Ian Ford

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).

OBJECTIVE: Neighborhood-level socioeconomic deprivation has been associated with poor cognitive function pertaining to language and the executive control. Few studies have explored the cortical morphology of regions most commonly associated with these functions. The aim of this study was to examine the association between neighborhood-level deprivation and the morphology of cortical regions associated with language and executive control in adults. METHODS: Using a cross-sectional study design, we compared the cortical morphology of 42 neurologically healthy adult men from the least deprived and most deprived neighborhoods of Glasgow. We performed surface-based morphometry on 3-T structural magnetic resonance imaging (MRI) images to extract the cortical morphology--volume, thickness (CT), and surface area (SA) of regions commonly associated with language and executive control. Cortical morphology was compared between the two groups. We used mediation analysis to examine whether cardiometabolic risk factors mediated the relationship between deprivation status and cortical morphology. RESULTS: Intracranial volume and mean total CT did not differ between groups. The deprived group had significantly smaller left posterior parietal cortex SA (Cohen d = 0.89) and fusiform cortex SA (Cohen d = 1.05). They also had thinner left Wernicke's area (Cohen d =0.93) and its right homologue (Cohen d = 1.12). Among the cardiometabolic markers, a composite factor comprising inflammatory markers mediated the relationship between deprivation status and Wernicke's area CT. CONCLUSIONS: A group of neurologically healthy men from deprived neighborhoods showed significantly smaller cortical morphology--both SA and CT--in regions of the brain pertaining to language and executive function. We provide additional evidence of a relationship between socioeconomic deprivation and cortical morphology.

The variability of eight linear and five angular dimensions measured on 124 lateral skull radiographs of 10-year-old boys was assessed by means of Bartlett's test for homogeneity of variances and Pitman's test for the comparison of correlated standard deviations. The linear dimensions which demonstrated the greatest variability within the four constituent Angle classes (N = 31) were mandibular body length, total cranial base length, total mandibular length and lower face height. The dimensions which demonstrated the least intra-group but greatest inter-group variability were maxillary length and Angle SNB. The Class II division 2 group exhibited the greatest variation in skeletal morphology; it is therefore postulated that its etiology is mainly dentoalveolar and soft tissue in origin.

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