***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: Purpose : To test the hypothesis that an experienced surgeon is associated with less postoperative nausea and vomiting ( PONV ) BACKGROUND Combination therapy has been widely used for the clinical management of acute pain .  By combining 2 drugs with different mechanisms of action , such therapy provides additive analgesic effects while reducing the risk for adverse effects . OBJECTIVE This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo in a dental pain model . METHODS This was a multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group , single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars . Patients were r and omly assigned to receive oxycodone 5 mg/ibuprofen 400 mg , oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , or placebo . The primary outcome measures were total pain relief through 6 hours after dosing ( TOTPAR6 ) , sum of pain intensity differences through 6 hours ( SPID6 ) , and adverse events . Secondary efficacy measures included SPID3 and TOTPAR3 , peak pain relief , peak pain intensity difference , time to onset of pain relief , time to use of rescue medication , proportion of patients reporting pain half gone , and the patient 's global evaluation . RESULTS Two hundred forty-nine patients ( 43.5 % male ; 87.5 % white ; mean age , 19.1 years ; mean body weight , 153.6 pounds ) were r and omized to treatment as follows : 62 to oxycodone 5 mg/ibuprofen 400 mg , 61 to oxycodone 5 mg/acetaminophen 325 mg , 63 to hydrocodone 7.5 mg/acetaminophen 500 mg , and 63 to placebo . Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo ( mean [ SD ] TOTPAR6 , 14.98 [ 5.37 ] , 9.53 [ 6.77 ] , 8.36 [ 6.68 ] , and 5.05 [ 6.49 ] , respectively ; P < 0.001 , oxycodone 5 mg/ibuprofen 400 mg vs all other treatments ) . SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments ( mean : 7.78 [ 4.11 ] , 3.58 [ 4.64 ] , 3.32 [ 4.73 ] , and 0.69 [ 4.85 ] ; P < 0.001 ) . Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points ( P < 0.001 , all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [ P = 0.006 ] ) , with the exception of the time to onset of analgesia . The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg ( 6.5 % and 3.2 % , respectively ) and placebo ( 3.2 % and 1.6 % ) . Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg ( P = 0.011 and P = 0.009 , respectively ) but not with hydrocodone 7.5 mg/acetaminophen 500 mg . CONCLUSIONS In this study in patients with moderate to severe pain after surgery to remove impacted third molars , oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested , and was associated with fewer adverse events In this double-blind , parallel-group study , we compared 3 oxymorphone immediate-release ( IR ) doses with placebo for efficacy and with oxycodone IR and placebo for safety in patients with acute moderate-to-severe postsurgical pain . During the single-dose phase ( n = 300 ) , patients received oxymorphone IR 10 , 20 , or 30 mg ; oxycodone IR 10 mg ; or placebo . All oxymorphone IR doses were superior for providing pain relief for 8 h ( P < 0.05 ) , with a significant analgesic dose response ( P < 0.001 ) . Significant pain intensity differences occurred by 45 min ( 20- and 30-mg doses ; P < 0.05 ) . Discontinuations for lack of efficacy totaled 42 % among placebo-treated patients and 27 % among those treated with oxymorphone IR . Patients requiring rescue medication after 3 h were allowed to receive additional study drug every 4 to 6 h as needed for the multiple-dose phase ( n = 164 ) . All oxymorphone groups maintained analgesia for 48 h. The median dosing interval was > 9.5 h for oxymorphone IR 30 mg and ≥7 h for the other groups . Opioid-related adverse events , similar among groups , were generally mild or moderate . Oxymorphone IR 10 , 20 , or 30 mg provided significant dose-related pain relief compared with placebo , and this relief was maintained over several days with a safety profile comparable to that of oxycodone IR The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug , flurbiprofen , and a long-acting local anesthetic , etidocaine , was evaluated for the suppression of  acute postoperative pain . Subjects having two impacted third molars removed at two appointments received either the experimental combination or st and ard treatment in a r and omized , crossover design . The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery , 1.5 % etidocaine with 1:200,000 epinephrine five minutes before surgery , and 100 mg flurbiprofen three hours after surgery . St and