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Gout: HELP
Articles from University of Edinburgh
Based on 22 articles published since 2008
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These are the 22 published articles about Gout that originated from University of Edinburgh during 2008-2019.
 
+ Citations + Abstracts
1 Guideline The British Society for Rheumatology Guideline for the Management of Gout. 2017

Hui, Michelle / Carr, Alison / Cameron, Stewart / Davenport, Graham / Doherty, Michael / Forrester, Harry / Jenkins, Wendy / Jordan, Kelsey M / Mallen, Christian D / McDonald, Thomas M / Nuki, George / Pywell, Anthony / Zhang, Weiya / Roddy, Edward / Anonymous6680907. ·Department of Rheumatology, Derby Teaching Hospitals NHS Foundation Trust, Derby. · Hamell1st Floor Dome Building, The Quadrant, Richmond, TW9 1DT UK. · Renal Medicine, Guy's Campus, Kings College London, London. · Research Institute for Primary Care and Health Sciences, Keele University, Keele. · Academic Rheumatology, University of Nottingham, Nottingham. · Rheumatology, Brighton and Sussex University Hospitals NHS Trust, Brighton. · Medicines Monitoring Unit, Ninewells Hospital and Medical School, Dundee. · Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh. · Haywood Academic Rheumatology Centre, Staffordshire and Stoke-on-Trent Partnership NHS Trust, Stoke-on-Trent, UK. ·Rheumatology (Oxford) · Pubmed #28549195.

ABSTRACT: -- No abstract --

2 Guideline The British Society for Rheumatology Guideline for the Management of Gout. 2017

Hui, Michelle / Carr, Alison / Cameron, Stewart / Davenport, Graham / Doherty, Michael / Forrester, Harry / Jenkins, Wendy / Jordan, Kelsey M / Mallen, Christian D / McDonald, Thomas M / Nuki, George / Pywell, Anthony / Zhang, Weiya / Roddy, Edward / Anonymous6650907. ·Department of Rheumatology, Derby Teaching Hospitals NHS Foundation Trust, Derby. · Hamell,1st Floor Dome Building, The Quadrant, Richmond TW9 1DT, UK. · Renal Medicine, Guy's Campus, Kings College London, London. · Research Institute for Primary Care and Health Sciences, Keele University, Keele. · Academic Rheumatology, University of Nottingham, Nottingham. · Rheumatology, Brighton and Sussex University Hospitals NHS Trust, Brighton. · Medicines Monitoring Unit, Ninewells Hospital and Medical School, Dundee. · Institute for Genetics and Molecular Medicine, University of Edinburgh. · Haywood Academic Rheumatology Centre, Staffordshire and Stoke-on-Trent Partnership NHS Trust, Stoke-on-Trent, UK. ·Rheumatology (Oxford) · Pubmed #28549177.

ABSTRACT: -- No abstract --

3 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.

4 Review Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. 2017

Li, Xue / Meng, Xiangrui / Timofeeva, Maria / Tzoulaki, Ioanna / Tsilidis, Konstantinos K / Ioannidis, John PA / Campbell, Harry / Theodoratou, Evropi. ·Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK. · Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. · Stanford Prevention Research Center, Stanford School of Medicine, Stanford, CA, USA. · Department of Health Research and Policy, Stanford School of Medicine, Stanford, CA, USA. · Department of Statistics, Stanford University, Stanford, CA, USA. · Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK E.Theodoratou@ed.ac.uk. ·BMJ · Pubmed #28592419.

ABSTRACT:

5 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.

6 Review An appraisal of the 2012 American College of Rheumatology Guidelines for the Management of Gout. 2014

Nuki, George. ·Institute of Genetics and Molecular Medicine, University of Edinburgh. ·Curr Opin Rheumatol · Pubmed #24492863.

ABSTRACT: PURPOSE OF REVIEW: Appraisal of the 2012 American College of Rheumatology (ACR) Guidelines for the Management of Gout. RECENT FINDINGS: The ACRs first clinical practice guidelines for the management of gout focus on recommendations for nonpharmacologic and pharmacologic approaches to hyperuricaemia and the treatment and prophylaxis of acute gouty arthritis. The RAND/UCLA appropriateness methodology employed assessed risks and benefits of alternative treatments for efficacy, safety and quality but not for cost-effectiveness. Novel recommendations include the use of either allopurinol or febuxostat for first-line urate-lowering drug therapy (ULT), screening for HLA-B*5801 prior to initiation of allopurinol in Asians at relatively high risk for allopurinol hypersensitivity, and the use of pegloticase for patients with severe, symptomatic, tophaceous gout refractory to, or intolerant of, appropriately dosed ULTs. Appraisal and comparison with other guidelines using Guidelines International Network and Appraisal of Guidelines, Research and Evaluation (AGREE II) criteria showed good scores for scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, editorial independence and, overall quality, but not for applicability. SUMMARY: The ACR guidelines provide comprehensive, up-to-date, good-quality, evidence-based, expert consensus recommendations for the management of gout in clinical practice but score poorly for applicability. To improve the management of gout in the community a summary of key recommendations, criteria for audit and standards of care are now required.

