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Gout: HELP
Articles by Tim L. Th A. Jansen
Based on 39 articles published since 2008
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Between 2008 and 2019, T. Jansen wrote the following 39 articles about Gout.
 
+ Citations + Abstracts
Pages: 1 · 2
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 Editorial The American College of Physicians and the 2017 guideline for the management of acute and recurrent gout: treat to avoiding symptoms versus treat to target. 2017

Jansen, Tim L / Janssen, Matthijs. ·Department of Rheumatology, VieCuri Medical Center, Venlo, The Netherlands. tjansen@VieCuri.nl. · Department of Rheumatology, VieCuri Medical Center, Venlo, The Netherlands. ·Clin Rheumatol · Pubmed #28920180.

ABSTRACT: -- No abstract --

3 Editorial Treat to target in gout by combining two modes of action. 2014

Jansen, Tim L. ·Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands tim.jansen@radboudumc.nl. ·Rheumatology (Oxford) · Pubmed #24758888.

ABSTRACT: -- No abstract --

4 Editorial Rheumatology meets radiology in the hot soup of Gutta. 2012

Jansen, Tim L. · ·Arthritis Res Ther · Pubmed #23256732.

ABSTRACT: If left untreated, gout may result in radiographic abnormalities, that is, cartilage loss and periarticular osteopenia plus more-or-less gout-specific radiographic abnormalities: spurs, sclerosis, and periostal new bone formation. In the current issue, Dalbeth and colleagues describe findings from about 800 joints in 20 mostly tophaceous patients, which can help clinicians to identify osteopathologic gout: spurs, osteosclerosis, ankylosis and periostal new bone formation, all symptoms of advanced, untreated gout. These are hallmarks of chronic untreated gout and are to be prevented.

5 Review Rational pharmacotherapy (RPT) in goutology: Define the serum uric acid target & treat-to-target patient cohort and review on urate lowering therapy (ULT) applying synthetic drugs. 2015

Jansen, Tim L. ·RadboudUMC, Rheumatology, Nijmegen, The Netherlands. Electronic address: t.jansen@radboudumc.nl. ·Joint Bone Spine · Pubmed #26113027.

ABSTRACT: A gout revolution is at hand as can be seen from the number of publications and our recent increase in a better understanding of gout regarding imaging, regarding pathogenetic involvement of crystals, cells and cytokines, as well as regarding new pharmacotherapeutic options. We should now focus on rational pharmacotherapy to significantly improve gout care. With modern combinations of xanthine oxidase inhibition PLUS uricosuric all serum urate concentrations can be targeted. The pharmacotherapeutic literature of synthetic urate lowering treatment is reviewed and a plea is given for rational pharmacotherapy combining different modes of action aiming at the rheumatologically predefined optimal serum urate concentrations instead of a more reluctant approach to just lower a serum urate to any lower level with a fixed dose allopurinol.

6 Review Imaging modalities for the classification of gout: systematic literature review and meta-analysis. 2015

Ogdie, Alexis / Taylor, William J / Weatherall, Mark / Fransen, Jaap / Jansen, Tim L / Neogi, Tuhina / Schumacher, H Ralph / Dalbeth, Nicola. ·Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Medicine, University of Otago, Wellington, New Zealand. · Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. · Sections of Epidemiology and Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA. · Department of Medicine, University of Auckland, Auckland, New Zealand. ·Ann Rheum Dis · Pubmed #24915980.

ABSTRACT: 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.

7 Review Improving cardiovascular and renal outcomes in gout: what should we target? 2014

Richette, Pascal / Perez-Ruiz, Fernando / Doherty, Michael / Jansen, Tim L / Nuki, George / Pascual, Eliseo / Punzi, Leonardo / So, Alexander K / Bardin, Thomas. ·Hôpital Lariboisière, Fédération de Rhumatologie, Centre Viggo Petersen 2, rue Ambroise Parè 75475 Cedex 10, Paris, France. · Servicio de Reumatología and BioCruces Health Research Institute, Cruces University Hospital, Plaza Cruces S/N, 48903 Barakaldo, Spain. · Division of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital Nottingham, Hucknall Road, Nottingham NG5 1PB, UK. · Department of Rheumatology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, Netherlands. · Department of Rheumatology, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK. · Department of Medicine, Rheumatology Section, Alicante University and General Hospital, University Miguel Hernández, Av. Pintor Baeza 12, Alicante 03010, Spain. · Department of Rheumatology, Rheumatology Unit, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. · Service of Rheumatology, Centre Hospitalier Universitaire Vaudois, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland. ·Nat Rev Rheumatol · Pubmed #25136785.

