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Gout: HELP
Articles from University of Sydney
Based on 18 articles published since 2008
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These are the 18 published articles about Gout that originated from University of Sydney during 2008-2019.
 
+ Citations + Abstracts
1 Review Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat. 2017

Kamel, Bishoy / Graham, Garry G / Williams, Kenneth M / Pile, Kevin D / Day, Richard O. ·School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. · Department of Clinical Pharmacology and Toxicology, Level 2 Xavier Building, St Vincent's Hospital, 390 Victoria Street, Darlinghurst, NSW, 2010, Australia. · Department of Medicine, Western Sydney University, Campbelltown, NSW, Australia. · School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. r.day@unsw.edu.au. · Department of Clinical Pharmacology and Toxicology, Level 2 Xavier Building, St Vincent's Hospital, 390 Victoria Street, Darlinghurst, NSW, 2010, Australia. r.day@unsw.edu.au. · St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia. r.day@unsw.edu.au. ·Clin Pharmacokinet · Pubmed #27753003.

ABSTRACT: Febuxostat is a xanthine oxidoreductase inhibitor that has been developed to treat chronic gout. In healthy subjects, the pharmacokinetic parameters of febuxostat after multiple oral dose administration include an oral availability of about 85 %, an apparent oral clearance (CL/F) of 10.5 ± 3.4 L/h and an apparent volume of distribution at steady state (V

2 Review Allopurinol hypersensitivity: investigating the cause and minimizing the risk. 2016

Stamp, Lisa K / Day, Richard O / Yun, James. ·Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch 8140, New Zealand. · Department of Clinical Pharmacology &Toxicology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia. · Department of Clinical Immunology and Allergy, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. ·Nat Rev Rheumatol · Pubmed #26416594.

ABSTRACT: Allopurinol is the most commonly prescribed urate-lowering therapy for the management of gout. Serious adverse reactions associated with allopurinol, while rare, are feared owing to the high mortality. Such reactions can manifest as a rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Risk factors for allopurinol-related severe adverse reactions include the recent introduction of allopurinol, the presence of the HLA-B(*)58:01 allele, and factors that influence the drug concentration. The interactions between allopurinol, its metabolite, oxypurinol, and T cells have been studied, and evidence exists that the presence of the HLA-B(*)58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide-oxypurinol-HLA-B(*)58:01 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction. This Review will discuss the above issues and place this in the clinical context of reducing the risk of serious adverse reactions.

3 Review Reflecting on the global burden of musculoskeletal conditions: lessons learnt from the global burden of disease 2010 study and the next steps forward. 2015

Hoy, Damian G / Smith, Emma / Cross, Marita / Sanchez-Riera, Lidia / Blyth, Fiona M / Buchbinder, Rachelle / Woolf, Anthony D / Driscoll, Tim / Brooks, Peter / March, Lyn M. ·School of Population Health, University of Queensland, Herston, Queensland, Australia. · Northern Clinical School, Institute of Bone and Joint Research, University of Sydney, St Leonards, New South Wales, Australia Department of Rheumatology, Royal North Shore Hospital, St Leonards, New South Wales, Australia. · Department of Rheumatology, Royal North Shore Hospital, Institute of Bone and Joint Research, University of Sydney, Australia and Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. · School of Public Health, University of Sydney, Camperdown, New South Wales, Australia. · Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia Monash Department of Clinical Epidemiology, Cabrini Hospital, Malvern, Victoria, Australia. · Department of Rheumatology, Royal Cornwall Hospital, Truro, UK. · Sydney School of Public Health, University of Sydney, Camperdown, New South Wales, Australia. · School of Population and Global Health, University of Melbourne and Northern Hospital, Parkville, Victoria, Australia. ·Ann Rheum Dis · Pubmed #24914071.

