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 Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis ( RA ) . However , their optimal use is yet to be determined . This 12-month double-blind study attempted remission induction using st and ard therapy with or without infliximab in patients with early , poor-prognosis RA . The primary end point was synovitis ( measured by magnetic resonance imaging [ MRI ] ) . Clinical observations continued to 24 months . METHODS All patients had fewer than 12 months of symptoms . Assessment s included full metrologic evaluation , laboratory tests , radiographs , functional evaluation using the Health Assessment Question naire ( HAQ ) , and quality of life measurement using the RA Quality of Life ( RAQoL ) question naire . MRI was performed at 0 , 4 , 14 , and 54 weeks ; MR images were scored blindly . Patients received methotrexate ( MTX ) and were r and omized to receive either infliximab or placebo for 12 months . RESULTS Twenty patients were recruited ( mean age 52 years , mean symptom duration 6 months , mean C-reactive protein level 42 mg/liter , and 65 % rheumatoid factor positive ) . At 1 year , all MRI scores were significantly better , with no new erosions in the infliximab plus MTX group ; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology ( ACR ) 50 % and 70 % improvement criteria ( 78 % versus 40 % in the placebo plus MTX group and 67 % versus 30 % , respectively ) and had a greater functional benefit ( P < 0.05 for all comparisons ) . Importantly , at 1 year after stopping induction therapy , response was sustained in 70 % of the patients in the infliximab plus MTX group , with a median Disease Activity Score in 28 joints ( DAS28 ) of 2.05 ( remission range ) . At 2 years , there were no significant between-group differences in the DAS28 , ACR response , or radiographic scores , but differences in the HAQ and RAQoL scores were maintained ( P < 0.05 ) . CONCLUSION Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year . At 2 years , functional and quality of life benefits were sustained , despite withdrawal of infliximab therapy . These data may have significant implication s for the optimal use of expensive biologic therapies OBJECTIVE Therapeutic strategies for rheumatoid arthritis ( RA ) have been evolving from the traditional " pyramid " approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs ( DMARDs ) , in the hope of improving long-term health outcomes . However , few data to have been presented to document the effects of this approach . We sought to directly assess associations between consistent DMARD use and long-term functional outcomes . METHODS We studied 2,888 RA patients who were followed up prospect ively for up to 20 years ( average 9 years ) at 8 data bank centers . The independent variable was the proportion of patient encounters that result ed in treatment with > or = 1 DMARD ( hydroxychloroquine , sulfasalazine , auranofin , intramuscular gold , D-penicillamine , methotrexate , and /or azathioprine ) . The dependent variable was each patient 's last recorded Disability Index value from the Health Assessment Question naire ( HAQ ) . RESULTS Increased DMARD use was strongly associated with better long-term Disability Index values ( P < 0.0001 ) . The association was strengthened when restricted to more seriously affected ( rheumatoid factor (RF)-positive ) patients . The magnitude of the effect , unadjusted , was a difference of 0.53 HAQ Disability units ( scale 0 - 3 ) between 100 % DMARD use and 0 % . Correlation coefficients ranged up to 0.26 . Effects were similar for all disease duration periods ( 0 - 4 , 5 - 9 , 10 - 14 , 15 - 19 , and 20 + years ) . " Control " correlations , with variables computed to represent the proportion of time in which patients were taking either nonsteroidal anti-inflammatory drugs or prednisone , failed to show positive associations . A multiple linear regression model , which controlled for age , disease duration , sex , RF positivity , proportion of visits under a prednisone regimen , and initial disability level , included the proportion of time in which patients were taking DMARDs ( P < 0.0001 ) , with a model R2 of 0.54 . These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDS more frequently , and despite absence of data on drug use early in the disease course of many patients . Thus , these results , which suggest up to a 30 percent reduction in long term disability with consistent DMARD use , are most likely conservative . CONCLUSION An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data Perioperative factors associated with late septic arthritis after knee and hip arthroplasties were prospect ively investigated . All patients received a short course of perioperative cefuroxime . After a follow-up of 1 year , septic arthritis was diagnosed in 9/362 patients ( 2.5 percent ) after knee arthroplasty and in 