ABSTRACT: Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.

8 Review New classification criteria for gout: a framework for progress. 2013

Dalbeth, Nicola / Fransen, Jaap / Jansen, Tim L / Neogi, Tuhina / Schumacher, H Ralph / Taylor, William J. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz. ·Rheumatology (Oxford) · Pubmed #23611919.

ABSTRACT: The definitive classification or diagnosis of gout normally relies upon the identification of MSU crystals in SF or from tophi. Where microscopic examination of SF is not available or is impractical, the best approach may differ depending upon the context. For many types of research, clinical classification criteria are necessary. The increasing prevalence of gout, advances in therapeutics and the development of international research collaborations to understand the impact, mechanisms and optimal treatment of this condition emphasize the need for accurate and uniform classification criteria for gout. Five clinical classification criteria for gout currently exist. However, none of the currently available criteria has been adequately validated. An international project is currently under way to develop new validated gout classification criteria. These criteria will be an essential step forward to advance the research agenda in the modern era of gout management.

9 Review Gout: why is this curable disease so seldom cured? 2012

Doherty, Michael / Jansen, Tim L / Nuki, George / Pascual, Eliseo / Perez-Ruiz, Fernando / Punzi, Leonardo / So, Alexander K / Bardin, Thomas. ·Department of Rheumatology, City Hospital, Nottingham, UK. Michael.Doherty@nottingham.ac.uk ·Ann Rheum Dis · Pubmed #22863577.

ABSTRACT: Gout is the most common inflammatory arthritis and one in which pathogenesis and risk factors are best understood. One of the treatment objectives in current guidelines is 'cure'. However, audits show that only a minority of patients with gout receive adequate advice and treatment. Suboptimal care and outcomes reflect inappropriately negative perceptions of the disease, both in patients and providers. Historically, gout has been portrayed as a benign and even comical condition that is self-inflicted through overeating and alcohol excess. Doctors often focus on managing acute attacks rather than viewing gout as a chronic progressive crystal deposition disease. Urate-lowering treatment is underprescribed and often underdosed. Appropriate education of patients and doctors, catalysed by recent introduction of new urate-lowering treatments after many years with no drug development in the field, may help to overcome these barriers and improve management of this easily diagnosed and curable form of potentially severe arthritis.

10 Review Therapeutic consequences of crystals in the synovial fluid: a review for clinicians. 2011

Jansen, Tim L / Rasker, Johannes J. ·Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. t.jansen@reuma.umcn.nl ·Clin Exp Rheumatol · Pubmed #22133072.

ABSTRACT: Many crystals may be found in arthritic joints. Rheumatologists are able to diagnose, with a high degree of probability, which crystals induce arthritis in the individual case. A definite diagnosis supported by polarisation microscopy may provide a firm basis for adequate long-term treatment. Recently new insights in the inflammatory processes induced the development of targeted therapies. We review novel developments in crystal-induced arthritis and gout in particular.

11 Review International position paper on febuxostat. 2010

Jansen, Tim L / Richette, Pascal / Perez-Ruiz, Fernando / Tausche, Anne-Kathrin / Guerne, Philip-André / Punzi, Leonardo / Leeb, Burkhard / Barskova, Victoria / Uhlig, Till / Pimentão, José / Zimmermann-Górska, Irena / Pascual, Elisio / Bardin, Thomas / Doherty, Michael. ·Department of Rheumatology, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands. t.jansen@znb.nl ·Clin Rheumatol · Pubmed #20401506.

ABSTRACT: This position paper aims to clarify the presumed place of febuxostat in the management of gout patients. Since this novel xanthine oxidase inhibitor is now available, an international group of gout experts decided to formulate an international consensus statement. This statement presents the place for this new xanthine oxidase inhibitor in the treatment of gout which may contribute to optimize treatment of gout patients in Europe and worldwide.

