174 results on '"Jaap Fransen"'
Search Results
2. Hit hard and early: analysing the effects of high-dose methylprednisolone on nailfold capillary changes and biomarkers in very early systemic sclerosis: study protocol for a 12-week randomised controlled trial
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Wieneke M. T. van den Hombergh, Brigit E. Kersten, Hanneke K. A. Knaapen-Hans, Rogier M. Thurlings, Peter M. van der Kraan, Frank H. J. van den Hoogen, Jaap Fransen, and Madelon C. Vonk
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Systemic sclerosis ,Methylprednisolone ,Randomised controlled trial ,Very early diagnosis of systemic sclerosis ,Nailfold capillaroscopy ,Medicine (General) ,R5-920 - Abstract
Abstract Background Mounting evidence indicates that inflammatory mechanisms drive systemic sclerosis (SSc) vasculopathy and fibrosis, especially early in the disease. Therefore, patients with very early SSc could benefit from early treatments targeting inflammation. Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. Several studies have demonstrated a mixed response to treatment with glucocorticoids in SSc, probably because it is seldom initiated at very early stages of the disease. We hypothesise that by inhibiting the inflammatory process driving SSc disease progression, glucocorticoid treatments will induce remission in patients with very early SSc. Methods/design This study is a 12-week, randomised, double-blind, placebo-controlled trial analysing the effects of high-dose intravenous methylprednisolone in very early SSc. Thirty patients who fulfil the criteria for very early SSc will be randomly assigned in a 2:1 ratio to receive either intravenous methylprednisolone or a placebo on three consecutive days over three consecutive months. In this study, the primary endpoint will be the change in capillary density between the baseline and after 12 weeks of treatment. The secondary outcomes of this study are a change in selected biomarkers, other changes in the nailfold capillaries, signs of established SSc and changes in physical function, general health and utilities, as reported through questionnaires. Discussion This trial is the first aiming to treat very early SSc and is promising because it targets the very early stages of the disease process by using an inexpensive and relatively safe treatment known to be highly effective against inflammation. The use of vasculopathy and inflammatory biomarkers as well as clinical signs and symptoms as the endpoints in our study enables us to meet the patient need for markers of disease activity. If it is possible to prevent clinically significant disease in patients with very early SSc by using a safe treatment, this will cause a paradigm shift in scleroderma care and research. Trial registration ClinicalTrials.gov Identifier: NCT03059979. Registered on 20 February 2017.
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- 2018
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3. Ultra-low dose of rituximab in rheumatoid arthritis: study protocol for a randomised controlled trial
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Alfons A. den Broeder, Lise M. Verhoef, Jaap Fransen, Rogier Thurlings, Bart J. F. van den Bemt, Steven Teerenstra, Nadine Boers, Nathan den Broeder, and Frank H. J. van den Hoogen
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Rheumatoid arthritis ,Dose reduction ,Rituximab ,Low dose ,Retreatment ,Randomised controlled trial ,Medicine (General) ,R5-920 - Abstract
Abstract Background A standard low-dosing schedule of rituximab (RTX; 2 × 500 mg or 1 × 1000 mg) is as effective for active rheumatoid arthritis (RA) as the registered dose (2 × 1000 mg). Moreover, several small uncontrolled studies suggest that even lower-dosed treatment with RTX also leads to good treatment response in patients with RA. Retreatment with such an ‘ultra-low’ dose RTX in patients who responded well to RTX induction treatment is of special interest, as long-term use of lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. However, the effect of ultra-low dose of RTX has not been investigated using a controlled trial of proper design and dimensions. Methods/Design REDO is an investigator driven six-month pragmatic, double-blind, randomised controlled non-inferiority trial on the effects of ultra-low-dose RTX (1 × 500 or 1 × 200 mg) compared to standard low dose (1 × 1000 mg) in RA patients who are being retreated with RTX. A total of 140 RA patients, having reached low disease activity (DAS28CRP
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- 2017
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4. Rheumatoid Arthritis Disadvantages Younger Patients for Cardiovascular Diseases: A Meta-Analysis.
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Jaap Fransen, Seyyed M R Kazemi-Bajestani, Sebastian J H Bredie, and Calin D Popa
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Medicine ,Science - Abstract
INTRODUCTION:The incidence of cardiovascular diseases (CVD) is increased in rheumatoid arthritis (RA) patients. It remains unclear whether the load of RA increases cardiovascular (CV) risk especially in female and in younger RA patients. In the present study we aim to analyse the influence of age and gender on CV risk in RA relative to the general population, using meta-analysis of direct comparative studies. METHOD:Systematic literature search was performed in MEDLINE for studies reporting on occurrence of CV events in RA as compared to the general population, stratified for gender and/or age. Quality was appraised using the Newcastle-Ottawa scale. Meta-analysis was performed on rate ratios using inverse variance methods. RESULTS:There were 1372 records screened and 13 studies included. RA females and males have a similar higher risk (95%CI) to develop stroke with RR 1.35 (1.30-1.40) and RR 1.31 (1.21-1.43); coronary artery disease with RR 1.65 (1.54-1.76) versus RR 1.55 ((1.41-1.69) in men; cardiovascular disease with RR 1.56 (1.49-1.62) versus 1.50 (1.41-1.60). The highest incidence of CV events was observed in the youngest patients, RR 2.59 (1.77-3.79), whereas older patients had the lowest relative risk when compared to the general population, RR 1.27 (1.16-1.38). CONCLUSION:The relative risk of RA patients for CVD is age dependent, but does not depend on gender: the relative risk on CVD appears to be equally raised for males and females, while relatively young RA patients (
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- 2016
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5. The Additive Value of Femoral Ultrasound for Subclinical Atherosclerosis Assessment in a Single Center Cohort of 962 Adults, Including High Risk Patients with Rheumatoid Arthritis, Human Immunodeficiency Virus Infection and Type 2 Diabetes Mellitus.
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Athanasios D Protogerou, Jaap Fransen, Evangelia Zampeli, Antonis A Argyris, Evagelia Aissopou, Aikaterini Arida, George D Konstantonis, Nikos Tentolouris, Konstantinos Makrilakis, Mina Psichogiou, George Daikos, George D Kitas, and Petros P Sfikakis
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Medicine ,Science - Abstract
Presence of femoral atheromatic plaques, an emerging cardiovascular disease (CVD) biomarker additional to carotid plaques, is poorly investigated in conditions associating with accelerated atherosclerosis such as Rheumatoid Arthritis (RA), Human Immunodeficiency Virus (HIV) infection and Type 2 Diabetes Mellitus (T2DM).To assess the frequency of femoral/carotid subclinical atheromatosis phenotypes in RA, HIV and T2DM and search for each disease-specific probability of either femoral and/or carotid subclinical atheromatosis, we examined by ultrasound a single-center cohort of CVD-free individuals comprised of consecutive non-diabetic patients with RA (n=226) and HIV (n=133), T2DM patients (n=109) and non-diabetic individuals with suspected/known hypertension (n=494) who served as reference group.Subclinical atheromatosis--defined as local plaque presence in at least on arterial bed--was diagnosed in 50% of the overall population. Among them, femoral plaques only were found in 25% of either RA or HIV patients, as well as in 16% of T2DM patients and 35% of reference subjects. After adjusting for all classical CVD risk factors, RA and HIV patients had comparable probability to reference group of having femoral plaques, but higher probability (1.75; 1.17-2.63 (odds ratio; 95% confidence intervals), 2.04; 1.14-3.64, respectively) of having carotid plaques, whereas T2DM patients had higher probability to have femoral and carotid plaques, albeit, due to their pronounced dyslipidemic profile.RA and HIV accelerate predominantly carotid than femoral. A "two windows" carotid/femoral, rather than carotid alone ultrasound, screening improves substantially subclinical atheromatosis detection in patients at high CVD risk.
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- 2015
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6. A replication study of the association between rheumatoid arthritis and deletion of the late cornified envelope genes LCE3B and LCE3C.
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Judith G M Bergboer, Maša Umićević-Mirkov, Jaap Fransen, Martin den Heijer, Barbara Franke, Piet L C M van Riel, Joost Schalkwijk, Marieke J H Coenen, and Nijmegen Biomedical Study principal investigators
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Medicine ,Science - Abstract
ObjectiveTwo recent studies, in a Spanish and a Chinese population, point to an association between rheumatoid arthritis (RA) risk and the deletion of the Late Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor for psoriasis. We aimed to replicate these studies in a large Dutch cohort.Methods1039 RA cases and 759 controls were genotyped for LCE3C_LCE3B-del. Association analysis was performed for the complete cohort and after stratification for the serologic markers anti-cyclic citrullinated peptide and rheumatoid factor. A meta-analysis was performed combining our data with the Spanish and Chinese datasets, resulting in an analysis including 2466 RA cases and 2438 controls.ResultsIn the Dutch cohort we did not observe a significant association of LCE3C_LCE3B-del (p = 0.093) with RA risk. A stratified analysis for the serologic positive and negative group did not show an association between the genetic variant and disease risk, either. The meta-analysis, however, confirmed a significant association (pConclusionOur meta-analysis confirms the association of the LCE3 deletion with RA, suggesting that LCE3C_LCE3B-del is a common risk factor for (auto)immune diseases.
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- 2012
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7. Atherogenic Index and High-Density Lipoprotein Cholesterol as Cardiovascular Risk Determinants in Rheumatoid Arthritis: The Impact of Therapy with Biologicals
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Calin D. Popa, Elke Arts, Jaap Fransen, and Piet L. C. M. van Riel
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Pathology ,RB1-214 - Abstract
Cardiovascular (CV) diseases are a serious concern in rheumatoid arthritis (RA), accounting for approximately one-third to one-half of all RA-related deaths. Besides the attempts to identify new risk factors, the proper management of traditional CV risk factors such as dyslipidemia should become a priority in the periodic evaluation of every RA patient. Atherogenic index has been suggested to be less susceptible to disease activity variation during large periods of time, making him more attractive to be used in CV risk prediction in this group of patients as compared to individual lipids concentrations. Nevertheless, inflammation may negatively impact HDL antiatherogenic properties, suggesting that HDL function assessment is of particular importance when predicting CV risk in these patients. A tight control of inflammation becomes therefore crucial for a successful CV risk management. The present paper debates these hypotheses focusing on the effects of therapy with biologicals on the above mentioned parameters.
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- 2012
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8. Systematic Analysis of the Literature in Search of Defining Systemic Sclerosis Subsets
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Matthew A. Turk, Dinesh Khanna, Sindhu R. Johnson, Christopher P. Denton, Janet E. Pope, Jaap Fransen, Tatiana Nevskaya, Marco Matucci-Cerinic, Jenny Shu, Frank J. A. van den Hoogen, April Marquardt, and Murray Baron
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Scleroderma, Systemic ,integumentary system ,Web of science ,Response to therapy ,business.industry ,Immunology ,MEDLINE ,Disease ,Prognosis ,Bioinformatics ,Original data ,Multisystem disease ,Phenotype ,All institutes and research themes of the Radboud University Medical Center ,Rheumatology ,Sample size determination ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Humans ,Immunology and Allergy ,Medicine ,Clinical phenotype ,business ,Autoantibodies - Abstract
ObjectiveSystemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis.An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria.MethodsMedline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions.ResultsOf 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy.ConclusionSubsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting.
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- 2021
9. 'Lessons learned from patients with access to an online self-management enhancing program for RA patients: Qualitative analysis of interviews alongside a randomized clinical trial'
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R. Zuidema, S. van Dulmen, Jaap Fransen, B.G.I. van Gaal, and M.W.G. Nijhuis-van der Sanden
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Adult ,Male ,medicine.medical_specialty ,MEDLINE ,Computer-Assisted Instruction ,law.invention ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Nonprobability sampling ,Arthritis, Rheumatoid ,Interviews as Topic ,Qualitative analysis ,All institutes and research themes of the Radboud University Medical Center ,Randomized controlled trial ,Patient Education as Topic ,law ,Medicine ,Humans ,Practical implications ,Qualitative Research ,Aged ,Motivation ,Self-management ,business.industry ,Self-Management ,General Medicine ,Middle Aged ,Family medicine ,Female ,business ,Qualitative research - Abstract
Objective This study aims to explain the earlier findings of a Randomized Controlled Trial (RCT), which showed that rheumatoid arthritis (RA) patients did not benefit from an online self-management program. Moreover, less patients than expected used the program. Methods As part of an explorative RCT, patients were interviewed to explore their (non) usage of the program. Purposive sampling (n = 21) was used to select patients from four groups of patients (n = 49): 1) non-users; 2) low users; 3) high users basic; 4) high users plus. Results The program supported only a small group of patients because: 1) not all patients were motivated to use the program, 2) patients had no clear expectation or had differing expectations of the program, 3) there was a mismatch between individual patients’ support needs and the needs included in the program, 4) reminders were only sent to fill in the diaries for pain and fatigue, not to use the program modules. Conclusion This study offers insights in the (non-) usage of online programs and how usage could be increased in practice. Practical implications Health professionals should be involved in the implementation of this online programs and should inform patients what the program could bring them.