17/2651 patients ( 0.64 percent ) after hip arthroplasty . For the knee , factors associated with septic arthritis after arthroplasty were rheumatoid arthritis , wound infection , an unhealed wound , and a painful , limited knee function at discharge from the hospital . For the hip , corresponding risk factors were diabetes , failed fracture osteo synthesis , a breakdown of sterility during operation , wound infection , postoperative urinary tract infection , and an unhealed wound at discharge from the hospital or a difficult rehabilitation course . Reoperation after knee and hip arthroplasty was also clearly associated with a higher incidence of septic arthritis This prospect i ve study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients ( 41 men and 37 women ) with a revision total knee or hip replacement . The mean age at the time of operation was 64.0 years ( 19 to 90 ) . Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement . The  white blood cell count , the erythrocyte sedimentation rate and levels of C-reactive protein , interleukin-6 , procalcitonin and tumour necrosis factor (TNF)-alpha  were measured in blood sample s before operation . The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis . C-reactive protein ( > 3.2 md/dl ) and interleukin-6 ( > 12 pg/ml ) have the highest sensitivity ( 0.95 ) . Interleukin-6 is less specific than C-reactive protein ( 0.87 vs 0.96 ) . Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant . Procalcitonin ( > 0.3 ng/ml ) and TNF-alpha ( > 40 ng/ml ) are very specific ( 0.98 vs 0.94 ) but have a low sensitivity ( 0.33 vs 0.43 ) . The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant . A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and /or interleukin-6 levels OBJECTIVES The British Society for Rheumatology Biologics Register ( BSRBR ) is a prospect i ve cohort study to determine the efficacy and toxicity of biological agents in rheumatoid arthritis ( RA ) patients compared with RA controls . Entry of patients to the register is a condition of use of anti-tumour necrosis factor ( anti-TNF ) therapy in the UK , but little is known of clinicians ' views of its usefulness . Data from the register suggest uneven provision of anti-TNF-alpha therapy . METHODS A question naire was sent on behalf of the BSRBR to all UK consultant rheumatologists concerning provision and use of anti-TNF-alpha therapy and their experience of working with the BSRBR . RESULTS  Response rate was 49.5 % representing 252 consultants . Fourty-six per cent had some limitation of access to anti-TNF-alpha drugs , usually a financial cap ( 70 % ) , even for RA patients meeting National Institute for Health and Clinical Excellence ( NICE ) criteria . Sixty-seven per cent could prescribe for ankylosing spondylitis ( AS ) or psoriatic arthritis ( PsA ) in some circumstances but only 25 and 35 % , respectively , could prescribe according to BSR guidance . More than 50 % found the workload involved in su bmi tting data to the registry at least difficult , but most had favourable impressions of the BSRBR and thought similar registries desirable or essential for PsA , AS and rituximab . CONCLUSIONS Access to anti-TNF therapy for patients with inflammatory arthritis is variable in the UK , even for RA where it is NICE-approved . Access is more limited for conditions where NICE has not yet issued guidance . The BSRBR generates a significant workload for rheumatology staff but is generally well-regarded OBJECTIVE To evaluate safety , efficacy , and radiographic progression in patients with early rheumatoid arthritis ( RA ) undergoing longterm treatment with etanercept .  METHODS Patients with early RA ( disease duration of 3 years or less ) who had completed a 2-year efficacy study comparing etanercept and methotrexate ( MTX ) were followed in an extension where they received 25 mg etanercept twice weekly . Safety was summarized descriptively and compared with data from the efficacy study . Efficacy and radiographic progression were assessed using American College of Rheumatology response criteria , disease activity scores , and Total Sharp Score ( TSS ) . RESULTS Rates of serious adverse events and serious infections did not increase with longterm exposure to etanercept , and were similar to rates reported for the blinded portion of the efficacy study . Efficacy was sustained in patients who completed 5 years of etanercept treatment at the time of this report ( N = 201 ) , even in those who decreased or discontinued use of MTX or corticosteroids . No radiographic progression ( change in TSS < or = 0 ) was seen in 55 % of patients with 5-year radiographs ; negative change ( TSS < 0 ) was seen in 11 % . CONCLUSION Etanercept treatment in patients with early RA was generally well tolerated for up to 5 years . The results indicate sustained efficacy and decreased rate of radiographic progression . The rate of radiographic progression was low compared with other studies , emphasizing the benefit gained in patients with early aggressive RA who undergo longterm treatment with etanercept The objective was to estimate the incidence of serious infections in the patients treated with anti-TNFalpha agents for rheumatoid arthritis ( RA ) recorded in the Lombardy Rheumatology Network ( LORHEN ) registry . The study inclusion criteria were met by 1064 of the 1114 patients with long-st and ing RA , 519 treated with infliximab , 303 with adalimumab , and 242 with etanercept ; their mean age was 55.8 years and the mean duration of RA 9.4 years . Seventy-three patients ( 6.9 % ) experienced a total of 74 serious infections , an incidence rate for all treatment courses of 35.9 per 1000 patient-years ( 95 % confidence interval [ 95 % CI ] 27.66 - 44.13 ) . Most were lower respiratory tract ( 34.2 % ) or skin and soft tissue infections ( 20.5 % ) . Of the 1064 patients , the 790 treated with anti-TNFalpha after March 2002 underwent screening tests for LTBI ; five patients developed active tuberculosis . Three patients died of septic shock . The type of anti-TNFalpha agent did not seem to affect the incidence or site of the infections . Both univariate and multivariate analyses identified age at the start of anti-TNFalpha treatment ( p=0.008 ) , baseline erythrocyte sedimentation rate ( [ ESR ] p=0.014 ) , and the concomitant use of corticosteroids ( p=0.029 ) as significant predictors of infections . There was no statistically significant difference in risk between the anti-TNFalpha agents Background There have been numerous studies with conflicting results regarding the use of anti-tumor necrosis factor ( TNF ) therapy and its relationship to postoperative outcome in Crohn disease . The aim of our study was to examine the rate of postoperative morbidity in patients receiving anti TNF therapy in the perioperative period . Methods All patients undergoing surgery for Crohn disease from 2005 till 2008 were abstract ed from a prospect i ve data base . Patients undergoing surgery which included a suture or staple line at risk for leaking were selected for the study . A retrospective review of medical records was performed . The study group comprised patients treated with perioperative anti TNF therapy ( defined as treatment within 8 weeks preoperatively or up to 30 days postoperatively ) . The remainder of the patients did not receive perioperative 
    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 Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis ( RA ) . However , their optimal use is yet to be determined . This 12-month double-blind study attempted remission induction using st and ard therapy with or without infliximab in patients with early , poor-prognosis RA . The primary end point was synovitis ( measured by magnetic resonance imaging [ MRI ] ) . Clinical observations continued to 24 months . METHODS All patients had fewer than 12 months of symptoms . Assessment s included full metrologic evaluation , laboratory tests , radiographs , functional evaluation using the Health Assessment Question naire ( HAQ ) , and quality of life measurement using the RA Quality of Life ( RAQoL ) question naire . MRI was performed at 0 , 4 , 14 , and 54 weeks ; MR images were scored blindly . Patients received methotrexate ( MTX ) and were r and omized to receive either infliximab or placebo for 12 months . RESULTS Twenty patients were recruited ( mean age 52 years , mean symptom duration 6 months , mean C-reactive protein level 42 mg/liter , and 65 % rheumatoid factor positive ) . At 1 year , all MRI scores were significantly better , with no new erosions in the infliximab plus MTX group ; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology ( ACR ) 50 % and 70 % improvement criteria ( 78 % versus 40 % in the placebo plus MTX group and 67 % versus 30 % , respectively ) and had a greater functional benefit ( P < 0.05 for all comparisons ) . Importantly , at 1 year after stopping induction therapy , response was sustained in 70 % of the patients in the infliximab plus MTX group , with a median Disease Activity Score in 28 joints ( DAS28 ) of 2.05 ( remission range ) . At 2 years , there were no significant between-group differences in the DAS28 , ACR response , or radiographic scores , but differences in the HAQ and RAQoL scores were maintained ( P < 0.05 ) . CONCLUSION Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year . At 2 years , functional and quality of life benefits were sustained , despite withdrawal of infliximab therapy . These data may have significant implication s for the optimal use of expensive biologic therapies OBJECTIVE Therapeutic strategies for rheumatoid arthritis ( RA ) have been evolving from the traditional " pyramid " approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs ( DMARDs ) , in the hope of improving long-term health outcomes . However , few data to have been presented to document the effects of this approach . We sought to directly assess associations between consistent DMARD use and long-term functional outcomes . METHODS We studied 2,888 RA patients who were followed up prospect ively for up to 20 years ( average 9 years ) at 8 data bank centers . The independent variable was the proportion of patient encounters that result ed in treatment with > or = 1 DMARD ( hydroxychloroquine , sulfasalazine , auranofin , intramuscular gold , D-penicillamine , methotrexate , and /or azathioprine ) . The dependent variable was each patient 's last recorded Disability Index value from the Health Assessment Question naire ( HAQ ) . RESULTS Increased DMARD use was strongly associated with better long-term Disability Index values ( P < 0.0001 ) . The association was strengthened when restricted to more seriously affected ( rheumatoid factor (RF)-positive ) patients . The magnitude of the effect , unadjusted , was a difference of 0.53 HAQ Disability units ( scale 0 - 3 ) between 100 % DMARD use and 0 % . Correlation coefficients ranged up to 0.26 . Effects were similar for all disease duration periods ( 0 - 4 , 5 - 9 , 10 - 14 , 15 - 19 , and 20 + years ) . " Control " correlations , with variables computed to represent the proportion of time in which patients were taking either nonsteroidal anti-inflammatory drugs or prednisone , failed to show positive associations . A multiple linear regression model , which controlled for age , disease duration , sex , RF positivity , proportion of visits under a prednisone regimen , and initial disability level , included the proportion of time in which patients were taking DMARDs ( P < 0.0001 ) , with a model R2 of 0.54 . These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDS more frequently , and despite absence of data on drug use early in the disease course of many patients . Thus , these results , which suggest up to a 30 percent reduction in long term disability with consistent DMARD use , are most likely conservative . CONCLUSION An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data Perioperative factors associated with late septic arthritis after knee and hip arthroplasties were prospect ively investigated . All patients received a short course of perioperative cefuroxime . After a follow-up of 1 year , septic arthritis was diagnosed in 9/362 patients ( 2.5 percent ) after knee arthroplasty and in 17/2651 patients ( 0.64 percent ) after hip arthroplasty . For the knee , factors associated with septic arthritis after arthroplasty were rheumatoid arthritis , wound infection , an unhealed wound , and a painful , limited knee function at discharge from the hospital . For the hip , corresponding risk factors were diabetes , failed fracture osteo synthesis , a breakdown of sterility during operation , wound infection , postoperative urinary tract infection , and an unhealed wound at discharge from the hospital or a difficult rehabilitation course . Reoperation after knee and hip arthroplasty was also clearly associated with a higher incidence of septic arthritis This prospect i ve study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients ( 41 men and 37 women ) with a revision total knee or hip replacement . The mean age at the time of operation was 64.0 years ( 19 to 90 ) . Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement . The  white blood cell count , the erythrocyte sedimentation rate and levels of C-reactive protein , interleukin-6 , procalcitonin and tumour necrosis factor (TNF)-alpha  were measured in blood sample s before operation . The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis . C-reactive protein ( > 3.2 md/dl ) and interleukin-6 ( > 12 pg/ml ) have the highest sensitivity ( 0.95 ) . Interleukin-6 is less specific than C-reactive protein ( 0.87 vs 0.96 ) . Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant . Procalcitonin ( > 0.3 ng/ml ) and TNF-alpha ( > 40 ng/ml ) are very specific ( 0.98 vs 0.94 ) but have a low sensitivity ( 0.33 vs 0.43 ) . The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant . A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and /or interleukin-6 levels OBJECTIVES The British Society for Rheumatology Biologics Register ( BSRBR ) is a prospect i ve cohort study to determine the efficacy and toxicity of biological agents in rheumatoid arthritis ( RA ) patients compared with RA controls . Entry of patients to the register is a condition of use of anti-tumour necrosis factor ( anti-TNF ) therapy in the UK , but little is known of clinicians ' views of its usefulness . Data from the register suggest uneven provision of anti-TNF-alpha therapy . METHODS A question naire was sent on behalf of the BSRBR to all UK consultant rheumatologists concerning provision and use of anti-TNF-alpha therapy and their experience of working with the BSRBR . RESULTS  Response