Deep Vein Thrombosis in Europe-Health-Related Quality of Life and Mortality.

OBJECTIVES: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT. METHODS: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL-as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)-was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression. RESULTS: At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%). CONCLUSIONS: Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT.

Deep-vein thrombosis in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

OBJECTIVES: Deep-vein thrombosis (DVT) forms a major healthcare burden in Europe, but exact estimates concerning the economic burden on society are lacking. This study reports results from the PREFER in VTE study concerning resource utilization and absence from work in DVT patients. METHODS: The PREFER in VTE registry was a prospective, observational, multicenter study carried out in Europe (France, Italy, Spain, the UK, and DACH [Germany, Switzerland and Austria]), designed to provide data concerning treatment patterns, resource utilization, mortality and quality of life. Patients with a first-time and/or recurrent DVT, were recruited and followed for 12 months. Data about resource utilization concerns resource utilization related to DVT. Specifically, treatment pattern, re-hospitalization rate, length of hospital stay, ambulatory/office visit, and proportion of patients returning to work, were analyzed and presented. Subgroup analysis by country and active cancer were also conducted. The length of hospital stay was analyzed as a function of demographics, previous events and co-morbidities using zero-inflated binomial negative regression. Similarly, time until return to work was analyzed using Cox regression. RESULTS: A total of 2056 patients with DVT were recruited, with an average age of 60 years. Patients with active cancer were mostly treated with heparin (83.9%), while patients without active cancer were treated with combinations of heparin, VKA and DOACs. DOACs were less often used in Spain and Italy (<7.0%). Following the management of their initial DVT 20.5% of the patients with and 12.2% of patients without active cancer (n = 88; n = 1462) were hospitalized for on average 8.2 and 10.1 days, respectively. The hospitalization-rate was highest in Italy (16.7%) and lowest in France (7.7%). Furthermore, the average length of stay was highest in Italy (16.6 days) and lowest in DACH (5.2 days). Physician visits were highest in DACH (9.3), lowest in the UK (2.6). Of those working, 50% returned to work at 1 month; >30% did not return to work within the year. CONCLUSIONS: Medical treatment of DVT differed between patients with active cancer and those without. Post-VTE or VTE-related resource utilization differs remarkably between countries. Work-loss seems high, but questions may be raised concerning the causality due to the presence of co-morbidities.

Survival after transfusion in the Netherlands.

BACKGROUND: Cost-effectiveness analyses of blood safety interventions require estimates of the life expectancy after blood product transfusion. These are best derived from survival after blood transfusion, per age group and blood component type. STUDY DESIGN AND METHODS: In the PROTON (PROfiles of TransfusiON recipients) study transfusion recipient data was collected from a hospital sample covering 28% of the total blood use between 1996 and 2006 in the Netherlands. The dataset includes date of transfusion, blood component type transfused and recipient identification details. PROTON data were individually matched to mortality data of the Netherlands. Survival after first transfusion and after any transfusion was calculated, per blood component type and age group. PROTON mortality rates were compared to mortality rates in the general population. The results were used to estimate survival beyond the study period and to estimate life expectancy after transfusion. RESULTS: Of all 2,405,012 blood product transfusions in the PROTON dataset, 92% was matched to the national Dutch Municipal Population Register, which registers all deaths. After 1 year, survival after any transfusion was 65·4%, 70·4% and 53·9% for RBC, FFP and PLT respectively. After 5 years, this was 46·6%, 58·8% and 39·3% for RBC, FFP and PLT, respectively. Ten years after transfusion, mortality rates of recipients are still elevated in comparison with the general population. CONCLUSION: Mortality rates of transfusion recipients are higher than those of the general population, but the increase diminishes over time. The mortality rates found for the Netherlands are lower than those found in comparable studies for other countries.

The PROTON study: profiles of blood product transfusion recipients in the Netherlands.

