***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: Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising  studies  for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding .  Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the appraisal process involves a detailed assessment of the patients ( for example , high , medium , or low risk ) , the study interventions ( for example , frequency , degree , and duration ) , and the outcome measurements ( for example , definitions and degree of surveillance ) The SimpliRed D-dimer assay is a whole blood agglutination test for the exclusion of pulmonary embolism ( PE ) and has been advocated as a reliable rapid bedside alternative to more time-consuming quantitative assays . However , widely differing negative predictive values ( 77 - 100 % ) are reported . This study assessed the intra- and interobserver variability as a possible cause for this wide accuracy range and evaluated the accuracy of the SimpliRed test in 81 consecutive patients with clinical ly suspected PE .  Absolute D-dimer concentration was measured using the Tinaquant ( Roche Diagnostics GmbH , Mannheim , Germany ) assay . Every assay was immediately scored by one observer and then photographed . Photos were r and omised and read twice by two other independent observers . The intraobserver reproducibility was good : kappa=0.81 and 0.73 . However , we found poor interobserver reproducibility with kappa=0.47 . This seems due to the fact that the SimpliRed test proved difficult to interpret in the 0.3 - 1.3 microg/mL plasma concentration D-dimer range , which contained 32/81 ( 40 % ) patients , 8 of whom had PE . Using pulmonary angiograms and ventilation perfusion lung scans with a concurrent spiral computed tomography scan as a gold st and ard ( 25 patients had PE ) , SimpliRed 's accuracy to exclude PE was moderate , with negative predictive values of 0.78 and 0.84 . In particular , the two observers scored the SimpliRed test as normal in 12 of 25 and 5 of 25 patients with proven PE . We conclude that SimpliRed is strongly observer-dependent . This explains the varying sensitivities for the detection of venous thromboembolism as reported in previous studies We investigated 128 patients with suspected deep vein thrombosis and 26 patients with suspected pulmonary embolism . Plasma cross-linked fibrin degradation products were measured instantly by a new rapid and fully quantitative immunoturbidimetric assay ( Boehringer Mannheim ) which recognizes the D-dimer epitope by antibody-coated latex particles . Diagnosis of deep vein thrombosis was established by either ascending venography ( n = 105 ) or colour duplex ultrasound ( n = 8) , whereas for the exclusion of deep vein thrombosis only venography was accepted . The sensitivity/specificity for the diagnosis of deep vein thrombosis was 98%/44 % . Patients with suspected pulmonary embolism were examined by pulmonary angiography ( n = 19 ) or perfusion lung scanning alone ( n = 6 ) , if sufficient . One pulmonary embolism was diagnosed at post-mortem examination . For pulmonary embolism , sensitivity/specificity was 100%/50 % . These findings indicate that the new immunoturbidimetric technique is as reliable as former ELISA methods and allows to rule out thromboembolic disorders . D-dimers showed a correlation to the extent of the deep vein thrombosis , proximal thrombosis producing higher D-dimer levels . Patients presenting immediately after the onset of symptoms were found to have higher D-dimers than patients examined after a few days . A quantitative D-dimer measurement thus seems to provide precious additional information of the duration and the extent of thromboembolic disease The performance of a new automated ELISA for a rapid , individual and quantitative measurement of plasma D-dimer ( VIDAS D-dimer ) has been evaluated . First , a study of 100 patients was performed in order to choose the best couple of antibodies in comparison with an already clinical ly vali date d ELISA . Then the results were certified in a prospect i ve study including 195 consecutive patients suspected of pulmonary embolism ( PE ) . For a cut-off level of 500 ng/ml VIDAS D-dimer showed a sensitivity of 100 % ( 95 % confidence interval 92 - 100 ) , a specificity of 37.6 % , a negative predictive value of 100 % ( 95 % CI 93.3 - 100 ) and a positive predictive value of 33.1 % . During a 6 months ' follow-up no patient ( 95 % CI 0 - 6.4 ) with D-dimer < 500 ng/ml presented a new suspicion of venous thromboembolic disease . These results suggest that this rapid and single-dose ELISA provides a very useful tool for the clinician to exclude on a day-to-day basis the diagnosis of PE The practical utility and diagnostic accuracy of two new rapid , automated and quantitative immunoturbidimetric D-dimer methods have been evaluated in a population of 123 r and omly selected patients with suspected VTE . The STA Liatest D-dimer and MDA D-dimer methods are based on the photo-optical measurement of the rate of agglutination of antibody-coated latex particles . The VIDAS D-dimer automated Elisa was used as the reference method . Diagnosis was confirmed in 51 patients ( 29 PE , 19 DVT , 3 DVT+PE ) . The immunoturbidimetric methods compared favorably with the VIDAS Elisa as judged from the correlation coefficients of linear regression lines ( r = 0.82 , MDA vs VIDAS ; r = 0.75 , STA vs VIDAS ) and areas under 
    Output:
    
The turbidimetric D-dimer test is sensitive but nonspecific for the detection of PE in the emergency department setting .
D-Dimer tests using latex turbidimetric methods appear to have test characteristics comparable to those for ELISA methods