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 To develop preliminary criteria for inactive disease and clinical remission for select categories of juvenile idiopathic arthritis ( JIA ) , and to decide what such clinical states should predict in terms of probability of disease recurrence . METHODS A Delphi serial question naire consensus-formation approach was used initially to gather criteria in use by pediatric rheumatologists ( PR ) for defining clinical remission in oligoarticular ( persistent and extended ) , rheumatoid factor ( RF ) positive and negative polyarticular , and systemic JIA . Results from sequential question naires provided an agenda for a nominal group technique ( NGT ) conference to reach consensus on unresolved questions . RESULTS One hundred and thirty PR from 34 countries responded to the question naires and 20 PR from 9 countries attended the conference . Draft criteria for inactive disease include the following : no active arthritis ; no fever , rash , serositis , splenomegaly , or generalized lymphadenopathy attributable to JIA ; no active uveitis ; normal erythrocyte sedimentation rate or C-reactive protein ; and a physician 's global assessment of disease activity rated at the best score possible for the instrument used . According to consensus vote , 6 continuous months of inactive disease on medication defines clinical remission on medication , while 12 months of inactive disease off all anti-arthritis ( and anti-uveitis ) medications defines clinical remission off medication . The finalized criteria for remission off medication ideally should predict that a patient has < /= 20 % probability of disease recurrence within the next 5 years . CONCLUSION Using consensus formation techniques , we formulated preliminary criteria for inactive disease and clinical remission on and off medication for use in select categories of JIA . Retrospective validation is in progress ; prospect i ve validation will follow . Future efforts will include other categories of JIA OBJECTIVE To determine the reliability of formal exercise testing and the reliability of functional and activity question naires in children with juvenile idiopathic arthritis ( JIA ) . METHODS Children with JIA of any subtype ages 8 - 16 years who were recruited to a r and omized trial comparing different exercise therapies participated in 2 preintervention sessions of exercise testing 2 - 6 weeks apart . Exercise testing included 1 ) submaximal oxygen uptake ( VO(2submax ) ) , 2 ) peak VO(2 ) ( VO(2peak ) ) , and 3 ) anaerobic power using modified Wingate tests ( W(ant ) ) . Two physical function question naires ( the Childhood Health Assessment Question naire [ C-HAQ ] and Revised Activity Scale for Kids [ ASK ] ) and 1 daily physical activity question naire ( the Habitual Activity Estimation Scale [ HAES ] ) were also completed at these times . Test-retest reliability was assessed using type 3 , intrarater intraclass correlation coefficient ( ICC(3,1 ) ) and Bl and and Altman plots were used to determine limits of agreement . RESULTS Data were available for 74 patients ( 58 girls ) .  VO(2submax ) , VO(2peak ) , and W(ant ) demonstrated high reliability ( ICC(3,1 ) 0.82 , 0.91 , and 0.94 , respectively ) . C-HAQ and ASK question naires also had very high reliability ( ICC(3,1 ) 0.82 and 0.91 , respectively ) . The HAES demonstrated low reliability for total activity score ( ICC(3,1 ) 0.15 ) and moderate reliability when the number of very active hours was analyzed separately ( ICC(3,1 ) 0.59 ) . CONCLUSION Results of this investigation suggest that exercise testing and functional question naires in children with JIA are consistent and reliable . Reliability of the HAES total score was poor , but moderate when the very active hours subscale score was used OBJECTIVE To develop preliminary criteria for defining disease flare in patients with polyarticular-course juvenile rheumatoid arthritis ( JRA ) . METHODS Data from a r and omized clinical trial of etanercept in JRA ( 51 patients ) and the 6 core response variables ( CRV ) for JRA were used to derive flare definitions . The criterion st and ard of flare was treatment with placebo . C and i date flare definitions were assessed by receiver-operator characteristic ( ROC ) curve properties and other statistics for diagnostic tests . RESULTS Of the possible flare definitions tested with acceptable statistical properties , the one that seemed to be the most useful was worsening in any 2/6 CRV by > or = 40 % without improvement in more than 1 of the remaining CRV by > or = 30 % . Two other superior flare definitions were ( 1 ) worsening in 3/6 CRV by > or = 30 % and ( 2 ) any worsening of the Childhood