***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 
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    ***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 BACKGROUND Aspirin is a widely used NSAID that has been extensively studied in numerous conditions . Nonprescription analgesics , such as aspirin , are frequently used for a wide variety of common ailments , including conditions such as dental pain and tension-type headache . OBJECTIVE We sought to compare the efficacy and safety profiles of aspirin , acetaminophen with codeine , and placebo in the treatment of post-operative dental pain and tension-type headache . METHODS These were 2 r and omized , double-blind , placebo-controlled , single-dose clinical trials that assigned participants ( 2:2:1 ) to receive either aspirin ( 1000 mg ) , acetaminophen ( 300 mg ) with codeine ( 30 mg ) , or placebo . The primary efficacy end point was the sum of pain intensity differences from baseline ( SPID ) over 6 hours for the dental pain study and over 4 hours for the tension-type headache study . Other common analgesic measures , in addition to safety , were also evaluated . RESULTS The results of the dental pain study for aspirin and acetaminophen with codeine suggest statistically significant efficacy for all measures compared with placebo at all time points . Aspirin provided statistically significant efficacy compared with acetaminophen with codeine for SPID(0 - 4 ) ( P = 0.028 ) . In the tension-type headache study , aspirin and acetaminophen with codeine provided statistically significant efficacy compared with placebo  for SPID(0 - 4 ) and SPID(0 - 6 ) ( P < 0.001 ) and for total pain relief ( P < 0.001 ) . There were no significant differences between aspirin and acetaminophen with codeine at any evaluation of SPID ( P ≥ 0.070 ) , complete relief ( P ≥ 0.179 ) , or time to meaningful relief ( P ≥ 0.245 ) . Regarding safety , there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies . CONCLUSIONS These 2 r and omized , double-blind , placebo-controlled studies demonstrate that treatment with aspirin ( 1000 mg ) provides statistically significant analgesic efficacy compared with placebo use and comparable efficacy with acetaminophen ( 300 mg ) with codeine ( 30 mg ) therapy after impacted third molar extraction and in tension- type headache Background . Primary headaches are underdiagnosed and undertreated , with a significant impact on social activities and work . Aim . To determine the last-year prevalence and health care utilization pattern of primary headaches at a tertiary centre . Methods . A cross-sectional study was carried out amongst staff of the Lagos State University Teaching Hospital in Lagos , Nigeria . 402 staff members were selected by simple r and om sampling and administered a detailed structured headache assessment question naire . Migraine and tension-type headache were diagnosed according to the criteria of the International Headache Society ( 2004 ) . Results . The participants comprised 168 males and 234 females . The mean age was 36.9 ± 7.9 years .  The overall headache prevalence was 39.3 % with female predominance ( P < 0.0001 ) . Tension-type headache was the most prevalent at 72.8 % and migraine at 18.9 % . Unclassifiable headache constituted 8.2 % . Migraine headache showed female preponderance ( P = 0.000 ) . 80.4 % of participants did not seek medical consultation compared with 19.6 % who did ( P = 0.000 ) . Of the latter , 83.9 % consulted the general practitioner ( GP ) , whilst 16.1 % consulted the neurologist . Conclusions . Primary headache prevalence is high in our population . It is not recognised as that requiring care by most of the staff of this tertiary health facility ; thus education is required to increase health care utilization Seven hundred three subjects completed a r and omized , double-blind , parallel-group , single-center study comparing the single-dose efficacy of ketoprofen 12.5 mg , ketoprofen 25 mg , acetaminophen 1000 mg , and placebo in the treatment of tension headache . For the primary efficacy variable , 4-hour sum of pain relief intensity differences , ketoprofen 25 mg was significantly superior to placebo . Ketoprofen 25 mg also demonstrated superior pain relief in the first hour after dosing , and the time to meaningful pain relief was significantly shorter for the ketoprofen 25-mg group . Ketoprofen 12.5 mg proved to be significantly superior to placebo for pain relief intensity difference and pain relief at 3 hours , global assessment of medication at 4 hours , and for time to onset of meaningful pain relief . The data suggest a dose response for ketoprofen 12.5 mg and 25 mg . Acetaminophen 1000 mg proved to be numerically more favorable than placebo in most variables , but could not be separated from placebo with statistical significance . In spite of possible inflation of the placebo response due to sensitivity limits of the study , ketoprofen 25 mg demonstrated a more rapid onset of analgesia compared to acetaminophen 1000 mg , and patients ' global assessment rated ketoprofen 25 mg higher than acetaminophen 1000 mg A double-blind , cross-over trial was made of three analgesic preparations -- paracetamol , paracetamol with caffeine ( Finimal ) and aspirin in the relief of  postoperative pain  in 72 orthopedic in patients and in 144 ambulatory out patients suffering form common idiopathic headache . The combination of paracetamol and caffeine ( Finimal ) in this study shows the greatest pain relief in both groups of patients . This evaluation supports the results of BOOY3 demonstrating the superiority of the paracetamol-caffeine combination to paracetamol alone or aspirin To refine the assessment of over‐the‐counter analgesic agents in the treatment of muscle‐contraction headache , we design ed a single‐dose model with attention to specific method ologic features and two relevant assessment s — the percentage of subjects who achieve complete relief and the time until pain is no longer experienced . Subjects were r and omly assigned to receive a single dose of 1000 mg acetaminophen , 1000 mg aspirin with 64 mg caffeine , or placebo . Under double‐blind conditions , subjects rated headache pain intensity and relief over 4 hours and provided a Comparative Evaluation at the end of the trial . Both active agents were significantly distinguished from placebo on the time‐point analyses ( p < 0.05 ) and summary end point measurements ( sum of pain intensity difference [ SPID ] , total of pain relief , percentage of patients with complete relief , percentage of treatment failures , and the Comparative Evaluation ) , as well as causing a faster elimination of headache ( p < 0.05 ) . The aspirin‐caffeine combination was rated higher than acetaminophen on all summary measurements , particularly SPID ( p < 0.05 ) , with significantly more patients obtaining complete relief with aspirin‐caffeine ( p < 0.01 ) than with acetaminophen . We conclude that this headache pain model can be used to demonstrate the efficacy of over‐the‐counter analgesic agents and to assess their relative efficacy Aims In September 2012 the UK ’s Commission on Human Medicines ( CHM ) recommended changes in the management of paracetamol poisoning : use of a single ‘ 100 mg l−1 ’ nomogram treatment line , ceasing risk assessment , treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine ( NAC ) infusion from 15 to 60 min . We evaluated the effect of this on presentation , admission , treatment , adverse reactions and costs of paracetamol poisoning . Methods Data were prospect ively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 ( year before and after change ) . Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre . A cost analysis from an NHS perspective was performed for 90 000 patients /annum with paracetamol overdose . Results There were increases in the numbers presenting to hospital ( before 1703 , after 1854 ; increase 8.9 % [ 95 % CI 1.9 , 16.2 ] , P = 0.011 ) ; admitted ( 1060/1703 [ 62.2 % ] vs. 1285/1854 [ 69.3 % ] ; increase 7.1 % [ 4.0 , 10.2 ] , P < 0.001 ) and proportion treated ( 626/1703 [ 36.8 % ] vs. 926/1854 [ 50.0 % ] ; increase : 13.2 % [ 95 % CI 10.0 , 16.4 ] , P < 0.001 ) . Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions ( 15 min 87/323 [ 26.9 % ] , 60 min 145/514 [ 28.2 % ] ; increase : 1.3 % [ 95 % CI –4.9 , 7.5 ] , P = 0.682 ) . Across the UK the estimated cost impact is £ 8.3 million ( 6.4 million–10.2 million ) annually , with a cost-per-life saved of £ 17.4 million ( 13.4 million–21.5 million ) . Conclusions The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions . A safety and cost-benefit review of the CHM guidance is warranted , including novel treatment protocol s and biomarkers in the assessment of poisoning The main aim of this study was to confirm in an Italian population affected by tension-type headache ( TTH ) the good profile of safety and tolerability of the combination paracetamol 1,000 mg – caffeine 130 mg ( PCF ) observed in previous studies , by a comparison with naproxen sodium 550 mg ( NAP ) and placebo ( PLA ) . A secondary objective was to assess the efficacy of PCF in the acute treatment of TTH . This was a multicentre , r and omised , double-blind , double-dummy , crossover , placebo-controlled trial . Tolerability was assessed by recording adverse events by the patient in the 4-h post-dose treatment . To assess the efficacy , the sum of pain intensity differences ( SPID ) and the total pain relief ( TOTPAR ) were calculated . Comparing PCF and NAP and PCF and PLA for tolerability , the difference was nonsignificant but the result regarding noninferiority was inconclusive , whilst NAP was noninferior to PLA . As regards SPID and TOTPAR , both PCF and NAP were better than placebo ( P < 0.05 ) , but not significantly different from each other . In conclusion , PCF was well-tolerated and effective in the treatment of acute TTH The aim of the study was to assess the efficacy and tolerability of a single oral dose of ketoprofen 25 mg in comparison with single doses of ketoprofen 2 × 25 mg , paracetamol 500 mg and 1,000 mg , and placebo in the treatment of episodic tension-type headache . The study was conducted as a single centre , double-blind , 
    Output:
    
Paracetamol 1000 mg provided a small benefit in terms of being pain free at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity