Novel biomarkers to detect occult cancer in patients with unprovoked venous thromboembolism: Rationale and design of the PLATO-VTE study

Occult cancer is detected in about 5% of patients with unprovoked venous thromboembolism (VTE) in the 12 months following VTE diagnosis. Current guidance suggests conducting a ‘limited’ cancer screening in these patients, consisting of medical history taking, physical examination, routine blood tests, chest X-ray, and age- and gender-specific testing, over full-body imaging. However, almost half of underlying cancers remain undetected with this approach. Blood-based liquid biopsies may provide an attractive addition or alternative to current cancer screening strategies, with a potentially higher detection rate while avoiding radiation or invasive testing. The PLATO-VTE study is an ongoing, investigator-initiated, multinational, prospective, observational cohort study comparing the sensitivity of novel biomarkers for detecting cancer with that of limited cancer screening in the setting of unprovoked VTE. Patients older than 40 years with a first episode of unprovoked VTE are eligible, while those with major and minor transient provoking risk factors for VTE are excluded. Patients undergo standard-of-care ‘limited’ cancer screening and are followed for 12 months for the occurrence of cancer. A blood sample for biomarker analysis is drawn within 10 days; a second sample is taken at 3 months to assess test result consistency over time. Three biomarkers are assessed: platelet mRNA, circulating tumor DNA, and plasma proteomics analysis. The sensitivity and predictive value of the biomarkers at baseline will be compared with those of limited screening. The results from the PLATO-VTE study may lead to reconsider current approaches for cancer screening in patients with unprovoked VTE

The rationale, design, and methods of a randomized, controlled trial to evaluate the efficacy and safety of an active strategy for the diagnosis and treatment of acute pulmonary embolism during exacerbations of chronic obstructive pulmonary disease

Introduction: Some previous studies have suggested a high prevalence of pulmonary embolism (PE) during exacerbations of chronic obstructive pulmonary disease (ECOPD). The SLICE trial aims to assess the efficacy and safety of an active strategy for the diagnosis and treatment of PE (vs usual care) in patients hospitalized because of ECOPD. Methods: SLICE is a phase III, prospective, international, multicenter, randomized, open-label, and parallel-group trial. A total of 746 patients hospitalized because of ECOPD will be randomized in a 1:1 fashion to receive either an active strategy for the diagnosis and anticoagulant treatment of PE or usual care (ie, standard care without any diagnostic test for diagnosing PE). The primary outcome is a composite of all-cause death, non-fatal (recurrent) venous thromboembolism (VTE), or readmission for ECOPD within 90 days after enrollment. Secondary outcomes are (a) death from any cause within 90 days after enrollment, (b) non-fatal (recurrent) VTE within 90 days after enrollment, (c) readmission within 90 days after enrollment, and (d) length of hospital stay. Results: Enrollment started in September 2014 and is expected to proceed until 2020. Median age of the first 443 patients was 71 years (interquartile range, 64-78), and 26% were female. Conclusions: This multicenter trial will determine the value of detecting PEs in patients with ECOPD. This has implications for COPD patient morbidity and mortality

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Maternal mortality and morbidity burden in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study.

OBJECTIVES: Assessing the burden of maternal mortality is important for tracking progress and identifying public health gaps. This paper provides an overview of the burden of maternal mortality in the Eastern Mediterranean Region (EMR) by underlying cause and age from 1990 to 2015. METHODS: We used the results of the Global Burden of Disease 2015 study to explore maternal mortality in the EMR countries. RESULTS: The maternal mortality ratio in the EMR decreased 16.3% from 283 (241-328) maternal deaths per 100,000 live births in 1990 to 237 (188-293) in 2015. Maternal mortality ratio was strongly correlated with socio-demographic status, where the lowest-income countries contributed the most to the burden of maternal mortality in the region. CONCLUSION: Progress in reducing maternal mortality in the EMR has accelerated in the past 15 years, but the burden remains high. Coordinated and rigorous efforts are needed to make sure that adequate and timely services and interventions are available for women at each stage of reproductive life

Data for: Relationship between type of unprovoked venous thromboembolism and cancer location: an individual patient data meta-analysis.