Health Assessment Question naire , worsening of erythrocyte sedimentation rate by > or = 30 % and worsening of the active joint count by > or = 10 % . CONCLUSIONS CRV are useful for defining flare in JRA . Worsening in any 2/6 CRV by > or = 40 % without concomitant improvement of more than one of the remaining CRV by > or = 30 % appears to be the most suitable preliminary flare definition . Because the proposed flare criteria were derived from a small number of patients , it is essential to perform more definitive testing of this and several alternative flare definitions in larger patient population The aim of this 12-month prospect i ve study was to compare reports describing the health-related quality of life ( HRQL ) of children with Juvenile idiopathic arthritis ( JIA ) obtained from parents and children , to investigate the extent to which the children ’s HRQL changed over a 12-month period , and to describe the relationship between children ’s HRQL , and their experience of pain and use of pain coping strategies . Fifty-four children aged 8–18 years with JIA and their parents completed st and ard question naires assessing children ’s HRQL , pain intensity , and pain coping strategies at baseline , 6 months , and 12 months . In general , children reported that their HRQL was better than was reported by parents . Both informants described children ’s HRQL as being very stable over the 12 months of the study . Consistent with the Biobehavioural Model of Pain , there was a significant negative relationship between children ’s HRQL and their experience of pain . However , there was little evidence that pain coping strategies mediated the relationship between children ’s experience of pain and their HRQL Background Many people suffer with Osteoarthritis ( OA ) and subsequent morbidity . Therefore , measuring outcome associated with OA is important . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) has been a widely used patient reported outcome in OA . However , there is relatively little evidence to support the use of the Visual Analogue Scale ( VAS ) version of the scale . We aim ed to explore the internal validity and responsiveness of this VAS version of the WOMAC . Methods Patients with chronic hip or knee pain of mechanical origin , waiting for a hip or knee joint replacement completed the WOMAC as part of a study to investigate the effects of acupuncture and placebo controls . Validity was tested using factor analysis and Rasch analysis , and responsiveness using st and ardised response means . Results Two hundred and twenty one patients ( mean age 66.8 , SD 8.29 , 58 % female ) were recruited . Factor and Rasch analysis confirmed unidimensional Pain and Physical Functioning scales , capable of transformation to interval scaling and invariant over time . Some Differential Item Functioning ( DIF ) was observed , but this cancelled out at the test level . The Stiffness scale fitted the Rasch model but adjustments for DIF could not be made due to the shortness of the scale . Using the interval transformed data , St and ardised Response Means were smaller than when using the raw , ordinal data . Conclusions The WOMAC Pain and Physical Functioning subscales satisfied unidimensionality and ordinal scaling tests , and the ability to transform to an interval scale . Some Differential Item Functioning was observed , but this cancelled out at the test level and , by doing so , at the same time removed the disturbance of unidimensionality . The scaling characteristics of sets of items which use VAS require further analysis , as it would appear that they can lead to spurious levels of responsiveness and scale compression because they exaggerate the distortion of the ordinal scale . Trial numberUKCRN study ID : 4881IS RCT This study represents a long-term effort to find optimal techniques for evaluating outcome in patients who have undergone total joint arthroplasty . Sensitivity of five health status question naires was studied in a longitudinal evaluation of orthopedic surgery . The question naires ( Arthritis Impact Measurement Scales [ AIMS ] , Functional Status Index [ FSI ] ,  Health  Assessment  Question naire [ HAQ ] , Index of  Well  Being [ IWB ] , and Sickness Impact Profile  [ SIP ] ) were administered to 38 patients with end-stage arthritis at three points in time : two weeks before hip or knee arthroplasty , and at three-month and 12- to 15-month follow-up . Response values ( i.e. , changes within patients ) were calculated on four scales : global health , pain , mobility , and social function . By the three-month follow-up , most instruments detected large mean responses in global health , pain scores , and mobility . Smaller changes on these scales were found between three and 12 to 15 months . Social function showed small to modest gains at successive follow-ups . St and ardized response means were calculated to assess sensitivity to detect change . Confidence intervals for these indices were constructed using a jackknife procedure , and significance tests were performed by pairing selected indices . Finally , the study projected sample sizes required to assess a new therapy , using each response . These statistical tools facilitated comparisons among instruments and may prove useful in other setting OBJECTIVE To assess the determinants and responsiveness of the Norwegian version of the Child Health Question naire ( CHQ ) in patients with early juvenile idiopathic arthritis ( JIA ) and to compare health status in patients and controls . METHODS A total of 116 children ( median age 8.4 yrs ) with JIA and < 2.5 years of disease duration ( median 11.0 mo ) were examined by a pediatric rheumatologist and reassessed after a median of 10.0 months . Physical and psychosocial health were assessed by means of the CHQ , which provides summary scores for physical and psychosocial health , the Childhood Health Assessment Question naire ( CHAQ ) , and the Child Behavior Checklist ( CBCL , n = 32 ) . Matched controls ( n = 116 ) , r and omly selected from the general population , completed the CHQ at baseline . RESULTS The patients with JIA had poorer physical health and slightly impaired psychosocial health compared with the controls [ 41.2 + /- 13.6 vs 55.2 + /- 7.3 ( p < 0.001 ) and 51.0 + /- 7.5 vs 54.1 + /- 5.7 ( p = 0.002 ) , respectively ] . The most important determinants of the CHQ physical summary score were the child 's pain , morning stiffness , the CHAQ disability index , erythrocyte sedimentation rate ( ESR ) , overall well-being , and physician 's global assessment of disease activity . The psychosocial summary score correlated with the CBCL level of internalizing , externalizing , and total behavior problems . The st and ardized response mean for the physical summary score was large ( 0.96 ) for those who improved , and moderate ( -0.60 ) for those who became worse . CONCLUSION The CHQ discriminated between patients with early JIA and controls . The most important determinants of the CHQ physical summary score were the child 's pain , morning stiffness , CHAQ , ESR , overall well-being , and physician 's global assessment of disease activity . The CHQ was sensitive to clinical changes in children with JIA OBJECTIVES To examine the change in health-related quality of life ( HRQOL ) and its determinants in children with juvenile idiopathic arthritis ( JIA ) treated with methotrexate ( MTX ) .  METHODS Patients were extracted from the PRINTO clinical trial which aim ed to evaluate the efficacy and safety profile of MTX administered in st and ard , intermediate or higher doses ( 10 , 15 and 30 mg/m(2)/week respectively ) . Children with polyarticular-course JIA , who were less than 18 years and had a complete HRQOL assessment were included . RESULTS A total of 521 children were included . At baseline , patients with JIA showed poorer HRQOL ( p<0.01 ) than healthy children . In 207/412 ( 50 % ) and 63 ( 15 % ) children , HRQOL values were 2 st and ard deviations below the mean of healthy controls in the physical and psychosocial summary scale , respectively . After 6 months of treatment with st and ard dose MTX , there was a statistically significant improvement in all HRQOL health concepts , particularly the physical ones . Similar improvements were observed in those who did not respond to a st and ard dose of MTX and were subsequently r and omised to a higher dose . The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with st and ard dose MTX . Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation , pain intensity and an antinuclear-antibody-negative status . CONCLUSIONS MTX treatment produces a significant improvement across a wide range of HRQOL components , particularly in the physical domains , in patients with JIA OBJECTIVE To identify a core set of outcome variables for the assessment of children with juvenile arthritis ( JA ) , to use the core set to develop a definition of improvement to determine whether 
    Output:
    
agent
The  Childhood Health Assessment Question naire ( C-HAQ )  was the most extensively studied instrument and had high reliability , but only moderate correlations with other indices of disease activity and poor responsiveness to change in disease status .
The physician global assessment of disease activity ( PGA ) and articular indices had the strongest association with disease activity and were the most responsive to change .
