***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: BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences Single oral doses of 100 and 200 mg indoprofen were compared with 600 mg aspirin and placebo in a double-blind , completely r and omized study of hospitalized patients with postoperative , post-fracture , or musculoskeletal pain . The patients evaluated their pain for 5 hours after administration of the study drug . Each of the three active treatments performed significantly better than placebo . The 200-mg dose level of indoprofen demonstrated the greatest analgesic activity based on pain intensity and pain relief scores and on the patients ' global evaluations . The analgesic activity of 100 mg indoprofen fell between that of 200 mg indoprofen and 600 mg aspirin and was not significantly different from either In a double-blind , single dose study of analgesic efficacy , 165 patients who were expected to develop moderate to severe pain following the removal of an impacted m and ibular third molar tooth were allocated to receive aspirin , placebo , or an increasing dose of a fixed ratio ibuprofen/codeine combination . The degree of pain experienced prior to medication was noted and the patients were asked to record the degree of pain and of pain relief hourly for the following 5 hours . The study produced clear evidence of the superior efficacy of the combinations when compared to placebo and aspirin . In addition , the high dose combination appeared to be superior with respect to pain relief and the need for additional analgesia compared to the low dose treatment . There were few side effects and only one severe reaction was reported by a patient in the high dose group . To avoid side effects it is suggested that the medium-dose combination , ibuprofen 400 mg/codeine 30 mg , is optimal To evaluate the analgesic efficacy of orally administered 50 mg propiram fumarate , 650 mg aspirin , 60 mg codeine phosphate , and placebo in acute post-impaction dental pain , 159 patients with moderate or severe pain were r and omly allocated to the four treatments in this single-dose double-blind , stratified , parallel-group study . A research nurse question ed the patients at 1/2 hour and hourly for 6 hours after medicating . A st and ard format was used to question subjects about their pain intensity and relief from the starting pain . Propiram , 50 mg , produced a level of analgesia approaching that of 650 mg aspirin in peak effect , total effect , and duration of action and was statistically superior to 60 mg codeine and placebo for every measure of analgesic efficacy . Several mild adverse effects were observed ; however , they appeared to be evenly distributed among the active treatments The object of a study was to evaluate the analgesic efficacy of ibuprofen for dental pain .  The subjects were out patients who were undergoing surgical removal of impacted teeth . We compared aspirin , 325 mg ; aspirin , 650 mg ; ibuprofen , 200 mg ; ibuprofen , 400 mg ; and placebo . Each patient received a single dose of one of the test medications ; there was a minimum of 37 patients in each treatment group . Patients recorded pain intensity before receiving medication ; then hourly , for four hours after medication , they recorded pain intensity , amount of relief , and side effects . Time-effect and dose-response curves were generated from the relief and change in pain-intensity scores . First-hour scores , peak scores , and total scores were analyzed . All active medications were significantly better than placebo and the mean effect for ibuprofen was significantly more than for aspirin Overemphasis on hypothesis testing-- and the use of P values to dichotomise significant or non-significant results --has detracted from more useful approaches to interpreting study results , such as estimation and confidence intervals . In medical studies investigators are usually interested in determining the size of difference of a measured outcome between groups , rather than a simple indication of whether or not it is statistically significant . Confidence intervals present a range of values , on the basis of the sample data , in which the population value for such a difference may lie . Some methods of calculating confidence intervals for means and differences between means are given , with similar information for proportions . The paper also gives suggestions for graphical display . Confidence intervals , if appropriate to the type of study , should be used for major findings in both the main text of a paper and its abstract Fluradoline ( 150 or 300 mg ) , a novel tricyclic with both antidepressant and analgesic properties in animals , was compared with aspirin , 650 mg , and placebo when given orally for postoperative orthopedic pain in a double‐blind , single‐dose , parallel‐group study . Analgesic measurements were made by two trained nurse observers using st and ard verbal rating and visual analogue scales . Aspirin was statistically superior to placebo on all analgesic measures , demonstrating assay sensitivity . Fluradoline , 300 mg , was distinguished from placebo and fluradoline , 150 mg , but not from aspirin , 650 mg . Overall , fluradoline , 300 mg , was equivalent to aspirin , 650 mg . Fluradoline , 300 mg , produced a significant elevation in mood score .  