***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 Eighty‐two out patients who received general anaesthesia for surgical removal of maxillary or m and ibular third molars were given either diclofenac 75 mg or nefopam 20 mg intramuscularly for postoperative pain control . They and the control group were also allowed oral paracetamol as required . The results showed that there was no significant pain relief from these single intramuscular injections A double-blind , between-patient , two-dose comparison was comparison was performed with pethidine and nefopam in 100 subjects , the majority of whom were recovering from upper abdominal surgery . Either 15 or 30 mg of nefopam or 50 or 100 mg of pethidine were given by i.m . injection in a r and om order . All assessment s were made by the same observer on the first day after operation , at least 4 h after the previous analgesic injection . Nefopam 15 mg was equipotent with pethidine 50 mg , peak analgesia being achieved 1 h after the i.m . injection . Pethidine 100 mg provided significantly better pain relief than nefopam 30 mg , the latter being not more effective than nefopam 15 mg apart from the duration of analgesia which was longer . The incidence of nausea and vomiting was similar after both drugs . Sweating and tachycardia were observed more frequently after nefopam , whereas sedative side-effects were more common after pethidine & NA ; We carried out a national survey on postoperative pain ( POP ) management in a representative sample ( public/private , teaching/non‐teaching , size ) of 76 surgical centers in France . Based on medical records and question naires , we evaluated adult patients 24 h after surgery , concerning information : pre and postoperative pain , evaluation , treatment and side effects . A local consultant provided information about POP management . Data were recorded for 1900 adult patients , 69.3 % of whom remembered information on POP . Information was mainly delivered orally ( 90.3 % ) and rarely noted on the patient ’s chart ( 18.2 % ) . Written evaluations of POP  were frequent on the ward ( 93.7 % ) with appropriate intervals ( 4.1 ( 4.0 ) h ) , but not frequently prescribed ( 32.7 % ) . Pain evaluations were based on visual analog scale ( 21.1 % ) , numerical scale ( 41.2 % ) , verbal scale ( 13.8 % ) or non‐numerical tool ( 24 % ) . Pain was rarely a criterion for recovery room discharge ( 19.8 % ) . Reported POP was mild at rest ( 2.7 ( 1.3 ) ) , moderate during movement ( 4.9 ( 1.9 ) ) and intense at its maximal level ( 6.4 ( 2.0 ) ) . Incidence of side effects was similar according to patient ( 26.4 % ) or medical chart ( 25.1 % ) including mostly nausea and vomiting ( 83.3 % ) . Analgesia was frequently initiated during anesthesia ( 63.6 % ) .  Patient‐controlled analgesia  ( 21.4 % ) was used less frequently than subcutaneous morphine ( 35.1 % ) whose prescription frequently did not follow guidelines . Non‐opioid analgesics used included paracetamol ( 90.3 % ) , ketoprofen ( 48.5 % ) and nefopam ( 21.4 % ) . Epidural ( 1.5 % ) and peripheral ( 4.7 % ) nerve blocks were under used . Evaluation ( 63.4 % ) or treatment ( 74.1 % ) protocol s were not available for all patients . This national , prospect i ve , patient‐based , survey reveals both progress and persistent challenges in POP management BACKGROUND Balanced postoperative analgesia combines non-narcotic drugs and opioids . We organized a large study to evaluate nefopam analgesia and tolerance in combination with morphine for patient-controlled analgesia ( PCA )  after orthopaedic surgery . METHODS Two hundred and one patients scheduled to undergo hip arthroplasty were included in this multicentre ( n=24 ) , double-blind , r and omized study comparing nefopam ( 20 mg every 4 h for 24 h ) with placebo , the first dose being infused peroperatively . The primary outcome measure was the cumulative morphine dose received postoperatively by PCA over 24 h. Secondary outcome measures were the amount of morphine received as a loading dose in the postanaesthesia care unit ( PACU ) and during the 24-h observation period , and pain assessment s using a visual analogue scale ( VAS ) and a verbal pain scale ( VPS ) , patient 's satisfaction with analgesia and treatment tolerance . RESULTS The two groups were comparable with respect to their characteristics and preoperative pain assessment . PCA-administered morphine over 24 h was significantly less for the nefopam group than the control group ( 21.2 ( 15.3 ) and 27.3 ( 19.2 ) mg respectively ; P=0.02 ) . This morphine-sparing effect was greater ( 35.1 % ) for patients with severe preoperative pain ( VAS>30/100 ) . For the entire study period ( loading dose and PCA ) , morphine use was less for the nefopam group ( 34.5 ( 19.6 ) vs 42.7 ( 23.6 ) mg ; P=0.01 ) . Pain VAS at PACU arrival and during the whole PACU period was significantly lower for the nefopam than for the placebo group ( P=0.002 and 0.04 respectively ) . Patient satisfaction was similar for the nefopam and placebo groups . CONCLUSION In combination with PCA morphine , nefopam gives significant morphine-sparing with lower immediate postoperative pain scores without major side-effects . This analgesic effect seems to be particularly notable for patients with intense preoperative 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 One hundred and ninety-six hospitalized patients were r and omly assigned to one of eight treatment groups consisting of oral or intramuscular analgesics and placebo . Patients were monitored for 6 hours for pain relief , vital signs , and side effects . No statistically significant differences in pain intensity or relief were seen for nefopam ( Acupan ) , diphenhydramine ( Benadryl ) , aspirin , or placebo despite a numerically higher score for nefopam . This is attributed to an unexpectantly high placebo response . Significant pain relief and reduction of pain intensity were seen with both parenteral nefopam and morphine .  Side effect incidence , in general , paralleled analgesic efficacy and was higher in patients receiving parenteral drugs . An early hypothermic effect was noted with oral and parenteral nefopam , aspirin , and morphine .  Lower temperatures persisted to a statistically significant degree only in nefopam-treated patients In immediate postoperative period , many injectable analgesics are being used with diverse side effects . The present study was conducted on 75 patients of both sexes , who underwent various types of surgery , to evaluate pain relief in immediate postoperative period . The drugs used for producing postoperative analgesia are buprenorphine , pentazocine and nefopam , all by intramuscular route & 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 A double-blind clinical study comparing a new non-narcotic analgesic , nefopam , with pentazocine was carried out on 50 Indian patients . Forty patients had undergone surgical procedures , and the remaining 10 had musculoskeletal or traumatic disorders . There were 25 patients in each group . It was observed that both drugs were capable of relieving post-surgical pain which was either very severe ( score 4 ) or severe ( score 3 ) . Their efficacy was comparable . In patients who had an initial pain score of 4 , a significant ( p less than 0.05 ) fall in the sum of pain intensity scores ( SPIS ) occurred in two days . For an initial pain score of 3 , a correspondingly significant fall in SPIS took three days . These results were statistically significant ( p less than 0.01 ) . Nefopam had a significantly better side effect profile than pentazocine . In the nefopam group , 4/25 patients had side effects , as opposed to 10/25 in the pentazocine group ( p less than 0.05 , Fisher 's exact probability test ) . It was also noted that the incidence of side effects was greater in the pentazocine group ( 61 ) than the nefopam group ( 22 ) , the difference being statistically highly 
    Output:
    
AUTHORS ' CONCLUSIONS In the absence of evidence of efficacy for oral nefopam in acute postoperative pain , its use in this indication is not justified .