***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 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 A double-blind , r and omized , placebo-controlled study has been carried out in order to assess the effects of the new topical cutaneous formulation , diclofenac hydroxyethylpyrrolidine ( DHEP ) plaster .  Sixty patients ( 10 M + 50 F , mean age 56.6 yrs ) suffering from local inflammatory processes in peri-articular/tendinous and /or extra-articular sites were involved in this study and r and omly given either DHEP plaster or placebo plaster . Plasters were applied and left on the site of inflammation b.i.d . ( at 8 a.m. and 8 p.m. ) for 14 days . Patients under stabilized systemic treatment with NSAIDs , glucocorticoids and /or basic therapy for over 2 months , maintained this treatment unchanged during the course of the study . Patients were examined on days 3 , 5 , 7 and 14 . The effects of the treatments were assessed using subjective , semi-quantitative ( provoked pain , peri-articular swelling , doctor-patient judgement , telethermographic index ) and quantitative variables ( spontaneous pain measured using a visual analogical scale ) . In the peri-articular pathologies , spontaneous and provoked pain decreased faster and in a clinical ly relevant manner in the group treated with DHEP plaster compared to the control group ( p < 0.01 ) . Local inflammation , objective ly evaluated using the telethermographic index , showed consistent reduction during the study which was statistically significant from day 3 onwards and significantly different compared to the control group . Global assessment of efficacy , expressed by the investigator and the patients , was significantly better ( good to excellent after only 7 days in 70 % of the cases ) in the DHEP group compared to the placebo group . In the extra-articular pathologies , results similar to those reported earlier were obtained . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE : To evaluate the efficacy and safety of a homeopathic gel vs an NSAID ( piroxicam ) gel in the treatment of osteoarthritis of the knee . METHOD : One hundred and eighty-four out- patients with radiographically confirmed symptomatic osteoarthritis of the knee were entered into a pragmatic , r and omized , double-blind controlled trial and treated with 1 g of gel three times daily for 4 weeks . Main outcome measures were pain on walking as a Visual Analogue Score ( VAS ) and a single-joint Ritchie index . RESULTS : One hundred and seventy-two of the 184 enrolled patients had endpoints for the main outcome parameters . The pain reduction was 16.5 mm VAS in the homeopathy group ( n = 86 ) and 8.1 mm in the piroxicam group ( n = 86 ) ; the difference between treatment groups was 8.4 mm ( 95 % confidence interval 0.8 - 15.9 ) , and after adjustment for pain at baseline it was 6.8 mm ( 95 % confidence interval -0.3 to 13.8 ) . There was no significant difference between treatment groups in the single-joint Ritchie index ( P = 0.78 ) . Adverse events occurred in 28 patients ( 12 homeopathy group , 5 withdrawn ; 16 piroxicam group , 9 withdrawn ) ; 18 of the events involved a local reaction ( 7 homeopathy group , 2 withdrawn ; 11 piroxicam group , 5 withdrawn ) . CONCLUSION : The homeopathic gel was at least as effective and as well tolerated as the NSAID gel . The presence of a clinical ly relevant difference between treatment groups can not be excluded . The homeopathic gel supplemented by simple analgesics if required may provide a useful treatment option for patients with osteoarthritis The objective of the present study was to establish the efficacy and tolerability of local action transcutaneous flurbiprofen ( flurbiprofen LAT ) in the treatment of soft tissue lesions . A r and omized , double-blind , parallel-group placebo-controlled study was carried out in two hospital outpatient rheumatology clinics . One hundred and four patients aged 18 - 75 yr were r and omized to receive a non-woven polyester-backed patch supporting a formulation containing 40 mg flurbiprofen 12-hourly over 14 days ; or a non-medicated ( but otherwise identical ) control . Statistically significant differences in favour of the active preparation were seen at both days 7 ( P = 0.02 ) and 14 ( P = 0.009 ) for the investigator 's overall opinion of severity of the condition , and at day 7 