12 Review Management of hyperuricemia in gout: focus on febuxostat. 2010

Reinders, Mattheus K / Jansen, Tim L Th A. ·Clinical Pharmacy, Atrium Medisch Centrum Parkstad, Heerlen, The Netherlands. m.reinders@atriummc.nl ·Clin Interv Aging · Pubmed #20169038.

ABSTRACT: Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than "standard dosage" allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol.

13 Review Gout--current diagnosis and treatment. 2009

Tausche, Anne-Kathrin / Jansen, Tim L / Schröder, Hans-Egbert / Bornstein, Stefan R / Aringer, Martin / Müller-Ladner, Ulf. ·Bereich Rheumatologie, Medizinische Klinik und Poliklinik III, Universitätsklinikum, Carl Gustav Carus an der TU Dresden, Dresden, Germany. anne-kathrin.tausche@uniklinikum-dresden.de ·Dtsch Arztebl Int · Pubmed #19795010.

ABSTRACT: BACKGROUND: Because of the changing dietary habits of an aging population, hyperuricemia is frequently found in combination with other metabolic disorders. Longstanding elevation of the serum uric acid level can lead to the deposition of monosodium urate crystals, causing gout (arthritis, urate nephropathy, tophi). In Germany, the prevalence of gouty arthritis is estimated at 1.4%, higher than that of rheumatoid arthritis. There are no German guidelines to date for the treatment of gout. Its current treatment is based largely on expert opinion. METHODS: Selective literature review on the diagnosis and treatment of gout. RESULTS AND CONCLUSIONS: Asymptomatic hyperuricemia is generally not an indication for pharmacological intervention to lower the uric acid level. When gout is clinically manifest, however, acute treatment of gouty arthritis should be followed by determination of the cause of hyperuricemia, and long-term treatment to lower the uric acid level is usually necessary. The goal of treatment is to diminish the body's stores of uric acid crystal deposits (the intrinsic uric acid pool) and thereby to prevent the inflammatory processes that they cause, which lead to structural alterations. In the long term, serum uric acid levels should be kept below 360 micromol/L (6 mg/dL). The available medications for this purpose are allopurinol and various uricosuric agents, e.g., benzbromarone. There is good evidence to support the treatment of gouty attacks by the timely, short-term use of non-steroidal anti-inflammatory drugs (NSAID), colchicine, and glucocorticosteroids.

14 Article A systematic literature review of patient-reported outcome measures used in gout: an evaluation of their content and measurement properties. 2019

Janssen, Carly A / Oude Voshaar, Martijn A H / Ten Klooster, Peter M / Jansen, Tim L Th A / Vonkeman, Harald E / van de Laar, Mart A F J. ·Department of Psychology, Health and Technology, University of Twente, PO BOX 217, 7500 AE, Enschede, the Netherlands. C.A.Janssen@utwente.nl. · Department of Psychology, Health and Technology, University of Twente, PO BOX 217, 7500 AE, Enschede, the Netherlands. · Department of Rheumatology, VieCuri Medical Center, Venlo, The Netherlands. · Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente, Enschede, The Netherlands. ·Health Qual Life Outcomes · Pubmed #30975212.

ABSTRACT: BACKGROUND: Gout is a common, monosodium urate crystal-driven inflammatory arthritis. Besides its clinical manifestations, patients often also suffer from pain, physical impairment, emotional distress and work productivity loss, as a result of the disease. Patient-reported outcome measures (PROMs) are commonly used to assess these consequences of the disease. However, current instrument endorsements for measuring such outcomes in acute and chronic gout clinical settings are based on limited psychometric evidence. The objective of this systematic literature review was to identify currently available PROMs for gout, and to critically evaluate their content and psychometric properties, in order to evaluate the current status regarding PROMs for use in gout patients. METHODS: Systematic literature searches were performed in the PubMed and EMBASE databases. The methodological quality of included papers was appraised using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist, and evaluation of measurement properties (reliability, responsiveness, construct validity, floor and ceiling effects) was done in accordance with published quality criteria. Item content was appraised by linking health concepts to the International Classification of Functioning Disability and Health (ICF) framework. RESULTS: In total, 13 PROMs were identified, of which three were targeted specifically at gout patients. The majority of the PROMs were rated positively for content validity. For most instruments, limited evidence was available for construct validity and reliability. Instruments to assess pain scored well on responsiveness and floor and ceiling effects, but not much is known about their reliability in gout. CONCLUSIONS: The physical functioning subscale of the SF-36v2 (Short Form-36 item version 2) is the only PROM that had sufficient supporting evidence for all its psychometric properties. Many of the commonly used PROMs in gout are currently not yet well supported and more studies on their measurement properties are needed among both acute and chronic gout populations.

