Determinants of the patient global assessment of well-being in early axial spondyloarthritis: 5-year longitudinal data from the DESIR cohort

Objectives. To investigate the determinants of patient well-being over time, and the influence of age, gender and education in patients with early axial spondyloarthritis (axSpA).Methods. Five-year data from DESIR, a cohort of early axSpA, were analysed. The outcome was the BAS-G over 5 years. Generalized estimating equations (GEE) were used to test the relationship between potential explanatory variables from five outcome domains (disease activity, physical function, spinal mobility, structural damage and axial inflammation) and BAS-G over time. Longitudinal relationships were analysed using an autoregressive GEE model. Age, gender and educational level were tested as effect modifiers or confounders.Results. A total of 708 patients were included. Higher BASDAI questions on fatigue [beta (95% CI): 0.17 (0.13, 0.22)], back pain [0.51 (0.46, 0.56)], peripheral joint pain [0.08 (0.04, 0.12)] and severity of morning stiffness [0.08 (0.03-0.13)], and higher BASFI [0.14 (0.08, 0.19)] were associated with a higher BAS-G. In the autoregressive model, the same variables except for morning stiffness were associated with a worsening in BAS-G. Age, gender and educational level were neither effect modifiers nor confounders.Conclusion. A higher level of back pain is associated with a worsening of patient well-being, as are, though to a lesser extent, higher levels of fatigue, peripheral joint pain and physical disability. Age, gender and educational level do not have an impact on these relationships.Pathophysiology and treatment of rheumatic disease

The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, but are not detectable in all RA patients. The aim of this study was to establish whether the clinical phenotypes of anti-CCP positive and negative disease are distinct at the earliest clinically apparent phase of disease.</p> <p>Methods</p> <p>Patients were recruited from the Birmingham early inflammatory arthritis clinic. Participants were included in the current study if they presented within 3 months of symptom onset and fulfilled 1987 ACR criteria for RA at some point during an 18 month follow-up. Data were collected on demographic variables, joint symptoms and tender (n = 68) and swollen (n = 66) joint counts. CRP, ESR, rheumatoid factor and anti-CCP2 status were measured.</p> <p>Results</p> <p>92 patients were included (48 anti-CCP positive). The anti-CCP positive and negative groups were comparable in terms of demographic variables, inflammatory markers, joint counts and 1987 ACR classification criteria, except that more anti-CCP positive patients were rheumatoid factor positive (83.3% vs. 11.4%, p < 0.01). There was no significant difference in the pattern of joint involvement, except for an increased prevalence of knee joint swelling in anti-CCP positive patients (42.9% vs. 22.2%, p = 0.03).</p> <p>Conclusions</p> <p>Patients with and without anti-CCP antibodies present in a similar way, even within three months of clinically apparent disease that eventually develops into RA.</p

Natuurverkenning 2010-2040 : visies op de ontwikkeling van natuur en landschap

De Natuurverkenning verschijnt in een turbulente tijd waarin natuur en landschap sterk gepolitiseerd zijn. Met de verkenning wil het PBL een bijdrage leveren aan het structureren van het debat over de vernieuwing van het langetermijnbeleid en een impuls geven aan de politieke afwegingen. Nieuw is het gebruik van normatieve toekomstscenario’s als hulpmiddel om de achterliggende drijfveren voor natuurbeleid te verhelderen

Social role participation questionnaire for patients with ankylosing spondylitis: Translation into Dutch, reliability and construct validity

Objective: The Social Role Participation Questionnaire (SRPQ) assesses the influence of health on participation in 11 specific and one general participation role across 4 participation dimensions: 'importance', 'satisfaction with time', 'satisfaction with performance' and 'physical difficulty'. This study aimed to translate the SRPQ into Dutch, and assess the clinimetric properties and aspects of its validity among patients with ankylosing spondylitis (AS). Methods: Translation was performed using the dual panel approach. For each participation dimension, internal consistency, test-retest reliability (n=31), and construct validity were assessed in 246 patients with AS. Results: The translation required only minor adaptations. Cronbach αs were α≥0.7. A strong correlation was present between satisfaction with 'time' and 'performance'(r=0.85). Test-retest reliability was satisfactory (κ=0.79-0.95). Correlations with participation domains of the Short- Form Health Survey 36 (SF-36), the WHO Disease Assessment Score II, and generic as well as disease-specific health outcomes (Physical and Mental component scale of the SF-36, Satisfaction With Life Scale, Bath Ankylosing Spondy