for the investigator 's assessment of pain severity ( P = 0.04 intention-to-treat ; P = 0.052 N.S. eligible data ) . The need for further treatment in the form of steroid injections after the trial was greater in the controls ( 29/44 , 66 % ) than in the flurbiprofen LAT group ( 17/46 , 37 % ) ( chi 2 = 7.54 on 1 d.o.f . , P = 0.006 ) . Plasma flurbiprofen levels in 11 patients ranged from 13.4 to 338.7 ng/ml ( mean 116 ; median 57.9 ) . Eight out of 53 ( 15 % ) patients receiving flurbiprofen LAT reported a total of 10 adverse events , compared with three out of 51 ( 6 % ) reporting seven events among controls . Patients found the patch convenient and soothing . We conclude that flurbiprofen LAT is an effective and acceptable treatment for soft tissue lesions , and should be considered as an alternative therapy to local steroid injection Percutaneous efficacy and tolerability of a new topical indomethacin spray compared with a corresponding placebo product were evaluated in a double-blind , r and omized crossover study in 30 patients with tendinitis , i.e. 28 patients with peri-arthritis of the shoulder and two with epicondylitis . Each patient was treated with 4 % indomethacin spray or the corresponding placebo product three to five times daily for a period of 14 days and then received the other treatment for the same period of time . The indomethacin spray demonstrated a clear efficacy compared with the placebo based on both objective criteria ( elevation , abduction and internal rotation ) and subjective criteria ( spontaneous pain , pain on movement , pressure-induced pain , functional disturbances and sleep disturbances ) . Tolerability was excellent : only two patients had minor local cutaneous irritation with the indomethacin spray , which did not require interruption of treatment . Treatment with indomethacin spray appeared to be effective in 80 % and well-tolerated in 93 % of the patients studied The efficacy and safety of a 5 % ibuprofen cream ( Dolgit cream ) in primary knee osteoarthritis was assessed in this double-blind , r and omized , placebo-controlled , parallel-group study with an adaptive sequential design . The background of the study was the need to confirm the efficacy of ibuprofen cream .  Patients aged 40 - 75 years , with a visual analog scale ( VAS ) score of pain on motion of 40 mm , a Lequesne index score of 5 - 13 points , and a Kellgren and Lawrence radiographic score of grade II-III were enrolled between September 1999 and November 2000 . The study medication was applied in a 10-cm strip t.i.d . for 7 days on the more painful knee . In the active group , each strip contained approximately 200 mg ibuprofen . The main outcome measure was the response rate to the treatment compared between both groups . Response was defined as a reduction of pain on motion , self-assessed on a VAS , of > or = 20 mm compared with baseline . The planned interim analysis after inclusion of 2 x 50 patients showed a response rate of 32 ( 64.0 % ) in the ibuprofen group and 15 ( 30.0 % ) in the placebo group ( p = 0.000615 ) . The study could then be terminated . All secondary endpoints , pain at rest , pain on pressure , Lequesne index and overall assessment , also confirmed the statistically significant differences between the groups . No drug-related adverse events were recorded . The study confirmed the efficacy of ibuprofen cream by demonstrating its statistically significant and clinical ly relevant superiority over the placebo cream in the treatment of primary knee osteoarthritis Topical application , 4 times daily for 2 weeks , of the diclofenac-hyaluronan gel to 59 osteoarthritis patients induced a significantly greater ( p = 0.057 ) analgesic effect than placebo gel lacking the active substance applied to 60 control patients THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard This r and omised , double-blind , placebo-controlled , parallel-group trial was carried out to assess the efficacy and tolerability of a new , locally acting , transcutaneous flurbiprofen preparation ( flurbiprofen LATTM , Boots Company PLC ) in the treatment of scapulohumeral periarthritis . The new preparation consists of a nonwoven polyester patch supporting a mentholated formulation containing flurbiprofen 40 mg .  E 
    Output:
    
Conclusions Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks .