human
***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 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 OBJECTIVE To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib . METHODS ; A multicentre , double-blind controlled study in which patients with knee OA and moderate pain were r and omized to one of the six arms : topical ketoprofen 50 or 100 mg in ultradeformable vesicles ( IDEA-033 ) , 2.2 or 4.4 g ketoprofen-free vehicle ( TDT 064 ) , oral celecoxib 100 mg or matching oral placebo , all bd . The primary outcome was change from baseline in the WOMAC pain subscale at week 12 . RESULTS A total of 1395 patients received treatment .  Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups . The mean reduction in WOMAC pain score at week 12 was -1.9 ( -40.8 % ) for ketoprofen 50 mg , -1.9 ( -40.9 % ) for ketoprofen 100 mg , -1.9 ( -39.8 % ) for 2.2 g TDT 064 , -1.8 ( -37.8 % ) for 4.4 g TDT 064 , -1.9 ( -40.4 % ) for celecoxib and -1.4 ( -29.3 % ) for oral placebo . IDEA-033 was not statistically superior to TDT 064 . All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib . The most frequent types of treatment-related adverse events reported were gastrointestinal for oral ( 15.9 % for celecoxib ) and dermal for topical applications ( 12.2 % for ketoprofen 100 mg ) . CONCLUSION IDEA-033 was not superior to ketoprofen-free vehicle , but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain . TRIAL REGISTRATION Clinical Trials.gov , http:// clinical trials.gov/ , NCT00716547 Objective To investigate the effect of epicutaneously applied Diractin ® ( ketoprofen in Transfersome ® gel ) on pain induced by eccentric muscle contractions . Methods Three pilot studies which were subsequently pooled for a meta- analysis compared the efficacy of a single application of 25 mg ketoprofen in Diractin ® to 25 mg oral ketoprofen and placebo for the treatment of pain induced by 50 eccentric contractions of the elbow flexor muscles . In addition , the effect of multiple usage of up to 100 mg ketoprofen in Diractin ® bid over seven days on pain induced by walking down stairs with a total altitude of 200 meters was investigated . Results A single dose of 25 mg ketoprofen in Diractin ® after the elbow flexion exercise was significantly superior to placebo from 5 to 12 hours after treatment and also to oral ketoprofen at some time points after treatment . In contrast , oral ketoprofen  was not different to placebo at any time after treatment . Multiple doses of up to 100 mg ketoprofen Diractin ® provided significant more pain relief than placebo on muscle pain induced by walking down stairs . Conclusions Eccentric exercise-induced muscle soreness was shown to be an appropriate acute pain model to evaluate the efficacy of nonsteroidal anti-inflammatory drugs applied epicutaneously with Transfersome ® carriers . Diractin ® proved to be efficacious in relieving pain from eccentric muscle contractions and muscle overexercise , respectively . The effect needs to be confirmed in a larger prospect i ve clinical trial BACKGROUND Orally administrated nonsteroidal anti-inflammatory drugs are effective in the treatment of a variety of acute and chronic pain conditions but their use may be associated with serious systemic adverse effects which are correlated with the therapeutic plasma levels of the drug . In order to minimize the incidence of drug related systemic events , topical formulations of the nonsteroidal anti-inflammatory drugs have been developed . A recently performed review of the evidence from r and omized , double-blind , placebo controlled trials with topically applied NSAIDs in the treatment of acute pain confirmed the previously described pain relief effectiveness . For all topical nonsteroidal anti-inflammatory drugs combined , in comparison to placebo , the number needed to treat ( NNT ) to achieve a clinical ly meaningful pain relief of 50 % was 4.5 ( 3.9 to 5.3 ) for treatment periods of 6 to 14 days . Local skin reactions were generally mild and transient , and did not differ from placebo . OBJECTIVES The present is an observational , multicenter , open-label , non-interventional , post-authorization safety study as it is defined by Article 21 of the European Clinical Trials Directive 2001/20/EC . The main objective of this study was to evaluate the local tolerability and the therapeutic efficacy of static and pain on movement intensity reduction of Ketospray ® 10 % cutaneous spray solution administered in accordance with the terms of the marketing authorization and last version of summary of product characteristics approved by National Medicines Agency of Romania . METHODS In compliance with the Post-marketing study type , the assignment of the patient to a particular therapeutic strategy fell within current practice . The prescription of the medicine was not subject to compliance with predefined patients ' characteristics . No specific , out of the daily practice routine diagnostic , monitoring , instrumental or laboratory assessment s were foreseen by the study protocol . Patients ' data were collected into respective