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The challenging clinical dilemma of detecting pulmonary embolism (PE) in suspected patients is encountered in a variety of healthcare settings. We hypothesized that the optimal diagnostic approach to detect these patients in terms of safety and efficiency depends on underlying PE prevalence, case mix, and physician experience, overall reflected by the type of setting where patients are initially assessed. The objective of this study was to assess the capability of ruling out PE by available diagnostic strategies across all possible settings. We performed a literature search (MEDLINE) followed by an individual patient data (IPD) meta-analysis (MA; 23 studies), including patients from self-referral emergency care (n = 12,612), primary healthcare clinics (n = 3,174), referred secondary care (n = 17,052), and hospitalized or nursing home patients (n = 2,410). Multilevel logistic regression was performed to evaluate diagnostic performance of the Wells and revised Geneva rules, both using fixed and adapted D-dimer thresholds to age or pretest probability (PTP), for the YEARS algorithm and for the Pulmonary Embolism Rule-out Criteria (PERC). All strategies were tested separately in each healthcare setting. Following studies done in this field, the primary diagnostic metrices estimated from the models were the \"failure rate\" of each strategy-i.e., the proportion of missed PE among patients categorized as \"PE excluded\" and \"efficiency\"-defined as the proportion of patients categorized as \"PE excluded\" among all patients. In self-referral emergency care, the PERC algorithm excludes PE in 21% of suspected patients at a failure rate of 1.12% (95% confidence interval [CI] 0.74 to 1.70), whereas this increases to 6.01% (4.09 to 8.75) in referred patients to secondary care at an efficiency of 10%. In patients from primary healthcare and those referred to secondary care, strategies adjusting D-dimer to PTP are the most efficient (range: 43% to 62%) at a failure rate ranging between 0.25% and 3.06%, with higher failure rates observed in patients referred to secondary care. For this latter setting, strategies adjusting D-dimer to age are associated with a lower failure rate ranging between 0.65% and 0.81%, yet are also less efficient (range: 33% and 35%). For all strategies, failure rates are highest in hospitalized or nursing home patients, ranging between 1.68% and 5.13%, at an efficiency ranging between 15% and 30%. The main limitation of the primary analyses was that the diagnostic performance of each strategy was compared in different sets of studies since the availability of items used in each diagnostic strategy differed across included studies; however, sensitivity analyses suggested that the findings were robust. The capability of safely and efficiently ruling out PE of available diagnostic strategies differs for different healthcare settings. The findings of this IPD MA help in determining the optimum diagnostic strategies for ruling out PE per healthcare setting, balancing the trade-off between failure rate and efficiency of each strategy.

In the treatment of patients with acute pulmonary embolism, the efficacy of rivaroxaban, a factor Xa inhibitor, was similar to that of traditional anticoagulation therapy. There was less bleeding in the group receiving rivaroxaban, which supports its use in the treatment of this condition. Pulmonary embolism is a common disease, with an estimated annual incidence of 70 cases per 100,000 population. 1 , 2 The condition usually leads to hospitalization and may recur; it can be fatal. 3 For half a century, the standard therapy for most patients with pulmonary embolism has been the administration of heparin, overlapped and followed by a vitamin K antagonist. 4 , 5 This regimen is effective but complex. 5 – 9 Recently developed oral anticoagulants that are directed against factor Xa or thrombin overcome some limitations of standard therapy, including the need for injection and for regular dose adjustments on the basis of laboratory monitoring. . . .

Acute pulmonary embolism may occur rapidly and unpredictably and may be difficult to diagnose. Treatment can reduce mortality, and appropriate primary prophylaxis is usually effective. This review focuses on the pathogenesis, diagnosis, and treatment of acute pulmonary embolism of thrombotic origin. Acute pulmonary embolism may occur rapidly and unpredictably and may be difficult to diagnose. This review focuses on the pathogenesis, diagnosis, and treatment of acute pulmonary embolism of thrombotic origin. Pulmonary embolism, most commonly originating from deep venous thrombosis of the legs, ranges from asymptomatic, incidentally discovered emboli to massive embolism causing immediate death. Chronic sequelae of venous thromboembolism (deep venous thrombosis and pulmonary embolism) include the post-thrombotic syndrome 1 and chronic thromboembolic pulmonary hypertension. 2 Acute pulmonary embolism may occur rapidly and unpredictably and may be difficult to diagnose. Treatment can reduce the risk of death, and appropriate primary prophylaxis is usually effective. Patients treated for acute pulmonary embolism appear to be almost four times as likely to die of recurrent thromboembolism in the next year as patients treated for deep . . .