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- 2019
10. Validation of a clinical pharmacogenetic model to predict methotrexate nonresponse in rheumatoid arthritis patients
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Henk-Jan Guchelaar, Jesse J. Swen, Cornelia F Allaart, Frank Eektimmerman, Moenira B. Madhar, Johanna M. W. Hazes, Alfons A den Broeder, Jaap Fransen, and Rheumatology
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rheumatoid arthritis ,Adult ,Hydroxymethyl and Formyl Transferases ,Male ,medicine.medical_specialty ,030226 pharmacology & pharmacy ,AMP Deaminase ,Arthritis, Rheumatoid ,Minor Histocompatibility Antigens ,03 medical and health sciences ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Multienzyme Complexes ,Positive predicative value ,Internal medicine ,Genetics ,Rheumatoid factor ,Medicine ,Humans ,Pyrophosphatases ,effectiveness of therapy ,Pharmacology ,Methylenetetrahydrofolate Dehydrogenase (NADP) ,Receiver operating characteristic ,business.industry ,Area under the curve ,Middle Aged ,medicine.disease ,Pharmacogenomic Testing ,prediction model ,Drug Combinations ,Methotrexate ,Treatment Outcome ,pharmacogenetic models ,Nucleotide Deaminases ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Antirheumatic Agents ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Molecular Medicine ,Female ,ITPA ,business ,Pharmacogenetics ,medicine.drug - Abstract
Aim: To study the performance of a clinical pharmacogenetic model for the prediction of nonresponse in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) in combination with other synthetic or biologic disease-modifying anti-rheumatic drugs . This prediction model includes gender, smoking status, rheumatoid factor positivity and four genetic variants in AMPD1 (rs17602729), ATIC (rs2372536), ITPA (rs1127354) and MTHFD1 (rs17850560). Methods: A total of 314 RA patients from three Dutch studies were retrospectively included. Eligible patients were adults diagnosed with RA and had a treatment duration with MTX and follow-up for at least two study evaluation visits. Prediction model risk scores at the first and second evaluation were calculated and compared with the actual nonresponse (disease activity score >2.4). Regression and receiver operating characteristic curve analyses of the prediction model were performed. Also, the sensitivity, specificity and the positive and negative predictive values (PPV and NPV) were determined. Results: The receiver operating characteristic area under the curve was 75% at first and 70% after second evaluation. At the second evaluation, prediction nonresponse had a sensitivity of 67% (CI: 54–78%), specificity of 69% (CI: 60–77%), PPV of 52% (CI: 45–60%) and NPV of 80% (CI: 73–85%). Conclusions: This study demonstrates that the clinical pharmacogenetic model has an inadequate performance for the prediction of nonresponse to MTX in RA patients treated with combination therapies.
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- 2019
11. Younger age and female gender are determinants of underestimated cardiovascular risk in rheumatoid arthritis patients: a prospective cohort study
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Alfons A den Broeder, Alexander J. Rennings, Jaap Fransen, Elke Arts, Calin D. Popa, Inger L. Meek, Eline H. M. van de Wetering, and Daphne C. Rohrich
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0301 basic medicine ,Male ,medicine.medical_specialty ,Younger age ,lcsh:Diseases of the musculoskeletal system ,Concordance ,Cardiovascular ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Age ,All institutes and research themes of the Radboud University Medical Center ,Internal medicine ,medicine ,Humans ,In patient ,Prospective Studies ,Rheumatoid arthritis ,Prospective cohort study ,030203 arthritis & rheumatology ,business.industry ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,Metabolic Disorders Radboud Institute for Health Sciences [Radboudumc 6] ,Gender ,medicine.disease ,INCEPTION COHORT ,Rheumatology ,030104 developmental biology ,Risk factors ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Orthopedic surgery ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Female ,lcsh:RC925-935 ,business ,Research Article - Abstract
Background Rheumatoid arthritis (RA) patients have an increased cardiovascular (CV) risk. Here, we aimed to investigate whether gender and age are contributing to the misclassification of CV risk in RA patients. Methods Prospectively collected data on cardiovascular risk factors and incident events from the Nijmegen inception cohort were analyzed, with up to 10 years follow-up. Original as well as the EULAR-modified (M)_SCORE algorithms were used to calculate CV risk. Patients were stratified in deciles according to predicted risk; the Hosmer-Lemeshow test was used to check concordance between observed and predicted risk, in subgroups of gender and age. Results There were 863 RA patients included with 128 incident CV events. When using SCORE in the whole group, there was evidence of a discrepancy between the predicted and observed CV risk (H-L test p p p Conclusion CV risk is especially underestimated in female and younger RA patients. This suggests that modifying the weight for the female gender and/or younger age in currently used CV risk algorithms might improve their predictive value in RA, contributing to better CV risk management.
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- 2021
12. Is Fatigue a Disease-Specific or Generic Symptom in Chronic Medical Conditions?
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Gijs Bleijenberg, Hans Knoop, Riet Strik-Albers, Martine M. Goedendorp, Hal A Droogleever Fortuyn, Jaap Fransen, Rogier Donders, Nens van Alfen, Sieberen P. van der Werf, Juliane Menting, Baziel G.M. van Engelen, Cees J. Tack, Joke S. Kalkman, Nicol C. Voermans, Psychology Other Research (FMG), VU University medical center, Medical psychology, APH - Mental Health, and Medical Psychology
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Male ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Cross-sectional study ,HIGHLY PREVALENT ,medicine.medical_treatment ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Disease ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,030212 general & internal medicine ,COGNITIVE-BEHAVIORAL THERAPY ,PREDICTORS ,Stroke ,Applied Psychology ,Fatigue ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,RANDOMIZED CONTROLLED-TRIAL ,Middle Aged ,Explained variation ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Cognitive behavioral therapy ,Psychiatry and Mental health ,Rheumatoid arthritis ,Female ,Psychosocial ,STROKE ,Clinical psychology ,DISORDERS ,Other Research Donders Center for Medical Neuroscience [Radboudumc 0] ,health-related factors ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,medicine ,Humans ,psychosocial factors ,business.industry ,DISABILITY ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,Metabolic Disorders Radboud Institute for Health Sciences [Radboudumc 6] ,medicine.disease ,transdiagnostic approach ,RHEUMATOID-ARTHRITIS ,MODEL ,Cross-Sectional Studies ,Chronic Disease ,business ,MULTIPLE-SCLEROSIS FATIGUE ,030217 neurology & neurosurgery - Abstract
Objective: Severe fatigue is highly prevalent in various chronic diseases. Disease-specific fatigue models have been developed, but it is possible that fatigue-related factors in these models are similar across diseases. The purpose of the current study was to determine the amount of variance in fatigue severity explained by: (a) the specific disease, (b) factors associated with fatigue across different chronic diseases (transdiagnostic factors), and (c) the interactions between these factors and specific diseases. Method: Data from 15 studies that included 1696 patients with common chronic diseases and disorders that cause long-term disabilities were analyzed. Linear regression analysis with the generalized least-squares technique was used to determine fatigue-related factors associated with fatigue severity, that is, demographic variables, health-related symptoms and psychosocial variables. Results: Type of chronic disease explained 11% of the variance noted in fatigue severity. The explained variance increased to 55% when the transdiagnostic factors were added to the model. These factors were female sex, age, motivational and concentration problems, pain, sleep disturbances, physical functioning, reduced activity and lower self-efficacy concerning fatigue. The predicted variance increased to 61% when interaction terms were added. Analysis of the interactions revealed that the relationship between fatigue severity and relevant predictors mainly differed in strength, not in direction. Conclusions: Fatigue severity can largely be explained by transdiagnostic factors; the associations vary between chronic diseases in strength and significance. This suggests that severely fatigued patients with different chronic diseases can probably benefit from a transdiagnostic fatigue-approach which focuses on individual patient needs rather than a specific disease.
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- 2018
13. Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison With Monosodium Urate Monohydrate Crystal Analysis as the Gold Standard
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Manuella Lima Gomes Ochtrop, Jiunn-Horng Chen, Tuhina Neogi, T.L.Th.A. Jansen, Chingtsai Lin, Matthijs Janssen, Hang-Korng Ea, Fernando Perez-Ruiz, Yin Yi Chou, Ole Slot, Geraldine M. McCarthy, Martijn Gerritsen, William J. Taylor, Douglas W. White, Juris Lazovskis, Lisa K. Stamp, Lorenzo Cavagna, Nicola Dalbeth, Janitzia Vázquez-Mellado, Worawit Louthrenoo, Till Uhlig, Anne Kathrin Tausche, H. Ralph Schumacher, Francisca Sivera, Maxim Eliseev, Jaap Fransen, Marco A. Cimmino, Giovanni Cagnotto, and Alexis Ogdie
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030203 arthritis & rheumatology ,medicine.medical_specialty ,business.industry ,Cross-sectional study ,medicine.medical_treatment ,Immunology ,Ultrasound ,Tophus ,Arthrocentesis ,Gold standard (test) ,Odds ratio ,medicine.disease ,Gastroenterology ,Confidence interval ,Surgery ,Gout ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Immunology and Allergy ,030212 general & internal medicine ,business - Abstract
Objective: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. Methods: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. Results: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23–10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68–8.17]), and serum urate level (OR 1.31 [95% CI 1.06–1.62]). Conclusion: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. (Less)
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- 2017
14. Cost-Effectiveness of Cardiovascular Screening in Patients With Rheumatoid Arthritis
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Jake S. F. Maurits, Wietske Kievit, Elke Arts, Jaap Fransen, Calin D. Popa, and Piet L. C. M. van Riel
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030203 arthritis & rheumatology ,Percentile ,Pediatrics ,medicine.medical_specialty ,Cost–benefit analysis ,Cost effectiveness ,business.industry ,Absolute risk reduction ,Arthritis ,medicine.disease ,Quality-adjusted life year ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Rheumatoid arthritis ,Medicine ,030212 general & internal medicine ,business ,Mass screening - Abstract
OBJECTIVE: Early detection and preemptive treatment of patients at risk is of great importance in reducing the excess risk of cardiovascular (CV) disease in rheumatoid arthritis (RA). However, it is unclear how much screening is cost-effective in RA. The objective is to assess whether CV screening in RA proves to be cost-effective from a medical perspective, using different scenarios based on different guidelines. METHODS: A Markov chain model was used with a time horizon of 10 years. Parameter values were mainly obtained from literature and from RA patients screened for CV diseases at the Radboud University Medical Centre, Nijmegen, The Netherlands. The primary outcome was incremental cost-effectiveness expressed as costs per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analysis was performed and described in willingness-to-pay curves; several scenarios were built. RESULTS: In the base case scenario, in 82% of the simulations, screening proved to be dominant compared to no screening. The mean QALY gain was 0.09 (95% percentile -0.07, 0.27), and the mean cost savings were euro-1,057 (95% percentile -euro2,825, euro333). Different scenarios showed small differences in cost-effectiveness; the probability that screening is dominant remained high with the lowest probability being 50% for a very conservative scenario. CONCLUSION: Screening for CV events in RA patients was estimated to be cost-effective with high chances of being less expensive and more effective. These results support endorsement of screening for CV risk in patients with RA.
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- 2017
15. Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial
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Aatke van der Maas, Ronald F van Vollenhoven, Chantal A M Bouman, Noortje van Herwaarden, Jaap Fransen, Alfons A den Broeder, Frank H J van den Hoogen, Johannes W. J. Bijlsma, AII - Inflammatory diseases, Rheumatology, Clinical Immunology and Rheumatology, AMS - Amsterdam Movement Sciences, AII - Amsterdam institute for Infection and Immunity, and Other departments
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Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Immunology ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,Etanercept ,Disease activity ,Arthritis, Rheumatoid ,03 medical and health sciences ,Disability Evaluation ,0302 clinical medicine ,Rheumatology ,Quality of life ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Adverse effect ,Aged ,030203 arthritis & rheumatology ,biology ,business.industry ,Tumor Necrosis Factor-alpha ,C-reactive protein ,Adalimumab ,Middle Aged ,medicine.disease ,Symptom Flare Up ,Surgery ,TNF inhibitor ,C-Reactive Protein ,Rheumatoid arthritis ,Antirheumatic Agents ,biology.protein ,Quality of Life ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Tumor necrosis factor alpha ,Dose reduction ,Female ,business ,Radiology - Abstract
Item does not contain fulltext OBJECTIVE: Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year data from the DRESS study (Dose REduction Strategy of Subcutaneous TNF inhibitors study). METHODS: In the intervention phase (month 0-18) of the DRESS study (Dutch trial register, NTR 3216), patients were randomised to DR or usual care (UC). In the extension phase (month 18-36), treatment strategies in both groups converged to continuation of protocolised tight control and allowed dose optimisation. Intention-to-treat analyses were done on flare, disease activity (28 joint count-based disease activity score with C reactive protein (DAS28-CRP)), functioning (health assessment questionnaire-disability index (HAQ-DI)), quality of life (Euroqol 5 dimensions 5 levels questionnaire (EQ5D-5L)), medication use, radiographic progression (Sharp van der Heijde score (SvdH)) and AE. RESULTS: 172/180 patients included in the DRESS study were included in the extension phase. Cumulative incidences of major flare were 10% and 12% (-2%, 95% CI -8 to 15) in DR and UC groups in the extension phase, and 17% and 14% (3%, 95% CI -9 to 13) from 0 to 36 months. Cumulative incidences of short-lived flares were 43% (33 to 52%)%) and 35% (23 to 49%)%) in DR and UC groups in the extension phase, and 83% (75 to 90%)%) and 44% (31 to 58%)%) from 0 to 36 months. Mean DAS28-CRP, HAQ-DI, EQ5D-5L and SvdH remained stable and not significantly different between groups. TNFi use remained low in the DR group and decreased in the UC group. Cumulative incidences of AE were not significantly different between groups. CONCLUSIONS: Safety and efficacy of disease activity guided TNFi DR in RA are maintained up to 3 years, with a large reduction in TNFi use, but no other benefits. Implementation of DR would vastly improve the cost-effective use of TNFi.
