BackgroundHyperuricaemia, the biochemical precursor to gout, has been shown to be an independent risk factor for mortality from cardiovascular disease (CVD), although studies examining the clinical phenomenon of gout and risk of CVD mortality report conflicting results. This study aimed to produce a pooled estimate of risk of mortality from cardiovascular disease in patients with gout.DesignSystematic review and meta-analysis.MethodsElectronic bibliographic databases were searched from inception to November 2012, with results reviewed by two independent reviewers. Studies were included if they reported data on CVD mortality in adults with gout who were free of CVD at time of entry into the study. Pooled hazard ratios (HRs) for this association were calculated both unadjusted and adjusted for traditional vascular risk factors.ResultsSix papers, including 223,448 patients, were eligible for inclusion (all (CVD) mortality n = 4, coronary heart disease (CHD) mortality n = 3, and myocardial infarction mortality n = 3). Gout was associated with an excess risk of CVD mortality (unadjusted HR 1.51 (95% confidence interval, CI, 1.17–1.84)) and CHD mortality (unadjusted HR 1.59, 95% CI 1.25–1.94)). After adjusting for traditional vascular risk factors, the pooled HR for both CVD mortality (HR 1.29, 95% CI 1.14–1.44) and CHD mortality (HR 1.42, 95% CI 1.22–1.63) remained statistically significant, but none of the studies reported a significant association with myocardial infarction.ConclusionsGout increases the risk of mortality from CVD and CHD, but not myocardial infarction, independently of vascular risk factors.

Association of two key variants mapping to the MTHFR gene (C677T (rs1801133) and A1298C (rs1801131)) with response to methotrexate (MTX) remains controversial. We investigated these and other markers spanning the gene as predictors of MTX efficacy and adverse events in a UK rheumatoid arthritis (RA) patient cohort and performed a meta-analysis of the two key variants using all published data. The tagging single nucleotide polymorphisms (SNPs) were genotyped in 309 patients with well-defined outcomes to MTX treatment and 17 studies were included in the metaanalysis. No association of the SNPs tested was detected with MTX efficacy or toxicity in our UK cohort. After combining our data with previous studies by meta-analysis, the random effects pooled odds ratios (OR) for both C677T and A1298C showed no association with efficacy or toxicity for either of the SNPs (efficacy: OR ¼ 1.05 (95% confidence interval (CI) 0.83-1.32) and OR ¼ 0.81 (95% CI 0.53-1.24), respectively; toxicity: OR ¼ 1.38 (95% CI 0.90-2.12) and OR ¼ 1.19 (95% CI 0.80-1.78), respectively). The available evidence suggests that the MTHFR C677T and A1298C gene polymorphisms are not reliable predictors of response to MTX treatment in RA patients.

Objective. To examine the role of adenosine receptor 2a gene (ADORA2a) polymorphisms on outcome of MTX treatment in RA.Methods. Subjects included 309 RA patients with a defined response to MTX. Patients were included if they were (i) good responders (n = 147) (ESR <20 for >6/12 on stable dose of MTX) (ii) inefficacy failures (n = 101) (physician statement and failure to reduce ESR/CRP by 20%) or (iii) adverse event (AE) failures (n = 61) (verified by medical record review). AEs were sub-divided into gastrointestinal (GI) (n = 24), abnormal LFTs (n = 20) or other (n = 17). 8 single nucleotide polymorphisms (SNPs) within ADORA2a were genotyped using the Sequenom MALDI-TOF platform.Results. Five SNPs within ADORA2a were associated with stopping MTX for AEs (OR 2.1–3.07, P < 0.05 for all). Analysis by AE type showed that the association was specific for GI toxicity. No association was observed between ADORA2a and inefficacy outcomes.Conclusion. Genetic variation within ADORA2a is significantly associated with AEs on MTX, specifically GI AEs. Knowledge of the ADORA2a genotype may help to improve identification of patients at high risk of GI toxicity with MTX.

The patient, a 47-year-old man, presented with a 7-year history of forearm pain. He noted that his symptoms were worse after lifting or driving, and he was unable to drive for more than a few minutes without tingling and pain. His symptoms resolved with rest but recurred with physical activity. There was no history of trauma or joint swelling. A left carpal tunnel release had been performed 8 years previously. His medical history was otherwise unremarkable, there were no other current health problems, and he was not taking any medication. He had regularly trained with weights until his symptoms prevented this.Results of a general physical and neurologic examination were normal. His forearms were noted to be well developed and bulky. In view of his symptoms, dynamic (pre-and post-exercise) magnetic resonance imaging (MRI) was performed, and the resultant findings led to the measurement of compartment pressures, via needle intracompartmental pressure monitoring. The left forearm showed a resting pressure of 33 mm Hg, increasing to 144 mm Hg after several minutes of repetitive wrist flexion and extension (which also caused his symptoms to occur). After 2 minutes of rest the pressure decreased to 62 mm Hg. The patient underwent fasciotomy of the forearm extensors (at which the fascia was noted to be thickened), after which his symptoms resolved completely. He later underwent fasciotomy of the right forearm extensors and has resumed unlimited physical activity. Radiologic findingsMRI revealed classic features of a compartment syndrome. Following exercise, there were high signal

Quality is a multidimensional construct. Self-report evaluation of real patient learning is feasible, and could be capitalised on to promote reflective self-direction. The social and material context of learning is an important dimension of educational quality.