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1.  A Review of Uric Acid, Crystal Deposition Disease, and Gout 
Advances in Therapy  2014;32:31-41.
There has been increased interest in gout in both academic and clinical practice settings. Several reasons may explain this. The prevalence of both hyperuricemia and gout has risen in the last decades in developed countries and therefore the burden of gout has increased. The association of hyperuricemia and gout with cardiovascular outcomes and the opportunity of further benefits of intervention on hyperuricemia have been recently highlighted in the literature. Imaging techniques have proven to be useful for detection of urate deposition, even prior to the first clinical symptoms, enabling the evaluation of the extent of deposition and providing objective measurement of crystal depletion during urate-lowering treatment. Treating to target is increasingly used as the approach to treatment of diverse diseases. Therefore, different targets have been recommended for different stages of the burden of disease and for different stages of treatment. The final strategic target, to which any effort should be taken into consideration, is to completely dissolve urate crystals in tissues and therefore avoid further symptoms and structural damage of involved musculoskeletal structures. In summary, evidence suggest that an early approach to the treatment of gout and associated comorbidities is advisable, that new imaging techniques may help to evaluate both the burden of deposition and response to urate-lowering treatment in selected patients, and finally that the final strategic objective of healthcare for patients with gout is to completely resolve urate crystal deposits.
Electronic supplementary material
The online version of this article (doi:10.1007/s12325-014-0175-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s12325-014-0175-z
PMCID: PMC4311063  PMID: 25533440
Crystal deposition disease; Gout; Hyperuricemia; Uric acid
2.  The burden of disease in Spain: results from the global burden of disease study 2010 
BMC Medicine  2014;12(1):2.
Background
We herein evaluate the Spanish population’s trends in health burden by comparing results of two Global Burden of Diseases, Injuries, and Risk Factors Studies (the GBD studies) performed 20 years apart.
Methods
Data is part of the GBD study for 1990 and 2010. We present results for mortality, years of life lost (YLLs), years lived with disability, and disability-adjusted life years (DALYs) for the Spanish population. Uncertainty intervals for all measures have been estimated.
Results
Non-communicable diseases accounted for 3,703,400 (95% CI 3,648,270–3,766,720) (91.3%) of 4,057,400 total deaths, in the Spanish population. Cardiovascular and circulatory diseases were the main cause of mortality among non-communicable diseases (34.7% of total deaths), followed by neoplasms (27.1% of total deaths). Neoplasms, cardiovascular and circulatory diseases, and chronic respiratory diseases were the top three leading causes for YLLs. The most important causes of DALYs in 2010 were neoplasms, cardiovascular and circulatory diseases, musculoskeletal disorders, and mental and behavioral disorders.
Conclusions
Mortality and disability in Spain have become even more linked to non-communicable diseases over the last years, following the worldwide trends. Cardiovascular and circulatory diseases, neoplasms, mental and behavioral disorders, and neurological disorders are the leading causes of mortality and disability. Specific focus is needed from health care providers and policy makers to develop health promotion and health education programs directed towards non-communicable disorders.
doi:10.1186/s12916-014-0236-9
PMCID: PMC4276068
Disability-adjusted life years; Global Burden of Diseases, Injuries, and Risk Factors Studies; Spain; Mortality; Years lived with disability; Years of life lost
3.  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 
BMJ Open  2014;4(7):e005354.
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).
doi:10.1136/bmjopen-2014-005354
PMCID: PMC4120410  PMID: 25011991
Cardiovascular Safety; Clinical Trial; Allopurinol; Febuxostat
6.  Long-term therapy for chronic gout results in clinically important improvements in the health-related quality of life: short form-36 is responsive to change in chronic gout 
Rheumatology (Oxford, England)  2010;50(4):740-745.
Objective. Short Form-36 (SF-36) is a validated outcome measure to assess health-related quality of life (HRQOL) in patients with gout. We assessed responsiveness to change of SF-36 in patients with gout.
Methods. SF-36 was administered at baseline and at yearly intervals. We assessed the minimal clinically important differences (MCIDs) at the first and second year. We also assessed the responsiveness to change (effect size) and interpreted it based on Cohen’s criteria. We modelled the improvement (defined as ≥MCID) in SF-36 scales and summary scores. Covariates included age, presence of tophi, comorbidities, baseline joint involvement, baseline serum urate, change in serum urate and the number of flares from baseline to 12 months.
Results. Of 99 subjects, 96 were male, mean age was 57.1 years, disease duration was 8.2 years and 40.4% had tophi. Ninety-two patients were treated with urate-lowering therapy (ULT) and daily colchicine, and seven were only on colchicine. Baseline mean serum urate level was 8.9 mg/dl and mean number of flares was 4.7 over last year. ULTs were associated with reduction in serum uric acid and number of flares (P < 0.001 for both) over 12 months. Therapy was associated with 22–70% of the patients achieving MCID in SF-36 scores at 12 months. Effect size estimates ranged from negligible to large (SF-36 mental component summary 0.08–bodily pain 1.09). Reduction in flares independently predicted improvements in three SF-36 physical scales (P = 0.001–0.06). Improvement in SF-36 scores was maintained at 2 years.
Conclusion. In our real-life observational cohort, chronic urate lowering therapy and colchicine was associated with clinically meaningful improvements in HRQOL at 1 year and then maintained at 2 years. SF-36, especially physical domains and physical component summary, are responsive to change in gout.
doi:10.1093/rheumatology/keq346
PMCID: PMC3060621  PMID: 21147824
Gout; Health-related quality of life; Quality of life; Flares; Urate-lowering therapy; Minimal clinically important differences; Minimally important differences; Short Form-36, Gout prophylaxis
7.  Gout. Imaging of gout: findings and utility 
Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic joint inflammation. Chronic gout is associated with changes in joint structures that may be evaluated with diverse imaging techniques. Plain radiographs show typical changes only in advanced chronic gout. Computed tomography may best evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate soft tissues, synovial membrane thickness, and inflammatory changes. Ultrasonography is a tool that may be used in the clinical setting, allowing evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Also ultrasound-guided puncture may be useful for obtaining samples for crystal observation. Any of these techniques deserve some consideration for feasibility and implementation both in clinical practice and as outcome measures for clinical trials. In clinical practice they may be considered mainly for evaluating the presence and extent of crystal deposition, and structural changes that may impair function or functional outcomes, and also to monitor the response to urate-lowering therapy.
doi:10.1186/ar2687
PMCID: PMC2714107  PMID: 19591633

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