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- 2017
16. Low disease activity (DAS28</=3.2) reduces the risk of first cardiovascular event in rheumatoid arthritis: a time-dependent Cox regression analysis in a large cohort study
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Jaap Fransen, Calin D. Popa, Alfons A den Broeder, Elke Arts, and Piet L. C. M. van Riel
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Oncology ,Male ,Time Factors ,Disease ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Systemic inflammation ,Severity of Illness Index ,Arthritis, Rheumatoid ,0302 clinical medicine ,Risk Factors ,Immunology and Allergy ,Medicine ,Prospective Studies ,Netherlands ,Absolute risk reduction ,Middle Aged ,Stroke ,Cardiovascular Diseases ,Ischemic Attack, Transient ,Rheumatoid arthritis ,Female ,medicine.symptom ,musculoskeletal diseases ,Cardiovascular event ,Adult ,medicine.medical_specialty ,Immunology ,General Biochemistry, Genetics and Molecular Biology ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Disease activity ,03 medical and health sciences ,Peripheral Arterial Disease ,Rheumatology ,Internal medicine ,Covariate ,Humans ,Angina, Stable ,Acute Coronary Syndrome ,Aged ,Proportional Hazards Models ,030203 arthritis & rheumatology ,Heart Failure ,Proportional hazards model ,business.industry ,medicine.disease ,Surgery ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,business ,Follow-Up Studies - Abstract
Item does not contain fulltext OBJECTIVE: Systemic inflammation appears to contribute to the excess risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objective of this study was to investigate the effect of different levels of disease activity over time, particularly low disease activity and remission, on CVD risk in patients with RA. METHODS: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events within the first 10 years of follow-up. Cut points of the DAS28 for remission (5.1) disease activity were used. The effect of disease activity on CVD risk was analysed using Cox-proportional hazards regression with DAS28 as a time-dependent covariate and also conventionally with time-averaged DAS28 as the primary dependent variable. RESULTS: Low DAS28 (3.2, both when included as a time-dependent covariate and as time-averaged DAS28
- Published
- 2017
17. Performance of the 2015 ACR-EULAR classification criteria for gout in a primary care population presenting with monoarthritis
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T.L.Th.A. Jansen, Matthijs Janssen, Hein J.E.M. Janssens, Jaap Fransen, Tuhina Neogi, William J. Taylor, Nicola Dalbeth, and H. Ralph Schumacher
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Male ,medicine.medical_specialty ,Gout ,Population ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Sensitivity and Specificity ,Decision Support Techniques ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Predictive Value of Tests ,Internal medicine ,medicine ,Monoarthritis ,Humans ,Pharmacology (medical) ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,education ,Aged ,Netherlands ,Retrospective Studies ,030203 arthritis & rheumatology ,education.field_of_study ,Primary Health Care ,Receiver operating characteristic ,business.industry ,Arthritis ,Retrospective cohort study ,Decision rule ,Middle Aged ,medicine.disease ,Uric Acid ,Surgery ,Clinical trial ,ROC Curve ,Predictive value of tests ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Female ,Crystallization ,business - Abstract
Item does not contain fulltext Objective: To test the performance of the 2015 ACR-EULAR gout classification criteria against presence of SF MSU crystals in a primary healthcare population. Methods: The criteria were applied to an existing dataset of consecutive patients with monoarthritis presenting to Dutch family physicians; all patients underwent microscopic SF analysis by design. The data had been prospectively collected to develop a diagnostic decision rule for gout in 2010. Diagnostic performance was assessed by calculating area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and constructing calibration plots for the full version of the criteria (including SF analysis results of all patients) and the clinical-only version (not including SF analysis results). Performance of both versions was compared with the 2010 diagnostic rule. Results: Of 381 patients enrolled into the study, 216 (57%) were MSU crystal-positive. The full and clinical-only versions of the criteria had satisfactory area under the receiver operating characteristic curve (0.96 and 0.87, respectively), high specificity (0.98 and 0.84), high PPV (0.98 and 0.84), but lower sensitivity (0.68 and 0.68) and NPV (0.70 and 0.67). Specificity and PPV of both versions were higher compared with 0.71 and 0.89 of the 2010 diagnostic decision rule. The decison rule had the highest sensitivity and NPV (0.99 and 0.97). Conclusion: This study presents the first external validation of the 2015 ACR-EULAR gout classification criteria in a primary healthcare setting. The criteria perform well in this setting in patients presenting with monoarthritis for the purpose of enrolling into gout clinical trials.
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- 2017
18. Crystal-proven gout patients have an increased mortality due to cardiovascular diseases, cancer, and infectious diseases especially when having tophi and/or high serum uric acid levels: a prospective cohort study
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Jaap Fransen, Gerard A. Rongen, T.L.Th.A. Jansen, Matthijs Janssen, Iris J.M. Disveld, Hein J.E.M. Janssens, Sahel Zoakman, and Laura B.E. Kienhorst
- Subjects
medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,General Medicine ,medicine.disease ,Rheumatology ,Gout ,chemistry.chemical_compound ,Standardized mortality ratio ,All institutes and research themes of the Radboud University Medical Center ,chemistry ,Internal medicine ,Cohort ,Medicine ,Uric acid ,Population study ,business ,education ,Prospective cohort study - Abstract
To investigate the cause-specific mortality and the possible involved clinical characteristics with increased mortality in a cohort of 700 patients with crystal-proven gout. The cause-specific mortality of gout was compared to the mortality of the general population. Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers Cohort (GOAL). Joint fluid analysis was performed in all patients and only crystal-proven gout patients were included in this study. At inclusion clinical characteristics and laboratory values were collected. At follow-up patients who died were identified. Standardized mortality ratios (SMRs) were calculated for all-causes, cardiovascular diseases, cancer, and infectious diseases using indirect standardization methods for mortality outcomes and compared with the general population. The clinical characteristics of the patients who died were compared with those of the survivors and were analyzed by a logistic regression analysis to identify any associations with mortality. The study population at inclusion contained 573 (81.9%) men and 127 (18.1%) females with an average age of 62.0 (SD 13.4). During 3500 person-years from inclusion visit till 31 May 2016, in 700 gout patients, 66 deaths (27 cardiovascular deaths, 15 cancer-related deaths, 8 infectious deaths, 16 various other causes) occurred in this cohort. The all-cause standardized mortality ratio in gout patients was 2.21 (95% CI 1.68–2.74). In this cohort, gout patients had a higher SMR for death attributed to cardiovascular diseases (6.75; 95% CI 4.64–8.86), infectious diseases (4.66; 95% CI 1.51–7.82) and cancer (3.58; 95% CI 1.77–5.39). Corrected for confounders high serum uric acid levels (SUA; > 0,56 mmol/L), tophaceous gout, a history of peripheral vascular disease, myocardial infarction, and heart failure at the inclusion visit were associated with increased mortality during follow-up. Compared to the general population, gout patients have an increased association with all-cause disease mortality, especially attributed to cardiovascular diseases, cancer, and infectious diseases. This association is strongest in hyperuricemic (uric acid levels > 0,56 mmol/l) and tophaceous patients and in those with a history of peripheral vascular disease, myocardial infarction, and heart failure. Preventive measures like treatment of high SUA levels and treatment of cardiovascular risk factors need to be considered and evaluated.
- Published
- 2019
19. Efficacy of a Web-Based Self-Management Enhancing Program for Patients with Rheumatoid Arthritis: Explorative Randomized Controlled Trial
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M.W.G. Nijhuis-van der Sanden, S. van Dulmen, R. Zuidema, I.L. Meek, B.G.I. van Gaal, C.H.M. van den Ende, and Jaap Fransen
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Male ,medicine.medical_specialty ,self-management ,Health Informatics ,law.invention ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Arthritis, Rheumatoid ,Intervention mapping ,All institutes and research themes of the Radboud University Medical Center ,Randomized controlled trial ,law ,Rating scale ,Intervention (counseling) ,Medicine ,Humans ,Original Paper ,Internet ,Self-management ,business.industry ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,Repeated measures design ,Middle Aged ,medicine.disease ,Rheumatoid arthritis ,Physical therapy ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Female ,business - Abstract
This is an open-access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. Background: Web-based self-management enhancing programs have the potential to support patients with rheumatoid arthritis(RA) in their self-management; for example, improve their health status by increasing their self-efficacy or taking their prescribedmedication. We developed a Web-based self-management enhancing program in collaboration with RA patients and professionalsas co-designers on the basis of the intervention mapping framework. Although self-management programs are complex interventions,it is informative to perform an explorative randomized controlled trial (RCT) before embarking on a larger trial.Objective: This study aimed to evaluate the efficacy of a Web-based self-management enhancing program for patients withRA and identify outcome measures most likely to capture potential benefits.Methods: A multicenter exploratory RCT was performed with an intervention group and a control group. Both groups receivedcare as usual. In addition, the intervention group received 12 months of access to a Web-based self-management program.Assessment occurred at baseline, 6 months, and 12 months. Outcome measures included self-management behavior (PatientActivation Measurement, Self-Management Ability Scale), self-efficacy (Rheumatoid Arthritis task-specific Self-Efficacy,Perceived Efficacy in Patient-Physician Interaction), general health status (RAND-36), focus on fatigue (Modified Pain CopingInventory for Fatigue), and perceived pain and fatigue (Numeric Rating Scales). A linear mixed model for repeated measures,using the intention-to-treat principle, was applied to study differences between the patients in the intervention (n=78) and control(n=79) groups. A sensitivity analysis was performed in the intervention group to study the influence of patients with high (N=30)and low (N=40) use of the intervention.Results: No positive effects were found regarding the outcome measurements. Effect sizes were low.Conclusions: Based on these results, it is not possible to conclude on the positive effects of the intervention or to select outcomemeasures to be regarded as the primary/main or secondary outcomes for a future trial. A process evaluation should be performedto provide more insight into the low compliance with and effectiveness of the intervention. This can determine for whom thissort of program will work and help to fine-tune the inclusion criteria.
- Published
- 2019
20. Survey Definitions of Gout for Epidemiologic Studies: Comparison With Crystal Identification as the Gold Standard
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Melanie Brown, Hang-Korng Ea, Martijn Gerritsen, Geraldo da Rocha Castelar-Pinheiro, Worawit Louthrenoo, Carlo Alberto Scirè, T.L.Th.A. Jansen, Maxim Eliseev, Matthijs Janssen, Geraldine M. McCarthy, Lisa K. Stamp, H. Ralph Schumacher, Jiunn-Horng Chen, Francisca Sivera, Anne Kathrin Tausche, Janitzia Vázquez-Mellado, Fernando Perez-Ruiz, Yin Yi Chou, William J. Taylor, Marco A. Cimmino, Nicola Dalbeth, Till Uhlig, Jaap Fransen, Tuhina Neogi, Lorenzo Cavagna, and Chingtsai Lin
- Subjects
musculoskeletal diseases ,030203 arthritis & rheumatology ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,business.industry ,MEDLINE ,Gold standard (test) ,medicine.disease ,Logistic regression ,Gout ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology ,Crystal identification ,Internal medicine ,Epidemiology ,medicine ,Hyperuricemia ,business ,Rheumatism - Abstract
Objective To identify the best-performing survey definition of gout from items commonly available in epidemiologic studies. Methods Survey definitions of gout were identified from 34 epidemiologic studies contributing to the Global Urate Genetics Consortium (GUGC) genome-wide association study. Data from the Study for Updated Gout Classification Criteria (SUGAR) were randomly divided into development and test data sets. A data-driven case definition was formed using logistic regression in the development data set. This definition, along with definitions used in GUGC studies and the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) gout classification criteria were applied to the test data set, using monosodium urate crystal identification as the gold standard. Results For all tested GUGC definitions, the simple definition of “self-report of gout or urate-lowering therapy use” had the best test performance characteristics (sensitivity 82%, specificity 72%). The simple definition had similar performance to a SUGAR data-driven case definition with 5 weighted items: self-report, self-report of doctor diagnosis, colchicine use, urate-lowering therapy use, and hyperuricemia (sensitivity 87%, specificity 70%). Both of these definitions performed better than the 1977 American Rheumatism Association survey criteria (sensitivity 82%, specificity 67%). Of all tested definitions, the 2015 ACR/EULAR criteria had the best performance (sensitivity 92%, specificity 89%). Conclusion A simple definition of “self-report of gout or urate-lowering therapy use” has the best test performance characteristics of existing definitions that use routinely available data. A more complex combination of features is more sensitive, but still lacks good specificity. If a more accurate case definition is required for a particular study, the 2015 ACR/EULAR gout classification criteria should be considered.