case report forms . Study medication , Ketoprofen 10 % Cutaneous Spray Solution was administered to the affected area at the dose of 3 - 6 spray puffs , 2 - 3 times a day , for 7 days . According to the study type , descriptive statistical methods were applied . Since almost half of the patients were treated with combination of the pain relieving medications , sizing of the pain relieving effects , as NNT , between the two groups was made . FINDINGS There were 2020 study subjects in safety and ITT analysis population and 1802 ( 89 % ) in PP efficacy analysis population . There were 4 types of injuries : non-complicated strain-sprain ( 555 ) , soft tissue contusion ( 323 ) , low back pain ( 461 ) and osteoarthritis ( 681 patients ) . Ten patients reported 13 side effects of which 10 were recognized by investigators as adverse drug reactions . All side effects were non-serious , listed , application site skin changes . Remarkable reductions of static and pain on movement intensity were experienced by patients irrespective of the type of the injury and the type of the treatment . However , a clinical ly meaningful benefit of the concomitantly prescribed pain relieving medications was not observed for any type of pain . The lowest NNT ( 14 ) was obtained for the reduction of pain at rest in patients with strain-sprain or soft tissue contusions . The highest NNT ( 283 ) was for pain at rest in patients treated for the exacerbation of the chronic pain . CONCLUSIONS The results of the current post-authorization study confirm beneficial pain intensity reducing efficacy of Ketospray 10 % associated with good local tolerability of 7 days treatment course . Concomitant administration of systemic pain relieving medication did not substantially contribute neither to the relief of pain at rest nor of pain on movement among the subjects of respective study population Objective To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs ( NSAIDs ) . Design R and omised controlled trial and patient preference study . Setting 26 general practice s. Participants People aged ≥50 with knee pain : 282 in r and omised trial and 303 in preference study . Interventions Advice to use topical or oral ibuprofen . Primary outcome measures WOMAC ( Western Ontario and McMaster Universities ) osteoarthritis index , major and minor adverse effects . Results Changes in global WOMAC scores at 12 months were equivalent . In the r and omised trial the difference ( topical minus oral ) was two points ( 95 % confidence interval −2 to 6 ) ; in the preference study , it was one point ( −4 to 6 ) . There were no differences in major adverse effects in the trial or study . The only significant differences in secondary outcomes were in the r and omised trial . The oral group had more respiratory adverse effects ( 17 % v 7%,95 % confidence interval for difference −17 % to −2 % ) , the change in serum creatinine was 3.7 mmol/l less favourable ( 0.9 µmol/l to 6.5 µmol/l ) ; and more participants changed treatments because of adverse effects ( 16 % v 1 % , −16 % to −5 % ) . In the topical group more participants had chronic pain grade III or IV at three months , and more participants changed treatment because of ineffectiveness . Conclusions Advice to use oral or topical preparations has an equivalent effect on knee pain over one year , and there are more minor side effects with oral NSAIDs . Topical NSAIDs may be a useful alternative to oral NSAIDs . Trial registration IS RCT N 79353052 Objective . This r and omized , double-blind , phase III study evaluated the efficacy and safety of ketoprofen in an ultradeformable vesicle gel compared with ketoprofen-free gel in osteoarthritis ( OA ) knee pain . Methods . Patients with American College of Rheumatology-defined OA of the knee and moderate pain were r and omized to receive 100 mg ketoprofen in 4.4 g transfersome gel ( IDEA-033 ) or 4.4 g ketoprofen-free vehicle ( TDT 064 ) topically , twice daily , for 12 weeks . The primary endpoint was mean change in Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale score from baseline to Week 12 . Results . Patients ( n = 555 ) were r and omized and treated .  Mean baseline WOMAC pain scores were 5.2 ( SD 1.0 ) for IDEA-033 and 5.3 ( SD 1.0 ) for TDT 064 . Mean change in WOMAC pain scores from baseline to Week 12 was 38.6 % for IDEA-033 and 44.6 % for TDT 064 ( Mann-Whitney estimator 0.4505 ; p = 0.022 ) . Both groups reported progressive decreases in pain and improvements in function and stiffness . Mean baseline WOMAC function scores decreased from 5.4 to 3.4 with IDEA-033 and 3.1 with TDT 064 at Week 12 . The proportion of patients achieving 
    Output:
    
agent
All topical ketoprofen in Transfersome gel groups ( 25 mg , 50 mg and 100 mg ) had improvements in pain that were superior to all other treatment arms , and the 50 mg topical ketoprofen in Transfersome gel group had functional gains that were superior to all other treatment arms .
The majority of the adverse events were non-serious and related to skin and subcutaneous tissue disorders , with erythema being the most common .
