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Gout: HELP
Articles by Hein J. E. M. Janssens
Based on 20 articles published since 2008
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Between 2008 and 2019, H. Janssens wrote the following 20 articles about Gout.
 
+ Citations + Abstracts
1 Guideline 2016 updated EULAR evidence-based recommendations for the management of gout. 2017

Richette, P / Doherty, M / Pascual, E / Barskova, V / Becce, F / Castañeda-Sanabria, J / Coyfish, M / Guillo, S / Jansen, T L / Janssens, H / Lioté, F / Mallen, C / Nuki, G / Perez-Ruiz, F / Pimentao, J / Punzi, L / Pywell, T / So, A / Tausche, A K / Uhlig, T / Zavada, J / Zhang, W / Tubach, F / Bardin, T. ·AP-HP, hôpital Lariboisière, service de Rhumatologie, F-75010 Paris, France; Inserm, UMR1132, Hôpital Lariboisière, F-75010 Paris, France; Universitè Paris Diderot, Sorbonne Paris Citè, F-75205 Paris, France. · Academic Rheumatology, University of Nottingham, Nottingham, UK. · Department of Rheumatology, Hospital General Universitario de Alicante, Alicante, Spain. · Institute of Rheumatology RAMS, Moscow, Russia. · Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland. · AP-HP, Dèpartement d'Epidèmiologie et Recherche Clinique, Hôpital Bichat, Paris, France: APHP, Centre de Pharmacoèpidèmiologie, Paris, France: Univ Paris Diderot, Paris, France: INSERM UMR 1123 ECEVE, Paris, France. · Patient from Nottingham, UK, Paris. · Department of Rheumatology, VieCuri Medical Centre, Venlo, and Scientific IQ HealthCare, Radboud UMC, Nijmegen, The Netherlands. · Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Netherlands. · Arthritis Research UK Primary Care Centre University of Keele, Keele, UK. · Osteoarticular Research Group, University of Edinburgh, Edinburgh, UK. · Seccion de Rheumatologia, Hospital de Cruces, Baracaldo, Spain. · Rheumatology Unit, Clínica Coração de Jesus, Lisbon, Portugal. · Rheumatology Unit, University of Padova, Padova, Italy. · Service de Rhumatologie, CHUV and Universitè de Lausanne, Lausanne, Switzerland. · Department of Rheumatology, University Clinic at the Technical University Dresden, Germany. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Czech Republic. ·Ann Rheum Dis · Pubmed #27457514.

ABSTRACT: BACKGROUND: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. METHODS: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. RESULTS: Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. CONCLUSIONS: These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.

2 Review Use of diuretics and the risk of gouty arthritis: a systematic review. 2012

Hueskes, Berdine A A / Roovers, Elisabeth A / Mantel-Teeuwisse, Aukje K / Janssens, Hein J E M / van de Lisdonk, Eloy H / Janssen, Matthijs. ·Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands. ·Semin Arthritis Rheum · Pubmed #22221907.

ABSTRACT: OBJECTIVE: To systematically review the literature investigating the relationship between use of diuretics and the risk of gouty arthritis. METHODS: PubMed (1950-October 2009), Embase (1974-October 2009), and the Cochrane Library (up to October 2009) were searched using keywords and MeSH terms diuretics, adverse effects, and gout. For this review, the technique of "best evidence synthesis" was used. Studies reporting frequency, absolute or relative risks, odds ratio, or rate ratio of gouty arthritis in diuretic users compared with nonusers were selected and evaluated. Studies had to be published in English. Checklists from the Dutch Cochrane Centre were used to assess the quality of randomized controlled trials (RCTs), cohort, and case-control studies. RESULTS: Two RCTs, 6 cohort studies, and 5 case-control studies met the inclusion criteria. The overall quality of the studies was moderate. In a RCT the rate ratio of gout for use of bendrofluazide vs placebo was 11.8 (95% CI 5.2-27.0). The other RCT found a rate ratio of 6.3 (95% CI 0.8-51) for use of hydrochlorothiazide plus triamterene vs placebo. Three cohort studies and 4 case-control studies found higher risks of gouty arthritis in users compared with nonusers of diuretics. CONCLUSIONS: There is a trend toward a higher risk for acute gouty arthritis attacks in patients on loop and thiazide diuretics, but the magnitude and independence is not consistent. Therefore, stopping these useful drugs in patients who develop gouty arthritis is not supported by the results of this review.

3 Review Systemic corticosteroids for acute gout. 2008

Janssens, H J E M / Lucassen, P L B J / Van de Laar, F A / Janssen, M / Van de Lisdonk, E H. ·Transeedijk 62, Lobith, Netherlands, 6915 XZ. h.janssens2@chello.nl ·Cochrane Database Syst Rev · Pubmed #18425920.

ABSTRACT: BACKGROUND: Gout is one of the most frequently occurring rheumatic diseases, worldwide. Given the well-known drawbacks of the regular treatments for acute gout (non-steroidal anti-inflammatory drugs (NSAIDs), colchicine), systemic corticosteroids might be safe alternatives. OBJECTIVES: To assess the efficacy and safety of systemic corticosteroids in the treatment of acute gout in comparison with placebo, NSAIDs, colchicine, other active drugs, other therapies, or no therapy. SEARCH STRATEGY: Searches were done in the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007); MEDLINE (1966 to 2007) through PubMed; EMBASE (1974 to 2007); Web of Science (1975 to 2007); LILACS (1986 to 2007); and databases of ongoing trials (up to April 2007). SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials investigating the use of systemic corticosteroids in the treatment of acute gout were included. DATA COLLECTION AND ANALYSIS: Two review authors decided independently which trials to include. The same review authors also collected the data in a standardised form and assessed the methodological quality of the trial using validated criteria. When possible, continuous and dichotomous data were summarised statistically. MAIN RESULTS: Three head to head trials involving 148 patients (74 systemic corticosteroids; 74 comparator drugs) were included. Placebo-controlled trials were not found. In the studies, different kinds of systemic corticosteroids and different kinds of control drugs were used, both administered in different routes. Intramuscular triamcinolone acetonide was compared respectively to oral indomethacine, and intramuscular adrenocorticotropic hormone (ACTH); oral prednisolone (together with a single intramuscular diclophenac injection) was compared to oral indomethacine (together with a single placebo injection). Outcome measurements varied: average number of days until total relief of signs, mean decrease of pain per unit of time in mm on a visual analogue scale (VAS) - during rest and activity. In the triamcinolone-indomethacine trial the clinical joint status was used as an additional outcome. Clinically relevant differences between the studied systemic corticosteroids and the comparator drugs were not found; important safety problems attributable to the used corticosteroids were not reported. The quality of the three studies was graded as very low to moderate. Statistical pooling of results was not possible. AUTHORS' CONCLUSIONS: There is inconclusive evidence for the efficacy and effectiveness of systemic corticosteroids in the treatment of acute gout. Patients with gout did not report serious adverse effects from systemic corticosteroids, when used short term.

4 Article Performance of the 2015 ACR-EULAR classification criteria for gout in a primary care population presenting with monoarthritis. 2017

Janssens, Hein J E M / Fransen, Jaap / Janssen, Matthijs / Neogi, Tuhina / Schumacher, H Ralph / Jansen, Tim L / Dalbeth, Nicola / Taylor, William J. ·Department of Primary and Community Care, Radboud University Medical Center, Nijmegen. · Department Family Physicians, Primary Healthcare Center Lobede, Lobith-Tolkamer. · Department of Rheumatology, Radboud University Medical Center, Nijmegen. · Department of Rheumatology, Rijnstate hospital, Arnhem, the Netherlands. · Department of Medicine, Boston University School of Medicine, Boston, MA. · Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Department of Rheumatology, Viecuri Medical Center, Venlo, the Netherlands. · School of Medicine, University of Auckland, Auckland. · Department of Medicine, University of Otago, Wellington, New Zealand. ·Rheumatology (Oxford) · Pubmed #28431109.

ABSTRACT: 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.

5 Article A pilot study of CXCL8 levels in crystal proven gout patients during allopurinol treatment and their association with cardiovascular disease. 2017

Kienhorst, Laura / Janssens, Hein / Radstake, Timothy / van Riel, Piet / Jacobs, Johannes / van Koolwijk, Elly / van Lochem, Ellen / Janssen, Matthijs. ·Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. Electronic address: l.b.e.kienhorst@umcutrecht.nl. · Department of Primary and Community Care, Radboud University Medical Center, PO Box 9101, 6500 Nijmegen, HB, The Netherlands; Department of Clinical Research, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, PO Box 85500, 3508 Utrecht, GA, The Netherlands; Department of Immunology, University Medical Center Utrecht, PO Box 85500, 3508 Utrecht, GA, The Netherlands. · Scientific Institute for Quality of Healthcare, Radboud University Medical Center, PO Box 9101, 6500 Nijmegen, HB, The Netherlands. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, PO Box 85500, 3508 Utrecht, GA, The Netherlands. · Department of Medical Microbiology and Immunology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. · Department of Clinical Research, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands; Department of Medical Microbiology and Immunology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. · Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. ·Joint Bone Spine · Pubmed #27894951.

