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: OBJECTIVE With the advent of new and expensive antirheumatic treatments with potentially serious side effects , it would be essential to identify as early as possible those rheumatoid arthritis ( RA ) patients who have a poor prognosis . Here study was made of the prognostic value of different markers recorded at the onset of RA . METHODS At the 20-year follow-up of our prospect i ve study , 66 patients had rheumatoid factor-positive ( RF+ ) RA . At commencement of follow-up ( disease duration < 6 months ) , the prognostic value of 19 demographic , laboratory , clinical and radiographic variables was tested to explain the 20-year Larsen score for peripheral joints and the Health Assessment  Question naire ( HAQ ) index using Somers'd for asymmetrical associations . RESULTS An association was observed between onset blood platelets ( 0.17 ) , serum IgG ( 0.18 ) , the onset Larsen score ( 0.33 ) and the 20-year Larsen score . Old age ( 0.30 ) , serum orosomucoid ( 0.17 ) , the function score ( 0.28 ) , morning stiffness ( 0.28 ) , and grip strength ( 0.24 ) were associated with the 20-year HAQ . CONCLUSION The correlation between the investigated entry variables and end-point outcome was poor . In our discussion we conclude that the most important prognostic factor in RF + RA is the treatment Introduction Benefits of disease-modifying anti-rheumatic drugs ( DMARD ) in early rheumatoid arthritis patients ( ERAP ) will be achieved if patients follow prescribed treatment . Objective was to investigate whether timing of first non-persistence period and /or duration of persistence during the first 4 years of follow-up predicted disease outcomes at the 5th year in a cohort of ERAP , initiated in 2004 . Patients and Methods Up to February 2015 , charts of 107 ERAP with at least 5 years of follow-up and prospect i ve 6-month assessment s of disease activity , disability and persistence were review ed . Non-persistence was defined as omission of DMARD and /or corticosteroids for at least 7 consecutive days ; regarding methotrexate , one weekly missing dose was considered non-persistence . Persistence was recorded through an interview ( up to 2008 ) and thereafter through a question naire ; persistence duration was recorded in months of continuous medicationtaking . At the 5th year , disease activity was defined according to Disease Activity Score (DAS)28 , and disability according to Health Assessment Question naire ( HAQ ) . Descriptive statistics and linear and Cox regression analyses were used . Results At study entry , patients were more frequently middle-aged ( 39.1 ± 13.3 years ) and female ( 88.8 % ) , as well as more likely to have  high disease activity and disability . Over the first 4 years of follow-up , 54.2 % of the patients had indications for oral corticosteroids and all traditional DMARDs . Almost 70 % had at least one period of non-persistence , and their follow-up ( median , 25th–75th interquartile range ) to first non-persistence period was 13 months ( 1–31 ) . Persistence duration during the first 4 years predicted subsequent DAS28 ( in addition to gender and baseline DAS28 ) and HAQ ( in addition to age ) . During the 5th year , 68 patients ( 56 women )  achieved sustained remission ( DAS28 < 2.6 ) . In female population ( n = 95 ) , baseline DAS28 ( odds ratio [ OR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.50–0.83 ; p = 0.001 ) and persistence duration ( OR , 1.04 ; 95 % CI , 1–1.08 ; p = 0.05 ) were predictors . Also , 84 patients  achieved sustained function ( HAQ < 0.21 ) , and baseline DAS28 and age were the only predictors . Timing of first non-persistence period did not impact outcomes . Conclusions Persistence duration with DMARDs within the first 4 years of RA predicted subsequent favorable outcomes in ERAP ; additional predictors were younger age , male gender and lower disease activity at diagnosis OBJECTIVES To determine whether magnetic resonance ( MR ) scans of the dominant wrist of patients with early rheumatoid arthritis ( RA ) can be used to predict functional outcome at 6 years ' follow up . METHODS  Dominant wrist MR scans were obtained in 42 patients with criteria for RA at first presentation . Patients were followed up prospect ively for 6 years , and further scans obtained at 1 year ( 42 patients ) and 6 years ( 31 patients ) . Two radiologists scored scans for synovitis , tendonitis , bone oedema , and erosions . The Stanford Health Assessment Question naire ( HAQ ) score , indicating functional outcome , and st and ard measures of disease activity were assessed at 0 , 1 , 2 , and 6 years . The physical function component of the SF-36 score ( PF-SF36 ) was also used as a functional outcome measure at 6 years . RESULTS Baseline MR parameters , including bone oedema score and the total baseline MR score , were predictive of the PF-SF36 at 6 years ( R2 = 0.22 , p = 0.005 and R2 = 0.16 , p = 0.02 , respectively ) . The PF-SF36 score correlated strongly with the HAQ score