Development and pilot-testing of a condition-specific instrument to assess the quality-of-life in children and adolescents born with esophageal atresia.

The survival rate of children with esophageal atresia has today reached 95%. However, children are at risk of chronic morbidity related to esophageal and respiratory dysfunction, and associated anomalies. This study describes the pilot testing of a condition-specific health-related quality-of-life instrument for children with esophageal atresia in Sweden and Germany, using a patient-derived development approach consistent with international guidelines. Following a literature review, standardized focus groups were conducted with 30 Swedish families of children with esophageal atresia aged 2-17 years. The results were used for item generation of two age-specific pilot questionnaire versions. These were then translated from Swedish into German with considerations of linguistic and semantical perspectives. The 30-item pilot questionnaire for children aged 2-7 years was completed by 34 families (parent report), and the 50-item pilot questionnaire for children aged 8-17 years was completed by 52 families (51 child report, 52 parent report), with an overall response rate of 96% in the total sample. Based on predefined psychometric criteria, poorly performing items were removed, resulting in an 18-item version with three domains (Eating, Physical health and treatment, Social isolation and stress,) for children aged 2-7 years and a 26-item version with four domains (Eating, Social relationships, Body perception, and Health and well-being) for children aged 8-17 years. Both versions demonstrated good internal consistency reliability and acceptable convergent and known-groups validity for the total scores. The study identified specific health-related quality-of-life domains for pediatric patients with esophageal atresia, highlighting issues that are important for follow-up care. After field testing in a larger patient sample, this instrument can be used to enhance the evaluation of pediatric surgical care.

Cost of treatment in patients with metastatic soft tissue sarcoma who respond favourably to chemotherpy. The SArcoma treatment and Burden of Illness in North America and Europe (SABINE) study.

Treatment of metastatic soft tissue sarcoma (mSTS) commonly includes multiple lines of chemotherapy, until a decline in performance status precludes further treatment. The primary objective of this study was to describe the lifetime healthcare resource utilisation and cost among mSTS patients with favourable response to chemotherapy. SABINE was a multi-centre (n = 25), multi-country (n = 9) retrospective chart review study of mSTS patients with favourable response to chemotherapy following 4 cycles. Healthcare resource utilisation was collected from first line until death or end of follow-up. Costs were analysed by health states (defined by treatment line, chemotherapy use and disease progression) and estimated by multiplying the mean weekly cost per health state by the expected number of weeks spent in each health state. Expected per-patient lifetime medical cost was €65 616 (95% CI: €51 454-€85 003); comprised of IV chemotherapy (31.7%), inpatient care (24.8%), concomitant medication (11.0%), oral chemotherapy (8.9%), outpatient visits (8.8%), radiotherapy (6.3%), hospice (4.0%), imaging (3.7%) and laboratory (0.7%). Weekly costs were 280-330% higher during chemotherapy treatment periods than off-chemotherapy, especially after disease progression. Per-patient costs were highest in the USA and lowest in the Netherlands and UK. The economic burden of mSTS is considerable and the amount of resources devoted to its treatment varies across countries.

Health economic evaluation of treatments for Alzheimer's disease: impact of new diagnostic criteria.

The socio-economic impact of Alzheimer's disease (AD) and other dementias is enormous, and the potential economic challenges ahead are clear given the projected future numbers of individuals with these conditions. Because of the high prevalence and cost of dementia, it is very important to assess any intervention from a cost-effectiveness viewpoint. The diagnostic criteria for preclinical AD suggested by the National Institute on Aging and Alzheimer's Association workgroups in combination with the goal of effective disease-modifying treatment (DMT) are, however, a challenge for clinical practice and for the design of clinical trials. Key issues for future cost-effectiveness studies include the following: (i) the consequences for patients if diagnosis is shifted from AD-dementia to predementia states, (ii) bridging the gap between clinical trial populations and patients treated in clinical practice, (iii) translation of clinical trial end-points into measures that are meaningful to patients and policymakers/payers and (iv) how to measure long-term effects. To improve cost-effectiveness studies, long-term population-based data on disease progression, costs and outcomes in clinical practice are needed not only in dementia but also in predementia states. Reliable surrogate end-points in clinical trials that are sensitive to detect effects even in predementia states are also essential as well as robust and validated modelling methods from predementia states that also take into account comorbidities and age. Finally, the ethical consequences of early diagnosis should be considered.

SCOPE: a scorecard for osteoporosis in Europe.

