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: OBJECTIVES To compare budesonide , a locally acting glucocorticoid with minimal systemic exposure , with conventional glucocorticoid treatment and placebo in rheumatoid arthritis . METHODS A double blind , r and omised , controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis , comparing budesonide 3 mg daily , budesonide 9 mg daily , prednisolone 7.5 mg daily , and placebo . Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment . RESULTS There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo ( 28 % for tender and 34 % for swollen joint counts , p<0.05 ) . Prednisolone 7.5 mg gave similar results , while budesonide 3 mg was less effective . ACR20 response criteria were met by 25 % of patients on placebo , 22 % on budesonide 3 mg , 42 % on budesonide 9 mg , and 56 % on prednisolone 7.5 mg . A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks . There was no evidence that budesonide provided a different pattern of symptom control from prednisolone , or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment . Adverse effects attributable to glucocorticoids were equally common in all groups . CONCLUSIONS The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment , are maintained for three months , and are not associated with any rebound in symptoms after stopping treatment Assessment of inflammation in rheumatoid arthritis ( RA ) has been studied in several different ways . Hart and Huskisson ( 1972 ) considered morning stiffness to be a reflection of inflammation with the disadvantage of being subjective . Boardman and Hart ( 1967 ) used proximal interphalangeal joint circumference which is at least objective , but may not be responsive to anti-inflammatory therapy , for example in patients with long-st and ing or ' burnt-out ' disease . Dick , Neufeld , Prentice , Woodburn , Whaley , Nuki , and Buchanan ( 1970 ) found that external count rates over single inflamed joints were greater than those over normal joints . They used technetium 99 ( 99Tc ) , an isotope with a half-life of 6 hours , and showed reduction in counts after treatment with anti-inflammatory drugs . In a previous study , Huskisson , Berry , Browett , and Balme ( 1973 ) showed , no relationship between technetium count over a single joint and any other measurement , arguing that reduction in count rate over a single joint could not be equated with anti-inflammatory effect . These authors also used an index based on counts over both wrists and knees , and in a small study there was a significant correlation with articular index . Though highly protein bound , 99Tc is presumably distributed to some extent in the extravascular extracellular space . Huskisson and others ( 1973 ) showed , by simultaneous counting of a blood sample and of soft tissues over the forearm , that 99Tc tended to remain more within the vascular compartment in patients with rheumatoid arthritis than in normals . Since most authors have suggested that 99Tc measures ' vascularity ' , an isotope which remains entirely within the circulation might be more useful for this purpose . In this study , Indium 113 ( 113In ) , a gamma emitter with a half-life of 99 5 minutes , was used . It is believed that it remains almost entirely within the circulation ( Stern , Goodwin , Scheffel , Wagner , and Kramer , 1967 ) . The 113kIn and 99Tc indices have been compared and their responsiveness to anti-inflammatory therapy assessed Indomethacin , 100 mg orally , was compared with prednisolone , 5 mg , as addititional therapy at night , in a two-week , double-blind , between-patient study in twenty-four in- patients with rheumatoid arthritis . Both therapies proved equally effective , and significantly lessened morning stiffness and increased grip strenght .  Two patients with dyspepsia were discontinued from the indomethacin group . Using indomethacin at night avoided the central nervous system side-effects frequently seen with this compound Prednisone , 5 mg taken each morning , was added to other drugs in 18 patients with rheumatoid arthritis . Sixteen patients were given a placebo  in this double blind study . After 24 weeks , all patients were given the placebo .  