Evaluation of the Fiscal Costs and Consequences of Alzheimer's Disease in Germany: Microsimulation of Patients' and Caregivers' Pathways.

BACKGROUND: Alzheimer's disease is a severe condition, impacting individual's wellbeing and independence in daily activities. Informal care provision is common and of great value to societies but is not without negative externalities to households and the broader economy. OBJECTIVES: Estimate the lifetime incremental fiscal consequences of Alzheimer's disease in community-based individuals and their informal caregivers. SETTING: The fiscal consequences of Alzheimer's disease was modeled using the German government and social security perspective. PARTICIPANTS: Synthetic cohort containing 1,000 pairs of people with Alzheimer's disease and their informal caregivers, compared to 1,000 demographically identical pairs from the general population. DESIGN: Disease progression was modeled using published equations and a state-transition microsimulation framework. Labor participation, financial support and paid taxes were estimated according to cognitive decline and caregiving responsibilities using German labor statistics and tax rates. Healthcare costs were sourced from several German publications. Costs and life-years were discounted at 3% annually. MEASUREMENTS: Results are reported as lifetime incremental differences in total tax revenue and transfer payments between the cohort affected by Alzheimer's disease and their general population analogues. RESULTS: The Alzheimer's disease-affected pair was associated with net incremental fiscal losses of €74,288 ($85,037) to the German government and social security over the lifetime of people with Alzheimer's disease. Most costs were lost taxes on employment earnings (48.4%) due to caregivers working reduced hours. Caregivers were estimated to earn €56,967 ($65,209) less than their general population analogues. Financial support for informal and formal care accounted for 20.4%, and medical healthcare costs represented 24.0% of the incremental fiscal losses. Sensitivity analyses confirmed the robustness of the model results. In a cohort with early onset Alzheimer's disease, incremental fiscal losses were predicted to be €118,533 ($114,209) over the lifetime of people with Alzheimer's disease. CONCLUSIONS: Alzheimer's disease externalities profoundly impact public economics for governments and should be considered to inform policy making and healthcare planning.

Major Cost Drivers in Assessing the Economic Burden of Alzheimer's Disease: A Structured, Rapid Review.

BACKGROUND: Alzheimer's Disease is the most common cause of dementia, affecting memory, thinking and behavior. Symptoms eventually grow severe enough to interfere with daily tasks. AD is predicted to increase healthcare spending and costs associated with formal and informal caregiving. The aim of this study was to identify and quantify the contribution of the different cost components associated with AD. METHODS: A structured literature review was conducted to identify studies reporting the economic burden of Alzheimer`s Disease beyond the healthcare setting. The search was conducted in Medline, Embase and EconLit and limited to studies published in the last 10 years. For each identified cost component, frequency weighted mean costs were calculated across countries to estimate the percentage contribution of each component by care setting and disease severity. Results obtained by each costing approach were also compared. RESULTS: For community-dwelling adults, the percentage of healthcare, social care and indirect costs to total costs were 13.9%, 17.4% and 68.7%, respectively. The percentage of costs varied by disease severity with 26.0% and 10.4% of costs spent on healthcare for mild and severe disease, respectively. The proportion of total spending on indirect costs changed from 60.7% to 72.5% as disease progressed. For those in residential care, the contribution of each cost component was similar between moderate and severe disease. Social care accounted on average for 85.9% of total costs. CONCLUSION: The contribution of healthcare costs to the overall burden was not negligible; but was generally exceeded by social and informal care costs.

Multi-criteria decision analysis (MCDA): testing a proposed MCDA framework for orphan drugs.

BACKGROUND: Since the introduction of the orphan drugs legislation in Europe, it has been suggested that the general method of assessing drugs for reimbursement is not necessarily suitable for orphan drugs. The National Institute for Health and Clinical Excellence indicated that several criteria other than cost and efficacy could be considered in reimbursement decisions for orphan drugs. This study sought to explore the multi-criteria decision analysis (MCDA) framework proposed by (Orphanet J Rare Dis 7:74, 2012) to a range of orphan drugs, with a view to comparing the aggregate scores to the average annual cost per patient for each product, and thus establishing the merit of MCDA as a tool for assessing the value of orphan drugs in relation to their pricings. METHODS: An MCDA framework was developed using the nine criteria proposed by (Orphanet J Rare Dis 7:74, 2012) for the evaluation of orphan drugs, using the suggested numerical scoring system on a scale of 1 to 3 for each criterion. Correlations between the average annual cost of the drugs and aggregate MCDA scores were tested and plotted graphically. Different weightings for each of the attributes were also tested. A further analysis was conducted to test the impact of including the drug cost as an attribute in the aggregate index scores. RESULTS: In the drugs studied, the R 2, that statistically measures how close the data are to the fitted regression line was 0.79 suggesting a strong correlation between the drug scores and the average annual cost per patient. CONCLUSION: Despite several limitations of the proposed model, this quantitative study provided insight into using MCDA and its relationship to the average annual costs of the products.