SUMMARY: The scorecard summarises key indicators of the burden of osteoporosis and its management in each of the member states of the European Union. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. INTRODUCTION: The scorecard for osteoporosis in Europe (SCOPE) is an independent project that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis. METHODS: The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union (EU27). The information researched covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap). RESULTS: There was a marked difference in fracture risk among the EU27. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For example, despite the wide availability of treatments to prevent fractures, in the majority of the EU27, only a minority of patients at high risk receive treatment for osteoporosis even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. CONCLUSIONS: The scorecard will enable healthcare professionals and policy makers to assess their country's general approach to the disease and provide indicators to inform future provision of healthcare.

Drivers of cost and health-related quality of life in patients with systemic lupus erythematosus (SLE): a Swedish nationwide study based on patient reports.

The objective of this paper is to investigate drivers of cost and health-related quality of life (HRQoL) related to disease activity and fatigue among patients with systemic lupus erythematous (SLE). A questionnaire was sent to members of a patient organization with a self-reported diagnosis of SLE, requesting information on demographics and disease characteristics, medications, resource utilization, informal care, loss of productivity, fatigue and HRQoL in relation to SLE. Mean annual costs per patient were estimated from a societal perspective. HRQoL was measured through EQ-5D and fatigue was measured through a 10 cm VAS scale. Patient-reported disease activity was measured through the Systemic Lupus Activity Questionnaire (SLAQ) and corticosteroid dose. Drivers of costs and HRQoL were analyzed through regression analysis. A total of 339 patients out of 737 returned the questionnaire. Mean age was 55; 94% were female. The mean HRQoL measured through the five-item EQ-5D instrument was 0.64 and total costs were estimated at €22,594 (direct costs €7818; indirect costs €14,776). Disease activity, fatigue and corticosteroid doses had a statistically significant impact on costs and HRQoL. This study demonstrates that Swedish patients with SLE have low HRQoL and incur high societal costs and that are both associated with and most likely driven by disease activity, fatigue and corticosteroid use.

Costs explained by function rather than diagnosis--results from the SNAC Nordanstig elderly cohort in Sweden.

BACKGROUND: Because the prevalence of many brain disorders rises with age, and brain disorders are costly, the economic burden of brain disorders will increase markedly during the next decades. AIM: The purpose of this study is to analyze how the costs to society vary with different levels of functioning and with the presence of a brain disorder. METHODS: Resource utilization and costs from a societal viewpoint were analyzed versus cognition, activities of daily living (ADL), instrumental activities of daily living (IADL), brain disorder diagnosis and age in a population-based cohort of people aged 65 years and older in Nordanstig in Northern Sweden. Descriptive statistics, non-parametric bootstrapping and a generalized linear model (GLM) were used for the statistical analyses. RESULTS: Most people were zero users of care. Societal costs of dementia were by far the highest, ranging from SEK 262,000 (mild) to SEK 519,000 per year (severe dementia). In univariate analysis, all measures of functioning were significantly related to costs. When controlling for ADL and IADL in the multivariate GLM, cognition did not have a statistically significant effect on total cost. The presence of a brain disorder did not impact total cost when controlling for function. The greatest shift in costs was seen when comparing no dependency in ADL and dependency in one basic ADL function. CONCLUSION: It is the level of functioning, rather than the presence of a brain disorder diagnosis, which predicts costs. ADLs are better explanatory variables of costs than Mini mental state examination. Most people in a population-based cohort are zero users of care.

The economic impact of dementia in Europe in 2008-cost estimates from the Eurocode project.

OBJECTIVE: Care for demented people is very resource demanding, the prevalence is increasing and there is so far no cure. Cost of illness (CoI) studies are important by identifying the distribution of costs between different payers of care. The European Union (EU) funded the European Collaboration on Dementia (Eurocode) as part of the EU's 2005 work plan of the Community public health programme. Eurocode was administered by Alzheimer Europe. The aim was to describe the economic impact of dementia in Europe in 2008. METHODS: Eurocode's new estimates for dementia prevalence were included in a cost model based on published European CoI papers. For countries where no CoI figures were available, imputation was used. RESULTS: The total CoI of dementia in the EU27 in 2008 was estimated to be €160 billion (€22 000 per demented per year), of which 56% were costs of informal care. The corresponding costs for the whole Europe was €177 billion. In northern Europe, the direct costs are estimated to be considerabe, while the cost of informal care is the major cost component in southern Europe. The sensitivity analysis showed a range for total EU27 costs between €111 and 168 billion. CONCLUSIONS: The estimated CoI in this study is higher than in previous studies. There are also large differences in different European regions. Notwithstanding the methodological challenges, the societal costs of dementia in Europe are very high which in turn have substantial resource impacts on the social and health care systems in Europe.

Assessment of potential measures in models of progression in Alzheimer disease.

BACKGROUND: In estimating the potential benefits of treatment, it is often necessary to extrapolate beyond clinical trial results using economic modeling. Previous attempts in Alzheimer disease (AD) were primarily based on the Mini-Mental State Examination (MMSE) due to its widespread use. These models were criticized as not accurately reflecting the total impact of the disease, providing untrustworthy estimates of treatment benefit. We compared 3 alternatives to the MMSE with respect to bridging between clinical outcomes needed for regulatory approval and economic and quality of life (QOL) outcomes important to reimbursement agencies. METHODS: The MMSE, Disability Assessment in Dementia (DAD) scale, Clinical Dementia Rating (CDR) scale, and Dependence Scale (DS) were compared in their ability to explain variation in cognitive, functional, and behavioral measures as well as economic and QOL outcomes using univariate (Pearson correlations) and multivariate (linear regression) analyses of data from research sites in the United States and Europe. RESULTS: Subjects with mild to moderate AD (n = 196; mean 75.9 years; 56% female) were evaluated. The DS, DAD, and CDR were moderately correlated with the MMSE (Pearson correlations, range 0.54-0.58) but performed better (higher adjusted R(2)) than the MMSE in explaining variations in subject behavior, QOL, and health status. The DS and DAD performed better in explaining variation in medical costs, caregiver QOL, and caregiver time. CONCLUSIONS: Measures of function (DAD) or dependence on others (DS), or global measures (CDR), appear to be better candidates than the MMSE for modeling AD progression.

Costs of dementia in Hungary.

OBJECTIVE: The main aim of this paper is to give an overview on the quality of life, health care utilisation and costs of dementia in Hungary. METHOD: A cross-sectional non-population based study of 88 consecutive dementia patients and their caregivers was conducted in three GP practices and one outpatient setting in 2008. Resource Utilization in Dementia (RUD), Mini Mental State Examination (MMSE) and quality of life (EQ-5D) were surveyed and cost calculations were performed. Costs of patients living at home were estimated by the current bottom-up cost-of-illness calculations, while costs of nursing home patients were considered by official reimbursement to determine the disease burden from a societal viewpoint. RESULTS: The mean age of the patients was 77.4 years (SD=9.2), 59% of them were female. The mean MMSE score was 16.70 (SD=7.24), and the mean EQ-5D score was 0.40 (SD=0.34). The average annual cost of dementia was 6,432 Euros per patient living at home and 6,086 Euros per patient living in nursing homes. For the whole demented population (based on EuroCoDe data) we estimated total annual costs of 846.8 million Euros; of which 55% are direct costs, 9% indirect costs and 36% informal care cost. Compared to acute myocardial infarction the total disease burden of dementia is 26.3 times greater. CONCLUSIONS: This is the first study investigating resource utilisation, costs, and quality of life of dementia patients in the Central and Eastern European region. Compared to the general population of Hungary EQ-5D values of the demented patients are lower in all age groups. Dementia related costs are much lower in Hungary compared to Western European countries. There is no remarkable difference between the costs of demented patients living at home and in nursing homes, from the societal point of view.

Differences in resource use and costs of dementia care between European countries: baseline data from the ICTUS study.

OBJECTIVES: This study aimed to estimate the costs of formal and informal care of patients with Alzheimer's disease, to compare care costs across European countries and identify potential differences in cost patterns between countries and regions. SETTING: The ICTUS study is a prospective, naturalistic observational study conducted in specialised memory clinics in 12 European countries. In total, 1385 patients diagnosed with Alzheimer's disease were enrolled at baseline. All subjects had a reliable informant (primary caregiver) and informed consent was obtained from patients or their primary caregiver. MAIN OUTCOME MEASURES: Resource utilization data was captured with the RUD Lite (Resource Utilization in Dementia) instrument and caregiver burden with the Zarit Burden Interview (ZBI). Patient disease severity was measured with the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog), Katz´ index (PADL), Instrumental activities of daily living (IADL) scale and Neuropsychiatric inventory (NPI). RESULTS: The mean annual cost of care per patient was estimated to €7,820 (95% CI: €7,194-€8,446), whereof 54% were costs of informal care, 16% direct medical costs and 30% community care costs. There were substantial differences in total resource utilization and also in the balance between formal and informal care between Northern, Western and Southern Europe. PADL scores were strongly associated with formal care costs while IADL scores correlated strongly with informal care costs. CONCLUSIONS: Costs of Alzheimer's disease are high across European countries. Activities of daily living is an important determinant of care costs. Formal care service use is lower and informal care higher in Southern Europe compared to Western and Northern Europe. Differences in resource utilization patterns are important to consider in international studies of dementia care costs as well as in economic evaluations of new treatments for dementia.