BACKGROUND: Transfusion recipient data are needed for correct estimation of cost-effectiveness in terms of recipient outcomes after transfusion. Also, such data are essential for monitoring blood use, estimation of future blood use and benchmarking. STUDY DESIGN AND METHODS: A sample of 20 of 93 Dutch hospitals was selected. Datasets containing all blood product transfusions between 1996 and 2006 were extracted from hospital blood bank computer systems, containing transfusion date, blood product type and recipient characteristics such as gender, address, date of birth. The datasets were appended and matched to national hospitalization datasets including primary discharge diagnoses (ICD-9). Using these data, we estimated distributions of blood recipient characteristics in the Netherlands. RESULTS: The dataset contains information on 290,043 patients who received 2,405,012 blood products (1,720,075 RBC, 443,697 FFP, 241,240 PLT) from 1996 to 2006. This is 28% of total blood use in the Netherlands during this period. Comparable diagnosis and age distributions of all hospitalizations indicate included hospitals to be representative, per hospital category, for the Netherlands. Of all red blood cells (RBC), fresh-frozen plasma (FFP) and platelets (PLT), respectively 1.7%, 2.5% and 4.5% were transfused to neonates. Recipients of 65 years or older received 57.6% of RBC, 41.4% of FFP and 29.0% of PLT. Most of the blood products were transfused to patients with diseases of the circulary system (25.1%) or neoplasms (22.0%). CONCLUSION: Transfusion data from a limited sample of hospitals can be used to estimate national distributions of blood recipient characteristics.

Cost-effectiveness of clopidogrel in STEMI patients in the Netherlands: a model based on the CLARITY trial.

OBJECTIVE: This study assesses the costs and effects of combination treatment with clopidogrel and aspirin in comparison to aspirin alone in patients with an ST-segment elevation myocardial infarction (STEMI) in a Dutch setting. METHODS: A decision tree model is used to combine data from different sources about efficacy, epidemiology and costs. In the short-run, cost-effectiveness is based on efficacy data derived from the CLARITY trial. The cost-effectiveness of continued treatment is addressed by analysing which conditions need to be fulfilled to deem the strategy 'cost-effective', and discussing whether it is likely that it is. Estimates concerning the benefits of preventing events are derived from Swedish registries. Approximations of both direct and indirect costs are derived from the literature. Effects are expressed as life years gained and Quality Adjust Life Years (QALYs). Uncertainties are addressed by uni- and multivariate sensitivity analyses with and without taking account of the dependency between the separate ischaemic events. RESULTS: A treatment regimen similar to that of the CLARITY trial, including patients similar to those in the trial, is estimated to result in 0.05 additional life years and 0.062 additional quality adjusted life years for a cost that is euro1929 lower than aspirin therapy. Continuation of treatment outside the trial period is expected to result in ICERs of below euro20,000 per QALY as long as the real risk reduction of combination treatment is greater than 0.487% per year. CONCLUSION: The results indicate that clopidogrel therapy combined with aspirin, according to the regimen seen in CLARITY, and using data from Swedish registries to inform the model, is cost-effective. Sensitivity analyses suggest that the model is robust to a wide range of parameter estimates, including those based on data from Swedish registries. Continued treatment is very likely to be cost effective in light of all the indirect evidence.

Economic evaluation of zoledronic acid for the prevention of osteoporotic fractures in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the UK.

BACKGROUND: Aromatase inhibitors are used as adjuvant therapy for breast cancer (BC) and are associated with accelerated bone loss. Zoledronic acid (ZOL) prevents aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with BC. This analysis assessed the cost-effectiveness of ZOL for prevention of fractures in postmenopausal women with BC. MATERIALS AND METHODS: A Markov model was developed to project lifetime incidence of fractures, quality-adjusted life years (QALY), and costs as a function of bone mineral density (BMD) for women with early-stage BC receiving letrozole alone or with ZOL. Two strategies of ZOL therapy were compared with no treatment: starting ZOL treatment only when BMD levels decreased ('delayed ZOL') and starting ZOL simultaneously with letrozole therapy ('upfront ZOL'). RESULTS: Delayed ZOL therapy was estimated to cost 16,069 pounds per QALY, when compared with not administering bisphosphonates for AIBL prevention. The corresponding cost per QALY gained for upfront ZOL versus no treatment was estimated at 21,973 pounds. The cost-effectiveness ratio for upfront versus delayed therapy was estimated at 24,868 pounds per QALY gained. CONCLUSION: Both delayed and upfront therapy with ZOL for the prevention of AIBL and fractures in BC patients in the UK appear to result in highly acceptable cost-effectiveness ratios.

Cost-effectiveness of additional hepatitis B virus nucleic acid testing of individual donations or minipools of six donations in the Netherlands.

