Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score

INTRODUCTION: Frequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs – termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) – would have comparable validity in clinical cohorts. METHOD: Data sources comprised an observational cohort of 767 RA patients (average disease duration 8.1 ± 10.6 years), and an independent inception cohort of 106 patients (disease duration 11.5 ± 12.5 weeks) who were followed prospectively. RESULTS: Our clinically based hypothesis was statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with DAS28 (R = 0.89–0.90) and comparably to the correlation of SDAI with DAS28 (R = 0.90–0.91). In additional analyses, the CDAI when compared to the SDAI and the DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably to the agreement between DAS28 and DAS28-CRP. All three scores correlated similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45–0.47). The average changes in all scores were greater in patients with better American College of Rheumatology response (P < 0.0001, analysis of variance; discriminant validity). All scores exhibited similar correlations with radiological progression (construct validity) over 3 years (R = 0.54–0.58; P < 0.0001). CONCLUSION: APRs add little information on top (and independent) of the combination of clinical variables included in the SDAI. A purely clinical score is a valid measure of disease activity and will have its greatest merits in clinical practice rather than research, where APRs are usually always available. The CDAI may facilitate immediate and consistent treatment decisions and help to improve patient outcomes in the longer term

VCAM-1 serum levels are associated with arthropathy in hereditary haemochromatosis

Objectives: The aim of this study was to assess the role of vascular adhesion molecule 1 (VCAM-1) in patients with hereditary haemochromatosis (HH) with or without arthropathy. Methods: Sera from a large cross-sectional cohort of unselected HH patients (n=147) were obtained and compared to an age-matched and sex-matched control group. Serum levels of VCAM-1 were measured by ELISA and were correlated with clinical measures. Results: VCAM-1 serum levels were elevated in HH patients as compared to matched controls (mean 913±456 vs 654±451 ng/ml, p<0.0001). Within the HH patient group, VCAM-1 levels were much higher in patients with arthropathy and joint replacement surgery. VCAM-1 levels correlated well with radiographic measures of HH arthropathy (r=0.36, p<0.0001). Multivariate regression analysis confirmed a highly significant association of VCAM-1 serum levels and the presence of HH arthropathy, independent from diabetes, body mass index and age. Conclusions: VCAM-1 serum levels emerge as a biomarker for haemochromatosis arthropathy

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

VCAM-1 serum levels are associated with arthropathy in hereditary haemochromatosis

Objectives: The aim of this study was to assess the role of vascular adhesion molecule 1 (VCAM-1) in patients with hereditary haemochromatosis (HH) with or without arthropathy. Methods: Sera from a large cross-sectional cohort of unselected HH patients (n=147) were obtained and compared to an age-matched and sex-matched control group. Serum levels of VCAM-1 were measured by ELISA and were correlated with clinical measures. Results: VCAM-1 serum levels were elevated in HH patients as compared to matched controls (mean 913±456 vs 654±451 ng/ml, p<0.0001). Within the HH patient group, VCAM-1 levels were much higher in patients with arthropathy and joint replacement surgery. VCAM-1 levels correlated well with radiographic measures of HH arthropathy (r=0.36, p<0.0001). Multivariate regression analysis confirmed a highly significant association of VCAM-1 serum levels and the presence of HH arthropathy, independent from diabetes, body mass index and age. Conclusions: VCAM-1 serum levels emerge as a biomarker for haemochromatosis arthropathy

Übersetzung der 2018 EULAR Empfehlungen zu körperlicher Aktivität von Menschen mit entzündlich-rheumatischen und degenerativen Erkrankungen ins Deutsche und sprachliche Validierung im deutschsprachigen Raum mit medizinischen Fachpersonen

Regular physical activity is beneficial for people with rheumatic diseases and one of the cornerstones in its management. Based on the international recommendations of the World Health Organization for the general population, the "2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis" provide evidence-based recommendations on the prescription, performance, and implementation of physical activity exercises in this population for the first time.; Translation of the 2018 EULAR recommendations into German and linguistic validation in Germany, Austria and Switzerland.; A professional translation of the EULAR recommendations into the German language was performed and revised by German-speaking experts from all three countries. The translation was validated by healthcare professionals consisting of rheumatologists, occupational therapists, physiotherapists, nurses, and medical assistants in a field test. In each of the three countries, eight structured interviews were conducted on comprehensibility, wording, completeness, and feasibility. The experts then discussed changes until consensus was reached and indicated the level of agreement with the final translation.; The translation of the EULAR recommendations was substantially revised. Based on the results of the cognitive test, formulations were adapted in order to increase comprehensibility. The level of agreement between 10 (SD 0.0) and 8.9 (SD 1.5) was very high.; The final German version of the EULAR recommendations is comprehensible and accepted across all three German-speaking countries. It can help to improve the structure and clarity of the handling of physical activity and promote physical activity for healthcare providers and patients

[Translation of the 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis and linguistic validation in German-speaking countries with healthcare professionals].

BACKGROUND Regular physical activity is beneficial for people with rheumatic diseases and one of the cornerstones in its management. Based on the international recommendations of the World Health Organization for the general population, the "2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis" provide evidence-based recommendations on the prescription, performance, and implementation of physical activity exercises in this population for the first time. AIM Translation of the 2018 EULAR recommendations into German and linguistic validation in Germany, Austria and Switzerland. METHODS A professional translation of the EULAR recommendations into the German language was performed and revised by German-speaking experts from all three countries. The translation was validated by healthcare professionals consisting of rheumatologists, occupational therapists, physiotherapists, nurses, and medical assistants in a field test. In each of the three countries, eight structured interviews were conducted on comprehensibility, wording, completeness, and feasibility. The experts then discussed changes until consensus was reached and indicated the level of agreement with the final translation. RESULTS The translation of the EULAR recommendations was substantially revised. Based on the results of the cognitive test, formulations were adapted in order to increase comprehensibility. The level of agreement between 10 (SD 0.0) and 8.9 (SD 1.5) was very high. DISCUSSION The final German version of the EULAR recommendations is comprehensible and accepted across all three German-speaking countries. It can help to improve the structure and clarity of the handling of physical activity and promote physical activity for healthcare providers and patients