Cost-effectiveness of DNA-diagnosis for four monogenic diseases

In this paper the costs and benefits associated with DNA-diagnosis of individuals who are at risk of a child with a monogenic disease and who seek genetic counselling because of their reproductive plans are predicted under various assumptions using a mathematical model. Four monogenic diseases have been considered: cystic fibrosis, Duchenne muscular dystrophy, myotonic dystrophy and fragile X syndrome. Counselling (triggered by prior information) on the basis of DNA-diagnosis is compared to the situation that only risk evaluation based on pedigree analysis is possible. The results show for each disease that with DNA-diagnosis couples can be more confident in choosing (further) offspring leading to the birth of more healthy children while the number of affected children is reduced. The costs minus savings within the health care sector depend on the prior risks and to the future burden of the monogenic illness considered. DNA-diagnosis of relative "low" prior risks of a child with CF (e.g. 1:180, 1:240 and 1:480) leads to costs in stead of savings. For higher prior risks of CF and for the three other diseases DNA-diagnosis induces considerable savings. This result remains valid when assumptions regarding behaviour regarding reproduction and receiving DNA-diagnosis under different circumstances are varied

Osteoporosis in the Netherlands; A burden of illness study commissioned by Merck Sharp & Dohme

This report provides an overview of the available quantitative information about osteoporosis in the Netherlands, and of the costs associated with it. We present information relevant for this country, making as few assumptions as possible. Although the main subject is osteoporosis, the focus in this report is on fractures, as these are the most relevant outcome events of this condition. Data were collected from publicly available data sources and from international literature and information is mostly about the year 1993. The reader finds detailed information about the occurrence of osteoporosis and fractures, the utilization of health care, mortality, and the costs in the results section of this report. In the conclusions, we present a synthesis of the most important findings. Osteoporosis is, by consensus, defined as a systemic skeletal disease, characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. There is an important age-related decrease in bone mass and bone strength. Osteoporosis is primarily described in post-menopausal women but men are not free from it; they also reach high fracture incidence rates at an older age. Combined with the longer survival of women, this leads to the observation that most osteoporotic fractures are encountered in females. Osteoporosis and fractures are a major source of illness and healthcare costs in the Netherlands, both today as in the foreseeable future. Especially the most serious consequence, hip fracture, is frequent and the incidence is increasing. The total number of hip fractures will inevitable rise if no serious prevention efforts are undertaken. For the prevention of osteoporotic fractures it is important to know who are at risk as well as which preventive strategy is effective for the different risk categories. The parameter that is most commonly used nowadays to determine fracture risk is bone mineral density (BMD), but also other factors are important contributors to the fracture risk, namely the previously mentioned bone quality and the propensity to fall. Prevention only focussed on bone mineral density will thus do nothing to prevent the hip fractures caused by the above mentioned factors. An additional effect of therapy on bone quality can be important and the intervention should certainly not have adverse effects on bone quality. Reducing the frequency and severity of falls, and the use of external protective devices, together with physical exercise and other lifestyle interventions, have been looked at as additional intervention possibilities. Patients with a hip fracture more often have concomitant illnesses and a poor general condition. This condition in itself can increase the risk of falling and the perioperative risk. This situation can also impair the rehabilitation after treatment and hamper mobilization. Osteoporosis and fractures are found to be an important cause of health care consumption. Hip fractures lead to long hospita

One year cost effectiveness of sirolimus eluting stents compared with bare metal stents in the treatment of single native de novo coronary lesions: an analysis from the RAVEL trial

OBJECTIVE: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. DESIGN: Multicentre, double blind, randomised trial. SETTING: Percutaneous coronary intervention for single de novo coronary lesions. PATIENTS: 238 patients with stable or unstable angina. INTERVENTIONS: Randomisation to sirolimus eluting stent or bare stent implantation. MAIN OUTCOME MEASURES: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. RESULTS: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the addit

Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease

BACKGROUND: The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS: A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS: At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were $4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be$2,973 per patient. CONCLUSION: As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization

Direct stenting with the Bx VELOCITY balloon-expandable stent mounted on the Raptor rapid exchange delivery system versus predilatation in a European randomized Trial: the VELVET trial.

Abstract AIMS: This study examined the six-month angiographic results of direct coronary stenting, and compared the nine-month safety, efficacy and cost of this strategy versus stenting after balloon predilatation. METHODS: In phase I of VELVET, 122 patients (mean age = 62.3 +/- 10.1 years, 77% male, 11% with diabetes) with angina pectoris or myocardial ischemia resulting from a single de novo 51% to 95% coronary stenosis underwent direct stenting. The endpoints of phase I included angiographic findings and rates of major adverse cardiac events up to six months of follow-up. In phase II, 401 patients (mean age = 61.3 +/- 10.8 years, 79% male, 16% with diabetes) with angina pectoris or documented myocardial ischemia resulting from single or multiple, de novo or restenotic, coronary lesions were randomized between direc

Exome sequencing and functional analyses suggest that SIX6 is a gene involved in an altered proliferation-differentiation balance early in life and optic nerve degeneration at old age