at 6 years ( rs = -0.725 , p<0.0001 ) ; none of the baseline MR parameters predicted the 6 year HAQ score . The total MR score obtained at 1 year was predictive of the 6 year HAQ ( R2 = 0.04 , p = 0.01 ) . St and ard clinical and radiographic measures at baseline were not predictive of the 6 year PF-SF36 , but when combined in a model with baseline MR oedema score , prediction increased from 0.09 to 0.23 , or 23 % of the 6 year variance . CONCLUSION MR imaging of the wrist  in patients with early RA can help to predict function at 6 years and could be used to plan aggressive management at an earlier stage Objective . To report the 5-year outcome of a large prospect i ve cohort of patients with very early rheumatoid arthritis ( RA ) , and to identify factors predictive of outcome . Methods . Patients were recruited if they had early arthritis of < 6 months ’ duration , had a high probability of developing RA , and had never been prescribed disease-modifying antirheumatic drugs ( DMARD ) or steroids . Logistic regression analysis was used to determine factors that predict outcome . Results . We included 813 patients from December 2002 to April 2005 . Age was 48.1 ± 12.6 years , delay before referral 103.1 ± 52.4 days  , 28-joint Disease Activity Score ( DAS28 ) 5.1 ± 1.3 , Health Assessment Question naire ( HAQ ) 1.0 ± 0.7 ; 45.8 % and 38.7 % had rheumatoid factor or antibodies to cyclic citrullinated peptide ( anti-CCP ) , respectively ; 22 % had h and or foot erosions ; 78.5 % fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8 % during followup . At 5 years , 573 patients were evaluated . The outcome was mild for most patients : disease activity ( median DAS28 = 2.5 ) and HAQ disability ( median 0.3 ) were well controlled over time ; 50.6 % achieved DAS28 remission and 64.7 % low disease activity . Radiographic progression was low ( 2.9 Sharp unit/year ) and only a few patients required joint surgery . Nevertheless , some patients developed new comorbidities . During the 5 years , 82.7 % of patients had received at least 1 DMARD ( methotrexate , 65.9 % ) , 18.3 % a biological DMARD , and about 60 % prednisone at least once . Anti-CCP was the best predictor of remaining in the cohort for 5 years , of prescription of synthetic or biologic DMARD , and of radiographic progression . Conclusion . The 5-year outcome of an early RA cohort in the 2000s was described . Anti-CCP was a robust predictor of outcome . The generally good 5-year outcome could be related to early referral and early effective treatment , key processes in the management of early RA in daily practice OBJECTIVE To investigate the relationship between functional capacity , disease activity , and joint destruction over the course of rheumatoid arthritis ( RA ) . METHODS The followup data on 378 patients with early RA ( duration < 1 year ) , included in an open , prospect i ve study since 1985 at the Department of Rheumatology of the University Medical Center Nijmegen , were used .  Functional capacity , disease activity , and joint destruction were assessed using the  Health Assessment Question naire disability index ( HAQ DI ) , the Disease Activity Score ( DAS ) , and a modification of the sharp radiographic damage score  , respectively . Multiple linear regression was used to model the data collected at 0 , 3 , 6 , and 9 years after study start , to investigate which variables influenced functional capacity during the disease course . A general linear mixed model for longitudinal data , which included the variables identified as significant in the multiple linear regression models and several interaction terms between the variables , was run . RESULTS On average , the functional capacity of the patients , as measured by the HAQ DI , worsened over the course of the disease after an initial improvement . After an initial reduction in the extent of disease activity , the mean DAS remained more or less stable over the course of the disease . The mean modified sharp joint damage score worsened over the course of the disease , with a slower progression rate later in the disease . In the multiple linear regression at 0 , 3 , and 6 years after study start , disease activity was found to be an important factor influencing functional capacity , and at 6 and 9 years , joint damage had an important effect on functional capacity . Furthermore , at 6 and 9 years , there was an interaction effect of joint destruction with disease activity . In the general linear mixed model , disease activity , joint damage , and an interaction effect of disease activity and joint damage were the main factors explaining functional capacity . CONCLUSION The effect of disease activity and joint destruction on functional capacity changes over the course of the disease . In early RA , functional capacity is most associated with disease activity , and in late disease , with joint damage Objective : To investigate outcome as measured by health status , disease process , and damage in an unselected group of patients with early rheumatoid arthritis ( RA ) monitored prospect ively for 10 years and to search for prognostic factors . Patients and methods : 183 patients with RA with disease duration < 2 years were assessed annually at a team care unit . Health status was measured by the  Health Assessment Question naire ( HAQ ) and functional class .  Disease process was assessed by clinical and laboratory measures of disease activity and evaluation of disease course . Damage was quantified as occurrence of major extra-articular manifestations and need for large joint replacements . Possible predictive factors were evaluated by logistic regression analyses . Results : 168/183 patients completed the entire follow up period . Of all 183 patients , 137 ( 75 % ) had been treated with disease modifying antirheumatic drugs and 84 ( 46 % ) with low dose oral glucocorticoids . After 10 years 158 patients ( 94 % ) managed daily life activities independently ( functional class I – II ) . As measured by the HAQ 20 % had almost no disability , 28 % were mildly disabled , and 10 % were seriously disabled . Median HAQ score had increased from 0.8 to 1.1 ( p<0.001 ) . Disease activity was significantly reduced . 133 patients ( 79 % ) had a relapsing remitting disease course and 30 patients ( 18 % ) were in remission as defined by the American College of Rheumatology criteria . Thirty patients ( 17 % ) had undergone large joint replacements . Fifteen patients ( 8 % ) had developed major extra-articular complications . The HAQ score during the first three months predicted disability at 10 years with an odds ratio of 13.4 . Conclusions : Prospect i ve studies such as this give important knowledge of the variable long term prognosis of RA and provide necessary background information for clinical trials of new treatment modalities Objectives Anticarbamylated protein ( anti-CarP ) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis . The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years ’ follow-up in a cohort of patients with inflammatory polyarthritis ( IP ) . Methods Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009 . At baseline , Health Assessment Question naire ( HAQ ) and 28 joint disease activity scores ( DAS28 ) were obtained , and C reactive protein , rheumatoid factor ( RF ) , anticitrullinated protein antibodies ( ACPA ) and anti-CarP antibodies were measured . Further HAQ scores and DAS28 were obtained at regular intervals over 20 years . Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores ; 
    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: OBJECTIVE With the advent of new and expensive antirheumatic treatments with potentially serious side effects , it would be essential to identify as early as possible those rheumatoid arthritis ( RA ) patients who have a poor prognosis . Here study was made of the prognostic value of different markers recorded at the onset of RA . METHODS At the 20-year follow-up of our prospect i ve study , 66 patients had rheumatoid factor-positive ( RF+ ) RA . At commencement of follow-up ( disease duration < 6 months ) , the prognostic value of 19 demographic , laboratory , clinical and radiographic variables was tested to explain the 20-year Larsen score for peripheral joints and the Health Assessment  Question naire ( HAQ ) index using Somers'd for asymmetrical associations . RESULTS An association was observed between onset blood platelets ( 0.17 ) , serum IgG ( 0.18 ) , the onset Larsen score ( 0.33 ) and the 20-year Larsen score . Old age ( 0.30 ) , serum orosomucoid ( 0.17 ) , the function score ( 0.28 ) , morning stiffness ( 0.28 ) , and grip strength ( 0.24 ) were associated with the 20-year HAQ . CONCLUSION The correlation between the investigated entry variables and end-point outcome was poor . In our discussion we conclude that the most important prognostic factor in RF + RA is the treatment Introduction Benefits of disease-modifying anti-rheumatic drugs ( DMARD ) in early rheumatoid arthritis patients ( ERAP ) will be achieved if patients follow prescribed treatment . Objective was to investigate whether timing of first non-persistence period and /or duration of persistence during the first 4 years of follow-up predicted disease outcomes at the 5th year in a cohort of ERAP , initiated in 2004 . Patients and Methods Up to February 2015 , charts of 107 ERAP with at least 5 years of follow-up and prospect i ve 6-month assessment s of disease activity , disability and persistence were review ed . Non-persistence was defined as omission of DMARD and /or corticosteroids for at least 7 consecutive days ; regarding methotrexate , one weekly missing dose was considered non-persistence . Persistence was recorded through an interview ( up to 2008 ) and thereafter through a question naire ; persistence duration was recorded in months of continuous medicationtaking . At the 5th year , disease activity was defined according to Disease Activity Score (DAS)28 , and disability according to Health Assessment Question naire ( HAQ ) . Descriptive statistics