***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: 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 Summary The pharmacokinetics of  aspirin ( ASA ) in acute migraine attacks , and the influence of metoclopramide on ASA disposition , were studied in 32 attacks in 30 patients . An intergroup comparison was made between normal volunteers , and the migraineurs , who were assigned at r and om to one of three treatment groups : a ) oral ASA only ( 900 mg ) ; b ) 10 mg oral metoclopramide + oral ASA 900 mg ; c ) 10 mg i. m. metoclopramide + oral ASA 900 mg .  Plasma ASA and SA levels were measured serially over 2 h , and the result ant data evaluated pharmacokinetically  . Metoclopramide plasma levels were also determined over 2 h , and the results compared with a second group of normal volunteers . The rates of oral ASA absorption and elimination were unaffected by migraine . Mean absorption rate constants of 14.15±9.48 h−1 ( normals ) , 7.91±3.42 h−1 ( ASA only ) , 6.74±3.26 h−1 ( ASA + oral metoclopramide ) and 8.12±2.82 h−1 ( ASA + i. m. metoclopramide ) were calculated . Mean elimination rate constants ranged from 2.56 h−1 to 3.37 h−1 , and did not differ significantly between controls and migrainous patients . Values for absorption lag time , however , were higher in migraine patients treated with ASA alone than in any other group . The amount of ASA absorbed unhydrolysed was also lower in this group . SA levels appeared unaffected either by the migraine attack , or by metoclopramide administration , over the period of study . Metoclopramide plasma levels were significantly lower during migraine attacks , and the amount of drug absorbed up to 2 h from dosing was also reduced , as compared with non-migrainous subjects . It was concluded that acute migraine caused a delay in orally administered ASA reaching its absorption sites , probably as a result of gastric stasis , and may have decreased the amount of ASA absorbed . The prior administration of metoclopramide , either orally or intramuscularly , reduced the absorption lag time , and thus promoted the early absorption of ASA , probably by restoring alimentary tract motility BACKGROUND Although most persons with migraine treat their headaches with over-the-counter medication , systematic data on the safety and efficacy of widely used treatment , including acetaminophen , are sparse . METHODS This is a r and omized , double-blind , placebo-controlled study comparing oral acetaminophen , 1000 mg ( two 500-mg Extra Strength Tylenol tablets ) , with identical placebo in the treatment of a single acute migraine attack . Eligible subjects met International Headache Society diagnostic criteria for migraine with or without aura . Patients who usually required bed rest with their headaches or who vomited more than 20 % of the time were excluded . MAIN OUTCOME MEASURES The percentage of subjects who , at 2 hours after dosing , experienced a change in baseline pain intensity from severe or moderate pain to mild or no pain ( headache response ) ; and pain intensity difference from baseline at the 2-hour postmedication assessment . RESULTS The headache response rate 2 hours after dosing was 57.8 % in the acetaminophen group and 38.7 % in the placebo group ( P = .002 ) . Pain-free rates at 2 hours were 22.4 % in the acetaminophen group and 11.3 % in the placebo group ( P = .01 ) . The mean pain intensity difference from baseline 2 hours after dosing was 1.08 in the acetaminophen group and 0.73 in the placebo group ( P<.001 ) . At 2 hours , other migraine headache characteristics , such as functional disability ( P = .002 ) , photophobia ( P = .02 ) , and phonophobia ( P = .08 ) , were significantly improved after treatment with acetaminophen vs placebo . CONCLUSIONS Acetaminophen was highly effective for treating pain , functional disability , photophobia , and phonophobia in a population -based sample of persons with migraine , excluding the most disabled persons with migraine . The drug also had an excellent safety profile and was well tolerated . Arch Intern Med . 2000;160:3486 - 3492 Objective : To estimate the 1-year prevalences of primary headache disorders and identify their principal risk factors in the general population of Russia . Methods : A countrywide population -based r and om sample of 2725 biologically unrelated adults in 35 cities and nine rural areas were interviewed in a door-to-door survey using a previously vali date d diagnostic question naire . Results : Of the 2725 eligible adults contacted , 2025 ( 74.3 % ) responded ( females 52.6 % , mean age 39.5 ± 13.4 years ) . Of these , 1273 ( 62.9 % ) reported headache ‘ not related to flu , hangover , cold , head injury ’ occurring at least once in the previous year . The gender- and age-st and ardized 1-year prevalence of migraine was 20.8 % . Female gender ( odds ratio ( OR ) = 3.8 ; 95 % confidence interval ( CI ) 2.8–5.1 ) and obesity ( OR = 1.5 ; 1.1–2.1 ) were positively associated with this type of headache . The gender- and age-st and ardized 1-year prevalence of tension-type headache ( TTH ) was 30.8 % . TTH was more prevalent in urban than in rural areas ( OR = 1.6 ; 1.3–2.0 ) . Headache on ≥15 days/month was reported by 213 ( 10.5 % ) respondents ( gender- and age-st and ardized prevalence 10.4 % ) , and associated with low socioeconomic status ( OR = 3.4 ; 2.4–4.9 ) , obesity ( OR = 3.0 ; 2.1–4.3 ) , female gender ( OR = 2.9 ; 2.1–4.1 ) and age over 40 years ( OR = 2.6 ; 1.9–3.6 ) . The majority of these respondents ( 68.1 % ) overused acute headache medications . Conclusion : The