Clinical Prediction

Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000 Mar;83(3):416-20.

“The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE."[/blockquote][/x_tab][x_tab active="false"]Geersing GJ, Erkens PM, Lucassen WA, et al. Safe exclusion of pulmonary embolism using the Wells rule and qualitative D-dimer testing in primary care: prospective cohort study. BMJ. 2012 Oct 4;345:e6564.

Geersing GJ, Erkens PM, Lucassen WA, et al.

“Pulmonary embolism can be safely excluded on the basis of a Wells score of ≤4 combined with a negative qualitative point of care D-dimer test result. Using a threshold of [less than] 2 is even safer.”Wells PS, Anderson DR, Rodger M, et al.

Venkatesh AK, Kline JA, Courtney DM, et al. Evaluation of pulmonary embolism in the emergency department and consistency with a national quality measure: quantifying the opportunity for improvement. Arch Intern Med. 2012 Jul 9;172(13):1028-32.

“In summary, we found that one-third of ED imaging studies for suspected PE are potentially avoidable. The opportunity for improving the efficiency of imaging for suspected PE is large. Future work should focus on interventions to close this performance gap.”Venkatesh AK, Kline JA, Courtney DM, et al.

Kline JA, Hogg MM, Courtney DM, et al. D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography. J Thromb Haemost. 2012 Apr;10(4):572-81.

“In conclusion, a screening strategy that doubles the threshold for an abnormal D-dimer concentration for patients over age 70 or patients with a Wells score ≤4 or an RGS ≤6 could significantly reduce the rate of CTPA with no net increase in the rate of missing larger than subsegmental PE and no increase the rate of missed pneumonia.”Kline JA, Hogg MM, Courtney DM, et al.

Warren DJ, Matthews S. Pulmonary embolism: investigation of the clinically assessed intermediate risk subgroup. Br J Radiol. 2012 Jan;85(1009):37-43.

“We demonstrate the high sensitivity and negative predictive power of the [plasma d-Dimer] tests in conjunction with the Wells PTP tool, with no demonstrable difference between exclusion in the intermediate subgroup and the retrospectively dichotomised PE unlikely group. Dichotomisation of the Wells scoring system further simplifies the pre-test risk stratification and permits safe exclusion of more patients from additional imaging assessment than the traditional simplified Wells criteria, with resultant beneficial financial and resource implications.”Warren DJ, Matthews S.

Miniati M, Cenci C, Monti S, Poli D. Clinical presentation of acute pulmonary embolism: survey of 800 cases. PLoS One. 2012;7(2):e30891.

“In summary, we found that the most reliable indicator of patients with PE is sudden onset dyspnea. Other symptoms include chest pain, fainting (or syncope), and hemoptysis. The occurrence of such symptoms, if not explained otherwise, should alert the clinicians to consider PE in differential diagnosis. This is the crucial step in the diagnostic work-up of PE. Next, the clinical probability should be assessed, ideally by means of a validated prediction model. If the clinical probability is low (20% or less), the most practical approach would be to measure the D-dimer concentration by a quantitative assay. If the D-dimer test is negative, PE can be safely ruled out; if positive, additional investigation is required. Should the clinical probability of PE be other than low, it would be sound to order immediately an appropriate imaging technique (multidetector CTA, or lung scintigraphy) to confirm or exclude the diagnosis.”Miniati M, Cenci C, Monti S, Poli D.

Lucassen W, Geersing GJ, Erkens PM, et al. Clinical decision rules for excluding pulmonary embolism: a meta-analysis. Ann Intern Med. 2011 Oct 4;155(7):448-60.

“Clinical decision rules and gestalt can safely exclude PE when combined with sensitive d-dimer testing. The authors recommend standardized rules because gestalt has lower specificity, but the choice of a particular rule and d-dimer test depend on both prevalence and setting.”Lucassen W, Geersing GJ, Erkens PM, et al.

Douma RA, Mos IC, Erkens PM, Nizet TA, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med. 2011 Jun 7;154(11):709-18.

“All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal d-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice.”Douma RA, Mos IC, Erkens PM, Nizet TA, et al.

Ceriani E, Combescure C, Le Gal G, et al. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost. 2010 May;8(5):957-70.

“Available CPR for assessing clinical probability of PE show similar accuracy. Existing scores are, however, not equivalent and the choice among various prediction rules and classification schemes (three- versus two-level) must be guided by local prevalence of PE, type of patients considered (outpatients or inpatients) and type of D-dimer assay applied.”Ceriani E, Combescure C, Le Gal G, et al.

Courtney DM, Kline JA, Kabrhel C, et al. Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: results of a prospective, multicenter study. Ann Emerg Med. 2010 Apr;55(4):307-315.e1.