Background Newly or already diagnosed cancer might significantly influence the clinical presentation, outcome, and therapy of acute pulmonary embolism (PE). Methods Out of 1745 patients with acute PE, 66 patients were diagnosed with cancer during an initial hospitalization due to acute PE (where PE was the first clinical manifestation of cancer), 165 patients had known cancer treated in the last 6 months, and 1514 patients had acute PE without known or suspected cancer. The primary end‐point of the present study was all‐cause hospital death. The secondary end‐points were the proportion of patients treated with thrombolysis and who had severe disease, and the ocurrence of major or clinically relevant nonmajor bleeding. Results Patients with PE as the first presentation of cancer had the highest hospital mortality rate compared to the other two groups (HR for the mortality rate in patients without cancer as a reference, adjusted to four‐stratum mortality risk, and Charlson's comorbidity index was 3.440; 95% confidence interval (CI), 1.795–6.591; p < 0.001). Patients with known cancer before PE had a significantly lower chance of being treated with thrombolysis than patients without cancer (OR, 0.523; 95% CI, 0.339–0.807; p = 0.003); additionally, this difference was attenuated but remained when the OR was adjusted to age (OR, 0.542; 95% CI, 0.351–0.838; p = 0.006). Patients with known cancer had a higher frequency of high‐risk PE compared with patients without cancer (18.2% vs. 12.8%; p < 0.001). Patients with PE as the first manifestation of cancer had a higher frequency of intermediate‐high‐risk PE than those without (36.4% vs. 30.9%; p < 0.001). There was no significant difference in bleeding during hospitalization between groups. Conclusion Patients with cancer had a more severe presentation of acute PE than patients without. Furthermore, patients with PE as the first manifestation of cancer had the highest hospital mortality rate, and patients with known cancer were least likely to be treated with thrombolysis. The results of our investigation have shown that patients with newly diagnosed malignant disease with acute PE and patients with known malignant disease and PE had much higher hospital mortality and more severe acute PE presentation than patients without malignant disease. We have also shown that patients with known malignant disease had a lower chance of thrombolysis treatment than patients without malignant disease.

