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: One hundred and four patients with ankylosing spondylitis were involved in a comparative trial carried out in one single centre . They were given either pirprofene ( 1000 mg/day ) , indomethacin ( 125 mg/day ) or a placebo for 6 consecutive weeks . Response to treatment was assessed after 1 , 2 , 4 and 6 weeks on the basis of 4 subjective criteria and 6 st and ard measurements . The overall therapeutic results were judged by the investigator to be satisfactory in 87 % of patients in the pirprofene group , 77 % in the indomethacin group and 29 % in the placebo group ( p less than 0.01 ) . A large number of patients in each group ( including 34 % on placebo ) reported side effects . Treatment was discontinued on account of gastric pain in two patients ( one on pirprofen , the other on indomethacin ) . No abnormalities were detected in laboratory tests Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Objective : The combined efficacy of selective and non-selective cyclo-oxygenase-2 ( COX-2 ) inhibition on the axial manifestations of ankylosing spondylitis ( AS ) in the presence or absence of chronic peripheral arthritis was evaluated . Methods : In a post hoc subgroup analysis of a 6 week , r and omised , double blind , placebo controlled trial , 387 patients with active axial AS were r and omised to receive etoricoxib 90 mg or 120 mg once a day , naproxen 500 mg twice daily , or placebo . R and omisation was stratified by the presence or absence of chronic peripheral arthritis . The primary outcome measure was the time weighted average change from baseline of spine pain intensity . Efficacy data from the three groups receiving active treatment ( the NSAID/COX-2 inhibitor group ) were combined to improve precision . An analysis of covariance model was used to evaluate the effect of peripheral disease on treatment response . Results : 93 patients were allocated to receive placebo and 294 to active treatment ( naproxen or etoricoxib ) . The combined NSAID/COX-2 inhibitor group had a significant treatment response compared with the placebo group for all efficacy measures , both in patients with and without peripheral arthritis . A significantly greater difference in mean patient assessment of spine pain was found between active and placebo treatments in patients without compared with those with peripheral arthritis ( p = 0.005 ; −32.5 mm v −17.0 mm , respectively ) . Similar differences , although not statistically significant , were seen for other end points . Conclusion : NSAIDs and COX-2 inhibitors have a clinical ly relevant symptomatic effect on axial AS irrespective of the presence of peripheral arthritis . In this exploratory analysis spinal improvement appeared to be greater in patients without peripheral disease Objective : To describe and assess the response to short-term etoricoxib as shown by MRI and clinical variables in patients with ankylosing spondylitis ( AS ) selected for eligibility for anti-tumour necrosis factor therapy .  Methods : In a 6-week open-label study , 22 patients with AS and eligible for biological therapy were treated with 90 mg of etoricoxib daily . Clinical and laboratory parameters were obtained and MRI of the sacroiliac joints and the lower thoracic and lumbar spine performed at baseline and at week 6 . The primary end point was the proportion of patients fulfilling the SpondyloArthritis international Society ( ASAS ) response criteria for biological therapies ( ASASBIO ) while secondary end points included the change in MRI-determined bone lesions . Results : Eight of 20 completers improved enough to meet the ASASBIO response criteria and most clinical variables improved significantly . Fifteen patients had a total of 63 MRI-detectable lesions ; overall , 13/60 lesions with paired scans either resolved completely or improved , while five lesions worsened or appeared during treatment . Conclusion : Etoricoxib is an effective symptomatic treatment for patients with AS ; however , its effect on MRI-detected lesions is small . Further studies are needed to determine the effect of etoricoxib on MRI-determined bone oedema OBJECTIVE To evaluate the efficacy and safety of celecoxib in patients with ankylosing spondylitis ( AS ) . METHODS This was a 12-week r and omized , double-blind , placebo-controlled study with 4 treatment arms : celecoxib 200 mg qd , celecoxib 400 mg qd , naproxen 500 mg bid , and placebo .  Patients ( age 18 - 75 yrs ) requiring daily treatment with nonselective nonsteroidal antiinflammatory drugs , and with a pain intensity on visual analog scale ( VAS ) > or = 50 mm worsening by 30 % compared with a pre inclusion visit ( 14 days prior ) were studied . Primary endpoints were least-squares mean changes from baseline in pain intensity , disease activity ( patient global assessment VAS ) , and functional impairment [ Bath Ankylosing Spondylitis Functional Index ( BASFI ) ] . Adverse events were monitored throughout the study . RESULTS Of 611 r and omized patients , 137 were allocated to celecoxib 200 mg , 161 to cele 