ABSTRACT: The objective of this paper is to provide an overview of the strengths, limitations and lessons learned from estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Disease 2010 Study (GBD 2010 Study). It should be read in conjunction with the other GBD 2010 Study papers published in this journal. The strengths of the GBD 2010 Study include: the involvement of a MSK expert group; development of new and more valid case definitions, functional health states, and disability weights to better reflect the MSK conditions; the extensive series of systematic reviews undertaken to obtain data to derive the burden estimates; and the use of a new, more advanced version of the disease-modelling software (DisMod-MR). Limitations include: many regions of the world did not have data; the extent of heterogeneity between included studies; and burden does not include broader aspects of life, such as participation and well-being. A number of lessons were learned. Ongoing involvement of experts is critical to ensure the success of future efforts to quantify and monitor this burden. A paradigm shift is urgently needed among global agencies in order to alleviate the rapidly increasing global burden from MSK conditions. Prevention and control of MSK disability are required, along with health system changes. Further research is needed to improve understanding of the predictors and clinical course across different settings, and the ways in which MSK conditions can be better managed and prevented.

4 Review The global burden of gout: estimates from the Global Burden of Disease 2010 study. 2014

Smith, Emma / Hoy, Damian / Cross, Marita / Merriman, Tony R / Vos, Theo / Buchbinder, Rachelle / Woolf, Anthony / March, Lyn. ·Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Institute of Bone and Joint Research, University of Sydney, St Leonards, New South Wales, Australia. · School of Population Health, University of Queensland, Herston, Queensland, Australia. · School of Medical Sciences, University of Otago, Dunedin, New Zealand. · School of Population Health, University of Queensland, Herston, Queensland, Australia Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, USA. · Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia Monash Department of Clinical Epidemiology, Cabrini Hospital, Melbourne, Victoria, Australia. · Department of Rheumatology, Royal Cornwall Hospital, Truro, UK. ·Ann Rheum Dis · Pubmed #24590182.

ABSTRACT: OBJECTIVE: Gout is the most common cause of inflammatory arthritis in men, but has not previously been included in Global Burden of Disease (GBD) studies. As part of the GBD 2010 Study, the Musculoskeletal Disorders and Risk Factors Expert Group estimated the global burden of gout. METHODS: The American Rheumatism Association 1977 case definition of primary gout was used in the study. A series of systematic reviews were conducted to gather the age-specific and sex-specific epidemiological data for gout prevalence, incidence, mortality risk and duration. Two main disabling sequelae of gout were identified; acute episode gout and chronic polyarticular gout, and used in the surveys to collect data to derive disability weights. The epidemiological data together with disability weights were then used to calculate years of life lived with disability (YLDs) for gout, for 1990 and 2010. No evidence of cause-specific mortality associated with gout was found. Gout disability-adjusted life years (DALYs), therefore, have the same value as YLDs. RESULTS: Global prevalence of gout was 0.08% (95% uncertainty interval (UI) 0.07 to 0.08). DALYs increased from 76 000 (95% UI 48 to 112) in 1990 to 114 000 (95% UI 72 to 167) in 2010. Out of all 291 conditions studied in the GBD 2010 Study, gout ranked 138th in terms of disability as measured by YLDs, and 173rd in terms of overall burden (DALYs). CONCLUSIONS: The burden of gout is rising. With increasing ageing populations globally, this evidence is a significant prompt to optimise treatment and management of gout at individual, community and national levels.

5 Review Epidemiology of gout: an update. 2010

Smith, E U R / Díaz-Torné, C / Perez-Ruiz, F / March, L M. ·Department of Rheumatology, Northern Clinical School, University of Sydney, Building 35, Block 4, Level 4, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. emma.smith@sydney.edu.au ·Best Pract Res Clin Rheumatol · Pubmed #21665128.

ABSTRACT: Gout is the most common inflammatory joint disease in men, characterised by formation of monosodium urate (MSU) crystals in the synovial fluid of joints and in other tissues. The epidemiology of gout provides us with the understanding of the disease distribution and its determinants. In an attempt to update the knowledge on the topic, more recent research reports on the descriptive epidemiology of gout are reviewed in this article. The review describes clinical characteristics and case definitions of gout, including the Rome and New York diagnosis criteria of gout, '1977 American Rheumatism Association (ARA) criteria' and the 10 key propositions of the European League Against Rheumatism (EULAR) recommendations. Gout incidence, prevalence, morbidity and mortality, geographical variation of the disease, relevant risk factors for both the occurrence and outcome of gout and trends of the disease over time are then described. Difficulties in obtaining the information and data reported are also discussed.