7 Review Recent insights into the pathogenesis of hyperuricaemia and gout. 2009

Riches, Philip L / Wright, Alan F / Ralston, Stuart H. ·Rheumatic Diseases Unit, University of Edinburgh, Edinburgh EH4 2XU, UK. priches@staffmail.ed.ac.uk ·Hum Mol Genet · Pubmed #19808794.

ABSTRACT: Gout is a common rheumatic disease in humans which is characterized by elevation in serum uric acid levels, and deposition of uric acid crystals in the joint. Hyperuricaemia is the primary risk factor for the development of gout and primates have uniquely high levels of serum uric acid due to missense mutations in the uricase gene. Levels of serum uric acid are known to be highly heritable, and mutations in genes which encode enzymes in the purine salvage pathway have long been recognized as rare causes of gout. Until recently, however, little has been known about the genetic determinants of urate metabolism and susceptibility to gout in the general population. Over recent months, a series of large scale genome wide association studies have been performed which have shed new light on the genes which regulate serum uric acid levels and susceptibility to gout. Most of these genes seem to be involved in regulating the renal excretion of uric acid which underscores the importance of reduced urate excretion as opposed to increased endogenous production as a cause of gout. Further work will now be required to investigate the mechanisms by which these genetic variants regulate urate excretion and serum urate levels. However, it seems likely that the genes so far identified will represent new molecular targets for the design of drugs to enhance urate excretion and the genetic variants that predispose to gout might be of value as genetic markers of susceptibility to gout.

8 Review Colchicine: its mechanism of action and efficacy in crystal-induced inflammation. 2008

Nuki, George. ·University of Edinburgh, Osteoarticular Research Group, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom. g.nuki@ed.ac.uk ·Curr Rheumatol Rep · Pubmed #18638431.

ABSTRACT: New light has been shed on the mechanisms of action of colchicine in crystal-associated arthropathies. Colchicine, long used to treat gout, arrests microtubule assembly and inhibits many cellular functions. At micromolar concentrations, it suppresses monosodium urate crystal-induced NACHT-LRR-PYD-containing protein-3 (NALP3) inflammasome-driven caspase-1 activation, IL-1beta processing and release, and L-selectin expression on neutrophils. At nanomolar concentrations, colchicine blocks the release of a crystal-derived chemotactic factor from neutrophil lysosomes, blocks neutrophil adhesion to endothelium by modulating the distribution of adhesion molecules on the endothelial cells, and inhibits monosodium urate crystal-induced production of superoxide anions from neutrophils. Cyto-chrome P450 3A4, the multidrug transporter P-glycoprotein, and the drugs that bind these proteins influence its pharmacokinetics and pharmacodynamics. Trial evidence supports its efficacy in acute gout and in preventing gout flares, but it has narrow therapeutic index, and overdosage is associated with gastrointestinal, hepatic, renal, neuromuscular, and cerebral toxicity; bone marrow damage; and high mortality.

9 Article Improving management of gout in primary care: a new UK management guideline. 2017

Mallen, Christian D / Davenport, Graham / Hui, Michelle / Nuki, George / Roddy, Edward. ·Institute for Primary Care and Health Sciences, Keele University, Keele. · Rheumatology, Derby Teaching Hospitals NHS Foundation Trust, Derby. · University of Edinburgh, Edinburgh. · Research Institute for Primary Care and Health Sciences, Keele University, Keele, and Haywood Academic Rheumatology Centre, Staffordshire and Stoke-on-Trent Partnership Trust, Stoke-on-Trent. ·Br J Gen Pract · Pubmed #28546417.

