Cost-effectiveness of oral alitretinoin in patients with severe chronic hand eczema - a long-term analysis from a Swiss perspective

BACKGROUND: The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland. METHODS: A long-term Markov cohort simulation model was used to estimate direct medical costs (euro) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions. RESULTS: Annual costs of alitretinoin treatment accounted for 2'212 euro. After a time horizon of 22.4 years, average remaining long-term costs accounted for 42'208 euro or 38'795 euro in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in 14'816 euro/QALY gained. These results were robust to changes in key model assumptions. CONCLUSION: The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland

Confusion and Conflict in Assessing the Physical Activity Status of Middle-Aged Men

BACKGROUND: Physical activity (including exercise) is prescribed for health and there are various recommendations that can be used to gauge physical activity status. The objective of the current study was to determine whether twelve commonly-used physical activity recommendations similarly classified middle-aged men as sufficiently active for general health. METHODS AND FINDINGS: We examined the commonality in the classification of physical activity status between twelve variations of physical activity recommendations for general health in ninety men aged 45-64 years. Physical activity was assessed using synchronised accelerometry and heart rate. Using different guidelines but the same raw data, the proportion of men defined as active ranged from to 11% to 98% for individual recommendations (median 73%, IQR 30% to 87%). There was very poor absolute agreement between the recommendations, with an intraclass correlation coefficient (A,1) of 0.24 (95% CI, 0.15 to 0.34). Only 8% of men met all 12 recommendations and would therefore be unanimously classified as active and only one man failed to meet every recommendation and would therefore be unanimously classified as not sufficiently active. The wide variability in physical activity classification was explained by ostensibly subtle differences between the 12 recommendations for thresholds related to activity volume (time or energy), distribution (e.g., number of days of the week), moderate intensity cut-point (e.g., 3 vs. 4 metabolic equivalents or METs), and duration (including bout length). CONCLUSIONS: Physical activity status varies enormously depending on the physical activity recommendation that is applied and even ostensibly small differences have a major impact. Approximately nine out of every ten men in the present study could be variably described as either active or not sufficiently active. Either the effective dose or prescription that underlies each physical activity recommendation is different or each recommendation is seeking the same prescriptive outcome but with variable success

The thrombotic potential of oral pathogens

In recent times the concept of infectious agents playing a role in cardiovascular disease has attracted much attention. Chronic oral disease such as periodontitis, provides a plausible route for entry of bacteria to the circulation. Upon entry to the circulation, the oral bacteria interact with platelets. It has been proposed that their ability to induce platelet aggregation and support platelet adhesion is a critical step in the pathogenesis of the infection process. Many published studies have demonstrated multiple mechanisms through which oral bacteria are able to bind to and activate platelets. This paper will review the various mechanisms oral bacteria use to interact with platelets

Transitions between explosive and effusive phases during the cataclysmic 2010 eruption of Merapi volcano, Java, Indonesia

Transitions between explosive and effusive activity are commonly observed during dome-forming eruptions and may be linked to factors such as magma influx, ascent rate and degassing. However, the interplay between these factors is complex and the resulting eruptive behaviour often unpredictable. This paper focuses on the driving forces behind the explosive and effusive activity during the well-documented 2010 eruption of Merapi, the volcano’s largest eruption since 1872. Time-controlled samples were collected from the 2010 deposits, linked to eruption stage and style of activity. These include scoria and pumice from the initial explosions, dense and scoriaceous dome samples formed via effusive activity, as well as scoria and pumice samples deposited during subplinian column collapse. Quantitative textural analysis of groundmass feldspar microlites, including measurements of areal number density, mean microlite size, crystal aspect ratio, groundmass crystallinity and crystal size distribution analysis, reveal that shallow pre- and syn-eruptive magmatic processes acted to govern the changing behaviour during the eruption. High-An (up to ∼80 mol% An) microlites from early erupted samples reveal that the eruption was likely preceded by an influx of hotter or more mafic magma. Transitions between explosive and effusive activity in 2010 were driven primarily by the dynamics of magma ascent in the conduit, with degassing and crystallisation acting via feedback mechanisms, resulting in cycles of effusive and explosive activity. Explosivity during the 2010 eruption was enhanced by the presence of a ‘plug’ of cooled magma within the shallow magma plumbing system, which acted to hinder degassing, leading to overpressure prior to initial explosive activity

Pre- and syn-eruptive degassing and crystallisation processes of the 2010 and 2006 eruptions of Merapi volcano, Indonesia

The 2010 eruption of Merapi (VEI 4) was the volcano’s largest since 1872. In contrast to the prolonged and effusive dome-forming eruptions typical of Merapi’s recent activity, the 2010 eruption began explosively, before a new dome was rapidly emplaced. This new dome was subsequently destroyed by explosions, generating pyroclastic density currents (PDCs), predominantly consisting of dark coloured, dense blocks of basaltic andesite dome lava. A shift towards open-vent conditions in the later stages of the eruption culminated in multiple explosions and the generation of PDCs with conspicuous grey scoria and white pumice clasts resulting from sub-plinian convective column collapse. This paper presents geochemical data for melt inclusions and their clinopyroxene hosts extracted from dense dome lava, grey scoria and white pumice generated during the peak of the 2010 eruption. These are compared with clinopyroxene-hosted melt inclusions from scoriaceous dome fragments from the prolonged dome-forming 2006 eruption, to elucidate any relationship between pre-eruptive degassing and crystallisation processes and eruptive style. Secondary ion mass spectrometry analysis of volatiles (H2O, CO2) and light lithophile elements (Li, B, Be) is augmented by electron microprobe analysis of major elements and volatiles (Cl, S, F) in melt inclusions and groundmass glass. Geobarometric analysis shows that the clinopyroxene phenocrysts crystallised at depths of up to 20 km, with the greatest calculated depths associated with phenocrysts from the white pumice. Based on their volatile contents, melt inclusions have re-equilibrated during shallower storage and/or ascent, at depths of ~0.6–9.7 km, where the Merapi magma system is interpreted to be highly interconnected and not formed of discrete magma reservoirs. Melt inclusions enriched in Li show uniform “buffered” Cl concentrations, indicating the presence of an exsolved brine phase. Boron-enriched inclusions also support the presence of a brine phase, which helped to stabilise B in the melt. Calculations based on S concentrations in melt inclusions and groundmass glass require a degassing melt volume of 0.36 km3 in order to produce the mass of SO2 emitted during the 2010 eruption. This volume is approximately an order of magnitude higher than the erupted magma (DRE) volume. The transition between the contrasting eruptive styles in 2010 and 2006 is linked to changes in magmatic flux and changes in degassing style, with the explosive activity in 2010 driven by an influx of deep magma, which overwhelmed the shallower magma system and ascended rapidly, accompanied by closed-system degassing