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- 2016
21. What Should Be the Cut Point for Classification Criteria of Studies in Gout? A Conjoint Analysis
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Tuhina Neogi, William J. Taylor, T.L.Th.A. Jansen, Wietske Kievit, Jaap Fransen, Ralph Schumacher, and Nicola Dalbeth
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musculoskeletal diseases ,medicine.medical_specialty ,business.industry ,030503 health policy & services ,Case-control study ,medicine.disease ,Rheumatology ,Surgery ,law.invention ,Gout ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Predictive value of tests ,medicine ,030212 general & internal medicine ,0305 other medical science ,business ,Cut-point ,Cohort study - Abstract
Objective To determine the acceptable level of positive predictive value (PPV) and negative predictive value (NPV) for classification criteria for gout, given the type of study. Methods We conducted an international web-based survey with 91 general practitioners and rheumatologists experienced in gout. Conjoint analysis was used as the framework for designing and analyzing pairs of 2 profiles, each describing a study type, a PPV, and an NPV. There were 5 study types presented: a phase III randomized controlled trial (RCT) of a nonsteroidal antiinflammatory drug versus prednisone for acute gout flares, a phase III RCT of a biologic agent for acute gout flares, a phase II RCT of a novel uricosuric drug of unknown efficacy and limited toxicity data, a case–control, genome-wide association study of gout, and a cohort study examining long-term outcomes of gout. PPV and NPV both had 5 levels ranging from 60–99%. Results The panelists in majority were male (65%) rheumatologists (93%) with an average of 19 years of practice, seeing 5 to 60 gout patients monthly. PPV was most highly weighted in decision making: the relative importance was 59% for PPV, 29% for NPV, and 13% for study type. The preferred PPV was 90% or 80%, with an accompanying NPV of 70% or 80%, dependent on study type. Conclusion Preferred PPVs and NPVs range between 70% and 90% and differ by study type. A single cut point can be a reasonable approach for all study types if a PPV of 90% and NPV of 80% is approximated.
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- 2016
22. An easy prediction rule for diffuse cutaneous systemic sclerosis using only the timing and type of first symptoms and auto-antibodies: derivation and validation
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Jaap Fransen, Patricia Carreira, Hanneke K. A. Knaapen-Hans, Wieneke M. T. van den Hombergh, Madelon C. Vonk, and Frank H J van den Hoogen
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Male ,medicine.medical_specialty ,Time Factors ,Logistic regression ,Systemic scleroderma ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Linear regression ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,030212 general & internal medicine ,Autoantibodies ,030203 arthritis & rheumatology ,business.industry ,Area under the curve ,Sclerodactyly ,Middle Aged ,Decision Support Systems, Clinical ,medicine.disease ,Surgery ,Clinical trial ,Scleroderma, Diffuse ,Cohort ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Female ,medicine.symptom ,business ,Cut-point - Abstract
Contains fulltext : 171205.pdf (Publisher’s version ) (Closed access) OBJECTIVE: DcSSc is associated with high morbidity related to widespread skin disease and poor prognosis due to earlier and more severe organ involvement. The objective of this study is to derive and validate a simple prediction rule for identifying patients at the time of initial diagnosis of SSc who are likely to progress to dcSSc. METHODS: The Nijmegen cohort consists of 619 SSc patients. Logistic regression was used for predictive modelling. A prediction rule was created by rounding regression coefficients. Patients were stratified as being at low risk (
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- 2016
23. Survival and organ involvement in patients with limited cutaneous systemic sclerosis and anti-topoisomerase-I antibodies: determined by skin subtype or auto-antibody subtype? A long-term follow-up study
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Hanneke K. A. Knaapen-Hans, Madelon C. Vonk, Frank H J van den Hoogen, Pim Kranenburg, Jaap Fransen, and Wieneke M. T. van den Hombergh
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Male ,medicine.medical_specialty ,Pathology ,Kaplan-Meier Estimate ,Systemic scleroderma ,Gastroenterology ,Scleroderma ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Scleroderma, Limited ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Autoantibodies ,Netherlands ,Skin ,030203 arthritis & rheumatology ,biology ,business.industry ,Confounding ,Interstitial lung disease ,Autoantibody ,Middle Aged ,medicine.disease ,DNA Topoisomerases, Type I ,Cohort ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,biology.protein ,Organ involvement ,Female ,Antibody ,business ,Follow-Up Studies - Abstract
Contains fulltext : 171578.pdf (Publisher’s version ) (Closed access) OBJECTIVE: LcSSc is associated with ACAs and a mild course, whereas dcSSc is associated with anti-topoisomerase antibodies (ATAs) and a more severe course. However, ATAs are also present in lcSSc. Little is known about survival and organ involvement in this subgroup. The aim of this study is to determine whether survival and organ involvement of lcSSc ATA-positive patients differs from lcSSc ATA-negative or dcSSc ATA-positive patients. Furthermore, transition from lcSSc to dcSSc was evaluated. METHODS: Data from The Nijmegen Systemic Sclerosis cohort were used, with up to 15 years of follow-up. Kaplan-Meier analysis was performed for survival and organ involvement, including interstitial lung disease, pulmonary arterial hypertension, cardiac involvement and Scleroderma Renal Crises. Cox proportional hazard modelling was performed to adjust for confounders. RESULTS: A total of 460 patients were included: 58 (13%) lcSSc ATA-positive patients, 237 (52%) lcSSc ATA-negative patients and 78 (17%) dcSSc ATA-positive patients. Cumulative survival in lcSSc ATA-positive patients was 75%, in lcSSc ATA-negative patients 58% and in dcSSc ATA-positive patients 53%. Interstitial lung disease was more prevalent in lcSSc ATA-positive patients (49%) than in lcSSc ATA-negative patients (25%), but less than in dcSSc ATA-positive patients (60%). Forty-eight patients developed dcSSc: 24 ATA-negative and 24 ATA-positive (P < 0.001). CONCLUSION: LcSSc ATA-positive patients differ from lcSSc ATA-negative patients and dcSSc ATA-positive patients concerning survival and organ involvement. LcSSc patients who are ATA-positive are more likely to develop dcSSc than lcSSc patients who are ATA negative.
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- 2016
24. The effect of curriculum sample selection for medical school
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Jaap Fransen, Marieke de Visser, Janke Cohen-Schotanus, Mieke Latijnhouwers, Cornelia R. M. G. Fluit, Roland Laan, and Lifelong Learning, Education & Assessment Research Network (LEARN)
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Male ,Predictive validity ,Educational measurement ,Adolescent ,020205 medical informatics ,education ,Population ,Context (language use) ,02 engineering and technology ,Undergraduate medical education ,Academic performance ,PREDICTIVE-VALIDITY ,Article ,Education ,Young Adult ,03 medical and health sciences ,Lottery ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,0202 electrical engineering, electronic engineering, information engineering ,Mathematics education ,Humans ,Medicine ,School Admission Criteria ,030212 general & internal medicine ,Selection ,Curriculum ,Schools, Medical ,Selection (genetic algorithm) ,Netherlands ,Medicine(all) ,education.field_of_study ,Medical education ,business.industry ,4. Education ,SUCCESS ,Regression analysis ,General Medicine ,PERFORMANCE ,Educational Status ,Female ,Educational Measurement ,business - Abstract
In the Netherlands, students are admitted to medical school through (1) selection, (2) direct access by high pre-university Grade Point Average (pu-GPA), (3) lottery after being rejected in the selection procedure, or (4) lottery. At Radboud University Medical Center, 2010 was the first year we selected applicants. We designed a procedure based on tasks mimicking the reality of early medical school. Applicants took an online course followed by an on-site exam, resembling courses and exams in early medical school. Based on the exam scores, applicants were selected or rejected. The aim of our study is to determine whether curriculum sample selection explains performance in medical school and is preferable compared to selection based on performance in secondary school. We gathered data on the performance of students of three consecutive cohorts (2010-2012, N = 954). We compared medical school performance (course credits and grade points) of selected students to the three groups admitted in other ways, especially lottery admissions. In regression analyses, we controlled for out of context cognitive performance by adjusting for pu-GPA. Selection-admitted students outperformed lottery-admitted students on most outcome measures, unadjusted as well as adjusted for pu-GPA (p aecurrency 0.05). They had higher grade points than non-selected lottery students, both unadjusted and adjusted for pu-GPA (p aecurrency 0.025). Adjusted for pu-GPA, selection-admitted students and high-pu-GPA students performed equally. We recommend this selection procedure as it adds to secondary school cognitive performance for the general population of students, is efficient for large numbers of applicants and not labour-intensive.
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- 2016
25. Circulating Apoptotic Microparticles in Systemic Lupus Erythematosus Patients Drive the Activation of Dendritic Cell Subsets and Prime Neutrophils for NETosis
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Jaap Fransen, Johan van der Vlag, Henry B.P.M. Dijkman, Astrid Thielen, Jürgen Dieker, Marinka A.H. Bakker, Nils Rother, Jurjen Tel, Elmar Pieterse, Jolanda M. de Vries, Luuk B. Hilbrands, and Jo H. M. Berden
- Subjects
0301 basic medicine ,CD86 ,education.field_of_study ,Lupus erythematosus ,business.industry ,Immunology ,Population ,hemic and immune systems ,Neutrophil extracellular traps ,Dendritic cell ,medicine.disease ,Cell-Derived Microparticles ,Proinflammatory cytokine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology ,medicine ,Immunology and Allergy ,skin and connective tissue diseases ,education ,business ,CD80 ,030215 immunology - Abstract
Objective Circulating chromatin-containing apoptotic material and/or neutrophil extracellular traps (NETs) have been proposed to be an important driving force for the antichromatin autoimmune response in patients with systemic lupus erythematosus (SLE). The aim of this study was to determine the exact nature of microparticles in the circulation of SLE patients and to assess the effects of the microparticles on the immune system. Methods We analyzed microparticles isolated from the plasma of patients with SLE, rheumatoid arthritis (RA), and systemic sclerosis (SSc), as well as from healthy subjects. The effects of the microparticles on blood-derived dendritic cells (DCs) and neutrophils were assessed by flow cytometry, enzyme-linked immunosorbent assay, and immunofluorescence microscopy. Results In SLE patients, we identified microparticles that were highly positive for annexin V and apoptosis-modified chromatin that were not present in healthy subjects or in RA or SSc patients. These microparticles were mostly CD31+/CD45– (endothelial), partly CD45+/CD66b+ (granulocyte), and negative for B and T cell markers. Microparticles isolated from the plasma of SLE patients increased the expression of the costimulatory surface molecules CD40, CD80, CD83, and CD86 and the production of proinflammatory cytokines interleukin-6, tumor necrosis factor, and interferon-α by blood-derived plasmacytoid DCs (PDCs) and myeloid DCs (MDCs). SLE microparticles also primed blood-derived neutrophils for NETosis. Microparticles from healthy subjects and from RA or SSc patients exhibited no significant effects on MDCs, PDCs, and NETosis. Conclusion Circulating microparticles in SLE patients include a population of apoptotic cell–derived microparticles that has proinflammatory effects on PDCs and MDCs and enhances NETosis. These results underline the important role of apoptotic microparticles in driving the autoimmune response in SLE patients.
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- 2016
26. Diagnostic Arthrocentesis for Suspicion of Gout Is Safe and Well Tolerated
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Geraldo da Rocha Castelar-Pinheiro, A.-K. Tausche, Fernando Perez-Ruiz, Francisca Sivera, Chingtsai Lin, Carlo A Scire, Matthijs Janssen, Jiunn-Horng Chen, Martijn Gerritsen, Till Uhlig, Yin-Yi Chou, Nicola Dalbeth, Melanie Brown, Lisa K. Stamp, Hang-Korng Ea, William J. Taylor, Worawit Louthrenoo, Maxim Eliseev, Ole Slot, H. Ralph Schumacher, Lorenzo Cavagna, Tuhina Neogi, Janitzia Vázquez-Mellado, Geraldine M. McCarthy, Tim L. Jansen, Marco A. Cimmino, Jaap Fransen, Taylor, W, Fransen, J, Dalbeth, N, Neogi, T, Schumacher, H, Brown, M, Louthrenoo, W, Vazquez-Mellado, J, Eliseev, M, Mccarthy, G, Stamp, L, Perez-Ruiz, F, Sivera, F, H. -K., E, Gerritsen, M, Scire, C, Cavagna, L, Lin, C, Chou, Y, Tausche, A, Da Rocha Castelar-Pinheiro, G, Janssen, M, Chen, J, Slot, O, Cimmino, M, Uhlig, T, and Jansen, T
- Subjects
Male ,ADVERSE EVENTS ,ARTHROCENTESIS ,GOUT ,Adult ,Age Distribution ,Aged ,Arthritis, Gouty ,Arthrocentesis ,Chi-Square Distribution ,Cohort Studies ,Confidence Intervals ,Female ,Follow-Up Studies ,Gout ,Humans ,Incidence ,Middle Aged ,New Zealand ,Poisson Distribution ,Risk Assessment ,Severity of Illness Index ,Sex Distribution ,Patient Safety ,Gouty ,medicine.medical_treatment ,0302 clinical medicine ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Incidence (epidemiology) ,Arthrocentesi ,Cohort study ,Adverse event ,medicine.medical_specialty ,Immunology ,NO ,03 medical and health sciences ,Rheumatology ,Internal medicine ,Severity of illness ,Adverse effect ,030203 arthritis & rheumatology ,business.industry ,Arthritis ,medicine.disease ,Surgery ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Septic arthritis ,business ,Chi-squared distribution - Abstract
Objective.To determine the frequency of adverse events of diagnostic arthrocentesis in patients with possible gout.Methods.Consecutive patients underwent arthrocentesis and were evaluated at 6 weeks to determine adverse events. The 95% CI were obtained by bootstrapping.Results.Arthrocentesis was performed in 910 patients, and 887 (97.5%) were evaluated for adverse events. Any adverse event was observed in 12 participants (1.4%, 95% CI 0.6–2.1). There was 1 case (0.1%, 95% CI 0–0.34) of septic arthritis.Conclusions.Diagnostic arthrocentesis is associated with a low frequency of adverse events. Septic arthritis rarely occurs.