15 Article Quality of care in gout: a clinical audit on treating to the target with urate lowering therapy in real-world gout patients. 2017

Janssen, Carly A / Jansen, Tim L Th A / Oude Voshaar, Martijn A H / Vonkeman, Harald E / van de Laar, Mart A F J. ·Department of Psychology, Health and Technology, Arthritis Center Twente, University of Twente, PO BOX 217, 7500 AE, Enschede, The Netherlands. C.A.Janssen@utwente.nl. · Department of Rheumatology, Viecuri Medical Center, Venlo, The Netherlands. · Department of Psychology, Health and Technology, Arthritis Center Twente, University of Twente, PO BOX 217, 7500 AE, Enschede, The Netherlands. · Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente, Enschede, The Netherlands. ·Rheumatol Int · Pubmed #28748426.

ABSTRACT: The current paper aimed to describe the quality of care for gout patients by showing the clinical outcomes achieved in two patient cohorts in which differing targeted urate lowering therapy (ULT) treatment approaches were employed, both aiming to reach the European League Against Rheumatism recommended serum urate (sUA) targets. A retrospective medical chart review study was conducted. Data from the medical records of gout patients from two clinical centers in The Netherlands, both applying targeted ULT treatments (albeit using different approaches), were reviewed. Patients in cohort A were given a combination of xanthine oxidase inhibitors with uricosurics if treatment with allopurinol monotherapy failed to reach sUA target levels, whereas patients in cohort B were treated with sequential monotherapy. Data on patient characteristics and clinical outcomes were collected. A total of 177 patient dossiers were included: 99 from cohort A and 78 from cohort B. The great majority (n = 146, 82.5%) of the patients in both cohorts had a current sUA level <360 µmol/L. In addition, more than half (n = 104, 58.8%) of the patients met the stringent sUA target level of <300 µmol/L. The largest reductions in mean sUA levels were observed for patients who were treated with combination therapy. This clinical audit of two cohorts of gout patients provides initial-yet promising-results regarding the proportion of real-world gout patients in whom recommended that sUA target levels can be achieved, and demonstrates the added value that a targeted treatment approach may have in reaching these goals.

16 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.

17 Article Crystal identification of synovial fluid aspiration by polarized light microscopy. An online test suggesting that our traditional rheumatologic competence needs renewed attention and training. 2017

Berendsen, D / Neogi, T / Taylor, W J / Dalbeth, N / Jansen, T L. ·Department of Rheumatology, Ziekenhuisgroep Twente, Almelo, The Netherlands. d.berendsen@zgt.nl. · Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, USA. · Department of Medicine, University of Otago, POB 7343, Wellington, Wellington, 6039, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Rheumatology, VieCuri MC, Venlo, The Netherlands. · Scientific IQ Healthcare RadboudUMC, Nijmegen, The Netherlands. ·Clin Rheumatol · Pubmed #27837341.