In patients with venous thromboembolism at high risk of recurrence for whom extended treatment with direct oral anticoagulants has been indicated, the optimal dose is unknown. We aimed to assess efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants in patients in whom extended anticoagulation has been indicated. RENOVE was a non-inferiority, investigator-initiated, multicentre, randomised, open-label, blinded endpoint trial done in 47 hospitals in France. Ambulatory patients aged 18 years or older with acute symptomatic venous thromboembolism (pulmonary embolism or proximal deep vein thrombosis) who had received 6–24 uninterrupted months of full-dose anticoagulation and for whom extended anticoagulation has been indicated were eligible. Eligible participants were categorised as having either a first unprovoked venous thromboembolism, recurrent venous thromboembolism, presence of persistent risk factors, or other clinical situations considered to be a high risk of recurrence. Participants were randomly assigned (1:1) to receive oral treatment with either a reduced dose of apixaban (2·5 mg twice daily) or rivaroxaban (10 mg once daily) or a full dose of apixaban (5 mg twice daily) or rivaroxaban (20 mg once daily) using a centralised randomisation procedure with an interactive web response system. The sequence generation method was a computerised random number generator and was balanced by blocks of different sizes. Randomisation was stratified by centre, type of direct oral anticoagulant, and antiplatelet drug. Physicians and participants were unmasked to treatment allocation; recurrent venous thromboembolism, clinically relevant bleeding, and all-cause death were adjudicated by an independent committee blinded to treatment allocation. The primary outcome was symptomatic recurrent venous thromboembolism, including recurrent fatal or non-fatal pulmonary embolism or isolated proximal deep vein thrombosis (non-inferiority hypothesis 90% power to exclude a hazard ratio [HR] of 1·7). The primary outcome and first two secondary outcomes were included in a hierarchical testing procedure. This trial is registered with ClinicalTrials.gov, NCT03285438. From Nov 2, 2017, to July 6, 2022, 2768 patients were enrolled and randomly assigned to the reduced-dose group (n=1383) or the full-dose group (n=1385). 970 (35·0%) participants were female, 1797 (65·0%) were male, and one (<0·1%) had sex not reported. Median follow-up was 37·1 months (IQR 24·0–48·3). Recurrent venous thromboembolism occurred in 19 of 1383 patients in the reduced-dose group (5-year cumulative incidence 2·2% [95% CI 1·1–3·3]) versus 15 of 1385 patients in the full-dose group (5-year cumulative incidence 1·8% [0·8–2·7]; adjusted HR 1·32 [95% CI 0·67–2·60]; absolute difference 0·40% [95% CI –1·05 to 1·85]; p=0·23 for non-inferiority). Major or clinically relevant bleeding occurred in 96 patients in the reduced-dose group (5-year cumulative incidence 9·9% [95% CI 7·7–12·1]) and 154 patients in the full-dose group (5-year cumulative incidence 15·2% [12·8–17·6]; adjusted HR 0·61 [95% CI 0·48–0·79]). 1136 (82·1%) of 1383 patients in the reduced-dose group and 1150 (83·0%) of 1385 in the full-dose group had an adverse event; 374 (27·0%) patients in the reduced-dose group and 420 (30·3%) in the full-dose group has a serious adverse event. 35 (5-year cumulative incidence 4·3% [95% CI 2·6–6·0]) patients in the reduced-dose group and 54 (5-year cumulative incidence 6·1% [4·3–8·0]) patients in the full-dose group died during the study period. In patients with venous thromboembolism requiring extended anticoagulation, reduction of the direct oral anticoagulant dose did not meet the non-inferiority criteria. However, the low recurrence rates in both groups and substantial reduction of clinically relevant bleeding with the reduced dose could support this regimen as an option. Further research will be needed to identify subgroups for whom the anticoagulation dose should not be reduced. French Ministry of Health.

The incidence of venous thromboembolic disease increases by a factor of four with pregnancy, and in developed countries pulmonary embolus is the leading cause of maternal death. This review provides guidance on the diagnosis and management of thromboembolic disease in pregnant women, including guidelines for the prophylactic use of anticoagulant agents in women at high risk during pregnancy and the puerperium. This review provides guidance on the diagnosis and management of thromboembolic disease in pregnant women, including guidelines for the prophylactic use of anticoagulant agents in women at high risk during pregnancy and the puerperium. Pulmonary embolism and deep-vein thrombosis are the two components of a single disease called venous thromboembolism. Approximately 30% of apparently isolated episodes of pulmonary embolism are associated with silent deep-vein thrombosis, and in patients presenting with symptoms of deep-vein thrombosis, the frequency of silent pulmonary embolism ranges from 40 to 50%. 1 , 2 Venous thromboembolism is both more common and more complex to diagnose in patients who are pregnant than in those who are not pregnant. The incidence of venous thromboembolism is estimated at 0.76 to 1.72 per 1000 pregnancies, which is four times as great as the risk in the . . .