Prevalence and clinical significance of lumbosacral transitional vertebra (LSTV) in a young back pain population with suspected axial spondyloarthritis: results of the SPondyloArthritis Caught Early (SPACE) cohort

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Thinking globally, working locally: employability and internationalization at home

As an approach to the internationalization of higher education, Internationalization at Home (IaH) looks beyond the mobility of a minority of students, emphasizing instead the delivery to all students of an internationally focused curriculum and the embedding of intercultural communication. This can be expanded to include extracurricular activities and building relationships with local cultural and ethnic community groups. The MA in international development at Nottingham Trent University, United Kingdom, has implemented this approach, looking beyond both mobility and curriculum to apply IaH directly to student employability, embracing intercultural competence as a key professional skill. This article explores the efficacy of this combination in the MA’s professional development pathway, which requires students to complete a placement, which demonstrates international and intercultural engagement, usually undertaken “at home,” and to critically reflect not just on their professional skills, but on their ability to engage in the ethical practice, which is a key element of IaH

Balans van de leefomgeving 2014 : de toekomst is nú

De Balans van de Leefomgeving geeft parlement, kabinet en samenleving een feitelijk onderbouwd inzicht in de huidige kwaliteit van de fysieke leefomgeving. De Balans is de tweejaarlijkse peilstok van het PBL die aangeeft in hoeverre de door de politiek zelf ten doel gestelde leefomgevingskwaliteit tijdig wordt bereikt. De Balans van de Leefomgeving 2014 heeft als motto meegekregen: de toekomst is nú

Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis

Background: Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form of anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated in established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those at risk of and those that develop RA, (2) evaluate the change in expression of miRNA from "at-risk" to early RA and (3) explore whether these miRNAs could inform a signature predictive of progression from "at-risk" to RA. Methods: We performed global profiling of 754 miRNAs per patient on a matched serum sample cohort of 12 anti-cyclic citrullinated peptide (CCP) + "at-risk" individuals that progressed to RA. Each individual had a serum sample from baseline and at time of detection of synovitis, forming the matched element. Healthy controls were also studied. miRNAs with a fold difference/fold change of four in expression level met our primary criterion for selection as candidate miRNAs. Validation of the miRNAs of interest was conducted using custom miRNA array cards on matched samples (baseline and follow up) in 24 CCP+ individuals; 12 RA progressors and 12 RA non-progressors. Results: We report on the first study to use matched serum samples and a comprehensive miRNA array approach to identify in particular, three miRNAs (miR-22, miR-486-3p, and miR-382) associated with progression from systemic autoimmunity to RA inflammation. MiR-22 demonstrated significant fold difference between progressors and non-progressors indicating a potential biomarker role for at-risk individuals. Conclusions: This first study using a cohort with matched serum samples provides important mechanistic insights in the transition from systemic autoimmunity to inflammatory disease for future investigation, and with further evaluation, might also serve as a predictive biomarker

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Genetics of rheumatoid arthritis: what have we learned?

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 0.5–1% of the population worldwide. The disease has a heterogeneous character, including clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although the pathogenesis of RA is poorly understood, progress has been made in identifying genetic factors that contribute to the disease. The most important genetic risk factor for RA is found in the human leukocyte antigen (HLA) locus. In particular, the HLA molecules carrying the amino acid sequence QKRAA, QRRAA, or RRRAA at positions 70–74 of the DRβ1 chain are associated with the disease. The HLA molecules carrying these “shared epitope” sequences only predispose for ACPA-positive disease. More than two decades after the discovery of HLA-DRB1 as a genetic risk factor, the second genetic risk factor for RA was identified in 2003. The introduction of new techniques, such as methods to perform genome-wide association has led to the identification of more than 20 additional genetic risk factors within the last 4 years, with most of these factors being located near genes implicated in immunological pathways. These findings underscore the role of the immune system in RA pathogenesis and may provide valuable insight into the specific pathways that cause RA