Benefit-risk assessment of cladribine using multi-criteria decision analysis (MCDA) for patients with relapsing-remitting multiple sclerosis

Purpose: We applied Multi-Criteria Decision Analysis (MCDA) methods in a structured benefit–risk assessment of cladribine and newer approved disease-modifying drugs (DMDs) for patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Decision conferencing with clinical neurologists as decision makers was used to create an MCDA model that incorporated available evidence on DMDs for RRMS and clinical judgments about the relevance of the evidence. Benefit–risk assessments were conducted for DMDs in both patients with RRMS and patients with RRMS with high disease activity (HDA; defined as ≥2 relapses in the previous year). Treatment options included cladribine and recently approved DMDs available in European Union countries at the time of assessment (December 2015): alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, and teriflunomide. To account for the relative importance of DMD effects, scores for the MCDA model were weighted to ensure that the most clinically important attributes carried more weight in the final benefit–risk calculation. The neurologists weighted different efficacy and safety profile attributes without any reference to individual DMDs to disassociate the assessment of weights with any specific DMD. The neurologists did not do direct comparisons between DMDs. Findings: The highest overall weighted preference value for the RRMS model was for dimethyl fumarate (63) followed closely by cladribine (62). For patients with RRMS and HDA, cladribine had the highest overall weighted preference value (76), followed by alemtuzumab (62) and natalizumab (61). The benefit–risk balance of cladribine in patients with RRMS and specifically patients with RRMS who exhibited HDA characterized by high relapse activity (≥2 relapses in the previous year) was more favorable than the other DMDs included in the model. Implications: The balance of high efficacy and the safety profile makes cladribine an important treatment option to consider, both in patients with RRMS and patients with HDA. Regular, single-country meetings could be organized to explore how differences in cultural values (scores and weights) and updated input data might affect the usefulness of MCDA in different, real-world, dynamic clinical settings

Die Didaktik des Fernunterrichts in Formalerschließung unter besonderer Berücksichtigung von Lernprogrammen

Die didaktischen Voraussetzungen und die informationstechnischen Methoden, die im Formalerschließungsfernunterricht und bei der Erstellung entsprechender Lernprogramme Anwendung finden können, wurden zunächst theoretisch untersucht und dann praktische Empfehlungen für den Formalerschließungsfernunterricht gegeben. Bei der Gestaltung des Fernunterrichts sollten mehrere Lerntheorien herangezogen werden. An Lehrinhalten sind neben Katalogs- und Regelwerkskunde auch die Umsetzung der Formalerschließung in die elektronische Datenverarbeitung, die Formalerschließung aus der Sicht der Benutzer und die Organisation der Formalerschließung zu fordern. Kognitive, pragmatische und affektive Lernziele wurden formuliert. Für die kognitiven Lernziele wurde die Lernzieltaxonomie von Bloom an die weitergehenden Erfordernisse des Formalerschließungsunterrichts angepasst. Daneben wurden persönliche Kompetenzen angegeben. Der Unterricht muss auf die Bedürfnisse der Zielgruppe abgestimmt sein. Zu beachten sind Alter, Bildungsgrad, fachspezifische Vorbildung, Geschlecht und die verschiedenen Lernstile. Besonders Fernstudien bedürfen entsprechender Motivierung der Lernenden. Dafür wurde die ARCS-Motivationstheorie um den Punkt "Freiheit" erweitert. Die neun Instruktionsereignisse von Gagné wurden durch konstruktivistische Methoden zu elf didaktischen Anweisungen ergänzt und für den Formalerschließungsfernunterricht ausformuliert. Die Vermittlung der Regelwerke geschieht am besten durch tutorielle Lernprogramme mit Hilfe von Hypermedia. Bei der Entwicklung von Lernprogrammen wurden dieselben didaktischen Überlegungen wie bei der Unterrichtsplanung realisiert. Die technische Umsetzung sollte in einfacher Weise erfolgen, damit das Lernprogramm flexibel bleibt. Um die Möglichkeit der Umsetzung aufzuzeigen, wurden die ersten beiden Module eines Lernprogramms "Umsetzung der RAK-WB in ALEPH500" entwickelt.The didactics of distance education in the area of descriptive cataloguing with special attention to computer aided instruction The didactic requirements and the methods of information technology that can be used in distance learning of descriptive cataloguing and in the preparation of appropriate computer aided instruction programs are first investigated theoretically and then practical recommendations are made. In the design of distance education several learning theories should be incorporated. The topics of instruction should include not only cataloguing and standards, but also the conversion of descriptive cataloguing to EDP formats, descriptive cataloguing from the perspective of the user and the organisation of descriptive cataloguing. Cognitive, pragmatic and affective learning objectives are set out. Bloom's taxonomy of learning objectives is adapted to meet the advanced needs of descriptive cataloguing. In addition, personal competences are reviewed. Instruction must correspond to the needs of the target group. Factors that must be taken into account are age, level of education, existing specialised knowledge, sex and different learning styles. The need to motivate learners is especially important in distance education. To this end ARCS-motivation theory is expanded to include the topic "freedom". Gagné's "Nine Events of Instruction" are expanded by methods of constructivism to encompass eleven didactic statements, which are formulated in terms of descriptive cataloguing. Standards can best be taught by means of computer aided tutorials using hypermedia. In the development of these tutorials the same didactic considerations are realised as in the planning of instruction. In order to assure the flexibility of tutorials, the technical design should be uncomplicated. The first two modules of a tutorial "Conversion of RAK-WB to ALEPH500" have been developed to demonstrate the feasibility and means of designing such a tutorial

Thermal energy storage – overview and specific insight into nitrate salts for sensible and latent heat storage

Thermal energy storage (TES) is capable to reduce the demand of conventional energy sources for two reasons: First, they prevent the mismatch between the energy supply and the power demand when generating electricity from renewable energy sources. Second, utilization of waste heat in industrial processes by thermal energy storage reduces the final energy consumption. This review focuses mainly on material aspects of alkali nitrate salts. They include thermal properties, thermal decomposition processes as well as a new method to develop optimized salt systems

Gender and autoimmune comorbidity in multiple sclerosis

Background: The female preponderance in incidence of multiple sclerosis (MS) calls for investigations into sex differences in comorbidity with other autoimmune diseases (ADs). Objectives: To determine whether male and female patients with MS have a higher frequency of autoimmune comorbidity than controls, and to describe the type and frequency of ADs that are associated with MS. Methods: Our database was established by linkage of the Danish MS Registry to The Danish National Patient Register and consisted of 1403 patients of both sexes with clinical onset of MS between 2000 and 2004, and 25 matched controls for every case. Results: None of the ADs occurred more frequently in female cases than in controls. Male cases were more likely to have Type I diabetes mellitus (odds ratio (OR) = 3.34; 95% CI 1.40 – 7.02; p &lt; 0.008), Crohn’s disease (OR = 5.03; 95% CI 1.18 – 16.10; p = 0.03) and systemic lupus erythematosus (OR = 12.55; 95% CI 1.62 – 69.95; p = 0.02) than male controls. Conclusions: Autoimmune disorders are rare, but some of them tend to occur together with MS at a higher rate than in controls. Although women are generally more prone to ADs than men, significantly increased occurrence of other ADs were only found in male MS patients. </jats:sec