6 Article Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals. 2018

Dai, Xiao-Juan / Tao, Jin-Hui / Fang, Xuan / Xia, Yuan / Li, Xiao-Mei / Wang, Yi-Ping / Li, Xiang-Pei. ·Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, No.17 LuJiang Road, Hefei, 230001, China. · Centre for Transplantation and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia. · Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, No.17 LuJiang Road, Hefei, 230001, China. lixiangpei55@126.com. ·Inflammation · Pubmed #30039428.

ABSTRACT: Acute gouty arthritis is the inflammation of joint tissues in the acute form due to the deposition of monosodium urate (MSU) crystals. Regulatory T cells (Tregs) and Th17 cells play an important role in the development and progression of inflammatory diseases. However, the expression and role of Tregs and Th17 cells are not clear in this disease. Here, we investigated the changes of Tregs, Th17 cells, and Treg/Th17 ratio in spleen, as well as the inflammatory cytokines in blood and joint tissue pathology in acute gouty arthritis rat induced by MSU. We found that both the percentages of Tregs and Th17 cells in spleen increased at an early stage (6 h). Tregs decreased at 12 and 24 h, and rise again at 48 and 72 h. However, Th17 cells reached its peak at 24 h, and then decreased after 48 h. Treg/Th17 ratio showed an initial decrease and then increase, and further reached its minimum value at 24 h. But the ratios of Treg/Th17at all times were lower than that of normal control. The level of serum cytokines (IL-1β, IL-6, IL-17, TNF-α, and IL-10) showed an opposite trend to Treg/Th17 ratio, except the level of TGF-β

7 Article Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study. 2018

Waldman, Boris / Ansquer, Jean-Claude / Sullivan, David R / Jenkins, Alicia J / McGill, Neil / Buizen, Luke / Davis, Timothy M E / Best, James D / Li, Liping / Feher, Michael D / Foucher, Christelle / Kesaniemi, Y Antero / Flack, Jeffrey / d'Emden, Michael C / Scott, Russell S / Hedley, John / Gebski, Val / Keech, Anthony C / Anonymous6130938. ·National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. · Centre Hospitalier Universitaire de Dijon, Dijon, France; Clinsciences, Dijon, France. · Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Chemical Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. · Sydney Medical School, University of Sydney, Sydney, NSW, Australia. · School of Medicine, University of Western Australia, Fremantle, WA, Australia. · Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Imperial College London, London, UK. · Lipid Clinic, Chelsea and Westminster Hospital Foundation Trust, London, UK; Department of Clinical and Experimental Medicine, University of Surrey, Surrey, UK. · Clinsciences, Dijon, France. · Oulu Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland. · South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia. · Endocrine Research Unit, Royal Brisbane Hospital, Brisbane, QLD, Australia. · Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand. · Department of Internal Medicine, Wairau Hospital, Blenheim, New Zealand. · National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. Electronic address: tony@ctc.usyd.edu.au. ·Lancet Diabetes Endocrinol · Pubmed #29496472.

ABSTRACT: BACKGROUND: Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. METHODS: In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up. We did a post-hoc analysis of recorded on-study gout attacks and plasma uric acid concentrations according to treatment allocation. The outcomes of this analysis were change in uric acid concentrations and risk of on-study gout attacks. The FIELD study is registered with ISRCTN, number ISRCTN64783481. FINDINGS: Between Feb 23, 1998, and Nov 3, 2000, 9795 patients were randomly assigned to fenofibrate (n=4895) or placebo (n=4900) in the FIELD study. Uric acid concentrations fell by 20·2% (95% CI 19·9-20·5) during the 6-week active fenofibrate run-in period immediately pre-randomisation (a reduction of 0·06 mmol/L or 1 mg/dL) and remained -20·1% (18·5-21·7, p<0·0001) lower in patients taking fenofibrate than in those on placebo in a random subset re-measured at 1 year. With placebo allocation, there were 151 (3%) first gout events over 5 years, compared with 81 (2%) among those allocated fenofibrate (HR with treatment 0·54, 95% CI 0·41-0·70; p<0·0001). In the placebo group, the cumulative proportion of patients with first gout events was 7·7% in patients with baseline uric acid concentration higher than 0·36 mmol/L and 13·9% in those with baseline uric acid concentration higher than 0·42 mmol/L, compared with 3·4% and 5·7%, respectively, in the fenofibrate group. Risk reductions were similar among men and women and those with dyslipidaemia, on diuretics, and with elevated uric acid concentrations. For participants with elevated baseline uric acid concentrations despite taking allopurinol at study entry, there was no heterogeneity of the treatment effect of fenofibrate on gout risk. Taking account of all gout events, fenofibrate treatment halved the risk (HR 0·48, 95% CI 0·37-0·60; p<0·0001) compared with placebo. INTERPRETATION: Fenofibrate lowered uric acid concentrations by 20%, and almost halved first on-study gout events over 5 years of treatment. Fenofibrate could be a useful adjunct for preventing gout in diabetes. FUNDING: None.

