The prognostic value of respiratory symptoms and performance status in ambulatory cancer patients and unsuspected pulmonary embolism; analysis of an international, prospective, observational cohort study.

BACKGROUND: Optimal risk stratification of unsuspected pulmonary embolism (UPE) in ambulatory cancer patients (ACPs) remains unclear. Existing clinical predictive rules (CPRs) are derived from retrospective databases and have limitations. The UPE registry is a prospective international registry with pre-specified characteristics of ACPs with a recent UPE. The aim of this study was to assess the utility of risk factors captured in the UPE registry in predicting proximate (30-, 90- and 180-day) mortality and how they performed when applied to an existing CPR. OBJECTIVES: To evaluate risk factors for proximate mortality, overall survival, recurrent venous thromboembolism and major bleeding, in the patients enrolled in the UPE registry cohort. METHODS: Data from the 695 ACPs in this registry were subjected to multivariate logistic regression analyses to identify predictors independently associated with proximate mortality and overall survival. The most consistent predictors were applied to the Hull CPR, an existing 5-point prediction rule. RESULTS: The most consistent predictors of mortality were patient-reported respiratory symptoms within 14 days before, and ECOG performance status at the time of UPE. These predictors applied to the Hull-CPR produced a consistent correlation with proximate mortality and overall survival (area under the curve [AUC] = 0.70 [95% CI 0.63, 077], AUC = 0.65 [95% CI 0.60, 070], AUC = 0.64 [95% CI 0.59, 068], and AUC = 0.61, 95% CI 0.57, 0.65, respectively). CONCLUSION: In ACPs with UPE, ECOG performance status logged contemporaneously to the UPE diagnosis and respiratory symptoms prior to UPE diagnosis can stratify mortality risk. When applied to the HULL-CPR these risk predictors confirmed the risk stratification clusters of low-intermediate and high-risk for proximate mortality as seen in the original derivation cohort.

Treatment and Long-Term Clinical Outcomes of Incidental Pulmonary Embolism in Patients With Cancer: An International Prospective Cohort Study.

PURPOSE: Pulmonary embolism is incidentally diagnosed in up to 5% of patients with cancer on routine imaging scans. The clinical relevance and optimal therapy for incidental pulmonary embolism, particularly distal clots, is unclear. The aim of the current study was to assess current treatment strategies and the long-term clinical outcomes of incidentally detected pulmonary embolism in patients with cancer. PATIENTS AND METHODS: We conducted an international, prospective, observational cohort study between October 22, 2012, and December 31, 2017. Unselected adults with active cancer and a recent diagnosis of incidental pulmonary embolism were eligible. Outcomes were recurrent venous thromboembolism, major bleeding, and all-cause mortality during 12 months of follow-up. Outcome events were centrally adjudicated. RESULTS: A total of 695 patients were included. Mean age was 66 years and 58% of patients were male. Most frequent cancer types were colorectal (21%) and lung cancer (15%). Anticoagulant therapy was initiated in 675 patients (97%), of whom 600 (89%) were treated with low-molecular-weight heparin. Recurrent venous thromboembolism occurred in 41 patients (12-month cumulative incidence, 6.0%; 95% CI, 4.4% to 8.1%), major bleeding in 39 patients (12-month cumulative incidence, 5.7%; 95% CI, 4.1% to 7.7%), and 283 patients died (12-month cumulative incidence, 43%; 95% CI, 39% to 46%). The 12-month incidence of recurrent venous thromboembolism was 6.4% in those with subsegmental pulmonary embolism compared with 6.0% in those with more proximal pulmonary embolism (subdistribution hazard ratio, 1.1; 95% CI, 0.37 to 2.9; P = .93). CONCLUSION: In patients with cancer with incidental pulmonary embolism, risk of recurrent venous thromboembolism is significant despite anticoagulant treatment. Patients with subsegmental pulmonary embolism seemed to have a risk of recurrent venous thromboembolism comparable to that of patients with more proximal clots.

Extended non-vitamin K antagonist oral anticoagulation therapy for prevention of recurrent venous thromboembolism.