IPECAD5--Fifth International Pharmaco-Economic Conference on Alzheimer's Disease.

The Fifth International Pharmaco-Economic Conference on Alzheimer's Disease was held in New York, on March 27-29 in 2008. The attendees included researchers and key opinion leaders within the academia, pharmaceutical industry, patient organizations and regulatory bodies, collecting the worldwide leading expertise in Alzheimer research today. A summary of the presentations and conclusions from the discussions are presented in this publication. Pharmaco-economics need to play a leading role in developing and communicating evidence of the value of anti-dementia drugs, now and in the future. For the development of evidence, the challenges include transparency and standardization of costs of care assessment, improved diagnostics for identifying target patient groups, improved endpoints for assessing outcomes and improved models for assessing the long term consequences of competing treatment strategies. For the communication of evidence, the challenge lies in convincing decision makers to recognize the integrated burden of the disease, including its interaction with co-morbidities and burden on caregivers, and to consider the consequences of competing treatment strategies from a societal perspective.

Cross sectional observational study on the societal costs of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is one of the most important causes of morbidity and functional decline among the elderly and gives rise to substantial costs for society. There is today limited data on resource utilization and quality of life in AD, in particular in the severe stage of disease. AIMS & METHODS: The objectives of this study were to estimate the relationship between costs, patient and caregiver quality of life, and disease severity. For 233 patients in Sweden and their caregivers cross-sectional data on cognitive function (MMSE), ADL ability, behavioral disturbances, formal and informal resource use and health related quality of life (HRQoL) were collected by questionnaires to caregivers and to the treating physician. Patients were stratified into the disease stages mild, moderate and severe AD based on MMSE-scores. RESULTS: The mean annual total cost in 2007 USD was 23,400 in mild, 56,800 in moderate and 71,400 in severe AD. Special forms of accommodation accounted for the majority of costs. Costs were higher for patients with lower cognitive function, lower ADL ability and more behavioral disturbances, with ADL ability being the most consistent predictor of costs. There were significant differences in HRQoL between the disease stages: health utility scores were 0.64 in mild, 0.39 in moderate and 0.24 in severe AD. CONCLUSIONS: The societal costs of AD are very high, especially for patients with moderate and severe AD. This implies that treatments with the ability to delay progression of the disease into more severe stages have the potential to save large costs for society.

Health-economic evaluation of three imaging strategies in patients with suspected colorectal liver metastases: Gd-EOB-DTPA-enhanced MRI vs. extracellular contrast media-enhanced MRI and 3-phase MDCT in Germany, Italy and Sweden.

The purpose of this study was to perform an economic evaluation of hepatocyte-specific Gd-EOB-DTPA enhanced MRI (PV-MRI) compared to extracellular contrast-media-enhanced MRI (ECCM-MRI) and three-phase-MDCT as initial modalities in the work-up of patients with metachronous colorectal liver metastases. The economic evaluation was performed with a decision-tree model designed to estimate all aggregated costs depending on the initial investigation. Probabilities on the need for further imaging to come to a treatment decision were collected through interviews with 13 pairs of each a radiologist and a liver surgeon in Germany, Italy and Sweden. The rate of further imaging needed was 8.6% after initial PV-MRI, 18.5% after ECCM-MRI and 23.5% after MDCT. Considering the cost of all diagnostic work-up, intra-operative treatment changes and unnecessary surgery, a strategy starting with PV-MRI with 959 Euro was cost-saving compared to ECCM-MRI (1,123 Euro) and MDCT (1,044 Euro) in Sweden. In Italy and Germany, PV-MRI was cost-saving compared to ECCM-MRI and had total costs similar to MDCT. In conclusion, our results indicate that PV-MRI can lead to cost savings by improving pre-operative planning and decreasing intra-operative changes. The higher cost of imaging with PV-MRI is offset in such a scenario by lower costs for additional imaging and less intra-operative changes.

Community occupational therapy for older patients with dementia and their care givers: cost effectiveness study.

OBJECTIVE: To assess the cost effectiveness of community based occupational therapy compared with usual care in older patients with dementia and their care givers from a societal viewpoint. DESIGN: Cost effectiveness study alongside a single blind randomised controlled trial. SETTING: Memory clinic, day clinic of a geriatrics department, and participants' homes. Patients 135 patients aged > or =65 with mild to moderate dementia living in the community and their primary care givers. INTERVENTION: 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision. MAIN OUTCOME MEASURES: Incremental cost effectiveness ratio expressed as the difference in mean total care costs per successful treatment (that is, a combined patient and care giver outcome measure of clinically relevant improvement on process, performance, and competence scales) at three months after randomisation. Bootstrap methods used to determine confidence intervals for these measures. RESULTS: The intervention cost 1183 euros (848 pounds sterling, $1738) (95% confidence interval 1128 euros (808 pounds sterling, $1657) to 1239 euros (888 pounds sterling, $1820)) per patient and primary care giver unit at three months. Visits to general practitioners and hospital doctors cost the same in both groups but total mean costs were 1748 euros (1279 pounds sterling, $2621) lower in the intervention group, with the main cost savings in informal care. There was a significant difference in proportions of successful treatments of 36% at three months. The number needed to treat for successful treatment at three months was 2.8 (2.7 to 2.9). CONCLUSIONS: Community occupational therapy intervention for patients with dementia and their care givers is successful and cost effective, especially in terms of informal care giving.

Assessing health economic outcome in Alzheimer's disease clinical trials.

This paper reviews methodological considerations in collecting data on economic endpoints and conducting economic evaluation alongside clinical trials in Alzheimer's disease (AD).

An estimate of the worldwide prevalence and direct costs of dementia in 2003.

Dementia disorders are today considered to be a major driver of costs in health care and social systems and worrying estimates of future dementia prevalence have been presented. It is of great interest for policy makers to have an estimate of dementia disorders' contribution to global social and health care costs, particularly in light of the demographic prognoses. The worldwide costs of dementia were estimated from prevalence figures for different regions, and cost-of-illness studies from key countries using a model based on the relationship between direct costs of care per demented and the gross domestic product per capita in each country. The worldwide direct costs for dementia in 2003 are estimated at 156 billion USD in the main scenario based on a worldwide prevalence of 27.7 million demented persons (sensitivity analysis: 129-159 billion USD). Ninety-two percent of the costs are found in the advanced economies with 38% of the prevalence. Although there are several sources of uncertainty, it is obvious that the worldwide costs are substantial and the expected increase in elderly people in the developing countries presents a great challenge.

The cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke: results from the Study on COgnition and Prognosis in the Elderly.

Patients who survive a first stroke are often left with permanent disabilities, and have significant needs for rehabilitation and long-term care. Antihypertensive treatment reduces the risk of cardiovascular events such as stroke. The purpose of this study was to investigate the cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke. The cost-effectiveness analysis was based on data from Study on COgnition and Prognosis in the Elderly (SCOPE), where patients were randomly assigned to receive the angiotensin receptor blocker candesartan or placebo, with open-label active antihypertensive treatment added as needed. The analysis was carried out using a Markov model, which combined clinical and resource utilization data from SCOPE with Swedish retail prices for drugs and unit costs for in-patient stays, and outpatient visits. The cost per patient was 1949 EUR in the candesartan group and 1578 EUR in the control group. The largest share of the cost was attributed to antihypertensive treatment in the candesartan group and to the long-term cost of stroke in the control group. Candesartan-based antihypertensive treatment was associated with 0.0289 additional quality-adjusted life-years (QALYs) per patient and an incremental cost per QALY gained of approximately 13,000 EUR. Sensitivity analyses showed that these results were fairly stable. In conclusion, the cost per QALY gained with candesartan-based antihypertensive treatment lies within the range of society's willingness to pay for health gains. The results indicate that candesartan-based antihypertensive treatment is cost-effective for the prevention of nonfatal stroke.

Denitrification rate and carbon source consumption in full-scale wastewater filtration.

In response to new demands for increased removal of nitrogen and phosphorus, the Henriksdal and Bromma treatment plants, with hydraulic loads of 283,000 and 148,000 m3/d, respectively, built filtration steps as a final process step in the plants. The denitrification rates in a full-scale and in a pilot plant filter are calculated to 13.1 and 21.3 g (NO3+NO2)-N/(m3 x h), respectively, in the total filter bed after 2.5-24.2 and 16.0-28.0 h of operational time, and 6.4 and 18.7 g (NO3+NO2)-N/(m3 x h), respectively, after 1.0 and 0.1-0.9 h of operational time. In composite samples, the denitrification rate in the total filter bed is 10-20 g (NO3+NO2)-N/(m3 x h) in the full-scale filter. The average values for k = deltaCODf/deltaC(T) are 1.6 and around 3 in the total filter bed in steady state and in the beginning of the experiments, respectively, both in the full-scale and in the pilot plant study. The carbon source costs for reducing the concentration of nitrate nitrogen in the Bromma plant from 12 to 8 mg/l in the effluent are 117,400 EUR and 147,400 EUR with methanol and ethanol, respectively, as a carbon source.