ard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery , 2 % lidocaine with 1:100,000 epinephrine five minutes before surgery , and a second dose of the oxycodone-acetaminophen combination three hours after surgery . Pain intensity was rated hourly from one to seven hours after surgery , using a variety of ordinal and analog scales . The flurbiprofen-etidocaine combination result ed in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients . This study shows that pretreatment with a nonsteroidal anti-inflammatory drug , flurbiprofen , in combination with a long-acting local analgesic , etidocaine , suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability STUDY OBJECTIVE To determine whether the addition of morphine to the axillary block local anesthetic solution provides improved or prolonged postoperative analgesia . DESIGN Prospect i ve , r and omized , double-blind clinical trial with 24-hour follow-up . SETTING Ambulatory unit of a large academic referral center . PATIENTS Consecutive healthy volunteers scheduled for elective upper extremity surgery . INTERVENTIONS Patients in the treatment group ( AX ) were given intravenous ( IV ) saline and had morphine 0.1 mg/kg added to their axillary block solution .  Control subjects ( CT ) received morphine 0.1 mg/kg IV and had saline added to their axillary block solution . All axillary blocks were performed using 0.55 ml/kg of 1.5 % lidocaine with epinephrine 1:200,000 . MEASUREMENTS AND MAIN RESULTS During the first 24 hours after surgery , visual analog scale ( VAS ) scores , supplementary analgesic ( oxycodone 5 mg with acetaminophen 500 mg ) use , and complications were recorded . Both groups had similar VAS scores throughout the study . In the 24-hour postoperative study period , AX patients required approximately half as many doses ( median , 2 doses ; range , 0 to 7 doses of supplemental analgesic as CT patients ( median , 4 doses ; range , 0 to 12 doses ) . There were no major complications in either group . CONCLUSIONS The addition of morphine 0.1 mg/kg to the local anesthetic axillary block solution provided improved postoperative analgesia without an increased frequency of side effects or major complications Fifty – four orthopaedic patients were given either indomethacin ( 25–50 mg bolus plus infusion , 5–7.5 mg h‐1 ) or only lactated Ringer solution intravenously over 20 h in a r and omized and double – blind fashion . The study was started at the casualty department as soon as possible after the decision to operate was made . The patients were given a spinal block with bupivacaine , and the evaluation included postoperative analgesia and IVY bleeding times . Indomethacin plasma concentrations were measured and found to be at a therapeutic level throughout the study . The oxycodone dose ( mean s.d . ) during the postoperative observation was lower in the indomethacin group ( 17.4 13.7 mg ) than in the control group ( 25.6 15.6 mg ) ( P = 0.05 ) . Fewer patients in the indomethacin group needed oxycodone  more than once during the follow – up period ( P < 0.001 ) . The mean IVY bleeding time was prolonged in the indomethacin group after 20 h of infusion ( P < 0.05 ) . No abnormal bleeding was observed immediately postoperatively . However , at the end of the infusion there were more patients who bled through their b and ages and casts in the indomethacin group ( 4/28 vs. 1/26 ) 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 Sixty patients who were scheduled to have an elective total hip or knee arthroplasty were r and omly assigned to one of three groups of twenty patients each before operation with spinal anesthesia . A double-blind technique was used throughout the study . The patients in Group I ( control group ) received hyperbaric 1 per cent tetracaine with epinephrine as the subarachnoid spinal anesthetic ; the patients in Group II ( morphine group ) , hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Duramorph ( morphine sulphate ) , 0.5 milligram ; and those in Group III ( Dilaudid group ) , hyperbaric 1 per cent tetracaine with epinephrine and a single sub 
    Output:
    
Adverse events occurred more frequently with combination therapy than placebo , but were generally described as mild to moderate in severity and rarely led to withdrawal .
Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg ; oxycodone is two to three times stronger than codeine .
Efficacy increases when combined with paracetamol .
Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated , comparable to commonly used non-steroidal anti-inflammatory drugs , with the benefit of longer duration of action