ABSTRACT: OBJECTIVES: Gout is associated with cardiovascular diseases, and systemic inflammation has a role in this. CXCL8 (interleukin-8) levels were increased in synovial fluid of gout patients, and in serum in gout patients irrespective of their disease activity. We hypothesized that the well-known cardiovascular protective effects of allopurinol could be related to effects of this drug on CXCL8 levels. METHODS: Patients with a crystal proven gout diagnosis, who newly started allopurinol treatment, were included in this prospective cohort study. After evaluation at baseline for cardiovascular diseases, tophi, uric acid, CRP and CXCL8 serum levels, patients were followed for changes in uric acid and CXCL8 levels. A subgroup analysis was performed in 10 patients with the longest follow-up period and at least 4 assessments of serum uric acid and CXCL8. RESULTS: Sixty patients were included, and patients known with cardiovascular diseases at baseline had significantly higher CXCL8 and uric acid levels (P<0.01). In the whole group, median CXCL8 levels had not decreased after a median (IQR) follow-up of 27 (12-44) weeks (P=0.66). In the subgroup analysis in 9 out of 10 patients, CXCL8 levels showed a slight decrease, sometimes after an initial increase after a median (IQR) follow-up of 51 (45-60) weeks. CONCLUSIONS: This pilot study indicates that higher CXCL8 levels were associated cardiovascular diseases in gout patients. Short-term use of allopurinol does not decrease CXCL8 levels in gout patients, but longer use possibly does. Further studies are warranted to establish the potential mechanisms of treatment and effects on CXCL8 levels.

6 Article Gout and rheumatoid arthritis, both to keep in mind in cardiovascular risk management: A primary care retrospective cohort study. 2017

Janssens, Hein J E M / Arts, Paul G J / Schalk, Bianca W M / Biermans, Marion C J. ·Department of primary and community care, Radboud university medical center, PO Box 9101, Internal code 117, 6500 HB Nijmegen, The Netherlands; Primary health care center Lobede, Lobith-Tolkamer, The Netherlands. Electronic address: Hein.Janssens@radboudumc.nl. · Department of primary and community care, Radboud university medical center, PO Box 9101, Internal code 117, 6500 HB Nijmegen, The Netherlands. ·Joint Bone Spine · Pubmed #27236260.

ABSTRACT: OBJECTIVES: To assess in one time window cardiovascular risks for both patients with gout and patients with rheumatoid arthritis in a Dutch primary care population. METHODS: Retrospective matched cohort study with data from the electronic health records of 51 Dutch general practices. Participants were patients aged 30 years or older with an incident diagnosis of gout (n=2655) or rheumatoid arthritis (n=513), and matched non-disease controls (n=7891 and n=1850 respectively). At disease incidence date, patients and controls were compared for prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and prior cardiovascular diseases. Patients without prior cardiovascular disease were followed for a first cardiovascular disease, and compared to controls using Kaplan-Meier survival curves and Cox proportional hazard analyses. RESULTS: Compared to controls, gout patients suffered more from hypertension (44.8%), diabetes (20.1%), hypercholesterolemia (13.7%), and prior cardiovascular disease (30%) (P<0.01), whereas rheumatoid arthritis patients (hypertension 28.5%; diabetes 11.7%; hypercholesterolemia 7.4%; prior cardiovascular disease 11.3%) did not (P>0.05). After adjustment, both gout and rheumatoid arthritis patients without prior cardiovascular disease were more likely to get a cardiovascular disease: hazard ratio (95% confidence interval) 1.44 (1.18 to 1.76), and 2.06 (1.34 to 3.16) respectively. CONCLUSIONS: This primary care study indicates that gout and rheumatoid arthritis are both independent risk factors for cardiovascular diseases, rheumatoid arthritis to some greater extent, whereas gout patients at first diagnosis had already an increased cardiovascular risk profile. It gives strong arguments for implementation of both rheumatic diseases in primary care guidelines on cardiovascular risk management.

7 Article Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial. 2016

Rainer, Timothy Hudson / Cheng, Chi Hung / Janssens, Hein J E M / Man, Chi Yin / Tam, Lai Shan / Choi, Yu Fai / Yau, Wah Hon / Lee, Ka Hing / Graham, Colin Alexander. · ·Ann Intern Med · Pubmed #26903390.