Follow-up after acute pulmonary embolism (PE) is important to assess recovery, consider the need for on-going anticoagulation and identify chronic thromboembolic pulmonary hypertension (CTEPH), a rare but serious complication of PE. 16 dilemmas in the follow-up of acute PE were identified by a steering committee of four pulmonologists and a haematologist with interest in PE and/or CTEPH. Current literature was reviewed and a practical approach suggested based on expert consensus. Dilemmas discussed included: (1) how to manage a breathless patient; (2) what to do if CTEPH is suspected; (3) the difference between CTEPH and post-PE syndrome, (4) testing for thrombophilia, (5) when to investigate for cancer, (6) anticoagulation duration and dose, (7) approaches to discussions and decision-making with respect to anticoagulation, (8) use of aspirin and whether antiplatelet therapy should be stopped during anticoagulation and (9) advice for patients on discharge from hospital at 3 months and information for first-degree relatives. Given the occurrence of complications that may require assessment, follow-up of patients post-PE should be systematic and consider the individual needs of the patient.

Pulmonary embolism (PE) is a significant cause of morbidity and mortality in pregnancy and the puerperium. In severe cases, it causes haemodynamic instability and can lead to cardiac arrest due to obstructive shock. Patients with acute PE can be risk stratified to guide their monitoring and treatment; this article focuses on intermediate- and high-risk PE. The criteria for defining high-risk PE can be used unmodified in pregnancy. Diagnostic imaging should not be delayed due to pregnancy. Low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) can be used during pregnancy and breastfeeding, and systemic thrombolysis can be used in obstetric patients, but there are significant bleeding risks and it should be reserved for high-risk PE with hypotension and shock. Although pregnancy and the puerperium are risk factors for PE, it is important to avoid early diagnostic closure, and to consider other causes for the patient’s presentation.

In this clinical trial, rivaroxaban, an oral factor Xa inhibitor, was effective in the initial and continued treatment of symptomatic venous thromboembolism; it may become part of the treatment armamentarium for this common clinical problem. Acute venous thromboembolism (i.e., deep-vein thrombosis [DVT] or pulmonary embolism) is a common disorder with an annual incidence of approximately 1 or 2 cases per 1000 persons in the general population. 1 , 2 Short-term treatment is effective, with the risk of recurrent disease — the major complication — reduced from an estimated 25% to about 3% during the first 6 to 12 months of therapy. 3 The risk of recurrence remains after treatment ends and can reach 5 to 10% during the first year. 4 , 5 Standard treatment for acute venous thromboembolism is limited by the need for parenteral heparin initially, with overlapping . . .

The decision by pulmonary embolism response teams (PERTs) to utilize anticoagulation (AC) with or without systemic thrombolysis (ST) or catheter-directed therapies (CDT) for pulmonary embolism (PE) is a balance between the desire for a positive outcome and safety. Our primary aim was to develop a predictive model of in-hospital mortality for patients with high- or intermediate-risk PE managed by PERT while externally validating this model. Our secondary aim was to compare the relative safety and efficacy of ST and CDT in this cohort. Consecutive patients hospitalized between June 2014 and January 2020 at the Cleveland Clinic Foundation and The University of Rochester with acute high- or intermediate-risk PE managed by PERT were retrospectively evaluated. Groups were stratified by treatment strategy. The primary outcome was in-hospital mortality, and secondary outcome was major bleeding. A logistic regression model to predict the primary outcome was built using the derivation cohort, with 100-fold bootstrapping for internal validation. External validation was performed and the area under the receiver operating curve (AUC) was calculated. Of 549 included patients, 421 received AC alone, 71 received ST, and 64 received CDT. Predictors of major bleeding include ESC risk category, PESI score, hypoxia, hemodynamic instability, and serum lactate. CDT trended towards lower mortality but with an increased risk of bleeding relative to ST (OR = 0.42; 95% CI [0.15, 1.17] and OR = 2.14; 95% CI [0.9, 5.06] respectively). In the multivariable logistic regression model in the derivation institution cohort, predictors of in-hospital mortality were age, cancer, hemodynamic instability requiring vasopressors, and elevated NT-proBNP (AUC = 0.86). This model was validated using the validation institution cohort (AUC = 0.88). We report an externally-validated model for predicting in-hospital mortality in patients with PE managed by PERT. The decision by PERT to initiate CDT or ST for these patients had no impact on mortality or major bleeding, yet the long-term efficacy of these interventions needs to be elucidated.