P. L. den Exter

Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta‐analysis

New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta‐analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.

The post-PE syndrome: a new concept for chronic complications of pulmonary embolism

Long-term follow-up studies have consistently demonstrated that after an episode of acute pulmonary embolism (PE), half of patients report functional limitations and/or decreased quality of life up to many years after the acute event. Incomplete thrombus resolution occurs in one-fourth to one-third of patients. Further, pulmonary artery pressure and right ventricular function remain abnormal despite adequate anticoagulant treatment in 10-30% of patients, and 0.5-4% is diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) which represents the most severe long term complication of acute PE. From these numbers, it seems that CTEPH itself is the extreme manifestation of a much more common phenomenon of permanent changes in pulmonary artery flow, pulmonary gas exchange and/or cardiac function caused by the acute PE and associated with dyspnea and decreased exercise capacity, which in analogy to post-thrombotic syndrome after deep vein thrombosis could be referred to as the post-pulmonary embolism syndrome. The acknowledgement of this syndrome would both be relevant for daily clinical practice and also provide a concept that aids in further understanding of the pathophysiology of CTEPH. In this clinically oriented review, we discuss the established associations and hypotheses between the process of thrombus resolution or persistence, lasting hemodynamic changes following acute PE as well as the consequences of a PE diagnosis on long-term physical performance and quality of life.

Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute non-massive pulmonary embolism: systematic review and meta-analysis.

The ability of computed tomography (CT)‐assessed right ventricular dysfunction (RVD) to identify normotensive patients with acute pulmonary embolism (PE) at high risk of mortality or adverse outcome lacks clarity.

Comparison of two methods for selection of out of hospital treatment in patients with acute pulmonary embolism

The aim of this study is to compare the performance of two clinical decision rules to select patients with acute pulmonary embolism (PE) for outpatient treatment: the Hestia criteria and the simplified Pulmonary Embolism Severity Index (sPESI). From 2008 to 2010, 468 patients with PE were triaged with the Hestia criteria for outpatient treatment: 247 PE patients were treated at home and 221 were treated as inpatients. The outcome of interest was all-cause 30-day mortality. In a post-hoc fashion, the sPESI items were scored and patients were classified according to the sPESI in low and high risk groups. Of the 247 patients treated at home, 189 (77%) patients were classified as low risk according to the sPESI and 58 patients (23%) as high risk. In total, 11 patients died during the first month; two patients treated at home and nine patients treated in-hospital. None of the patients treated at home died of fatal PE. Both the Hestia criteria and sPESI selected >50% of patients as low risk, with good sensitivity and negative predictive values for 30-day mortality: 82% and 99% for the Hestia criteria and 91% and 100% for the sPESI, respectively. The Hestia criteria and the sPESI classified different patients eligible for outpatient treatment, with similar low risks for 30-day mortality. This study suggests that the Hestia criteria may identify a proportion of high risk sPESI patiennts who can be safely treated at home, this however requires further validation.

Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.

Essentials We performed a pooled analysis of 926 patients with cancer‐associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE.

Intravesical gentamicin for recurrent urinary tract infection in patients with intermittent bladder catheterisation

Clean intermittent catheterisation (CIC) of the bladder is used to imitate normal bladder emptying in patients with bladder dysfunction. CIC is associated with urinary tract infection (UTI) that may be difficult to treat in the case of antimicrobial resistance. The aim of this study was to establish the effect and safety of intravesical gentamicin treatment in such settings. In 2009, intravesical gentamicin treatment was started in selected patients. Here we describe our experience with two patients treated until March 2010. Two patients using CIC suffering recurrent UTI with multiresistant Escherichia coli were treated with daily administration of 80 mg intravesical gentamicin. On treatment they appeared asymptomatic. During 8- and 9-month follow-up they were free of UTI, urine cultures were negative and there were no side effects. A systematic review was conducted through searches of PubMed and other databases. Clinical trials that met the eligibility criteria and displayed the efficacy or safety of intravesical aminoglycoside treatment in patients using CIC were studied. Study selection was performed by two independent reviewers. Eight studies were included for review. Owing to study heterogeneity, a meta-analysis could not be performed. Of four controlled studies using neomycin or kanamycin, two demonstrated a significant reduction in bacteriuria, whilst two other trials did not. One case series on neomycin/polymyxin showed that the majority of patients still developed bacteriuria. Three case series using gentamicin all pointed towards a significant reduction in bacteriuria and UTIs. There were no clinically relevant side effects reported but follow-up in all studies was limited. Although data are limited, intravesical treatment with gentamicin might be a reasonable treatment option in selected patients practicing CIC who suffer recurrent UTIs with highly resistant microorganisms.

A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism.

An ‘unlikely’ clinical decision rule with a negative D‐dimer result safely excludes pulmonary embolism (PE) in 30% of presenting patients. We aimed to simplify this diagnostic approach and to increase its efficiency.

Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer‐associated venous thromboembolism during anticoagulant treatment

Information on recurrent venous thromboembolic events (VTEs) and major bleeding risks during anticoagulant treatment in patients with cancer‐associated VTEs and chronic kidney disease (CKD) is scarce, although it is of relevance in establishing better tailored management strategies in these patients.

Embolic burden of incidental pulmonary embolism diagnosed on routinely performed contrast-enhanced computed tomography imaging in cancer patients.

Since the quality of computed tomography (CT) imaging techniques has improved, pulmonary embolism (PE) has increasingly been detected incidentally on routine CT examination. In particular, in patients with malignancy, who are known to be at elevated risk of developing venous thromboembolic events, and who frequently undergo CT scanning for reasons such as diagnosing, staging, and treatment evaluation, incidental PE has become a relatively common finding [1]. There is limited information on the embolic burden in patients in whom PE goes clinically unnoticed. It may be theorized that, in patients without symptoms suggestive of PE, the emboli may more frequently be localized distally, leading to a smaller obstruction index. The first aim of the present study was to assess the embolic burden of patients with incidental PE and compare it with that of patients with symptomatic PE. The second aim was to assess the impact of the embolic burden on the outcome of the patients. Consecutive adult patients with active malignancy who received a diagnosis of incidental PE between January 2003 and July 2012 in our hospital were included. The characteristics of this cohort have, in part, been described previously [2]. Incidental PE was defined as a diagnosis of PE detected on CT scans ordered for reasons other than suspected PE [3]. Institutional review board approval was waived for this observational and retrospective study. Imaging was performed with multidetector CT scanners (four-slice, 16-slice, 64-slice and 320-slice CT scanners; Toshiba, Otawara, Japan). Images were reconstructed with a slice thickness of 1.0 mm. All CT images were reviewed on a PACS workstation by an experienced thoracic radiologist (L.J.M.K.), who was blinded to the original CT report, the location of the filling defect, and the clinical information of the patients. Both the degree of pulmonary artery obstruction, according to the scoring system of Qanadli, and the largest pulmonary artery involved, i.e. central or interlobar, segmental, or subsegmental, were assessed. The Qanadli obstruction index was defined as the number of segmental artery branches that are blocked, with one point assigned for partial blockage, or two points for complete obstructive PE. With this scoring system, 40 is the highest possible score, corresponding to a 100% obstruction index [4]. To compare the obstruction indexes of patients with incidental PE with those of patients with symptomatic PE, we used a previously described cohort of 113 consecutive patients with acute symptomatic PE diagnosed on CT pulmonary angiography (CTPA) as a reference group [2,5]. A retrospective chart review was performed to record the clinical outcome. All patients were followed for 6 months for the occurrence of death. The cause of mortality was assessed by reviewing the pathology report. In the cases in which an autopsy was not performed, the likely cause of death was verified with the treating physician by reviewing the medical records and death certificates. The obstruction indexes of patients with incidental and symptomatic PE were compared for statistical difference with the Mann–Whitney test. Cox regression analyses were performed to assess the impact of the level of obstruction on survival during 6 months of follow-up. The hazard ratio (HR) was adjusted for potential confounders, including age, gender, and stage of the malignancy (i.e. localized vs. metastatic). SPSS version 20 (SPSS, Chicago, IL, USA) was used for all analyses. During the study period, incidental PE was diagnosed in a total of 65 patients. The original CT images could Correspondence: Paul den Exter, Department of Thrombosis and Hemostasis, Leiden University Medical Center C7-68, Albinusdreef 2, P.O Box 9600, 2300 RC, Leiden, the Netherlands. Tel.: + 31 71 526 2085; fax: +31 71 524 8140. E-mail: p.l.den_exter@lumc.nl

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.