8 Article How is symptom flare defined in musculoskeletal conditions: A systematic review. 2018

Costa, Nathalia / Ferreira, Manuela L / Cross, Marita / Makovey, Joanna / Hodges, Paul W. ·Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Queensland 4072 Australia. · The University of Sydney, Institute of Bone and Joint Research, The Kolling Institute, Sydney Medical School, Sydney, Australia. · Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Queensland 4072 Australia. Electronic address: p.hodges@uq.edu.au. ·Semin Arthritis Rheum · Pubmed #29496226.

ABSTRACT: OBJECTIVE: To systematically review the definitions for "flare" in musculoskeletal conditions, the derivation processes, and validation of definitions for the 12 most burdensome musculoskeletal conditions. METHODS: A literature search was conducted in MEDLINE, EMBASE, CINAHL, AMED, PsycInfo and Lilacs to identify studies that investigated derivation or validation of a flare definition, which we considered as a phrase or group of domains. RESULTS: Reports of derivation of flare definitions were identified for 9/12 musculoskeletal conditions. Validation of flare definitions was initiated for 4/12. For each condition, different derivation and validation methods have been used, with variable levels of consumer involvement, and in some cases different groups have worked on the process in parallel. Although some flare definitions began simply as "symptom worsening" or "change in treatment", most evolved into multidimensional definitions that include: pain, impact on function, joint symptoms, and emotional elements. Frequently initial attempts to create phrase to define the term flare evolved into consensus on the breadth of domains involved. Validation has compared flare definitions/domains against measures of disease activity, clinicians' diagnosis, response to drug therapy, or a combination. CONCLUSION: This review suggests that greater characterisation and definition of flares in musculoskeletal conditions are linked to the inclusion of multiple perspectives, multifaceted domains and compound comparators for their validation. Further work is required to optimise and test the derived definitions for most musculoskeletal conditions. As some elements are disease-specific, flare definitions cannot be extrapolated to other conditions. Research regarding flare in back pain (most burdensome disease) is limited.

9 Article Effectiveness of an electronic patient-centred self-management tool for gout sufferers: a cluster randomised controlled trial protocol. 2017

Day, Richard O / Frensham, Lauren J / Nguyen, Amy D / Baysari, Melissa T / Aung, Eindra / Lau, Annie Y S / Zwar, Nicholas / Reath, Jennifer / Laba, Tracey / Li, Ling / McLachlan, Andrew / Runciman, William B / Buchbinder, Rachelle / Clay-Williams, Robyn / Coiera, Enrico / Braithwaite, Jeffrey / McNeil, H Patrick / Hunter, David J / Pile, Kevin D / Portek, Ian / WIlliams, Kenneth Mapson / Westbrook, Johanna I. ·Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. · St Vincent's Clinical School, St Vincent's Hospital, University of New South Wales, Sydney, Australia. · Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, Australia. · Centre for Health Informatics, Australian Institute of Health Innovation, Macquarie University, Sydney, Australia. · School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia. · School of Medicine, Western Sydney University, Sydney, Australia. · The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, Australia. · The Menzies Centre for Health Policy, Sydney Medical School, The University of Sydney, Sydney, Australia. · The Centre for Clinical Epidemiology and Evaluation, The University of British Columbia, Vancouver, Canada. · Faculty of Pharmacy and Centre for Education and Research on Ageing, University of Sydney, Sydney, Australia. · School of Health Sciences, University of South Australia, Adelaide, Australia. · Monash Department of Clinical Epidemiology, Cabrini Institute and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. · Institute of Bone and Joint Research, Kolling Institute, Sydney Medical School, The University of Sydney, Sydney, Australia. · Department of Rheumatology, Royal North Shore Hospital, Sydney, Australia. · Department of Medicine, Western Sydney University, Sydney, Australia. · Department of Rheumatology, Campbelltown Hospital, Sydney, Australia. · St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia. · Department of Rheumatology, St George Hospital, Sydney, Australia. ·BMJ Open · Pubmed #29042386.