Universal coverage of IVF pays off.

STUDY QUESTION: What was the clinical and economic impact of universal coverage of IVF in Quebec, Canada, during the first calendar year of implementation of the public IVF programme? SUMMARY ANSWER: Universal coverage of IVF increased access to IVF treatment, decreased the multiple pregnancy rate and decreased the cost per live birth, despite increased costs per cycle. WHAT IS KNOWN ALREADY: Public funding of IVF assures equality of access to IVF and decreases multiple pregnancies resulting from this treatment. Public IVF programmes usually mandate a predominant SET policy, the most effective approach for reducing the incidence of multiple pregnancies. STUDY DESIGN, SIZE, DURATION: This prospective comparative cohort study involved 7364 IVF cycles performed in Quebec during 2009 and 2011 and included an economic analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF cycles performed in the five centres offering IVF treatment in Quebec during 2009, before implementation of the public IVF programme, were compared with cycles performed at the same centres during 2011, the first full calendar year following implementation of the programme. Data were obtained from the Canadian Assisted Reproductive Technologies Register (CARTR). Comparisons were made between the two periods in terms of utilization, pregnancy rates, multiple pregnancy rates and costs. MAIN RESULTS AND THE ROLE OF CHANCE: The number of IVF cycles performed in Quebec increased by 192% after the new policy was implemented. Elective single-embryo transfer was performed in 1.6% of the cycles during Period I (2009), and increased to 31.6% during Period II (2011) (P < 0.001). Although the clinical pregnancy rate per embryo transfer was lower in 2011 than in 2009 (24.9 versus 39.9%, P < 0.001), the multiple pregnancy rate was greatly reduced (6.4 versus 29.4%, P < 0.001). The public IVF programme increased government costs per IVF treatment cycle from CAD$3730 to CAD$4759. Despite increased costs per cycle, the efficiency defined by the cost per live birth, which factored in downstream health costs up to 1 year post delivery, decreased from CAD$49 517 to CAD$43 362 per baby conceived by either fresh and frozen cycles. LIMITATIONS, REASONS FOR CAUTION: The costs described in the economic model are likely an underestimate as they do not factor in many of the long-term costs that can occur after 1 year of age. The information collected in the Canadian ART register precludes the calculation of cumulative pregnancy rates. WIDER IMPLICATIONS OF THE FINDINGS: Our study confirms that the implementation of a public IVF programme favouring eSET not only sharply decreases the incidence of multiple pregnancy, but also reduces the cost per live birth. STUDY FUNDING/COMPETING INTEREST(S): M.P.V. holds a fellowship award from the Canadian Institutes of Health Research (CIHR). The economic analysis performed by M.P.C. was supported by an unrestricted grant from Ferring Pharmaceutical.

The economics of mesalazine in active ulcerative colitis and maintenance in the Netherlands.

BACKGROUND: In this study we investigate the costs and benefits of topical mesalazine combined with oral mesalazine therapy for active ulcerative colitis (UC), and once daily (OD ) mesalazine 2 grams versus twice daily (BID ) for maintaining UC remission. METHODS: Two decision analytic models were constructed to evaluate treatment costs and quality-adjusted life years (QALYs) associated with mesalazine. The first model explored 4 g oral mesalazine in combination with 1 g topical mesalazine during active UC compared with 4 g oral mesalazine monotherapy for achieving clinical remission. The second model compared remission rates at one year for OD 2 g oral mesalazine compared with BID 1 g adjusted for compliance. All direct costs were obtained from established treatment costs in the Netherlands. RESULTS: The average cost of treatment to transition an active UC patient into remission using oral plus topical mesalazine or oral mesalazine monotherapy was v2207 (95% CI: v1402 to v3332) and v2945 (95% CI: v1717 to v4592), respectively. The annual average cost-saving of adding topical mesalazine delivered for four weeks during active UC was v738. The average annual costs of maintenance of remission with OD and BID therapy were v1293 (95% CI: v1062 to v1496) and v1502 (95% CI: v1262 to 1708), respectively with an annual average per person savings of v209. CONCLUSION: Topical mesalazine during acute UC flares results in lower costs due to reduced healthcare consumption attributed to faster symptom resolution. Furthermore, as a result of lower costs and modest QALY gains, maintenance therapy using OD mesalazine is the dominant treatment option if compared with BID mesalazine.

