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Background to the diseaseGout is the most common cause of inflammatory arthritis worldwide. In UK general practice, the overall prevalence has increased from 1.4% in 1999 to 2.49% in 2012 1 , despite the availability of effective and potentially 'curative' urate-lowering drugs for more than 50 years and evidence-based British and European management guidelines for nearly a decade 2;3 . Clinical manifestations of gout resulting from monosodium urate (MSU) crystal deposition, include tophi, chronic arthritis, urolithiasis and renal disease as well as recurrent acute arthritis, bursitis and cellulitis. Gouty arthritis and tophi are associated with chronic disability, impairment of health-related quality of life (HRQOL) [4][5][6][7] , increased use of healthcare resources, and reduced productivity 8 . Gout is also frequently associated with co-morbidities such as obesity, dyslipidaemia, diabetes mellitus, chronic renal insufficiency, hypertension, cardiovascular disease, hypothyroidism, anaemia, psoriasis, chronic pulmonary diseases, depression and osteoarthritis 1 as well as with an increase in all-cause mortality (adjusted hazard ratio 1.13, 95% CI 1.08 to 1.18) and urogenital malignancy 1;9 . Sustained hyperuricaemia is the single most important risk factor for the development of gout. Hyperuricaemia occurs secondary to reduced fractional clearance of uric acid in more than 90% of patients with gout 10 . Age, male gender, menopausal status in females, impairment of renal function, hypertension and the co-morbidities that comprise the metabolic syndrome are all risk factors for incident Recently published guidelines include the 2012 American College of Rheumatology Guidelines for the Management of Gout 34,35 and the 2013 evidence-based recommendations for the diagnosis and management of gout by a multinational panel of rheumatologists participating in the 3e initiative 36 . Other National and Regional guidelines include the US Government 2014 Agency for Healthcare Research and Quality (AHRQ) Guidelines for the Diagnosis and Management of Gout 37,38 , and the Australian and New Zealand 39 and Portuguese 40 recommendations for the diagnosis and management of gout which arose from the 3e initiative. 36 Updated EULAR recommendations for the management of gout will be published in 2016. ObjectiveThis guideline aims to offer revised and updated, concise, patient-focussed, evidence-based, expert recommendations for the management of gout in the UK.

Scope and purpose of the guideline Need for a revised management guidelineThe British Society for Rheumatology/British Health Professionals in Rheumatology guideline for the management of gout was published in 2007 1 . A revised and updated guideline is now required because of the availability of new pharmaceutical treatment options; recent increases in the incidence, prevalence and severity of gout 2 ; continuing suboptimal management in both primary and secondary care 2,3 ; and better understanding of patient and provider barriers to effective care. 4,5 Objectives of the guidelineTo offer revised and updated, concise, patient-focussed, evidence-based, expert recommendations for the management of gout in the UK.