ABSTRACT: INTRODUCTION: Gout is increasing despite effective therapies to lower serum urate concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with rates of less than 50% 1 year after initiation of ULT. Attempts to increase adherence in gout patients have been disappointing. We aim to evaluate the effectiveness of use of a personal, self-management, 'smartphone' application (app) to achieve target serum urate concentrations in people with gout. We hypothesise that personalised feedback of serum urate concentrations will improve adherence to ULT. METHODS AND ANALYSIS: Setting and designPrimary care. A prospective, cluster randomised (by general practitioner (GP) practices), controlled trial. PARTICIPANTS: GP practices will be randomised to either intervention or control clusters with their patients allocated to the same cluster. INTERVENTION: The intervention group will have access to the Healthy.me app tailored for the self-management of gout. The control group patients will have access to the same app modified to remove all functions except the Gout Attack Diary. PRIMARY AND SECONDARY OUTCOMES: The proportion of patients whose serum urate concentrations are less than or equal to 0.36 mmol/L after 6 months. Secondary outcomes will be proportions of patients achieving target urate concentrations at 12 months, ULT adherence rates, serum urate concentrations at 6 and 12 months, rates of attacks of gout, quality of life estimations and process and economic evaluations. The study is designed to detect a ≥30% improvement in the intervention group above the expected 50% achievement of target serum urate at 6 months in the control group: power 0.80, significance level 0.05, assumed 'dropout' rate 20%. ETHICS AND DISSEMINATION: This study has been approved by the University of New South Wales Human Research Ethics Committee. Study findings will be disseminated in international conferences and peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12616000455460.

10 Article Individualising the dose of allopurinol in patients with gout. 2017

Kannangara, Diluk R W / Graham, Garry G / Wright, Daniel F B / Stocker, Sophie L / Portek, Ian / Pile, Kevin D / Barclay, Murray L / Williams, Kenneth M / Stamp, Lisa K / Day, Richard O. ·Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. · School of Medical Sciences, University of New South Wales, Sydney, Australia. · School of Pharmacy, University of Otago, Dunedin, New Zealand. · Department of Rheumatology, St George Hospital, Sydney, Australia. · Department of Medicine, Western Sydney University, Campbelltown, Australia. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand. · St Vincent's Clinical School, University of New South Wales, Sydney, Australia. ·Br J Clin Pharmacol · Pubmed #28417592.

ABSTRACT: AIMS: The aims of the study were to: 1) determine if a plasma oxypurinol concentration-response relationship or an allopurinol dose-response relationship best predicts the dose requirements of allopurinol in the treatment of gout; and 2) to construct a nomogram for calculating the optimum maintenance dose of allopurinol to achieve target serum urate (SU) concentrations. METHODS: A nonlinear regression analysis was used to examine the plasma oxypurinol concentration- and allopurinol dose-response relationships with serum urate. In 81 patients (205 samples), creatinine clearance (CL RESULTS: The final plasma oxypurinol concentration-response relationship (U CONCLUSIONS: Plasma oxypurinol concentrations, CL

11 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.

12 Article Achieving serum urate targets in gout: an audit in a gout-oriented rheumatology practice. 2017

Corbett, Elizabeth J M / Pentony, Peta / McGill, Neil W. ·Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. · Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. · Department of Rheumatology, University of Sydney, Sydney, New South Wales, Australia. ·Int J Rheum Dis · Pubmed #28205336.

ABSTRACT: AIM: To assess the proportion of patients with gout who achieve target serum urate levels, the drug regime required and the reasons for failing to do so. METHODS: We reviewed the files of all patients with gout who presented to a gout-oriented rheumatology practice between January 2010 and September 2014. RESULTS: Two hundred and thirty patients agreed to commence urate lowering therapy (ULT); 73% achieved their urate target, including 74% with non-tophaceous gout (target ≤ 0.36 mmol/L) and 71% with tophi (target ≤ 0.30 mmol/L). Of the 62 who failed to reach target, in 61 it was due to non-adherence and in one due to inefficacy. CONCLUSION: Adherence remains the major challenge to successful long-term gout management.

