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The optimal strength of compression needed to prevent post-thrombotic syndrome (PTS) after a proximal deep vein thrombosis (DVT) is debated. We aimed to assess whether 25 mm Hg elastic compression stockings (ECS) are non-inferior to 35 mm Hg ECS in preventing PTS after a DVT.In this multicentre, double-blind, non-inferiority, randomised controlled trial, we enrolled adults (≥18 years) with a first ipsilateral proximal DVT attending 46 French vascular medicine hospital departments or private practices. Participants were randomly allocated (1:1, stratified by centre, age, and sex; with varying block sizes of two and four) to wear 25 mm Hg or 35 mm Hg ECS for 2 years. The primary outcome was the cumulative rate of PTS 2 years after inclusion, defined by a Villalta scale (≥5). Efficacy was assessed by intention-to-treat and in eligible participants who had complete primary outcome data. A per-protocol analysis was also conducted among compliant patients as a secondary outcome measure. Safety was assessed in all participants who used ECS at least once, and for which we have at least some tolerance information during follow-up. The margin for non-inferiority was 12·5%. This study is registered with ClinicalTrials.gov, NCT01578122, and has been completed.Between June 28, 2012, and July 21, 2017, we enrolled 341 eligible participants who consented to randomisation. 233 (68%) were men and median age was 59 years (IQR 45-70). Collection of ethnicity and race as a routine research variable is not authorised in France. Median follow-up was 735 days (IQR 721-760). 249 (73%) had complete data at 2 years. For the primary analysis, 40 (31%) of 129 participants with complete data in the 25 mm Hg ECS group and 40 (33%) of 120 in the 35 mm Hg group had PTS (absolute difference -2·3% [90% CI -12·1 to 7·4], pAlthough we did not reach the prespecified sample size, our results suggest that 25 mm Hg ECS are non-inferior to 35 mm Hg ECS in preventing PTS. Larger more powerful studies are needed.Laboratoires Innothera, France.

International audience; Background: Hemoptysis is not common in pulmonary embolism (PE) and lacks specificity for its diagnosis. However, this item is present in different validated scores that estimate the clinical probability of PE. The relevance of this item in clinical decision rules (CDRs) is not clearly established.Objective: The aim of this study was to evaluate the impact of removing the "hemoptysis" item from the PERC, YEARS, and PEGeD CDR in patients with low clinical probability of PE.Design: This was a post hoc analysis of two European prospective cohorts, which included 2968 patients presenting to the ED with a low clinical probability of PE (PROPER and PERCEPIC) and a 3-month follow-up. The primary endpoint was the false-negative rate of a CDR score without the hemoptysis item. Secondary endpoints included the potential reduction of chest imaging if the item hemoptysis was to be removed and risk stratification of the Geneva and Wells scores without the hemoptysis item.Results: Of 2968 patients included (mean ± SD age 46 ± 18 years, 53% female), 87 patients (3%) had a PE diagnosed at 3 months. A total of 2908 were followed-up at 3 months and analyzed. Using the PERC rule with and without the hemoptysis item, there were 13 and 14 missed cases of PE, respectively (failure rate 0.45% [95% CI 0.25%-0.78%] and 0.48% [95% CI 0.27%-0.82%]). Using the YEARS strategy, there were 11 missed PE cases with or without the hemoptysis item (false-negative rate 0.57% [95% CI 0.30%-1.05%]). With the PERC and YEARS rule, removing the hemoptysis item would have led to a 1% reduction in chest imaging. The PEGeD strategy was not modified by the removal of the hemoptysis item.Conclusions: The hemoptysis item could be safely removed from the PERC, YEARS, and PEGeD CDRs. However, there was no subsequent clinically relevant reduction of chest imaging.