ABSTRACT: Testing a reading exercise for identification of several typical crystal such as the negatively birefringent needle-shaped crystals that are under polarized light microscopy is the gold standard for diagnosing gout. The objective of this study was to assess current performance of crystal identification by professionals involved in examining synovial fluid in routine care. Rheumatologists, trainees, lab technicians, and other physicians with an interest in crystal arthritis completed an online test. The test consisted of 30 images: 8 monosodium urate (MSU) crystals, 5 calcium pyrophosphate (CPP), 4 cholesterol, 2 depot methylprednisolone, 2 calcium oxalate, 2 rice bodies, 1 hydroxyapatite, 1 liquid lipid, 1 fibrin, 1 Charcot-Leyden, and 5 different artifacts. Of the 22 non-MSU slides, a subset of 8 was pre-designated that were thought to be clinically important to be identified as non-MSU. The primary outcome was defined as the correct identification of all eight MSU slides plus the identification of all eight pre-defined non-MSU slides as non-MSU. The online test was completed by 110 participants. The primary outcome was achieved by 39%. Correct identification of all MSU images was achieved by 81%, correct identification of all 8 pre-defined non-MSU, CPP images, and all 22 non-MSU images as non-MSU by 68, 68, and 23%, respectively. MSU crystals were well identified, but incorrect identification of non-MSU crystals occurred frequently. This study suggests that there is room for improvement regarding crystal identification of particularly CPP and other non-MSU crystals even in this highly motivated group.

18 Article Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison With Monosodium Urate Monohydrate Crystal Analysis as the Gold Standard. 2017

Ogdie, Alexis / Taylor, William J / Neogi, Tuhina / Fransen, Jaap / Jansen, Tim L / Schumacher, H Ralph / Louthrenoo, Worawit / Vazquez-Mellado, Janitzia / Eliseev, Maxim / McCarthy, Geraldine / Stamp, Lisa K / Perez-Ruiz, Fernando / Sivera, Francisca / Ea, Hang-Korng / Gerritsen, Martijn / Cagnotto, Giovanni / Cavagna, Lorenzo / Lin, Chingtsai / Chou, Yin-Yi / Tausche, Anne-Kathrin / Lima Gomes Ochtrop, Manuella / Janssen, Matthijs / Chen, Jiunn-Horng / Slot, Ole / Lazovskis, Juris / White, Douglas / Cimmino, Marco A / Uhlig, Till / Dalbeth, Nicola. ·University of Pennsylvania, Philadelphia. · University of Otago, Wellington, New Zealand. · Boston University School of Medicine, Boston, Massachusetts. · VieCuri Medical Centre, Venlo, The Netherlands, and Scientific IQ HealthCare, Radboud University Medical Center, Nijmegen, The Netherlands. · Chiang Mai University, Chiang Mai, Thailand. · Hospital General de México, Mexico City, Mexico. · Nasonova Research Institute of Rheumatology of Russia, Moscow, Russia. · University College Dublin and Mater Misericordiae University Hospital, Dublin, Ireland. · University of Otago Christchurch, Christchurch, New Zealand. · Hospital Universitario Cruces, BioCruces Health Research Institute, and Basque Country University, Barakaldo, Spain. · Hospital General Universitario de Elda, Alicante, Spain. · Université Paris Diderot, INSERM UMR 1132 and Service de Rhumatologie, Hôpital Lariboisière, AP-HP, Paris, France. · Westfries Gasthuis, Hoorn, The Netherlands. · University of Pavia and IRCCS Policlinico San Matteo Foundation, Pavia, Italy, and Skane University Hospital Malmö/Lund, Lund, Sweden. · University of Pavia and IRCCS Policlinico San Matteo Foundation, Pavia, Italy. · Taichung Veterans' General Hospital, Taichung, Taiwan, Republic of China. · University Hospital Carl Gustav Carus, Dresden, Germany. · Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Rijnstate Hospital, Arnhem, The Netherlands. · China Medical University Hospital, Taichung, Taiwan, Republic of China. · Copenhagen University Hospital Glostrup, Glostrup, Denmark. · Riverside Professional Centre, Sydney, Nova Scotia, Canada. · Waikato District Health Board and Waikato Clinical School, Hamilton, New Zealand. · University of Genoa, Genoa, Italy. · Diakonhjemmet Hospital, Oslo, Norway. · University of Auckland, Auckland, New Zealand. ·Arthritis Rheumatol · Pubmed #27748084.

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.