Slight functional improvement was noted in the prednisone group during the 24-week period , but deterioration after switching to placebo was sustained for at least 8 weeks . Progression of h and erosions occurred in 1 prednisone-treated patient , and in 4 controls . An asymptomatic vertebral spine compression fracture developed in 2 patients given prednisone ; this was the only toxicity noted possibly due to this therapy . Minimal dose prednisone may be useful as " bridge " therapy between nonsteroidal antiinflammatory therapy and use of disease-modifying drugs Measurement of digital joint circumference by using a plastic spring gauge has been carefully evaluated in rheumatoid patients . There is very small Ultra-observer but large inter-observer variation . A diurnal change in joint size could not be confirmed . Provided that joints affected by soft tissue swelling are used , the measure is a useful Index of the effect of anti-inflammatory drugs . John Webb Centre for Rheumatic Diseases 35 Baird Street Glasgow , G. 40 EH Scotl A 14-day , single-blind trial of prednisone , aspirin , and placebo was carried out in 128 patients suffering from rheumatoid arthritis , using subjective criteria only ( severity of pain daily on a pain chart and assessment of the drug for effectiveness ) . The average treated pain rating , mean patient satisfaction rating , and mean number of days withdrawn from each drug all showed significant differences between prednisone , aspirin , and placebo . Of various pretreatment observations , only the initial pain score and articular index of joint tenderness were significantly related to the average treated pain rating . The trial method is simple and allows many patients to participate without being time consuming for patient or physician . The method seems to have potential in comparing the comparative effectiveness of anti-inflammatory analgesics used in the treatment of patients with rheumatoid arthritis BACKGROUND Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory . Studies showing radiological benefit suggest that continued treatment is required to sustain the effect . OBJECTIVE To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years . DESIGN Double blind placebo controlled trial . METHODS Patients with rheumatoid arthritis , duration <3 years ( n = 167 ) , were started on a disease modifying antirheumatic drug ( DMARD ; sulphasalazine )  and allocated by stratified r and omisation to prednisolone 7 mg/day or placebo . Primary outcome measure was radiological damage , assessed by the modified Sharp method . Clinical benefit was a secondary outcome . A proactive approach to identifying and treating corticosteroid adverse events was adopted . Patients who discontinued sulphasalazine were offered an alternative DMARD . RESULTS 90 of 257 patients eligible for the study refused to participate ( more women than men ) . Of those enrolled , 84 % were seropositive for rheumatoid factor , median age 56 years , median disease duration 12 months , female to male ratio 1.8:1 .  Prednisolone was given to 84 patients ; of these 73 % continued prednisolone and 70 % sulphasalazine at 2 years . Of the 83 patients on placebo , 80 % continued placebo and 64 % sulphasalazine at 2 years . There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years . CONCLUSIONS Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years . Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs OBJECTIVE Prednisolone reduced the progression of joint destruction over 2 yr in early , active rheumatoid arthritis . The response to discontinuation of prednisolone under double-blind conditions is now reported . METHODS A r and omized , double-blind , placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis , using radiological progression ( changes in the Larsen score ) and the development of erosions as primary outcome measures . Study medication was blindly discontinued and follow-up maintained for a further year . Other assessment s included disability , joint inflammation , pain and the acute-phase response . RESULTS Similar results were obtained when all available radiographs were included for each year of assessment ( maximum 114 ) and when only patients with radiographs at all time points were included ( 75 patients ) . In these 75 , the mean progression in the prednisolone group was 0.21 Larsen units in year 1 , 0.04 units in year 2 and 1.01 units in year 3 ( P = 0.587 , 0.913 and 0.039 for change within each year , respectively ) . The equivalent placebo group means were 2.34 , 1.00 and 1.63 Larsen units ( P = 0.001 , 0.111 and 0.012 ; difference between groups : 2.13 , 0.96 and 0.67 units , P = 0.082 , 0.02 and 0.622 ) . The percentage of h and s which had erosions at each time point was : prednisolone group : 27.8 , 29.2 , 34.7 and 39.2 ; placebo group : 28.2 , 48.7 , 59.0 and 66.5 . There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone . CONCLUSION Joint destruction resumed after discontinuation of prednisolone . This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis BACKGROUND Bone damage in rheumatoid arthritis presents as osteoporosis and joint erosions . Prednisolone has been shown to reduce the rate of h and joint destruction as seen on radiography but has not been shown to reduce the rate of h and bone loss . METHODS In a double-blind study comparing oral prednisolone ( 7.5 mg/d for 2 years ) with placebo ,  h and bone density assessed with digital x-ray radiogrammetry was examined in 95 patients with rheumatoid arthritis with disease duration of less than 2 years . RESULTS The mean loss of h and bone density was less in prednisolone-treated patients compared with placebo-treated patients at the 1-year follow-up ( -0.011 vs -0.022 g/cm(2 ) ) ( P = .005 ) and at the 2-year follow-up ( -0.026 vs -0.039 g/cm(2 ) ) ( P = .03 ) . The mean percentage group difference in loss of h and bone density was 2.8 % ( P = .004 ) at the 1-year follow-up and 3.5 % ( P = .01 ) at the 2-year follow-up . In the first year , C-reactive protein , a marker of inflammation , was strongly correlated with h and bone loss in placebo-treated patients but not in prednisolone-treated patients , suggesting that prednisolone breaks the link between bone loss and inflammation . CONCLUSIONS To our knowledge , this is the first double-blind r and omized study to show that disease-related loss of h and bone density in rheumatoid arthritis can be decelerated by prednisolone . This finding suggests that the deleterious effect of prednisolone on bone may be counteracted by its anti-inflammatory effect Ibuprofen ( 2 - 4'-isobutylphenylpropionic acid ) is one of a series of phenylalkanoic acids which have been found to possess analgesic , anti-inflammatory and antipyretic properties . The first of these to be successful in the treatment of rheumatoid arthritis was Ibufenac ( isobutylphenylacetic acid ) ( Chalmers , 1963 ; Thompson , Stephenson , and Percy , 1964 ; Hart and Boardman , 1965 ) and the most recent of the series is Ibuprofen . Pharmacological studies have shown that the compound is between two to eight times more potent than aspirin ( Adams , Cliffe , Lessel , and Nicholson , 1967 ) . In this paper we report a double-blind cross-over study of the analgesic and anti-inflammatory activity in rheumatoid arthritis of a daily dose of 750 mg . Ibuprofen compared with aspirin 5g./day and prednisolone 15 mg./day ; each drug being administered orally for a period of one week Published data on the effects of 
    Output:
    
agent
***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: OBJECTIVES To compare budesonide , a locally acting glucocorticoid with minimal systemic exposure , with conventional glucocorticoid treatment and placebo in rheumatoid arthritis . METHODS A double blind , r and omised , controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis , comparing budesonide 3 mg daily , budesonide 9 mg daily , prednisolone 7.5 mg daily , and placebo . Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment . RESULTS There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo ( 28 % for tender and 34 % for swollen joint counts , p<0.05 ) . Prednisolone 7.5 mg gave similar results , while budesonide 3 mg was less effective . ACR20 response criteria were met by 25 % of patients on placebo , 22 % on budesonide 3 mg , 42 % on budesonide 9 mg , and 56 % on prednisolone 7.5 mg . A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks . There was no evidence that budesonide provided a different pattern of symptom control from prednisolone , or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment . Adverse effects attributable to glucocorticoids were equally common in all groups . CONCLUSIONS The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment , are maintained for three months , and are not associated with any rebound in symptoms after stopping treatment Assessment of inflammation in rheumatoid arthritis ( RA ) has been studied in several different ways . Hart and Huskisson ( 1972 ) considered morning stiffness to be a reflection of inflammation with the disadvantage of being subjective . Boardman and Hart ( 1967 ) used proximal interphalangeal joint circumference which is at least objective , but may not be responsive to anti-inflammatory therapy , for example in patients with long-st and ing or ' burnt-out ' disease . Dick , Neufeld , Prentice , Woodburn , Whaley , Nuki , and Buchanan ( 1970 ) found that external count rates over single inflamed joints were greater than those over normal joints . They used technetium 99 ( 99Tc ) , an isotope with a half-life of 6 hours , and showed reduction in counts after treatment with anti-inflammatory drugs . In a previous study , Huskisson , Berry , Browett , and Balme ( 1973 ) showed , no relationship between technetium count over a single joint and any other measurement , arguing that reduction in count rate over a single joint could not be equated with anti-inflammatory effect . These authors also used an index based on counts over both wrists and knees , and in a small study there was a significant correlation with articular index . Though highly protein bound , 99Tc is presumably distributed to some extent in the extravascular extracellular space . Huskisson and others ( 1973 ) showed , by simultaneous counting of a blood sample and of soft tissues over the forearm , that 99Tc tended to remain more within the vascular compartment in patients with rheumatoid arthritis than in normals . Since most authors have suggested that 99Tc measures ' vascularity ' , an isotope which remains entirely within the circulation might be more useful for this purpose . In this study , Indium 113 ( 113In ) , a gamma emitter with a half-life of 99 5 minutes , was used . It is believed that it remains almost entirely within the circulation ( Stern , Goodwin , Scheffel , Wagner , and Kramer , 1967 ) . The 113kIn and 99Tc indices have been compared and their responsiveness to anti-inflammatory therapy assessed Indomethacin , 100 mg orally , was compared with prednisolone , 5 mg , as addititional therapy at night , in a two-week , double-blind , between-patient study in twenty-four in- patients with rheumatoid arthritis . Both therapies proved equally effective , and significantly lessened morning stiffness and increased grip strenght .  Two patients with dyspepsia were discontinued from the indomethacin group . Using indomethacin at night avoided the central nervous system side-effects frequently seen with this compound Prednisone , 5 mg taken each morning , was added to other drugs in 18 patients with rheumatoid arthritis . Sixteen patients were given a placebo  in this double blind study . After 24 weeks , all patients were given the placebo .  Slight functional improvement was noted in the prednisone group during the 24-week period , but deterioration after switching to placebo was sustained for at least 8 weeks . Progression of h and erosions occurred in 1 prednisone-treated patient , and in 4 controls . An asymptomatic vertebral spine compression fracture developed in 2 patients given prednisone ; this was the only toxicity noted possibly due to this therapy . Minimal dose prednisone may be useful as " bridge " therapy between nonsteroidal antiinflammatory therapy and use of disease-modifying drugs Measurement of digital joint circumference by using a plastic spring gauge has been carefully evaluated in rheumatoid patients . There is very small Ultra-observer but large inter-observer variation . A diurnal change in joint size could not be confirmed . Provided that joints affected by soft tissue swelling are used , the measure is a useful Index of the effect of anti-inflammatory drugs . John Webb Centre for Rheumatic Diseases 35 Baird Street Glasgow , G. 40 EH Scotl A 14-day , single-blind trial of prednisone , aspirin , and placebo was carried out in 128 patients suffering from rheumatoid arthritis , using subjective criteria only ( severity of pain daily on a pain chart and assessment of the drug for effectiveness ) . The average treated pain rating , mean patient satisfaction rating , and mean number of days withdrawn from each drug all showed significant differences between prednisone , aspirin , and placebo . Of various pretreatment observations , only the initial pain score and articular index of joint tenderness were significantly related to the average treated pain rating . The trial method is simple and allows many patients to participate without being time consuming for patient or physician . The method seems to have potential in comparing the comparative effectiveness of anti-inflammatory analgesics used in the treatment of patients with rheumatoid arthritis BACKGROUND Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory . Studies showing radiological benefit suggest that continued treatment is required to sustain the effect . OBJECTIVE To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years . DESIGN Double blind placebo controlled trial . METHODS Patients with rheumatoid arthritis , duration <3 years ( n = 167 ) , were started on a disease modifying antirheumatic drug ( DMARD ; sulphasalazine )  and allocated by stratified r and omisation to prednisolone 7 mg/day or placebo . Primary outcome measure was radiological damage , assessed by the modified Sharp method . Clinical benefit was a secondary outcome . A proactive approach to identifying and treating corticosteroid adverse events was adopted . Patients who discontinued sulphasalazine were offered an alternative DMARD . RESULTS 90 of 257 patients eligible for the study refused to participate ( more women than men ) . Of those enrolled , 84 % were seropositive for rheumatoid factor , median age 56 years , median disease duration 12 months , female to male ratio 1.8:1 .  Prednisolone was given to 84 patients ; of these 73 % continued prednisolone and 70 % sulphasalazine at 2 years . Of the 83 patients on placebo , 80 % continued placebo and 64 % sulphasalazine at 2 years . There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years . CONCLUSIONS Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years . Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs OBJECTIVE Prednisolone reduced the progression of joint destruction over 2 yr in early , active rheumatoid arthritis . The response to discontinuation of prednisolone under double-blind conditions is now reported . METHODS A r and omized , double-blind , placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis , using radiological progression ( changes in the Larsen score ) and the development of erosions as primary outcome measures . Study medication was blindly discontinued and follow-up maintained for a further year . Other assessment s included disability , joint inflammation , pain and the acute-phase response . RESULTS Similar results were obtained when all available radiographs were included for each year of assessment ( maximum 114 ) and when only patients with radiographs at all time points were included ( 75 patients ) . In these 75 , the mean progression in the prednisolone group was 0.21 Larsen units in year 1 , 0.04 units in year 2 and 1.01 units in year 3 ( P = 0.587 , 0.913 and 0.039 for change within each year , respectively ) . The equivalent placebo group means were 2.34 , 1.00 and 1.63 Larsen units ( P = 0.001 , 0.111 and 0.012 ; difference between groups : 2.13 , 0.96 and 0.67 units , P = 0.082 , 0.02 and 0.622 ) . The percentage of h and s which had erosions at each time point was : prednisolone group : 27.8 , 29.2 , 34.7 and 39.2 ; placebo group : 28.2 , 48.7 , 59.0 and 66.5 . There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone . CONCLUSION Joint destruction resumed after discontinuation of prednisolone . This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis BACKGROUND Bone damage in rheumatoid arthritis presents as osteoporosis and joint erosions . Prednisolone has been shown to reduce the rate of h and joint destruction as seen on radiography but has not been shown to reduce the rate of h and bone loss . METHODS In a double-blind study comparing oral prednisolone ( 7.5 mg/d for 2 years ) with placebo ,  h and bone density assessed with digital x-ray radiogrammetry was examined in 95 patients with rheumatoid arthritis with disease duration of less than 2 years . RESULTS The mean loss of h and bone density was less in prednisolone-treated patients compared with placebo-treated patients at the 1-year follow-up ( -0.011 vs -0.022 g/cm(2 ) ) ( P = .005 ) and at the 2-year follow-up ( -0.026 vs -0.039 g/cm(2 ) ) ( P = .03 ) . The mean percentage group difference in loss of h and bone density was 2.8 % ( P = .004 ) at the 1-year follow-up and 3.5 % ( P = .01 ) at the 2-year follow-up . In the first year , C-reactive protein , a marker of inflammation , was strongly correlated with h and bone loss in placebo-treated patients but not in prednisolone-treated patients , suggesting that prednisolone breaks the link between bone loss and inflammation . CONCLUSIONS To our knowledge , this is the first double-blind r and omized study to show that disease-related loss of h and bone density in rheumatoid arthritis can be decelerated by prednisolone . This finding suggests that the deleterious effect of prednisolone on bone may be counteracted by its anti-inflammatory effect Ibuprofen ( 2 - 4'-isobutylphenylpropionic acid ) is one of a series of phenylalkanoic acids which have been found to possess analgesic , anti-inflammatory and antipyretic properties . The first of these to be successful in the treatment of rheumatoid arthritis was Ibufenac ( isobutylphenylacetic acid ) ( Chalmers , 1963 ; Thompson , Stephenson , and Percy , 1964 ; Hart and Boardman , 1965 ) and the most recent of the series is Ibuprofen . Pharmacological studies have shown that the compound is between two to eight times more potent than aspirin ( Adams , Cliffe , Lessel , and Nicholson , 1967 ) . In this paper we report a double-blind cross-over study of the analgesic and anti-inflammatory activity in rheumatoid arthritis of a daily dose of 750 mg . Ibuprofen compared with aspirin 5g./day and prednisolone 15 mg./day ; each drug being administered orally for a period of one week Published data on the effects of 
    Output:
    