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- 2016
27. Efficacy of a Web-Based Self-Management Enhancing Program for Patients with Rheumatoid Arthritis: Explorative Randomized Controlled Trial (Preprint)
- Author
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Rixt Zuidema, Sandra van Dulmen, Maria Nijhuis-van der Sanden, Inger Meek, Cornelia van den Ende, Jaap Fransen, and Betsie van Gaal
- Abstract
BACKGROUND Web-based self-management enhancing programs have the potential to support patients with rheumatoid arthritis (RA) in their self-management; for example, improve their health status by increasing their self-efficacy or taking their prescribed medication. We developed a Web-based self-management enhancing program in collaboration with RA patients and professionals as co-designers on the basis of the intervention mapping framework. Although self-management programs are complex interventions, it is informative to perform an explorative randomized controlled trial (RCT) before embarking on a larger trial. OBJECTIVE This study aimed to evaluate the efficacy of a Web-based self-management enhancing program for patients with RA and identify outcome measures most likely to capture potential benefits. METHODS A multicenter exploratory RCT was performed with an intervention group and a control group. Both groups received care as usual. In addition, the intervention group received 12 months of access to a Web-based self-management program. Assessment occurred at baseline, 6 months, and 12 months. Outcome measures included self-management behavior (Patient Activation Measurement, Self-Management Ability Scale), self-efficacy (Rheumatoid Arthritis task-specific Self-Efficacy, Perceived Efficacy in Patient-Physician Interaction), general health status (RAND-36), focus on fatigue (Modified Pain Coping Inventory for Fatigue), and perceived pain and fatigue (Numeric Rating Scales). A linear mixed model for repeated measures, using the intention-to-treat principle, was applied to study differences between the patients in the intervention (n=78) and control (n=79) groups. A sensitivity analysis was performed in the intervention group to study the influence of patients with high (N=30) and low (N=40) use of the intervention. RESULTS No positive effects were found regarding the outcome measurements. Effect sizes were low. CONCLUSIONS Based on these results, it is not possible to conclude on the positive effects of the intervention or to select outcome measures to be regarded as the primary/main or secondary outcomes for a future trial. A process evaluation should be performed to provide more insight into the low compliance with and effectiveness of the intervention. This can determine for whom this sort of program will work and help to fine-tune the inclusion criteria. CLINICALTRIAL Netherlands Trial Register NTR4871; https://www.trialregister.nl/trial/4726
- Published
- 2018
28. Crystal-proven gout patients have an increased mortality due to cardiovascular diseases, cancer, and infectious diseases especially when having tophi and/or high serum uric acid levels: a prospective cohort study
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Iris J M, Disveld, Sahel, Zoakman, Tim L Th A, Jansen, Gerard A, Rongen, Laura B E, Kienhorst, Hein J E M, Janssens, Jaap, Fransen, and Matthijs, Janssen
- Subjects
Male ,Gout ,Hyperuricemia ,Middle Aged ,Communicable Diseases ,Uric Acid ,Logistic Models ,Cardiovascular Diseases ,Risk Factors ,Cause of Death ,Neoplasms ,Humans ,Female ,Prospective Studies ,Aged ,Netherlands - Abstract
To investigate the cause-specific mortality and the possible involved clinical characteristics with increased mortality in a cohort of 700 patients with crystal-proven gout. The cause-specific mortality of gout was compared to the mortality of the general population.Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers Cohort (GOAL). Joint fluid analysis was performed in all patients and only crystal-proven gout patients were included in this study. At inclusion clinical characteristics and laboratory values were collected. At follow-up patients who died were identified. Standardized mortality ratios (SMRs) were calculated for all-causes, cardiovascular diseases, cancer, and infectious diseases using indirect standardization methods for mortality outcomes and compared with the general population. The clinical characteristics of the patients who died were compared with those of the survivors and were analyzed by a logistic regression analysis to identify any associations with mortality.The study population at inclusion contained 573 (81.9%) men and 127 (18.1%) females with an average age of 62.0 (SD 13.4). During 3500 person-years from inclusion visit till 31 May 2016, in 700 gout patients, 66 deaths (27 cardiovascular deaths, 15 cancer-related deaths, 8 infectious deaths, 16 various other causes) occurred in this cohort. The all-cause standardized mortality ratio in gout patients was 2.21 (95% CI 1.68-2.74). In this cohort, gout patients had a higher SMR for death attributed to cardiovascular diseases (6.75; 95% CI 4.64-8.86), infectious diseases (4.66; 95% CI 1.51-7.82) and cancer (3.58; 95% CI 1.77-5.39). Corrected for confounders high serum uric acid levels (SUA; 0,56 mmol/L), tophaceous gout, a history of peripheral vascular disease, myocardial infarction, and heart failure at the inclusion visit were associated with increased mortality during follow-up.Compared to the general population, gout patients have an increased association with all-cause disease mortality, especially attributed to cardiovascular diseases, cancer, and infectious diseases. This association is strongest in hyperuricemic (uric acid levels 0,56 mmol/l) and tophaceous patients and in those with a history of peripheral vascular disease, myocardial infarction, and heart failure. Preventive measures like treatment of high SUA levels and treatment of cardiovascular risk factors need to be considered and evaluated.
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- 2018
29. AB0787 The eular systemic sclerosis impact of disease (SCLEROID) score – a new patient-reported outcome measure for patients with systemic sclerosis
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Ulf Müller-Ladner, Roger Hesselstrand, Inge C. Olsen, Turid Heiberg, Mike O Becker, Gunnel Sandqvist, Madelon C. Vonk, Marco Matucci-Cerinic, Kim Fligelstone, Ana Maria Gheorghiu, Rucsandra Dobrota, Cosimo Bruni, C. Mihai, O. Distler, L. Czirják, Jaap Fransen, Yannick Allanore, A. Tyrrell Kennedy, Patricia Carreira, Christopher P. Denton, and Otylia Kowal-Bielecka
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Clinical trial ,Final version ,medicine.medical_specialty ,Hand function ,business.industry ,Family medicine ,medicine ,Impact score ,Patient-reported outcome ,Sensitivity to change ,business ,Cohort study ,Unmet needs - Abstract
Background: Patient reported outcome measures (PROM) are important for clinical practice and research. Given the unmet need for a comprehensive PROM for systemic sclerosis (SSc), the ScleroID questionnaire was developed by a joint team of patients with SSc and medical experts. This is intended as a brief, specific, patient-derived, disease impact score for research and clinical use in SSc. Objectives: Here, we present the validation and final version of the ScleroID. Methods: This EULAR-endorsed project involves 9 European expert SSc centers. Patients fulfilling the ACR/EULAR 2013 criteria were prospectively included since 05/16 in a large observational cohort study. Patients completed the ScleroID and comparators SHAQ, EQ5D, SF36. They also weighted the 10 dimensions of the ScleroID by distributing 100 points according to the perceived impact on their health. The final score calculation is based on the ranking of the weights. The validation study included a reliability arm and a longitudinal arm, looking at sensitivity to change at follow-up. Results: Of the 472 patients included at baseline, 109 patients also had a reliability visit and 113 patients a follow-up visit. 84.5% of patients were female, 29.8% had diffuse SSc, mean age was 54.6 years, and mean disease duration 9.5 years. The highest weights were assigned by the patients to Raynaud`s phenomenon, fatigue, hand function and pain, confirming our previous results. The total ScleroID score showed good Spearman correlation coefficients with the comparators (SHAQ, 0.73; EQ5D -0.48; Patient’s global assessment, VAS 0.77; HAQ-DI 0.62; SF36 physical score -0.62; each p Conclusion: The EULAR ScleroID is a novel PROM designed for use in clinical practice and clinical trials to reflect the disease impact of SSc, showing good performance in the validation study. Importantly, Raynaud syndrome, impaired hand function, pain and fatigue were the main patient reported drivers of disease impact. Disclosure of Interests: Mike O. Becker: None declared, Rucsandra Dobrota: None declared, Kim Fligelstone: None declared, Annelise Roennow: None declared, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Laszlo Czirjak Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Roger Hesselstrand: None declared, Gunnel Sandqvist: None declared, Otylia Kowal-Bielecka Consultant of: Bayer, Boehringer Ingelheim, Inventiva, MSD, Medac, Novartis, Roche and Sandoz, Speakers bureau: Bayer, Boehringer Ingelheim, Inventiva, MSD, Medac, Novartis, Roche and Sandoz, Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Marco Matucci Cerinic: None declared, Carina Mihai: None declared, Ana Maria Gheorghiu: None declared, Ulf Muller-Ladner Speakers bureau: Biogen, Joe Sexton: None declared, Turid Heiberg: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche
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- 2018
30. OP0158-HPR Effectiveness of an e-health tailored self-management program for patients with rheumatoid arthritis: an explorative rct
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I. Meek, R. Nijhuis, E. van den Ende, Jaap Fransen, B.G.I. van Gaal, S. van Dulmen, and R. Zuidema
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medicine.medical_specialty ,Intention-to-treat analysis ,business.industry ,Psychological intervention ,Repeated measures design ,medicine.disease ,law.invention ,Randomized controlled trial ,law ,Intervention (counseling) ,Rheumatoid arthritis ,Physical therapy ,Medicine ,In patient ,Self management program ,business - Abstract
Background E-health programs have potential to support RA patients in self-management. However, many of these programs are developed without involving patients. As a consequence, patient preferences for program use are not well known and these programs may not well suit patient’s needs for self-management support. We developed a tailored e-health self-management program for patients with RA with the help of a patient panel. While self-management interventions are complex interventions, it is informative to perform an explorative RCT before embarking on a larger trial. Objectives 1) Evaluate the potential effectiveness in patients with RA of a 12 month tailored e-health self-management program, versus ‘usual care’, on self-management behaviour, self-efficacy, general health status, focus on fatigue and the level of pain and fatigue; 2) exploration of floor and ceiling effects of the potential outcome measures at baseline and effect sizes at 6 and 12 months after baseline were used to identify outcome measures most likely to capture potential benefits Methods The RCT was performed in out-patients from two hospitals in the Netherlands. Inclusion criteria were RA patients 18 years or older, being able to speak and read Dutch and having access to internet. Patients were randomised to ‘e-health’ in addition to ‘usual care’ or to ‘usual care’ alone. The ‘e-health’ group received 12 months access to the online self-management program. Assessment of outcomes occurred at baseline, 6 and 12 months. Outcome measures included self-management behaviour (PAM-13, SMAS-S), self-efficacy (RASE, PEPPI-5), general health status (RAND-36), focus on fatigue (MPCI-F), pain and fatigue (NRS scales). A linear mixed model for repeated measures, using the intention to treat principle was used to study differences between intervention and control groups. A sensitivity analysis was performed to study the influence of high and low compliance in the intervention group Results In total 157 patients (n=78 intervention group versus n=79 control group) were included in the study. A statistically significant (p Conclusions Based on these results it is not possible to conclude on possible positive effects of the intervention: for all outcomes the effect sizes were low. Consequently, it is not possible to select outcome measures to be regarded as primary/main secondary outcomes for a larger trial. A process evaluation should be performed to give an explanation for the findings of this study. Disclosure of Interest None declared
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- 2018
31. The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries
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Anna Molto, Joanna Nicklin, Ingemar F Petersson, Laure Gossec, Mart A F J van de Laar, Georg Schett, Sarah Hewlett, Matthias Englbrecht, Rosemary Greenwood, Fiona Cramp, John R. Kirwan, Emma Dures, Sofia Hagel, Christina Bode, L. Carmona, Marta Redondo, Jaap Fransen, and Psychology, Health & Technology
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rheumatoid arthritis ,Male ,Coping (psychology) ,Time Factors ,RAID ,Disease ,Severity of Illness Index ,law.invention ,Arthritis, Rheumatoid ,PROMs ,0302 clinical medicine ,Cost of Illness ,law ,Germany ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,skin and connective tissue diseases ,Fatigue ,Netherlands ,validation ,Clinical Science ,Middle Aged ,Rheumatoid arthritis ,impact ,Female ,France ,Clinical psychology ,Adult ,Psychometrics ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Rheumatology ,Cronbach's alpha ,Rating scale ,Humans ,Factor analysis ,Sweden ,030203 arthritis & rheumatology ,business.industry ,cultural ,Reproducibility of Results ,Construct validity ,medicine.disease ,Health Surveys ,United Kingdom ,Cross-Sectional Studies ,Spain ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Factor Analysis, Statistical ,business - Abstract
Objective To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. Methods We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach’s α and construct validity by Spearman’s correlation. Results A total of 1276 patients participated (76% female, 25% with a disease duration
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- 2018
32. There is a need for new systemic sclerosis subset criteria. A content analytic approach
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Marco Matucci-Cerinic, Martin Baron, L. Czirják, John Varga, N. Hunzelmann, Ariane L. Herrick, Tracy M. Frech, Lorinda Chung, Bashar Kahaleh, V. Steen, F. Del Galdo, Armando Gabrielli, Gabriela Riemekasten, Nemanja Damjanov, Madelon C. Vonk, Richard M. Silver, Daniel E. Furst, L.A. Saketkoo, Thomas A. Medsger, Ulrich A. Walker, Ulf Müller-Ladner, I. Foeldvari, Dinesh Khanna, Sindhu R. Johnson, Frank A. Wollheim, M.L. Soowamber, Janet E. Pope, Jaap Fransen, Maurizio Cutolo, J. H. W. Distler, Shervin Assassi, Christopher P. Denton, Patricia Carreira, Charles Murray, Luc Mouthon, Otylia Kowal-Bielecka, and F.H.J. van den Hoogen
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Adult ,Male ,medicine.medical_specialty ,Cross-sectional study ,Immunology ,MEDLINE ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,skin and connective tissue diseases ,030203 arthritis & rheumatology ,Scleroderma, Systemic ,business.industry ,Disease progression ,General Medicine ,Prognosis ,Cross-Sectional Studies ,Conceptual framework ,Family medicine ,Respondent ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Disease Progression ,Organ involvement ,Female ,business - Abstract
Contains fulltext : 181772.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).
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- 2018
33. Crystal-proven Gout and Characteristic Gout Severity Factors Are Associated with Cardiovascular Disease
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Sahel Zoakman, Hein J.E.M. Janssens, Jaap Fransen, Matthijs Janssen, Iris J.M. Disveld, Gerard A. Rongen, and Laura B.E. Kienhorst
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musculoskeletal diseases ,Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Gout ,Immunology ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Arthritis ,Disease ,Comorbidity ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Prevalence ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Aged ,030203 arthritis & rheumatology ,Acid level ,business.industry ,Confounding ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Uric Acid ,Serum urate ,Cross-Sectional Studies ,Cardiovascular Diseases ,Cohort ,Polyarthritis ,Female ,business - Abstract
Objective.Our aim was to examine the prevalence of cardiovascular disease (CVD) in patients with crystal-proven gout compared to arthritis controls. Further, we analyzed the association between characteristic gout severity factors and CVD to provide further support for a pathogenetic relationship between gout and CVD.Methods.Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers cohort. Joint fluid analysis was performed in all referred patients; controls were negative for crystals. Patients’ characteristics and different manifestations of CVD and gout severity factors (disease duration, attack frequency, tophi, affected joints, high serum urate acid level, joint damage) were collected. Gout patients were compared with controls for the prevalence of CVD. In addition, the association between characteristic gout severity factors and presence of CVD was analyzed.Results.Data from 700 gout patients and 276 controls were collected. CVD was present in 47% (95% CI 44%–51%) and 24% (95% CI 19%–29%) of gout patients and controls, respectively. Corrected for confounders, gout was still strongly associated with an increased prevalence of CVD compared to controls (OR 3.39, 95% CI 2.37–4.84). In patients with gout, disease duration ≥ 2 years, oligo- or polyarthritis, serum urate acid > 0.55 mmol/l at presentation, and joint damage were independently (p < 0.05) associated with prevalent CVD.Conclusion.Crystal-proven gout was strongly associated with an increased prevalence of CVD. In patients with gout, characteristic gout severity factors were associated with CVD.
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- 2017
34. 2015 Gout Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative
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Anne-Kathrin Tausche, Janitzia Vaquez-Mellado, Steven A. Yarows, Dianne Berendsen, William J. Taylor, John S. Sundy, Tuhina Neogi, George Nuki, Kenneth G. Saag, T.L.Th.A. Jansen, Fernando Perez-Ruiz, Melanie Brown, Jaap Fransen, Frédéric Lioté, H. Ralph Schumacher, Raymond P. Naden, Jasvinder A. Singh, N. Lawrence Edwards, Hyon K. Choi, Alexis Ogdie, Hein J.E.M. Janssens, and Nicola Dalbeth
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musculoskeletal diseases ,030203 arthritis & rheumatology ,medicine.medical_specialty ,business.industry ,Immunology ,Gold standard ,MEDLINE ,Tophus ,medicine.disease ,Rheumatology ,3. Good health ,Gout ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Physical therapy ,Immunology and Allergy ,Synovial fluid ,030212 general & internal medicine ,business ,Rheumatism ,Decision analysis - Abstract
Objective Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. Methods An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. Results The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). Conclusion The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.
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- 2015
35. Effect of Aerobic Exercise Training on Fatigue in Rheumatoid Arthritis: A Meta-Analysis
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Gijs Bleijenberg, H. Repping-Wuts, George S. Metsios, W.B. (Wilbert) van den Hout, M. Flendrie, P.L.C.M. van Riel, A. Reid, Geri B. Neuberger, S. Rongen-van Dartel, Jaap Fransen, and C.H.M. van den Ende
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medicine.medical_specialty ,business.industry ,Cochrane Library ,medicine.disease ,Confidence interval ,law.invention ,Rheumatology ,Randomized controlled trial ,Strictly standardized mean difference ,law ,Meta-analysis ,Rheumatoid arthritis ,Heart rate ,medicine ,Physical therapy ,Aerobic exercise ,business - Abstract
OBJECTIVE: Rheumatoid arthritis (RA) fatigue is not being well-managed currently, and evidence of effective interventions is limited. Aerobic exercise may provide benefit to treat fatigue in RA. Therefore, the purpose of this meta-analysis is to analyze the effect of aerobic land-based exercise on fatigue in RA. METHODS: A literature search was conducted using PubMed, Cochrane Library, Embase, and trial registers to identify randomized controlled trials (RCTs) with a supervised land-based aerobic exercise program performed with an intensity between 50% and 90% of maximal heart rate, of at least 15 minutes' duration, performed at least 2 times a week, and lasting for a time period of at least 4 consecutive weeks. Risk of bias was assessed using the Cochrane tool. A meta-analysis of fatigue outcomes was performed by calculating the standardized mean difference (SMD) using a random-effects model. RESULTS: Five RCTs were included. None of the trials selected patients with RA for having fatigue. Risk of bias was low in 3 RCTs and unclear in 2. Land-based aerobic exercise programs had a positive effect on fatigue in RA compared to no exercise at 12 weeks, SMD -0.31 (95% confidence interval [95% CI] -0.55, -0.06). At 24 weeks, the effect of aerobic land-based exercise was smaller and not statistically significant: SMD -0.15 (95% CI -0.33, 0.02). CONCLUSION: There is evidence with low risk of bias that an aerobic exercise program is effective in reducing fatigue among patients with RA, especially in the short term; however, effects are small. To substantiate the evidence, RCTs should be performed in patients with RA selected for having fatigue.
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- 2015
36. Personalizing treatment targets in rheumatoid arthritis by using a simple prediction model
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T.L.Th.A. Jansen, Jaap Fransen, Alfons A den Broeder, Yvonne M R de Punder, Piet L. C. M. van Riel, and Annelies E. van Ede
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Oncology ,Adult ,Male ,musculoskeletal diseases ,medicine.medical_specialty ,Hand Joints ,Immunology ,Logistic regression ,Peptides, Cyclic ,Risk Assessment ,Severity of Illness Index ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Disease activity ,Arthritis, Rheumatoid ,Treatment targets ,Rheumatology ,Internal medicine ,Foot Joints ,medicine ,Immunology and Allergy ,Humans ,In patient ,Risk factor ,Precision Medicine ,skin and connective tissue diseases ,Aged ,Autoantibodies ,business.industry ,Acute-phase protein ,Middle Aged ,Models, Theoretical ,medicine.disease ,Prognosis ,Radiography ,Rheumatoid arthritis ,Antirheumatic Agents ,Cohort ,Physical therapy ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Disease Progression ,Female ,business - Abstract
Objective.To develop a personalized treatment target approach in patients with rheumatoid arthritis (RA) based on baseline risk factors for joint damage progression in combination with disease activity over time.Methods.Data were used from the Nijmegen early RA cohort. Presence or absence of anticyclic citrullinated peptide antibodies (anti-CCP), high erythrocyte sedimentation rate, and erosions were translated into 4 risk profiles: 0, 1, 2, and 3. Joint damage progression was assessed with the Ratingen score, and disease activity with the original Disease Activity Score (DAS) over 3 years. The probability for joint damage progression was calculated for each risk profile and each DAS category using logistic regression models. The probabilities were translated into personalized disease activity treatment targets.Results.More risk factors at baseline as well as a higher DAS level resulted in a higher probability for joint damage progression in a dose-dependent way. Low DAS corresponded with a probability of 0.0, 0.08, 0.20, and 0.58 in patients with 0, 1, 2, and 3 risk factors, respectively. Moderate DAS corresponded with a probability of 0.06 in patients with 0 risk factors and 0.35 with 1 risk factor. High DAS resulted in a probability of 0.50 with no risk factors present at baseline.Conclusion.Presence of anti-CCP, acute-phase response, and erosions at baseline can be used to set individual treatment targets in RA. In patients without these risk factors, a moderate DAS as a target is sufficient, while for patients with all 3 risk factors, a low DAS is not strict enough to limit the risk for joint damage.
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- 2015
37. The effect of disease duration and disease activity on the risk of cardiovascular disease in rheumatoid arthritis patients
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Elke Arts, Calin D. Popa, Alfons A den Broeder, Jaap Fransen, and Piet L. C. M. van Riel
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Adult ,Male ,Risk ,medicine.medical_specialty ,Time Factors ,Disease duration ,Immunology ,Kaplan-Meier Estimate ,Disease ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Arthritis, Rheumatoid ,Cohort Studies ,Disease activity ,Peripheral Arterial Disease ,Rheumatology ,Internal medicine ,Myocardial Revascularization ,medicine ,Humans ,Immunology and Allergy ,Angina, Stable ,Longitudinal Studies ,Prospective Studies ,Acute Coronary Syndrome ,Survival analysis ,Aged ,Netherlands ,Proportional Hazards Models ,Cerebral Revascularization ,business.industry ,Smoking ,Confounding ,Middle Aged ,medicine.disease ,Connective tissue disease ,Surgery ,Stroke ,Cardiovascular Diseases ,Ischemic Attack, Transient ,Rheumatoid arthritis ,Cohort ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Female ,business - Abstract
ObjectiveDisease duration and disease activity may be associated with an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objectives of this study were to investigate (1) the relationship between duration of inflammation and the development of CVD in RA patients and (2) the relationship between RA disease activity over time and CVD in patients with RA.MethodsRA patients with a follow-up of ≥6 months in the Nijmegen early RA cohort without prior CVD were included. Disease activity over time was calculated using the time-averaged 28 joint disease activity score (DAS28) for each patient. Kaplan–Meier survival analysis and Cox proportional hazards regression were used for the analyses.ResultsDuring follow-up of the 855 patients that were included, 154 CV events occurred. The course of hazards over time did not indicate a change in the risk of CVD over the course of RA (disease duration), which is also reflected by the absence of a deflection in the survival curves. The survival distributions did not differ between patients with a disease duration of 10 years (Log-rank test: p=0.82). Time-averaged DAS28 was significantly associated with CVD (p=0.002) after correction for confounders.ConclusionsDisease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.
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- 2015
38. Ultra-low dose of rituximab in rheumatoid arthritis: study protocol for a randomised controlled trial
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Frank H J van den Hoogen, Lise M Verhoef, Jaap Fransen, Bart J F van den Bemt, Nathan den Broeder, Rogier M Thurlings, Alfons A den Broeder, Steven Teerenstra, and Nadine Boers
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Time Factors ,Cost-Benefit Analysis ,Dose reduction ,Medicine (miscellaneous) ,law.invention ,Non-inferiority ,Arthritis, Rheumatoid ,Study Protocol ,Disability Evaluation ,0302 clinical medicine ,Clinical Protocols ,Quality of life ,Randomized controlled trial ,law ,Infusions, Parenteral ,Pharmacology (medical) ,030212 general & internal medicine ,Lead (electronics) ,Netherlands ,Randomised controlled trial ,lcsh:R5-920 ,3. Good health ,Treatment Outcome ,Research Design ,Antirheumatic Agents ,Rheumatoid arthritis ,Retreatment ,Rituximab ,lcsh:Medicine (General) ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] ,medicine.drug ,medicine.medical_specialty ,Design ,Lower risk ,Drug Costs ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,03 medical and health sciences ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,Adverse effect ,030203 arthritis & rheumatology ,Decremental cost-effectiveness ratio (DCER) ,business.industry ,medicine.disease ,Surgery ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Low dose ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Quality of Life ,business - Abstract
Background A standard low-dosing schedule of rituximab (RTX; 2 × 500 mg or 1 × 1000 mg) is as effective for active rheumatoid arthritis (RA) as the registered dose (2 × 1000 mg). Moreover, several small uncontrolled studies suggest that even lower-dosed treatment with RTX also leads to good treatment response in patients with RA. Retreatment with such an ‘ultra-low’ dose RTX in patients who responded well to RTX induction treatment is of special interest, as long-term use of lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. However, the effect of ultra-low dose of RTX has not been investigated using a controlled trial of proper design and dimensions. Methods/Design REDO is an investigator driven six-month pragmatic, double-blind, randomised controlled non-inferiority trial on the effects of ultra-low-dose RTX (1 × 500 or 1 × 200 mg) compared to standard low dose (1 × 1000 mg) in RA patients who are being retreated with RTX. A total of 140 RA patients, having reached low disease activity (DAS28CRP
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- 2017
39. Clinical quality management in rheumatoid arthritis: putting theory into practice
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T. Langenegger, E. Uitz, Gerold Stucki, Jaap Fransen, University of Zurich, and Fransen, J
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medicine.medical_specialty ,business.industry ,2745 Rheumatology ,MEDLINE ,Arthritis ,610 Medicine & health ,medicine.disease ,142-005 142-005 ,Rheumatology ,Internal medicine ,Rheumatoid arthritis ,Severity of illness ,Health care ,medicine ,Physical therapy ,2736 Pharmacology (medical) ,Pharmacology (medical) ,Clinical quality ,business ,Rheumatoid arthritis disease activity - Abstract
Clinical quality management (CQM) in rheumatoid arthritis (RA) aims to reduce inflammatory activity and pain in the short term, and damage, and consequently disability, in the long term. Within CQM as used in Switzerland rheumatologists are provided with a measurement feedback system with which they can regularly follow their patients. Inflammatory activity is measured with the Disease Activity Score (DAS28) and the Rheumatoid Arthritis Disease Activity Index questionnaire (RADAI), damage with an X-ray score and disability with the Stanford Health Assessment Questionnaire (HAQ). Feedback is used to optimize therapy, which in the short term allows the activity of the inflammatory process to be adjusted or 'titrated'. In the long term, the therapy result for the individual patient is monitored by the course of disability and damage. In this paper we present a series of cases to illustrate the usefulness of the CQM system in the management of individual RA patients. CQM in RA may be helpful when making decisions about adjustment of treatment, and to document and communicate these decisions based on quantitative data.
