Economic evaluation of sirolimus-eluting stents

Background

Sirolimus-eluting stents have recently been shown to reduce the risk of restenosis among patients who undergo percutaneous coronary intervention (PCI). Given that sirolimus-eluting stents cost about 4 times as much as conventional stents, and considering the volume of PCI procedures, the decision to use sirolimus-eluting stents has large economic implications.

Methods

We performed an economic evaluation comparing treatment with sirolimus-eluting and conventional stents in patients undergoing PCI and in subgroups based on age and diabetes mellitus status. The probabilities of transition between clinical states and estimates of resource use and health-related quality of life were derived from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Information on effectiveness was based on a meta-analysis of randomized controlled clinical trials (RCTs) comparing sirolimus-eluting and conventional stents.

Results

Cost per quality-adjusted life year (QALY) gained in the baseline analysis was Can$58 721. Sirolimus-eluting stents were more cost-effective in patients with diabetes and in those over 75 years of age, the costs per QALY gained being $44 135 and $40 129, respectively. The results were sensitive to plausible variations in the cost of stents, the estimate of the effectiveness of sirolimus-eluting stents and the assumption that sirolimus-eluting stents would prevent the need for cardiac catheterizations in the subsequent year when no revascularization procedure was performed to treat restenosis.

Interpretation

The use of sirolimus-eluting stents is associated with a cost per QALY that is similar to or higher than that of other accepted medical forms of therapy and is associated with a significant incremental cost. Sirolimus-eluting stents are more economically attractive for patients who are at higher risk of restenosis or at a high risk of death if a second revascularization procedure were to be required.Restenosis is a major limitation to the long-term success of percutaneous coronary intervention (PCI). It is estimated that 14% of patients who undergo PCI with stent implantation require a second intervention within a year to manage restenosis.¹ A second coronary procedure carries a significant risk of death or impairment in health-related quality of life (HRQOL).² Moreover, given that approximately 21 200 PCIs with stenting were performed in Canada in 1999, restenosis has major economic implications.³Drug-eluting stents are the most recent technologic advance in restenosis prevention. To date, 4 randomized controlled clinical trials (RCTs) have compared the efficacy of sirolimus-eluting stents (the first available drug-eluting stent) and standard uncoated stents in the treatment of de novo native coronary artery disease and published their findings: RAVEL⁴ (RAndomized study with the sirolimus-eluting VELocity balloon-expandable stent), SIRIUS⁵ (study of the SIRolImUS-eluting stent), and C-SIRIUS⁶ and E-SIRIUS,⁷ the Canadian and European arms of SIRIUS. These trials all found notable reductions in the incidence of radiographic evidence of restenosis and symptomatic restenosis with the use of sirolimus-eluting stents. However, the overall survival rate was not affected. Currently, the cost of sirolimus-eluting stents (about Can$2900 per stent) is nearly 4 times that of conventional stents.⁸ Given the volume of PCIs performed annually, decision-makers must determine their optimal use.Using a subset of the cohort in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH),⁹ we estimated clinical event rates, HRQOL and health care costs for patients undergoing PCI with implantation of a conventional stent. Combining this information with data from the 4 RCTs, we estimated the cost per quality-adjusted life-year (QALY) gained by using sirolimus-eluting stents rather than conventional stents for such patients.     

A novel approach to investigate biofilm accumulation and bacterial transport in porous matrices

Knowledge of bacterial transport through, and biofilm growth in, porous media is vitally important in numerous natural and engineered environments. Despite this, porous media systems are generally oversimplified and the local complexity of cell transport, biofilm formation and the effect of biofilm accumulation on flow patterns is lost. In this study, cells of the sulphate-reducing bacterium, Desulfovibrio sp. EX265, accumulated primarily on the leading faces of obstructions and developed into biofilm, which grew to narrow and block pore throats (at a rate of 12 micro m h(-1) in one instance). This pore blocking corresponded to a decrease in permeability from 9.9 to 4.9 Darcy. Biofilm processes were observed in detail and quantitative data were used to describe the rate of biofilm accumulation temporally and spatially. Accumulation in the inlet zone of the micromodel was 10% higher than in the outlet zone and a mean biofilm height of 28.4 micro m was measured in a micromodel with an average pore height of 34.9 microm. Backflow (flow reversal) of fluid was implemented on micromodels blocked with biofilm growth. Although biofilm surface area cover did immediately decrease (approximately 5%), the biofilm quickly re-established and permeability was not significantly affected (9.4 Darcy). These results demonstrate that the glass micromodel used here is an effective tool for in situ analysis and quantification of bacteria in porous media.     

Effects of prostaglandin F2 alpha-induced luteolysis on the populations of cells in the ovine corpus luteum

Receptors for prostaglandin (PG) F2 alpha in the ovine corpus luteum are localized on large steroidogenic luteal cells. Therefore, it was hypothesized that during luteolysis, the first demonstrable effects of PGF2 alpha would occur in the population of large luteal cells. To test this hypothesis, the numbers and sizes of large and small luteal cells, fibroblasts, capillary endothelial cells, and pericytes were determined in corpora lutea collected 12, 24, or 36 h (6 animals/group) following administration of PGF2 alpha on Day 10 postestrus and from untreated ewes on Days 10 and 12 postestrus. The numbers and sizes of luteal cells were determined after enzymatic dissociation of the luteal tissue into single cell suspensions and by morphometric analysis of luteal slices. Serum levels of progesterone decreased (p less than 0.05) within 12 h of treatment, indicating that luteolysis was induced. Recovery of the two types of steroidogenic luteal cells following enzymatic dissociation was different (p less than 0.05). Recovery of both steroidogenic cell types decreased with time after PGF2 alpha treatment, suggesting that they had become more fragile. As determined by morphometry, the number of large luteal cells was not different at any time point examined; however, by 36 h after treatment, the average diameter of large luteal cells had decreased (p less than 0.05). In contrast, by 24 h after treatment, there was a decrease in the number of small luteal cells (p less than 0.05) but no change in their diameter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of preovulatory follicles expected to form short-lived corpora lutea in beef cows

Oestrus, expected to be followed by a short luteal phase, was induced in post-partum cows by weaning their calves at 35 days after parturition. Ovaries containing the first preovulatory follicles (Type F) formed after parturition were collected 3 h after the onset of oestrus. For comparison, preovulatory follicles (Type C) were collected 3 h after the onset of oestrus in normally cycling cows. The number of granulosa cells was determined and the concentrations of receptors for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in granulosa cells and for LH in theca cells were measured. Concentrations of oestradiol-17 beta, testosterone, androstenedione and progesterone in follicular fluid were also measured. Type F follicles contained about twice the number of granulosa cells (based on DNA) as did Type C follicles (45.8 +/- 11.3 and 24.5 +/- 3.9 micrograms DNA/follicle, respectively; P less than 0.05) but these cells had fewer receptors for LH (0.13 +/- 0.02 vs 0.29 +/- 0.03 fmol/micrograms DNA; P less than 0.01) and FSH (0.61 +/- 0.08 vs 1.3 +/- 0.29 fmol/micrograms DNA; P less than 0.08) than did those from Type C follicles. Additionally, there were fewer receptors for LH in theca tissue from Type F than from Type C follicles (28.3 +/- 5.2 vs 51.3 +/- 6.1 fmol/follicle; P less than 0.01). Concentrations of oestradiol-17 beta (475.8 +/- 85.6 vs 112.9 +/- 40.0 ng/ml; P less than 0.01) and androstenedione (214.1 +/- 48.7 vs 24.7 +/- 7.7 ng/ml; P less than 0.01) in follicular fluid were higher in Type C than in Type F follicles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lethal freeze-dehydration injury of dogwood stem tissue does not change the activation energy of water permeability

The Arrhenius activation energy for water permeability, (ΔE_a,H2O) through stem cortical tissue of red osier dogwood (Cornus sericea L.) was determined after treatments which cause membrane rupture as well as after a lethal slow freeze and subsequent slow rewarming. The latter value was higher than the former, but was indistinguishable from the ΔE_a,H2O found for healthy tissue. It was concluded that membrane permeability to water is not altered during the first 24 to 48 hours after exposure of nonacclimated red osier dogwood to lethal freeze dehydration injury.     

Erythrocyte membrane alterations in Huntington disease: Effects of γ-aminobutyric acid

The interaction of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) with erythrocyte membranes from patients with Huntington disease and normal controls has been studied by electron spin resonance. GABA affects the physical state of erythrocyte membrane proteins in control and Huntington disease differently. In addition, after exposure of spin-labeled Huntington disease erythrocyte membranes to 0.1 mM GABA, the relevant electron spin resonance parameters reflecting the physical state of membrane proteins are indistinguishable from those of untreated control membranes. These findings support the concept that this disease is associated with a generalized membrane defect.     

The effect of newt toxin on an invasive snail

Hydrobiologia - Invasive species are well documented to impact native species where they are introduced. In the Santa Monica Mountains, a native species of amphibian, the California newt (Taricha...     

Life cycle alterations of the micro-dielectrophoretic effects of cells

Living cells are observed to be the source of rapidly oscillating electric fields. These can be detected under the microscope by watching their accumulation of highly polarizable particles as compared to their behavior with relatively unpolarized particles, e.g. BaTiO₃ vs. BaSO₄, or NaNbO₃ vs. SiO₂. The ac fields produced by the cells are divergent. This can evoke dielectrophoretic motion of tiny test particles about them, a process called micro-dielectrophoresis. The microdielectrophoretic effect of yeast cells is observed to peak during the mitotic phase. This indicates that the electric fields are associated with cell division.