***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: In a double-blind , r and omized , multicentre clinical study , the efficacy and tolerance of a herbal medicine product , Harpadol ( 6 capsules/day , each containing 435 mg of powdered cryoground powder Harpagophytum procumbens ) , was compared with diacerhein 100 mg/day in the treatment , for 4 months , of 122 patients suffering from osteoarthritis of the knee and hip . Assessment s of pain and functional disability were made on a 10 cm horizontal visual analogue scale ; severity of osteoarthritis was evaluated by Lequesne 's index . Spontaneous pain showed a significant improvement during the course of the study and there was no difference in the efficacy of the two treatments . Similarly , there was a progressive and significant reduction in the Lequesne functional index and no statistical difference was found between Harpadol and diacerhein . At completion of the study , patients taking Harpadol  were using significantly less NSAIDs and antalgic drugs . The frequency of adverse events was significantly lower in the  Harpadol group . The most frequent event reported was diarrhea , occurring in 8.1 % and 26.7 % of Harpadol and diacerhein patients respectively . The global tolerance assessment by patients at the end of treatment favoured Harpadol . The results of this study demonstrate that Harpadol is comparable in efficacy and superior in safety to diacerhein BACKGROUND Diacerein is a drug used in osteoarthritis ( OA ) that elicits an inhibitory effect on interleukin-1 and metalloproteases . Although diacerein has shown modest efficacy and safety in the treatment of knee and hip OA , there have been no placebo-controlled clinical trials for h and OA . OBJECTIVE The aim of the current study was to investigate the efficacy and tolerability of diacerein in patients with h and OA . METHODS Patients fulfilling the American College of Rheumatology criteria for h and OA participated in this r and omized , double-blind , placebo-controlled study . Eligible patients were > 40 years of age , had at least 1 tender joint , and had a joint pain visual analog scale of > 30 mm . Patients received diacerein ( 50 mg ) or placebo BID for 12 weeks . The primary end point was the Australian/Canadian Osteoarthritis H and Index ( AUSCAN ) pain score at 4 weeks . Secondary end points were AUSCAN pain score at 12 weeks and AUSCAN physical function and stiffness score , patient and physician global assessment , functional index of h and OA scores , and multidimensional health assessment question naire results at 4 weeks and 12 weeks . RESULTS Eighty-six Korean patients were enrolled ( 42 diacerein , 44 placebo ) . The intention-to-treat and per- protocol analyses revealed no significant differences between the 2 groups in terms of change in AUSCAN pain score at 4 weeks , except for improvement in physician global assessment at 4 weeks ( per- protocol analysis , P = 0.004 ) . The safety profile of diacerein was comparable to placebo , except for frequent discoloration of the urine ( 88 % vs 20 % ) . CONCLUSION These results suggest that diacerein 50 mg BID may be ineffective in controlling the symptoms of h and OA . Clinical Trials.gov identifier : NCT00685542 Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should Objectives : To present the prevalence of  self reported musculoskeletal diseases  , the coexistence of these diseases , the test-retest reliability with six months in between , and the association with musculoskeletal pain symptoms . Methods : Twelve layman descriptions of common musculoskeletal diseases were part of the question naires of a prospect i ve cohort study of a r and om sample in the general Dutch population aged 25 years or more ( baseline : n=3664 , follow up after six months : n=2338 ) . Data collection also included information about pain relating to five different anatomical areas . Results : Osteoarthritis of the knee ( men 10.1 % , women 13.6 % ) was amongst the most reported musculoskeletal diseases , whereas the figures for self reported rheumatoid arthritis ( RA ) were 1.6 % and 4.6 % for men and women , respectively . The coexistence of these diseases is high : 47 of the 66 combinations were reported more often than would be expected if they were independent of each other ( p<0.05 ) . For most diseases the test-retest reliability was good ( κ between 0.6 and 0.8 ) , but for repetitive strain injury ( κ=0.37 ) and chronic arthritis other than RA ( κ=0.44 ) the agreement was fair to moderate . All complaints of pain were more often reported by those with musculoskeletal diseases than those without those diseases , and the pain pattern was disease-specific . Conclusions : Self reported musculoskeletal diseases are highly prevalent , with a fair to good reliability and a disease-specific pain pattern . Health surveys are a limited but valuable source of information for this group of health problems , which is not available from most other sources of information OBJECTIVE To estimate the prevalence of radiographic and symptomatic knee osteoarthritis ( OA ) in a population -based sample of elderly subjects in Beijing , China and compare it with that reported in the Framingham ( Massachusetts ) OA Study . METHODS We recruited a sample of persons age > or = 60 , using door-to-door enumeration in r and omly selected neighborhoods in Beijing . Subjects completed a home interview including questions on knee symptoms and a hospital examination including knee radiographs obtained during weight bearing . The protocol was identical to that used in the Framingham OA Study . A reader read intermingled Beijing and Framingham Study films to ensure high reliability . We defined a subject as having radiographic knee OA when the Kellgren/Lawrence grade was > or = 2 in at least 1 knee . Symptomatic knee OA was recorded as present when knee pain was reported and the symptomatic knee had radiographic OA . We estimated the prevalence of these entities in elderly subjects in Beijing and compared it with OA prevalence in Framingham , using an age-st and ardized prevalence ratio . RESULTS Of 2,180 age-eligible Beijing subjects contacted , knee radiographs  were obtained in 1,787 ( 82.0 % ) . The prevalence of radiographic knee OA was 42.8 % in women and 21.5 % in men . Symptomatic knee OA occurred in 15.0 % of women and 5.6 % of men . Compared with women of the same age in Framingham , women in Beijing had a higher prevalence of radiographic knee OA ( prevalence ratio 1.45 , 95 % confidence interval 1.31 - 1.60 ) and of symptomatic knee OA ( prevalence ratio 1.43 , 95 % confidence interval 1.16 - 1.75 ) . The prevalence of knee OA in Chinese men was similar to that in their white US counterparts ( for radiographic OA , prevalence ratio 0.90 ; for symptomatic OA , prevalence ratio 1.02 ) . CONCLUSION Using identical methods and definitions to evaluate the prevalence of OA across population s , we found , surprisingly , that older Chinese women have a higher prevalence of knee OA than women in Framingham , Massachusetts . The prevalence in men was comparable . Possible explanations for these differences range from genetic differences to heavy physical activity among Chinese 71 patients with variously located osteoarthrosis or primary fibromyalgic syndrome were treated with oral diacereine ( DAR ) . The case series was accumulated in successive periods and may be divided into three groups . An " open " test on DAR ( 100 mg/die for 4 weeks ) was conducted on the first group of 31 arthrosis patients . On the second group of 20 other arthrosis patients a " double-blind , cross-over " test was carried out using DAR ( 100 mg/die ) and naproxene ( 500 mg/die ) both for 2 weeks . The third group of 20 patients with fibromyalgia was treated with DAR alone : 100 mg/die 5 days a week for 12 weeks . The efficacy of the treatment was judged on the basis of the following parameters : rest pain , pressure pain , pain on active and passive movement , and functional limitation . In the first group a positive therapeutic effect was noted in 20 cases ( 68.9 % ) . There were side effects ( moderate diarrhea ) in 3 patients 2 of whom suspended treatment . In the second group , DAR and naproxene had an almost identical effect . However 7 patients ( 36.8 % ) expressed a preference for  DAR , 9 ( 47.4 % ) expressed no preference and only 3 ( 15.8 % ) preferred naproxene .  Side effects were encountered in 3 patients treated with naproxene ( 2 cases of epigastralgia and pyrosis and 1 case of dyspnea so marked as to require suspension of treatment ) and in 3 treated with DAR ( modest diarrhea ) . In the third group , a positive therapeutic effect was noted in 68.4 % of the patients with fibromyalgia with a 15 % incidence of side effects consisting of slight abdominal pain ( diarrhea caused suspension of treatment in 1 case only ) . Blood chemical parameters were studied in all three groups and no alterations attributable to the treatment were found . The obtained result suggests that the new drug is effective and well tolerated in the envisaged indications A single-blind , placebo controlled study was carried out over a 12-week period in 12 patients with osteoarthritis of the hip or knee to assess the effectiveness of 50 mg diacetylrhein per day . The 4 weeks of active treatment were preceded and followed by periods on placebo . Response to treatment as assessed by pain score , walking time and the number of ' rescue ' analgesic tablets ( paracetamol ) consumed showed that 6 patients improved , 4 were unchanged and 2 deteriorated . Improvement was not apparent for several weeks after starting active treatment and remission lasted for 2 weeks to 3 or more months after the drug was withdrawn . The action of diacetylrhein is not yet established , but it does not appear to be related to analgesia or inhibition of prostagl and in synthetase activity . It is considered that further studies of this interesting drug are warranted to determine the most effective dose and duration of treatment The index for hip disease ( ISH ) was established , vali date d and appraised as a new assessment test for the trial of new drugs as well as for long-term follow-up of patients , and to help with future indications for surgery . The ISH deals with pain , maximum walking distance , and some activities of daily living . Inter-observer reproducibility is good ( mean deviation 0.55 points ; p less than 0.05 ) . In a short-term , double-blind crossover trial , the ISH , judged according to its power to distinguish between the active drug period and the placebo period , appears as one of the best assessment tests . In the long term , total hip prosthesis is most often justified when the ISH score reaches 10 - 12 points . The index of severity for knee disease ( ISK ) was vali date d and appraised by the same statistical methods . Its value in non-steroidal anti-inflammatory drug ( NSAID ) or analgesic trials is lower than the value of the ISH . However , its use is still justified for that purpose , and for long-term follow-up of osteoarthritis of the knee Summary This 9-month pragmatic study compared 2 therapeutic regimens in the management of osteoarthritis of the hip and knee . Patients received either diacerein 100 mg/day plus st and ard osteoarthritic therapy for 6 months , followed by a 3-month monitoring period without diacerein , or st and ard therapy alone for the entire 9-month period . A total of 207 patients with osteoarthritis of the knee and hip were enrolled .  Improvements in Lequesne ’s functional index and quality -of-life scores ( revised Arthritis Impact Measurement Scales Health Status Question naire and Nottingham Health Profile ) , and decreases in nonsteroidal anti-inflammatory drug and analgesic consumption were significantly greater with diacerein plus st and ard therapy than with st and ard therapy alone . The overall assessment of therapy by patients was good or excellent for 60 % of those who received diacerein plus st and ard therapy , compared with 26 % who received st and ard therapy alone . Medical and paramedical procedures carried out in addition to those stipulated in the protocol ( medical consultations , physiotherapy , nursing , etc . ) , osteoarthritis-related , were fewer and less costly in the diacerein plus st and ard therapy group than in the st and ard therapy 
    Output:
    
This benefit may not be clinical ly significant .
We confirmed that symptomatic benefit provided by diacerein in terms of pain reduction is minimal .
The small benefit derived in terms of joint space narrowing is of question able clinical relevance and was observed only for OA of the hip .
With respect to adverse effects of diacerein , diarrhoea was most frequent .