***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: 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 Eighty-nine patients who had been treated by ileal resection for Crohn 's disease between 1979 and 1984 were included in a prospect i ve cohort follow up to study the natural course of early postoperative lesions . Recurrent lesions were observed endoscopically in the neoterminal ileum within 1 year of surgery in 73 % of the patients , although only 20 % of the patients had symptoms . Three years after surgery , the endoscopic recurrence rate had increased to 85 % and symptomatic recurrence occurred in 34 % . The ultimate course of the disease was best predicted by the severity of the early postoperative lesions , as observed at ileoscopy . Clinical parameters that influenced outcome were preoperative disease activity , the indication for surgery , and the number of surgical resections . When patients were stratified for preoperative disease activity , the severity of lesions found at endoscopy remained a strong predictive factor for symptomatic recurrence . In 22 other patients su bmi tted to " curative " ileal resection and ileocolonic anastomosis , the segment to be used as neoterminal ileum was carefully examined during surgery , and two large biopsies were taken before making the anastomosis . An ileoscopy was performed 6 months after surgery . Although all patients had a macroscopically normal neoterminal ileum and 19 had entirely normal biopsies at the time of surgery , 21 patients were found at ileoscopy to have developed ileitis involving a 15-cm segment ( range , 4 - 30 cm ) , and 20 had unequivocal microscopic lesions on biopsies . These studies suggest that early lesions in the neoterminal ileum after Crohn 's resection do not originate from microscopic inflammation present in this bowel segment at the time of surgery . The early postoperative lesions in the neoterminal ileum seem to be a suitable model to study the pathogenesis of Crohn 's disease and also to evaluate new therapeutic modalities , either to prevent development of these early lesions or to treat progressive recurrence OBJECTIVES : We evaluated the effects of treatment on health-related quality of life ( HRQoL ) during a r and omized controlled trial of natalizumab maintenance therapy ( ENACT-2 ) using both disease-specific and generic measures . METHODS : Crohn 's disease patients who received natalizumab as induction therapy in ENACT-1 ( N = 724 ) and responded ( N = 339 ) were re-r and omized to ENACT-2 in which they received natalizumab 300 mg ( N = 168 ) or placebo ( N = 171 ) every 4 wk for 48 additional wk . Outcome measures were the change from baseline on the inflammatory bowel disease question naire ( IBDQ ) , the short form-36 ( SF-36 ) , the EuroQol-5D ( EQ-5D ) , and a subject global assessment . RESULTS : At entry into ENACT-1 , scores indicated substantially impaired HRQoL for both the disease-specific and general measures . Natalizumab responders showed clinical ly meaningful improvement in HRQoL over the course of the ENACT-1 study . During maintenance therapy , IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-r and omized to receive the drug in ENACT-2 ( N = 168 ) remained stable , while those re-r and omized to placebo ( N = 171 ) worsened . At week 60 , 48 wk after the initiation of maintenance therapy , the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab ( P < 0.001 for all scales ) . The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36 . CONCLUSIONS : The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy OBJECTIVE To investigate the relationship between inflammatory bowel disease ( IBD ) patients ' disease-related worries and concerns and their disease-related data , sociodemographic variables and perceived information level with respect to IBD . STUDY DESIGN Prospect i ve evaluation of disease-related concerns . SETTING Out-patient IBD clinic of a university hospital . STUDY POPULATION The study included 105 patients with IBD ( 72 with Crohn 's disease and 33 with ulcerative colitis ) . MEASUREMENTS Worries and concerns were measured using the st and ardized 25-item rating form of IBD patient concerns ; actual disease activity was assessed by physicians using the Crohn 's disease and clinical activity indices . Sociodemographic and other disease-related data were collected using a structured question naire . Patients '  perceived information level was measured using a visual analogue scale . RESULTS The issues of greatest concern to our patients were , in descending order of importance , having an ostomy bag ( mean score + /- SD 63.6 + /- 38 ) , the effects of medication ( 53.1 + /- 34 ) , having surgery ( 51.6 + /-  
    Output:
    
Work disability , increased disease activity , number of relapses , corticosteroid treatment and hospitalization rate were significantly associated with a lower HRQOL in the majority of included studies .
Biological treatment positively influenced HRQOL .
HRQOL of adult CD patients is consistently determined by markers of active disease , including work disability , increased disease activity , number of relapses , biological treatment and hospitalization rate .
These determinants may refine possibilities to improve HRQOL