study demonstrated a high prevalence of migraine and a very high prevalence of headache on ≥15 days/month , and revealed unmet health-care needs of people with headache in Russia OBJECTIVE To evaluate the efficacy and safety of acetaminophen 1000 mg for the treatment of episodic migraine headache . BACKGROUND While acetaminophen is commonly used to treat migraine , there have been limited published clinical trial efficacy results . DESIGN / METHODS Ten investigators at 13 private , ambulatory , primary care sites in the United States enrolled and treated 346 outpatient adults 18 - 72 years of age with migraine headache of moderate to severe intensity into a r and omized , placebo-controlled , double-blind clinical trial of 6 hours duration . Each patient was r and omly assigned to a single dose of study medication of acetaminophen 1000 mg ( n = 177 ) or placebo ( n = 169 ) . The percentage of patients with a reduction in baseline headache pain intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures . Other measures of pain relief , severity differences from baseline for migraine-associated symptoms of nausea , photophobia , phonophobia , and functional disability , and percentage of patients with migraine-associated symptoms reduced to none were also assessed . RESULTS Significantly ( P = .001 ) more patients treated with acetaminophen 1000 mg reported mild to no pain after 2 hours ( 52.0 % ) compared with those treated with placebo ( 32.0 % ) . The mean pain intensity difference from baseline measured at 2 hours was significantly ( P < .001 ) greater for patients treated with acetaminophen 1000 mg ( 0.82 ) compared with those treated with placebo ( 0.46 ) . A significant difference in favor of acetaminophen 1000 mg over placebo was also observed at 1 hour after treatment for the percentage of patients with mild to no pain and for mean pain intensity difference from baseline .  Acetaminophen 1000 mg was significantly more effective than placebo for all but 1 ( pain reduced to none at 2 hours ) clinical ly important secondary pain relief outcomes . Mean severity changes from baseline in migraine-associated symptoms of nausea , photophobia , phonophobia , and functional disability at 2 and 6 hours were significantly ( P < .001 ) in favor of acetaminophen over placebo ; the percentage of patients with no symptoms at 2 and 6 hours statistically significantly favored acetaminophen in 6 of 8 comparisons . Adverse events , overall , and specifically for nausea , were reported more frequently in the placebo group . CONCLUSIONS Acetaminophen 1000 mg , a nonprescription drug , is an effective and well-tolerated treatment for episodic and moderate migraine headache . In addition , acetaminophen generally provided a beneficial effect on associated symptoms of migraine including nausea , photophobia , phonophobia , and functional disability In a double‐blind cross‐over study we compared tolfenamic acid with paracetamol in out‐ patients with common migraine ( migraine without aura ) . Each patient was treated during ( at least ) 4 attacks with one of the following alternatives : tolfenamic acid 200 mg , tolfenamic acid 400 mg , paracetamol 500 mg or paracetamol 1000 mg in a r and omized sequence . The same sequence of treatments was applied to ( preferably ) 4 more attacks . Dosage was repeated after 2 h if the attack had not abated . Escape medication was allowed after 4 h if the treatment was inefficient . A total of 83 patients were admitted to the study , but 3 dropped out , while 10 completed less than 4 attacks . Seventy completed 4 attacks , and 58 completed all 8 . The total number of attacks treated was 545 . We found a significant superiority of tolfenamic acid over paracetamol with regard to effect on pain after 2 h ( p < 0.01 ) , patients ’ global evaluation ( p < 0.001 ) , and use of escape medication ( p < 0.02 ) . The trend was the same for duration of attacks , confinement to bed during attack and nausea , but the results were not statistically significant . There was no significant difference between the smaller and the larger dose of either drug nor between the need for escape medication , although the trend favoured tolfenamic acid . Side effects were few . Tolfenamic acid is evidently valuable in treatment of migraine OBJECTIVE To evaluate the efficacy and tolerability of coadministration of rizatriptan and acetaminophen in the acute treatment of migraine . BACKGROUND Rizatriptan is a selective 5-HT1B/1D agonist approved for the acute treatment of migraine . Acetaminophen has been studied for acute migraine treatment . In consideration of the prominent central and peripheral mechanisms in migraine , the use of " multi-mechanism therapy " is gaining momentum in the treatment of acute migraine attacks . STUDY DESIGN This was a r and omized , double-blind , placebo- 
    Output:
    
Paracetamol 1000 mg alone is statistically superior to placebo in the treatment of acute migraine , but the NNT of 12 for pain-free response at two hours is inferior to at of other commonly used analgesics .
Given the low cost and wide availability of paracetamol , it may be a useful first choice drug for acute migraine in those with contraindications to , or who can not tolerate , non-steroidal anti-inflammatory drugs ( NSAIDs ) or aspirin .
The addition of 10 mg metoclopramide gives short-term efficacy equivalent to oral sumatriptan 100 mg .
Adverse events with paracetamol did not differ from placebo ;  serious and /or severe adverse events were slightly more common with sumatriptan than with paracetamol plus metoclopramide