ABSTRACT: BACKGROUND: Two recent double-blind, randomized, controlled trials (RCTs) showed that oral steroids and nonsteroidal anti-inflammatory drugs have similar analgesic effectiveness for management of gout, but the trials had small sample sizes and other methodological limitations. OBJECTIVE: To compare the effectiveness and safety of oral prednisolone versus oral indomethacin in patients presenting to emergency departments (EDs) with acute gout. DESIGN: Multicenter, double-blind, randomized equivalence trial. Patients were randomly assigned (1:1 ratio) to receive either indomethacin or prednisolone. (ISRCTN registry number: ISRCTN45724113). SETTING: Four EDs in Hong Kong. PARTICIPANTS: 416 patients aged 18 years or older. MEASUREMENTS: Analgesic effectiveness was defined as changes in pain (at rest or with activity) greater than 13 mm on a 100-mm visual analogue scale. Outcomes were measured during the first 2 hours in the ED and from days 1 to 14. RESULTS: 376 patients completed the study. Equivalent and clinically significant within-group reductions in mean pain score were observed with indomethacin and prednisolone in the ED (approximately 10 mm [rest] and 20 mm [activity]) and from days 1 to 14 (approximately 25 mm [rest] and 45 mm [activity]). No major adverse events occurred during the study. During the ED phase, patients in the indomethacin group had more minor adverse events than those in the prednisolone group (19% vs. 6%; P < 0.001). During days 1 to 14, 37% of patients in each group had minor adverse events. LIMITATION: Diagnosis of gout was usually based on clinical criteria rather than examination of joint fluid. CONCLUSION: Oral prednisolone and indomethacin had similar analgesic effectiveness among patients with acute gout. Prednisolone is a safe, effective first-line option for treatment of acute gout. PRIMARY FUNDING SOURCE: Health and Health Services Research Grant Committee of the Hong Kong Government.

8 Article Knowledge, illness perceptions and stated clinical practice behaviour in management of gout: a mixed methods study in general practice. 2016

Spaetgens, Bart / Pustjens, Tobias / Scheepers, Lieke E J M / Janssens, Hein J E M / van der Linden, Sjef / Boonen, Annelies. ·Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. bartholomeus.spaetgens@mumc.nl. · CAPHRI Research Institute, University Maastricht, Maastricht, The Netherlands. bartholomeus.spaetgens@mumc.nl. · Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. · CAPHRI Research Institute, University Maastricht, Maastricht, The Netherlands. · Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, The Netherlands. · Primary Health Care Centre Lobede, Lobith-Tolkamer, The Netherlands. ·Clin Rheumatol · Pubmed #26898982.

ABSTRACT: The objective of the present study is to explore knowledge, illness perceptions and stated practice behaviour in relation to gout in primary care. This is a mixed methods study among 32 general practitioners (GPs). The quantitative assessment included the Gout Knowledge Questionnaire (GKQ; range 0-10; better) and Brief Illness Perceptions Questionnaire (BIPQ; nine items, range 0-10; stronger). Structured individual interviews obtained further qualitative insight into knowledge and perceptions, in the context of daily practice. Among 32 GPs, 18 (56.3 %) were male, mean age 44.4 years (SD 9.6) and mean working experience 17.1 years (SD 9.7). Median score [interquartile ranges (IQR)] on the GKQ was 7.8 [6.7-8.9] and 9.0 [8.0-10.0], when presented as open or multiple-choice questions, respectively. The BIPQ (median; [IQR]) revealed that gout was seen as a chronic disease (8.0; [7.0-9.0]), affecting life and emotions moderately (6.5; [5.0-7.0]), having many severe symptoms (8.0; [7.0-9.0]) and in which treatment could be very helpful (8.0; [7.0-9.0]). Further interviews revealed large variation in specific aspects of knowledge and about gaps concerning indications for uric acid-lowering therapy (UALT), duration of UALT, target serum uric acid (sUA) level or duration of prophylactic treatment. Finally, patients' adherence was not checked systematically. Specific knowledge gaps and discrepancies between perceptions and stated practice behaviour were identified, which might hamper effective management of this well-treatable disease. Improving evidence on the rationale and effectiveness of treatment targets and adherence interventions, tailoring guidelines to general practice and intensification of implementation of guidelines in primary health care seem to be needed.

9 Article 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 2015

Neogi, Tuhina / Jansen, Tim L Th A / Dalbeth, Nicola / Fransen, Jaap / Schumacher, H Ralph / Berendsen, Dianne / Brown, Melanie / Choi, Hyon / Edwards, N Lawrence / Janssens, Hein J E M / Lioté, Frédéric / Naden, Raymond P / Nuki, George / Ogdie, Alexis / Perez-Ruiz, Fernando / Saag, Kenneth / Singh, Jasvinder A / Sundy, John S / Tausche, Anne-Kathrin / Vaquez-Mellado, Janitzia / Yarows, Steven A / Taylor, William J. ·Boston University School of Medicine, Boston, Massachusetts, USA. · Viecuri Medical Center, Venlo, The Netherlands Radboud University Medical Center, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · Radboud University Medical Center, Nijmegen, The Netherlands. · University of Pennsylvania, Philadelphia, Pennsylvania, USA. · University of Otago, Wellington, New Zealand. · University of Florida, Gainesville, Florida, USA. · INSERM UMR 1132, Hôpital Lariboisière, AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · McMaster University Medical Centre, Hamilton, Ontario, Canada. · University of Edinburgh, Edinburgh, UK. · Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya, Spain. · University of Alabama at Birmingham, Birmingham, Alabama, USA. · Birmingham VA Medical Center and University of Alabama at Birmingham, and Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Duke University and Duke University Medical Center, Durham, North Carolina, USA Gilead Sciences, Foster City, California, USA. · University Hospital Carl Gustav Carus, Dresden, Germany. · Hospital General de Mexico, Mexico City, Mexico. · University of Michigan Health System, Chelsea. ·Ann Rheum Dis · Pubmed #26359487.

