***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 The effect of analgesics on pathological pain in a double‐blind , complete cross‐over design was assessed by means of two rating scales , a  verbal rating scale ( VRS ) and visual analogue scale ( VAS ) .  The VRS is widely used , but has several disadvantages as compared to the  VAS  . The results obtained by means of the VRS showed higher F‐ratios ( analysis of variance and Kruskall‐Wallis H‐test ) than those obtained by means of the VAS . The VRS , which transfers a continous feeling into a digital system , seems to augment artificially the measurement of effects produced by analgesics , and the VAS seems to assess more closely what a patient actually experiences with respect to change in pain intensities . The correlation between the two scales was highly significant ( r = 0.81 , P < 0.001 ) . The calculated regression line ( y = −29.6 + 0.55 · x ) was not similar to the line of identity and showed much lower values for the VAS , supporting our intepretation . The distribution of the variances of the values obtained by means of both scales was not homogenous . This indicates that the homogeneity of the distribution of variances should always be checked and a Kruskall‐Wallis H‐test used , if they are inhomogenously distributed BACKGROUND Ankle arthritis can cause substantial pain and functional limitation . Previous studies have indicated that five weekly intra-articular injections of hyaluronate were safe and effective in the treatment of ankle osteoarthritis . The purpose of this study was to evaluate the effect and safety of three weekly injections of hyaluronate in patients with unilateral ankle arthritis . METHODS Fifty patients who had had unilateral ankle pain for at least six months and were classified radiographically as having Kellgren-Lawrence grade -2 or 3 ankle arthritis were recruited for a prospect i ve study . Patients received three weekly intra-articular injections of hyaluronate . The primary outcome was the change in the Ankle Osteoarthritis Scale score at six months after the third injection . Secondary outcomes included the American Orthopaedic Foot & Ankle Society ( AOFAS ) Ankle-Hindfoot Score , four clinical tests of balance , consumption of rescue analgesics , and global patient satisfaction . RESULTS Forty-six participants completed the study . A significant reduction in the mean Ankle Osteoarthritis Scale score was noted at one , three , and six months after the third injection ( p < 0.05 for each follow-up visit compared with baseline ) . The mean AOFAS Ankle-Hindfoot Score improved from 60.5 points at baseline to 73.5 , 75.5 , and 76.7 points at one , three , and six months of follow-up , respectively ( p < 0.05 ) . The patients demonstrated significant improvement on all four balance tests at each follow-up visit ( p < 0.05 for each test compared with baseline ) . Acetaminophen consumption dropped significantly following treatment ( p < 0.05 ) . The patients ' satisfaction rate was high , and no serious adverse events were reported . CONCLUSIONS This study suggests that three weekly injections of hyaluronate are well-tolerated and can provide pain relief and improve function and balance in patients with unilateral ankle arthritis . Larger controlled trials with longer follow-up are necessary to verify the effects of hyaluronate in the treatment of ankle arthritis BACKGROUND Osteoarthritis ( OA ) is the most common joint disease encountered throughout Europe . A task force for the EULAR St and ing Committee for Clinical Trials met in 1998 to determine the method ological and logistical approach required for the development of evidence based guidelines for treatment of knee OA . The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinical ly and /or radiographically affecting any compartment of the knee . METHODS The first stage was the selection of treatment modalities to be considered . The second stage comprised a search of the electronic data bases Medline and Embase using a combination of subject headings and keywords . All European language publications in the form of systematic review s , meta-analyses , r and omised controlled trials , controlled trials , and observational studies were included . During stage three all the relevant studies were quality scored . The summary statistics for vali date d outcome measures , when available , were recorded and , where practical , the numbers needed to treat and the effect size for each treatment were calculated . In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach . The final stage ranked these propositions according to the available evidence . A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach . RESULTS Over 2400 English language publications and 400 non-English language publications were identified . Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA . Quantitative analysis of treatment effect was possible in only 61 studies . Recommendations for the management of knee OA based on currently available data and expert opinion are presented . Proposals for a future research agenda are highlighted . CONCLUSIONS These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities . It is apparent that certain clinical propositions are supported by substantial research based evidence , while others are not . There is thus an urgent need for future well design ed trials to consider key clinical questions Five hundred subjects with symptomatic limb joint osteoarthritis , who had been referred to a rheumatologist , were enrolled into a continuing study . They comprised 342 women ( mean age 65.3 ) and 158 men ( mean age 59.7 ) , with a mean symptom duration of 15.4 years at entry . Only 31 patients ( 6 % ) had symptomatic osteoarthritis of one joint alone ; however , in a further 205 ( 41 % ) the disease was limited to one site . One hundred and eighty two ( 36.4 % ) had two sites affected and 82 ( 16.4 % ) three or more sites of symptomatic osteoarthritis . Of 847 affected joints the most commonly involved were 349 ( 41.2 % ) knees , 254 ( 30 % ) h and s , and 161 ( 19 % ) hips . Hip disease stood out as a separate entity , often occurring alone , and having a stronger male preponderance and different associations than osteoarthritis at other joint sites . Knee and h and disease were significantly associated in women . Obesity , hypertension , and Heberden 's nodes were common . The number of sites affected , as well as the distribution , was strongly related to age as well as sex , suggesting that polyarticular osteoarthritis arises from slow acquisition of new joint sites in a non-r and om distribution . ' Generalised ' osteoarthritis did not emerge as a distinct entity Background There was an increasing requirement for novel treatments of osteoarthritis ( OA ) . The aim was to compare the efficacy of intraarticular Botulinum toxin type A ( BoNT-A ) and intraarticular hyaluronate plus rehabilitation exercise in patients with ankle OA . Methods This was a prospect i ve , r and omized , assessor-blinded study with a 6-month follow-up period , conducted in the outpatient rehabilitation department at a university-affiliated tertiary care medical center . Seventy-five patients with symptomatic ankle OA ( Kellgren-Lawrence grade 2 ) were r and omized to receive either a single 100-unit BoNT-A injection into the target ankle ( n = 38 ) or a single hyaluronate injection plus 12 sessions of rehabilitation exercise ( 30 minutes/day , 3 times/week for 4 weeks ) ( n = 37 ) . The primary outcome measure was the Ankle Osteoarthritis Scale ( AOS ) . Secondary outcome measures included American Orthopedic Foot and Ankle Society ( AOFAS ) Ankle/Hindfoot Score , visual analog scale ( VAS ) for ankle pain , single leg stance test ( SLS ) , Timed “ Up- and -Go ” test ( TUG ) , consumption of rescue analgesics and global patient satisfaction . Results There were no significant between-group differences in total AOS scores , pain subscale and disability subscale scores ( adjusted mean difference AMD = -0.2 , 95 % CI = ( -0.5 , 0.2 ) , p = 0.39 ; AMD = -0.1 , 95 % CI = ( -0.5 , 0.3 ) , p = 0.57 ; AMD = -0.2 , 95 % CI = ( -0.6 , 0.2 ) , p = 0.36 ) . The 2 groups showed no significant differences in AOFAS , VAS , SLS , TUG scores and consumption of rescue analgesics at each follow-up visit , except that the hyaluronate group improved more in SLS than the BoNT-A group at 1-month follow-up . Patients ’ satisfaction rate was high , with no serious adverse events . There was no difference in adverse events between the two groups ( p = 1.00 ) . Conclusions Treatment with intraarticular BoNT-A or hyaluronate injection plus rehabilitation exercise was associated with improvements in pain , physical function and balance in patients with ankle OA . These effects were rapid at 2 weeks and might last for at least 6 months . There was no difference in effectiveness between the two interventions .Trial registration The trial was registered at clinical trials.gov ( Registry number NCT01760577 ) OBJECTIVE The goal of this study has been to determine whether hyaluronic acid ( HA ) or exercise therapy can improve functional parameters in patients with osteoarthritis ( OA ) of the ankle . METHODS In a prospect i ve clinical trial , 43 ankles ( 30 patients ) with radiographic Kellgren Lawrence grade III OA were r and omized to receive three intra-articular HA injections , with one-week interval of or exercise therapy for six weeks . Patients were evaluated by the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle-Hindfoot Scale and followed-up after 12 months . RESULTS Total AOFAS Ankle-Hindfoot score of OA patients has improved in both groups , varying from 61.6+/-16.8 to 90.1+/-9.7 with HA treatment and from 72.1+/-16.6 to 87.5+/-17.5 using  exercise therapy  at the end of the trial ( p<0.01 ) . There were no statistically significant differences between the groups . CONCLUSION This prospect i ve r and omized trial confirmed that , both HA injections and exercise therapy provide functional improvement . However , larger trials with longer follow-up are necessary for more definite conclusions BACKGROUND Investigators seeking to underst and the impact of musculoskeletal disorders commonly use vali date d outcome instruments to assess the effect of diseases on physical function and quality of life . However , the influence of concomitant systemic or musculoskeletal comorbidities on these scores has not been widely considered in orthopaedic research . The purpose of this study was to determine how morbidity unrelated to the ankle influences the perception of physical function and pain by patients with ankle osteoarthritis . METHODS  Short Form-36 ( SF-36 ) Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) scores , Ankle Osteoarthritis Scale ( AOS ) pain scale scores ,  demographic data  , and systemic and musculoskeletal comorbidities were determined prospect ively for 195 patients with ankle osteoarthritis and ninety-five age and gender-matched controls . The effect of systemic and musculoskeletal comorbidities on each of the scores was determined . RESULTS On the average , patients with ankle osteoarthritis had a relatively normal MCS score ( 47 + /- 13 points ) and a markedly diminished PCS score ( 32 + /- 8 points ) . Both of these scores averaged 50 + /- 9 points in the control group . The AOS pain score averaged 61 + /- 23 points in the group with ankle osteoarthritis , whereas it averaged 10 + /- 15 points in the control group . We found the perception of ankle pain by patients with ankle osteoarthritis to be significantly and linearly associated with the number of other musculoskeletal problems ( not related to the foot or ankle ) . CONCLUSIONS The degree of physical impairment associated with ankle osteoarthritis , as measured with the SF-36 , is equivalent to that reported to be associated with severely disabling medical problems including end-stage kidney disease and congestive heart failure . The perception of ankle health status as measured with a vali date d , patient-oriented , anatomically specific instrument is influenced by the patients ' perception of their overall musculoskeletal comorbidity status . The authors of clinical studies using these instruments should adjust for concomitant musculoskeletal disease Sixty-two consecutive patients with painful limited dor siflexion of the ankle not responding to nonoperative treatment participated in a prospect i ve study . All 42 men and 20 women ( average age , 31 years ) under went arthroscopic surgery .  Preoperative radiographs were grade d according to an osteoarthritic and an impingement classification . St and ardized followup took place at 4 months and 1 and 2 years after surgery . Results showed that the degree of osteoarthritic changes is a better prognostic factor for the outcome of arthroscopic surgery for anterior ankle impingement than size and location of the spurs . The hypothesis is that osteophytes without joint space narrowing are not a manifestation of osteoarthritic changes but rather the result of local (micro)tra 
    Output:
    
No minimal important clinical difference is known for this score .
Simple analgesics as recommended for hip and knee OA seem however a reasonable first step to treat ankle OA .
Inconclusive results were found comparing HA to other treatments .
It remains unclear which patients ( age , grade of ankle OA ) benefit the most from HA injections and which dosage schedule should be used