N. van Es

The original and simplified Wells rules and age-adjusted D-dimer testing to rule out pulmonary embolism: an individual patient data meta-analysis

Essentials Evidence for the simplified Wells rule in ruling out acute pulmonary embolism (PE) is scarce. This was a post‐hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The simplified Wells rule combined with age‐adjusted D‐dimer testing may safely rule out PE. Given its ease of use, the simplified Wells rule is to be preferred over the original Wells rule.

Current management strategies and long-term clinical outcomes of upper extremity venous thrombosis.

Essentials Few data exist on outcome of upper extremity deep and superficial vein thrombosis (UEDVT and UESVT). We followed 102 and 55 patients with UEDVT or UESVT, respectively, for a median of 3.5 years. Risk of recurrent venous thromboembolism was low in both diseases, and the mortality high. Postthrombotic symptoms were infrequent and cancer patients had a higher risk of recurrent VTE.

Is a normal computed tomography pulmonary angiography safe to rule out acute pulmonary embolism in patients with a likely clinical probability

A normal computed tomography pulmonary angiography (CTPA) remains a controversial criterion for ruling out acute pulmonary embolism (PE) in patients with a likely clinical probability. We set out to determine the risk of VTE and fatal PE after a normal CTPA in this patient category and compare these risk to those after a normal pulmonary angiogram of 1.7 % (95 %CI 1.0-2.7 %) and 0.3 % (95 %CI 0.02-0.7 %). A patient-level meta-analysis from 4 prospective diagnostic management studies that sequentially applied the Wells rule, D-dimer tests and CTPA to consecutive patients with clinically suspected acute PE. The primary outcome was the 3-month VTE incidence after a normal CTPA. A total of 6,148 patients were included with an overall PE prevalence of 24 %. The 3-month VTE incidence in all 4,421 patients in whom PE was excluded at baseline was 1.2 % (95 %CI 0.48-2.6) and the risk of fatal PE was 0.11 % (95 %CI 0.02-0.70). In patients with a likely clinical probability the 3-month incidences of VTE and fatal PE were 2.0 % (95 %CI 1.0-4.1 %) and 0.48 % (95 %CI 0.20-1.1 %) after a normal CTPA. The 3-month incidence of VTE was 6.3 % (95 %CI 3.0-12) in patients with a Wells rule >6 points. In conclusion, this study suggests that a normal CTPA may be considered as a valid diagnostic criterion to rule out PE in the majority of patients with a likely clinical probability, although the risk of VTE is higher in subgroups such as patients with a Wells rule >6 points for which a closer follow-up should be considered.

Is stand-alone D-dimer testing safe to rule out acute pulmonary embolism?

Essentials A stand‐alone D‐dimer below 750 μg/L has been proposed to rule out acute pulmonary embolism (PE). This was a post‐hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The negative predictive value of a D‐dimer <750 μg/L ranged from 79% to 96% in various subgroups. Stand‐alone D‐dimer testing seems to be unsafe to rule out PE in all patients.

Improving the diagnostic management of upper extremity deep vein thrombosis.

Essentials The Constans score and D‐dimer can rule out upper extremity deep vein thrombosis without imaging. We evaluated the performance of an extended Constans score and an age‐adjusted D‐dimer threshold. The extended Constans score did not increase the efficiency compared to the original score. Age‐adjusted D‐dimer testing safely increased the efficiency by 4%, but this needs validation.

Sex-specific performance of pre-imaging diagnostic algorithms for pulmonary embolism

Essentials Decision rules for pulmonary embolism are used indiscriminately despite possible sex‐differences. Various pre‐imaging diagnostic algorithms have been investigated in several prospective studies. When analysed at an individual patient data level the algorithms perform similarly in both sexes. Estrogen use and male sex were associated with a higher prevalence in suspected pulmonary embolism.

Incidental pulmonary embolism in cancer patients: Interobserver agreement on the diagnosis and extent with a focus on distal clots.