rate was 49.5 % representing 252 consultants . Fourty-six per cent had some limitation of access to anti-TNF-alpha drugs , usually a financial cap ( 70 % ) , even for RA patients meeting National Institute for Health and Clinical Excellence ( NICE ) criteria . Sixty-seven per cent could prescribe for ankylosing spondylitis ( AS ) or psoriatic arthritis ( PsA ) in some circumstances but only 25 and 35 % , respectively , could prescribe according to BSR guidance . More than 50 % found the workload involved in su bmi tting data to the registry at least difficult , but most had favourable impressions of the BSRBR and thought similar registries desirable or essential for PsA , AS and rituximab . CONCLUSIONS Access to anti-TNF therapy for patients with inflammatory arthritis is variable in the UK , even for RA where it is NICE-approved . Access is more limited for conditions where NICE has not yet issued guidance . The BSRBR generates a significant workload for rheumatology staff but is generally well-regarded OBJECTIVE To evaluate safety , efficacy , and radiographic progression in patients with early rheumatoid arthritis ( RA ) undergoing longterm treatment with etanercept .  METHODS Patients with early RA ( disease duration of 3 years or less ) who had completed a 2-year efficacy study comparing etanercept and methotrexate ( MTX ) were followed in an extension where they received 25 mg etanercept twice weekly . Safety was summarized descriptively and compared with data from the efficacy study . Efficacy and radiographic progression were assessed using American College of Rheumatology response criteria , disease activity scores , and Total Sharp Score ( TSS ) . RESULTS Rates of serious adverse events and serious infections did not increase with longterm exposure to etanercept , and were similar to rates reported for the blinded portion of the efficacy study . Efficacy was sustained in patients who completed 5 years of etanercept treatment at the time of this report ( N = 201 ) , even in those who decreased or discontinued use of MTX or corticosteroids . No radiographic progression ( change in TSS < or = 0 ) was seen in 55 % of patients with 5-year radiographs ; negative change ( TSS < 0 ) was seen in 11 % . CONCLUSION Etanercept treatment in patients with early RA was generally well tolerated for up to 5 years . The results indicate sustained efficacy and decreased rate of radiographic progression . The rate of radiographic progression was low compared with other studies , emphasizing the benefit gained in patients with early aggressive RA who undergo longterm treatment with etanercept The objective was to estimate the incidence of serious infections in the patients treated with anti-TNFalpha agents for rheumatoid arthritis ( RA ) recorded in the Lombardy Rheumatology Network ( LORHEN ) registry . The study inclusion criteria were met by 1064 of the 1114 patients with long-st and ing RA , 519 treated with infliximab , 303 with adalimumab , and 242 with etanercept ; their mean age was 55.8 years and the mean duration of RA 9.4 years . Seventy-three patients ( 6.9 % ) experienced a total of 74 serious infections , an incidence rate for all treatment courses of 35.9 per 1000 patient-years ( 95 % confidence interval [ 95 % CI ] 27.66 - 44.13 ) . Most were lower respiratory tract ( 34.2 % ) or skin and soft tissue infections ( 20.5 % ) . Of the 1064 patients , the 790 treated with anti-TNFalpha after March 2002 underwent screening tests for LTBI ; five patients developed active tuberculosis . Three patients died of septic shock . The type of anti-TNFalpha agent did not seem to affect the incidence or site of the infections . Both univariate and multivariate analyses identified age at the start of anti-TNFalpha treatment ( p=0.008 ) , baseline erythrocyte sedimentation rate ( [ ESR ] p=0.014 ) , and the concomitant use of corticosteroids ( p=0.029 ) as significant predictors of infections . There was no statistically significant difference in risk between the anti-TNFalpha agents Background There have been numerous studies with conflicting results regarding the use of anti-tumor necrosis factor ( TNF ) therapy and its relationship to postoperative outcome in Crohn disease . The aim of our study was to examine the rate of postoperative morbidity in patients receiving anti TNF therapy in the perioperative period . Methods All patients undergoing surgery for Crohn disease from 2005 till 2008 were abstract ed from a prospect i ve data base . Patients undergoing surgery which included a suture or staple line at risk for leaking were selected for the study . A retrospective review of medical records was performed . The study group comprised patients treated with perioperative anti TNF therapy ( defined as treatment within 8 weeks preoperatively or up to 30 days postoperatively ) . The remainder of the patients did not receive perioperative 
    Output:
    