BACKGROUND: To further reduce the risk of hepatitis B virus (HBV) transmission by blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this study is to estimate the incremental cost-effectiveness ratio (ICER) in the Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection in individual donations (ID-NAT) or in minipools of 6 donations (MP-6-NAT), compared to a triplex NAT assay in minipools of 24 donations (MP-24-NAT). STUDY DESIGN AND METHODS: A mathematical model was made of the whole transfusion chain from donors to recipients of blood in the Netherlands. The annual number of avoided HBV transmissions was estimated with the window-period incidence model. The natural history of a HBV infection in recipients is described by a Markov model. RESULTS: The ICER of adding HBV MP-6-NAT or HBV ID-NAT in the Netherlands is Euro303,218 (95% confidence interval [CI], Euro233,001-Euro408,388) and Euro518,995 (95% CI, Euro399,359-Euro699,120) per quality-adjusted life-year, respectively. The ICER strongly correlates with the age of transfusion recipients. CONCLUSION: The cost-effectiveness of additional HBV NAT is limited by the limited loss of life caused by HBV transmission. Despite a higher effectiveness, HBV ID-NAT is less cost-effective than MP-6-NAT due to higher costs. A future equivalent participation of immigrants from HBV-endemic countries in the donor base renders HBV NAT only slightly more cost-effective.

Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression.

The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 microg kg(-1) rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg(-1) aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h.

Monitoring viral incidence rates: tools for the implementation of European Union regulations.

BACKGROUND AND OBJECTIVES: European legislation requires manufacturers of plasma products to report epidemiological data on human immunodeficiency virus, hepatitis B virus and hepatitis C virus in donor populations. The incidence rates of such infections are directly related to the risk of infection transmission. We propose two statistical tests to evaluate these incidence rates. MATERIALS AND METHODS: Infection data of the four Dutch blood collection centres from 2003 through 2006 were analysed. For transversal comparison of centres and detection of increased incidence rates, a new statistical test was developed (outlier test). For longitudinal detection of trends in incidence rates, a generic test for trend is proposed. The power and risk of non-detection are evaluated for both tests. RESULTS: Application of the outlier test did not reveal any significantly increased incidence rates among centres in The Netherlands. The test for trend showed no significant increase in incidence rates in individual centres, but on national level a statistically significant increase in hepatitis C virus incidence was observed (P-value of 0.01). CONCLUSION: The proposed tests allow signalling of outlier centres and trends in incidence rates both at individual centre and at national levels. Graphical support and the use of as much relevant historical data as possible is recommended. The statistical tests described are generic and can be applied by any blood establishment and plasma fractionation institute.

Recommendations for reporting economic evaluations of haemophilia prophylaxis: a nominal groups consensus statement on behalf of the Economics Expert Working Group of The International Prophylaxis Study Group.

BACKGROUND: The need for clearly reported studies evaluating the cost of prophylaxis and its overall outcomes has been recommended from previous literature. OBJECTIVES: To establish minimal ''core standards'' that can be followed when conducting and reporting economic evaluations of hemophilia prophylaxis. METHODS: Ten members of the IPSG Economic Analysis Working Group participated in a consensus process using the Nominal Groups Technique (NGT). The following topics relating to the economic analysis of prophylaxis studies were addressed; Whose perspective should be taken? Which is the best methodological approach? Is micro- or macro-costing the best costing strategy? What information must be presented about costs and outcomes in order to facilitate local and international interpretation? RESULTS: The group suggests studies on the economic impact of prophylaxis should be viewed from a societal perspective and be reported using a Cost Utility Analysis (CUA) (with consideration of also reporting Cost Benefit Analysis [CBA]). All costs that exceed $500 should be used to measure the costs of prophylaxis (macro strategy) including items such as clotting factor costs, hospitalizations, surgical procedures, productivity loss and number of days lost from school or work. Generic and disease specific quality of lífe and utility measures should be used to report the outcomes of the study. CONCLUSIONS: The IPSG has suggested minimal core standards to be applied to the reporting of economic evaluations of hemophilia prophylaxis. Standardized reporting will facilitate the comparison of studies and will allow for more rational policy decisions and treatment choices.

Cost-effectiveness and budget impact of long-acting risperidone in Portugal: a modeling exercise.