Topical ketoprofen in Transfersome gel is an effective means of treating symptoms of knee OA , and is superior to oral celecoxib , oral placebo and topical placebo .
The most commonly reported adverse events associated with the use of topical ketoprofen in Transfersome gel were non-severe skin and subcutaneous tissue disorders .
Furthermore , as topical ketoprofen in Transfersome gel was associated with fewer adverse events when compared with oral celecoxib , and had rates of GI adverse events comparable with those of topical placebo , it may be ideal for those who are unable to take oral NSAIDs
***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 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 OBJECTIVE To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib . METHODS ; A multicentre , double-blind controlled study in which patients with knee OA and moderate pain were r and omized to one of the six arms : topical ketoprofen 50 or 100 mg in ultradeformable vesicles ( IDEA-033 ) , 2.2 or 4.4 g ketoprofen-free vehicle ( TDT 064 ) , oral celecoxib 100 mg or matching oral placebo , all bd . The primary outcome was change from baseline in the WOMAC pain subscale at week 12 . RESULTS A total of 1395 patients received treatment .  Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups . The mean reduction in WOMAC pain score at week 12 was -1.9 ( -40.8 % ) for ketoprofen 50 mg , -1.9 ( -40.9 % ) for ketoprofen 100 mg , -1.9 ( -39.8 % ) for 2.2 g TDT 064 , -1.8 ( -37.8 % ) for 4.4 g TDT 064 , -1.9 ( -40.4 % ) for celecoxib and -1.4 ( -29.3 % ) for oral placebo . IDEA-033 was not statistically superior to TDT 064 . All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib . The most frequent types of treatment-related adverse events reported were gastrointestinal for oral ( 15.9 % for celecoxib ) and dermal for topical applications ( 12.2 % for ketoprofen 100 mg ) . CONCLUSION IDEA-033 was not superior to ketoprofen-free vehicle , but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain . TRIAL REGISTRATION Clinical Trials.gov , http:// clinical trials.gov/ , NCT00716547 Objective To investigate the effect of epicutaneously applied Diractin ® ( ketoprofen in Transfersome ® gel ) on pain induced by eccentric muscle contractions . Methods Three pilot studies which were subsequently pooled for a meta- analysis compared the efficacy of a single application of 25 mg ketoprofen in Diractin ® to 25 mg oral ketoprofen and placebo for the treatment of pain induced by 50 eccentric contractions of the elbow flexor muscles . In addition , the effect of multiple usage of up to 100 mg ketoprofen in Diractin ® bid over seven days on pain induced by walking down stairs with a total altitude of 200 meters was investigated . Results A single dose of 25 mg ketoprofen in Diractin ® after the elbow flexion exercise was significantly superior to placebo from 5 to 12 hours after treatment and also to oral ketoprofen at some time points after treatment . In contrast , oral ketoprofen  was not different to placebo at any time after treatment . Multiple doses of up to 100 mg ketoprofen Diractin ® provided significant more pain relief than placebo on muscle pain induced by walking down stairs . Conclusions Eccentric exercise-induced muscle soreness was shown to be an appropriate acute pain model to evaluate the efficacy of nonsteroidal anti-inflammatory drugs applied epicutaneously with Transfersome ® carriers . Diractin ® proved to be efficacious in relieving pain from eccentric muscle contractions and muscle overexercise , respectively . The effect needs to be confirmed in a larger prospect i ve clinical trial BACKGROUND Orally administrated nonsteroidal anti-inflammatory drugs are effective in the treatment of a variety of acute and chronic pain conditions but their use may be associated with serious systemic adverse effects which are correlated with the therapeutic plasma levels of the drug . In order to minimize the incidence of drug related systemic events , topical formulations of the nonsteroidal anti-inflammatory drugs have been developed . A recently performed review of the evidence from r and omized , double-blind , placebo controlled trials with topically applied NSAIDs in the treatment of acute pain confirmed the previously described pain relief effectiveness . For all topical nonsteroidal anti-inflammatory drugs combined , in comparison to placebo , the number needed to treat ( NNT ) to achieve a clinical ly meaningful pain relief of 50 % was 4.5 ( 3.9 to 5.3 ) for treatment periods of 6 to 14 days . Local skin reactions were generally mild and transient , and did not differ from placebo . OBJECTIVES The present is an observational , multicenter , open-label , non-interventional , post-authorization safety study as it is defined by Article 21 of the European Clinical Trials Directive 2001/20/EC . The main objective of this study was to evaluate the local tolerability and the therapeutic efficacy of static and pain on movement intensity reduction of Ketospray ® 10 % cutaneous spray solution administered in accordance with the terms of the marketing authorization and last version of summary of product characteristics