19 Article Discrepancies in how the impact of gout is assessed in outcomes research compared to how health professionals view the impact of gout, using the lens of the International Classification of Functioning, Health and Disability (ICF). 2016

Kool, Eveline M / Nijsten, Marieke J / van Ede, Annelies E / Jansen, Tim L / Taylor, William J. ·Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. · VieCuri Medical Center Noord-Limburg, Venlo, The Netherlands and Scientific Institute for Quality of Healthcare (IQ Healthcare), Nijmegen, The Netherlands. · Department of Medicine, University of Otago Wellington, PO Box 7343, Wellington, New Zealand. will.taylor@otago.ac.nz. ·Clin Rheumatol · Pubmed #27300705.

ABSTRACT: The International Classification of Functioning, Disability and Health (ICF) provides a common language to understand what health means. An ICF core set, a list of ICF categories affected by a certain disease, is useful to objectify the content validity of a health status measurement. This study aims to identify the potential items of a gout specific 'ICF core set'. A three-round Delphi exercise was conducted, using web-based questionnaires. Health professionals, specialized in gout, nominated and subsequently rated the relevance of life areas divided into ICF categories. Agreement was determined by using the UCLA/RAND criteria. Simultaneously, a systematic review of gout measure outcomes was conducted. The results of these studies were compared using the second level of the ICF categories. In the Delphi study, consensus was found for 136 relevant ICF categories. The literature study extracted 134 different ICF categories in 149 articles. Three hundred and ten were non-defined outcomes. A large number of ICF categories were deemed to be relevant for people with gout. Only 29.7 % (19/64) of the level 2 categories, deemed to be relevant by health professionals, had been assessed as relevant in at least 5 % of gout outcome studies. Conversely, 70 % (19/27) of level 2 ICF categories assessed in at least 5 % of outcome studies were deemed relevant by health professionals. These ICF codes, which are found relevant in both studies, should be considered as mandatory in further research to a validated and practical core set of ICF categories. Published gout outcomes research fails to evaluate many life areas that are thought relevant by health professionals.

20 Article Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout. 2016

Rasheed, Humaira / Phipps-Green, Amanda J / Topless, Ruth / Smith, Malcolm D / Hill, Catherine / Lester, Susan / Rischmueller, Maureen / Janssen, Matthijs / Jansen, Timothy L / Joosten, Leo A / Radstake, Timothy R / Riches, Philip L / Tausche, Anne-Kathrin / Lioté, Frederic / So, Alexander / van Rij, Andre / Jones, Gregory T / McCormick, Sally P / Harrison, Andrew A / Stamp, Lisa K / Dalbeth, Nicola / Merriman, Tony R. ·Department of Biochemistry, University of Otago, Dunedin, New Zealand Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide. · Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA, Australia. · Department of Rheumatology, Rijnstate Hospital, Arnhem. · Department of IQ HealthCare, VieCuri Medical Centre, Venlo. · Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. · Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Department of Rheumatology, University Clinic Carl-Gustav-Carus, Dresden, Germany. · INSERM, UMR-S 1132, Hospital Lariboisière University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, F-75205, France. · DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé 05-5029, Lausanne, Switzerland. · Department of Surgery, University of Otago, Dunedin. · Department of Medicine, University of Otago, Wellington. · Department of Medicine, University of Otago, Christchurch. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Biochemistry, University of Otago, Dunedin, New Zealand tony.merriman@otago.ac.nz. ·Rheumatology (Oxford) · Pubmed #27094595.

ABSTRACT: OBJECTIVE: Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. METHODS: We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). RESULTS: In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). CONCLUSION: Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.

21 Article Survey Definitions of Gout for Epidemiologic Studies: Comparison With Crystal Identification as the Gold Standard. 2016

