***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: Background : Osteoarthritis ( OA ) affects mainly older people who are more sensitive to adverse effects of classic nonsteroidal anti-inflammatory drugs . Recent publications indicate that topically applied nonsteroidal anti-inflammatory drugs are effective and much safer than their oral analogues . Objectives : In this double-blind , r and omized , placebo-controlled study design , we aim ed to investigate whether topical nimesulide treatment has any beneficial effect in knee OA patients . Methods : Seventy-four adult knee OA out patients were enrolled . We used Western Ontario and McMaster Universities OA Index ( WOMAC ) , Nottingham Health Profile ( NHP ) , and patient and physician global satisfaction scores . WOMAC and NHP scores were measured at the initial and final visit . Treatment group received topical nimesulide gel 1 % on the knee skin 3 times a day whereas placebo group received an identical-appearing gel for 30 days . Results : There was a significant improvement in the nimesulide treatment group for all 3 parameters and overall score of WOMAC between pretreatment and posttreatment values . The overall WOMAC scores was significantly better than placebo ( P = 0.03 ) , but physical functioning , stiffness , and pain scales did not reach statistical significance . For the NHP scores there was an improvement at “ energy level , ” “ pain , ” “ physical motion , ” and “ NHP distress ” scores in the treatment group whereas no improvement was found in the placebo group . Between-group differences were not significant . Both patient and physician satisfaction scores were significantly better in the treatment group . Conclusion : This study shows that topical nimesulide gel can have beneficial effects and can improve quality of life in patients with knee OA UNLABELLED In order to assess the efficacy and safety of a new patch containing 14 mg of piroxicam ( CAS 36322 - 90 - 4 ) 1 % , applied once daily , in comparison with a reference marketed formulation , piroxicam 1 % cream applied three times a day , placebo patch applied once daily , a r and omized , placebo-controlled , parallel-group clinical trial was carried out by general practitioners in patients with lumbar osteoarthritis aged between 18 and 75 years .  Pain during daily activities scored on a 100 mm visual analogue scale was the primary outcome measure . Other secondary outcome measures were pain on isometric contraction , on full passive motion , and on pressure , and functional disability . Statistical analysis was performed on the differences between the three groups in the intention-to-treat population ( ITT ) . One hundred and eighty patients were enrolled . The available ITT population comprised 179 patients . The compliance was very good . Decrease in pain score during daily activities after the eight days of study treatment ( at the final visit , Vf ) was 42.2 % , 41.7 % and 25.8 % in the piroxicam patch , piroxicam cream and placebo groups , respectively . The difference between the pain scores in two active treatments arms was not statistically significant at the Vf whereas the differences between the pain scores of two active treatment arms vs the placebo arm were statistically significant validating the study design . All efficacy measures improved during the study , for both the active treatment groups , and the results for the secondary efficacy variables were generally consistent with those concerning the main efficacy criterion . The difference between the two active treatments in pain during daily activities were statistically significant at the final visit ; in fact the 95 % CI of the difference between the mean of responder rate of the piroxicam patch and piroxicam cream was -18.3 % , + 24.4 % indicating a trend of superiority of the piroxicam patch versus the cream ( per- protocol analysis ) . The data obtained during the intermediate visit ( V2 , day 4 ) allow us to assess that the piroxicam patch was on average better than the piroxicam cream in terms of fast pain reduction ( change from baseline : - 29.1 % for piroxicam patch in comparison to -24.6 % for piroxicam cream ) . Moreover the piroxicam patch proved to be on average more effective than the piroxicam cream in terms of secondary efficacy endpoints . Safety was considered satisfactory in all groups . CONCLUSIONS The piroxicam patch is effective in the treatment of lumbar osteoarthritis and has demonstrated to be well tolerated and it improves patients compliance . The piroxicam patch offers a comparable alternative to the marketed piroxicam cream for the treatment of  lumbar osteoarthritis  with the advantage of a better compliance with the once a day application of the patch compared to three daily applications for the piroxicam cream 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 A double-blind , placebo (PBO)-controlled trial was carried out on 155 adult out patients with painful ( Huskisson 's analogical scale > 40 mm ) monolbilateral femorotibial and /or femoropatellar osteoarthritis of the knee , radiologically confirmed . Patients were r and omly given either diclofenac hydroxyethylpyrrolidine plasters ( DHEP , 78 patients ) , containing 180 mg of active drug each , or matched PBO ( 77 ptns ) . Plasters were applied b.i.d . ( at 8 a.m. and 8 p.m. ) on the affected joint , for 15 days . No NSAID treatment was allowed during the trial , while paracetamol was admitted from the 4th day on and its daily intake carefully recorded . Huskisson 's test and Lequesne 's index were assessed at days 0 , 4 , 7 and 15 . Patients were asked to fill in a daily cared with Huskisson 's scale and subjective evaluations . Differences in favour of DHEP were observed from the first assessment ( 4th d. ) on Huskisson 's scale and Lequesne 's index ( p < 0.001 ) . According to the patients ' subjective evaluation , pain decreased as soon as the first day in both groups , with significant differences in favour of DHEP ( p < 0.005 ) . Even the number of night awakenings recorded by the patient was significantly in favour of DHEP ( p < 0.005 ) . It is worth noting that these results were obtained in spite of a significant reduction of paracetamol intake in DHEP patients in comparison with PBO patients ( p < 0.01 ) . Tolerability was judged good or excellent in the majority of cases : only minor side effects occurred in five patients ( 4 PBO , 1 DHEP ) and the interruption of treatment was required for only one of the PBOs . This study shows that DHEP plaster significantly differs from matched PBO in the improvement of pain and patient 's condition in painful knee osteoarthritis Background Topical nonsteroidal anti-inflammatory drug ( NSAID ) formulations , which produce less systemic exposure compared with oral formulations , are an option for the management of osteoarthritis ( OA ) . However , the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial . Methods Two 12-week , double-blind , double-dummy , r and omized , controlled , multicenter studies compared the safety and efficacy profiles of diclofenac topical solution ( TDiclo ) with oral diclofenac ( ODiclo ) . Each study independently showed that TDiclo had similar efficacy to ODiclo . To compare the safety profiles of TDiclo and ODiclo , a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee . This pooled analysis included patients treated with TDiclo , containing 45.5 % dimethyl sulfoxide ( DMSO ) , and those treated with ODiclo . Safety assessment s included monitoring of adverse events ( AEs ) , recording of vital signs , dermatologic evaluation of the study knee , and clinical laboratory evaluation . Results AEs occurred in 312 ( 67.1 % ) patients using  TDiclo  versus 298 ( 64.5 % ) of those taking ODiclo . The most common AE with TDiclo  was dry skin at the application site ( 24.1 % vs 1.9 % with ODiclo ; P < 0.0001 ) . Fewer gastrointestinal ( 25.4 % vs 39.0 % ; P < 0.0001 ) and cardiovascular ( 1.5 % vs 3.5 % ; P = 0.055 ) AEs occurred with TDiclo compared with ODiclo . ODiclo was associated with significantly greater increases in liver enzymes and creatinine , and greater decreases in creatinine clearance and hemoglobin ( P < 0.001 for all ) . Conclusions These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA , with a more favorable safety profile Objective To evaluate the safety and efficacy of ketoprofen in Transfersome ® gel ( IDEA-033 ) in comparison with a ketoprofen-free vehicle ( TDT 064 ) for the treatment of osteoarthritis ( OA ) of the knee . Methods Patients with knee OA ( N = 866 ) were r and omly assigned to receive topical IDEA-033 containing 100 , 50 , or 25 mg ketoprofen , or TDT 064 twice daily for 12 weeks , in a double-blind trial . The primary efficacy endpoint was the change in the Western Ontario and McMaster Universities ( WOMAC ® ) Osteoarthritis Index pain subscale score . The co primary efficacy endpoints were the WOMAC function subscale score and the patient global assessment of response to therapy . The secondary endpoints included the numeric pain rating for the first 14 days of treatment and the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International ( OARSI ) responder rates . Results The WOMAC pain scores were reduced by approximately 50 % or more in all four groups . The 100 and 50 mg ketoprofen groups , but not the 25 mg group , showed a superior reduction in the WOMAC pain score versus the TDT 064 group ( 100 mg : −57.4 % [ P = 0.0383 ] ; 50 mg : −57.1 % [ P = 0.0204 ] ; and 25 mg : −53.4 % [ P = 0.3616 ] versus TDT 064 : −49.5 % ) . The superiority of the ketoprofen-containing formulations was not demonstrated for the WOMAC function subscale score , whereas the patient global assessment of 50 mg ketoprofen group , but not the 100 or 25 mg group , was superior to that of the TDT 064 group ( P = 0.0283 ) . Responder rates were significantly higher for all the IDEA-033 groups versus the TDT 064 group , but were high in all groups ( 100 mg : 88.6 % ; 50 mg : 86.8 % ; 25 mg : 88.6 % ; and TDT 064 : 77.5 % ) . Dermal reactions were the only relevant drug-related adverse events in all four groups . Conclusion The 50 and 100 mg ketoprofen doses of IDEA-033 were only marginally superior to TDT 064 for reducing pain associated with knee OA . The study indicates a high treatment response to the topical ketoprofen-free vehicle TDT 064 Of 100 patients suffering chiefly from soft tissue rheumatism 48 were treated in a double-blind study with an ointment containing flufenamic acid ( Mobilisin ) and 52 with a control preparation . The test ointment brought about good to very good results in 43 patients ( 89,5 % ) whereas only 26 patients ( 50 % ) of the control 
    Output:
    
These efficacy results were almost completely derived from people with knee osteoarthritis .
There was an increase in local adverse events ( mostly mild skin reactions ) with topical diclofenac compared with carrier or oral NSAIDs , but no increase with topical ketoprofen ( moderate quality evidence ) .
Reporting of systemic adverse events ( such as gastrointestinal upsets ) was poor , but where reported there was no difference between topical NSAID and carrier ( very low quality evidence ) .
Serious adverse events were infrequent and not different between topical NSAID and carrier ( very low quality evidence ) .
Topical diclofenac and topical ketoprofen can provide good levels of pain relief beyond carrier in osteoarthritis for a minority of people , but there is no evidence for other chronic painful conditions .
There is emerging evidence that at least some of the substantial placebo effects seen in longer duration studies derive from effects imparted by the NSAID carrier itself , and that NSAIDs add to that