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- 2017
40. AB0669 The eular systemic sclerosis impact of disease (SCLEROID) score – a new patient-reported outcome measure for patients with systemic sclerosis – preliminary results from the ongoing validation study
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Otylia Kowal-Bielecka, Christopher P. Denton, Ana Maria Gheorghiu, Roger Hesselstrand, Carina Mihai, Rucsandra Dobrota, Madelon C. Vonk, Turid Heiberg, Mike O Becker, Ann Tyrrell Kennedy, Yannick Allanore, Ulf Müller-Ladner, Jaap Fransen, M. Matucci Cerinic, Patricia Carreira, Oliver Distler, Kim Fligelstone, Gunnel Sandqvist, and L. Czirják
- Subjects
medicine.medical_specialty ,Validation study ,Hand function ,business.industry ,Disease ,Clinical trial ,Family medicine ,Cohort ,medicine ,Physical therapy ,Patient-reported outcome ,Sensitivity to change ,business ,Cohort study - Abstract
Background Patient reported outcome measures (PROM) are required as key outcomes in therapeutic trials in systemic sclerosis (SSc). Given the unmet need of a validated, comprehensive PROM in SSc, the ScleroID questionnaire was developed by a team of patients with SSc and medical experts in the field. This is intended as a brief, disease-specific, patient-derived, disease impact score for scientific and clinical use in SSc. Objectives To present a preliminary analysis from the ongoing ScleroID validation study. Methods This EULAR-endorsed project involves 11 European centers specialized in SSc. Patients fullfilling the ACR/EULAR 2013 criteria were prospectively included since 05/16 in the ongoing observational cohort study. Patients filled in the ScleroID questionnaire (Figure 1), as well as selected comparators SHAQ, EQ5D, SF36. Additionally, they weighted the 10 dimensions of the ScleroID by distributing 100 points according to the perceived impact on their health. The final score calculation will be based on the ranking of the weights. The study includes a reliability arm (follow-up questionnaire 7–10 days from baseline), as well as a longitudinal arm, looking at sensitivity to change at follow-up visits after 6 and 12 months from baseline. Results As of 01/2017 the study cohort included 224 patients with valid baseline data, 44 also had a reliability visit and 6 a 6-months follow-up visit. 84.4% of patients were female, 54.4% had limited SSc, median age 58, and median disease duration 8 years. The highest preliminary median weights for ScleroID domains were for Raynaud, impaired hand function, fatigue and pain (Table 1). Except for pain, these dimensions were also scored most highly in the ScleroID questionnaire at baseline. Conclusions The EULAR ScleroID score is a novel tool designed for use in clinical practice and clinical trials to display the disease impact of SSc. In this preliminary analysis, Raynaud syndrome, impaired hand function, and fatigue were the main patient reported drivers of disease impact, however, further recruitment and validation of this new instrument is ongoing. Disclosure of Interest R. Dobrota: None declared, M. Becker: None declared, K. Fligelstone: None declared, J. Fransen: None declared, A. Kennedy: None declared, Y. Allanore Grant/research support from: Grant/research support from: Bristol-Myers Squibb, Roche/Genentech, Inventiva, Pfizer, Sanofi, and Servier, Consultant for: Actelion, Bayer, Roche/Genentech, Inventiva, Medac, Pfizer, Sanofi, Servier, and UCB, P. Carreira: None declared, L. Czirjak: None declared, C. Denton: None declared, R. Hesselstrand: None declared, G. Sandqvist: None declared, O. Kowal-Bielecka: None declared, M. Matucci Cerinic: None declared, C. Mihai: None declared, A. Gheorghiu: None declared, U. Muller-Ladner: None declared, M. Vonk: None declared, T. Heiberg: None declared, O. Distler Grant/research support from: 4 D Science, AbbVie, Actelion, Active Biotec, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, ChemomAb, EpiPharm, espeRare foundation, Genentech/Roche, GSK, Inventiva, iQone Healthcare, Lilly, medac, Mepha, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Pfizer, Sanofi, Serodapharm and Sinoxa, Consultant for: 4 D Science, AbbVie, Actelion, Active Biotec, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, ChemomAb, EpiPharm, espeRare foundation, Genentech/Roche, GSK, Inventiva, iQone Healthcare, Lilly, medac, Mepha, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Pfizer, Sanofi, Serodapharm and Sinoxa
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- 2017
41. THU0428 On the incidence of gout flares in primary care: a retrospective cohort study
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M. Flendrie, Michael Janssen, Jaap Fransen, and Hein J.E.M. Janssens
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Pediatrics ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Medical record ,Tophus ,Pharmacy ,Retrospective cohort study ,Logistic regression ,medicine.disease ,Gout ,Cohort ,medicine ,business - Abstract
Background From rheumatologist point of view (secondary care) there is a serious concern about suboptimal treatment of gout patients in primary care with warnings for worse prognostic consequences.(1) Some refer even to a “state of suboptimal gout care” promoted by “substantial gaps between rheumatologists and primary care providers” in their approaches to gout care:(2) the strategy of “treating-to-target” (to lower serum uric acid (SUA) levels Objectives To quantify the occurrence of flares and the use of ULT, in primary care patients with gout, and to analyze patient characteristics related to low or high flare frequency. Methods A retrospective cohort study (setting one Dutch primary care center with an integrated medical praxis and pharmacy). Electronic medical records of ca. 5800 enlisted patients were used to select all patients with gout, to analyze their ULT use, and to assess flare frequency in a 2-year time window (2014–2015). Flare was defined as each pharmacy delivery of an anti-inflammatory drug or pain killer linked to a morbidity code for gout. Associations were studied between high or low flare frequency and patient characteristics by univariate logistic regression. Results Of 173 included patients (prevalence 3%; mean age 66.4 yr; 75.7% men) 38.7% used ULT persistently during the 2-year time-window. Median time after initial diagnosis was 8.0 yr (IQR 3.0–14.5). Mean total numbers of flares in two years was 2.7 (SD: 4.7), median 1.0 (IQR: 0.0–4.0). Of the patients not receiving ULT (n=106, 61.3%) 41.5% had never, 25.5% one or two, and 6.6% more than six flares during two years. No associations were found between patient characteristics (e.g. age, time after initial diagnosis, crystal diagnosis, ULT use, cardiovascular co-morbidity, diuretic use) to differentiate patients with “no-or-1-flare” and “2-or-more-flares” per two years. Conclusions Occurrence of flares in this stringently observed primary care cohort of patients with gout was very low, even if most patients did not use prophylactic ULT. Only 6.6% of patients experienced >6 flares in two years. Patients, in particular those not using ULT and with a low flare frequency (the majority), may reflect individuals with a distinctive (moderate) disease activity. They probably do not fulfill the general accepted advancing course of gout with ongoing and increasing flare frequency, MSU deposition, tophus formation, and joint damage. Immediate lifelong ULT for them may not be automatically indicated. Our study shows that suboptimal gout management in the perception of rheumatologists (secondary care) does not lead to an abundant number of gout flares in primary care patients. This urges to caution when recommendations based upon secondary care guide lines are advised for primary care patients with gout. References Doherty M, et al. Ann Rheum Dis 2012;71:1765–70. Dalbeth N, et al. Arthritis Rheumatol 2017;69:22–34. McLean RM, et al. Ann Intern Med 2017;166:73–4. Morillon MB, et al. BMJ Open 2016;6:e012026. Disclosure of Interest None declared
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- 2017
42. AB0652 Early organ involvement, survival and causes of death in an unselected cohort of dutch patients with systemic sclerosis
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W. Van Den Hombergh, Madelon C. Vonk, F.H.J. van den Hoogen, Jaap Fransen, and Hanneke K. A. Knaapen
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medicine.medical_specialty ,Pathology ,business.industry ,Scleroderma Renal Crisis ,Interstitial lung disease ,medicine.disease ,Rheumatology ,Scleroderma ,Internal medicine ,Cohort ,medicine ,skin and connective tissue diseases ,business ,Survival rate ,Survival analysis ,Cohort study - Abstract
Background Systemic sclerosis (SSc) patients are at risk for organ involvement and premature death. The occurrence of organ involvement that is reported differs widely between various long term cohort studies; ILD 25–90%, PAH 8–32%, CI 5–30%, and SRC 4–12%. Differences in findings also apply to survival, the 5- and 10-year survival rates between studies vary from 80% to 90% and from 60% to 85% respectively (1–3). Objectives To assess the occurrence of organ involvement and death in a large, unselected cohort of Dutch SSc patients at the moment of diagnosis and during 5 years of follow-up, stratified by disease subtype and auto-antibodies. Methods Up to 2015, 690 SSc patients were included in the Nijmegen SSc cohort. Occurrence of interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), cardiac involvement (CI), scleroderma renal crisis (SRC) and occurrence of death were determined using survival analysis, stratified by disease subtype (limited cutaneous SSc and diffuse cutaneous SSc) and auto-antibodies (ACA, ATA, anti-RNP). Results Organ involvement was already present at SSc diagnosis in 32% of patients. In 25%, organ involvement developed during follow-up, mostly ILD (22%). Significant differences between lcSSc and dcSSc were found in SRC at baseline and ILD, PAH and SRC during follow-up. Between the autoantibody subgroups, the occurrence of ILD, PAH and SRC at baseline and ILD during follow-up differed. There were no differences in survival between subtypes and auto-antibodies. The overall 5-year survival rate was 89%. Patients without organ involvement at SSc diagnosis had a better 5-year survival rate than patients with organ involvement at SSc diagnosis: 95% versus 73% respectively (p Conclusions In many SSc patients, organ involvement is already present at diagnosis or develops in the first 5 years after diagnosis. Survival is significantly worse in patients who already have involvement at the moment of SSc diagnosis. References Muangchan C, Canadian Scleroderma Research G, Baron M, Pope J. The 15% rule in scleroderma: the frequency of severe organ complications in systemic sclerosis. A systematic review. The Journal of rheumatology. 2013;40(9):1545–56. Vonk MC, Broers BM, Heijdra YF, Ton E, Snijders R, van Dijk AP, et al. Systemic sclerosis and its pulmonary complications in the Netherlands An epidemiological study. AnnRheumDis. 2008. Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis & rheumatology. 2014;66(6):1625–35. Disclosure of Interest None declared
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- 2017
43. Anticyclic Citrullinated Peptide Antibodies and Rheumatoid Factor as Risk Factors for 10-year Cardiovascular Morbidity in Patients with Rheumatoid Arthritis: A Large Inception Cohort Study
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Jaap Fransen, Calin D. Popa, Alfons A den Broeder, Marissa C. van Maaren, Elke Arts, and Mike L.T. Berendsen
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Adult ,Male ,musculoskeletal diseases ,medicine.medical_specialty ,Immunology ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Disease ,030204 cardiovascular system & hematology ,Anti-Citrullinated Protein Antibodies ,Arthritis, Rheumatoid ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Rheumatoid Factor ,Risk Factors ,Internal medicine ,Immunology and Allergy ,Medicine ,Rheumatoid factor ,Humans ,skin and connective tissue diseases ,Aged ,030203 arthritis & rheumatology ,biology ,business.industry ,Proportional hazards model ,Confounding ,Anti–citrullinated protein antibody ,Middle Aged ,medicine.disease ,Surgery ,Cardiovascular Diseases ,Rheumatoid arthritis ,Cohort ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,biology.protein ,Female ,business ,Cohort study ,Follow-Up Studies - Abstract
Objective.To determine whether anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) are risk factors for 10-year cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).Methods.Analyses were performed using data from the Nijmegen early RA inception cohort, in which patients with newly diagnosed RA, consecutively included since 1985, were regularly followed up. Anti-CCP and RF were determined at baseline (diagnosis). Outcome was the first cardiovascular disease (CVD) event [ischemic heart disease, nonhemorrhagic cerebrovascular accident (CVA), or peripheral artery disease (PAD)] after baseline as retrieved from physician diagnosis. Fatality was checked against death certificates. Cox regression including correction for baseline confounders was performed to estimate the effect of anti-CCP, RF, and their interaction on 10-year CVD-free survival.Results.Of 929 patients included, 628 were anti-CCP–positive and 697 were RF-positive. During followup, with a median of 7.5 years, 162 CV events were observed (101 ischemic heart disease, 45 CVA, and 16 PAD), of which 15 were fatal. The HRadjusted for anti-CCP was 1.17 (95% CI 0.82–1.67) and the HRadjusted for RF was 1.52 (95% CI 1.00–2.30). The association of RF positivity with CVD was even stronger in the anti-CCP–negative patients: HRadjusted 2.09 (95% CI 1.18–3.71). There was no significant interaction (p = 0.098) between anti-CCP and RF.Conclusion.Rather than anti-CCP, presence of RF was associated with CVD in this cohort of patients with RA.