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 multi-criterion 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 one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, 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 CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: 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.

10 Article 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 2015

Neogi, Tuhina / Jansen, Tim L Th A / Dalbeth, Nicola / Fransen, Jaap / Schumacher, H Ralph / Berendsen, Dianne / Brown, Melanie / Choi, Hyon / Edwards, N Lawrence / Janssens, Hein J E M / Lioté, Frédéric / Naden, Raymond P / Nuki, George / Ogdie, Alexis / Perez-Ruiz, Fernando / Saag, Kenneth / Singh, Jasvinder A / Sundy, John S / Tausche, Anne-Kathrin / Vazquez-Mellado, Janitzia / Yarows, Steven A / Taylor, William J. ·Boston University School of Medicine, Boston, Massachusetts. · Viecuri Medical Center, Venlo, The Netherlands, and Radboud University Medical Center, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · Radboud University Medical Center, Nijmegen, The Netherlands. · University of Pennsylvania, Philadelphia. · University of Otago, Wellington, New Zealand. · University of Florida, Gainesville. · Frédéric Lioté, MD, PhD: INSERM UMR 1132, Hôpital Lariboisière, AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · McMaster University Medical Centre, Hamilton, Ontario, Canada. · University of Edinburgh, Edinburgh, UK. · Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya, Spain. · University of Alabama at Birmingham. · Birmingham VA Medical Center and University of Alabama at Birmingham, and Mayo Clinic College of Medicine, Rochester, Minnesota. · Gilead Sciences, Foster City, California). · University Hospital Carl Gustav Carus, Dresden, Germany. · Hospital General de Mexico, Mexico City, Mexico. · University of Michigan Health System, Chelsea. ·Arthritis Rheumatol · Pubmed #26352873.

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.

11 Article Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin-8 (CXCL8), Myeloid-Related Protein 8/Myeloid-Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease. 2015

Kienhorst, Laura B E / van Lochem, Ellen / Kievit, Wietske / Dalbeth, Nicola / Merriman, Marilyn E / Phipps-Green, Amanda / Loof, Arnoud / van Heerde, Waander / Vermeulen, Sita / Stamp, Lisa K / van Koolwijk, Elly / de Graaf, Jacqueline / Holzinger, Dirk / Roth, Johannes / Janssens, Hein J E M / Merriman, Tony R / Broen, Jasper C A / Janssen, Matthijs / Radstake, Timothy R D J. ·Rijnstate Hospital, Arnhem, The Netherlands. · Radboud University Medical Center, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · University of Otago, Dunedin, New Zealand. · University of Otago, Christchurch, New Zealand. · University Hospital Muenster, Muenster, Germany. · Radboud University Medical Center, Nijmegen, The Netherlands, and Rijnstate Hospital, Arnhem, The Netherlands. · University Medical Center Utrecht, Utrecht, The Netherlands. ·Arthritis Rheumatol · Pubmed #26248007.

ABSTRACT: OBJECTIVE: The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients. METHODS: We studied 330 gout patients from 3 independent cohorts and compared them with 144 healthy individuals and 276 disease controls. We measured circulating levels of interleukin-8 (IL-8)/CXCL8, IL-1β, IL-6, IL-10, IL-12, and tumor necrosis factor, after which we performed proteome-wide analysis in a selection of samples to identify proteins that were possibly prognostic for the development of comorbidities. Replication analysis was performed specifically for myeloid-related protein 8 (MRP-8)/MRP-14 complex. RESULTS: Compared to healthy controls and disease control patients, patients with gouty arthritis (n = 48) had significantly higher mean levels of CXCL8 (P < 0.001), while other cytokines were almost undetectable. Similarly, patients with intercritical gout showed high levels of CXCL8. CXCL8 was independently associated with diabetes mellitus in patients with intercritical gout (P < 0.0001). Proteome-wide analysis in gouty arthritis (n = 18) and intercritical gout (n = 39) revealed MRP-8 and MRP-14 as the proteins with the greatest differential expression between low and high levels of CXCL8 and also showed a positive correlation of MRP8/MRP14 complex with CXCL8 levels (R(2)  = 0.49, P < 0.001). These findings were replicated in an independent cohort. The proteome of gout patients with high levels of CXCL8 was associated with diabetes mellitus (odds ratio 16.5 [95% confidence interval 2.8-96.6]) and CVD (odds ratio 3.9 [95% confidence interval 1.0-15.3]). CONCLUSION: Circulating levels of CXCL8 are increased during both the acute and intercritical phases of gout, and they coincide with a specific circulating proteome that is associated with risk of diabetes mellitus and CVD. Further research focused on the roles of CXCL8 and MRP8/MRP14 complex in patients with gout is warranted.

