Performance of the 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) in the diagnostic management of pulmonary embolism:An external validation study

Background: The recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE). Aim: To externally validate the performance of 4PEPS in an independent cohort. Methods: In this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer &lt;1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold. Results: Of the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80–0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57–60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86–1.9). Conclusion: In this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study.</p

Current practice patterns of outpatient management of acute pulmonary embolism: A post-hoc analysis of the YEARS study

Background: Studies have shown the safety of home treatment of patients with pulmonary embolism (PE) at low risk of adverse events. Management studies focusing on home treatment have suggested that 30% to 55% of acute PE patients could be treated at home, based on the HESTIA criteria, but data from day-to-day clinical practice are largely unavailable. Aim: To determine current practice patterns of home treatment of acute PE in the Netherlands. Method: We performed a post-hoc analysis of the YEARS study. The main outcomes were the proportion of patients who were discharged <24 h and reasons for admission if treated in hospital. Further, we compared the 3-month incidence of PE-related unscheduled readmissions between patients treated at home and in hospital. Results: Of the 404 outpatients with PE included in this post-hoc analysis of the YEARS study, 184 (46%) were treated at home. The median duration of admission of the hospitalized patients was 3.0 days. The rate of PE-related readmissions of patients treated at home was 9.7% versus 8.6% for hospitalized patients (crude hazard ratio 1.1 (95% CI 0.57–2.1)). The 3-month incidence of any adverse event was 3.8% in those treated at home (2 recurrent VTE, 3 major bleedings and two deaths) compared to 10% in the hospitalized patients (3 recurrent VTE, 6 major bleedings and fourteen deaths). Conclusions: In the YEARS study, 46% of patients with PE were treated at home with low incidence of adverse events. PE-related readmission rates were not different between patients treated at home or in hospital

Treatment Patterns of Cancer-associated Thrombosis in the Netherlands: The Four Cities Study

Background Current guidelines recommend either low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) as first-line treatment in cancer-associated venous thromboembolism (VTE)

Use of the National Early Warning Score for predicting deterioration of patients with acute pulmonary embolism: a post-hoc analysis of the YEARS Study

Background The Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning Score (NEWS) is a general prognostic risk score for multiple clinical settings. We investigated whether the NEWS had a comparable performance with the PESI and sPESI, for predicting intensive care unit (ICU) admission and death in patients with acute PE. Methods In haemodynamically stable patients with confirmed PE from the YEARS Study (2013-2015), we evaluated the performance of the NEWS, PESI and sPESI for predicting 7-day ICU admission and 30-day mortality. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. Results Of 352 patients, 12 (3.4%) were admitted to the ICU and 5 (1.4%) died. The AUC of the NEWS for ICU admission was 0.80 (95% CI 0.66 to 0.94) and 0.92 (95% CI 0.82 to 1.00) for 30-day mortality. At a threshold of 3 points, NEWS yielded a sensitivity and specificity of 92% and 53% for ICU admission and 100% and 52% for 30-day mortality. The AUC of the PESI was 0.64 (95% CI 0.48 to 0.79) for ICU admission and 0.94 (95% CI 0.87 to 1.00) for mortality. At a threshold of 66 points, PESI yielded a sensitivity of 75% and a specificity of 38% for ICU admission. For mortality, these were 100% and 37%, respectively. The performance of the sPESI was similar to that of PESI. Conclusion In comparison with PESI and sPESI, NEWS adequately predicted 7-day ICU admission as well as 30-day mortality, supporting its potential relevance for clinical practice

Home Treatment Compared to Initial Hospitalization in Normotensive Patients with Acute Pulmonary Embolism in the Netherlands: A Cost Analysis

Background Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking. Aim The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized. Methods Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital. Results Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home (n = 181) and 4.3 days for those initially treated in hospital (n = 202). Total average costs per hospitalized patient were €3,209 and €1,512 per patient treated at home. The adjusted mean difference was €1,483 (95% confidence interval: €1,181-1,784). Conclusion Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of €1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients

Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis

The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) is challenging, because persistent intravascular abnormalities after previous DVT often hinder a diagnosis by compression ultrasonography. Magnetic resonance direct thrombus imaging (MRDTI), a technique without intravenous contrast and with a 10-minute acquisition time, has been shown to accurately distinguish acute recurrent DVT from chronic thrombotic remains. We have evaluated the safety of MRDTI as the sole test for excluding recurrent ipsilateral DVT. The Theia Study was a prospective, international, multicenter, diagnostic management study involving patients with clinically suspected acute recurrent ipsilateral DVT. Treatment of the patients was managed according to the result of the MRDTI, performed within 24 hours of study inclusion. The primary outcome was the 3-month incidence of venous thromboembolism (VTE) after a MRDTI negative for DVT. The secondary outcome was the interobserver agreement on the MRDTI readings. An independent committee adjudicated all end points. Three hundred five patients were included. The baseline prevalence of recurrent DVT was 38%; superficial thrombophlebitis was diagnosed in 4.6%. The primary outcome occurred in 2 of 119 (1.7%; 95% confidence interval [CI], 0.20-5.9) patients with MRDTI negative for DVT and thrombophlebitis, who were not treated with any anticoagulant during follow-up; neither of these recurrences was fatal. The incidence of recurrent VTE in all patients with MRDTI negative for DVT was 1.1% (95% CI, 0.13%-3.8%). The agreement between initial local and post hoc central reading of the MRDTI images was excellent (κ statistic, 0.91). The incidence of VTE recurrence after negative MRDTI was low, and MRDTI proved to be a feasible and reproducible diagnostic test. This trial was registered at www.clinicaltrials.gov as #NCT02262052

Non-invasive diagnostic work-up patients with clinically suspected pulmonary embolism; results of a management study

Background: Clinicians often deviate from the recommended algorithm for the diagnosis of pulmonary embolism consisting of ventilation-perfusion scintigraphy and pulmonary angiography. Objectives: To assess the safety and feasibility of a diagnostic algorithm which reduces the need for lung scintigraphy and avoids the use of angiography. Patients and methods: Consecutive patients with a clinical suspicion of pulmonary embolism were prospectively investigated according to an algorithm in which the diagnosis of pulmonary embolism was excluded after a low clinical probability estimate and a normal D-dimer test result, a normal perfusion scintigraphy result, or a non-high probability scintigraphy result in combination with normal serial ultrasonography of the legs. In these patients anticoagulant treatment was withheld and they were followed up for 3 months to record possible thromboembolic events. During the study period, 923 consecutive patients were seen, of whom 292 were excluded because of predefined criteria. Results: Of the 631 included patients, the diagnosis was refuted on the basis of a low clinical probability estimate and a normal D-dimer test result (95 patients), normal perfusion scintigraphy (161 patients) and non-high probability lung scintigraphy followed by normal serial ultrasonography (210 patients). Of these 466 patients, venous thromboembolic complications during follow-up occurred in six (complication rate 1.3%, 95% confidence interval 0.5, 2.8). The diagnostic protocol was completed in 92% of all included patients. Conclusion: The diagnosis of pulmonary embolism can be safely ruled out by a non-invasive algorithm consisting of D-dimer testing combined with a clinical probability estimate, lung scintigraphy, or serial ultrasonography of the legs (in case of non-diagnostic lung scintigraphy)

Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism

Acute pulmonary embolism is one of the leading causes of maternal death, with the overall incidence reported to be 1.72 cases per 1000 deliveries, accounting for approximately 1 death in every 100,000 deliveries. Since the D-dimer test has low specificity and sensitivity, it is common for pregnant women with suspected pulmonary embolism to undergo computed tomography (CT) pulmonary angiography or ventilation-perfusion (V/Q) scanning, both of which involve radiation exposure to the mother and fetus. It is unknown whether a pregnancy-adapted clinical screening algorithm could be used to safely avoid diagnostic imaging in a subset of pregnant women with suspected pulmonary embolism. The researchers performed a multicenter, international, prospective study of pregnant women with suspected pulmonary embolism. They assessed 3 criteria from the YEARS algorithm (clinical signs of deep vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the D-dimer level as components of the screening algorithm. Pulmonary embolism was ruled out if none of the 3 criteria were met and the D-dimer level was less than 1000 ng/mL, or if 1 or more of the 3 criteria were met and the D-dimer level was less than 500 ng/mL. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep vein thrombosis; if the results were positive (ie, a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out by screening criteria underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism (VTE) at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval, 0.0%–1.2%); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% confidence interval, 35%–44%). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. The researchers concluded that the pregnancy-adapted YEARS diagnostic algorithm safely ruled out acute pulmonary embolism in pregnant patients who were referred for suspected pulmonary embolism. Using this approach, they found that the main advantage was that CT pulmonary angiography was averted in 32% to 65% of the patients, depending on the trimester of presentation, without compromising safety

Cost-Effectiveness of Performing Reference Ultrasonography in Patients with Deep Vein Thrombosis

Background The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison. Objectives To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients. Methods Patient-level data (n = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared. Results All six scenarios including reference CUS had higher estimated 1-year costs ( 1,763 1,913) than the six without reference CUS ( 1,192 1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8 17.9 per 10,000 patients) and without reference CUS (14.0 18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS. Conclusion One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS