Health-related quality of life and mortality in patients with pulmonary embolism: a prospective cohort study in seven European countries.

PURPOSE: Little is known about the quality of life following pulmonary embolism (PE). The aim of the study was to assess the 12-month illness burden in terms of health-related quality of life (HrQoL) and mortality, in relation to differences in patient characteristics. METHODS: The PREFER in VTE registry, a prospective, observational study conducted in seven European countries, was used. Within 2 weeks following an acute symptomatic PE, patients were recruited and followed up for 12 months. Associations between patient characteristics and HrQoL (EQ-5D-5L) and mortality were examined using a regression approach. RESULTS: Among 1399 PE patients, the EQ-5D-5L index score at baseline was 0.712 (SD 0.265), which among survivors gradually improved to 0.835 (0.212) at 12 months. For those patients with and without active cancer, the average index score at baseline was 0.658 (0.275) and 0.717 (0.264), respectively. Age and previous stroke were significant factors for predicting index scores in those with/without active cancer. Bleeding events but not recurrences had a noticeable impact on the HrQoL of patients without active cancer. The 12-month mortality rate post-acute period was 8.1%, ranging from 1.4% in Germany, Switzerland, and Austria to 16.8% in Italy. Mortality differed between patients with active cancer and those without (42.7% vs. 4.7%). CONCLUSION: PE is associated with a substantial decrease in HrQoL at baseline which normalizes following treatment. PE is associated with a high mortality rate especially in patients with cancer, with significant country variation. Bleeding events, in particular, impact the burden of PE.

Comparison of quality of life measurements: EQ-5D-5L versus disease/treatment-specific measures in pulmonary embolism and deep vein thrombosis.

INTRODUCTION: There is a lack of performance comparisons of the generic quality of life tool EQ-5D-5L against disease- and treatment-specific measures in venous thromboembolism (VTE). The aim of this study was to compare EQ-5D-5L against the pulmonary embolism (PE)-specific PEmb-QoL and the deep vein thrombosis (DVT)-specific VEINES-QOL/Sym, and PACT-Q2 (treatment-specific) questionnaires in five language settings. METHODS: PREFER in VTE was a non-interventional disease registry conducted between 2013 and 2014 in primary and secondary care across seven European countries with five languages, including English, French, German, Italian and Spanish. Consecutive patients with acute PE/DVT were enrolled and followed over 12 months. Only patients who completed all three questionnaires at baseline were included in the study sample. The psychometric properties examined included acceptability (missing, ceiling and floor effects), validity (convergent and known-groups validity), and responsiveness. Known groups validity and responsiveness were assessed using both effect size (Cohen's d) and relative efficiency (F-statistic). All analyses were conducted in each language version and the total sample across all languages. RESULTS: A total of 1054 PE and 1537 DVT patients were included. 14% of PE and 10% of DVT patients had the maximum EQ-5D-5L index score. EQ-5D-5L was low to moderately correlated with other measures (r < 0.5). EQ-5D-5L was associated with larger effect size/relative efficiency in most of known group comparisons in both VTE groups. Similar results were observed for responsiveness. EQ-5D-5L performed relatively better in French, Italian and Spanish language versions. CONCLUSION: Overall EQ-5D-5L is comparable to PEmb-QoL, VEINES-QOL/Sym and PACT-Q2 in terms of acceptability, validity and responsiveness in both PE and DVT populations in English, French, German, Italian and Spanish language version. Nevertheless, it should be noted that each measure is designed to capture different aspects of health-related quality of life.

The impact of co-morbidity on the disease burden of VTE.

Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confound data interpretation concerning VTE-related mortality, costs and quality of life. We aimed to assess the contribution of co-morbidities to the burden of VTE. The PREFER in VTE registry, across seven European countries, documented and followed acute VTE patients over 12 months. Patients with co-morbidities were grouped in major co-morbidity groups: cancer, cardiovascular (CV) comorbidity (other than VTE), CV risks, venous, renal, liver, respiratory, bone and joint diseases, and lower extremity paralysis. Mortality rates and health-related quality of life (HrQoL) utility values grouped per co-morbidity were compared to the UK general population. Regression analyses were performed to determine the impact of co-morbidities on mortality and HrQoL. VTE were analyzed together and separately as pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 3455 patients were included, 40.5% with PE and 59.5% with DVT. 13% and 16% of the PE and DVT patients had no co-morbidities and had a 12-month mortality rate of 1.8% and 1.7%, respectively. Frequency and severity of co-morbidities increased mortality rates up to 30%. The EQ-5D-5L index in patients without co-morbidities were 0.826 and 0.838 for PE and DVT. These scores decreased to 0.638 and 0.555 in the presence of co-morbidities. Co-morbidities in VTE patients are common. VTE had an impact on mortality and HrQoL, and additional impact of co-morbidities was seen. Awareness of the presence of co-morbidities is important when making VTE-related treatment decisions. The presence of co-morbidities in PE and DVT patients is common and their frequency and severity in VTE patients have a substantial impact on mortality rates and HrQoL. When adjusting for co-morbidities, the impact of VTE on mortality as well as health-related quality of life remains present. Assessing patients without consideration of co-morbidities might lead to misinterpretations of the disease burden of PE and DVT.