Dalbeth, Nicola / Schumacher, H Ralph / Fransen, Jaap / Neogi, Tuhina / Jansen, Tim L / Brown, Melanie / Louthrenoo, Worawit / Vazquez-Mellado, Janitzia / Eliseev, Maxim / McCarthy, Geraldine / Stamp, Lisa K / Perez-Ruiz, Fernando / Sivera, Francisca / Ea, Hang-Korng / Gerritsen, Martijn / Scire, Carlo A / Cavagna, Lorenzo / Lin, Chingtsai / Chou, Yin-Yi / Tausche, Anne-Kathrin / da Rocha Castelar-Pinheiro, Geraldo / Janssen, Matthijs / Chen, Jiunn-Horng / Cimmino, Marco A / Uhlig, Till / Taylor, William J. ·University of Auckland, Auckland, New Zealand. · University of Pennsylvania, Philadelphia. · Radboud University Medical Centre, Nijmegen, The Netherlands. · Boston University School of Medicine, Boston, Massachusetts. · Viecuri Medical Center, Venlo, The Netherlands. · University of Otago, Wellington, New Zealand. · Chiang Mai University, Chiang Mai, Thailand. · Hospital General de Mexico, Mexico City, Mexico. · Nasonova Research Institute of Rheumatology of Russia, Moscow, Russia. · Geraldine McCarthy, MD, FRCPI, University College Dublin School of Medicine and Medical Science, Dublin, Ireland. · University of Otago, Christchurch, New Zealand. · Hospital Universitario Cruces & BioCruces Health Research Institute, Vizcaya, Spain. · Hospital General Universitario de Elda, Alicante, Spain. · Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, INSERM, UMR 1132, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, and Hôpital Lariboisière, Paris, France. · Westfries Gasthuis, Hoorn, The Netherlands. · Carlo A. Scire, MD, PhD, Italian Society for Rheumatology, Milan, Italy. · University and IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. · Taichung Veterans General Hospital, Taichung, Taiwan. · University Hospital Carl Gustav Carus, Dresden, Germany. · Universidade de Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Rijnstate Hospital, Arnhem, The Netherlands. · China Medical University School of Medicine, Taichung, Taiwan. · University of Genoa, Genoa, Italy. · Diakonhjemmet Hospital, Oslo, Norway. ·Arthritis Care Res (Hoboken) · Pubmed #27014846.

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.

22 Article What Should Be the Cut Point for Classification Criteria of Studies in Gout? A Conjoint Analysis. 2016

Fransen, Jaap / Kievit, Wietske / Neogi, Tuhina / Schumacher, Ralph / Jansen, Tim / Dalbeth, Nicola / Taylor, William J. ·Radboud University Medical Centre, Nijmegen, The Netherlands. Jaap.Fransen@Radboudumc.nl. · Radboud University Medical Centre, Nijmegen, The Netherlands. · Boston University Schools of Medicine and of Public Health, Boston, Massachusetts. · University of Pennsylvania and VA Medical Center, Philadelphia, Pennsylvania. · Vie Curi Medical Centre Venlo, Venlo, and Radboud University Medical Centre, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · University of Otago, Wellington, New Zealand. ·Arthritis Care Res (Hoboken) · Pubmed #26945554.

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.

23 Article The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets. 2016

Rasheed, Humaira / McKinney, Cushla / Stamp, Lisa K / Dalbeth, Nicola / Topless, Ruth K / Day, Richard / Kannangara, Diluk / Williams, Kenneth / Smith, Malcolm / Janssen, Matthijs / Jansen, Tim L / Joosten, Leo A / Radstake, Timothy R / Riches, Philip L / Tausche, Anne-Kathrin / Lioté, Frederic / Lu, Leo / Stahl, Eli A / Choi, Hyon K / So, Alexander / Merriman, Tony R. ·Department of Biochemistry, University of Otago, Dunedin, New Zealand. · University of Engineering and Technology, Lahore, Pakistan. · Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. · School of Medical Sciences, University of New South Wales, Sydney, Australia. · Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. · Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide, Australia. · Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands. · Department of IQ HealthCare, VieCuri Medical Centre, Venlo, The Netherlands. · Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. · Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. · Department of Rheumatology, University Clinic "Carl-Gustav-Carus", Dresden, Germany. · INSERM, UMR-S 1132, Hospital Lariboisière, Paris, France. · University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, France. · Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America. · Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America. · DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé, Lausanne, Switzerland. ·PLoS One · Pubmed #26808548.

ABSTRACT: Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association.