    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: One hundred and four patients with ankylosing spondylitis were involved in a comparative trial carried out in one single centre . They were given either pirprofene ( 1000 mg/day ) , indomethacin ( 125 mg/day ) or a placebo for 6 consecutive weeks . Response to treatment was assessed after 1 , 2 , 4 and 6 weeks on the basis of 4 subjective criteria and 6 st and ard measurements . The overall therapeutic results were judged by the investigator to be satisfactory in 87 % of patients in the pirprofene group , 77 % in the indomethacin group and 29 % in the placebo group ( p less than 0.01 ) . A large number of patients in each group ( including 34 % on placebo ) reported side effects . Treatment was discontinued on account of gastric pain in two patients ( one on pirprofen , the other on indomethacin ) . No abnormalities were detected in laboratory tests Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Objective : The combined efficacy of selective and non-selective cyclo-oxygenase-2 ( COX-2 ) inhibition on the axial manifestations of ankylosing spondylitis ( AS ) in the presence or absence of chronic peripheral arthritis was evaluated . Methods : In a post hoc subgroup analysis of a 6 week , r and omised , double blind , placebo controlled trial , 387 patients with active axial AS were r and omised to receive etoricoxib 90 mg or 120 mg once a day , naproxen 500 mg twice daily , or placebo . R and omisation was stratified by the presence or absence of chronic peripheral arthritis . The primary outcome measure was the time weighted average change from baseline of spine pain intensity . Efficacy data from the three groups receiving active treatment ( the NSAID/COX-2 inhibitor group ) were combined to improve precision . An analysis of covariance model was used to evaluate the effect of peripheral disease on treatment response . Results : 93 patients were allocated to receive placebo and 294 to active treatment ( naproxen or etoricoxib ) . The combined NSAID/COX-2 inhibitor group had a significant treatment response compared with the placebo group for all efficacy measures , both in patients with and without peripheral arthritis . A significantly greater difference in mean patient assessment of spine pain was found between active and placebo treatments in patients without compared with those with peripheral arthritis ( p = 0.005 ; −32.5 mm v −17.0 mm , respectively ) . Similar differences , although not statistically significant , were seen for other end points . Conclusion : NSAIDs and COX-2 inhibitors have a clinical ly relevant symptomatic effect on axial AS irrespective of the presence of peripheral arthritis . In this exploratory analysis spinal improvement appeared to be greater in patients without peripheral disease Objective : To describe and assess the response to short-term etoricoxib as shown by MRI and clinical variables in patients with ankylosing spondylitis ( AS ) selected for eligibility for anti-tumour necrosis factor therapy .  Methods : In a 6-week open-label study , 22 patients with AS and eligible for biological therapy were treated with 90 mg of etoricoxib daily . Clinical and laboratory parameters were obtained and MRI of the sacroiliac joints and the lower thoracic and lumbar spine performed at baseline and at week 6 . The primary end point was the proportion of patients fulfilling the SpondyloArthritis international Society ( ASAS ) response criteria for biological therapies ( ASASBIO ) while secondary end points included the change in MRI-determined bone lesions . Results : Eight of 20 completers improved enough to meet the ASASBIO response criteria and most clinical variables improved significantly . Fifteen patients had a total of 63 MRI-detectable lesions ; overall , 13/60 lesions with paired scans either resolved completely or improved , while five lesions worsened or appeared during treatment . Conclusion : Etoricoxib is an effective symptomatic treatment for patients with AS ; however , its effect on MRI-detected lesions is small . Further studies are needed to determine the effect of etoricoxib on MRI-determined bone oedema OBJECTIVE To evaluate the efficacy and safety of celecoxib in patients with ankylosing spondylitis ( AS ) . METHODS This was a 12-week r and omized , double-blind , placebo-controlled study with 4 treatment arms : celecoxib 200 mg qd , celecoxib 400 mg qd , naproxen 500 mg bid , and placebo .  Patients ( age 18 - 75 yrs ) requiring daily treatment with nonselective nonsteroidal antiinflammatory drugs , and with a pain intensity on visual analog scale ( VAS ) > or = 50 mm worsening by 30 % compared with a pre inclusion visit ( 14 days prior ) were studied . Primary endpoints were least-squares mean changes from baseline in pain intensity , disease activity ( patient global assessment VAS ) , and functional impairment [ Bath Ankylosing Spondylitis Functional Index ( BASFI ) ] . Adverse events were monitored throughout the study . RESULTS Of 611 r and omized patients , 137 were allocated to celecoxib 200 mg , 161 to cele 
    Output:
    