***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 Abstract Pre clinical studies of chemoprevention drugs given in combination at low doses show remarkable efficacy in preventing adenomas with little additional toxicities , suggesting a strategy to improve risk to benefit ratios for preventing recurrent adenomas . Three hundred seventy-five patients with history of resected ( ≥3 mm ) adenomas were r and omly assigned to receive oral difluoromethylornithine ( DFMO ) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months , stratified by use of low-dose aspirin ( 81 mg ) at baseline and clinical site . Follow-up colonoscopy was done 3 years after r and omization or off- study . Colorectal adenoma recurrence was compared among the groups with log-binomial regression . Comparing the outcome in patients receiving placebos to those receiving active intervention , ( a ) the recurrence of one or more adenomas was 41.1 % and 12.3 % ( risk ratio , 0.30 ; 95 % confidence interval , 0.18 - 0.49 ; P < 0.001 ) ; ( b ) 8.5 % had one or more advanced adenomas , compared with 0.7 % of patients ( risk ratio , 0.085 ; 95 % confidence interval , 0.011 - 0.65 ; P < 0.001 ) ; and ( c ) 17 ( 13.2 % ) patients had multiple adenomas ( > 1 ) at the final colonoscopy , compared with 1 ( 0.7 % ; risk ratio , 0.055 ; 0.0074 - 0.41 ; P < 0.001 ) . Serious adverse events ( grade ≥3 ) occurred in 8.2 % of patients in the placebo group , compared with 11 % in the active intervention group ( P = 0.35 ) . There was no significant difference in the proportion of patients reporting hearing changes from baseline . Recurrent adenomatous polyps can be markedly reduced by a combination of low oral doses of DFMO and sulindac and with few side effects 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 & 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 OBJECTIVE The purpose of this study was to establish whether nimesulide causes fewer fetal side effects than indomethacin or sulindac after short-term maternal exposure for tocolysis . STUDY DESIGN This was a double-blind , double-dummy prospect i ve r and omized study with three drug treatment groups ( n = 10 per group ) that were comprised of subjects who were at 28 to 32 weeks of gestation with preterm contractions . The subjects were treated in the delivery suites of two busy inner-city teaching hospitals ; the intervention consisted of 48 hours of treatment and with 72 hours of follow-up observation with indomethacin 100 mg ( twice daily ) , sulindac 200 mg ( twice daily ) , or nimesulide 200 mg ( twice daily ) . The amniotic fluid index , hourly fetal urine production , and ductal Doppler pulsatility index observations were monitored before the treatment and at 4 , 24 , 48 , 72 , and 120 hours after the treatment was started . The statistical analysis used repeated measures analysis of variance , Bonferroni test , and Bl and -Altman agreement . Significance assumed when the probability value was < .05 . RESULTS Each drug caused a significant reduction in all three observations over the 48-hour treatment period , which recovered to pretreatment levels by 72 hours after treatment . There were no significant differences among drugs for any of these effects . CONCLUSION Nimesulide causes similar short-term fetal side effects to indomethacin and sulindac ABSTRACT Objective : To evaluate the effects of long-term treatment with sulindac on the progression of diabetic retinopathy ( DR ) . Research design and methods : 40 Japanese patients with type 2 diabetes were enrolled in a r and omized , single-blind controlled trial in which the effects of sulindac ( 200 mg/day , 100 mg twice a day ; n = 16 patients ) on the progression of DR were compared to controls ( 24 patients ) for 3 years . All patients were comparable in their age , gender , duration of disease , body mass index , dipstick proteinuria , insulin therapy , glycemic control , and clinical stages of DR . Outcome was determined by comparing parameters of retinopathy in fundus photographs that were taken at time 0 to those taken 1 , 2 , and 3 years after the initiation of treatment . Results : Patients in the sulindac group did not develop DR during the course of treatment nor was there progression of pathology in those who began the study with mild non-proliferative DR ( NPDR ) . On the other h and , six patients progressed to mild NPDR in the control group – three at year 1 and three at year 3 – and an additional patient progressed to severe NPDR from mild NPDR by year 1 and to proliferative DR by year 2 . The findings at year 3 in the sulindac group were significantly ( p < 0.05 ) different from the control group . None of the patients experienced any adverse effects of treatment . Conclusions : Long-term treatment with sulindac was clinical ly effective in decreasing the progression of mild DR in type 2 diabetic patients in this pilot study & 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 Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics .  Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain .  The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale The elderly ( age > 65 years ) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs ( NSAIDs ) . We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis , 65 years of age or older .  Sulindac was chosen because of its possible renal sparing effects , and ketoprofen SR because of its short half life and sustained release delivery system . Eighty patients were entered . More patients withdrew from the study due to side-effects in the sulindac group ; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs , demonstrating that the elderly are susceptible to side-effects from NSAID 
    Output:
    
AUTHORS ' CONCLUSIONS In the absence of evidence of efficacy , at present , for oral sulindac in acute postoperative pain , its use in this indication is not justified .