13 Article Cross-sectional analysis of nutrition and serum uric acid in two Caucasian cohorts: the AusDiab Study and the Tromsø study. 2015

Zykova, Svetlana N / Storhaug, Hilde M / Toft, Ingrid / Chadban, Steven J / Jenssen, Trond G / White, Sarah L. ·Clinical Research Department, University Hospital of North Norway, 9038, Tromsø, Norway. svetlana.zykova@uit.no. · University of Tromsø-The Arctic University of Norway, Tromsø, Norway. hilde-merete.storhaug@uit.no. · Clinical Research Department, University Hospital of North Norway, 9038, Tromsø, Norway. ingrid.toft@unn.no. · University of Tromsø-The Arctic University of Norway, Tromsø, Norway. ingrid.toft@unn.no. · Royal Prince Alfred Hospital, Sydney, Australia. steve.chadban@sswahs.nsw.gov.au. · Sydney Medical School, University of Sydney, Sydney, Australia. steve.chadban@sswahs.nsw.gov.au. · University of Tromsø-The Arctic University of Norway, Tromsø, Norway. trond.g.jenssen@uit.no. · Oslo University Hospital, Oslo, Norway. trond.g.jenssen@uit.no. · Sydney Medical School, University of Sydney, Sydney, Australia. sarah.white@sydney.edu.au. ·Nutr J · Pubmed #25971955.

ABSTRACT: BACKGROUND: Hyperuricemia can lead to gout, and may be a risk factor for cardiovascular events, hypertension, diabetes and renal disease. There is well-known link between gout and habitual intake of meat and seafood, however the association between hyperuricemia and micro-and macro-nutrient intake has not been established. METHODS: We studied associations between intakes of food categories, macro-and micronutrients and serum uric acid (SUA) levels in two cross-sectional surveys of Caucasian adults deriving from different food traditions: Australian Diabetes, Obesity and Lifestyle Study 1999/00 (n=9734, age 25-91) and Tromsø Study 4 1994/95 (n = 3031, age 25-69). Dietary intake was calculated from self-administered Food Frequency Questionnaires. In some analyses we stratified according to abdominal obesity status and gender. RESULTS: In both cohorts, lower levels of SUA were found in subjects with higher consumption of carbohydrates, calcium and vitamin B2, while higher fat intake was associated with higher SUA, after adjustment for age, body mass index, estimated glomerular filtration rate, physical activity, total energy intake, use of diuretics, presence of hypertension, diabetes and gout. Among individual food items, high consumption of dairy products, high-fibre bread, cereals and fruits were associated with lower SUA in most subject groups while consumption of meat, eggs, beer and spirits, but not wine, with elevated levels. CONCLUSIONS: Healthy food choices with high intake of carbohydrates, dairy products, fiber and micronutrient-rich foods, and limited intake of fat, beer and spirits, might be recommended to prevent high SUA. Dietary factors seem to have qualitatively similar impact on SUA in obese and non-obese men and women from Australia and Norway.

14 Article Alcohol quantity and type on risk of recurrent gout attacks: an internet-based case-crossover study. 2014

Neogi, Tuhina / Chen, Clara / Niu, Jingbo / Chaisson, Christine / Hunter, David J / Zhang, Yuqing. ·Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Mass. Electronic address: tneogi@bu.edu. · Data Coordinating Center, Boston University School of Public Health, Boston, Mass. · Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Mass. · Kolling Institute, University of Sydney and Royal North Shore Hospital, New South Wales, Australia. ·Am J Med · Pubmed #24440541.