Appendix 1. Risk of bias assessment with QUADAS-2 toolAppendix 2. Risk of bias assessment with Newcastle-Ottawa ScaleAppendix ReferencesTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Predicting the risk of cancer after unprovoked venous thromboembolism: external validation of the RIETE score

International audienc

Development of a Risk Prediction Score for Occult Cancer in Patients With VTE.

The benefits of a diagnostic workup for occult cancer in patients with VTE are controversial. Our aim was to provide and validate a risk score for occult cancer in patients with VTE. We designed a nested case-control study in a cohort of patients with VTE included in the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry from 2001 to 2014. Cases included cancer detected beyond the first 30 days and up to 24 months after VTE. Control subjects were defined as patients with VTE with no cancer in the same period. Of 5,863 eligible patients, 444 (7.6%; 95% CI, 6.8%-8.2%) were diagnosed with occult cancer. On multivariable analysis, variables selected were male sex, age > 70 years, chronic lung disease, anemia, elevated platelet count, prior VTE, and recent surgery. We built a risk score assigning points to each variable. Internal validity was confirmed using bootstrap analysis. The proportion of patients with cancer who scored ≤ 2 points was 5.8% (241 of 4,150) and that proportion in those who scored ≥ 3 points was 12% (203 of 1,713). We also identified scores divided by sex and age subgroups. This is the first risk score that has identified patients with VTE who are at increased risk for occult cancer. Our score needs to be externally validated

Dyslipidemia as a long-term marker for survival in pulmonary embolism

Objectives: To analyse survival rate after 24 months in consecutive patients with a diagnosis of PE as well as associated factors. Methods: Prospective cohort study during a follow-up period of two years in a series of consecutive patients with PE. Results: During the follow-up period, 34 out of 148 patients died (23%). Factors independently associated with reduced survival rate were: creatinine levels > 2 (OR, 8.8; 95% CI, 1.1 - 70.87), previous neoplasm (OR, 8.8; 95% CI, 3.69 - 20.98), dementia (OR, 6.85; 95% CI, 2.1 - 22.33) and dyslipidemia (OR, 5.07; 95% CI, 1.92 - 13.44). Forty four percent of the patients with dyslipidemia died vs. 20.8% of patients without this condition. Conclusions: In our study dyslipidemia shows as a long-term negative prognostic marker for survival in patients with EP. Resumo: Objetivos: Analisar a taxa de sobrevivência após 24 meses, em pacientes consecutivos com diagnóstico de PE, bem como fatores associados. Métodos: Estudo prospectivo durante um período de seguimento de dois anos em uma série consecutiva de pacientes com PE. Resultados: Durante o período de acompanhamento, 34 dos 148 pacientes morreram (23%). Fatores independentemente associados à reduzida taxa de sobrevivência foram: os níveis de creatinina> 2 (OR, 8,8; 95% CI, 1,1-70,87), neoplasia anterior (OR, 8,8; IC 95%, 3,69-20,98), demência (OR, 6,85; 95% CI, 2,1-22,33) e dislipidemia (OR, 5,07; IC 95%, 1,92-13,44). Quarenta e quatro por cento dos pacientes com dislipidemia morreram contra 20,8% dos pacientes sem essa condição. Conclusões: No nosso estudo, a dislipidemia mostra-se um marcador prognóstico negativo de longo prazo na sobrevida de pacientes com EP. Keywords: Dyslipidemia, Lipid metabolic disorders, Pulmonary embolism, Survival analysis, Venous thromboembolism, Palavras-chave: Dislipidemia, Doenças metabólicas lipídicas, Embolia pulmonar, Análise de sobrevivência, Tromboembolismo venos