and linear and Cox regression analyses were used . Results At study entry , patients were more frequently middle-aged ( 39.1 ± 13.3 years ) and female ( 88.8 % ) , as well as more likely to have  high disease activity and disability . Over the first 4 years of follow-up , 54.2 % of the patients had indications for oral corticosteroids and all traditional DMARDs . Almost 70 % had at least one period of non-persistence , and their follow-up ( median , 25th–75th interquartile range ) to first non-persistence period was 13 months ( 1–31 ) . Persistence duration during the first 4 years predicted subsequent DAS28 ( in addition to gender and baseline DAS28 ) and HAQ ( in addition to age ) . During the 5th year , 68 patients ( 56 women )  achieved sustained remission ( DAS28 < 2.6 ) . In female population ( n = 95 ) , baseline DAS28 ( odds ratio [ OR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.50–0.83 ; p = 0.001 ) and persistence duration ( OR , 1.04 ; 95 % CI , 1–1.08 ; p = 0.05 ) were predictors . Also , 84 patients  achieved sustained function ( HAQ < 0.21 ) , and baseline DAS28 and age were the only predictors . Timing of first non-persistence period did not impact outcomes . Conclusions Persistence duration with DMARDs within the first 4 years of RA predicted subsequent favorable outcomes in ERAP ; additional predictors were younger age , male gender and lower disease activity at diagnosis OBJECTIVES To determine whether magnetic resonance ( MR ) scans of the dominant wrist of patients with early rheumatoid arthritis ( RA ) can be used to predict functional outcome at 6 years ' follow up . METHODS  Dominant wrist MR scans were obtained in 42 patients with criteria for RA at first presentation . Patients were followed up prospect ively for 6 years , and further scans obtained at 1 year ( 42 patients ) and 6 years ( 31 patients ) . Two radiologists scored scans for synovitis , tendonitis , bone oedema , and erosions . The Stanford Health Assessment Question naire ( HAQ ) score , indicating functional outcome , and st and ard measures of disease activity were assessed at 0 , 1 , 2 , and 6 years . The physical function component of the SF-36 score ( PF-SF36 ) was also used as a functional outcome measure at 6 years . RESULTS Baseline MR parameters , including bone oedema score and the total baseline MR score , were predictive of the PF-SF36 at 6 years ( R2 = 0.22 , p = 0.005 and R2 = 0.16 , p = 0.02 , respectively ) . The PF-SF36 score correlated strongly with the HAQ score at 6 years ( rs = -0.725 , p<0.0001 ) ; none of the baseline MR parameters predicted the 6 year HAQ score . The total MR score obtained at 1 year was predictive of the 6 year HAQ ( R2 = 0.04 , p = 0.01 ) . St and ard clinical and radiographic measures at baseline were not predictive of the 6 year PF-SF36 , but when combined in a model with baseline MR oedema score , prediction increased from 0.09 to 0.23 , or 23 % of the 6 year variance . CONCLUSION MR imaging of the wrist  in patients with early RA can help to predict function at 6 years and could be used to plan aggressive management at an earlier stage Objective . To report the 5-year outcome of a large prospect i ve cohort of patients with very early rheumatoid arthritis ( RA ) , and to identify factors predictive of outcome . Methods . Patients were recruited if they had early arthritis of < 6 months ’ duration , had a high probability of developing RA , and had never been prescribed disease-modifying antirheumatic drugs ( DMARD ) or steroids . Logistic regression analysis was used to determine factors that predict outcome . Results . We included 813 patients from December 2002 to April 2005 . Age was 48.1 ± 12.6 years , delay before referral 103.1 ± 52.4 days  , 28-joint Disease Activity Score ( DAS28 ) 5.1 ± 1.3 , Health Assessment Question naire ( HAQ ) 1.0 ± 0.7 ; 45.8 % and 38.7 % had rheumatoid factor or antibodies to cyclic citrullinated peptide ( anti-CCP ) , respectively ; 22 % had h and or foot erosions ; 78.5 % fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8 % during followup . At 5 years , 573 patients were evaluated . The outcome was mild for most patients : disease activity ( median DAS28 = 2.5 ) and HAQ disability ( median 0.3 ) were well controlled over time ; 50.6 % achieved DAS28 remission and 64.7 % low disease activity . Radiographic progression was low ( 2.9 Sharp unit/year ) and only a few patients required joint surgery . Nevertheless , some patients developed new comorbidities . During the 5 years , 82.7 % of patients had received at least 1 DMARD ( methotrexate , 65.9 % ) , 18.3 % a biological DMARD , and about 60 % prednisone at least once . Anti-CCP was the best predictor of remaining in the cohort for 5 years , of prescription of synthetic or biologic DMARD , and of radiographic progression . Conclusion . The 5-year outcome of an early RA cohort in the 2000s was described . Anti-CCP was a robust predictor of outcome . The generally good 5-year outcome could be related to early referral and early effective treatment , key processes in the management of early RA in daily practice OBJECTIVE To investigate the relationship between functional capacity , disease activity , and joint destruction over the course of rheumatoid arthritis ( RA ) . METHODS The followup data on 378 patients with early RA ( duration < 1 year ) , included in an open , prospect i ve study since 1985 at the Department of Rheumatology of the University Medical Center Nijmegen , were used .  