***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: In an open trial of three months ' duration the clinical effect of tolfenamic acid , a new nonsteroid anti-inflammatory analgesic , was found to be good in 85 patients suffering from rheumatoid arthritis . Both subjective and objective parameters clearly improved , and corticoid therapy could be ab and oned by 21 % of the patients . Tolfenamic acid was for the most part better than or as good as , the previous medication by which the disease had been brought to a stabile state . Side-effects were mild , no severe adverse reactions were observed which could be definitely attributed to tolfenamic acid We conducted a case-control study in five general hospitals in the region of Antwerp , study ing 161 patients ( 102 men , 59 women ) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from ' erosive lesions ' ( peptic oesophagitis , gastric erosions , gastric ulcer(s ) , or duodenal ulcer(s ] . There was a highly significant difference between cases and control subjects in the use of non-steroidal anti-inflammatory drugs ( NSAIDs , excluding aspirin ) ( odds ratio 7.4 , p less than 0.001 ; 95 % confidence interval odds ratio 3.7 to 14.7 ) . There also was a significant difference in the use of aspirin  ( odds ratio 2.2 , p = 0.025 ; 95 % CI odds ratio 1.3 to 4.0 ) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease ( odds ratio 5.5 , p less than 0.001 ; 95 % CI odds ratio 3.2 to 9.6 ) . There was no significant difference in the use of other drugs , paracetamol and corticosteroids  in particular , nor in the use of alcohol or tobacco . The patient group using NSAIDs  was older , had more women , and had a higher mortality than the group not using NSAIDs . Among patients with bleeding gastric or duodenal ulcer(s ) , NSAID users were not more or less likely to have had symptoms of peptic ulcer disease , and had no higher frequency of multiple gastric or duodenal ulcers . The attributable risk for NSAID use was 0.30 ( 95 % CI 0.23 to 0.37 ) and for aspirin use 0.14 ( 95 % CI 0.08 to 0.20 ) Summary A r and omised double-blind placebo-controlled crossover study evaluated the effects of  zileuton 600 mg 4 times daily on the pharmacokinetics of prednisolone after a single 40 mg oral dose of prednisone . The effects of the single prednisone dose on the steady-state pharmacokinetics of zileuton were also evaluated . Multiple doses of zileuton had no significant effects on mean peak plasma concentration ( Cmax ) , time to Cmax(tmax ) , or area under the plasma concentrationtime curve from 0 to infinity ( AUC0-∞ ) values for prednisolone after oral administration of prednisone 40 mg . A slight but statistically significant increase in the mean half-life ( t½ ) of prednisolone  was detected with zileuton + prednisone administration compared with prednisone + placebo ( from 2.8 to 2.9 hours ) ; however , this change was of no clinical relevance .Mean Cmax values of zileuton after coadministration with prednisone were similar to those of zileuton alone . While the single 40 mg dose of prednisone result ed in a slight but statistically significant decrease in the mean zileuton AUC value from 0 to 6 hours ( AUC0–6 ) [ from 23 to 20 mg/L·h ] and a reduction in tmax ( from 2.3 to 1.7 hours ) , these results were not considered to be clinical ly significant . Therefore , it is concluded that zileuton and prednisone may be coadministered with minimal risk of a clinical ly significant pharmacokinetic interaction BACKGROUND & AIMS Epidemiologic data indicate that the risk of nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal ( GI ) clinical events varies based on patients ' clinical characteristics . The authors determined risk factors for NSAID-related clinical upper GI events and the event rates , absolute risk reductions , and numbers needed to treat for individual risk factors for a nonselective NSAID and a selective cyclooxygenase 2 inhibitor in a double-blind outcomes trial . METHODS Eight thous and seventy-six rheumatoid arthritis patients aged > or=50 years ( or > or=40 on corticosteroid therapy ) were r and omly assigned to rofecoxib 50 mg daily or naproxen 500 mg twice daily for a median of 9 months . The development of clinical upper GI events ( bleeding , perforation , obstruction , and symptomatic ulcer identified on clinical ly indicated work-up ) was assessed . RESULTS Significant risk factors included prior upper GI events , age > or=65 , and severe rheumatoid arthritis ( RR , 2.3 - 3.9 ) . Patients administered naproxen who had prior upper GI complications or who were aged > or=75 years had 18.84 or 14.46 events per 100 patient-years , and the risk of events remained constant over time . The reduction in events with rofecoxib was similar in high- and low-risk subgroups ( RR , 0.31 - 0.68 ) . The number needed to treat with rofecoxib instead of naproxen to avert 1 GI event was 10 - 12 in highest risk patients ( prior event , age > or=75 years , or severe rheumatoid arthritis ) , 17 - 33 in patients with other risk factors , and 42 - 106 in low-risk patients . CONCLUSIONS NSAID-related GI events increase dramatically with risk factors such as prior events or older age . Ten to twelve high-risk patients need to be treated with a protective strategy such as the selective cyclooxygenase 2 inhibitor , rofecoxib , to avert a clinical GI event BACKGROUND & AIMS Epidemiologic studies suggest nonsteroidal anti-inflammatory drugs ( NSAIDs ) increase the risk for lower gastrointestinal ( GI ) clinical events , but data from prospect i ve trials are lacking . Cyclooxygenase (COX)-2-selective inhibitors decrease upper GI clinical events but the effect on lower GI events has not been determined . We performed a post hoc analysis of serious lower GI clinical events with a nonselective