Real-Time Dissemination of Aggregate Data on Presentation and Outcomes of Patients With Venous Thromboembolism : The RIETE Infographics Project

In the current era of patient empowerment and precision medicine, access to timely information is critical to decision-making. Unfortunately, we currently lack patient-specific, real-time data about clinical presentation, risk of thrombotic or hemorrhagic events, key risk factors, and adverse outcomes in patients with venous thromboembolism (VTE). Accordingly, the egistro nformatizado nfermedad rombombólica (RIETE) investigators developed a tool to provide an open-source, real-time graphic representation of VTE-related data derived from over 90 000 patients with confirmed VTE. This information is intended to facilitate discussion in the informed decision-making process. The current article describes the aims, rationale, methods, and ongoing and future efforts of the real-time VTE infographics developed by the RIETE registry collaborators

Hospital volume and outcomes for acute pulmonary embolism: Multinational population based cohort study

[Objectives] To evaluate the association between experience in the management of acute pulmonary embolism, reflected by hospital case volume, and mortality.[Design] Multinational population based cohort study using data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry between 1 January 2001 and 31 August 2018.[Setting] 353 hospitals in 16 countries.[Participants] 39 257 consecutive patients with confirmed diagnosis of acute symptomatic pulmonary embolism.[Main] outcome measure Pulmonary embolism related mortality within 30 days after diagnosis of the condition.[Results] Patients with acute symptomatic pulmonary embolism admitted to high volume hospitals (>40 pulmonary embolisms per year) had a higher burden of comorbidities. A significant inverse association was seen between annual hospital volume and pulmonary embolism related mortality. Admission to hospitals in the highest quarter (that is, >40 pulmonary embolisms per year) was associated with a 44% reduction in the adjusted odds of pulmonary embolism related mortality at 30 days compared with admission to hospitals in the lowest quarter (<15 pulmonary embolisms per year; adjusted risk 1.3% v 2.3%; adjusted odds ratio 0.56 (95% confidence interval 0.33 to 0.95); P=0.03). Results were consistent in all sensitivity analyses. All cause mortality at 30 days was not significantly reduced between the two quarters (adjusted odds ratio 0.78 (0.50 to 1.22); P=0.28). Survivors showed little change in the odds of recurrent venous thromboembolism (odds ratio 0.76 (0.49 to 1.19)) or major bleeding (1.07 (0.77 to 1.47)) between the low and high volume hospitals.[Conclusions] In patients with acute symptomatic pulmonary embolism, admission to high volume hospitals was associated with significant reductions in adjusted pulmonary embolism related mortality at 30 days. These findings could have implications for management strategies.Peer reviewe

Risk of recurrent venous thromboembolism in patients with autoimmune diseases:data from the Registro Informatizado de Enfermedad TromboEmbolica (RIETE) registry

Autoimmune disease is a risk factor for first incident venous thromboembolism (VTE). However, data on the risk of recurrent VTE in people with autoimmune disease is sparse. We explored the risk of recurrent VTE using the RIETE registry, comparing people with autoimmune disease (n = 1305) to those without (n = 50608). Overall rates were 6.5 and 5.1 recurrent VTE/100 years for patients with autoimmune disease vs controls, respectively. After adjustment for sex and unprovoked/provoked VTE yielded an adjusted hazard ratio of 1.29 (95%CI 1.03-1.62). The analysis was limited by short median follow up time (161 days overall), precluding definitive conclusions on recurrent VTE risks

Role of a clinical prediction score in a chronic thromboembolic pulmonary hypertension rule-out strategy

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Machine learning to predict major bleeding during anticoagulation for venous thromboembolism: possibilities and limitations

Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE-BLEED scores were used for comparisons. External validation was performed with the COMMAND-VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE-BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE-BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE-BLEED scores only in the prospective validation cohort, but not in the external validation cohort

Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair

The highly conserved ectodysplasin A (EDA)/EDA receptor signaling pathway is critical during development for the formation of skin appendages. Mutations in genes encoding components of the EDA pathway disrupt normal appendage development, leading to the human disorder hypohidrotic ectodermal dysplasia. Spontaneous mutations in the murine Eda (Tabby) phenocopy human X-linked hypohidrotic ectodermal dysplasia. Little is known about the role of EDA signaling in adult skin homeostasis or repair. Because wound healing largely mimics the morphogenic events that occur during development, we propose a role for EDA signaling in adult wound repair. Here we report a pronounced delay in healing in Tabby mice, demonstrating a functional role for EDA signaling in adult skin. Moreover, pharmacological activation of the EDA pathway in both Tabby and wild-type mice significantly accelerates healing, influencing multiple processes including re-epithelialization and granulation tissue matrix deposition. Finally, we show that the healing promoting effects of EDA receptor activation are conserved in human skin repair. Thus, targeted manipulation of the EDA/EDA receptor pathway has clear therapeutic potential for the future treatment of human pathological wound healing

Pulmonary embolism in Europe - Burden of illness in relationship to healthcare resource utilization and return to work

Objectives Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from patients in Europe is scarce. The aim of this study was to report the impacts of PE on healthcare resource utilization (HCRU) and return to work using the PREFER in VTE registry. Methods The PREFER in VTE registry was a prospective, observational, multicenter study in seven European countries, aiming to provide data concerning treatment patterns, HCRU, mortality, quality of life and work-loss. Patients with a first-time or recurrent PE were included and followed up at 1, 3, 6 and 12 months. Treatment patterns, re-hospitalization rates, length of hospital stays (LOS), and ambulatory/office visits, as well as proportion of patients returning to work, were assessed. Subgroups by country and with/without active cancer were examined separately. Zero-inflated negative binomial and Cox regression were applied to investigate the relationship between baseline characteristics and LOS and return to work, respectively. Results Amongst 1399 patients with PE, 53.2% were male and the average age was 62.3 ± 17.1 years old. Overall, patients were treated with combinations of heparin, vitamin K antagonists (VKA) and the non-VKA oral anticoagulants (NOACs) (50.0% treated with the combination of heparin with VKA). Patients with active cancer were primarily treated with heparin (84.9%). NOACs were used more frequently in DACH (Germany, Austria and Switzerland) and France (55.2% and 32.6%) compared to Italy and Spain (4.5% and 6.1%). The VTE-related re-hospitalization rate within 12 months and the average LOS varied substantially between countries, from 26.2% in UK to 12.3% in France, and from 12.9 days in Italy to 3.9 days in France. PE patients were often co-managed by general practitioners in France and DACH (>84%), and less frequently in other countries (<47%). The regression results confirmed the country variation of HCRU. Of the employed patients (n = 385), 60% returned to work at 1 month but 27.8% had not after one year. PE patients with DVT were more likely to return to work. Active cancer was a significant predictor for not returning to work, as well as smoking history. Conclusions Medical treatment of PE differed between patients with active cancer and patients without active cancer. VTE-related resource utilization differed markedly between countries. While the reported ’not return to work’ was high for patients with PE, this may at least in part reflect the presence of co-morbidities such as cancer

The significance of heart failure in hospitalised patients with pulmonary embolism. A gender‐specific analysis

Background: Heart failure (HF) is a risk factor for the development of pulmonary embolism (PE). Few studies have examined sex differences in risk of PE among HF patients. Aims: (a) To examine the incidence, characteristics and in-hospital outcomes among patients hospitalised with PE according to HF status; (b) to compare the in-hospital mortality (IHM) after PE between HF and non-HF patients and (c) to identify variables associated with IHM. All analyses were stratified by sex. Methods: We included all adult patients hospitalised for PE from 1 January 2016 to 31 December 2018. Data were collected from the Spanish National Hospital Discharge Database. Poisson regression models were constructed to quantify the difference in the incidences between HF and non-HF populations. Propensity score matching (PSM) was used to obtain comparable subgroups by sex and HF status. Results: We identified 46,835 PE hospitalisations, 11.4% with HF. Adjusted incidence of PE was higher in HF patients than in those without HF (Incidence Rate Ratio 1.11; 95% CI 1.08-1.13). Crude and PSM adjusted IHM were significantly higher in men and women hospitalised with PE suffering HF than in men and women without HF (P < .001). Women with HF who suffered a PE had lower IHM than men with this condition (P < .001) after adjusting. Conclusions: Adjusted incidence of PE was higher in HF patients than in those without HF. After PSM suffering, HF was associated to higher IHM in men and women. Women with PE and HF had lower IHM than men with these conditions

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Full list of RIETE Investigators is provided in the Appendix of this article. V.Ģībietis, D.Kigitoviča and A.Skride are mentioned in the Appendix.Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.publishersversionPeer reviewe

Health-related quality of life and mortality in patients with pulmonary embolism: a prospective cohort study in seven European countries

PURPOSE: Little is known about the quality of life following pulmonary embolism (PE). The aim of the study was to assess the 12-month illness burden in terms of health-related quality of life (HrQoL) and mortality, in relation to differences in patient characteristics. METHODS: The PREFER in VTE registry, a prospective, observational study conducted in seven European countries, was used. Within 2 weeks following an acute symptomatic PE, patients were recruited and followed up for 12 months. Associations between patient characteristics and HrQoL (EQ-5D-5L) and mortality were examined using a regression approach. RESULTS: Among 1399 PE patients, the EQ-5D-5L index score at baseline was 0.712 (SD 0.265), which among survivors gradually improved to 0.835 (0.212) at 12 months. For those patients with and without active cancer, the average index score at baseline was 0.658 (0.275) and 0.717 (0.264), respectively. Age and previous stroke were significant factors for predicting index scores in those with/without active cancer. Bleeding events but not recurrences had a noticeable impact on the HrQoL of patients without active cancer. The 12-month mortality rate post-acute period was 8.1%, ranging from 1.4% in Germany, Switzerland, and Austria to 16.8% in Italy. Mortality differed between patients with active cancer and those without (42.7% vs. 4.7%). CONCLUSION: PE is associated with a substantial decrease in HrQoL at baseline which normalizes following treatment. PE is associated with a high mortality rate especially in patients with cancer, with significant country variation. Bleeding events, in particular, impact the burden of PE