ABSTRACT: -- No abstract --

10 Article Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990-2013: findings from the Global Burden of Disease Study 2013. 2017

Moradi-Lakeh, Maziar / Forouzanfar, Mohammad H / Vollset, Stein Emil / El Bcheraoui, Charbel / Daoud, Farah / Afshin, Ashkan / Charara, Raghid / Khalil, Ibrahim / Higashi, Hideki / Abd El Razek, Mohamed Magdy / Kiadaliri, Aliasghar Ahmad / Alam, Khurshid / Akseer, Nadia / Al-Hamad, Nawal / Ali, Raghib / AlMazroa, Mohammad AbdulAziz / Alomari, Mahmoud A / Al-Rabeeah, Abdullah A / Alsharif, Ubai / Altirkawi, Khalid A / Atique, Suleman / Badawi, Alaa / Barrero, Lope H / Basulaiman, Mohammed / Bazargan-Hejazi, Shahrzad / Bedi, Neeraj / Bensenor, Isabela M / Buchbinder, Rachelle / Danawi, Hadi / Dharmaratne, Samath D / Zannad, Faiez / Farvid, Maryam S / Fereshtehnejad, Seyed-Mohammad / Farzadfar, Farshad / Fischer, Florian / Gupta, Rahul / Hamadeh, Randah Ribhi / Hamidi, Samer / Horino, Masako / Hoy, Damian G / Hsairi, Mohamed / Husseini, Abdullatif / Javanbakht, Mehdi / Jonas, Jost B / Kasaeian, Amir / Khan, Ejaz Ahmad / Khubchandani, Jagdish / Knudsen, Ann Kristin / Kopec, Jacek A / Lunevicius, Raimundas / Abd El Razek, Hassan Magdy / Majeed, Azeem / Malekzadeh, Reza / Mate, Kedar / Mehari, Alem / Meltzer, Michele / Memish, Ziad A / Mirarefin, Mojde / Mohammed, Shafiu / Naheed, Aliya / Obermeyer, Carla Makhlouf / Oh, In-Hwan / Park, Eun-Kee / Peprah, Emmanuel Kwame / Pourmalek, Farshad / Qorbani, Mostafa / Rafay, Anwar / Rahimi-Movaghar, Vafa / Shiri, Rahman / Rahman, Sajjad Ur / Rai, Rajesh Kumar / Rana, Saleem M / Sepanlou, Sadaf G / Shaikh, Masood Ali / Shiue, Ivy / Sibai, Abla Mehio / Silva, Diego Augusto Santos / Singh, Jasvinder A / Skogen, Jens Christoffer / Terkawi, Abdullah Sulieman / Ukwaja, Kingsley N / Westerman, Ronny / Yonemoto, Naohiro / Yoon, Seok-Jun / Younis, Mustafa Z / Zaidi, Zoubida / Zaki, Maysaa El Sayed / Lim, Stephen S / Wang, Haidong / Vos, Theo / Naghavi, Mohsen / Lopez, Alan D / Murray, Christopher J L / Mokdad, Ali H. ·Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, USA. · Department of Community Medicine, Preventive Medicine and Public Health Research Center, Iran University of Medical Sciences, Tehran, Iran. · Norwegian Institute of Public Health, Bergen, Norway. · Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. · Japan International Cooperation Agency, Lusaka, Zambia. · Ophthalmology resident in Aswan University Hospital, Aswan, Egypt. · Clinical Epidemiology Unit, Department of Clinical Sciences Lund, Orthopedics, Lund University, Lund, Sweden. · Murdoch Childrens Research Institute, Melbourne, Victoria, Australia. · The University of Melbourne, Melbourne, Victoria, Australia. · The University of Sydney, Sydney, New South Wales, Australia. · Hospital for Sick Children, Toronto, Ontario, Canada. · University of Toronto, Toronto, Ontario, Canada. · Food and Nutrition Administration, Ministry of Health, Safat, Kuwait. · University of Oxford, Oxford, UK. · Saudi Ministry of Health, Riyadh, Saudi Arabia. · Division of Physical Therapy, Department of Rehabilitation Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan. · Charité Universitätsmedizin, Berlin, Germany. · King Saud University, Riyadh, Saudi Arabia. · Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan. · Public Health Agency of Canada, Toronto, Ontario, Canada. · Department of Industrial Engineering, School of Engineering, Pontificia Universidad Javeriana, Bogota, Colombia. · Charles R. Drew University of Medicine and Science, Los Angeles, California, USA. · David Geffen School of Medicine, University of California at Los Angeles (UCLA), California, USA. · College of Public Health and Tropical Medicine, Jazan, Saudi Arabia. · University of São Paulo, São Paulo, Brazil. · Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Victoria, Australia. · Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Walden University, Minneapolis, Minnesota, USA. · Department of Community Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka. · Clinical Investigation Centre INSERM (the National Institute for Health and Medical Research), Université de Lorraine, Vandoeuvre les Nancy, France. · Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. · Harvard/MGH Center on Genomics, Vulnerable Populations, and Health Disparities, Mongan Institute for Health Policy, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institute, Stockholm, Sweden. · Non-Communicable Diseases Research Center, Endocrine and Metabolic Research Institute, Tehran University of Medical Sciences, Tehran, Iran. · Bielefeld University, Bielefeld, Germany. · West Virginia Bureau for Public Health, Charleston, West Virginia, USA. · Arabian Gulf University, Manama, Bahrain. · Hamdan Bin Mohammed Smart University, Dubai, United Arab Emirates. · Nevada Division of Behavior and Public Health, Carson City, Nevada, USA. · Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA. · Public Health Division, Secretariat of the Pacific Community, Noumea, New Caledonia. · Salah Azaiz Institute, Tunis, Tunisia. · Institute of Community and Public Health, Birzeit University, Birzeit, Palestine. · Health Economics Research Unit, University of Aberdeen, Aberdeen, UK. · Department of Ophthalmology, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany. · Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran. · Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. · Health Services Academy, Islamabad, Pakistan. · Ball State University, Muncie, Indiana, USA. · Department of Health Registries, Norwegian Institute of Public Health, Bergen, Norway. · University of British Columbia, Vancouver, British Columbia, Canada. · Aintree University Hospital National Health Service Foundation Trust, Liverpool, UK. · School of Medicine, University of Liverpool, Liverpool, UK. · Mansoura Faculty of Medicine, Mansoura, Egypt. · Imperial College London, London, UK. · Digestive Disease Research Institute, Tehran Universities of Medical Sciences, Tehran, Iran. · McGill University, Montreal, Quebec, Canada. · College of Medicine, Howard University, Washington DC, USA. · Thomas Jefferson University, Philadelphia, Pennsylvania, USA. · College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. · Hunger Action Los Angeles, Los Angeles, California, USA. · Health Systems and Policy Research Unit, Ahmadu Bello University, Zaria, Nigeria. · Institute of Public Health, Heidelberg University, Heidelberg, Germany. · International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. · Faculty of Health Sciences, Center for Research on Population and Health, American University of Beirut, Beirut, Lebanon. · Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, South Korea. · Department of Medical Humanities and Social Medicine, College of Medicine, Kosin University, Busan, South Korea. · National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. · Noncommunicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. · Contech International Health Consultants, Lahore, Pakistan. · Contech School of Public Health, Lahore, Pakistan. · Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran. · Finnish Institute of Occupational Health, Helsinki, Finland. · Sweidi Hospital, Riyadh, Saudi Arabia. · Society for Health and Demographic Surveillance, Suri, India. · Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. · Independent Consultant, Karachi, Pakistan. · Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK. · Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK. · Department of Epidemiology & Population Health, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon. · Federal University of Santa Catarina, Florianópolis, Brazil. · University of Alabama at Birmingham, and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA. · Alcohol and Drug Research Western Norway, Stavanger University Hospital, Stavanger, Norway. · Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA. · Outcomes Research Consortium, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Anesthesiology, King Fahad Medical City, Riyadh, Saudi Arabia. · Department of Internal Medicine, Federal Teaching Hospital, Abakaliki, Nigeria. · Federal Institute for Population Research, Wiesbaden, Germany. · German National Cohort Consortium, Heidelberg, Germany. · Department of Biostatistics, School of Public Health, Kyoto University, Kyoto, Japan. · Department of Preventive Medicine, College of Medicine, Korea University, Seoul, South Korea. · Jackson State University, Jackson, Mississippi, USA. · University Hospital, Setif, Algeria. · Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia. ·Ann Rheum Dis · Pubmed #28209629.

ABSTRACT: OBJECTIVES: We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). METHODS: The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). RESULTS: For musculoskeletal disorders, the crude DALYs rate per 100 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3-1703.4) in 1990 to 1606.0 (95% UI 1141.2-2130.4) in 2013. During 1990-2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7-3.0) in 1990 to 4.7% (95% UI 3.6-5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2-136.0 for low back pain, 27.3-49.7 for neck pain, 9.7-37.3 for osteoarthritis (OA), 0.6-2.2 for rheumatoid arthritis and 0.1-0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. CONCLUSIONS: This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness.

11 Article Gout in immigrant groups: a cohort study in Sweden. 2017

Wändell, Per / Carlsson, Axel C / Li, Xinjun / Gasevic, Danijela / Ärnlöv, Johan / Holzmann, Martin J / Sundquist, Jan / Sundquist, Kristina. ·Department of Neurobiology, Care Sciences and Society, Division of Family Medicine, Karolinska Institutet, Alfred Nobels Allé 23, SE-141 83, Huddinge, Sweden. per.wandell@ki.se. · Department of Neurobiology, Care Sciences and Society, Division of Family Medicine, Karolinska Institutet, Alfred Nobels Allé 23, SE-141 83, Huddinge, Sweden. · Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden. · Center for Primary Health Care Research, Lund University, Malmö, Sweden. · Usher Institute of Population Health Sciences and Informatics, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK. · Department of Emergency Medicine, Karolinska University Hospital, Huddinge, Sweden. · Department of Internal Medicine Solna, Karolinska Institutet, Stockholm, Sweden. ·Clin Rheumatol · Pubmed #28091806.