Pulmonary embolism in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

OBJECTIVES: Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from patients in Europe is scarce. The aim of this study was to report the impacts of PE on healthcare resource utilization (HCRU) and return to work using the PREFER in VTE registry. METHODS: The PREFER in VTE registry was a prospective, observational, multicenter study in seven European countries, aiming to provide data concerning treatment patterns, HCRU, mortality, quality of life and work-loss. Patients with a first-time or recurrent PE were included and followed up at 1, 3, 6 and 12 months. Treatment patterns, re-hospitalization rates, length of hospital stays (LOS), and ambulatory/office visits, as well as proportion of patients returning to work, were assessed. Subgroups by country and with/without active cancer were examined separately. Zero-inflated negative binomial and Cox regression were applied to investigate the relationship between baseline characteristics and LOS and return to work, respectively. RESULTS: Amongst 1399 patients with PE, 53.2% were male and the average age was 62.3 ±â€¯17.1 years old. Overall, patients were treated with combinations of heparin, vitamin K antagonists (VKA) and the non-VKA oral anticoagulants (NOACs) (50.0% treated with the combination of heparin with VKA). Patients with active cancer were primarily treated with heparin (84.9%). NOACs were used more frequently in DACH (Germany, Austria and Switzerland) and France (55.2% and 32.6%) compared to Italy and Spain (4.5% and 6.1%). The VTE-related re-hospitalization rate within 12 months and the average LOS varied substantially between countries, from 26.2% in UK to 12.3% in France, and from 12.9 days in Italy to 3.9 days in France. PE patients were often co-managed by general practitioners in France and DACH (>84%), and less frequently in other countries (<47%). The regression results confirmed the country variation of HCRU. Of the employed patients (n = 385), 60% returned to work at 1 month but 27.8% had not after one year. PE patients with DVT were more likely to return to work. Active cancer was a significant predictor for not returning to work, as well as smoking history. CONCLUSIONS: Medical treatment of PE differed between patients with active cancer and patients without active cancer. VTE-related resource utilization differed markedly between countries. While the reported 'not return to work' was high for patients with PE, this may at least in part reflect the presence of co-morbidities such as cancer.

Cost-effectiveness of edoxaban compared to warfarin for the treatment and secondary prevention of venous thromboembolism in the UK.

Background: Venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is the third most common acute cardiovascular disease and represents an important burden for patients and payers. Objective: The aim was to estimate the cost-effectiveness of edoxaban, a non-VKA oral anticoagulant vs. warfarin, the currently most prescribed treatment for VTE in the UK. Study design: A Markov model was built using data from the Hokusai-VTE randomised controlled trial to estimate the lifetime costs and quality-adjusted life years (QALYs) in patients with VTE treated with edoxaban or warfarin over a lifetime horizon, from the UK National Health Services perspective. The model included VTE recurrences, VTE-related complications (post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension), and several types of bleeds associated with anticoagulation treatment. Patients were treated during a period of 6 months after the first VTE event, followed by flexible treatment duration (from 6 months to lifetime) after recurrence, i.e., tertiary prevention. Results: Edoxaban was found dominant vs. warfarin with 0.033 additional QALY and £55 less costs. The reduction of patient management costs, specifically monitoring costs, outweighed the higher drug costs. Edoxaban was dominant in all subgroups (index DVT only, all PE cases (PE with or without DVT), PE without DVT and PE with DVT). Cost-savings ranged from £54 to £81 while additional QALYs ranged from 0.031 to 0.046. Edoxaban was found dominant in 88.6% of cases and cost-effective in additional 10.9% of cases considering a £20,000 threshold in the probabilistic sensitivity analysis. Conclusion: Edoxaban may improve patients' quality of life in a lifetime horizon without additional costs for the healthcare system due to lower bleeding risk and no monitoring cost compared to warfarin.

Epidemiological characteristics and societal burden of varicella zoster virus in the Netherlands.