NSAID and a COX-2-selective agent in a prospect i ve , double-blind , r and omized GI outcomes trial . METHODS A total of 8076 rheumatoid arthritis patients 50 years or older ( or 40 years or older on corticosteroid therapy ) expected to require NSAIDs for 1 year or greater were r and omly assigned to naproxen 500 mg twice daily or rofecoxib 50 mg daily . The rate of serious lower GI clinical events , defined as bleeding with a 2 g/dL drop in hemoglobin or hospitalization , or hospitalization for perforation , obstruction , ulceration , or diverticulitis , was determined . RESULTS The rate of serious lower GI events per 100 patient-years was 0.41 for rofecoxib and 0.89 for naproxen ( relative risk , 0.46 ; 95 % confidence interval [ CI ] , 0.22 - 0.93 ; P = 0.032 ) . Serious lower GI events accounted for 39.4 % of all serious GI events ( complicated upper GI event or lower GI event ) among patients taking naproxen and 42.7 % among those taking rofecoxib . CONCLUSIONS Serious lower GI events occurred at a rate of 0.9 % per year in rheumatoid arthritis patients taking the nonselective NSAID naproxen , accounting for nearly 40 % of the serious GI events that developed in these patients . Serious lower GI events were 54 % lower with the use of the selective COX-2 inhibitor rofecoxib OBJECTIVE It has been suggested that rheumatoid arthritis ( RA ) itself may be a risk factor for adverse gastrointestinal ( GI ) events , but this hypothesis has not been studied in a large sample , nor has the effect of time on risk factors been studied . We investigated rates and risk factors for GI events in RA and osteoarthritis ( OA ) and assessed the additional risks conveyed by having RA . METHODS A prospect i ve study of patients with OA and RA from a single center was undertaken using question naires mailed at 6 month intervals . The relationship between drug therapy and GI events was assessed in the same 6 month time frame . Over 13 years of biannual assessment s , 2,131 patients were studied for serious GI events and adverse GI symptoms during 9,621 patient-years of observation . RESULTS The incidence rate ( IR ) for GI hospitalization was 1.56 and 1.28 per 100 patient-years , and for GI bleeding or perforation was 0.50 and 0.58 for RA and OA , respectively . After controlling for age , sex , nonsteroidal antiinflammatory drug ( NSAID ) and steroid use , the incidence rate ratio ( IRR ) for RA versus OA did not differ for hospitalization [ IRR 1.07 ( 95 % CI 0.66 , 1.74 ) ] or for bleeding or perforation [ IRR 0.63 ( 95 % CI 0.29 , 1.35 ) ] . In multivariate analyses for both groups combined , the IRR was 2.95 ( 2.05 , 4.24 ) for prednisone use , 1.41 ( 1.08 , 1.85 ) for NSAID use , and 1.46 ( 1.22 , 1.74 ) for every 10 year increase in age . In additional multivariate models , Health Assessment Question naire disability was also a significant risk factor . During the study period , the odds of  NSAID use decreased 2.94 times per 10 year period , while the odds of prednisone use increased by 1.49 . Dysphagia [ IRR 1.11 ( 1.00 , 1.24 ) ] , anorexia [ IRR 1.13 ( 1.03 , 1.23 ) ] , nausea [ IRR 1.13 ( 1.04 , 1.25 ) ] , heartburn [ IRR 1.12 ( 1.05 , 1.19 ) ] , vomiting [ IRR 1.20 ( 1.02 , 1.42 ) ] , peptic ulcer symptoms [ IRR 1.20 ( 1.11 , 1.29 ) ] , and abdominal pain [ IRR 1.11 ( 1.01 , 1.22 ) ] were associated with NSAID use , but not with steroids . CONCLUSION Patients with RA and OA do not differ in the rates and risk factors for GI hospitalizations and symptoms after controlling for age , steroid use , NSAID use , or ( for OA ) body mass index . Prednisone is a more important risk factor among patients with RA than NSAID A group of 50 patients with rheumatoid arthritis ( half of whom received prednisone for 12 weeks before and then during the study ) participated in a double-blind trial evaluating the efficacy and safety of 3 dosages of naproxen ( 125 , 250 , and 500 mg b.i.d . ) . Increasing dosages of naproxen were associated with increasing levels of therapeutic response and increasing serum levels of naproxen with no evidence of toxicity .  Corticosteroid patients did not exhibit the same pattern of increasing levels of efficacy . The study demonstrates a dosage-related increasing pattern of efficacy for naproxen up to 1,000 mg/day , a pattern not yet demonstrated for the other non-steroidal antinflammatory drugs A double-blind placebo controlled trial was carried out in 14 steroid-dependent patients with rheumatoid arthritis to assess the effectiveness and steroid-sparing action of flurbiprofen over a 4-week period . During the first week , the patients ' steroid dosage was stabilized at the minimum necessary to control symptoms . They were then treated with either 100 mg flurbiprofen or placebo 3-times daily for 3 weeks . Steroid dosage was initially reduced to 50 % of the stabilized dose and reduced further if practicable , depending on therapeutic response . Clinical assessment s were made , at weekly intervals , of pain , swelling , tenderness , erythema , range of movement , grip strength , walking time , and duration of morning stiffness . Joint scanning of 99mTc uptake was also measured before and after treatment in 11 patients . The results showed that whereas 3 out of 6 patients on placebo has distinct inflammatory flare-up , this did not occur in any of the 8 patients on flurbiprofen . Moreover , 3 of the flurbiprofen group showed improvement and a further reduction in steriod dosage was possible in 3 patients . Improvements in joint scans correlated well with the clinical findings in 6 of 11 patients Background The risk factors that precipitate the 
    Output:
    
CONCLUSIONS The use of NSAID and low dose of steroids in patients with musculoskeletal diseases does not seem to increase the risk of gastrointestinal adverse events