***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 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 1 The absorption of effervescent aspirin  was studied in two groups of patients during attacks of migraine . The first group received effervescent aspirin alone whilst the second group received intramuscular metoclopramide before effervescent aspirin . 2 After effervescent aspirin alone there was significant impairment in the rate of aspirin absorption during migraine attacks compared with the rate of  aspirin absorption in normal volunteers and in the same patients when headache-free . 3 When metoclopramide was given before effervescent aspirin the rate of aspirin absorption during migraine attacks was not significantly different from that obtained in normal volunteers given effervescent aspirin alone or from that obtained in the patients themselves when given both metoclopramide and effervescent aspirin when headache-free . 4 It is concluded that the impairment of absorption of effervescent aspirin  during migraine attacks is related to impaired gastro-intestinal motility with delayed gastric emptying and that this impaired motility can be overcome by parenteral metoclopramide & NA ; A data base of r and omised  clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics .  Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain .  The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale 
    Output:
    
Aspirin 1000 mg is an effective treatment for acute migraine headaches , similar to sumatriptan 50 mg or 100 mg .
Addition of metoclopramide 10 mg improves relief of nausea and vomiting .
Adverse events were mainly mild and transient , and were slightly more common with aspirin than placebo , but less common than with sumatriptan 100 mg