***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Context Is it safe to withhold additional testing in patients with suspected pulmonary embolism ( PE ) and negative d-dimer test results ? Contribution This r and omized trial evaluated the effect of further testing after negative d-dimer test results in patients with low pretest probability ( group A ) or moderate or high pretest probability ( group B ) of PE . At 6 months , 0 of 182 ( group A ) and 1 of 41 ( group B ) patients with no further testing had had symptomatic venous thromboembolism , compared with 1 of 185 ( group A ) and 0 of 41 ( group B ) patients with further testing . Caution s Few moderate- or high-probability patients were studied . Implication s Additional diagnostic testing seems unnecessary in patients with low pretest probability of PE and negative d-dimer test results . The Editors d-Dimer is a fibrin-derived fragment that is released into the circulation when cross-linked fibrin is broken down by the fibrinolytic system ( 1 , 2 ) . Because elevated levels of d-dimer are common in patients with venous thromboembolism , negative d-dimer test results can help to exclude pulmonary embolism ( 2 - 9 ) . In a previous cohort study ( 6 ) , we showed that negative erythrocyte agglutination d-dimer test results had the potential to exclude pulmonary embolism in 2 subgroups of patients : those with a low clinical probability of embolism and those with a moderate or high clinical probability of embolism who had nondiagnostic ventilationperfusion lung scan and no proximal deep venous thrombosis on venous ultrasonography . However , management decisions were not made on the basis of d-dimer test results in the earlier study . Several subsequent management studies also supported the safety of withholding anticoagulant therapy and additional diagnostic testing in patients with a low clinical suspicion of pulmonary embolism who have negative erythrocyte agglutination d-dimer test results ( 2 , 4 , 7 , 10 ) . However , to our knowledge , the safety of using negative d-dimer test results to exclude pulmonary embolism has never been compared with additional diagnostic testing in a r and omized , controlled trial ( 11 ) . Consequently , we studied 2 subgroups of patients with suspected pulmonary embolism and negative erythrocyte agglutination test results : patients with a low clinical probability of pulmonary embolism and those with a moderate or high clinical probability of pulmonary embolism who had a nondiagnostic ventilationperfusion lung scan and no proximal deep venous thrombosis on venous ultrasonography . Our goal was to test the hypothesis that patients with negative d-dimer test results who do not undergo further testing for pulmonary embolism will not have a higher frequency of venous thromboembolism during follow-up than patients who receive usual diagnostic testing and management . Methods Patients In patients and out patients with suspected pulmonary embolism who were referred to the thrombosis service of 7 university-affiliated hospitals were prospect ively assessed for enrollment ( Figure 1 ) . The referring physicians included primary care physicians , general internists , surgeons , and emergency department physicians . Patients were excluded if they had undergone ventilationperfusion lung scan or venous ultrasonography , had received full-dose heparin therapy for more than 24 hours or long-term warfarin therapy , had a comorbid condition that limited their expected survival to less than 3 months , had a contraindication to radiographic contrast , or were asymptomatic within 7 days of presentation . Pregnant women were excluded , as were individuals who resided in a location where they could not access follow-up . Some patients were also excluded because their physicians considered them to be inappropriate c and i date s for the study ( for example , they were scheduled to have surgery ) . The institutional review boards of all participating centers approved the study , and patients provided written informed consent . Figure 1 . Study flow diagram . Clinical Assessment Before any diagnostic testing was performed , a physician or nurse from the thrombosis service used the Wells 7-item prediction rule ( 12 ) to categorize the patient 's clinical probability of pulmonary embolism as either low or moderate to high ( Table 1 ) . The clinician was not allowed to assign a clinical probability that differed from the prediction rule . Table 1 . Clinical Model for Predicting the Pretest Probability of Pulmonary Embolism  Patients with Low Clinical Probability of Pulmonary Embolism  d-Dimer testing with the SimpliRED assay ( Agen Biomedical Ltd. , Brisbane , Australia ) was performed on all patients with a low clinical probability of pulmonary embolism ( Figure 2 ) . With