Detection of pulsed gamma rays above 100 GeV from the Crab pulsar.

We report the detection of pulsed gamma rays from the Crab pulsar at energies above 100 giga-electron volts (GeV) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) array of atmospheric Cherenkov telescopes. The detection cannot be explained on the basis of current pulsar models. The photon spectrum of pulsed emission between 100 mega-electron volts and 400 GeV is described by a broken power law that is statistically preferred over a power law with an exponential cutoff. It is unlikely that the observation can be explained by invoking curvature radiation as the origin of the observed gamma rays above 100 GeV. Our findings require that these gamma rays be produced more than 10 stellar radii from the neutron star.

Quality of life improvements attributed to combination therapy with oral and topical mesalazine in mild-to-moderately active ulcerative colitis.

BACKGROUND/AIM: To investigate patient-reported health-related quality of life (HRQoL) in data collected from a multinational randomized double-blind controlled trial comparing oral mesalazine (4 g) + topical mesalazine enema (1 g) to oral mesalazine alone (4 g). METHODS: HRQoL was collected using the EQ-5D at baseline and weeks 2, 4 and 8. The EQ-5D assesses mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Scores from each dimension were reported individually, and converted into a weighted health state which reflects an individual's perception of their health condition. RESULTS: At week 4, a significant HRQoL improvement was observed for patients on mesalazine enemas compared to placebo enemas, with EQ-5D scores of 0.906 and 0.838, respectively (p < 0.05). Mesalazine enema was found to reduce the probability of impairment at week 4 for mobility (p = 0.049) and anxiety/depression (p = 0.048), and was of borderline significance for pain/discomfort (p = 0.053); there was also an increased probability of influencing HRQoL changes for mobility (p < 0.005), usual activities (p < 0.005), pain/discomfort (p < 0.005) and anxiety/depression (p < 0.005), based on reported HRQoL problems at baseline. CONCLUSIONS: Including 1 g mesalazine enemas with 4 g oral mesalazine significantly improved HRQoL in patients with active ulcerative colitis. The improvement in QoL of patients with UC preceded clinical remission, and this underlines the importance of including QoL instruments in clinical studies.

The impact of introducing patient co-payments in Germany on the use of IVF and ICSI: a price-elasticity of demand assessment.

BACKGROUND: Authorities concerned by rising healthcare costs have a tendency to target reproductive treatments because of the perception that infertility is a low priority. In 2004 German health authorities introduced a 50% co-payment for patients, in an effort to save cost. We explored the impact of this pricing policy on the utilization of reproductive treatments in Germany. METHODS: Using aggregated annual in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycle data in Germany, we evaluated the relationship between changes in the number of cycles in relation to changes in costs faced by consumers following the introduction of a patient co-payment from 'no fees' to 1500-2000 euros by estimating the short-run price-elasticity of demand. The impact of introducing patient co-payments for IVF/ICSI on the likelihood of switching to other low-cost fertility treatments was evaluated using the cross-price elasticity methodology. RESULTS The reduction in demand for IVF and ICSI cycles in the year following the introduction of patient co-payments resulted in elasticities of -0.41 and -0.34, respectively. The price-elasticity for the combined reduction of IVF/ICSI in relation to the co-payment was estimated to be -0.36. The cross-price elasticity for clomifene was close to zero (-0.01) suggesting that demand for these interventions are independent of each other and no substitution occurred. CONCLUSIONS: We report price elasticities for IVF and ICSI of -0.41 and -0.34 after introducing a 500-2000 euros co-payment. These findings likely represent short-run elasticities that are likely to vary over time as factors that influence the supply and demand for fertility treatments change.

Rapid kinetics of G protein subunit association: a rate-limiting conformational change?

G protein subunit association and dissociation are thought to play an important role in signal transduction. We measured alpha beta gamma heterocomplex formation using resonance energy transfer. Fluorescein-labelled alpha(F-alpha) emission was quenched approximately 10% on mixing with eosin-labelled beta gamma(E-beta gamma). Unlabelled beta gamma did not quench F-alpha fluorescence. Stopped-flow kinetics showed a t1/2 ranging from 2.5 s to 0.25 s for 50 nM to 1200 nM E-beta gamma. The rate saturated at high E-beta gamma concentrations consistent with a two-step mechanism. We report the first rapid-mix studies of G protein subunit association kinetics which suggest that alpha and beta gamma combine by a two-step process with a maximal rate of 4.1 +/- 0.4 s-1.