“In this large sample of symptomatic ED patients tested for PE, several clinical characteristics that are not part of existing prediction rules were identified as significantly associated with the outcome of PE or DVT within 45 days. These included patient history of thrombophilic condition, pleuritic chest pain, and family history of VTE. Predictors from existing pretest probability scoring systems that were validated here as strongly associated with the outcome of VTE included: history of past PE or DVT, unilateral leg swelling, surgery within the past 4 weeks requiring general anesthesia, estrogen use, oxygen saturation of less than 95%, and active or metastatic malignancy. Future decision rules for PE should include these variables and clinicians who use an unstructured approach should use these variables accordingly to help them estimate the pretest probability of PE.”Courtney DM, Kline JA, Kabrhel C, et al.

Bahloul M, Chaari A, Kallel H, et al. Pulmonary embolism in intensive care unit: Predictive factors, clinical manifestations and outcome. Ann Thorac Med. 2010 Apr;5(2):97-103.

“In our study, estimates of the clinical probability of PE was performed in all patients according to two scoring systems, which have been tested prospectively and validated in large clinical trials: the Wells’ score and the Geneva revised score. These scores may be used to define the probability of PE as low, moderate or high with the prevalence of PE increasing across the three groups. However, in our study according to these scores, only 5 (5.7%) patients have a high probability according to the Wells’ score and 6 (6.9%) patients have a high probability according to the Geneva revised score.”Bahloul M, Chaari A, Kallel H, et al.

Douma RA, le Gal G, Söhne M, et al. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. BMJ. 2010 Mar 30;340:c1475.

“The study shows that an age adjusted cut-off level for the D-dimer test for exclusion of pulmonary embolism doubles the proportion of older patients ([greater than] 70 years) in whom pulmonary embolism can be safely excluded in comparison with the conventional cut-off value of 500 μg/l. We derived and validated this new cut-off value in three large cohorts of consecutive patients with suspected pulmonary embolism, totalling over 5000 patients. In these three cohorts, the number of older patients in which pulmonary embolism could be safely ruled out was consistent, between 25% and 30%.”Douma RA, le Gal G, Söhne M, et al.

Douma RA, Gibson NS, Gerdes VE, et al. Validity and clinical utility of the simplified Wells rule for assessing clinical probability for the exclusion of pulmonary embolism. Thromb Haemost. 2009 Jan;101(1):197-200.

“In this external retrospective validation study, the simplified Wells rule appeared to be safe and clinically useful, although prospective validation remains necessary. Simplification of the Wells rule may enhance the applicability.”Douma RA, Gibson NS, Gerdes VE, et al.

Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315.

“In summary, clinical evaluation makes it possible to classify patients into probability categories corresponding to an increasing prevalence of PE, whether assessed by implicit clinical judgement or by a validated prediction rule.”Torbicki A, Perrier A, Konstantinides S, et al.

Gibson NS, Sohne M, Kruip MJ, et al. Further validation and simplification of the Wells clinical decision rule in pulmonary embolism. Thromb Haemost. 2008 Jan;99(1):229-34.

“The venous thromboembolism incidence at three months in the group of patients with a Wells score [≤]4 and a normal D-dimer was 0.5%, versus 0.3% with a modified rule and 0.5% with a simplified rule. The proportion of patients safely excluded for PE was 32%, versus 31% and 30%, respectively. This study further validates the diagnostic utility of the Wells rule and indicates that the scoring system can be simplified to one point for each variable.”Gibson NS, Sohne M, Kruip MJ, et al.

Qaseem A, Snow V, Barry P, et al. Current Diagnosis of Venous Thromboembolism in Primary Care: A Clinical Practice Guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Fam Med. 2007 Jan; 5(1): 57–62.

“Strong evidence supports the use of clinical prediction rules to establish pretest probability of [Venous Thromboembolism (VTE)] before further testing. Use of a high-sensitivity D-dimer assay in patients who have a low pretest probability of VTE has a high negative predictive value; it is highest for younger patients with low pretest probability, no associated comorbidity or previous DVT, and a short duration of symptoms.”Qaseem A, Snow V, Barry P, et al.

Kearon C, Ginsberg JS, Douketis J, et al. An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial. Ann Intern Med. 2006 Jun 6;144(11):812-21.

“We conclude that pulmonary embolism can be excluded in patients who have a low clinical probability of pulmonary embolism and negative erythrocyte agglutination d-dimer test results and that further diagnostic testing is not beneficial to this population. These findings are present in approximately 50% of outpatients and 20% of inpatients with suspected pulmonary embolism.”Kearon C, Ginsberg JS, Douketis J, et al.