Measures of psychosocial function and quality of life were moderately associated with measures of disease activity , but were less responsive to changes in disease status .
In children with JIA , no single instrument was superior in reliability or validity or in describing the impact of JIA .
Although the C-HAQ has been extensively evaluated , the PGA and articular indices appear to have the highest responsiveness to change and , therefore , the highest potential for detecting important differences in treatment response
***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 To develop preliminary criteria for inactive disease and clinical remission for select categories of juvenile idiopathic arthritis ( JIA ) , and to decide what such clinical states should predict in terms of probability of disease recurrence . METHODS A Delphi serial question naire consensus-formation approach was used initially to gather criteria in use by pediatric rheumatologists ( PR ) for defining clinical remission in oligoarticular ( persistent and extended ) , rheumatoid factor ( RF ) positive and negative polyarticular , and systemic JIA . Results from sequential question naires provided an agenda for a nominal group technique ( NGT ) conference to reach consensus on unresolved questions . RESULTS One hundred and thirty PR from 34 countries responded to the question naires and 20 PR from 9 countries attended the conference . Draft criteria for inactive disease include the following : no active arthritis ; no fever , rash , serositis , splenomegaly , or generalized lymphadenopathy attributable to JIA ; no active uveitis ; normal erythrocyte sedimentation rate or C-reactive protein ; and a physician 's global assessment of disease activity rated at the best score possible for the instrument used . According to consensus vote , 6 continuous months of inactive disease on medication defines clinical remission on medication , while 12 months of inactive disease off all anti-arthritis ( and anti-uveitis ) medications defines clinical remission off medication . The finalized criteria for remission off medication ideally should predict that a patient has < /= 20 % probability of disease recurrence within the next 5 years . CONCLUSION Using consensus formation techniques , we formulated preliminary criteria for inactive disease and clinical remission on and off medication for use in select categories of JIA . Retrospective validation is in progress ; prospect i ve validation will follow . Future efforts will include other categories of JIA OBJECTIVE To determine the reliability of formal exercise testing and the reliability of functional and activity question naires in children with juvenile idiopathic arthritis ( JIA ) . METHODS Children with JIA of any subtype ages 8 - 16 years who were recruited to a r and omized trial comparing different exercise therapies participated in 2 preintervention sessions of exercise testing 2 - 6 weeks apart . Exercise testing included 1 ) submaximal oxygen uptake ( VO(2submax ) ) , 2 ) peak VO(2 ) ( VO(2peak ) ) , and 3 ) anaerobic power using modified Wingate tests ( W(ant ) ) . Two physical function question naires ( the Childhood Health Assessment Question naire [ C-HAQ ] and Revised Activity Scale for Kids [ ASK ] ) and 1 daily physical activity question naire ( the Habitual Activity Estimation Scale [ HAES ] ) were also completed at these times . Test-retest reliability was assessed using type 3 , intrarater intraclass correlation coefficient ( ICC(3,1 ) ) and Bl and and Altman plots were used to determine limits of agreement . RESULTS Data were available for 74 patients ( 58 girls ) .  VO(2submax ) , VO(2peak ) , and W(ant ) demonstrated high reliability ( ICC(3,1 ) 0.82 , 0.91 , and 0.94 , respectively ) . C-HAQ and ASK question naires also had very high reliability ( ICC(3,1 ) 0.82 and 0.91 , respectively ) . The HAES demonstrated low reliability for total activity score ( ICC(3,1 ) 0.15 ) and moderate reliability when the number of very active hours was analyzed separately ( ICC(3,1 ) 0.59 ) . CONCLUSION Results of this investigation suggest that exercise testing and functional question naires in children with JIA are consistent and reliable . Reliability of the HAES total score was poor , but moderate when the very active hours subscale score was used OBJECTIVE To develop preliminary criteria for defining disease flare in patients with polyarticular-course juvenile rheumatoid arthritis ( JRA ) . METHODS Data from a r and omized clinical trial of etanercept in JRA ( 51 patients ) and the 6 core response variables ( CRV ) for JRA were used to derive flare definitions . The criterion st and ard of flare was treatment with placebo . C and i date flare definitions were assessed by receiver-operator characteristic ( ROC ) curve properties and other statistics for diagnostic tests . RESULTS Of the possible flare definitions tested with acceptable statistical properties , the one that seemed to be the most useful was worsening in any 2/6 CRV by > or = 40 % without improvement in more than 1 of the remaining CRV by > or = 30 % . Two other superior flare definitions were ( 1 ) worsening in 3/6 CRV by > or = 30 % and ( 2 ) any worsening of the Childhood Health Assessment Question naire , worsening of erythrocyte sedimentation rate by > or = 30 % and worsening of the active joint count by > or = 10 % . CONCLUSIONS CRV are useful for defining flare in JRA . Worsening in any 2/6 CRV by > or = 40 % without concomitant improvement of more than one of the remaining CRV by > or = 30 % appears to be the most suitable preliminary flare definition . Because the proposed flare criteria were derived from a small number of patients , it is essential to perform more definitive testing of this and several alternative flare definitions in larger patient population The aim of this 12-month prospect i ve study was to compare reports describing the health-related quality of life ( HRQL ) of children with Juvenile idiopathic arthritis ( JIA ) obtained from parents and children , to investigate the extent to which the children ’s HRQL changed over a 12-month period , and to describe the relationship between children ’s HRQL , and their experience of pain and use of pain coping strategies . Fifty-four children aged 8–18 years with JIA and their parents completed st and ard question naires assessing children ’s HRQL , pain intensity , and pain coping strategies at baseline , 6 months , and 12 months . In general , children reported that their HRQL was better than was reported by parents . Both informants described children ’s HRQL as being very stable over the 12 months of the study . Consistent with the Biobehavioural Model of Pain , there was a significant negative relationship between children ’s HRQL and their experience of pain . However , there was little evidence that pain coping strategies mediated the relationship between children ’s experience of pain and their HRQL Background Many people suffer with Osteoarthritis ( OA ) and subsequent morbidity . Therefore , measuring outcome associated with OA is important . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) has been a widely used patient reported outcome in OA . However , there is relatively little evidence to support the use of the Visual Analogue Scale ( VAS ) version of the scale . We aim ed to explore the internal validity and responsiveness of this VAS version of the WOMAC . Methods Patients with chronic hip or knee pain of mechanical origin , waiting for a hip or knee joint replacement completed the WOMAC as part of a study to investigate the effects of acupuncture and placebo controls . Validity was tested using factor analysis and Rasch analysis , and responsiveness using st and ardised response means . Results Two hundred and twenty one patients ( mean age 66.8 , SD 8.29 , 58 % female ) were recruited . Factor and Rasch analysis confirmed unidimensional Pain and Physical Functioning scales , capable of transformation to interval scaling and invariant over time . Some Differential Item Functioning ( DIF ) was observed , but this cancelled out at the test level . The Stiffness scale fitted the Rasch model but adjustments for DIF could not be made due to the shortness of the scale . Using the interval transformed data , St and ardised Response Means were smaller than when using the raw , ordinal data . Conclusions The WOMAC Pain and Physical Functioning subscales satisfied unidimensionality and ordinal scaling tests , and the ability to transform to an interval scale . Some Differential Item Functioning was observed , but this cancelled out at the test level and , by doing so , at the same time removed the disturbance of unidimensionality . The scaling characteristics of sets of items which use VAS require further analysis , as it would appear that they can lead to spurious levels of responsiveness and scale compression because they exaggerate the distortion of the ordinal scale . Trial numberUKCRN study ID : 4881IS RCT This study represents a long-term effort to find optimal techniques for evaluating outcome in patients who have undergone total joint arthroplasty . Sensitivity of five health status question naires was studied in a longitudinal evaluation of orthopedic surgery . The question naires ( Arthritis Impact Measurement Scales [ AIMS ] , Functional Status Index [ FSI ] ,  Health  Assessment  Question naire [ HAQ ] , Index of  Well  Being [ IWB ] , and Sickness Impact Profile  [ SIP ] ) were administered to 38 patients with end-stage arthritis at three points in time : two weeks before hip or knee arthroplasty , and at three-month and 12- to 15-month follow-up . Response values ( i.e. , changes within patients ) were calculated on four scales : global health , pain , mobility , and social function . By the three-month follow-up , most instruments detected large mean responses in global health , pain scores , and mobility . Smaller changes on these scales were found between three and 12 to 15 months . Social function showed small to modest gains at successive follow-ups . St and ardized response means were calculated to assess sensitivity to detect change . Confidence intervals for these indices were constructed using a jackknife procedure , and significance tests were performed by pairing selected indices . Finally , the study projected sample sizes required to assess a new therapy , using each response . These statistical tools facilitated comparisons among instruments and may prove useful in other setting OBJECTIVE To assess the determinants and responsiveness of the Norwegian version of the Child Health Question naire ( CHQ ) in patients with early juvenile idiopathic arthritis ( JIA ) and to compare health status in patients and controls . METHODS A total of 116 children ( median age 8.4 yrs ) with JIA and < 2.5 years of disease duration ( median 11.0 mo ) were examined by a pediatric rheumatologist and reassessed after a median of 10.0 months . Physical and psychosocial health were assessed by means of the CHQ , which provides summary scores for physical and psychosocial health , the Childhood Health Assessment Question naire ( CHAQ ) , and the Child Behavior Checklist ( CBCL , n = 32 ) . Matched controls ( n = 116 ) , r and omly selected from the general population , completed the CHQ at baseline . RESULTS The patients with JIA had poorer physical health and slightly impaired psychosocial health compared with the controls [ 41.2 + /- 13.6 vs 55.2 + /- 7.3 ( p < 0.001 ) and 51.0 + /- 7.5 vs 54.1 + /- 5.7 ( p = 0.002 ) , respectively ] . The most important determinants of the CHQ physical summary score were the child 's pain , morning stiffness , the CHAQ disability index , erythrocyte sedimentation rate ( ESR ) , overall well-being , and physician 's global assessment of disease activity . The psychosocial summary score correlated with the CBCL level of internalizing , externalizing , and total behavior problems . The st and ardized response mean for the physical summary score was large ( 0.96 ) for those who improved , and moderate ( -0.60 ) for those who became worse . CONCLUSION The CHQ discriminated between patients with early JIA and controls . The most important determinants of the CHQ physical summary score were the child 's pain , morning stiffness , CHAQ , ESR , overall well-being , and physician 's global assessment of disease activity . The CHQ was sensitive to clinical changes in children with JIA OBJECTIVES To examine the change in health-related quality of life ( HRQOL ) and its determinants in children with juvenile idiopathic arthritis ( JIA ) treated with methotrexate ( MTX ) .  METHODS Patients were extracted from the PRINTO clinical trial which aim ed to evaluate the efficacy and safety profile of MTX administered in st and ard , intermediate or higher doses ( 10 , 15 and 30 mg/m(2)/week respectively ) . Children with polyarticular-course JIA , who were less than 18 years and had a complete HRQOL assessment were included . RESULTS A total of 521 children were included . At baseline , patients with JIA showed poorer HRQOL ( p<0.01 ) than healthy children . In 207/412 ( 50 % ) and 63 ( 15 % ) children , HRQOL values were 2 st and ard deviations below the mean of healthy controls in the physical and psychosocial summary scale , respectively . After 6 months of treatment with st and ard dose MTX , there was a statistically significant improvement in all HRQOL health concepts , particularly the physical ones . Similar improvements were observed in those who did not respond to a st and ard dose of MTX and were subsequently r and omised to a higher dose . The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with st and ard dose MTX . Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation , pain intensity and an antinuclear-antibody-negative status . CONCLUSIONS MTX treatment produces a significant improvement across a wide range of HRQOL components , particularly in the physical domains , in patients with JIA OBJECTIVE To identify a core set of outcome variables for the assessment of children with juvenile arthritis ( JA ) , to use the core set to develop a definition of improvement to determine whether 
    Output:
    