<p>The current climate trajectory in conjunction with agricultural intensification and the reliance on synthetic fertilisers, present further threat to the resilience of future food production through their contributions to soil degradation and consequent climatic feedback. Innovative sustainable agricultural technologies are needed to produce nutritious and equitable food products in line with the UN’s goal for Zero Hunger and sustainable development. Glacial Rock Flour (GRF) is a fine mineral rock dust, made available through the glacial abrasion of bedrock, and is often enriched in nutrients (e.g. Potassium, Phosphorous, Silicon, trace elements) but low in Nitrogen. It would therefore be a suitable soil fertility amendment for legume crops grown in acidic, nutrient poor soils often found in many mountainous regions (e.g. Hindu Kush Himalaya), where GRF is considered an alluvial ‘waste’ silting up dams and reservoirs. We have investigated the effect of GRF soil amendments in soil-plant mesocosms using a typical UK silt loam arable soil (pH~7) for cultivating red clover (<em>Trifolium pratense</em>) inoculated with <em>Rhizobium</em>. GRF from the Chhota Shigri (India) and Sólheimajökull (Iceland) glaciers were applied at 2 and 20 T/ha, while no GRF treatments included synthetic fertilizer applications of phosphorus (P), potassium (K) and P+K, and they were all compared against control red clover plants grown with no soil amendments. The nitrogen fixation capacity of red clover was estimated via <sup>15</sup>N natural abundance against a rye grass control (<em>Lolium perenne</em>) in two harvests on weeks 14 and 19. Both 20 T/ha GRF treatments appeared to stimulate fixed nitrogen yield compared to synthetic fertilizer treatments and control red clover plants, while the stimulation was more pronounced in the 2<sup>nd</sup> harvest as the soil nutrients were progressively depleted. Soil greenhouse gas fluxes over the growth period (weeks 4-14) were monitored by enclosing pots in sealed chambers. While no difference was observed in carbon dioxide fluxes between treatments, nitrous oxide (N<sub>2</sub>O) flux was negative for all red clover mesocosms with the N<sub>2</sub>O reduction being more prominent in both 20 T/ha GRF treatments towards the end of the first growth period (week 14). Gross N mineralization and nitrification were estimated in post-harvest soils from all the mesocosms using the isotope dilution method, while <sup>15</sup>N-N<sub>2</sub>O and <sup>15</sup>N-N<sub>2</sub> production were also measured after amending the soils with 98 at% <sup>15</sup>N-NH<sub>4</sub><sup>+</sup> and <sup>15</sup>N-NO<sub>3</sub><sup>-</sup><sub>. </sub> Gross N mineralization was not different between treatments, while nitrification was non-detectable, indicating a very tightly coupled N cycle between <em>Rhizobium </em>and red clover. However, when excess nitrate was applied, bacterial denitrification was active but the amendment of the soils with GRF appeared to reduce the production of N<sub>2</sub>O and promote complete denitrification to N<sub>2</sub>. Our novel study on the properties and application of GRF as a sustainable soil fertility amendment under a low nitrogen cropping system, holds promise that it can promote leguminous nitrogen fixation and a tightly-coupled N cycle that maximises N-use efficiency while mitigating N<sub>2</sub>O emissions by promoting complete denitrification.</p>

Background/Aims Initiating urate-lowering therapy for gout commonly triggers a gout flare and hence co-prescription of colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis is recommended. However, little is known about the incidence of adverse events associated with prophylaxis. We aimed to determine the risk of adverse events severe enough to warrant seeking healthcare associated with colchicine or NSAID prophylaxis when initiating allopurinol for gout. Methods We conducted two matched retrospective cohort studies, using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) datasets. Adults aged ≥18 years with a Read code for gout and a new allopurinol prescription between 1997 and 2016 were identified. We compared those prescribed (1) colchicine or (2) NSAID prophylaxis with those prescribed no prophylaxis, individually matched by age, sex and propensity to receive prophylaxis, to reduce the impact of confounding by indication. Adverse events were identified in CPRD and HES using Read and ICD10 codes respectively. Associations between colchicine or NSAID prophylaxis and the first occurrence of each outcome were investigated using weighted Cox proportional hazards models. CPRD Gold and Aurum datasets were analysed separately and then combined using 2-stage individual patient data meta-analysis. Results 13,945 individuals who initiated allopurinol with colchicine prophylaxis were matched to 13,945 who initiated without prophylaxis (mean age 63.62 years [95%CI 63.54, 63.70]; 78% male). Diarrhoea was the most common adverse event in the colchicine group, followed by nausea/vomiting, myocardial infarction (MI), neuropathy, myalgia, and bone marrow suppression (Table). Diarrhoea, MI, neuropathy, myalgia, and bone marrow suppression were significantly more common with colchicine prophylaxis compared with no prophylaxis. 22,880 individuals who initiated allopurinol with NSAID prophylaxis were matched to 22,880 who initiated without prophylaxis (mean age 63.34 years [95%CI 63.26, 63.42]; 78% male). Angina, acute kidney injury, MI, and peptic ulcer disease were significantly more common with NSAID prophylaxis than without (Table). Conclusion Gastrointestinal, cardiorenal, myoneuropathic, and haematological adverse events were associated with prophylaxis, although absolute event rates were low. This information can inform treatment decisions and choice of colchicine or NSAID for prophylaxis when initiating allopurinol. Disclosure E. Roddy: None. R. Bajpai: None. H. Forrester: None. R. Partington: None. C.D. Mallen: Grants/research support; Keele University School Of Medicine has received funding from BMS to support a non-pharmacological atrial fibrillation screening study. L. Clarson: None. N. Padmanabhan: None. R. Whittle: None. S. Muller: None.