***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 To investigate the combined analgesic and spasmolytic effect of dipyrone , 104 patients suffering from “ severe ” or “ excruciating ” colic pain due to a confirmed calculus in the upper urinary tract were r and omized to receive i.v . either 2.5 g dipyrone ( 36 patients ) , 100 mg tramadol ( 35 patients ) , or 20 mg butylscopolamine ( 33 patients ) in a multicentre , observer-blind , parallel-group study conducted in 8 German centres . The three treatment groups were homogeneous when analyzed by age , sex , height , and baseline pain intensity . Dipyrone was significantly more effective than tramadol in reducing pain for the primary endpoint , pain intensity differences ( PID ) at 20 , 30 , and 50 min after drug administration , and was significantly more effective than butylscopolamine at 30 and 50 min for the secondary efficacy endpoint , pain intensity differences on a categorical scale . Dipyrone had the highest SPID0–2 h of the three drugs ( P<0.05 ) . Only 5 patients receiving dipyrone needed “ rescue ” medication as compared with 13 patients given tramadol and 11 patients receiving butylscopolamine .  Adverse events were observed in 4 patients receiving butylscopolamine and in 1 patient each given dipyrone and tramadol . “ Distinct ” pain relief as assessed on a visual analogue scale ( VAS ) is a reliable method of determining the onset of analgesic action in the colic pain model A comparative , r and omized , double-blind study of diclofenac sodium 75 mg i m versus Baralgin ( a combination drug composed of dipyrone and two spasmolytics ) 5 mL iv was performed on 57 patients with renal colic . Both groups were comparable as to age , sex , pain evolution time before treatment , and no treatment for renal colic in the six hours preceding trial drug administration . No significant differences were found between the two groups with respect to the evolution of pain after the first dose or in the frequency of administration of a second dose . Tolerability was good in both groups , but sweating and pain throughout the vein were observed in one patient in the Baralgin group . We concluded that diclofenac sodium constitutes an excellent alternative to pyrazolone analgesics , with the advantages of being monotherapy and having good tolerability , when used as intramuscular injection in ambulatory patients 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 double-blind r and omized , clinical trial was conducted in 43 patients to evaluate the efficacy of sublingual nifedipine in the treatment of pain in renal colic .  Comparison was made with a combination of dipyrone , pitofenone and fenpipramide , which is usually administered intravenously in Spain . With nifedipine , pain completely disappeared in 44 % of the cases , and with the combination of drugs , in 89 % ( p less than 0.005 ) . More adverse effects were noted with the combination than with nifedipine . Both treatments brought about a slight drop in arterial pressure without leading to hypotension in any case . There was no change in heart rate . The possible causes of the relatively low level of success with nifedipine were analyzed . The possibility of using nifedipine under certain circumstances in which other drugs are contraindicated or when their administration is unfeasible is suggested & 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 In a double-blind , double-dummy r and omized controlled clinical trial , the onset and duration of the analgesic effect of dipyrone , 1 or 2 g , and diclofenac sodium , 75 mg , by either the i.m . or the i.v . route were compared in 293 patients ( aged 18–70 years ) with acute renal colic . A level of ≥ 50 mm on the 100-mm visual analogue scale was required for inclusion in the study . Patients were r and omly allocated to six treatment groups , receiving dipyrone 1 g i.m . , dipyrone 1 g i.v . , dipyrone 2 g i.m . , dipyrone 2 g i.v . , diclofenac sodium 75 mg i.m . ; and diclofenac sodium 75 mg i.v , respectively . Evaluations were performed at 10 , 20 , 30 , and 60 min and 2 , 4 , and 6 h after treatment ( time 0 ) . Primary efficacy end points included course of pain , total pain , percentage of patients with a pain improvement of 50 % or more at each evaluation time , pain intensity evaluated by the investigator on a 0–3 scale , and differences in pain intensity . The analgesic response was more marked and prolonged among patients receiving dipyrone 2 g i.m . or dipyrone 2 g i.v . There were no significant differences between dipyrone 1 g and diclofenac sodium 75 mg , by either the i.m . or the i.v . route . All treatment regimens were well tolerated & 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 Summary A r and omized , double-blind clinical trial in 50 patients was done to compare the efficacy and tolerance of single doses of intramuscular diclofenac 75 mg and dipyrone 2 g in acute renal colic . Both drugs were equally effective , but diclofenac was better in terms of complete relief of pain . Vital signs were affected according to the stress and pain A single-blind , r and omized clinical trial was carried out to compare the analgesic effectiveness in patients with renal colic of single intramuscular doses of diclofenac sodium ( 75 mg ) versus a dipyrone ( 1 g)/spasmolytics combination , and diclofenac sodium ( 75 mg ) versus pethidine ( 75 mg ) . The first study involved three centres , the second study one centre . In total , 107 patients were treated with diclofenac sodium , 85 with dipyrone/spasmolytics , and 25 with pethidine . Assessment s were made during the first hour after drug administration of the degree of pain relief , the severity of pain using a visual analogue scale , and the duration of analgesia . A global assessment of treatment efficacy was made by the participating physicians at the end of the study period . Patients treated with diclofenac sodium showed an earlier onset of analgesia and a higher incidence of total pain relief compared to those treated with dipyrone/spasmolytics or pethidine . Although the mean duration of analgesia was only slightly greater in the diclofenac sodium group than in the dipyrone/spasmolytics group , a significantly longer effect was seen when diclofenac sodium was compared with pethidine ( p less than 0.01 ) . Pain severity assessment s revealed that diclofenac sodium caused a significantly greater improvement in pain after 60 minutes compared to dipyrone/spasmolytics ( p less than 0.05 ) and after 30 minutes compared to pethidine ( p less than 0.05 ) . Global efficacy assessment s by the physician rated diclofenac sodium as significantly superior to dipyrone/spasmolytics ( p less than 0.01 ) and pethidine ( p less than 0.001 ) . Moreover , diclofenac sodium was better tolerated than either of the comparative treatments . The results indicate that intramuscular diclofenac sodium is a useful alternative to the drugs commonly used in India in the treatment of renal colic Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain 
    Output:
    
REVIEW ER 'S CONCLUSIONS Limited available data indicated that single dose dipyrone was of similar efficacy to other analgesics used in renal colic pain , although intramuscular dipyrone was less effective than diclofenac 75 mg .
Combining dipyrone with antispasmolytic agents did not appear to improve its efficacy .
Intravenous dipyrone was more effective than intramuscular dipyrone .
Dry mouth and somnolence were commonly reported with intravenous dipyrone .