12 Article The validation of a diagnostic rule for gout without joint fluid analysis: a prospective study. 2015

Kienhorst, Laura B E / Janssens, Hein J E M / Fransen, Jaap / Janssen, Matthijs. ·Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands. lkienhorst@rijnstate.nl. · Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands. Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands. · Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands. ·Rheumatology (Oxford) · Pubmed #25231179.

ABSTRACT: OBJECTIVE: The gold standard for diagnosing gout is the identification of MSU crystals in joint fluid. In secondary care, the facilities or expertise to analyse joint fluid are not always available and gout is diagnosed clinically. To improve the predictive value of the clinical diagnosis of gout in secondary care, a diagnostic rule developed in primary care could be helpful. The aim of this study was to validate this diagnostic rule in a secondary care population with the gold standard as reference test. METHODS: Three hundred and ninety patients with monoarthritis were included. The variables of the diagnostic rule (male sex, previous arthritis attack, onset <1 day, joint redness, involvement of the first MTP joint, hypertension or one or more cardiovascular disease, and serum uric acid >5.88 mg/dl) were collected and scored. The affected joint was aspirated and joint fluid was analysed for the presence of MSU crystals. RESULTS: In 219 patients (56%) MSU crystals were found. The positive predictive value of a score of ≥8 points was 0.87, the negative predictive value of a score of ≤4 points was 0.95. The area under the receiver operating characteristic curve for the diagnostic rule was 0.86 (95% CI 0.82, 0.89). The Hosmer-Lemeshow goodness-of-fit test showed that the difference between the expected and the observed probability was non-significant (P = 0.64), indicating good agreement. CONCLUSION: An easy-to-use diagnostic rule for gout developed in primary care shows good performance in secondary care and improves the predictive value of the clinical diagnosis of gout when joint fluid analysis is not available.

13 Article Arthritis of the first metatarsophalangeal joint is not always gout: a prospective cohort study in primary care patients. 2014

Kienhorst, Laura B E / Janssens, Hein J E M / Fransen, Jaap / van de Lisdonk, Eloy H / Janssen, Matthijs. ·Department of Rheumatology, Rijnstate Hospital, Arnhem, PO Box 8, 6880 AA, Velp, The Netherlands. Electronic address: lkienhorst@rijnstate.nl. · Department of Primary and Community Care, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands; Department of Clinical Research, Rijnstate Hospital, Arnhem, PO Box 8, 6880 AA, Velp, The Netherlands. · Department of Rheumatology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. · Department of Primary and Community Care, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. · Department of Rheumatology, Rijnstate Hospital, Arnhem, PO Box 8, 6880 AA, Velp, The Netherlands. ·Joint Bone Spine · Pubmed #24468668.

ABSTRACT: OBJECTIVES: Arthritis of the first metatarsophalangeal joint has been considered pathognomonic for gout, but it is unknown how frequently other forms of arthritis occur in this joint. The aims were to determine the validity of the general practitioner's clinical diagnosis using joint fluid analysis as the reference test, the prevalence of other diagnoses than gout, and the signs and symptoms that discriminate between gout and non-gout patients. METHODS: This prospective cohort study comprised primary care patients with monoarthritis of the first metatarsophalangeal joint. After patient recruitment by general practitioners, patients' characteristics were collected by a rheumatologist. Joint fluid was analyzed for the presence of monosodium urate-crystals. If crystals were absent, patients entered a follow-up period of 6 years, or until a definite diagnosis. If during follow-up crystals were identified, the patient was classified as already having gout at baseline assessment. RESULTS: One hundred and fifty-nine primary care patients were included. At baseline the clinical diagnosis was gout in 98%. The positive and negative predictive values of the diagnosis of gout were 0.79 and 0.75, respectively. After follow-up 77% had gout, 8% had another rheumatic disease, and 15% had a transient unspecified monoarthritis. Gout patients had discriminating signs and symptoms from non-gout patients. CONCLUSIONS: Gout is an important but certainly not an exclusive cause of arthritis of the first metatarsophalangeal joint.