Primary open-angle glaucoma (POAG) is a hereditary neurodegenerative disease, characterized by optic nerve changes including increased excavation, notching and optic disc hemorrhages. The excavation can be described by the vertical cup-disc ratio (VCDR). Previously, genome-wide significant evidence for the association of rs10483727 in SIX1-SIX6 locus with VCDR and subsequent POAG was found. Using 1000 genomes-based imputation of four independent population-based cohorts in the Netherlands, we identified a missense variant rs33912345 (His141Asn) in SIX6 associated with VCDR (Pmeta = 7.74 × 10-7, n = 11 473) and POAG (Pmeta = 6.09 × 10-3, n = 292). Exome sequencing analysis revealed another missense variant rs146737847 (Glu129Lys) also in SIX6 associated with VCDR (P = 5.09 × 10-3, n = 1208). These two findings point to SIX6 as the responsible gene for the previously reported association signal. Functional characterization of SIX6 in zebrafish revealed that knockdown of six6b led to a small eye phenotype. Histological analysis showed retinal lamination, implying an apparent normal development of the eye, but an underdeveloped lens, and reduced optic nerve diameter. Expression analysis of morphants at 3 dpf showed a 5.5-fold up-regulation of cdkn2b, a cyclin-dependent kinase inhibitor, involved in cell cycle regulation and previously associated with VCDR and POAG in genome-wide association studies (GWASs). Since both six6b and cdkn2b play a key role in cell proliferation, we assessed the proliferative activity in the eye of morphants and found an alteration in the proliferative pattern of retinal cells. Our findings in humans and zebrafish suggest a functional involvement of six6b in early eye development, and open new insights into the genetic architecture of POAG

Economic outcomes of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with left main or three-vessel coronary artery disease: One-year results from the SYNTAX trial

Objectives: To evaluate the cost-effectiveness of alternative approaches to revascularization for patients with three-vessel or left main coronary artery disease (CAD). Background: Previous studies have demonstrated that, despite higher initial costs, long-term costs with bypass surgery (CABG) in multivessel CAD are similar to those for percutaneous coronary intervention (PCI). The impact of drug-eluting stents (DES) on these results is unknown. Methods: The SYNTAX trial randomized 1,800 patients with left main or three-vessel CAD to either CABG (n = 897) or PCI using paclitaxel-eluting stents (n = 903). Resource utilization data were collected prospectively for all patients, and cumulative 1-year costs were assessed from the perspective of the U.S. healthcare system. Results: Total costs for the initial hospitalization were $5,693/patient higher with CABG, whereas follow-up costs were$2,282/patient higher with PCI due mainly to more frequent revascularization procedures and higher outpatient medication costs. Total 1-year costs were thus $3,590/patient higher with CABG, while quality-adjusted life expectancy was slightly higher with PCI. Although PCI was an economically dominant strategy for the overall population, cost-effectiveness varied considerably according to angiographic complexity. For patients with high angiographic complexity (SYNTAX score > 32), total 1-year costs were similar for CABG and PCI, and the incremental cost-effectiveness ratio for CABG was$43,486 per quality-adjusted life-year gained. Conclusions: Among patients with three-vessel or left main CAD, PCI is an economically attractive strategy over the first year for patients with low and moderate angiographic complexity, while CABG is favored among patients with high angiographic complexity

Randomized comparison of primary stenting and provisional balloon angioplasty guided by flow velocity measurement.

BACKGROUND: Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may have other disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive. METHODS AND RESULTS: To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is "optimal." An optimal result was defined as a flow reserve >2.5 and a diameter stenosis <36%. Bailout stenting was needed in 129 patients (25%) who were randomized to balloon angioplasty, and an optimal result was obtained in 184 of the 523 patients (35%). There was no significant difference in event-free survival at 1 year between primary stenting (86.6%) and provisional angioplasty (85.6%). Costs after 1 year were significantly higher for provisional angioplasty (EUR 6573 versus EUR 5885; P:=0.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P:=0. 066). CONCLUSIONS: After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty

The costs and effects of Regranex® in the treatment of diabetic feet ulcera (in Dutch)

Doel. Het verkrijgen van inzicht in de balans tussen kosten en effecten van Regranex, als toevoeging aan de standaard behandeling van diabetische voetulcera van neuropatische standaardbehandeling oorsprong met adequate bloedvoorziening. Methode. Kosten en effecten worden berekend van met behulp van een Markov-model waarin - met een tijdshorizon van respectievelijk 1 en 2 jaar - Amerikaanse gegevens omtrent het natuurlijke beloop van de ziekte worden gecombineerd met 1) Nederlands/Zweedse kostenramingen en 2) gegevens omtrent de effectiviteit van Regranex ontleend aan gerandomiseerd

Costs and effects of c7E3 in high risk PTCA patients. An indirect analysis for The Netherlands

A cost effectiveness study is presented on the use of c7E3 in high risk patients undergoing percutaneous coronary angioplasty (PTCA). The results from the EPIC study have been combined with cost data from The Netherlands. The study took account of the number of survivors without ischaemic events, and the number with neither ischaemic events nor bleeding (both measured after 6 months). It is estimated that the initial costs of c7E3 and the additional costs due to the increased risk of bleeding are almost entirely counterbalanced by the savings, as a result of fewer myocardial infarctions and revascularizations. The additional costs per additional patient without ischaemic events are approximately DFL 5235. The additional costs per additional patient with neither ischaemic events nor bleeding are estimated at DFL 15,685. Both figures are less than the average for similar procedures without c7E3. Sensitivity analysis supports the conclusion that c7E3 treatment is efficient. However, cost effectiveness could be further improved if patients are carefully selected