***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 a multicentre double-blind cross-over trial , oral diclofenac at a dose of 50 mg to 100 mg was compared to placebo in the acute treatment of  migraine attacks . A hundred and seven patients suffering from migraine without aura were included , and 91 were analysed for efficacy ;  they had to treat four successive attacks-two with diclofenac and two with placebo . Diclofenac was significantly more effective than placebo ( p < 0.05 ) on the main judgement parameter , which was the number of attacks aborted within 2 h of drug intake , as well as on the following secondary parameters : the necessity for an escape medication and the evaluation of global efficacy .  Diclofenac was well tolerated . This trial demonstrates the efficacy of diclofenac in the acute treatment of migraine attacks . It confirms the good clinical relevance of the main judgement parameter chosen , which is the one recommended by the International Headache Society , but appears to be a severe one in terms of successes The efficacy of ibuprofen in comparison with that of placebo was assessed in the treatment of acute migraine attacks . The material consisted of 40 migraine patients . Each treatment period continued for five migraine attacks . The initial dose of ibuprofen was 800 mg , with additional 400 mg taken if and when needed . The mean duration of migraine attacks treated with ibuprofen was significantly shorter than the duration of migraine attacks treated with placebo .  Need for supplementary medication was also significantly lower in the ibuprofen-treated migraine attack group . Ibuprofen was well tolerated and no marked side effects were reported during the trial Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size STUDY OBJECTIVES By evaluating the efficacy of metoclopramide alone and in combination with ibuprofen versus placebos , this study was design ed to both evaluate the efficacy of metoclopramide and eluci date its mechanism of action in the treatment of  migraine headache .  DESIGN The study was conducted over a two-year period and was a r and omized , double-blind , placebo-controlled study . SETTING An urban teaching hospital . PARTICIPANTS Patients enrolled were at least 18 years old and had recurring headaches with one or more of the following characteristics : unilateral , preceded by neurologic symptoms , significant nausea and vomiting , or mood changes and photophobia . INTERVENTION Ten milligrams of metoclopramide or an equal volume of IV normal saline was given and 600 mg of ibuprofen or identical-appearing placebo was given orally at time 0 . Patients rated their pain and nausea at time 0 , 30 minutes , and 60 minutes using visual-analog scales . RESULTS The differences in pain and nausea scores for the metoclopramide + placebos group versus the other three groups were tested using exact nonparametric ( Mann-Whitney ) statistical procedures . The metoclopramide + placebos group had significantly better relief of pain compared with the placebos + ibuprofen and placebos + placebos groups . The metoclopramide + placebos group had significantly better relief of nausea than the ibuprofen + placebos group ; nausea scores for the placebos + placebos group could not be analyzed due to excessive variance from the other groups at baseline . The differences between the metoclopramide + placebos group and the metoclopramide + ibuprofen group were not statistically significant with regard to either pain or nausea . CONCLUSION Metoclopramide is efficacious in the treatment of both the pain and nausea of migraine headache . This is a direct action that is not dependent on the concomitant administration of another agent OBJECTIVE A phase II , r and omized , double-blind , crossover study was design ed to evaluate the efficacy of 100-mg diclofenac sodium softgel ( formulated using ProSorb technology ) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks . BACKGROUND Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies . A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain , and may have advantages in migraine treatment . In addition , caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics . The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications ( ie , aspirin , acetaminophen , ibuprofen , and ergotamine ) . METHODS The 3-period crossover study was design ed to compare diclofenac softgel 100 mg , diclofenac softgel 100 mg plus caffeine 100 mg , and placebo in the acute treatment of migraine . Subjects treated one moderate or severe attack with each study medication . The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo . Though the sample size estimate required that 72 subjects treat 3 separate attacks , 51 subjects treated 1 migraine attack , 44 treated 2 attacks , and 39 treated 3 attacks . Results .-In the placebo group , 6 ( 14 % ) of 43 subjects reported headache relief at 60 minutes versus 12 ( 27 % ) of 45 subjects in the diclofenac softgel group , and 19 ( 41 % ) of 46 subjects in the diclofenac softgel plus caffeine group . Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo ( odds ratio , 4.2 ; 95 % confidence interval , 1.3 to 13.7 ) . Rescue medication was used by 27 ( 63 % ) of 43 subjects treated with placebo , 15 ( 33 % ) of 45 subjects treated with diclofenac softgel , and 14 ( 30 % ) of 46 subjects treated with diclofenac softgel plus caffeine . This result is highly statistically significant ( chi22= 11.56 , P=.003 ) . Both the diclofenac plus caffeine ( P < .03 ) and diclofenac only ( P < .03 ) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes . CONCLUSIONS The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes . Diclofenac softgel alone did not differ significantly from placebo , perhaps due to limits in sample size . Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels A double-blind , cross-over , r and omized study of acute migraine attack compared treatment results of naproxen with that of placebo . Each treatment period continued for either three months or six migraine attacks , whichever occurred first . The initial dose of naproxen was 750 mg , with additional 250–500 mg doses taken if and when required , to a maximum of five 250 mg tablets within a period of 24 h in each migraine attack . Forty-one patients were enrolled in the study ; they had all experienced at least two but not more than eight migraine attacks a month during the preceding year . Thirty-two patients completed the two treatment periods . Naproxen was statistically significantly superior to placebo in reducing the severity of head pain , nausea , and photophobia ; in shortening the duration of head pain , nausea , vomiting , photophobia , and lightheadedness ; in diminishing the frequency of vomiting ; and in decreasing the need for escape medication . Both patient and physician treatment preferences significantly favoured naproxen .  Nine side effects were experienced by seven patients while receiving placebo and seven by five patients during naproxen treatment . Mild gastrointestinal discomfort was the main complaint . Only one patient withdrew from treatment because of a side effect , which occurred while receiving placebo Background : Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action . Its role in migraine has not been systematic ally evaluated . Aim : To study the efficacy of rofecoxib in migraine . Method : In a r and omised placebo controlled trial rofecoxib 25 mg , ibuprofen 400 mg , and placebo were compared regarding their efficacy in relieving  acute migraine attack . Migraine patients with 2–6 attacks per month were recruited .  Headache severity , functional disability , and severity of associated symptoms were grade d on a 0–3 scale . The primary endpoint was pain relief at two hours . Relief of associated symptoms and sustained pain relief for 24 hours were also noted . Result : One hundred and twenty four patients were r and omised into rofecoxib ( 42 ) , ibuprofen ( 40 ) , and placebo ( 42 ) groups . One hundred and one patients were followed up : 33 on rofecoxib , 35 ibuprofen , and 33 placebo .  Patients ’ ages ranged from 16–62 ( mean 31.4 ) years , and 83 were females .  Pain relief at two hours was noted in 45.5 % on rofecoxib , 55.6 % on ibuprofen , and 9.1 % in the placebo group . The associated symptoms at two hours were reduced in 39.4 % on rofecoxib , 50 % on ibuprofen , and 9.1 % in the placebo group . Sustained 24 hour pain relief was noted in 36.4 % on rofecoxib , 41 % on ibuprofen , and 6.1 % in the placebo group . In the ibuprofen group , five patients had abdominal pain but there were no side effects in those on rofecoxib or in the control group . Both rofecoxib and ibuprofen were significantly effective in relieving pain , associated symptoms at two hours , and in sustained pain relief . There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks . Conclusions : Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack , and there was no significant difference in their efficacy in an acute migraine attack The purpose of this study was to compare the efficacy and tolerance of a single dose of the acetaminophen 400 mg-codeine 25 mg combination ( ACC ) aspirin 1000 mg ( A ) and a placebo ( P ) for the treatment of acute migraine attack . The study design was r and omized , multicentre , double-blind and double dummy with cross-over on three periods . Of the 198 patients who had three attacks 29.8 % , 52.3 % and 49.7 % had recorded the complete or almost complete disappearance of the pain at 2 h after P , A and ACC respectively . When compared with the placebo , the difference was significant for the A and ACC . When complete disappearance of pain at 2 h was used as a criterion , no significant difference was observed . These results enabled the sensitivity of the evaluation criteria suggested for clinical trials of migraine attack to be discussed OBJECTIVE To investigate the efficacy , tolerability , and safety of rofecoxib and ibuprofen for acute migraine treatment . BACKGROUND Rofecoxib was effective and well tolerated in a previous study of treatment of a single migraine attack . We sought to replicate these findings for a single attack and also study the clinical profile of rofecoxib in the acute treatment of multiple migraine attacks . Ibuprofen was included as a reference nonselective NSAID . METHODS Adult migraineurs ( n = 783 ) treated one migraine attack with either rofecoxib ( 25 or 50 mg ) , ibuprofen 400 mg , or placebo in a r and 
    Output:
    
Soluble formulations of ibuprofen 400 mg were better than st and ard tablets for 1-hour , but not 2-hour headache relief .
Ibuprofen 400 mg did not differ from rofecoxib 25 mg for 2-hour headache relief or 24-hour headache relief .
Ibuprofen is an effective treatment for  acute migraine headaches  , providing pain relief in about half of sufferers , but complete relief from pain and associated symptoms for only a minority .
NNTs for all efficacy outcomes were better with 400 mg than 200 mg in comparisons with placebo , and soluble formulations provided more rapid relief .
Adverse events were mostly mild and transient , occurring at the same rate as with placebo