ABSTRACT: OBJECTIVES: Although beer and liquor have been associated with risk of incident gout, wine has not. Yet anecdotally, wine is thought to trigger gout attacks. Further, how much alcohol intake is needed to increase the risk of gout attack is not known. We examined the quantity and type of alcohol consumed on risk of recurrent gout attacks. METHODS: We conducted a prospective Internet-based case-crossover study in the US among participants with gout and who had at least one attack during the 1 year of follow-up. We evaluated the association of alcohol intake over the prior 24 hours as well as the type of alcoholic beverage with risk of recurrent gout attack, adjusting for potential time-varying confounders. RESULTS: This study included 724 participants with gout (78% men, mean age 54 years). There was a significant dose-response relationship between amount of alcohol consumption and risk of recurrent gout attacks (P <.001 for trend). The risk of recurrent gout attack was 1.36 (95% confidence interval [CI], 1.00-1.88) and 1.51 (95% CI, 1.09-2.09) times higher for >1-2 and >2-4 alcoholic beverages, respectively, compared with no alcohol consumption in the prior 24 hours. Consuming wine, beer, or liquor was each associated with an increased risk of gout attack. CONCLUSIONS: Episodic alcohol consumption, regardless of type of alcoholic beverage, was associated with an increased risk of recurrent gout attacks, including potentially with moderate amounts. Individuals with gout should limit alcohol intake of all types to reduce the risk of recurrent gout attacks.

15 Article OMERACT endorsement of measures of outcome for studies of acute gout. 2014

Singh, Jasvinder A / Taylor, William J / Dalbeth, Nicola / Simon, Lee S / Sundy, John / Grainger, Rebecca / Alten, Rieke / March, Lyn / Strand, Vibeke / Wells, George / Khanna, Dinesh / McQueen, Fiona / Schlesinger, Naomi / Boonen, Annelies / Boers, Maarten / Saag, Kenneth G / Schumacher, H Ralph / Edwards, N Lawrence. ·From Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Medicine, University of Otago, Wellington; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; SDG LLC, Cambridge, Massachusetts,; Duke University School of Medicine, Durham, North Carolina, USA, and Duke-National University of Singapore Graduate Medical School, Singapore; Schlosspark-Klinik Teaching Hospital of the Charité, University Medicine Berlin, Berlin, Germany; University of Sydney Institute of Bone and Joint Research and Department of Rheumatology, Royal North Shore Hospital, Sydney, Australia; Stanford University Division of Immunology and Rheumatology, Portolo Valley, California, USA; University of Ottawa, London, Ontario, Canada; University of Michigan Medical School, Ann Arbor, Michigan, USA; University of Auckland, Department of Molecular Medicine and Pathology, Grafton, Auckland, New Zealand; Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA; Maastricht University Medical Center, Division of Rheumatology, and Caphri Research Institute, University Maastricht; VU University Medical Center, Amsterdam, the Netherlands; University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Rheumatology, University of Florida, Gainsville, Florida, USA. ·J Rheumatol · Pubmed #24334651.

ABSTRACT: OBJECTIVE: To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements of truth, discrimination, and feasibility; and where future research efforts need to be directed. METHODS: Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted "don't know"). RESULTS: The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed. CONCLUSION: Measures of pain, joint swelling, joint tenderness, and patient global assessment in acute gout were endorsed at OMERACT 11. These measures should now be used in clinical trials of acute gout.

16 Article The pharmacokinetics of oxypurinol in people with gout. 2012

Stocker, Sophie L / McLachlan, Andrew J / Savic, Radojka M / Kirkpatrick, Carl M / Graham, Garry G / Williams, Kenneth M / Day, Richard O. ·Faculty of Pharmacy, University of Sydney, NSW, Australia. ·Br J Clin Pharmacol · Pubmed #22300439.

ABSTRACT: AIMS: Our aim was to identify and quantify the sources of variability in oxypurinol pharmacokinetics and explore relationships with plasma urate concentrations. METHODS: Non-linear mixed effects modelling was applied to concentration-time data from 155 gouty patients with demographic, medical history and renal transporter genotype information. RESULTS: A one compartment pharmacokinetic model with first order absorption best described the oxypurinol concentration-time data. Renal function and concomitant medicines (diuretics and probenecid), but not transporter genotype, significantly influenced oxypurinol pharmacokinetics and reduced the between subject variability in the apparent clearance of oxypurinol (CL/F(m)) from 65% to 29%. CL/F(m) for patients with normal, mild, moderate and severe renal impairment was 1.8, 0.6, 0.3 and 0.18 l h(-1), respectively. Model predictions showed a relationship between plasma oxypurinol and urate concentrations and failure to reach target oxypurinol concentrations using suggested allopurinol dosing guidelines. CONCLUSIONS: In conclusion, this first established pharmacokinetic model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopurinol therapy in gouty patients with various degrees of renal impairment.

