***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: OBJECTIVE : The aim of this study was to compare the upper GI mucosal effects of i.v . parecoxib sodium with i.v . ketorolac tromethamine and placebo in healthy elderly subjects . METHODS : This was a two-center , double-blind , r and omized , placebo-controlled study . Healthy subjects aged 65–75 yr who were shown at baseline endoscopy to have no gastric or duodenal lesions received either parecoxib sodium 40 mg b.i.d . for 7 days , ketorolac 15 mg q.i.d . for 5 days , or placebo for 7 days . Endoscopy was repeated at the end of dosing . Measures of upper GI effects were : 1 ) ulceration , 2 ) incidence of an ulcer and /or any erosions , and 3 ) incidence of an ulcer and /or ≥11 erosions in the stomach , duodenum , or both . RESULTS : No gastric or duodenal ulcers occurred in any subjects receiving parecoxib sodium ( n = 29 ) or placebo ( n = 32 ) . In contrast , seven ( 23 % ) of the 31 ketorolac subjects had at least one ulcer ; five ( 16 % ) had gastric ulcers , and two ( 6 % ) had duodenal ulcers ( p < 0.05 vs parecoxib sodium and placebo for gastroduodenal ulcers and for gastric ulcers ) . A total of 28 ( 90 % ) ketorolac subjects had an ulcer or at least one erosion in the stomach , compared with incidences of four ( 14 % ) and two ( 6 % ) for parecoxib sodium and placebo , respectively . Incidences of duodenal ulcers/erosions were 45 % ( n = 14 ) for ketorolac , 10 % ( n = 3 ) for parecoxib sodium , and none for placebo . The differences between ketorolac and both other treatment groups were statistically significant for both stomach and duodenum . No parecoxib sodium or placebo subjects had an ulcer or ≥11 erosions in the stomach , compared with eight ( 26 % ) ketorolac subjects ( p < 0.05 vs both parecoxib sodium and placebo ) . No subject in any group had ≥11 duodenal erosions . CONCLUSIONS : These results indicate that multiple dose administration of parecoxib sodium is safe and well tolerated in healthy elderly subjects , with a decreased risk of gastroduodenal mucosal injury compared with ketorolac Background : The gastrointestinal safety of the novel injectable cyclooxygenase-2 selective inhibitor , parecoxib sodium , was compared with the nonselective nonsteroidal anti-inflammatory drug , ketorolac , and placebo in healthy subjects . Study : In a multicenter , r and omized , double-blind , placebo-controlled design , 123 adults with endoscopically-confirmed normal upper gastrointestinal mucosae received parecoxib sodium 40 mg twice daily ( 7 days ) ; placebo ( 2 days ) followed by ketorolac 30 mg 4 times daily ( 5 days ) ; or placebo ( 7 days ) ( each group n = 41 ) . Posttreatment endoscopy scores were analyzed at 3 levels of severity : ulcers ( scores of 7 ) , ≥11 erosions/ulcers ( scores of 5–7 ) , and any erosions/ulcers ( scores of 3–7 ) . Results : No subjects treated with parecoxib sodium or placebo developed gastroduodenal ulcers or ≥11 erosions/ulcers . Parecoxib sodium was comparable to placebo with respect to the combined incidence of erosions/ulcers ( 12 % vs. 7 % , P = 0.419 ) . In contrast , in the ketorolac group , 11 ( 28 % ) subjects developed ulcers , 19 ( 48 % ) subjects developed ≥11 gastroduodenal erosions/ulcers , and the rate of combined ulcers/erosions was 85 % ( P < 0.001 vs. placebo and parecoxib sodium ) . Conclusions : Parecoxib sodium 40 mg twice daily for 7 days has a gastrointestinal safety profile superior to ketorolac 30 mg 4 times daily for 5 days , and comparable to placebo 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 BACKGROUND : This multicenter , multiple-dose , r and omized , double-blind , parallel-group study compared the analgesic efficacy and safety of two dosing regimens of parecoxib sodium ( parecoxib ) versus placebo  after total hip arthroplasty . METHODS : On study Day 1 , 490 patients received a postoperative initial loading dose of IV parecoxib 40 mg , followed by a re-dose of parecoxib 20 mg in 484 of 490 patients . Subsequently , 479 r and omized patients received double-blind treatment with parecoxib 20 mg bid ( n = 159 ) , parecoxib 20 mg qd ( n = 159 ) followed by placebo , or placebo ( n = 161 ) on Day 2 . RESULTS : Patients treated with parecoxib 20 mg bid reported significantly lower summed pain intensity over 24 h ( SPI-24 ) scores and improved patients ’ global evaluation of study medication ( PGESM ) ratings compared with placebo-treated patients on Days 2 to 5 ( P < 0.05 ) . For patients treated with parecoxib 20 mg qd , SPI-24 scores were significantly lower on Days 3 and 4 ( P < 0.05 ) , and PGESM ratings significantly improved on Day 5 compared with placebo . The incidence of adverse events was similar in all treatment groups with the exception of fever , vomiting and impaired concentration , which were significantly more common in the placebo group compared with one or other of the parecoxib treatment groups ( P < 0.05 ) . CONCLUSION : Multiple-day administration of parecoxib 20 mg once or twice daily is effective and generally well tolerated after total hip arthroplasty & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with  placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely Background : Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting . The authors conducted a r and omized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures . Methods : The trial was r and omized and double-blind , with 10 days of treatment and 30 days of follow-up . Patients ( n = 1,062 ) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout . The frequency of predefined adjudicated postr and omization adverse events , including cardiovascular thromboembolism , renal dysfunction , gastroduodenal ulceration , and wound-healing complications , was assessed in each group . Secondary efficacy endpoints included patients ' pain ratings , opioid analgesic consumption ( recorded as morphine equivalents ) , and reports of opioid-related adverse effects . Results : Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib ( 2.7 % ) and placebo patients ( 3.2 % ) ( P = 0.58 ) , including cardiovascular thromboembolic events ( 1.0 % in each group ; P = 1.0 ) . Placebo patients consumed more morphine equivalents ( 66.2 ± 92.4 mg ) than did patients receiving parecoxib and valdecoxib ( 43.2 ± 65.7 mg ) ( P < 0.001 ) . Placebo patients had higher mean pain ratings on each of study days 2–10 ( P < 0.01 ) and reported more opioid-related symptom distress on days 2–6 ( P < 0.01 ) . Conclusions : Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients . Further study will be required to determine the safety profile of parecoxib and valdecoxib administered to patients with known atherosclerotic disease after noncardiac surgery BACKGROUND This multicentre , double-blind , placebo-controlled study compared the opioid-sparing effectiveness and clinical safety of parecoxib sodium over 48 h , in 195 postoperative patients after routine total knee replacement surgery . METHODS Elective total primary knee arthroplasty was performed under spinal anaesthesia , with a single dose of spinal bupivacaine 10 - 20 mg , and intraoperative sedation with midazolam 0.5 - 1.0 mg i.v . , or propofol < 6 mg kg(-1)h(-1 ) . Patients were r and omized to receive either parecoxib sodium 20 mg twice daily ( bd ) i.v . ( n=65 ) , parecoxib sodium 40 mg bd i.v . ( n=67 ) , or placebo ( n=63 ) at the completion of surgery , and after 12 , 24 , and 36 h. Morphine ( 1 - 2 mg ) was taken by patient-controlled analgesia or by bolus doses after 30 min . RESULTS Patients receiving parecoxib sodium 20 mg bd and 40 mg bd consumed 15.6 % and 27.8 % less morphine at 24 h than patients taking placebo ( both P<0.05 ) . Both doses of parecoxib sodium administered with morphine provided significantly greater pain relief than morphine alone from 6 h ( P<0.05 ) . A global evaluation of study medication demonstrated a greater level of satisfaction among patients taking parecoxib sodium than those taking placebo . Parecoxib sodium administered in combination with morphine was well tolerated . However , a reduction in opioid-type side-effects was not demonstrated in the parecoxib sodium groups . CONCLUSION Parecoxib sodium provides opioid-sparing analgesic effects in postoperative patients Background Clinical trials suggest that cyclo-oxygenase-2 specific inhibitors ( coxibs ) are an effective treatment for acute postoperative pain . The aims of this systematic review were to examine the evidence for oral valdecoxib and injected parecoxib , and quantify efficacy and adverse 
    Output:
    
Adverse events were generally mild to moderate , rarely led to withdrawal , and did not differ in frequency between groups .
A single dose of parecoxib 20 mg or 40 mg provided effective analgesia for 50 to 60 % of those treated compared to about 15 % with placebo , and was well tolerated .
Duration of analgesia was longer , and significantly fewer participants required rescue medication over 24 hours with the higher dose