***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 The aim of this study was to evaluate the comparative efficacy of three commonly used analgesics ( Panadeine , Diflunisal and Etodolac ) in the control of pain after third molar surgery under local anaesthesia . METHODS A r and omized control study . Outcome of primary efficacy was judged by overall assessment of the area under the curve of graphs for pain intensity , measured from serial visual analogue scales over a 24-hour period . Other measures of efficacy included the number ( per cent ) of patients who took ' additional ' analgesics and the incidence of adverse effects occurring in each treatment group over the study period . RESULTS The three drugs were effective in the control of post-operative pain ( p<0.01 ) . Variations in pain intensity and the use of additional medication between the treatment groups were observed over the study period . The Diflunisal group experienced less pain than the Panadeine or Etodolac group ( p<0.01 ) . Furthermore , a lesser number of those in the Diflunisal group used additional medication compared to the other two groups ( p<0.01 ) . The incidence of side effects from all three drugs was low . CONCLUSION Diflunisal is superior in the control of  pain following third molar surgery under local anaesthesia than either Panadeine or Etodolac , and has few side effects The efficacy of oral ketorolac 5 mg and 10 mg taken qid was compared in a r and omized double-blind study with that of oral diflunisal 500 mg bid ( interleaved with placebo twice daily ) and of placebo , in 120 patients suffering at least moderate pain following meniscectomy . The trial comprised two phases : ( 1 ) an acute phase ( the first postoperative day ) and ( 2 ) a chronic phase ( days 2 - 5 postoperatively ) . Acutely , pain was assessed before drug administration , and then 0.5 , 1.0 , 2.0 , 3.0 , 4.0 , 6.0 , 8.0 , and 9.0 hours after the first dose . The second of the four daily doses was administered at four hours after the first dose . During the chronic phase , pain was assessed using visual analogue scales at 8 AM and 4 PM daily . The acute phase results show that all the active treatments were statistically significantly superior to placebo but were not distinguished from each other . Over the chronic phase , ketorolac 5 mg and placebo showed similar results , with diflunisal showing the least pain relief and ketorolac 10 mg the most . All the active treatments showed a low incidence of side effects and , in an overall evaluation , no one treatment was distinguishable . Ketorolac would seem to be an acceptable therapy for acute postoperative pain 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 A double-blind , r and omized analgesic trial was carried out in 150 patients undergoing surgical removal of their 2 impacted lower wisdom teeth . The analgesic efficacy of effervescent acetaminophen 500 or 1000 mg in a 2-dose regimen was compared with that of diflunisal 500 mg in a single dose . Each dose was taken when subjectively needed and the pain intensity was measured on a visual analog scale during the 10-hour period after first medication . The best pain reduction was achieved with diflunisal . The difference between diflunisal 500 mg and acetaminophen 1000 mg was significant , as was that between acetaminophen 1000 and 500 mg . The peak effect after the first dose occurred later but was greater with diflunisal than with acetaminophen . Patients needing analgesics at low pain intensities seemed to discriminate better between treatments , and the efficacy of acetaminophen was weakly dependent on the initial pain intensity . This intensity was difficult to predict , and only a poor correlation was found between the initial pain intensity and the patient 's prior estimate of this 1 . Seven hundred and forty patients complaining of pain after oral or orthopaedic surgery or episiotomy were studied in five single dose or short-term double-blind , controlled , r and omized studies comparing efficacy and safety of diflunisal with that of acetylsalicylic acid , glafenin or placebo . 2 . Diflunisal was found to be effective in relieving postoperative pain in 75 - 85 % of patients . A twice day dosage schedule seems to be clinical ly adequate , 375 mg twice daily proving to be equally effective as glafenin 200 mg three times daily . No serious drug-related clinical or laboratory adverse experiences were encountered in any of the five studies 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 A total of 100 patients were enrolled after orthopaedic surgery in a multiple-dose , r and omized , double-blind , parallel-group study to compare the analgesic efficacy and safety of 10 mg ketorolac tromethamine given orally four times daily for 3 days with 500 mg diflunisal given orally twice daily plus placebo twice daily for 3 days . Ketorolac was significantly ( P = 0.04 ) superior to diflunisal in reducing the pain severity during the first 9 h of treatment ; a difference possibly related to the more flexible dosage regimen of ketorolac . Patients and the investigator , however , rated ketorolac and diflunisal as being equally effective in terms of the overall drop in severity of pain and pain relief at the end of days 1 , 2 and 3 . Ketorolac-treated patients reported a total of nine adverse events and diflunisal-treated patients reported 13 . It is concluded that in the treatment of acute post-operative pain a drug with a more flexible dosage regimen may provide superior pain relief A double-blind , completely r and omized study was carried out on 169 patients to compare the analgesic efficacy and tolerability of diflunisal with that of Veralgin  after surgical removal of impacted third molars . One group received 1000 mg diflunisal ( Donobid , MSD ) 2 h preoperatively and then 500 mg twice daily for 2.5 days , and the other group Veralgin ( aminophenazon . 286 mg , barbital . 114 mg , aethylmorph . hydrochlorid . 20 mg , Orion ) , a fixed combination widely used in Finl and , 1 tablet twice daily beginning 2 h prior to operation . Visual analogue scales were used to estimate pain . Diflunisal was found to be superior in relieving pain in the early postoperative period , the associated frequency of adverse clinical experiences was lower and the final evaluation of analgesic efficacy by both the patients and the investigators , was in its favour . The study confirms that postoperative pain after third molar surgery can be controlled well without the use of mainly central ly acting combination analgesics & NA ; 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 , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics .  Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal ( Dolobid ) , a new nonsteroidal anti-inflammatory analgesic , was compared in a double-blind study with that of acetaminophen , 600 mg , the combination of acetaminophen , 600 mg , with codeine phosphate , 60 mg , and placebo in 159 oral surgery out patients . Using a self-rating record , patients rated their pain and its relief hourly for 12 hours after medication . Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination . Diflunisal proved to have an unusually long duration of analgesic action .  Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5 , respectively ; both doses of diflunisal were significantly superior through the end of the 12-hour observation period . None of the active treatments produced more side effects than the placebo Two-hundred and one out patients with postoperative pain following oral surgery were r and omly assigned , on a double-blind basis , a single oral dose of diflunisal ( 250 , 500 , or 1000 mg ) , aspirin ( 650 mg ) , or placebo . Using a self-rating record , the subjects rated their pain and its relief hourly for 12 hours after medication . Measures of peak and total analgesia were derived from the patients ' subjective reports . Diflunisal 250 and 1000 mg were significantly superior to aspirin for every measure of total and peak analgesia ; the 500-mg diflunisal dose 
    Output:
    
Diflunisal has an analgesic effect similar to other NSAIDs in single dose , but benefits from providing significant analgesia for about twelve hours .
This property may be useful when regular dosing is needed , or when taking several doses of a shorter acting analgesic is impractical