ABSTRACT: Our aim was to study the association between country of birth and incidence of gout in different immigrant groups in Sweden. The study population included the whole population of Sweden. Gout was defined as having at least one registered diagnosis in the National Patient Register. The association between incidence of gout and country of birth was assessed by Cox regression, with hazard ratios (HRs) and 95% confidence intervals (95% CI), using Swedish-born individuals as referents. All models were conducted in both men and women, and the full model was adjusted for age, place of residence in Sweden, educational level, marital status, neighbourhood socio-economic status and co-morbidities. The risk of gout varied by country of origin, with highest estimates, compared to Swedish born, in fully adjusted models among men from Iraq (HR 1.82, 95% CI 1.54-2.16), and Russia (HR 1.69, 95% CI 1.26-2.27), and also high among men from Austria, Poland, Africa and Asian countries outside the Middle East; and among women from Africa (HR 2.23, 95% CI 1.50-3.31), Hungary (HR 1.98, 95% CI 1.45-2.71), Iraq (HR 1.76, 95% CI 1.13-2.74) and Austria (HR 1.70, 95% CI 1.07-2.70), and also high among women from Poland. The risk of gout was lower among men from Greece, Spain, Nordic countries (except Finland) and Latin America and among women from Southern Europe, compared to their Swedish counterparts. The increased risk of gout among several immigrant groups is likely explained by a high cardio-metabolic risk factor pattern needing attention.

12 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.

13 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.

14 Article Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout. 2015

McKinney, Cushla / Stamp, Lisa K / Dalbeth, Nicola / Topless, Ruth K / Day, Richard O / Kannangara, Diluk Rw / Williams, Kenneth M / Janssen, Matthijs / Jansen, Timothy L / Joosten, Leo A / Radstake, Timothy R / Riches, Philip L / Tausche, Anne-Kathrin / Lioté, Frederic / So, Alexander / Merriman, Tony R. ·Department of Biochemistry, University of Otago, Box 56, Dunedin, 9054, New Zealand. cushla.mckinney@otago.ac.nz. · Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz. · Department of Medicine, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz. · Department of Biochemistry, University of Otago, Box 56, Dunedin, 9054, New Zealand. ruth.topless@otago.ac.nz. · School of Medical Sciences, University of New South Wales, Sydney, Australia. r.day@unsw.edu.au. · Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. r.day@unsw.edu.au. · School of Medical Sciences, University of New South Wales, Sydney, Australia. r.kannangara@unsw.edu.au. · Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. r.kannangara@unsw.edu.au. · School of Medical Sciences, University of New South Wales, Sydney, Australia. ken.williams@unsw.edu.au. · Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. ken.williams@unsw.edu.au. · Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands. matthijs.janssen@rijnstate.nl. · Department of IQ HealthCare, VieCuri Medical Centre, Venlo, The Netherlands. tim.jansen@radboudumc.nl. · Scientific Institute of Quality in HealthCare, Radboud University Medical Centre, Nijmegen, The Netherlands. tim.jansen@radboudumc.nl. · Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands. l.joosten@aig.umcn.nl. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, University Medical Centre Utrecht, PO Box 85500, 3508, GA, Utrecht, The Netherlands. tradstake73@googlemail.com. · Department of Immunology, University Medical Centre Utrecht, PO Box 85500, 3508, GA, Utrecht, The Netherlands. tradstake73@googlemail.com. · Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. priches@staffmail.ed.ac.uk. · Department of Rheumatology, University Clinic Carl-Gustav-Carus", Dresden, Germany. anne-kathrin.tausche@uniklinikum-dresden.de. · INSERM, UMR-S 1132, Hospital Lariboisière, F-75010, Paris, France. frederic.liote@lrb.aphp.fr. · University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, F-75205, Paris, France. frederic.liote@lrb.aphp.fr. · DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé 05-5029, 1011, Lausanne, Switzerland. alexanderkai-lik.so@chuv.ch. · Department of Biochemistry, University of Otago, Box 56, Dunedin, 9054, New Zealand. tony.merriman@otago.ac.nz. ·Arthritis Res Ther · Pubmed #26462562.

ABSTRACT: INTRODUCTION: The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. METHODS: 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. RESULTS: Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P < 0.05) associations with gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. CONCLUSION: There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases expression of IL-1β - the multiplicative interaction with CARD8 would be consistent with a synergy of greater inflammasome activity (resulting from reduced CARD8) combined with higher levels of pre-IL-1β expression leading to increased production of mature IL-1β in gout.

15 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.

16 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.

17 Article Modulation of genetic associations with serum urate levels by body-mass-index in humans. 2015

Huffman, Jennifer E / Albrecht, Eva / Teumer, Alexander / Mangino, Massimo / Kapur, Karen / Johnson, Toby / Kutalik, Zoltán / Pirastu, Nicola / Pistis, Giorgio / Lopez, Lorna M / Haller, Toomas / Salo, Perttu / Goel, Anuj / Li, Man / Tanaka, Toshiko / Dehghan, Abbas / Ruggiero, Daniela / Malerba, Giovanni / Smith, Albert V / Nolte, Ilja M / Portas, Laura / Phipps-Green, Amanda / Boteva, Lora / Navarro, Pau / Johansson, Asa / Hicks, Andrew A / Polasek, Ozren / Esko, Tõnu / Peden, John F / Harris, Sarah E / Murgia, Federico / Wild, Sarah H / Tenesa, Albert / Tin, Adrienne / Mihailov, Evelin / Grotevendt, Anne / Gislason, Gauti K / Coresh, Josef / D'Adamo, Pio / Ulivi, Sheila / Vollenweider, Peter / Waeber, Gerard / Campbell, Susan / Kolcic, Ivana / Fisher, Krista / Viigimaa, Margus / Metter, Jeffrey E / Masciullo, Corrado / Trabetti, Elisabetta / Bombieri, Cristina / Sorice, Rossella / Döring, Angela / Reischl, Eva / Strauch, Konstantin / Hofman, Albert / Uitterlinden, Andre G / Waldenberger, Melanie / Wichmann, H-Erich / Davies, Gail / Gow, Alan J / Dalbeth, Nicola / Stamp, Lisa / Smit, Johannes H / Kirin, Mirna / Nagaraja, Ramaiah / Nauck, Matthias / Schurmann, Claudia / Budde, Kathrin / Farrington, Susan M / Theodoratou, Evropi / Jula, Antti / Salomaa, Veikko / Sala, Cinzia / Hengstenberg, Christian / Burnier, Michel / Mägi, Reedik / Klopp, Norman / Kloiber, Stefan / Schipf, Sabine / Ripatti, Samuli / Cabras, Stefano / Soranzo, Nicole / Homuth, Georg / Nutile, Teresa / Munroe, Patricia B / Hastie, Nicholas / Campbell, Harry / Rudan, Igor / Cabrera, Claudia / Haley, Chris / Franco, Oscar H / Merriman, Tony R / Gudnason, Vilmundur / Pirastu, Mario / Penninx, Brenda W / Snieder, Harold / Metspalu, Andres / Ciullo, Marina / Pramstaller, Peter P / van Duijn, Cornelia M / Ferrucci, Luigi / Gambaro, Giovanni / Deary, Ian J / Dunlop, Malcolm G / Wilson, James F / Gasparini, Paolo / Gyllensten, Ulf / Spector, Tim D / Wright, Alan F / Hayward, Caroline / Watkins, Hugh / Perola, Markus / Bochud, Murielle / Kao, W H Linda / Caulfield, Mark / Toniolo, Daniela / Völzke, Henry / Gieger, Christian / Köttgen, Anna / Vitart, Veronique. ·Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom. · Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. · King's College London, St. Thomas' Hospital Campus, London, United Kingdom. · Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. · Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy. · Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy. · Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland. · Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America. · Clinical Research Branch, National Institute on Aging, Baltimore, MD, United States of America. · Member of Netherlands Consortium for Healthy Aging (NCHA) sponsored by Netherlands Genomics Initiative (NGI), Leiden, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Institute of Genetics and Biophysics "A. Buzzati-Traverso"-Consiglio Nazionale delle Ricerche (CNR), Naples, Italy. · Biology and Genetics section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy. · Icelandic Heart Association Research Institute, Kopavogur, Iceland; University of Iceland, Reykjavik, Iceland. · Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. · Institute of Population Genetics, National Research Council of Italy, Sassari, Italy. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Uppsala Clinical Research Center, Uppsala University Hospital, Upsalla, Sweden; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden. · Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy; Affiliated Institute of the University of Lübeck, Lübeck, Germany. · Faculty of Medicine, University of Split, Croatia, Soltanska 2, Split, 21000, Croatia. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Broad Institute, Cambridge, MA, United States of America; Children's Hospital Boston, Boston, MA, United States of America. · Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom; Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom. · Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom. · Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom; Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom. · Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany. · Icelandic Heart Association Research Institute, Kopavogur, Iceland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Welch Center for Prevention, Epidemiology and Clinical Research, John Hopkins University, Baltimore, MD, United States of America. · Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy. · Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland. · Tallinn University of Technology, Department of Biomedical Engineering, Chair of Medical Physics, Tallinn, Estonia; Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany. · Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany; Klinikum Grosshadern, Munich, Germany. · Bone and Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Psychiatry/EMGO Institute, VU University Medical Centre, Amsterdam, the Netherlands. · Laboratory of Genetics, National Institute on Aging (NIA), Baltimore, MD, United States of America. · Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Turku, Finland. · University Hospital Regensburg, Regensburg, Germany. · Department of Medicine, Nephrology Division, Lausanne University Hospital, Lausanne, Switzerland. · Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany. · Max Planck Institute of Psychiatry, Munich, Germany. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Turku, Finland; Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; University of Helsinki, Institute of Molecular Medicine, Helsinki, Finland. · Department of Mathematics and Informatics, Università di Cagliari, Cagliari, Italy; Department of Statistics, Universidad Carlos III de Madrid, Madrid, Spain. · Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom. · Faculty of Medicine, University of Split, Croatia, Soltanska 2, Split, 21000, Croatia; Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom. · Queen Mary, University of London, London, United Kingdom. · Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Institute of Internal Medicine, Renal Program, Columbus-Gemelli University Hospital, Catholic University, Rome, Italy. · Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden. · on behalf of PROCARDIS; Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland; University of Helsinki, Institute of Molecular Medicine, Helsinki, Finland. · University Institute of Social and Preventive Medicine, Lausanne, Switzerland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Renal Division, Freiburg University Hospital, Freiburg, Germany. ·PLoS One · Pubmed #25811787.

ABSTRACT: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

18 Article Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia. 2014

MacDonald, Thomas M / Ford, Ian / Nuki, George / Mackenzie, Isla S / De Caterina, Raffaele / Findlay, Evelyn / Hallas, Jesper / Hawkey, Christopher J / Ralston, Stuart / Walters, Matthew / Webster, John / McMurray, John / Perez Ruiz, Fernando / Jennings, Claudine G / Anonymous3571005. ·Medicines Monitoring Unit (MEMO), Ninewells Hospital, University of Dundee, Dundee, UK. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK. · Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK. · Cardiovascular Division, SS Annunziata Hospital, and Center of Excellence on Aging (Ce.S.I), G d'Annunzio University, Chieti, Italy. · University of Southern Denmark, Odense, Denmark. · NDDC, Queen's Medical Centre, University of Nottingham, Nottingham, UK. · Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. · School of Medicine, University of Aberdeen, Aberdeen, UK. · Rheumatology Division, Hospital de Cruces, Vizcaya, Spain. ·BMJ Open · Pubmed #25011991.

ABSTRACT: INTRODUCTION: Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST). METHODS AND ANALYSIS: FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3. ETHICS AND DISSEMINATION: FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal. TRIAL REGISTRATION NUMBER: FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).

19 Article Up-titration of allopurinol in patients with gout. 2014

Jennings, Claudine G / Mackenzie, Isla S / Flynn, Rob / Ford, Ian / Nuki, George / De Caterina, Raffaele / Riches, Philip L / Ralston, Stuart H / MacDonald, Thomas M / Anonymous160786. ·Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK. Electronic address: claudine@memo.dundee.ac.uk. · Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK. · University of Glasgow, Robertson Centre for Biostatistics, UK. · Western General Hospital, Centre for Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Cardiovascular Division, G d'Annunzio University, SS. Annunziata Hospital, and Center of Excellence on Aging (Ce.S.I), Chieti, Italy. ·Semin Arthritis Rheum · Pubmed #24560169.

ABSTRACT: OBJECTIVES: European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many gout patients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels. METHOD: The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients. RESULTS: Of 400 patients, 144 (36%) had urate levels ≥357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal. CONCLUSION: Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients.

20 Article The association of dietary intake of purine-rich vegetables, sugar-sweetened beverages and dairy with plasma urate, in a cross-sectional study. 2012

Zgaga, Lina / Theodoratou, Evropi / Kyle, Janet / Farrington, Susan M / Agakov, Felix / Tenesa, Albert / Walker, Marion / McNeill, Geraldine / Wright, Alan F / Rudan, Igor / Dunlop, Malcolm G / Campbell, Harry. ·Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom. lina.zgaga@ed.ac.uk ·PLoS One · Pubmed #22701608.