17 Article Measurement of urinary oxypurinol by high performance liquid chromatography-tandem mass spectrometry. 2010

Stocker, Sophie L / Franklin, Michael E / Anderson, Jacqueline M / Pillans, Peter I / Williams, Kenneth M / McLachlan, Andrew J / Day, Richard O / Taylor, Paul J. ·Faculty of Pharmacy, University of Sydney, NSW 2006, Australia. ·J Chromatogr B Analyt Technol Biomed Life Sci · Pubmed #20702150.

ABSTRACT: Oxypurinol is the active metabolite of allopurinol which is used to treat hyperuricaemia associated with gout. Both oxypurinol and allopurinol inhibit xanthine oxidase which forms uric acid from xanthine and hypoxanthine. Plasma oxypurinol concentrations vary substantially between individuals and the source of this variability remains unclear. The aim of this study was to develop an HPLC-tandem mass spectrometry method to measure oxypurinol in urine to facilitate the study of the renal elimination of oxypurinol in patients with gout. Urine samples (50 microL) were prepared by dilution with a solution of acetonitrile/methanol/water (95/2/3, v/v; 2 mL) that contained the internal standard (8-methylxanthine; 1.5 mg/L), followed by centrifugation. An aliquot (2 microL) was injected. Chromatography was performed on an Atlantis HILIC Silica column (3 microm, 100 mm x 2.1mm, Waters) at 30 degrees C, using a mobile phase comprised of acetonitrile/methanol/50 mM ammonium acetate in 0.2% formic acid (95/2/3, v/v). Using a flow rate of 0.35 mL/min, the analysis time was 6.0 min. Mass spectrometric detection was by selected reactant monitoring (oxypurinol: m/z 150.8-->108.0; internal standard: m/z 164.9-->121.8) in negative electrospray ionization mode. Calibration curves were prepared in drug-free urine across the range 10-200 mg/L and fitted using quadratic regression with a weighting factor of 1/x (r(2) > 0.997, n=7). Quality control samples (20, 80, 150 and 300 mg/L) were used to determine intra-day (n=5) and inter-day (n=7) accuracy and imprecision. The inter-day accuracy and imprecision was 96.1-104% and <11.2%, respectively. Urinary oxypurinol samples were stable when subjected to 3 freeze-thaw cycles and when stored at room temperature for up to 6h. Samples collected from 10 patients, not receiving allopurinol therapy, were screened and showed no significant interferences. The method was suitable for the quantification of oxypurinol in the urine of patients (n=34) participating in a clinical trial to optimize therapy of gout with allopurinol.

18 Article Allopurinol for pain relief: more than just crystal clearance? 2009

Connor, Mark. ·Pain Management Research Institute, Kolling Institute, University of Sydney at Royal North Hospital St Leonards, Camperdown, New South Wales, Australia. markc@med.usyd.edu.au ·Br J Pharmacol · Pubmed #19133987.

ABSTRACT: Gout and pain are synonymous, and a study in this issue of the BJP reports a novel anti-nociceptive effect of allopurinol, the drug most commonly used to treat gout. Allopurinol works by inhibiting xanthine oxidase (XO), the enzyme responsible for converting hypoxanthine to uric acid which is deposited as crystals in the joints of gout sufferers. Hypoxanthine is a metabolite of, and a possible precursor to, adenosine. Schmidt et al., find that acute inhibition of XO with allopurinol produces a modest adenosine A(1) receptor-mediated anti-nociceptive effect in common tests of chemical and thermal nociception in mice. A concomitant increase in cerebrospinal fluid levels of adenosine supports their hypothesis that inhibiting XO increases adenosine levels via salvage from hypoxanthine. Elevating endogenous adenosine levels by inhibiting metabolism is a well-established strategy for producing anti-nociception in many preclinical models, but inhibiting XO is likely to be particularly beneficial in some chronic pain states because of the pro-nociceptive reactive oxygen species that are produced by XO activity. Thus, allopurinol may have unexpected benefits in pain associated with chronic inflammation, diabetes and vascular dysfunction.