***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 & NA ; The efficacy of ketorolac , a non‐steroidal anti‐inflammatory drug , in the management of moderate to severe pain in adults , has led us to conduct a trial of this analgesic in children following tonsillectomy . Children were r and omized to receive intramuscular ( i.m . ) ketorolac ( 1 mg/kg , EXP group , n = 45 ) or saline ( CTL group , n = 42 ) at the completion of surgery . Intravenous ( i.v . ) fentanyl ( 0.5 & mgr;g/kg/dose ) was administered in repeated doses postoperatively . Pain intensity was measured using both the Oucher and the Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) to allow for comparison between self‐report and behavioral measures of pain intensity . Severity of postoperative bleeding was measured using a 4‐point rating scale . The EXP group had a significant reduction in total fentanyl dose ( mean : 35.9 & mgr;g ) compared to the CTL group ( mean : 48.3 & mgr;g , t = −2.21 , P < 0.03 ) . There was a statistically significant decrease in pre‐fentanyl CHEOPS scores in the Post‐Anesthesia Care Unit ( PACU ) in the ketorolac group ( F ( 2,30 ) = 5.34 , P < 0.01 ) , but not in the saline group ( F ( 2.24 ) = 2.46 , P > 0.05 ) . In the first hour postoperatively , the CHEOPS demonstrated significant decreases in pain intensity scores in response to opioids , in both groups . In the PACU , children were unable to provide a self‐report of pain intensity potentially due to a variety of factors ( e.g. , emergence delirium , agitation , excitement , sedation , and /or pain ) . However , during the remainder of the postoperative stay , the photographic scale of the Oucher was a more valid measure of pain intensity than the CHEOPS . There were no differences between the 2 groups in the severity of postoperative bleeding . Children in the EXP group were discharged significantly earlier ( i.e. , 30 min , t = −2.22 , P < 0.03 ) . Our data demonstrate that i.m . administration of ketorolac , at the end of surgery , significantly reduces opioid requirements and shortens length of stay without any evidence of increased bleeding . In addition , our data suggest that the patient 's altered level of consciousness and attention span may diminish the utility of self‐report measures of  pain intensity  in the immediate postoperative period Prophylactic administration of analgesics before surgery can decrease the intraoperative anaesthetic requirement and decrease pain during the early postoperative period . In a doubleblind , placebocontrolled study involving 90 healthy ASA physical status I or II children undergoing bilateral myringotomy , we compared the postoperative analgesic effects of oral acetaminophen and ketorolac , when administered 30 min before induction of anaesthesia . Patients were r and omized to receive saline ( 0.1 ml · kg−1 ) , acetaminophen ( 10 mg · kg−1 ) or ketorolac ( 1 mg · kg−1 ) diluted in cherry syrup to a total volume of 5 ml . Anaesthesia was induced and maintained with halothane and nitrous oxide via a face mask . Postoperative pain was assessed by a blinded observer using an objective pain scale . The three study groups were similar with respect to demographic data , duration of anaesthesia and surgery , induction behaviour , oxygen saturation , incidence of postoperative emesis and , recovery times . The ketorolac group had lower postoperative pain scores and required less frequent analgesic therapy in the early postoperative period compared with the acetaminophen and placebo groups . In contrast , there were no differences in pain scores or analgesic requirements between the acetaminophen and the placebo groups . We conclude that the preoperative administration of oral ketorolac , but not acetaminophen , provided better postoperative pain control than placebo in children undergoing bilateral myringotomy . RésuméL’administration prophylactique d’analgésiques avant la chirurgie peut diminuer les besoins anesthésiques peropératoires et la douleur durant la période postopératoire immédiate . Quatrevingtdix enfants avec un état physique ASA I ou II devant subir une myringotomie bilatérale participent à cette étude à doubleinsu avec un groupe contrôleplacebo . Sont comparés les effets analgésiques postopératoires de l’acétaminophène et du kétoralac administrés par voie orale 30 minutes avant l’induction anesthésique . Les patients reçoivent au hasard soit de la solution saline ( 0.1 ml · kg−1 ) , soit de l’acétaminophène ( 10 mg · kg−1 ) , soit du kétoralac ( 1 mg · kg−1 ) . Chacune des préparations est diluée dans un sirop à saveur de cerise pour faire un total de 5 ml . L’induction et l’entretien de l’anesthésie se font avec de l’halothane et du protoxyde d’azote administrés par masque . Un observateur non informé du médicament donné au patient évalue la douleur postoperatoire à l’aide d’une échelle de douleur objective . Les variables démographiques , la durée de l’anesthésie et de la chirurgie , le comportement à l’induction , la saturation artérielle en oxygène , l’incidence des vomissements postopératoires et le temps d’éveil sont comparables entre les trois groupes . Les patients du groupe kétoralac ont un pointage de douleur postopératoire plus bas que ceux