this qualitative red cell agglutination assay , a drop of whole blood obtained from a venipuncture or finger stick is mixed for 2 minutes with a test reagent that contains a bivalent antibody that binds to both d-dimer and erythrocyte membranes . In the presence of elevated d-dimer levels , the test reagent induces agglutination of erythrocytes . Any agglutination is considered a positive result and no agglutination is considered a negative result . Figure 2 . Diagnostic algorithm and patient outcomes for patients with a low clinical probability of pulmonary embolism . Patients with negative d-dimer test results were r and omly assigned to 1 ) receive no additional diagnostic testing and no treatment with anticoagulant therapy or 2 ) undergo additional diagnostic testing , starting with a ventilationperfusion lung scan ( Figure 2 ) . If the lung scan showed no abnormalities , pulmonary embolism was excluded ; if there were 1 or more segmental perfusion defects that were normally ventilated , the scan was considered diagnostic for pulmonary embolism ( high-probability scan ) ; and if there were perfusion defects that did not meet criteria for a high-probability scan , the scan was considered nondiagnostic . Patients with nondiagnostic lung scans underwent bilateral ultrasonography of the proximal veins of the legs .  The sole criterion for diagnosis of deep venous thrombosis was inability to fully compress the lumen of the deep veins with application of ultrasonography probe pressure anywhere from the common femoral vein to the calf vein trifurcation ( 13 ) ; if deep venous thrombosis was present , pulmonary embolism was diagnosed . If ultrasonography results were normal , the test was repeated after 7 and 14 days ( serial ultrasonography ) ; anticoagulant therapy was only given if deep venous thrombosis developed . A ventilationperfusion lung scan was performed on all patients with positive d-dimer test results . Results of the lung scan dictated subsequent management , as previously described ( Figure 2 ) . Patients with Moderate or High Clinical Probability of Pulmonary Embolism A ventilationperfusion lung scan was performed on all patients with a moderate or high clinical probability of pulmonary embolism ; the lung scan findings determined subsequent management , as previously described ( Figure 3 ) . Patients with a nondiagnostic lung scan , normal bilateral venous ultrasonography results , and negative d-dimer test results were r and omly assigned to receive either no additional diagnostic testing or serial ultrasonography ( Figure 3 ) . Figure 3 . Diagnostic algorithm and outcomes for patients with a moderate or high probability of pulmonary embolism . R and omization Protocol A biostatistician used a computer program to generate separate r and omization sequences , equal in proportion and stratified by clinical center , for each of the 2 eligible groups of patients . Allocations were concealed in consecutively numbered , sealed , opaque envelopes that were distributed to each of the clinical centers . Patients opened the next consecutively numbered envelope at that clinical center to determine their group allocation ; this allocation group could not be changed by opening another envelope . Follow-up and Outcome Measures All enrolled patients , including those who did not undergo r and omization , were followed for 6 months to determine if venous thromboembolism developed after initial diagnostic testing . In addition , patients were alerted to the symptoms of deep venous thrombosis and pulmonary embolism and were advised to return to the hospital immediately if any of these symptoms developed . In patients with suspected deep venous thrombosis , venography or compression ultrasonography of the proximal deep veins was performed . Ultrasonography was repeated if the initial results were normal ( 13 ) . In patients with suspected pulmonary embolism , a ventilationperfusion lung scan was performed . If the lung scan was nondiagnostic , the patient underwent compression ultrasonography of the proximal deep veins or pulmonary angiography ( 5 ) . d-Dimer testing was not used to evaluate suspected venous thromboembolism during follow-up . In patients who died , pulmonary embolism was reported as the cause of death if there was substantive evidence or if the death was sudden and of uncertain cause . Among patients who were r and omly assigned , episodes of bleeding and deaths were evaluated as secondary outcomes . Study personnel who performed routine and unscheduled follow-up assessment s were not precluded from knowing initial test results or r and omization group assignments . A central adjudication committee review ed information regarding all suspected outcome events ; members of this committee were unaware of test results at