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- 2017
44. IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis
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Michelle S M A Damen, Mihai G. Netea, Jacqueline de Graaf, Bas Heinhuis, Jaap Fransen, Calin D. Popa, Michael T. Nurmohamed, Marieke J H Coenen, Suzanne Holewijn, Charles A. Dinarello, Jéssica Cristina dos Santos, Leo A. B. Joosten, Rabia Agca, Piet L. C. M. van Riel, Rheumatology, AII - Inflammatory diseases, ICaR - Circulation and metabolism, ACS - Microcirculation, and ACS - Atherosclerosis & ischemic syndromes
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Male ,0301 basic medicine ,Genotype ,Lipoproteins ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Biology ,Polymorphism, Single Nucleotide ,Article ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Arthritis, Rheumatoid ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,High-density lipoprotein ,Gene Frequency ,Polymorphism (computer science) ,Prevalence ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Allele ,Promoter Regions, Genetic ,Alleles ,Aged ,030203 arthritis & rheumatology ,Multidisciplinary ,Cholesterol ,Interleukins ,Cholesterol, HDL ,Middle Aged ,medicine.disease ,030104 developmental biology ,chemistry ,Cardiovascular Diseases ,Genetic Loci ,Rheumatoid arthritis ,Immunology ,Cohort ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Female ,Lipoprotein - Abstract
Contains fulltext : 169697.pdf (Publisher’s version ) (Open Access) Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a functional genetic variant of IL-32 on lipid profiles and CVD risk was therefore studied in whole blood from individuals from the NBS cohort and RA patients from 2 independent cohorts. Lipid profiles were matched to the specific IL-32 genotypes. Allelic distribution was similar in all three groups. Interestingly, significantly higher levels of high density lipoprotein cholesterol (HDLc) were observed in individuals from the NBS cohort and RA patients from the Nijmegen cohort homozygous for the C allele (p = 0.0141 and p = 0.0314 respectively). In contrast, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals at higher risk for CVD (plaque positive) (p = 0.0396; p = 0.0363 respectively). Our study shows a functional effect of a promoter single-nucleotide polymorphism (SNP) in IL32 on lipid profiles in RA patients and individuals, suggesting a possible protective role of this SNP against CVD.
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- 2017
45. L’arthrite de la première métatarsophalangienne n’est pas toujours une goutte : étude d’une cohorte prospective chez des patients en soins primaires
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Jaap Fransen, Eloy H. van de Lisdonk, Hein J.E.M. Janssens, Laura B.E. Kienhorst, and Matthijs Janssen
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Rheumatology - Abstract
Resume Objectifs L’arthrite de la premiere metatarsophalangienne a ete consideree comme pathognomonique de la goutte, mais il est inconnu si les autres formes d’arthrite peuvent survenir au niveau de cette articulation. Les objectifs de ce travail etaient de determiner la validite du diagnostic clinique du medecin generaliste en utilisant comme test de reference l’analyse du liquide synovial, de definir la prevalence des autres diagnostics que la goutte ainsi que les signes et les symptomes qui permettent de differencier les patients goutteux des non goutteux. Methodes Cette etude de cohorte prospective avait inclus des patients de soins primaires presentant une monoarthrite de la premiere metatarsophalangienne. Apres un recrutement des patients par leurs medecins generalistes, les donnees des patients ont ete colligees par un rhumatologue. Le liquide synovial avait ete analyse a la recherche de cristaux d’urate monosodique. Si les cristaux etaient absents, les patients etaient suivis sur une periode de 6 ans, ou jusqu’a ce qu’un diagnostic precis soit etabli. Si durant la periode de suivi des cristaux sont identifies, le patient est classe comme ayant presente une goutte a l’evaluation initiale. Resultats Cent cinquante-neuf patients de soins primaires ont ete inclus. A l’inclusion, le diagnostic clinique avait ete pose dans 98 % des cas. Les valeurs predictives positive et negative de la goutte etaient respectivement de 0,79 et de 0,75. Apres la periode de suivi, 77 % avaient une goutte, 8 % avaient une autre affection rhumatismale et 15 % avaient une monoarthrite transitoire non specifique. Les patients goutteux avaient des signes les discriminant des patients non goutteux. Conclusions La goutte est une cause frequente mais non exclusive des arthrites de la premiere metatarsophalangienne.
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- 2014
46. Generalization and Extrapolation of Treatment Effects From Clinical Studies in Rheumatoid Arthritis
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Jaap Fransen, Floris P J G Lafeber, Rosan W. Janse, S.C. Nair, Johannes W. J. Bijlsma, Paco M J Welsing, and Wietske Kievit
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musculoskeletal diseases ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,medicine.disease ,law.invention ,Clinical trial ,Rheumatology ,Randomized controlled trial ,law ,Internal medicine ,Relative risk ,Rheumatoid arthritis ,Cohort ,medicine ,Physical therapy ,Observational study ,skin and connective tissue diseases ,education ,business ,Cohort study - Abstract
Objective Pragmatic clinical trials have been proposed as a solution for nongeneralizability of randomized clinical trial (RCT) results. We investigated whether treatment effects of pragmatic clinical trials are indeed generalizable to clinical practice and how efficacy estimates from published RCTs can be translated to daily practice populations. Methods Data from pragmatic clinical trials of the Utrecht Rheumatoid Arthritis Cohort and the observational Nijmegen Early Rheumatoid Arthritis inception cohort were used. The treatment effects of methotrexate and hydroxychloroquine as opposed to the pyramid approach were compared between the trials and observational study using a modified comprehensive cohort design analysis. The changes from baseline in disease activity (Disease Activity Score in 28 joints [DAS28]) and functional disability (Health Assessment Questionnaire [HAQ]) and European League Against Rheumatism (EULAR) response at 6 months were studied. The influence of population and treatment characteristics on the American College of Rheumatology 50% improvement criteria response compared with control therapy also at 6 months from RCTs was assessed using the relative risk (RR) and risk difference (RD). Results The DAS28 and HAQ generally improved more in patients in the pragmatic trials than in daily practice. However, using EULAR response as outcome, the treatment effect was not found to be different. In published RCT data, higher glucocorticoid use, disease duration, and cotreatment with disease-modifying antirheumatic drugs increased the RR. Use of glucocorticoids increased the RD, and higher values of baseline DAS28 and HAQ decreased the RR and RD. Conclusion Pragmatic clinical trials might be directly generalizable only regarding relative treatment response. In extrapolating published RCT results to daily practice, population characteristics associated with disease severity, disease duration, and treatment history or cotreatment need to be taken into account.
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- 2014
47. Imaging modalities for the classification of gout: systematic literature review and meta-analysis
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Jaap Fransen, Tuhina Neogi, T.L.Th.A. Jansen, Schumacher Hr, Nicola Dalbeth, William J. Taylor, Alexis Ogdie, and Mark Weatherall
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medicine.medical_specialty ,Gout ,Immunology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Imaging modalities ,Rheumatology ,Monosodium urate ,medicine ,Humans ,Immunology and Allergy ,Ultrasonography ,medicine.diagnostic_test ,business.industry ,Projectional radiography ,Tophus ,Gold standard (test) ,medicine.disease ,Magnetic Resonance Imaging ,Uric Acid ,Systematic review ,Meta-analysis ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Radiology ,Tomography, X-Ray Computed ,business - Abstract
Item does not contain fulltext BACKGROUND: Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques. OBJECTIVE: To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria. METHODS: We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated. RESULTS: 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively. CONCLUSIONS: US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.
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- 2014
48. Relationship Between Objectively Assessed Physical Activity and Fatigue in Patients With Rheumatoid Arthritis: Inverse Correlation of Activity and Fatigue
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P.L.C.M. van Riel, S. Rongen-van Dartel, Jaap Fransen, Hans Knoop, D. van Hoogmoed, Gijs Bleijenberg, and H. Repping-Wuts
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Activity level ,medicine.medical_specialty ,Cross-sectional study ,business.industry ,Arthritis ,Regression analysis ,medicine.disease ,Rheumatology ,Rheumatoid arthritis ,Linear regression ,medicine ,Physical therapy ,Outpatient clinic ,business ,Cohort study - Abstract
Objective Fatigue is generally associated with low physical activity in patients with various chronic medical conditions. However, such an association has not been reported among patients with rheumatoid arthritis (RA). The objectives of this study were to investigate whether daily activity level is associated with fatigue in patients with RA, and whether pain, disability, coping, and/or cognition are associated with the level of daily activity. Methods Patients with RA who visited our outpatient clinic were recruited consecutively. Fatigue severity was measured using the Checklist Individual Strength (CIS20). Physical activity was measured for 14 consecutive days using an ankle-worn actometer. The daily activity level of each patient was calculated, and each patient was classified as having a low or high activity level with respect to the group average. Data were analyzed by linear regression. Results A total of 167 patients were included in the analysis; 25% had a low activity level and 75% had a high activity level. A regression analysis revealed that higher activity levels were associated with reduced fatigue (P = 0.008). The mean ± SD CIS fatigue score was 30.9 ± 12.3 among the patients with a high activity level and 35.7 ± 12.8 among the patients with a low activity level (P = 0.03). Pain, disability, coping, and cognition were not associated significantly with daily activity level. Conclusion Among patients with RA, a higher level of daily physical activity was associated with reduced levels of fatigue. This relationship was not explained by differences in sex, age, disease duration, pain, disability, or other fatigue-related factors.
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- 2014
49. Multicriteria decision analysis methods with 1000Minds for developing systemic sclerosis classification criteria
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Madelon C. Vonk, Virginia D. Steen, Barri J. Fessler, Maureen D. Mayes, Susanna Cappelli, James R. Seibold, Marco Matucci-Cerinic, Janet E. Pope, Sindhu R. Johnson, Murray Baron, Raymond P. Naden, Ulf Mueller-Ladner, Frank J. A. van den Hoogen, Yannick Allanore, Gabriela Riemekasten, Ulrich A. Walker, John Varga, Dinesh Khanna, Jaap Fransen, Lorinda Chung, Thomas A. Medsger, Richard M. Silver, Oliver Distler, Alan Tyndall, Christopher P. Denton, Jacob M van Laar, Peter A. Merkel, Armando Gabrielli, Patricia Carreira, P. J. Clements, University of Zurich, and Johnson, Sindhu R
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Multicriteria decision ,Pathology ,medicine.medical_specialty ,Biomedical Research ,Consensus ,Epidemiology ,Intraclass correlation ,610 Medicine & health ,Article ,Decision Support Techniques ,Consistency (statistics) ,Content validity ,medicine ,Humans ,Muscle contracture ,Scleroderma, Systemic ,integumentary system ,business.industry ,Two-alternative forced choice ,10051 Rheumatology Clinic and Institute of Physical Medicine ,Reproducibility of Results ,Confidence interval ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Physical therapy ,Feasibility Studies ,business ,Decision analysis ,2713 Epidemiology - Abstract
Contains fulltext : 137489.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Classification criteria for systemic sclerosis (SSc) are being developed. The objectives were to develop an instrument for collating case data and evaluate its sensibility; use forced-choice methods to reduce and weight criteria; and explore agreement among experts on the probability that cases were classified as SSc. STUDY DESIGN AND SETTING: A standardized instrument was tested for sensibility. The instrument was applied to 20 cases covering a range of probabilities that each had SSc. Experts rank ordered cases from highest to lowest probability; reduced and weighted the criteria using forced-choice methods; and reranked the cases. Consistency in rankings was evaluated using intraclass correlation coefficients (ICCs). RESULTS: Experts endorsed clarity (83%), comprehensibility (100%), face and content validity (100%). Criteria were weighted (points): finger skin thickening (14-22), fingertip lesions (9-21), friction rubs (21), finger flexion contractures (16), pulmonary fibrosis (14), SSc-related antibodies (15), Raynaud phenomenon (13), calcinosis (12), pulmonary hypertension (11), renal crisis (11), telangiectasia (10), abnormal nailfold capillaries (10), esophageal dilation (7), and puffy fingers (5). The ICC across experts was 0.73 [95% confidence interval (CI): 0.58, 0.86] and improved to 0.80 (95% CI: 0.68, 0.90). CONCLUSIONS: Using a sensible instrument and forced-choice methods, the number of criteria were reduced by 39% (range, 23-14) and weighted. Our methods reflect the rigors of measurement science and serve as a template for developing classification criteria.
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- 2014
50. Evolving Concepts of Diagnosis and Classification
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Sindhu R. Johnson, Lorinda Chung, Jaap Fransen, and Frank H. J. Van den Hoogen
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- 2016
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