des groupes acétaminophène et placebo , et Us nécessitent moins souvent un supplément analgésique . D’autre part , il n’ya pas de différence entre les groupes acétaminophène et placebo pour la douleur et les besoins analgésiques postopératoires . En conclusion , le kétoralac , mais pas l’acétaminophène , administré par la bouche avant la chirurgie assure une meilleure analgésie postopératoire qu’un placebo chez les enfants subissant une myringotomie bilatérale We studied the analgesic efficacy of tramadol 2 mg kg(-1 ) for post-operative analgesia after day-case adenoidectomy in children aged 1 - 3 yr . Eighty children were allocated r and omly to receive tramadol 2 mg kg(-1 ) i.v . or placebo immediately after induction of anaesthesia . Anaesthesia was induced with alfentanil 10 microg kg(-1 ) and propofol 4 mg kg(-1 ) followed by mivacurium 0.2 mg kg(-1 ) for tracheal intubation . Anaesthesia was continued with sevoflurane in nitrous oxide and oxygen . All children were given ibuprofen rectally at approximately 10 mg kg(-1 ) before the start of surgery . Post-operative pain and recovery assessment s were performed by a nurse blinded to the analgesic treatment using the Aldrete recovery score , the pain/discomfort scale and measurement of recovery times .  Rescue medication ( pethidine in increments of 5 mg i.v . ) was administered according to the pain scores . A post-operative question naire was used to evaluate the need for analgesia at home up to 24 h after operation . Rescue analgesic at home was rectal or oral ibuprofen 125 mg . Children in the tramadol group required fewer  pethidine doses than those in the placebo group ( P = 0.014 ) . Forty-five per cent of children receiving tramadol did not require post-operative analgesia at all compared with 15 % of children receiving placebo ( P = 0.003 ) . Recovery times and the incidence of adverse effects were similar in the two groups in the recovery room and at home . The requirement for rectal ibuprofen at home did not differ between groups UNLABELLED In this r and omized , double-blinded , placebo-controlled , prospect i ve study , we evaluated the analgesic efficacy of dextromethorphan 0.5 mg/kg or 1.0 mg/kg p.o . 1 h before adenotonsillectomy in 57 children 6 - 12 yr of age . Anesthetic management was st and ardized . Morphine 0.075 mg/kg i.v . and acetaminophen 25 - 35 mg/kg p.r . were administered after anesthetic induction but before the start of surgery . A 4-point behavioral score ( 1 = asleep , 2 = awake and calm , 3 = awake and crying , 4 = thrashing ) was recorded on admission to and discharge from the postanesthesia care unit ( PACU ) . In the PACU , pain was assessed with Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) and recorded every 15 min until the patient was transferred to the day surgery unit ( DSU ) . In the DSU , patients rated their pain using a 10-cm baseline 0 - 10 visual analog pain scale ( VAS ) every 30 min until they were discharged home . A 24-h VAS was obtained by phone interview , and parental satisfaction was scored ( yes/no ) regarding their child 's postoperative analgesia . Morphine 0.025 mg/kg i.v . was administered to children with CHEOPS score > 6 , who verbalized pain , or who were crying in any consecutive 5-min observation periods in the PACU . Total morphine consumption was recorded . The study groups were comparable with respect to demographic variables . We were unable to detect any differences between study groups with respect to postoperative morphine consumption , CHEOPS , behavior scores , VAS , or parental satisfaction . IMPLICATION S Premedication with dextromethorphan 0.5 or 1.0 mg/kg p.o . does not improve postoperative analgesia in school-aged children who receive preemptive morphine 0.075 mg/kg i.v . and acetaminophen 25 - 35 mg/kg p.r . during nitrous oxide and desflurane anesthesia for adenotonsillectomy After umbilical hernia surgery , and wound infiltration with bupivacaine 0.5 % , 17 children were given ketorolac 0.5 mg.kg-1 , with 18 controls receiving only the wound infiltration . No child experienced severe pain , but moderate pain was noted in patients in both groups . Objective and subjective pain scores were not different statistically at any point up to the morning after surgery Administration of analgesics before surgery can decrease the intra-operative anesthetic requirement and pain during the early post-operative period ( pre-emptive analgesia ) . The objective of this study was to evaluate an intra-muscular preparation of ketoprofen as analgesic in mild to moderate pain in children . In a double-blind placebo-controlled study , 91 healthy ASA I or II children undergoing squint opthalmic surgery was undertaken in the Ophthalmic Services at King Abdel-Aziz University Hospital Riyadh . The postoperative analgesic effects of intra-muscular pethidine and ketoprofen , just after the induction of anesthesia were compared . Patients were r and omized to receive ketoprofen ( 1 mg W kg-1 ) , pethidine ( 1 mg W kg-1 ) or saline ( 0.1 ml W kg-1 ) . Anesthesia was induced and maintained with halothane and nitrous oxide via 
    Output:
    
Placebo control groups can be used in paediatric analgesic studies to demonstrate internal sensitivity