***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 Forty to 78 % of the patients using sumatriptan for the acute treatment of migraine may present recurrence at least occasionally . The concomitant use of a NSAID ( nonsteroidal anti-inflammatory drug ) has been recommended to decrease the recurrence rate .  Sixty seven patients that treated successfully 8 migraine attacks with 100 mg of sumatritpan PO and presented recurrence in at least 5 attacks were studied prospect ively . The patients received 100 mg of sumatriptan and 550 mg of naproxen sodium PO to treat 4 consecutive moderate or severe migraine attacks . The recurrence rate , once at least 62.5 % ( 5 out of 8 attacks ) , decreased to 14.2 % ( 38 out of 268 attacks ) with the combination of compounds ( p<0.0001 ) . We then studied two groups of 13 patients made r and omicaly from the 67 initially evaluated , that were given sumatriptan 100 mg plus naproxen sodium 550 mg or placebo , in a double-blind design , to treat 3 other consecutive migraine attacks . Each group of patients treated 39 attacks . The recurrence among the patients taking sumatriptan plus placebo was 59 % ( 23 out of 39 attacks ) and the recurrence presented by the group taking sumatriptan plus naproxen was 25.5 % ( 10 out of 39 attacks ) ( p<0.0003 ) . We concluded that the combination of sumatriptan plus naproxen sodium decreases significantly migraine recurrence presented by patients taking sumatriptan alone Objective Probable migraine is a common , disabling migraine subtype fulfilling all but one of the diagnostic criteria for migraine . This study was conducted to evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura . Methods Patients treated a headache of probable migraine without aura when pain was moderate or severe with sumatriptan/naproxen sodium ( n = 222 intent-to-treat ( ITT ) ) or placebo ( n = 221 ITT/complete case analysis a ) in this r and omized , double-blind , parallel-group study . Results Sumatriptan/naproxen sodium was more effective than placebo with respect to the co- primary efficacy endpoints two-hour pain-free response ( 29 % sumatriptan/naproxen sodium vs 11 % placebo , p < 0.001 ) and two- to 24-hour sustained pain-free response ( 24 % sumatriptan/naproxen sodium vs 9 % placebo , p < 0.001 ) . Sumatriptan/naproxen sodium was significantly more effective than placebo with respect to the secondary efficacy endpoints of pain-free response four hours postdose ( p < 0.001 ) , pain-free response maintained one to two hours postdose ( p = 0.034 ) and two to four hours postdose ( p < 0.001 ) , headache relief four hours postdose ( p < 0.001 ) , headache relief maintained two to four hours postdose ( p = 0.015 ) , sustained headache relief two through 24 hours postdose ( p = 0.002 ) , and rescue medication use ( p < 0.001 ) ; but not productivity scores . The most common adverse events were dizziness ( 4 % sumatriptan/naproxen sodium,<1 % placebo ) , dry mouth ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) , and nausea ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) . Conclusion Sumatriptan/naproxen sodium is effective in the acute treatment of probable migraine as demonstrated by higher rates of freedom from pain and restoration of function 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 OBJECTIVES To evaluate the long-term safety and tolerability of sumatriptan-naproxen sodium for the treatment of moderate to severe acute migraines and to assess the safety of administration of an optional second dose . PATIENTS AND METHODS A 12-month , multicenter , open-label safety study was conducted in adults treated for migraine attacks of moderate to severe intensity from April 14 , 2004 , to August 18 , 2005 . Safety evaluations included adverse events and laboratory tests . RESULTS Of 600 patients enrolled , 565 ( 94 % ) were treated for at least 1 migraine . Of treated patients , 414 ( 73 % ) and 362 ( 64 % ) completed 6 and 12 months of treatment , respectively . Of the 24,485 attacks treated , 17,144 ( 70 % ) were treated with only 1 dose . On average , patients treated 5 migraine attacks per month , with a median of 6 days between attacks . The most common treatment-related adverse events were nausea , muscle tightness , and dizziness . Fourteen patients reported 1 or more serious adverse event with only 1 judged probably related to treatment . No deaths occurred . Eight percent of patients discontinued participation in the study because of adverse events or pregnancy . The rates of adverse events reported were no higher after treatment with 2 tablets ( at least 2 hours apart ) compared with 1 tablet . CONCLUSIONS In this 12-month data set of more than 24,000 migraine attacks in 565 patients , sumatriptan-naproxen sodium formulated in a single tablet was well tolerated when used episodically for the treatment of acute migraine . The adverse events did not differ from those expected for the individual components alone , and no new or unexpected findings occurred OBJECTIVE To describe return to normal function , productivity , and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium , sumatriptan alone , naproxen sodium alone , or placebo . PATIENTS , DESIGN , AND SETTING Patients in 2 identical , US , phase 3 , r and omized , double-blind , parallel-group , placebo-controlled , single-dose , multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium ( 85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation ) , sumatriptan , naproxen sodium , or placebo . MAIN OUTCOME MEASURES Ability to function ( not impaired , mildly impaired , severely impaired , or required bed rest ) was collected in diary cards completed immediately prior to treatment , every 30 minutes for the first 2 hours , and hourly from 2 to 24 hours while awake . Patients completed the Productivity Assessment Question naire ( PAQ ) 24 hours after study drug administration . The Patient Perception of Migraine Question naire ( PPMQ ) was administered at screening and 24 hours post treatment to capture patient satisfaction . RESULTS Compared with the other groups , the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing . They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies , and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications . CONCLUSIONS Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly , and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups . Overall productivity loss was significantly reduced following use of sumatriptan/naproxen sodium CONTEXT Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex , and multimechanism-targeted therapy may confer advantages over monotherapy . OBJECTIVE To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine . DESIGN , SETTING , AND PARTICIPANTS Two replicate , r and omized , double-blind , single-attack , parallel-group studies conducted among 1461 ( study 1 ) and 1495 ( study 2 ) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack . INTERVENTIONS Patients were r and omized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan , 85 mg , and naproxen sodium , 500 mg ; sumatriptan , 85 mg ( monotherapy ) ; naproxen sodium , 500 mg ( monotherapy ) ; or placebo , to be used after onset of a migraine with moderate to severe pain . MAIN OUTCOME MEASURES Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing , absence of photophobia , absence of phonophobia , and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo , and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy . RESULTS Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing ( study 1 , 65 % vs 28 % ; P<.001 and study 2 , 57 % vs 29 % ; P<. 
    Output:
    
Overall , the combination was better than placebo for the primary outcomes of pain-free and headache relief at two hours .
Using 50 mg of sumatriptan , rather than 85 mg , in the combination did not significantly change the result .
Treating early , when pain was still mild , was significantly better than treating once pain was moderate or severe for pain-free responses at two hours and during the 24 hours post dose .
Adverse events were mostly mild or moderate in severity and rarely led to withdrawal ; they were more common with the combination than with placebo ( moderate quality evidence ) .Where the data allowed direct comparison , combination treatment was superior to either monotherapy , but adverse events were less frequent with naproxen than with sumatriptan ( moderate quality evidence ) .
Combination treatment was effective in the acute treatment of  migraine headaches .
The effect was greater than for the same dose of either sumatriptan or naproxen alone , but additional benefits over sumatriptan alone were not large .
More participants achieved good relief when medication was taken early in the attack , when pain was still mild .
Adverse events were more common with the combination and sumatriptan alone than with placebo or naproxen alone