), but methods employed were heterogeneous. The health states most frequently employed were ‘alive’ and ‘dead’, with outcomes such as hospitalization or New York Heart Association (NYHA) class distribution most commonly considered within the ‘alive’ state. Results: A 2-state Markov model with ‘alive’ and ‘dead’ states was developed using three multivariate regression models to predict the risks of mortality, hospitalisation and the trajectory of health-related quality of life over time within the ‘alive’ state. NYHA class was not used as a basis for health states, as the extrapolation of clinical improvements beyond the observed data was considered clinically implausible. Parametric survival models, negative binomial models and multilevel models are used to predict mortality, hospitalisation, and HRQL, respectively, allowing extrapolation to a lifetime time horizon. The model of HRQL attempts to capture the effects of baseline characteristics, hospitalisation, adverse events and time on EQ-5D. Clinical experts were consulted to validate the regression models and their respective predictions. Conclusions: The new framework employs similar methods to decision analytic models developed previously in heart failure, however models health-related quality of life as a function of time directly, thereby providing a parsimonious approach with improved clinical plausibility compared to other model structures in the literature

Status of the TRIUMF annular chamber for the tracking and identification of charged particles (TACTIC)

TACTIC (TACTIC web site: http://tactic.triumf.ca) is a new detector for low-energy nuclear reactions currently under development at TRIUMF. The cylindrical ionization chamber allows three-dimensional reconstruction of particle tracks by means of a two-dimensional anode array combined with a TOF measurement of the drift electrons. In addition, the integrated charge for each pulse provides information about the energy loss of the particle and therefore allows a better identification of the nuclear species producing the track. The geometry of TACTIC covers a large angular range permitting the measurement of differential cross-sections over a large solid angle. It will be ideal for investigations of nuclear processes pertinent to the field of nuclear astrophysics

Search for the 2 + excitation of the Hoyle state in 12 C using the 12 C( 12 C,3α) 12 C reaction

A search for the 2+ excitation of the Hoyle state in 12C has been performed using the 12C(12C, 3α)12C reaction at a beam energy of 101.5 MeV. An angular correlation analysis was used to suppress known contributions to the excitation energy spectrum, enh