14 Article A delphi exercise to identify characteristic features of gout - opinions from patients and physicians, the first stage in developing new classification criteria. 2013

Prowse, Rebecca L / Dalbeth, Nicola / Kavanaugh, Arthur / Adebajo, Adewale O / Gaffo, Angelo L / Terkeltaub, Robert / Mandell, Brian F / Suryana, Bagus P P / Goldenstein-Schainberg, Claudia / Diaz-Torne, Cèsar / Khanna, Dinesh / Lioté, Frederic / Mccarthy, Geraldine / Kerr, Gail S / Yamanaka, Hisashi / Janssens, Hein / Baraf, Herbert F / Chen, Jiunn-Horng / Vazquez-Mellado, Janitzia / Harrold, Leslie R / Stamp, Lisa K / Van De Laar, Mart A / Janssen, Matthijs / Doherty, Michael / Boers, Maarten / Edwards, N Lawrence / Gow, Peter / Chapman, Peter / Khanna, Puja / Helliwell, Philip S / Grainger, Rebecca / Schumacher, H Ralph / Neogi, Tuhina / Jansen, Tim L / Louthrenoo, Worawit / Sivera, Francisca / Taylor, William J / Alten, Rieke. ·University of Otago, Dunedin, New Zealand. ·J Rheumatol · Pubmed #23418379.

ABSTRACT: OBJECTIVE: To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout. METHODS: Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index. RESULTS: Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory. CONCLUSION: Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms.

15 Article A case-control study of determinants for the occurrence of gouty arthritis in heart failure patients. 2012

Hueskes, Berdine A A / Willems, Frank F / Leen, Aukelien C / Ninaber, Patricia A / Westra, Richard / Mantel-Teeuwisse, Aukje K / Janssens, Hein J E M / van de Lisdonk, Eloy H / Roovers, Elisabeth A / Janssen, Matthijs. ·Department of Rheumatology, Rijnstate, 6883 AZ Velp, The Netherlands. ·Eur J Heart Fail · Pubmed #22723658.

ABSTRACT: AIMS: Gouty arthritis is a frequent and disabling complication in heart failure patients. This study aimed to investigate which factors are associated with the occurrence of gouty arthritis in these patients. METHODS AND RESULTS: A case-control study was performed in heart failure patients (February 2007 to October 2009). Cases were defined as patients with gouty arthritis. Factors that are possibly associated with gouty arthritis and/or heart failure were evaluated. Echocardiographic dimensions and laboratory values including glomerular filtration rate (GFR) and fractional excretion of uric acid (FEUA) were measured. Logistic regression analysis was used to determine crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for possibly associated factors. In total, 188 patients (59 with gouty arthritis) were included. Spironolactone use was associated with a decreased occurrence of gouty arthritis (OR 0.32, 95% CI 0.13-0.77). Independently associated with an increased occurrence of gouty arthritis were hypertensive heart failure (OR 3.6, 95% CI 1.6-8.2), New York Heart Association (NYHA) class III/IV (OR 4.5, 95% CI 1.8-11.0), lower GFR (P < 0.001), and FEUA <4% (OR 3.3, 95% CI 1.4-7.9). Among the four age/gender groups, the strongest association with gouty arthritis was found in men <65 years. CONCLUSION: Our identification of factors that are associated with the occurrence of gouty arthritis makes it possible to develop strategies to improve further the quality of life in heart failure patients. The possible decreased occurrence of gouty arthritis in spironolactone users has to be confirmed in prospective studies.

16 Article A diagnostic rule for acute gouty arthritis in primary care without joint fluid analysis. 2010

Janssens, Hein J E M / Fransen, Jaap / van de Lisdonk, Eloy H / van Riel, Piet L C M / van Weel, Chris / Janssen, Matthijs. ·Department of Primary and Community Care, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, the Netherlands. h.janssens@elg.umcn.nl ·Arch Intern Med · Pubmed #20625017.