BACKGROUND The incidence of incidental pulmonary embolism (IPE) in cancer patients is increasing. There is scant information on the interobserver agreement among radiologists about the diagnosis of distal incidental clots and the actual radiologic extension of IPE. METHODS A total of 88 contrast-enhanced computed tomography (CT) scans of cancer patients with IPE were reassessed blindly by two expert thoracic radiologists. First, 62 scans were reassessed and the interobserver agreement on most proximal extent of IPE was calculated between the two expert radiologists as well as between the initial and expert reading, using the kappa statistic. The sample was enriched with 26 additional scans for a total of 30 segmental and 29 subsegmental IPE to determine the interobserver agreement on distal clots. RESULTS The level of agreement regarding the most proximal extent of IPE between the expert radiologists was very good (kappa 0.84; 95% CI, 0.73-0.95) and poor between the original radiologist and expert radiologists (kappa 0.39; 95% CI, 0.22-0.56). In the patients with segmental or subsegmental IPE on initial reading, the expert radiologists agreed with the segmental location in 12 out of 30 patients (40%) and with the subsegmental location in 17 out of 29 patients (59%). The interobserver agreement between the expert radiologists was good (kappa 0.68; 95% CI, 0.46-0.90) and moderate (kappa 0.48; 95% CI, 0.25-0.71), respectively. CONCLUSIONS While the interobserver agreement between radiologists on the most proximal location of IPE in cancer patients appears to be fairly good, it decreases significantly for more distally located incidental clots.

Questioning the use of an age-adjusted D-dimer threshold to exclude venous thromboembolism: comment

D-dimer testing is a cornerstone of the diagnostic management of deep vein thrombosis (DVT) and pulmonary embolism (PE). Over the past decade, the threshold used to exclude venous thromboembolism (VTE) has transitioned from a fixed threshold to an age-adjusted threshold [1] and, more recently, to a clinical probability dependent threshold [2]. This transition intended to increase the proportion of patients in whom imaging can be withheld, without jeopardizing safety. In a post-hoc analysis of two prospective diagnostic management studies, Takach Lapner and colleagues found no differences in diagnostic accuracy between an age-adjusted, an increased fixed, and an inverse age-adjusted D-dimer threshold [3]. This article is protected by copyright. All rights reserved.

Ruling out pulmonary embolism across different subgroups of patients and healthcare settings: protocol for a systematic review and individual patient data meta-analysis (IPDMA)

BackgroundDiagnosing pulmonary embolism in suspected patients is notoriously difficult as signs and symptoms are non-specific. Different diagnostic strategies have been developed, usually combining clinical probability assessment with D-dimer testing. However, their predictive performance differs across different healthcare settings, patient subgroups, and clinical presentation, which are currently not accounted for in the available diagnostic approaches.MethodsThis is a protocol for a large diagnostic individual patient data meta-analysis (IPDMA) of currently available diagnostic studies in the field of pulmonary embolism. We searched MEDLINE (search date January 1, 1995, till August 25, 2016) to retrieve all primary diagnostic studies that had evaluated diagnostic strategies for pulmonary embolism. Two authors independently screened titles, abstracts, and subsequently full-text articles for eligibility from 3145 individual studies. A total of 40 studies were deemed eligible for inclusion into our IPDMA set, and principal investigators from these studies were invited to participate in a meeting at the 2017 conference from the International Society on Thrombosis and Haemostasis. All authors agreed on data sharing and participation into this project. The process of data collection of available datasets as well as potential identification of additional new datasets based upon personal contacts and an updated search will be finalized early 2018. The aim is to evaluate diagnostic strategies across three research domains: (i) the optimal diagnostic approach for different healthcare settings, (ii) influence of comorbidity on the predictive performance of each diagnostic strategy, and (iii) optimize and tailor the efficiency and safety of ruling out PE across a broad spectrum of patients with a new, patient-tailored clinical decision model that combines clinical items with quantitative D-dimer testing.DiscussionThis pre-planned individual patient data meta-analysis aims to contribute in resolving remaining diagnostic challenges of time-efficient diagnosis of pulmonary embolism by tailoring available diagnostic strategies for different healthcare settings and comorbidity.Systematic review registrationProspero trial registration: ID 89366.