Functional capacity , disease activity , and joint destruction were assessed using the  Health Assessment Question naire disability index ( HAQ DI ) , the Disease Activity Score ( DAS ) , and a modification of the sharp radiographic damage score  , respectively . Multiple linear regression was used to model the data collected at 0 , 3 , 6 , and 9 years after study start , to investigate which variables influenced functional capacity during the disease course . A general linear mixed model for longitudinal data , which included the variables identified as significant in the multiple linear regression models and several interaction terms between the variables , was run . RESULTS On average , the functional capacity of the patients , as measured by the HAQ DI , worsened over the course of the disease after an initial improvement . After an initial reduction in the extent of disease activity , the mean DAS remained more or less stable over the course of the disease . The mean modified sharp joint damage score worsened over the course of the disease , with a slower progression rate later in the disease . In the multiple linear regression at 0 , 3 , and 6 years after study start , disease activity was found to be an important factor influencing functional capacity , and at 6 and 9 years , joint damage had an important effect on functional capacity . Furthermore , at 6 and 9 years , there was an interaction effect of joint destruction with disease activity . In the general linear mixed model , disease activity , joint damage , and an interaction effect of disease activity and joint damage were the main factors explaining functional capacity . CONCLUSION The effect of disease activity and joint destruction on functional capacity changes over the course of the disease . In early RA , functional capacity is most associated with disease activity , and in late disease , with joint damage Objective : To investigate outcome as measured by health status , disease process , and damage in an unselected group of patients with early rheumatoid arthritis ( RA ) monitored prospect ively for 10 years and to search for prognostic factors . Patients and methods : 183 patients with RA with disease duration < 2 years were assessed annually at a team care unit . Health status was measured by the  Health Assessment Question naire ( HAQ ) and functional class .  Disease process was assessed by clinical and laboratory measures of disease activity and evaluation of disease course . Damage was quantified as occurrence of major extra-articular manifestations and need for large joint replacements . Possible predictive factors were evaluated by logistic regression analyses . Results : 168/183 patients completed the entire follow up period . Of all 183 patients , 137 ( 75 % ) had been treated with disease modifying antirheumatic drugs and 84 ( 46 % ) with low dose oral glucocorticoids . After 10 years 158 patients ( 94 % ) managed daily life activities independently ( functional class I – II ) . As measured by the HAQ 20 % had almost no disability , 28 % were mildly disabled , and 10 % were seriously disabled . Median HAQ score had increased from 0.8 to 1.1 ( p<0.001 ) . Disease activity was significantly reduced . 133 patients ( 79 % ) had a relapsing remitting disease course and 30 patients ( 18 % ) were in remission as defined by the American College of Rheumatology criteria . Thirty patients ( 17 % ) had undergone large joint replacements . Fifteen patients ( 8 % ) had developed major extra-articular complications . The HAQ score during the first three months predicted disability at 10 years with an odds ratio of 13.4 . Conclusions : Prospect i ve studies such as this give important knowledge of the variable long term prognosis of RA and provide necessary background information for clinical trials of new treatment modalities Objectives Anticarbamylated protein ( anti-CarP ) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis . The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years ’ follow-up in a cohort of patients with inflammatory polyarthritis ( IP ) . Methods Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009 . At baseline , Health Assessment Question naire ( HAQ ) and 28 joint disease activity scores ( DAS28 ) were obtained , and C reactive protein , rheumatoid factor ( RF ) , anticitrullinated protein antibodies ( ACPA ) and anti-CarP antibodies were measured . Further HAQ scores and DAS28 were obtained at regular intervals over 20 years . Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores ; 
    Output:
    