ABSTRACT: INTRODUCTION: Hyperuricemia is a strong risk factor for gout. The incidence of gout and hyperuricemia has increased recently, which is thought to be, in part, due to changes in diet and lifestyle. Objective of this study was to investigate the association between plasma urate concentration and: a) food items: dairy, sugar-sweetened beverages (SSB) and purine-rich vegetables; b) related nutrients: lactose, calcium and fructose. METHODS: A total of 2,076 healthy participants (44% female) from a population-based case-control study in Scotland (1999-2006) were included in this study. Dietary data was collected using a semi-quantitative food frequency questionnaire (FFQ). Nutrient intake was calculated using FFQ and composition of foods information. Urate concentration was measured in plasma. RESULTS: Mean urate concentration was 283.8±72.1 mmol/dL (females: 260.1±68.9 mmol/dL and males: 302.3±69.2 mmol/dL). Using multivariate regression analysis we found that dairy, calcium and lactose intakes were inversely associated with urate (p = 0.008, p = 0.003, p = 0.0007, respectively). Overall SSB consumption was positively associated with urate (p = 0.008), however, energy-adjusted fructose intake was not associated with urate (p = 0.66). The intake of purine-rich vegetables was not associated to plasma urate (p = 0.38). CONCLUSIONS: Our results suggest that limiting purine-rich vegetables intake for lowering plasma urate may be ineffectual, despite current recommendations. Although a positive association between plasma urate and SSB consumption was found, there was no association with fructose intake, suggesting that fructose is not the causal agent underlying the SSB-urate association. The abundant evidence supporting the inverse association between plasma urate concentration and dairy consumption should be reflected in dietary guidelines for hyperuricemic individuals and gout patients. Further research is needed to establish which nutrients and food products influence plasma urate concentration, to inform the development of evidence-based dietary guidelines.

21 Article Management of the nontraumatic hot swollen joint. 2012

Reed, Matthew J / Carachi, Andrew. ·Department of Emergency Medicine, Emergency Medicine Research Group, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK. matthew.reed@luht.scot.nhs.uk ·Eur J Emerg Med · Pubmed #21730866.

ABSTRACT: AIM: To audit the management of nontraumatic hot swollen joints presenting to a large UK university teaching hospital and to design a simple emergency department (ED) algorithm to improve patient care based on existing guidelines and our experience. METHODS: Prospective audit. RESULTS: Between 2 February and 8 May 2009, 77 patients were enrolled. Median age was 58 years (range 19-89 years) and 57% were male patients. The most commonly affected joint was the knee (38%), with the knee, wrist, ankle, hip and elbow comprising 87% of affected joints. Thirty-three (43%) joints were aspirated; no organisms were found on microscopy or cultured in any aspirates; crystals were found in eight aspirates. Twenty-four patients were admitted. Gout was the most common final diagnosis in 14 (18%) patients, with cellulitis being the next most common diagnosis (n=9; 12%). Bursitis (n=7; 9%), nonspecific arthritis (n=7; 9%) and reactive arthritis (n=6; 8%) were also not uncommon. Four (5%) patients were treated for possible septic arthritis. It was noticed that many patients spent a long time in the ED waiting firstly for a decision to aspirate, and secondly for a senior clinician to perform this. CONCLUSION: Patients presenting with nontraumatic hot swollen joints are common and the knee, wrist, ankle, hip and elbow are commonly affected. Joint aspirate is required to rule out septic arthritis, should be considered early and appropriate personnel called, and can show the presence of gout or pseudogout. Septic arthritis should still be considered in patients with a negative aspirate in whom there is high clinical suspicion. Our simple ED algorithm may improve patient care.

22 Article SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. 2008

Vitart, Veronique / Rudan, Igor / Hayward, Caroline / Gray, Nicola K / Floyd, James / Palmer, Colin N A / Knott, Sara A / Kolcic, Ivana / Polasek, Ozren / Graessler, Juergen / Wilson, James F / Marinaki, Anthony / Riches, Philip L / Shu, Xinhua / Janicijevic, Branka / Smolej-Narancic, Nina / Gorgoni, Barbara / Morgan, Joanne / Campbell, Susan / Biloglav, Zrinka / Barac-Lauc, Lovorka / Pericic, Marijana / Klaric, Irena Martinovic / Zgaga, Lina / Skaric-Juric, Tatjana / Wild, Sarah H / Richardson, William A / Hohenstein, Peter / Kimber, Charley H / Tenesa, Albert / Donnelly, Louise A / Fairbanks, Lynette D / Aringer, Martin / McKeigue, Paul M / Ralston, Stuart H / Morris, Andrew D / Rudan, Pavao / Hastie, Nicholas D / Campbell, Harry / Wright, Alan F. ·MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK. ·Nat Genet · Pubmed #18327257.

ABSTRACT: Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.