Hogg K, Dawson D, Mackway-Jones K. Outpatient diagnosis of pulmonary embolism: the MIOPED (Manchester Investigation Of Pulmonary Embolism Diagnosis) study. Emerg Med J. 2006 Feb; 23(2): 123–127.

“The MIOPED study is the first study to propose this unique combination of D‐dimer, clinical probability, ventilation‐perfusion scanning, CT pulmonary angiography, and digital subtraction angiography. …The MIOPED study has verified that an outpatient diagnostic protocol can safely exclude pulmonary embolism in patients presenting to the emergency department with pleuritic chest pain.”Hogg K, Dawson D, Mackway-Jones K.

van Belle A, Buller HR, Huisman MV, et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-9.

“In conclusion, a diagnostic management strategy using a simple clinical decision rule, D-dimer testing, and CT is as effective as other more complex diagnostic strategies in the evaluation and management of patients with clinically suspected pulmonary embolism. Its use is associated with low risk for subsequent fatal and nonfatal VTE.”van Belle A, Buller HR, Huisman MV, et al.

Anderson DR, Kovacs MJ, Dennie C, et al. Use of spiral computed tomography contrast angiography and ultrasonography to exclude the diagnosis of pulmonary embolism in the emergency department. J Emerg Med. 2005 Nov;29(4):399-404.

“Three-hundred sixty-nine (369) patients had low pretest probability and negative D-dimer results and no further diagnostic tests were performed. None of these patients subsequently developed venous thromboembolic complications (0%, 95% confidence interval [CI] 0% to 1.0%).”Anderson DR, Kovacs MJ, Dennie C, et al.

Runyon MS, Webb WB, Jones AE, Kline JA. Comparison of the unstructured clinician estimate of pretest probability for pulmonary embolism to the Canadian score and the Charlotte rule: a prospective observational study. Acad Emerg Med. 2005 Jul;12(7):587-93.

“We found the unstructured clinician estimate to compare favorably with the Canadian [(Wells)] score and the Charlotte rule for the estimation of low pretest probability for PE. Interobserver agreement was moderate for the unstructured estimate. These findings warrant study in a multicenter trial to assess their external validity.”Runyon MS, Webb WB, Jones AE, Kline JA.

Söhne M, Kamphuisen PW, van Mierlo PJ, Büller HR. Diagnostic strategy using a modified clinical decision rule and D-dimer test to rule out pulmonary embolism in elderly in- and outpatients. Thromb Haemost. 2005 Jul;94(1):206-10.

“In elderly outpatients the combination of a non-high CDR and a normal d-dimer result is a safe strategy to rule out pulmonary embolism. However, in inpatients this algorithm is not reliable to safely exclude pulmonary embolism. In addition, the proportion of patients [greater than] 65 years in which this strategy excludes pulmonary embolism is markedly lower compared to younger patients.”Söhne M, Kamphuisen PW, van Mierlo PJ, Büller HR.

Rodger MA, Maser E, Stiell I, et al. The interobserver reliability of pretest probability assessment in patients with suspected pulmonary embolism. Thromb Res. 2005;116(2):101-7.

“In conclusion, given the inadequate interobserver reliability of pretest probability assessment by overall impression (or gestalt), physicians should use explicit clinical models in the diagnostic management of patients with suspected pulmonary embolism. Research efforts must continue to develop simple, objective, and reliable tools (e.g., methodologically valid clinical prediction rules) to assist clinicians in a wide variety of clinical settings to accurately and reliably assign pretest probability in patients with suspected PE.”Rodger MA, Maser E, Stiell I, et al.

Wolf SJ, McCubbin TR, Feldhaus KM, et al. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med. 2004 Nov;44(5):503-10.

“In summary, we conclude that Wells Criteria appears to have a moderate to substantial interrater reliability, affording emergency medicine care providers with a reproducible means of determining pretest probability among ED patients for whom the diagnosis of pulmonary embolism is being considered.”Wolf SJ, McCubbin TR, Feldhaus KM, et al.

Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001 Jul 17;135(2):98-107.

“Our study represents an advance over previous studies that used diagnostic algorithms. We demonstrated that by combining consideration of pretest clinical probability, which was determined according to a clinical model, and results on the SimpliRED d-dimer test, pulmonary embolism can be diagnosed or ruled out safely, with a dramatic reduction in the need for imaging procedures. …If adopted, the application of our bedside method in emergency department patients may save health care resources, reduce inconvenience to patients, and limit risks to patients by averting unnecessary presumptive treatment and further diagnostic testing.”Wells PS, Anderson DR, Rodger M, et al.