***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: One hundred patients who presented to the accident and emergency ( A&E ) department with an acute ankle sprain were entered into a study to determine the efficacy of topical ibuprofen cream by using a double-blind placebo controlled design in a single type of soft-tissue injury . The subjects were given either topical ibuprofen cream or a placebo cream in addition to the st and ard management of the department . Patients kept diaries recording walking ability and pain visual analogue scales for resting , st and ing and walking . A total of 51 patients returned diaries that were suitable for analysis . Patients using the topical ibuprofen cream had significant reduction in pain scores over the first 48 h of treatment 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-controlled , multi-centre study was carried out to assess the efficacy and tolerability of percutaneous niflumic acid gel in the treatment of uncomplicated ankle sprains . Sixty patients were enrolled in three centres and were r and omly allocated to receive treatment with 2.5 % percutaneous niflumic acid gel or placebo gel applied 3-times daily for 7 days . Clinical evaluations were made on entry to the study , after 3 days and at the end of treatment . The major efficacy criteria were the pain felt by the patient and the investigators ' and patients ' global evaluation of effectiveness of the treatment . Adverse events that occurred were also noted . The results showed that topically applied 2.5 % niflumic acid gel was superior to placebo in the treatment of ankle sprains in respect of all major parameters studied . Niflumic acid gel and the placebo were shown to be equally well tolerated . The study findings indicate that treatment with topical niflumic acid gel is effective in treating uncomplicated ankle sprains and results in improved clinical signs on Day 4 and after 7 days Topical anti-inflammatory management of superficial and deep phlebopathy with feprazone and benzidamine was compared in a double-blind test . Both drugs were active and well tolerated . Significantly less time was needed to obtain a cure with feprazone Objectives : To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries . Methods : This was a r and omised , placebo controlled , double blind , multicentre study in 120 patients with traumatic blunt soft tissue injury . Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days . Patients were r and omised ( 1:1 ) to two parallel groups . Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7 . Tenderness was defined as the amount of pressure ( measured by a calibrated caliper at the centre of the injury ) that first produced a pain reaction as reported by the patient . Results : The primary efficacy variable was the area under the curve for tenderness over the first 3 days . The diclofenac patch was significantly more effective than placebo ( p<0.0001 ) . The treatment effect was 64.7 kp h/cm2 ( 95 % confidence interval 48.7 to 80.9 ) between diclofenac and placebo patches . These results were supported by all secondary efficacy variables . The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo ( p<0.0001 ) . The diclofenac patch was well tolerated . The most frequently observed adverse events were local cutaneous adverse reactions ( pruritus , rash ) of minor severity occurring with the same frequency as in the placebo group . Conclusions : A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries Introduction Gastrointestinal upset and local pain commonly limit the use of oral nonsteroidal anti-inflammatory drugs and corticosteroid injection as treatments for lateral epicondylitis . Transdermal administration of an anti-inflammatory drug could avoid these adverse effects . Purpose To determine the effectiveness of topical diclofenac as a treatment of lateral epicondylitis . Methods A convenience sample of 14 subjects meeting clinical criteria of chronic lateral epicondylitis participated in this r and omized , double blind , crossover study . Each subject applied a plutonic lecithin liposomal organo-gel ( PLO ) over the affected lateral elbow three times daily for 1 week , followed by a 1-week “ washout ” period of no gel . A second topical PLO gel was then applied similarly for 1 week . Both gels were identical , but only one gel contained 2 % diclofenac . Treatment order was r and omized , and both the subject and tester were blinded . Pain and isometric wrist extension strength were measured using a visual analog pain scale ( VAS ) and a mounted manual muscle testing dynamometer , respectively , at the following time periods : just before application of the first gel , the last day of using the first gel , the last day of the washout week , and the last day of using the second gel . Analysis was performed using repeated measures analysis of variance . Results When subjects used diclofenac PLO , pain was significantly less than that during the pretreatment , washout , and placebo PLO periods ( mean VAS ; diclofenac PLO , 2.1 ; pretreatment , 3.5 ; washout , 3.4 ; placebo PLO , 3.6 ) . Average wrist extension strength was significantly greater when subjects used diclofenac PLO ( 8.4 kg ) than it was before treatment ( 5.9 kg ) . One subject developed a local rash while using diclofenac PLO . Conclusion Topical 2 % diclofenac in PLO appears to provide effective short-term reduction in elbow pain and wrist extensor weakness associated with chronic lateral epicondylitis A double-blind study vs placebo was carried out on 82 pts suffering from soft tissue trauma , to evaluate the efficacy and tolerance of a new anti-inflammatory , non-steroidal analgesic for topical use , 3 % BPAA . Clinical results obtained by the group treated with BPAA gel were highly significant ( p = 0.01 ) and positive , showing absence of local and systemic side-effects . Accordingly , BPAA gel can be recommended for treatment of soft tissue trauma One hundred and thirty-one male and