BACKGROUND: Previous analyses have shown that long-acting risperidone (LAR) is cost-effective in several Western countries. In Portugal, however, the costs of key services are lower. Therefore, available evidence in other countries may have limited relevance. OBJECTIVE: To estimate costs and effects of LAR versus a conventional depot and a short-acting oral atypical antipsychotic over a 5-year period in Portugal. METHODS: An existing discrete event model was adapted to reflect the Portuguese healthcare setting, based on expert opinion, clinical, epidemiological, and cost data. The model compares three scenarios. In scenario 1, patients start with a conventional depot; in scenario 2, with LAR; and in scenario 3, with oral risperidone. The model simulates individual patient histories while taking into account patient characteristics such as risk to society and side-effects. Subsequently, the model simulates patient histories in terms of outpatient appointments, psychotic episodes, treatment, compliance, symptom scores, lack of ability to take care presenting an actual risk, and treatment setting. Outcomes were number of psychotic episodes, cumulative symptom score and direct medical costs. Univariate sensitivity analyses were carried out. RESULTS: Compared to a conventional depot and an oral atypical, LAR was estimated to save approximately euro 3603 and euro 4682 per patient (respectively) and avoid 0.44 and 0.59 relapses per patient in 5 years. Sensitivity analyses showed that the outcome of dominance was only sensitive to estimates about unit costs of hospital/institutionalization, potential risk, and to the reduction in symptoms by use of atypicals. CONCLUSION: Based on this modeling exercise, it could be expected that LAR may be a cost-effective treatment with limited budget impact in Portugal. However, further studies are required to test the generalizability of the results of the present modeling study to the larger population of Portugal.

Cost effectiveness of adalimumab for the treatment of ankylosing spondylitis in the United Kingdom.

OBJECTIVES: This study evaluated the cost effectiveness of adalimumab vs conventional therapy in patients with active ankylosing spondylitis (AS). METHODS: The analysis was based on pooled data from two Phase III studies of adalimumab in active AS. Patients with an inadequate response to >/=1 NSAID received adalimumab 40 mg every other week (n = 246) or placebo (n = 151) for 24 weeks. A microsimulation model was developed with patients being treated with adalimumab according to the International ASAS Consensus Statement and BSR guidelines. The pooled adalimumab data, as well as data from the Outcome Assessment in AS International Study (OASIS) database and the literature, were used to model patients' BASDAI and BASFI scores and costs and health-related quality of life associated with various degrees of disease activity. Costs (in 2004 British pound) of AS, drug, administration, monitoring, hospitalization and AEs were calculated from the perspective of the UK NHS. Discounting was applied at 3.5% per year for costs and benefits as per the NICE reference case for economic evaluations. Uncertainty was addressed via sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) of adalimumab vs conventional therapy was estimated to improve with longer time horizons (48 weeks to 5 and 30 yrs). The central estimate was that, over 30 yrs, adalimumab therapy yielded 1.03 more quality-adjusted life-years (QALYs) per patient initiating therapy. Some AS treatment-related costs were estimated to be offset by adalimumab (at 10,750 pounds/patient), leaving a total incremental cost (adalimumab vs conventional therapy) at 23,857 pounds per patient. The 30-yr ICER of adalimumab vs conventional therapy was estimated at 23 pounds 097/QALY. Sensitivity analyses demonstrated robustness of results. When indirect costs were also included (analysis from societal perspective), ICER improved to 5093 pounds/QALY. CONCLUSIONS: This analysis indicates that adalimumab, when used according to UK treatment guidelines, is cost-effective vs conventional therapy for treating AS patients.

The use of a surgical sealant (CoSeal) in cardiac and vascular reconstructive surgery: an economic analysis.

AIM: We designed a study to estimate the economic impact of CoSeal Surgical Sealant for the prevention of anastomotic bleeding in cardiac and vascular surgery. We also explored the potential economic value of CoSeal as a means of inhibiting the formation of pericardial tissue adhesions. METHODS: A Delphi panel of 6 expert vascular and cardiac surgeons provided the assumptions and estimates needed to develop a decision analysis model to assess the impact of sealant on the costs associated with low- and high-risk forms of cardiac (valve replacement/reconstruction) and vascular (abdominal aortic aneurysm [AAA] repair, femoral bypass grafting) surgery. The primary outcome was incremental cost per patient. RESULTS: For valve repair/replacement surgery, sealant was expected to confer cost-savings in high-risk but not low-risk procedures. Predicted cost savings for high-risk AAA repairs were substantial, but minimal in the overall AAA group. Cost-savings were predicted for sealant use in all femoral-popliteal ePTFE bypass grafts, but in high-risk femoral-femoral ePTFE bypass grafts only. CONCLUSIONS: According to our decision analysis model, routine use of surgical sealant in select subgroups may confer considerable economic benefits to health service budgets. Future research should aim at testing this model in a real-world hospital setting. Assessment of the value of CoSeal in the prevention of postsurgical adhesions showed that expert surgeons see a need for effective prophylaxis. Further research into the clinical and economic benefit of this intervention is required.

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 additional one year costs at 166. CONCLUSIONS: The one year data from RAVEL suggest an attractive balance between costs and effects for sirolimus eluting stents in the treatment of single native de novo coronary lesions. The cost effectiveness of drug eluting stents in more complex lesion subsets remains to be determined.

[Sepsis, a complicated syndrome with major medical and social consequences]. / Sepsis, een gecompliceerd syndroom met belangrijke medische en maatschappelijke consequenties.

Severe sepsis is a life-threatening complication of infection. Due to associated organ-failure treatment in an Intensive Care Unit is usually indicated. Since sepsis is defined by the combination and progression of clinical events, correct definitions are essential to enable good comparison between study results and determination of suitable treatment. Severe sepsis is associated with a mortality of 20-60% and decreases the health-related quality of life in survivors. It is estimated that annually in the Netherlands 9000 patients are admitted to an Intensive Care Unit with severe sepsis. Direct medical costs of severe sepsis are estimated at [symbol: see text] 19,500 per patient. Costs correlate strongly with the length of stay. Annually Euro dollar 168,6 million is spent on severe sepsis, which represents 0.5% of all health-care costs and 1.7% of the annual hospital budget in the Netherlands.

Quality of life and NYHA class 30 years after mechanical aortic valve replacement.

OBJECTIVE: (1) To evaluate the quality of life (QoL) scores, assessed with SF36 and EuroQol (EQ-5D), of long term survivors after mechanical aortic valve replacement (mAVR); (2) to study the association of QoL with NYHA score, number of major bleeding and thrombo-embolic events and follow-up time; (3) to compare QoL scores of long term mAVR survivors with QoL scores of other populations. METHODS: In total 312 patients had a mAVR between 1964 and 1974 at St. Antonius Hospital Nieuwegein (NL). Mean age at operation was 41 (sd=12). Mean postoperative NYHA class at 1-year follow-up was 1.7 (sd=0.7). In 2001 the survivors (n=78; 25%) were followed-up for late events, NYHA class and QoL scores. 69 patients (93%) returned completed questionnaires. RESULTS: Mean duration of follow-up was 30 years (sd=1.8). Mean age of responders was 65 years (sd=10, range 47-93). In 2001, NYHA class of responders was 2 (sd=0.9). The mean (sd) SF36 scores for responders were: 64 (29) for physical function, 64 (29) for role-physical, 80 (30) for bodily pain, 55 (25) for general health, 63 (23) for vitality, 73 (29) for social functioning, 70 (38) for role-emotional, 76 (18) for mental health. The mean EQ-5D score of responders was: 61 (13). These SF36 and EQ-5D scores are comparable to those of other populations (e.g. cancer, diabetes type-2, migraine, chronic liver disease and iliac artery occlusive disease and Dutch general population). For responders a moderate to high association of SF36 and EQ-5D scores and their NYHA scores (R2=0.36) was found. The number of major bleeding events, age, sex and survival time were not related to QoL. CONCLUSION: At long term follow-up (mean 30 years) of patients who had mAVR, QoL was relatively high; it was moderately to highly associated with their NYHA class; bleeding and thromboembolic events seem to be of little importance for the QoL at long term follow-up. QoL at long term follow-up of patients who had mAVR is comparable to other cross sectional designed studies with short term follow-up and other population.

Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use.

BACKGROUND: Proton pump inhibitors have a prominent role in the management of acid-related diseases. Controlling expenses on proton pump inhibitors would yield great economic benefits for Dutch health care. AIM: To investigate whether clinical differences in proton pump inhibitors exist. METHODS: We searched Medline, EMBASE and the Cochrane Library. We identified papers in English, German, French or Dutch in which two or more proton pump inhibitors were compared under the same clinical conditions in gastro-oesophageal reflux disease, peptic ulcer disease or Helicobacter pylori eradication. The pooled relative risks were calculated using the Mantel-Haenszel method. RESULTS: Two significant differences were found in the proton pump inhibitors compared. In gastro-oesophageal reflux disease, esomeprazole 40 mg was superior to omeprazole 20 mg (relative risk, 1.18; 95% confidence interval, 1.14-1.23). In peptic ulcer disease, pantoprazole 40 mg was superior to omeprazole 20 mg (relative risk, 1.07; 95% confidence interval, 1.02-1.13). In Helicobacter pylori eradication, no significant differences were found. CONCLUSIONS: Both significant differences found were in favour of the highest dose of proton pump inhibitor on a milligram basis. This indicates that the difference may be dose dependent and not proton pump inhibitor specific. Therefore, when prescribing proton pump inhibitors, arguments other than clinical efficacy, such as those related to pharmaco-economics, may be considered.