enrollment or patients ' group assignments . Subject to availability , data provided to this committee included case report forms , clinic notes , original investigations ( for example , lung scans and venography ) , interpreted reports of original investigations , and autopsy reports . Statistical Analysis Among each r and omized group of patients with a low clinical probability for pulmonary embolism and a negative d-dimer result , the 95 % CIs around the observed proportion of patients who had symptomatic venous thromboembolism during follow-up should be narrow ( that is , 2 % ) . We used this requirement as the basis CONTEXT Previous studies have evaluated the safety of relatively complex combinations of clinical decision rules and diagnostic tests in patients with suspected pulmonary embolism . OBJECTIVE To assess the clinical effectiveness of a simplified algorithm using a dichotomized clinical decision rule , D-dimer testing , and computed tomography ( CT ) in patients with suspected pulmonary embolism . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of consecutive patients with clinical ly suspected acute pulmonary embolism , conducted in 12 centers in the Netherl and s from November 2002 through December 2004 . The study population of 3306 patients included 82 % out patients and 57 % women . INTERVENTIONS Patients were categorized as " pulmonary embolism unlikely " or " pulmonary embolism likely " using a dichotomized version of the Wells clinical decision rule . Patients classified as unlikely had D-dimer testing , and pulmonary embolism was considered excluded if the D-dimer test result was normal . All other patients underwent CT , and pulmonary embolism was considered present or excluded based on the results . Anticoagulants were withheld from patients classified as excluded , and all patients were followed up for 3 months . MAIN OUTCOME MEASURE Symptomatic or fatal venous thromboembolism ( VTE ) during 3-month follow-up . RESULTS Pulmonary embolism was classified as unlikely in 2206 patients ( 66.7 % ) . The combination of pulmonary embolism unlikely and a normal D-dimer test result occurred in 1057 patients ( 32.0 % ) , of whom 1028 were not treated with anticoagulants ; subsequent nonfatal VTE occurred in 5 patients ( 0.5 % [ 95 % confidence interval { CI } , 0.2%-1.1 % ] ) . Computed tomography showed pulmonary embolism in 674 patients ( 20.4 % ) . Computed tomography excluded pulmonary embolism in 1505 patients , of whom 1436 patients were not treated with anticoagulants ; in these patients the 3-month incidence of VTE was 1.3 % ( 95 % CI , 0.7%-2.0 % ) . Pulmonary embolism was considered a possible cause of death in 7 patients after a negative CT scan ( 0.5 % [ 95 % CI , 0.2%-1.0 % ] ) . The algorithm was completed and allowed a management decision in 97.9 % of patients . CONCLUSIONS A diagnostic management strategy using a simple clinical decision rule , D-dimer testing , and CT is effective in the evaluation and management of patients with clinical ly suspected pulmonary embolism . Its use is associated with low risk for subsequent fatal and nonfatal VTE BACKGROUND Clinicians frequently use their experience to determine the pretest probability of pulmonary embolism ( PE ) , although scoring systems are promoted as being more reliable . The Canadian Pulmonary Embolism Score ( CPES ) combines six objective questions and one subjective question . The CPES has been vali date d and appears to be useful for risk-stratifying patients . However , research suggests that subjective gestalt performs similarly to the CPES , and the influence of the subjective question on the predictive value of the CPES is not clear . OBJECTIVES To determine the test characteristics of the CPES , its subjective question , and the degree to which the predictive value of the CPES is influenced by its individual questions . METHODS The authors performed a prospect i ve observational study on a cohort of emergency department patients suspected of having PE . The authors compared patients ' CPES  results with the diagnosis of PE , calculated the test characteristics of the  CPES  , and determined the contribution of individual CPES questions to the score 's overall predictive value . RESULTS Of 607 patients , 61 ( 10 % ) had PE . Of low-risk patients ( CPES < or = 4 ) , 5.54 % ( n = 449 ; 95 % confidence interval [ 95 % CI ] = 3.64 % to 8.11 % ) had PE . The sensitivity ( 59.0 % ; 95 % CI = 47.4 % to 69.8 % 
    Output:
    
Combining a decision rule or gestalt with d-dimer testing seemed safe for all strategies , except when the less-sensitive Wells rule ( cutoff value ≤4 ) was combined with less-sensitive qualitative d-dimer testing .
CONCLUSION Clinical decision rules and gestalt  can safely exclude PE when combined with sensitive d-dimer testing .