***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practice d despite lack of proven benefit . We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and /or severity of acute gout flares . METHODS Patients starting allopurinol for crystal-proven chronic gouty arthritis were r and omized to receive colchicine 0.6 mg po bid or placebo in a r and omized , prospect i ve , double blind , placebo controlled trial . Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl . Treatment arms were analyzed regarding frequency of flares , likelihood of any flare or multiple flares , severity of flares on the visual analog scale ( VAS ) , and length of flares in days . RESULTS Forty-three subjects were studied . Subjects treated with colchicine experienced fewer total flares ( 0.52 vs 2.91 , p = 0.008 ) , fewer flares from 0 to 3 months ( 0.57 vs 1.91 , p = 0.022 ) , fewer flares 3 - 6 months ( 0 vs 1.05 , p = 0.033 ) , less severe flares as reported on VAS ( 3.64 vs 5.08 , p = 0.018 ) , and fewer recurrent gout flares ( p = 0.001 ) . Colchicine was well tolerated . CONCLUSION Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares , and reduces the likelihood of recurrent flares . Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data OBJECTIVE To determine if lowering of serum uric acid ( SUA ) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout . METHODS A prospect i ve study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl . We recalled all 57 patients who were available during 1999 . Patients were divided into 2 groups : Group A , with SUA still > 6 mg/dl , and Group B , with SUA < or = 6 mg/dl . A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals . RESULTS There were no differences between the groups in age , sex , duration of gout , or serum creatinine . Group A ( n = 38 ) had a mean of 6 attacks of gout for the recent year , those with tophi having the most frequent attacks . Among the 16 patients in this group who agreed to knee aspiration , monosodium urate ( MSU ) crystals were found in 14 , although they were asymptomatic at the time . Nineteen patients ( Group B ) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months . Nearly half of them had no attack of gout for 2 or more years , with a mean of 1 attack in the last year for the whole group . Three patients in whom tophi were found did not have major flares of gout within the past year . Knee joint aspiration was done on 16 asymptomatic patients . Seven ( 44 % ) still had MSU crystals present in their knees . Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years , although the frequency of attacks was less in those who continued colchicine . CONCLUSION A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years . The mechanisms for persistence in some patients , and whether such crystals have clinical implication s , are not known . Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks CONTEXT Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition . Pegloticase , monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase , was developed to fulfill this need . OBJECTIVE To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout . DESIGN , SETTING , AND PATIENTS Two replicate , r and omized , double-blind , placebo-controlled trials ( C0405 and C0406 ) were conducted between June 2006 and October 2007 at 56 rheumatology practice s in the United States , Canada , and Mexico in patients with severe gout , allopurinol intolerance or refractoriness , and serum uric acid concentration of 8.0 mg/dL or greater . A total of 225 patients participated : 109 in trial C0405 and 116 in trial C0406 . INTERVENTION Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion ( biweekly treatment group ) , pegloticase alternating with placebo at successive infusions ( monthly treatment group ) , or placebo ( placebo group ) . MAIN OUTCOME MEASURE Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6 . RESULTS In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group ( 47 % ; 95 % CI , 31%-62 % ) , 8 of 41 patients in the monthly group ( 20 % ; 95 % CI , 9%-35 % ) , and in 0 patients treated with placebo ( 0/20 ; 95 % CI , 0%-17 % ; P < .001 and < .04 for comparisons between biweekly and monthly groups vs placebo , respectively ) . Among patients treated with pegloticase in trial C0406 , 16 of 42 in the biweekly group ( 38 % ; 95 % CI , 24%-54 % ) and 21 of 43 in the monthly group ( 49 % ; 95 % CI , 33%-65 % ) achieved the primary end point ; no placebo-treated patients reached the primary end point ( 0/23 ; 95 % CI , 0%-15 % ; P = .001 and < .001 , respectively ) . When data in the 2 trials were pooled , the primary end point was achieved in 36 of 85 patients in the biweekly group ( 42 % ; 95 % CI , 32%-54 % ) , 29 of 84 patients in the monthly group ( 35 % ; 95 % CI , 24%-46 % ) , and 0 of 43 patients in the placebo group ( 0 % ; 95 % CI , 0%-8 % ; P < .001 for each comparison ) . Seven deaths ( 4 in patients receiving pegloticase and 3 in the placebo group ) occurred between r and omization and closure of the study data base ( February 15 , 2008 ) . CONCLUSION Among patients with chronic gout , elevated serum uric acid level , and allopurinol intolerance or refractoriness , the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months result ed in lower uric acid levels compared with placebo . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325195 BACKGROUND Steroids are the st and ard treatment for polymyalgia rheumatica . The efficacy of the c and i date drug methotrexate has not yet been demonstrated in controlled studies . OBJECTIVE To compare the efficacy and safety of prednisone plus methotrexate and prednisone alone in patients with polymyalgia rheumatica . DESIGN Multicenter r and omized , double-blind , placebo-controlled trial . SETTING 5 Italian rheumatology clinics . PATIENTS 72 patients with newly diagnosed polymyalgia rheumatica . MEASUREMENTS The proportion of patients no longer taking prednisone  , the number of flare-ups , and the cumulative prednisone dose after 76 weeks . INTERVENTION Prednisone dosage ( 25 mg/d ) was tapered to 0 mg/d within 24 weeks and was adjusted if flare-ups occurred . Oral methotrexate ( 10 mg ) or placebo , with folinic acid supplementation ( 7.5 mg ) , was given weekly for 48 weeks . RESULTS Twenty-eight of 32 patients in the methotrexate group and 16 of 30 patients in the placebo group were no longer taking prednisone  at 76 weeks ( P = 0.003 ) . The risk difference was 34 percentage points ( 95 % CI , 11 to 53 percentage points ) . Similar results were obtained after adjustment for C-reactive protein level and duration of symptoms in a multivariate model . Fifteen of 32 patients in the methotrexate group and 22 of 30 patients in the placebo group had at least 1 flare-up by the end of follow-up ( P = 0.04 ) . The median prednisone dose was 2.1 g in the methotrexate group and 2.97 g in the placebo group ( P = 0.03 ) . The rate and severity of adverse events were similar . LIMITATIONS Follow-up was short , and a high dose of folinic acid and a relatively high starting dosage of prednisone were used . Ten of 72 patients ( 14 % ) discontinued treatment or were lost to follow-up . CONCLUSIONS Prednisone plus methotrexate is associated with shorter prednisone treatment and steroid sparing . It may be useful in patients at high risk for steroid-related toxicity OBJECTIVE To evaluate the effect of local application of ice on duration and severity of  acute gouty arthritis . METHODS Nineteen patients with acute gout were enrolled and r and omized into 2 groups . Group A ( n = 10 ) received topical ice therapy , oral prednisone 30 mg PO tapered to 0 over 6 days and colchicine 0.6 mg/day . Group B was the control group ( n = 9 ) , given the same regimen but without the ice therapy . The patients were followed for one week . RESULTS The mean reduction in pain for those patients treated with ice therapy was 7.75 cm ( on 10 cm visual analog scale ) with st and ard deviation + /- 2.58 compared with 4.42 cm ( + /- SD 2.96 ) for the control group . Using a Wilcoxon rank-sum test there was a significant difference ( p = 0.021 ) in pain reduction between the ice therapy and control groups . Joint circumference and synovial fluid volume also tended to be more effectively reduced after one week of therapy in the ice group compared with controls , but these did not achieve statistical significance . CONCLUSION The group treated with ice had a significantly greater reduction in pain compared with the control group . Although the clinical improvement was impressive , due to the small sample size we could not show statistically significant improvement in all the variables that tended to suggest that effect was more than simply analgesic . Cold applications may be a useful adjunct to treatment of acute gouty arthritis OBJECTIVE A series of patients with polymyalgia rheumatica ( PMR ) who received the steroid-sparing combination therapy , prednisone and methotrexate ( MTX )  , underwent a long-term follow-up study at five years to investigate possible reductions of steroid-related side effects . Additional end-points were the number of patients still in need of steroid treatment , the cumulative steroid dose , and the number of flare-ups of PMR . PATIENTS AND METHODS Fifty-seven PMR patients who were enrolled in a double-blind placebo-controlled r and omised trial on the efficacy of MTX added to st and ard steroid treatment were review ed after 5 years . Information was collected on the patients ' previous health conditions or causes of death through a st and ardized question naire by direct visit , chart review , or interviews with relatives . RESULTS After 6 years from initiation of therapy , MTX-treated patients had lower ESR ( 17.1+/-9.7 mm/h vs. 26.8+/-22.9 mm/h , p=0.08 ) and CRP ( 2.7+/-2.3 mg/L vs. 10.2+/-16.4 mg/L , p=0.04 ) . 31 % MTX-treated patients were still on steroids in comparison with 39.3 % controls . The mean cumulative dosage of prednisone in MTX-treated patients was 2.6+/-3.8 g in comparison with 3.2+/-4.1 g for controls ( p=0.6 ) . PMR flare-ups were seen in 30.8 % of MTX-treated patients and in 44.4 % of controls ( p=0.39 ) . During the follow-up , 58 and 55 side effects were observed in MTX-treated patients and in controls , respectively . CONCLUSIONS 
    Output:
    
15 van der Veen MJ , Dinant HJ , van BoomaFrankfort C et al. Can methotrexate be used as a steroid-sparing agent in the treatment of polymyalgia rheumatica and giant cell arteritis ?