***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: Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often , initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons that multiple studies of the same marker lead to differing conclusions . A variety of method ologic problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of  tumor marker studies  was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines suggest helpful presentations of data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply Background —Vascular cell adhesion molecule (VCAM)-1 , intercellular adhesion molecule (ICAM)-1 , and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability . In a prospect i ve study , we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease ( CAD ) . Methods and Results —We obtained baseline sample s from a prospect i ve cohort of 1246 patients with CAD . Besides various markers of inflammation ,  soluble VCAM-1 ( sVCAM-1 ) , sICAM-1 , and  sE-selectin  were determined . Follow-up information on cardiovascular events was obtained ( mean , 2.7 ; maximum , 4.1 years ) . Independently higher levels of  sVCAM-1  ( 1932 versus 1128 ng/mL;P < 0.0001 ) ,  sICAM-1  ( 353 versus 287 ng/mL;P = 0.015 ) , and  sE-selectin  ( 81 versus 63 ng/mL;P = 0.003 ) were observed in patients with future death from cardiovascular causes . In a multivariate model , fatal risk was 2.1-fold ( 1.1 to 4.0 ) higher in patients within the top quartile of baseline sVCAM-1 concentrations compared with lower quartiles . This association was present independent of general inflammatory response as reflected by low or high C-reactive protein ( hs-CRP ) levels . In a model that simultaneously controlled for all inflammatory and soluble adhesion markers determined , only sVCAM-1 remained independently significant for future fatal cardiovascular events , with a 2.8-fold increase in risk ( P = 0.003 ) . Conclusions —Soluble adhesion molecules  sVCAM-1  , sICAM-1 , and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD . Especially sVCAM-1 added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death Low- grade inflammation as detected by increased C-reactive protein ( CRP ) levels predicts the risk of cardiovascular events . However , there is still controversy over the mid-term predictive value of CRP in patients referred for elective percutaneous coronary revascularization ( PCI ) for stable angina pectoris . The aim of this study was to assess the relationship between baseline CRP level and mid-term outcome of patients undergoing PCI . Two groups of patients with stable angina pectoris were prospect ively studied . Group A consisted of 150 consecutive patients with a CRP level < or = 3 mg/L , and group B consisted of 150 consecutive patients with a CRP level > 3 mg/L undergoing PCI at our institution .  Comparing both groups of patients , the analysis confirmed a significant difference between medians of the CRP levels ( 0.5 versus 8 mg/mL ; P < 0.001 ) . A higher level of CRP in group B was associated with a lower presence of male gender ( P < 0.05 ) and history of myocardial infa rct ion ( P < 0.05 ) . On the other h and , in group B there was higher occurrence of smoking ( P < 0.001 ) , hypertension ( P < 0.05 ) , hypertriglyceridemia ( P < 0.001 ) , and diabetes mellitus ( P < 0.01 ) . The incidence of myocardial infa rct ion based on post-interventional release of TnI > 1.5 ng/mL reached 12 % in group A and 14 % in group B ( P = 0.73 ) . Analyses were repeated with adjustment for significant baseline variables , which did not change our findings . The incidence of adverse cardiovascular events during a six month follow-up was 13 % in both groups ( NS ) . Increased CRP serum prior to PCI was not associated with the risk and extent of procedure-related myocardial injury measured by TnI release and does not portend heightened cardiovascular risk at six months after percutaneous revascularization . On the other h and , a CRP level > 3 mg/L was associated with a higher occurrence of cardiovascular risk factors ( smoking , hypertension , hypertriglyceridemia , and diabetes mellitus ) Background —We previously demonstrated that the risk of coronary artery disease ( CAD ) increased in relation to the number of pathogens ( the “ pathogen burden ” ) in a cross-sectional study . In the present prospect i ve study with a different patient cohort , we evaluated the effect of pathogen burden on the risk of myocardial infa rct ion ( MI ) or death among CAD patients . Methods and Results —IgG antibodies to cytomegalovirus ( CMV ) , hepatitis A virus ( HAV ) , herpes simplex virus type 1 ( HSV1 ) , HSV type 2 ( HSV2 ) , Chlamydia pneumoniae and Helicobacter pylori , and C-reactive protein ( CRP ) levels were tested in baseline blood sample s from 890 patients who had significant CAD on angiography . The mean follow-up period was 3 years . The baseline prevalence of antibodies directed against CMV , HAV , HSV1 , or HSV2 , but not C pneumoniae and H pylori , was significantly higher among patients who subsequently developed MI or death than among control subjects . After adjustment for traditional risk factors , number of diseased vessels , and clinical presentation , relative hazards ( 95 % confidence limits ) for MI or death were 2.0 ( 1.4 to 3.2 ) for CMV , 1.6 ( 1.1 to 2.3 ) for HAV , and 1.5 ( 1.0 to 2.2 ) for HSV2 . Increasing pathogen burden was significantly associated with increasing risk of MI or death in a dose-response fashion . Adjusted relative hazards of MI or death associated with pathogen burden were significant among individuals with low or high CRP levels . Conclusions —The results suggest that infection plays an important role in incident MI or death and that the risk posed by infection is independently related to the pathogen burden Background —Although severe chronic kidney disease ( CKD ) is an independent predictor of mortality among patients with coronary artery disease , the impact of mild CKD on morbidity and mortality has not been fully defined . Methods and Results —Morbidity and mortality for the 3608 patients with multivessel coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation r and omized trial and registry were compared on the basis of the presence and absence of CKD , defined as a preprocedure serum creatinine level of > 1.5 mg/dL. Seventy-six patients had CKD . Patients with renal insufficiency were older and more likely to have a history of diabetes , hypertension , and other comorbidities . Among patients undergoing PTCA , patients with CKD had a greater frequency of in-hospital death and cardiogenic shock ( P < 0.05 and 0.01 , respectively ) . There was a trend toward a larger proportion of patients with CKD experiencing angina at 5 years ( P = 0.079 ) . Patients with CKD had more cardiac admissions ( P = 0.003 and < 0.0001 for patients undergoing PTCA and CABG , respectively ) and a shorter time to subsequent CABG after initial revascularization than patients without CKD ( P = 0.01 ) . CKD was associated with a higher risk of death at 7 years , both of all causes ( relative risk 2.2 , P < 0.001 ) and of cardiac causes ( relative risk 2.8 , P < 0.001 ) . Conclusions —CKD is associated with an increased risk of recurrent hospitalization , subsequent CABG , and mortality . This increased risk of death is independent of and additive to the risk associated with diabetes 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 
    Output:
    
The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information .
Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate ( eGFR ) was cost-effective .
These results were robust to most alternative scenarios investigating other sources of uncertainty .
However , the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein ( CRP ) was potentially sensitive to the cost of the CRP test itself ( assumed to be 6 pounds in the base-case scenario ) .
Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes .
The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker ( eGFR ) .
The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP , singly or in combination with other biomarkers , in terms of waiting list prioritisation is unlikely to be cost-effective