ABSTRACT: BACKGROUND: Most cases of acute gouty arthritis are diagnosed in primary care and without joint fluid analysis in many instances. Our objectives were to estimate the validity of this diagnosis by family physicians and to develop a diagnostic rule. METHODS: Patients with monoarthritis recruited in an open Dutch population with gout by family physician diagnosis were enrolled in a diagnostic study (March 24, 2004, through July 14, 2007). Validity variables were estimated using 2 x 2 tables, with the presence of synovial monosodium urate crystals as the reference test. For development of the diagnostic rule, clinical variables (including the presence of synovial monosodium urate crystals) were collected within 24 hours. Statistically significant variables and predefined variables were separately entered in multivariate logistic regression models to predict the presence of synovial monosodium urate crystals. Diagnostic performance of the models was tested by receiver operating characteristic curve analysis. The most appropriate model was transformed to a clinically useful diagnostic rule. RESULTS: Three hundred twenty-eight patients were included in the study. The positive and negative predictive values of family physician diagnosis of gout were 0.64 and 0.87, respectively. The most appropriate model contained the following predefined variables: male sex, previous patient-reported arthritis attack, onset within 1 day, joint redness, first metatarsophalangeal joint (MTP1) involvement, hypertension or 1 or more cardiovascular diseases, and serum uric acid level exceeding 5.88 mg/dL (to convert serum uric acid level to micromoles per liter, multiply by 59.485). The area under the receiver operating characteristic curve for this model was 0.85 (95% confidence interval, 0.81-0.90). Performance did not change after transforming the regression coefficients to easy-to-use scores and was almost equal to that of the statistically optimal model (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.83-0.91). CONCLUSIONS: The validity of family physician diagnosis of acute gouty arthritis was moderate in this study. An easy-to-use diagnostic rule without joint fluid analysis was developed for their use.

17 Article Limited validity of the American College of Rheumatology criteria for classifying patients with gout in primary care. 2010

Janssens, Hein J E M / Janssen, Mathijs / van de Lisdonk, Eloy H / Fransen, Jaap / van Riel, Piet L C M / van Weel, Chris. · ·Ann Rheum Dis · Pubmed #19910298.

ABSTRACT: -- No abstract --

18 Article Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. 2008

Janssens, Hein J E M / Janssen, Matthijs / van de Lisdonk, Eloy H / van Riel, Piet L C M / van Weel, Chris. ·Department of General Practice, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. h.janssens@hag.umcn.nl ·Lancet · Pubmed #18514729.

ABSTRACT: BACKGROUND: Non-steroidal anti-inflammatory drugs and colchicine used to treat gout arthritis have gastrointestinal, renal, and cardiovascular adverse effects. Systemic corticosteroids might be a beneficial alternative. We investigated equivalence of naproxen and prednisolone in primary care. METHODS: We did a randomised clinical trial to test equivalence of prednisolone and naproxen for the treatment of monoarticular gout. Primary-care patients with gout confirmed by presence of monosodium urate crystals were eligible. 120 patients were randomly assigned with computer-generated randomisation to receive either prednisolone (35 mg once a day; n=60) or naproxen (500 mg twice a day; n=60), for 5 days. Treatment was masked for both patients and physicians. The primary outcome was pain measured on a 100 mm visual analogue scale and the a priori margin for equivalence set at 10%. Analyses were done per protocol and by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN14648181. FINDINGS: Data were incomplete for one patient in each treatment group, so per-protocol analyses included 59 patients in each group. After 90 h the reduction in the pain score was 44.7 mm and 46.0 mm for prednisolone and naproxen, respectively (difference 1.3 mm; 95% CI -9.8 to 7.1), suggesting equivalence. The difference in the size of change in pain was 1.57 mm (95% CI -8.65 to 11.78). Adverse effects were similar between groups, minor, and resolved by 3 week follow-up. INTERPRETATION: Oral prednisolone and naproxen are equally effective in the initial treatment of gout arthritis over 4 days.

19 Minor The detection of monosodium urate crystals in synovial fluid after long-term and varying storage conditions. 2015

Kienhorst, Laura B E / Janssens, Hein J E M / Eijgelaar, Roelant S / Radstake, Tim R D J / van Riel, Piet L C M / Janssen, Matthijs. ·Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 TA, Arnhem, The Netherlands. Electronic address: lkienhorst@rijnstate.nl. · Department of Primary and Community Care, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands; Department of Clinical Research, Rijnstate Hospital, PO Box 9555, 6800 TA, Arnhem, The Netherlands. · University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. · Scientific Institute for Quality of Healthcare, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. · Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 TA, Arnhem, The Netherlands. ·Joint Bone Spine · Pubmed #25921802.

ABSTRACT: -- No abstract --

20 Minor Comment on: The validation of a diagnostic rule for gout without joint fluid analysis: a prospective study: reply. 2015

Kienhorst, Laura B E / Janssens, Hein J E M / Fransen, Jaap / Janssen, Matthijs. ·Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands lkienhorst@rijnstate.nl. · Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands lkienhorst@rijnstate.nl. · Department of Rheumatology, Rijnstate Hospital, Arnhem, Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Department of Clinical Research, Rijnstate Hospital, Arnhem and Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands. ·Rheumatology (Oxford) · Pubmed #25796559.

ABSTRACT: -- No abstract --