Evidence from the use of traditional therapy (low-molecular-weight heparin/vitamin K antagonists) for venous thromboembolism (VTE) treatment and prevention suggests that extending treatment beyond the acute phase reduces recurrence. More recently, several non-vitamin K antagonist oral anticoagulants (NOACs) have been approved in the acute setting; accumulating evidence suggests continuing treatment with these agents beyond 12months offers additional benefits to patients with VTE. This review examines the evidence for NOAC use in longer-duration anticoagulation treatment, and discusses guidelines from major societies. Clinical data from the phase III extension studies for apixaban, dabigatran and rivaroxaban are presented, and the clinical and economic costs and benefits are examined. Evidence from other therapy areas utilising extended treatment regimens highlights the possible impact of factors relevant to extended anticoagulation therapy. Phase IV studies of NOACs are presented. US and European guidelines advise long-term therapy in certain instances, taking into account evidence on NOAC use in VTE accumulated recently. They support NOAC use where they have been selected as the initial therapy choice and therapy needs to be extended beyond 3months. The phase III extension studies demonstrate the benefits of extended NOAC use versus treatment cessation, with reduced recurrence rates versus placebo, although associated with a potential moderate increase in bleeding risk. Phase IV data are also emerging, with the recent XALIA study showing that a broad range of patients with VTE can benefit from continued rivaroxaban treatment; ongoing research will yield data on long-term use of the other NOACs in routine clinical practice.

Acute pulmonary embolism: risk assessment, risk stratification and treatment options.

INTRODUCTION: Pulmonary embolism (PE) is a potentially life-threatening cardiovascular emergency with a high mortality rate. Rapid diagnosis and treatment are important in optimising clinical outcomes in patients with PE, and anticoagulants are the mainstay of treatment. Traditionally, anticoagulant therapy involves parenteral anticoagulants, overlapping with and followed by oral vitamin K antagonists. Direct oral anticoagulants (DOACs), including the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin inhibitor dabigatran etexilate, have been developed to address limitations associated with traditional anticoagulant therapy. Apixaban, dabigatran and rivaroxaban have recently been approved for the treatment of acute deep vein thrombosis (DVT) and PE and prevention of recurrent DVT or PE. Edoxaban is approved in the United States but not currently in the European Union for the treatment of DVT and PE; approval of edoxaban in Europe is anticipated in the near future. OBJECTIVE: To summarise the management of patients with suspected PE in accordance with recent guidelines, and to discuss the evidence behind the recent approvals of the DOACs for the treatment of PE. DISCUSSION: Diagnosis and treatment of PE is guided by clinical probability scoring systems and tools for prognostic stratification and early mortality risk evaluation. Anticoagulants remain the mainstay of treatment. Successful phase III trials have demonstrated the efficacy of the DOACs for the treatment of DVT and PE, with a potentially improved safety profile, leading to their recent approval in this indication, and giving the clinician greater choice of anticoagulant therapies in this setting. CONCLUSIONS: DOACs offer an alternative and potentially simplified option for anticoagulation therapy in patients with PE compared with traditional anticoagulants and are likely to assist physicians in optimising management of patients with PE and improve clinical outcomes.

New anticoagulants in the management of venous thromboembolism in women.

Objective diagnosis and treatment are important in optimizing clinical outcomes in patients with venous thromboembolism (VTE), and anticoagulants are the mainstay of treatment. Traditionally, anticoagulant therapy involves parenteral anticoagulants, overlapping with and followed by oral vitamin K antagonists. Recently, direct oral anticoagulants (DOACs), including the Factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin inhibitor dabigatran etexilate, have been developed to address limitations associated with traditional anticoagulant therapy. DOACs have recently been approved for the treatment of acute deep vein thrombosis (DVT) and pulmonary embolism (PE). Successful phase III trials have demonstrated their efficacy for the treatment of DVT and PE, with a potentially improved safety profile. Recent evidence suggests that women bleed more compared to men when treated with DOACs for VTE without differences in treatment efficacy. Future clinical trials should include outcomes stratified by sex, and should investigate the clinical impact of this sex-related safety difference.

Pathways to psychiatric care in Eastern Europe.

BACKGROUND: There has been almost no research into mental health services in Eastern Europe. A pathways study is a quick and useful starting point, requiring few resources. AIMS: To improve understanding of prior care-seeking and treatment of new patients seen at mental health services. METHOD: Pathways diagrams were drawn showing the routes of care-seeking for 50 new patients in eight centres. Patterns of care-seeking, durations and previous treatments were compared for ICD-10 diagnostic groups. RESULTS: The diagnoses varied according to the organisation of services. Major pathways included general practitioners, direct access and hospital doctors. General practitioners have a limited role as 'gatekeeper' in centres in Albania, Croatia, Macedonia, Romania and Serbia-Montenegro, and rarely prescribed treatment, except sedatives, for mental disorders. CONCLUSIONS: Findings highlight areas that require attention if aspirations for community-oriented mental health care are to be realised, particularly integration of mental health into primary care.