24 Article Diagnostic Arthrocentesis for Suspicion of Gout Is Safe and Well Tolerated. 2016

Taylor, William J / Fransen, Jaap / Dalbeth, Nicola / Neogi, Tuhina / Ralph Schumacher, H / Brown, Melanie / Louthrenoo, Worawit / Vazquez-Mellado, Janitzia / Eliseev, Maxim / McCarthy, Geraldine / Stamp, Lisa K / Perez-Ruiz, Fernando / Sivera, Francisca / Ea, Hang-Korng / Gerritsen, Martijn / Scire, Carlo A / Cavagna, Lorenzo / Lin, Chingtsai / Chou, Yin-Yi / Tausche, Anne-Kathrin / da Rocha Castelar-Pinheiro, Geraldo / Janssen, Matthijs / Chen, Jiunn-Horng / Slot, Ole / Cimmino, Marco / Uhlig, Till / Jansen, Tim L. ·From the University of Otago, Wellington; University of Auckland, Auckland; Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand; Radboud University Medical Centre, Nijmegen; Amsterdam Rheumatology Immunology Center (ARC), Department of Rheumatology, Westfries Gasthuis, Hoorn; Rijnstate Hospital, Arnhem, the Netherlands; Boston University School of Medicine, Boston, Massachusetts; University of Pennsylvania, Philadelphia, Pennsylvania, USA; Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Servicio de Reumatología, Hospital General de México, México City, México; Nasonova Research Institute of Rheumatology of Russia, Moscow, Russia; School of Medicine and Medical Science, University College Dublin; Mater Misericordiae University Hospital, Dublin, Ireland; Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya; Department Reumatologia, Hospital General Universitario de Elda, Alicante, Spain; Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine; Institut national de la santé et de la recherche médicale (INSERM), UMR 1132, Hôpital Lariboisière; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Lariboisière, Service de Rhumatologie, Centre Viggo Petersen, Pôle Appareil Locomoteur, Paris, France; Epidemiology Unit, Italian Society for Rheumatology (SIR), Milan; Division of Rheumatology, University and IRCCS Policlinico S. Matteo Foundation, Pavia; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; Division of Rheumatology and Immunology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taichung Veterans' General Hospital; School of Medicine, China Medical University; Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; Division of Rheumatology, Department of In ·J Rheumatol · Pubmed #26628602.

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.

25 Article Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra. 2016

Crișan, Tania O / Cleophas, Maartje C P / Oosting, Marije / Lemmers, Heidi / Toenhake-Dijkstra, Helga / Netea, Mihai G / Jansen, Tim L / Joosten, Leo A B. ·Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Radboud Institute of Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. · Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Radboud Institute of Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Rheumatology, VieCuri Medical Centre, Venlo, The Netherlands. ·Ann Rheum Dis · Pubmed #25649144.

ABSTRACT: OBJECTIVES: The study of the proinflammatory role of uric acid has focused on the effects of its crystals of monosodium urate (MSU). However, little is known whether uric acid itself can directly have proinflammatory effects. In this study, we investigate the priming effects of uric acid exposure on the cytokine production of primary human cells upon stimulation with gout-related stimuli. METHODS: Peripheral blood mononuclear cells (PBMCs) were harvested from patients with gout and healthy volunteers. Cells were pretreated with or without uric acid in soluble form for 24 h and then stimulated for 24 h with toll-like receptor (TLR)2 or TLR4 ligands in the presence or absence of MSU crystals. Cytokine production was measured by ELISA; mRNA levels were assessed using qPCR. RESULTS: The production of interleukin (IL)-1β and IL-6 was higher in patients compared with controls and this correlated with serum urate levels. Proinflammatory cytokine production was significantly potentiated when cells from healthy subjects were pretreated with uric acid. Surprisingly, this was associated with a significant downregulation of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra). This effect was specific to stimulation by uric acid and was exerted at the level of gene transcription. Epigenetic reprogramming at the level of histone methylation by uric acid was involved in this effect. CONCLUSIONS: In this study we demonstrate a mechanism through which high concentrations of uric acid (up to 50 mg/dL) influence inflammatory responses by facilitating IL-1β production in PBMCs. We show that a mechanism for the amplification of IL-1β consists in the downregulation of IL-1Ra and that this effect could be exerted via epigenetic mechanisms such as histone methylation. Hyperuricaemia causes a shift in the IL-1β/IL-1Ra balance produced by PBMCs after exposure to MSU crystals and TLR-mediated stimuli, and this phenomenon is likely to reinforce the enhanced state of chronic inflammation.

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