***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: BACKGROUND Febuxostat , a novel nonpurine selective inhibitor of xanthine oxidase , is a potential alternative to allopurinol for patients with hyperuricemia and gout . METHODS We r and omly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter ( 480 micromol per liter ) to receive either febuxostat ( 80 mg or 120 mg ) or allopurinol ( 300 mg ) once daily for 52 weeks ; 760 received the study drug . Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8 . The primary end point was a serum urate concentration of less than 6.0 mg per deciliter ( 360 micromol per liter ) at the last three monthly measurements . The secondary end points included reduction in the incidence of gout flares and in tophus area . RESULTS The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat , 62 percent of those receiving 120 mg of febuxostat , and 21 percent of those receiving allopurinol ( P<0.001 for the comparison of each febuxostat group with the allopurinol group ) . Although the incidence of gout flares diminished with continued treatment , the overall incidence during weeks 9 through 52 was similar in all groups : 64 percent of patients receiving 80 mg of febuxostat , 70 percent of those receiving 120 mg of febuxostat , and 64 percent of those receiving allopurinol ( P=0.99 for 80 mg of febuxostat vs. allopurinol ; P=0.23 for 120 mg of febuxostat vs. allopurinol ) . The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat , as compared with 50 percent in those receiving allopurinol ( P=0.08 for 80 mg of febuxostat vs. allopurinol ; P=0.16 for 120 mg of febuxostat vs. allopurinol ) . More patients in the high-dose febuxostat group than in the allopurinol group ( P=0.003 ) or the low-dose febuxostat group discontinued the study . Four of the 507 patients in the two febuxostat groups ( 0.8 percent ) and none of the 253 patients in the allopurinol group died ; all deaths were from causes that the investigators ( while still blinded to treatment ) judged to be unrelated to the study drugs ( P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group ) . CONCLUSIONS Febuxostat , at a daily dose of 80 mg or 120 mg , was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate . Similar reductions in gout flares and tophus area occurred in all treatment groups 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 Introduction The purpose of this study was to compare urate-lowering ( UL ) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate ( sUA ) ≥ 8.0 mg/dL in a six-month trial . Methods Subjects ( n = 2,269 ) were r and omized to febuxostat 40 mg or 80 mg , or allopurinol 300 mg ( 200 mg in moderate renal impairment ) . Endpoints included the proportion of all subjects with sUA < 6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA < 6.0 mg/dL. Safety assessment s included blinded adjudication of each cardiovascular ( CV ) adverse event ( AE ) and death . Results Comorbidities included : renal impairment ( 65 % ) ; obesity ( 64 % ) ; hyperlipidemia ( 42 % ) ; and hypertension ( 53 % ) . In febuxostat 40 mg , febuxostat 80 mg , and allopurinol groups , primary endpoint was achieved in 45 % , 67 % , and 42 % , respectively . Febuxostat 40 mg UL was statistically non-inferior to allopurinol , but febuxostat 80 mg was superior to both ( P < 0.001 ) . Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg ( 72 % ; P < 0.001 ) compared with febuxostat 40 mg ( 50 % ) or allopurinol ( 42 % ) , but febuxostat 40 mg showed greater efficacy than allopurinol ( P = 0.021 ) . Rates of AEs did not differ across treatment groups . Adjudicated ( APTC ) CV event rates were 0.0 % for febuxostat 40 mg and 0.4 % for both febuxostat 80 mg and allopurinol . One death occurred in each febuxostat group and three in the allopurinol group . Conclusions Urate-lowering efficacy  of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol ( 300/200 mg ) , which were comparable . In subjects with mild/moderate renal impairment , both febuxostat doses were more efficacious than allopurinol and equally safe . At the doses tested , safety of febuxostat and allopurinol was comparable . Clinical Trial Registration BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions The diurnal change of sUA and the effect of febuxostat on this change were investigated in 10 patients with gout and /or hyperuricemia . The diurnal sUA change after the last dose during the 4‐week treatment phase ( 20 mg , QD ) was almost the same as the pre‐treatment value . Considering the dose , the AUCobs and C max of unchanged drug in patients with gout and /or hyperuricemia were estimated to be similar to those of healthy male adults . The results show that a 6‐week treatment  with febuxostat is safe and well‐tolerated in the target patient population for this drug OBJECTIVE Gout affects approximately 1 - 2 % of the American population . Current options for treating hyperuricemia in chronic gout are limited . The purpose of this study was to assess the safety and efficacy of febuxostat , a nonpurine selective inhibitor of xanthine oxidase , in establishing normal serum urate ( sUA ) concentrations in gout patients with hyperuricemia ( > or=8.0 mg/dl ) . METHODS We conducted a phase II , r and omized , double-blind , placebo-controlled trial in 153 patients ( ages 23 - 80 years ) . Subjects received febuxostat ( 40 mg , 80 mg , 120 mg ) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after r and omization . The primary end point was the proportion of subjects with sUA levels < 6.0 mg/dl on day 28 . RESULTS Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level < 6.0 mg/dl at each visit ( P < 0.001 for each comparison ) . The targeted sUA level was attained on day 28 in 0 % of those taking placebo and in 56 % of those taking 40 mg , 76 % taking 80 mg , and 94 % taking 120 mg of febuxostat . The mean sUA reduction from baseline to day 28 was 2 % in the placebo group and 37 % in the 40-mg , 44 % in the 80-mg , and 59 % in the 120-mg febuxostat groups . Gout flares occurred with similar frequency in the placebo ( 37 % ) and 40-mg febuxostat ( 35 % ) groups and with increased frequency in the higher dosage febuxostat groups ( 43 % taking 80 mg ; 55 % taking 120 mg ) . During colchicine prophylaxis , gout flares occurred less frequently ( 8 - 13 % ) . Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups . CONCLUSION Treatment with febuxostat result ed in a significant reduction of sUA levels at all dosages . Febuxostat therapy was safe and well tolerated Objective . To determine longterm urate-lowering efficacy and clinical benefits and safety of therapy with febuxostat or allopurinol in subjects with gout . Methods . Subjects ( n = 1086 ) in this open-label extension study were assigned to fixed-dose daily urate-lowering 
    Output:
    
Although the incidence of gout flares requiring treatment may be increased in patients taking  febuxostat compared to placebo or allopurinol during early treatment , no such increase in gout flares was observed in the long-term follow-up study when compared to allopurinol .
Febuxostat at any dose was shown to be beneficial in achieving serum uric acid levels < 6.0 mg/dL and reducing serum uric acid levels in the period from baseline to final visit when compared to placebo and to allopurinol .