Objective: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health... Show moreObjective: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). Method: First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. Results: The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. Conclusions: An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health. Show less
We have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins... Show moreWe have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins of many venomous snakes binds to this receptor in its location at the neuromuscular junction in all vertebrates. Furthermore, some animals have evolved resistance to snake venoms and show modifications in the ligand binding domain of the nAChR which inhibit the binding of snake α-neurotoxins. Our analysis has shown that numerous vertebrate species, most of which were not previously known to possess α-neurotoxin resistance, do actually contain resistance-related modifications. These modifications are present in most of the taxa in our dataset, with the unexpected exclusion of the birds. It was particularly surprising to us that the snake-specialist predatory birds Circaetus pectoralis (black-chested snake eagle) and Sagittarius serpentarius (secretary bird) did not possess resistance modifications. There were also relatively few resistance-related mutations within the mammals. By contrast, there were multiple convergent evolutions of the well-characterised N-glycosylation motif within the squamate reptiles—particularly the snakes. We also identified a number of sites under positive selection, such as mutations to the proline subsite. Future functional testing will be needed to validate that these modifications do indeed confer resistance. To provide functional confirmation that resistance-related modifications do indeed reduce susceptibility to toxins, we used developmental bioassays. These assays showed that two species possessing resistance-related modifications of the nAChR (stickleback and bearded dragon) were less susceptible to the toxic effects of cobra venom than two species that lacked such modifications (zebrafish and chicken). In summary, we demonstrate that the range of mechanisms along with the phylogenetic distribution of resistance to snake α-neurotoxin appears to be more extensive than was previously appreciated. It also shows strong evidence of the convergent evolution of the same resistance mutations in independent linages. Our findings also support the notion that the mutations we have identified in this thesis may represent adaptive change in response to selective pressures exerted by α-neurotoxic snake venoms in an evolutionary arms race. Thus, we conclude that the evolutionary arms race between predator and prey appears to be a pervasive feature of the trophic interactions surrounding venomous snakes, which is shaping the molecular evolution of the nAChR in the vertebrates. Show less
NTRODUCTION:The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health... Show moreNTRODUCTION:The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages.METHODS:Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included.RESULTS:The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness.DISCUSSION:This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures. Show less
Kiltz, U.; Heijde, D. van der; Boonen, A.; Cieza, A.; Stucki, G.; Khan, M.A.; ... ; Braun, J. 2015
This first up date of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the... Show moreThis first up date of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in de tail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good. Show less