BACKGROUND: Varicella and herpes zoster are both caused by varicella zoster virus (VZV) infection or reactivation and may lead to complications associated with a (severe) societal burden. Because the epidemiology of VZV-related diseases in the Netherlands remains largely unknown or incomplete, the main objective of this study was to study the primary care incidence, associated complications and health care resource use. METHODS: We investigated the incidence of VZV complications in the Dutch general practitioner (GP) practices and pharmacies in a retrospective population-based cohort study (2004-2008) based on longitudinal GP data including free text fields, hospital referral and discharge letters from approximately 165,000 patients. RESULTS: The average annual incidence of varicella GP-consultations was 51.5 per 10,000 (95% CI 44.4-58.7) overall; 465.5 per 10,000 for 0-1 year-olds; 610.8 per 10,000 for 1-4 year-olds; 153.5 per 10,000 for 5-9 year-olds; 8,3 per 10,000 for >10 year olds. When only ICPC coded diagnoses were analyzed the incidence was 27% lower. The proportion of complications among varicella patients was 34.9%. Most frequently complications were upper respiratory tract infections. Almost half of the varicella patients received medication. The referral rate based on GP consultations was 1.7%. The average annual incidence of herpes zoster GP-consultations was 47.5 per 10,000 (95% CI 40.6-54.4). The incidence increased with age; 32.8 per 10,000 for <60 year-olds; 93.1 per 10,000 for 60-64 year-olds and 113.2 per 10,000 for >65 year olds. When estimating herpes zoster incidence only on ICPC coded information, the incidence was 28% lower. The complication rate of herpes zoster was 32.9%. Post herpetic neuralgia was seen most often. Of patients diagnosed with herpes zoster 67.8% received medication. The referral rate based on GP consultations was 3.5%. CONCLUSIONS: For varicella the highest incidence of GP-consultations was found in 1-4 year-olds, for herpes zoster in the >65 years olds. The occurrence of complications was not age-dependent but varies per complication. When estimating incidence of VZV-related diseases in primary care, based on diagnostic codes only, one should be aware of a gross underestimation of the incidence. Our analysis may have important implications for the outcomes of upcoming cost-effectiveness analyses on VZV vaccination.

The burden of varicella from a parent's perspective and its societal impact in The Netherlands: an Internet survey.

BACKGROUND: Varicella is a common childhood disease. Only 5% of first varicella-zoster-virus infections occur asymptomatically. Most data on the burden of varicella stem from health service databases. This study aims to provide insight in the burden of varicella from a parent's perspective including cases outside the healthcare system. METHODS: An internet questionnaire was developed for parents in the Netherlands to report health care resource use and productivity losses during the varicella episode in their child younger than 6 years. 11,367 invitations were sent out to members with children of an internet panel of a market research agency. 4,168 (37%) parents started the questionnaire (response rate), of which 360 (9%) stopped before completion and 1,838 (44%) were out of the target group. In total 1,970 parents completed the questionnaire. The questionnaire provided a symptom list ranging from common symptoms, such as skin vesicles, itching to fits or convulsions. A posteriori, in the analyses, the symptoms 'skin infections', 'fits/convulsions', 'unconsciousness', and 'balance and movement disorders' were labelled as complications. There was no restriction to time since the varicella episode for inclusion in the analyses. RESULTS: The 1,970 respondents had in total 2,899 children aged younger than six years, of which 2,564 (88%) children had had varicella. In 62% of the episodes the parent did not seek medical help. In 18% of all episodes symptoms labelled as complications were reported; in 11% of all episodes parents visited a medical doctor (MD) for a complication. Reporting of complications did not differ (X2 ; p = 0.964) between children with a recent (≤ 12 months ago) or a more distant (> 12 months) history of varicella. Prescription drugs were used in 12% of the children with varicella; OTC drugs in 72%. Parents reported work loss in 17% of the varicella-episodes (23% when MD visit; 14% when no MD-visit) for on average 14 hours, which equals to 2.5 hours of work loss for any given varicella-episode. CONCLUSIONS: This study shows the full spectrum of varicella-episodes and associated healthcare use, including the large proportion of cases not seeking medical care and the societal impact associated with those cases.

Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution.

AIMS: To assess the potential annual savings due to generic and therapeutic substitution of statin therapy for the general Dutch population, taking the patients medical history into account. METHODS: We conducted a population-based costing study using the PHARMO Record Linkage System (RLS). PHARMO RLS contains drug dispensing records from a representative sample of pharmacies located in more than 50 regions in the Netherlands. We selected all statin users in the database since 2003. The cost-savings of generic substitution of statin therapy for all simvastatin and pravastatin users, and of therapeutic substitution of statin therapy for other statin users were calculated. Substituting current users and new users of statins were considered separately. Therapeutic substitution was based on the medical history of the individual patient. Patients were only substituted if there was an appropriate substitute available. The appropriateness of substitution was based on drug-drug interactions between statins and possible comedication and the availability of an equipotent alternative. RESULTS: Substituting (generic and therapeutic) statin therapy for all current users would lead to potential annual savings of approximately 87 million euros. Substituting (generic and therapeutic) all starters on statin therapy would lead to potential annual savings of around 51 million euros. In the case of generic substitution only, the potential annual savings for all current simvastatin and pravastatin users would be 2.4 million euros and for the new users about 1.8 million euros. CONCLUSIONS: From an economic point of view, society could gain a lot from substituting statin therapy, especially from therapeutic substitution.

Economic evaluations of cholesterol-lowering drugs: a critical and systematic review.

The wide availability of economic evaluations and their increasing importance for decision making emphasises the need for economic evaluations that are methodologically sound. The aim of this review was to provide users of economic evaluations of cholesterol-lowering drugs with an insight into the quality of these evaluations. By focusing on the most relevant studies, the gap between research and policy making may be narrowed. A systematic review was conducted. All Dutch and English publications on economic evaluations of cholesterol-lowering drugs were identified by searching PubMed, the Centre for Reviews and Dissemination database (CRD), the NHS Economic Evaluation Database (NHS EED), the Health Technology Assessment database (HTA) and the Database of Abstracts of Reviews of Effects (DARE). A search strategy was set up to identify the articles to be included. The quality of these articles was assessed using Drummond's checklists. The scoring was performed by at least two reviewers. When necessary, disagreement between these reviewers was decided upon in a consensus meeting. We calculated an average quality score for the included articles. The search identified 1390 articles, of which 23 were included. Most studies measured the costs per life-year gained. The overall score per study was disappointing and varied between 2.7 and 7.7, with an average of 5.5. Most studies scored high on the measurement of costs and consequences, whereas the establishment of effectiveness left room for improvement. Only two studies included a well performed incremental analysis. This study noted an increase of quality of economic evaluations over time, suggesting the value of cost-effectiveness studies for policy decisions increases over time. In general, piggy-back evaluations tended to score higher on quality and may therefore be more valuable in decision making.

Drug costs associated with non-adherence to cholesterol management guidelines for primary prevention of cardiovascular disease in an elderly population: the Rotterdam study.

BACKGROUND: In The Netherlands, costs of HMG-CoA reductase inhibitor (statin) use have recently increased sharply compared with costs of other drugs. However, several studies have established both undertreatment and non-guidelines-indicated treatment with statins, suggesting a suboptimal use of resources. OBJECTIVE: To estimate the drug costs associated with non-guidelines-indicated treatment and undertreatment with statins in an elderly population. PATIENTS AND SETTING: Data were obtained from the Rotterdam Study, a population-based prospective cohort study which began in 1990 with 7983 participants aged > or =55 years. Subjects with a history of cardiovascular disease (CVD) were excluded. Pharmacy records were used to assess patterns of medication use in daily medical practice. MAIN OUTCOME MEASURE: Non-guidelines-indicated treatment and undertreatment with statins were established in relation to Dutch cholesterol management guidelines for all participants. We calculated the costs of statin therapy associated with non-guidelines-indicated treatment, and the costs of statins if all those undertreated were to receive statins. The results were projected on to the Dutch population to determine the economic implications of non-adherence to cholesterol management guidelines in the elderly. RESULTS: Of the participants who started treatment with statins for the primary prevention of CVD during follow-up, 69% received non-guidelines-indicated treatment. More men (7.5%) were undertreated than women (1.6%) and more women (6.2%) received non-guidelines-indicated treatment than men (1.5%). Among the participants without CVD who were still alive at 1 January 2002, 14% were eligible for statin therapy but were untreated. After projection of the prevalence of non-guidelines-indicated treatment and undertreatment to the Dutch population, the absolute costs for non-guidelines-indicated treatment with statins in 2005 were estimated to be approximately 23 million euro(uncertainty limits [UL]: 19-28 million euro), while the cost to eliminate undertreatment was also 23 million euro (UL: 19-28 million euro). CONCLUSION: Reallocation of resources used for statin therapy from those receiving non-guidelines-indicated treatment to those being undertreated could lead to a more efficient use of resources.