female out patients , aged 18 - 70 yr , with acute pain in the ankle joint caused by a post-traumatic sprain , entered a multicentre , r and omised , double-blind , parallel-group , study . The patients were assigned to a 40 mg flurbiprofen patch ( n = 65 ) or a non-medicated ( but otherwise identical ) control ( n = 66 ) , 12-hourly over 7 days , and were assessed at entry and after 3 and 7 days treatment . On day 7 , spontaneous pain ( the prime efficacy parameter ) , as evaluated by the patient on a visual analogue scale in the physician 's office , showed significant improvement in the 40 mg flurbiprofen patch group compared to control ( change from baseline ) ( p = 0.039 ) , a result corroborated by the evaluation of the periarticular oedema : a reduction of 77.4 % was observed in the 40 mg flurbiprofen patch group , compared with 63.8 % in the control group ( p = 0.025 ) . The other selected efficacy criteria showed changes with a trend in favour of the 40 mg flurbiprofen patch but without statistical significance . Two mild and local adverse events were reported by two flurbiprofen patch patients , but neither patients discontinued the treatment prematurely . Physicians and patients found the flurbiprofen patch to be efficacious and well tolerated . Compliance was excellent in both groups . The efficacy and tolerability of the 40 mg flurbiprofen patch are therefore confirmed in the treatment of acute ankle sprains Abstract Objective : To determine whether inappropriate subgroup analysis together with chance could change the conclusion of a systematic review of several r and omised trials of an ineffective treatment . Design : 44 r and omised controlled trials of DICE therapy for stroke were performed ( simulated by rolling different coloured dice ; two trials per investigator ) . Each roll of the dice yielded the outcome ( death or survival ) for that “ patient . ” Publication bias was also simulated . The results were combined in a systematic review . Setting : Edinburgh . Main outcome measure — Mortality . Results : The “ hypothesis generating ” trial suggested that DICE therapy provided complete protection against death from acute stroke . However , analysis of all the trials suggested a reduction of only 11 % ( SD 11 ) in the odds of death . A predefined subgroup analysis by colour of dice suggested that red dice therapy increased the odds by 9 % ( 22 ) . If the analysis excluded red dice trials and those of poor method ological quality the odds decreased by 22 % ( 13 , 2P=0.09 ) . Analysis of “ published ” trials showed a decrease of 23 % ( 13 , 2P=0.07 ) while analysis of only those in which the trialist had become familiar with the intervention showed a decrease of 39 % ( 17 , 2P=0.02 ) . Conclusion : The early benefits of DICE therapy were not confirmed by subsequent trials . A plausible ( but inappropriate ) subset analysis of the effects of treatment led to the qualitatively different conclusion that DICE therapy reduced mortality , whereas in truth it was ineffective . Chance influences the outcome of clinical trials and systematic review s of trials much more than many investigators realise , and its effects may lead to incorrect conclusions about the benefits of treatment Anecdotally many athletes use non-steroidal anti-inflammatory gels during competition to allow continued participation . To determine if this clinical practice is useful a r and omised placebo-controlled study was conducted at the 5-day 2004 Red Cross Murray River Marathon . Forty-two kayakers presented with wrist extensor tenosynovitis while competing in the single and double kayak events . All subjects received st and ard treatment of ice , stretches and massage for wrist tenosynovitis before being r and omised into a placebo or 1 % diclofenac gel group . Evaluation was done by using a visual analogue scale ( 0 - 10 ) for pain and by clinical grading ( 0 - 3 ) . The main outcome measurements were reduction in pain and clinical grading , the requirement for a rescue medication ( paracetamol or diclofenac tablets ) and effect on performance times . Both groups had similar pain scores and clinical grading on the first and fifth days of pain . On the second to fourth days of pain there was clearly no benefit and possibly a detrimental effect on pain with diclofenac gel relative to placebo . However , diclofenac tablets were possibly beneficial for pain relative to paracetamol tablets . The effects of pain and the various treatments on performance time were either trivial ( < 0.5 % ) or small , but none was particularly clear . We conclude that st and ard treatment appears to be sufficient for the management of wrist extensor tenosynovitis during competition To evaluate the efficacy and tolerability of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel ( DHEP lecithin gel , with 1.3 % DHEP and 2.4 % lecithin ) compared with the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel ( DHEP gel ) in peri and extraarticular inflammatory states , a controlled , r and omized , double-blind clinical study was conducted . Two groups of 50 patients each were enrolled and were given one of the two different formulations with a slight massage on the painful area three times a day for 10 consecutive days . Patients received a self-evaluation notebook in which to record daily assessment of spontaneous pain ( Huskisson 's visual analogue scale ) . On days 0 , 3 and 10 , the patients were visited by the investig 
    Output:
    
Topical diclofenac , ibuprofen , ketoprofen , and piroxicam were of similar efficacy , but indomethacin and benzydamine were not significantly better than placebo .
Local skin reactions were generally mild and transient , and did not differ from placebo .
There were very few systemic adverse events or withdrawals due to adverse events .
Topical NSAIDs can provide good levels of pain relief , without the systemic adverse events associated with oral NSAIDs , when used to treat acute musculoskeletal conditions