Neither aspirin , 650 mg , nor fluradoline  caused untoward side effects , but fluradoline , 300 mg , increased blood pressure In a double-blind study , 198 out patients with pain after oral surgery were r and omly assigned to treatment with a single oral dose of naproxen sodium 550 mg , codeine sulfate 60 mg , a combination of naproxen sodium 550 mg with codeine sulfate 60 mg , aspirin 650 mg or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 12 hours after medication . Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia ; the codeine effect was significant for total and peak pain relief and patients ' overall evaluation . The naproxen-codeine interaction was not statistically significant for any measure , which suggests that the analgesic effect of the combination represents the additive effect of its constituents . Based on pairwise comparisons , aspirin was significantly superior to placebo for most measures of effect , naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients ' overall evaluation . No more patients experienced adverse effects with aspirin or naproxen than with placebo , but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen Summary The efficacy of single doses ( 1.2 g ) of soluble aspirin and aspirin tablets was determined in a r and omised , placebo-controlled , double-blind , parallel study in 90 patients ( 45 females ) with postoperative pain after removal of impacted lower third molars . Also investigated was the relationship between plasma  aspirin esterase activity and overall pain scores after both aspirin preparations . Patients reported significantly less pain ( p<0.001 ) after treatment with aspirin than after treatment with placebo . However , patients receiving soluble aspirin reported both an earlier onset and a longer duration of pain relief than those who received aspirin tablets . A significant correlation was observed between plasma aspirin esterase activity and overall pain scores after both soluble aspirin ( r=0.57,p<0.01 ) and aspirin tablets ( r=0.51,p<0.02 ) . It is concluded that soluble aspirin is the preferred aspirin formulation for treating postoperative pain after third molar surgery and that plasma aspirin esterase activity is a determinant of a patient 's analgesic response to aspirin in postoperative dental pain Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score  ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form Suprofen is a new , orally effective nonsteroidal antiinflammatory analgesic of the propionic acid chemical class . Three separate single-dose studies were performed to evaluate the efficacy of suprofen in acute pain associated with periodontal surgery and removal of impacted third molars . Study medications were : A -- suprofen 200 mg , codeine 60 mg , propoxyphene HCl 65 mg , and placebo ; B -- suprofen 400 mg and 200 mg , aspirin 650 mg , and placebo ; C -- suprofen 400 mg and 200 mg , aspirin 650 mg with codeine 60 mg , aspirin 650 mg alone , and placebo .  Analgesic and side effect data were collected over a 6-hour period after patients medicated for moderate to severe pain . All studies were r and omized , double-blinded , and parallel-group in design . Suprofen was significantly more effective than codeine 60 mg , propoxyphene HCl 65 mg , and aspirin 650 mg . Suprofen 400 mg appeared to be clinical ly more effective than the aspirin-codeine combination and the difference was statistically significant for most of the analgesic variables . Of the 224 patients who received suprofen in the 3 studies , 16 reported  drowsiness  and 1 reported constipation A double-blind r and omized single dose study of the analgesic effects of 650 mg aspirin , 250 mg mefenamic acid , the combination of 650 mg aspirin and 250 mg mefenamic acid and placebo on 120 patients with pain following oral surgery was conducted . Patients evaluated their pain intensity and extent of pain relief at 1 , 2 , 3 and 4 h after drug administration . For most parameters , including the sum of the pain intensity differences and the sum of the hourly pain relief scores , each of the drugs was more effective than placebo . Aspirin – mefenamic acid in combination was more effective than both drugs alone , and aspirin and mefenamic acid alone were equally effective for most of the analgesic variables The safety and efficacy of single oral doses of Oxaprozin ( 1200 mg ) , aspirin ( 650 mg ) , and placebo were compared in an 8-hour double-blind study of 105 patients with moderate to severe post-operative dental-surgical pain . As measured by mean and cumulative mean scores obtained with the pain intensity and verbal pain relief scales , both active drugs produced significantly ( p < 0·05 ) more analgesia than did placebo . A significantly ( p < 0·05 ) greater proportion of patients reported effective ( moderate or better ) pain relief in the Oxaprozin and aspirin groups than in the placebo group at 2 , 3 , and 4 hours ; significant ( p < 0·05 ) differences between the Oxaprozin and placebo groups continued for the entire 8 hours . Oxaprozin provided more pain relief  than aspirin during the latter part of the study . There were no statistically significant differences , however , in any of the efficacy assessment s between the Ox 
    Output:
    
Type of pain model , pain measurement , sample size , quality of study design , and study duration had no significant impact on the results .
There was a clear dose-response for pain relief with aspirin , even though these were single dose studies .
Adverse effects , drowsiness and gastric irritation were also evident in the single dose studies .
The pain relief achieved with aspirin was very similar milligram for milligram to that seen with paracetamol