approved by National Medicines Agency of Romania . METHODS In compliance with the Post-marketing study type , the assignment of the patient to a particular therapeutic strategy fell within current practice . The prescription of the medicine was not subject to compliance with predefined patients ' characteristics . No specific , out of the daily practice routine diagnostic , monitoring , instrumental or laboratory assessment s were foreseen by the study protocol . Patients ' data were collected into respective case report forms . Study medication , Ketoprofen 10 % Cutaneous Spray Solution was administered to the affected area at the dose of 3 - 6 spray puffs , 2 - 3 times a day , for 7 days . According to the study type , descriptive statistical methods were applied . Since almost half of the patients were treated with combination of the pain relieving medications , sizing of the pain relieving effects , as NNT , between the two groups was made . FINDINGS There were 2020 study subjects in safety and ITT analysis population and 1802 ( 89 % ) in PP efficacy analysis population . There were 4 types of injuries : non-complicated strain-sprain ( 555 ) , soft tissue contusion ( 323 ) , low back pain ( 461 ) and osteoarthritis ( 681 patients ) . Ten patients reported 13 side effects of which 10 were recognized by investigators as adverse drug reactions . All side effects were non-serious , listed , application site skin changes . Remarkable reductions of static and pain on movement intensity were experienced by patients irrespective of the type of the injury and the type of the treatment . However , a clinical ly meaningful benefit of the concomitantly prescribed pain relieving medications was not observed for any type of pain . The lowest NNT ( 14 ) was obtained for the reduction of pain at rest in patients with strain-sprain or soft tissue contusions . The highest NNT ( 283 ) was for pain at rest in patients treated for the exacerbation of the chronic pain . CONCLUSIONS The results of the current post-authorization study confirm beneficial pain intensity reducing efficacy of Ketospray 10 % associated with good local tolerability of 7 days treatment course . Concomitant administration of systemic pain relieving medication did not substantially contribute neither to the relief of pain at rest nor of pain on movement among the subjects of respective study population Objective To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs ( NSAIDs ) . Design R and omised controlled trial and patient preference study . Setting 26 general practice s. Participants People aged ≥50 with knee pain : 282 in r and omised trial and 303 in preference study . Interventions Advice to use topical or oral ibuprofen . Primary outcome measures WOMAC ( Western Ontario and McMaster Universities ) osteoarthritis index , major and minor adverse effects . Results Changes in global WOMAC scores at 12 months were equivalent . In the r and omised trial the difference ( topical minus oral ) was two points ( 95 % confidence interval −2 to 6 ) ; in the preference study , it was one point ( −4 to 6 ) . There were no differences in major adverse effects in the trial or study . The only significant differences in secondary outcomes were in the r and omised trial . The oral group had more respiratory adverse effects ( 17 % v 7%,95 % confidence interval for difference −17 % to −2 % ) , the change in serum creatinine was 3.7 mmol/l less favourable ( 0.9 µmol/l to 6.5 µmol/l ) ; and more participants changed treatments because of adverse effects ( 16 % v 1 % , −16 % to −5 % ) . In the topical group more participants had chronic pain grade III or IV at three months , and more participants changed treatment because of ineffectiveness . Conclusions Advice to use oral or topical preparations has an equivalent effect on knee pain over one year , and there are more minor side effects with oral NSAIDs . Topical NSAIDs may be a useful alternative to oral NSAIDs . Trial registration IS RCT N 79353052 Objective . This r and omized , double-blind , phase III study evaluated the efficacy and safety of ketoprofen in an ultradeformable vesicle gel compared with ketoprofen-free gel in osteoarthritis ( OA ) knee pain . Methods . Patients with American College of Rheumatology-defined OA of the knee and moderate pain were r and omized to receive 100 mg ketoprofen in 4.4 g transfersome gel ( IDEA-033 ) or 4.4 g ketoprofen-free vehicle ( TDT 064 ) topically , twice daily , for 12 weeks . The primary endpoint was mean change in Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale score from baseline to Week 12 . Results . Patients ( n = 555 ) were r and omized and treated .  Mean baseline WOMAC pain scores were 5.2 ( SD 1.0 ) for IDEA-033 and 5.3 ( SD 1.0 ) for TDT 064 . Mean change in WOMAC pain scores from baseline to Week 12 was 38.6 % for IDEA-033 and 44.6 % for TDT 064 ( Mann-Whitney estimator 0.4505 ; p = 0.022 ) . Both groups reported progressive decreases in pain and improvements in function and stiffness . Mean baseline WOMAC function scores decreased from 5.4 to 3.4 with IDEA-033 and 3.1 with TDT 064 at Week 12 . The proportion of patients achieving 
    Output:
    