International audience; Background: Severely ill patients with SARS-CoV-2 have an increased risk of venous thromboembolism (VTE) i.e., deep vein thrombosis and pulmonary embolism. However, the VTE risk in patients with mild and moderate COVID-19, hospitalized or managed at home, remain uncertain. The aims of this study were to assess the rate and the risk factors symptomatic VTE, in patients with mild and moderate COVID-19 and to compare them to a cohort of similar patients without COVID-19. Methods: Patients presenting to the emergency department (ED) of participating centers for confirmed or probable mild or moderate COVID-19 and not having acute VTE were included. This COVID-19 cohort was retrospectively compared to a prospective cohort of similar ED patients using propensity score matching. The main outcome was the rate of symptomatic VTE within the 28 days after ED presentation. Results: A total of 2292 patients were included in the COVID-19 cohort. The 28-day incidence of symptomatic VTE was 1.3% (n = 29/2292, 95%CI: 0.9 to 1.8), 2.3% (n = 20/866, 95%CI: 1.5 to 3.5) in moderate COVID-19 patients and 0.6% (n = 9/1426; 95%CI: 0.3 to 1.2) in mild COVID-19 patients managed as outpatients. An age over 65 years and hospitalization were independent risk factors of VTE. After adjustment, patients in the COVID19 cohort had an absolute increase in over symptomatic VTE risk of +1.69% (95%CI, 0.88 to 2.51) versus patients in the comparison cohort (n = 1539). Conclusions: Patients with moderate COVID-19 presenting to the ED had a high risk of subsequent VTE. Trial registration: Ethics committee of the CHU of Angers (N degrees 2020/87).

The optimal strategy for the diagnosis of pulmonary embolism (PE) in the emergency department (ED) remains debated. To reduce the need of imaging testing, several rules have been recently validated using an elevated D-dimer threshold.To validate the safety of different diagnostic strategies and compare the efficacy in terms of chest imaging testing.Post-hoc analysis of individual data of 3330 adult patients without a high clinical probability of PE in the ED followed-up at 3 months in France and Spain (1916 from the PROPER cohort, 1414 from the MODIGLIANI cohort).Four diagnostic strategies with an elevated D-dimer threshold if PE is unlikely. The YEARS combined with Pulmonary Embolism Rule-out Criteria (PERC) the pulmonary embolism graduated D-dimer (PEGeD) combined with PERC and the 4-level pulmonary embolism probability score (4PEPS) rules were assessed. A modified simplified (MODS) rule with a simplified YEARS reduced to the sole item of "Is PE the most likely diagnosis" combined with PERC was also tested.The primary outcome was the proportion of diagnosed PE or deep venous thrombosis at 3 months in patients in whom PE could have been excluded without chest imaging according to the tested strategy. The safety of a strategy was confirmed if the failure rate was less than 1.85%. The secondary outcome was the use of imaging testing according to each rule.Among 3330 analyzed patients, 150 (4.5%) had a PE. The number of missed PEs were 25, 29, 30 and 26 for the PERC+YEARS, PERC+PEGeD, 4PEPS and MODS rules respectively, with a failure rate of 0.75% (95% CI 0.51% to 1.10%), 0.87% (0.61% to 1.25%), 0.90% (0.63% to 1.28%) and 0.78% (0.53% to 1.14%) respectively. There was no significant difference in the failure rate between rules. Except for a significant lower use of chest imaging for 4PEPS compared to YEARS (14.9% vs 16.3%, difference -1.4% [95%CI -2.1% to -0.8%]), there was no difference in the proportion of imaging testing.In this post-hoc analysis of patients with suspicion of PE, YEARS and PEGeD combined with PERC, and 4PEPS were safe to exclude PE. The safety of the modified simplified MODS strategy was also confirmed. There was no significant difference of the failure rate between strategies.

International audience; Aims: The objective was to compare major bleeding risk of direct oral anticoagulants (DOACs; per type and dose) with vitamin K antagonists (VKAs), irrespective of indication, using real-world data.Methods: A population-based prospective cohort study, using the French national health data system (SNIIRAM), identified 47 469 adults living within 5 well-defined geographical areas, who were new users of oral anticoagulants in the period 2013-2015: 20 205 VKA users, 19 579 rivaroxaban users, 4225 dabigatran users and 3460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism).Results: Compared to VKAs, high and low-dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37-0.82 and 0.54, 0.26-1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29-0.58 and 0.41, 0.22-0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding.Conclusion: There is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.

Background 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. Methods and findings 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. Conclusions 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.

Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. Data Sources: MEDLINE from 1 January 1995 until 1 January 2021. Study Selection: 16 studies assessing at least 1 diagnostic strategy. Data Extraction: Individual-patient data from 20553 patients. Data Synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE con -sidered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probabil-ity-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresh-olds, with failure rates varying between 2% and 4% in the pre-defined patient subgroups. Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verifica-tion bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Conclusion: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. Primary Funding Source: Dutch Research Council. (PROSPERO: CRD42018089366)

BackgroundThe aim was to describe the organisational changes in French EDs in response to the COVID-19 pandemic with regard to architectural constraints and compare with the recommendations of the various bodies concerning the structural adjustments to be made in this context.MethodsAs part of this cross-sectional study, all heads of emergency services or their deputies were contacted to complete an electronic survey. This was a standardised online questionnaire consisting of four parts: characteristics of the responding centre, creation of the COVID-19 zone and activation of the hospital’s emergency operations plan, flow and circulation of patients and, finally, staff management. Each centre was classified according to its workload related to COVID-19 and its size (university hospital centre, high-capacity hospital centre and low-capacity hospital centre). The main endpoint was the frequency of implementation of international guidelines for ED organisation.ResultsBetween 11 May and 20 June 2020, 57 French EDs completed the online questionnaire and were included in the analysis. Twenty-eight EDs were able to separate patient flows into two zones: high and low viral density (n=28/57, 49.1%). Of the centres included, 52.6% set up a specific triage area for patients with suspected COVID-19 (n=30/57). Whereas, in 15 of the EDs (26.3%), the architecture made it impossible to increase the surface area of the ED.ConclusionAll EDs have adapted, but many of the changes recommended for the organisation of ED could not be implemented. ED architecture constrains adaptive capacities in the context of COVID-19.

AIMS: The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment. METHODS AND RESULTS: Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm. CONCLUSIONS: For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications., SCOPUS: ar.j, info:eu-repo/semantics/published

International audience; Purpose Low-dose parenteral anticoagulation has demonstrated its efficacy for venous thromboembolism prophylaxis in randomized trials. However, current practice is not widely documented. In ambulatory settings, we aimed to provide an overview of the clinical use of low-dose parenteral anticoagulation in France and to assess the incidence of major bleeding and death rates. Methods A population-based prospective cohort study using the French national health data system (SNIIRAM) identified 142,815 adults living in five well-defined geographical areas who had a course of low-dose parenteral anticoagulants (a total of 150,389 courses) in the period 2013-2015. The main outcome measures were the types of low-dose parenteral anticoagulant, the duration and the clinical context. Adjusted incidence rate ratios (IRR) were derived from Poisson models. Results Enoxaparin was the most frequently prescribed anticoagulant (58.9%) followed by tinzaparin (27.3%) and fondaparinux (10.9%). Patients receiving unfractionated heparin (N= 766, 0.53%) were older, more frequently had renal disease (48.75%) and had a higher modified HAS-B(L)ED score (>= 3 in 61.6%) than patients receiving low-molecular weight heparin (LMWH). Surgical thrombo-prophylaxis was the most frequent indication (47.6%), followed by medical prophylaxis (29.9%). Course durations were in line with regulatory agency specifications. Only 43 (0.028%) major bleeding events and 478 (0.32%) deaths were observed. Adjusted IRRs for major bleeding or death were not significantly different for dalteparin/nadroparin, tinzaparin or fondaparinux compared to enoxaparin. Conclusion Very low incidence rates of major bleeding and all-cause mortality were observed. Our study confirms the safety of LMWHs and fondaparinux in thrombo-prophylaxis in ambulatory settings.

Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE.Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE?In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months.Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97).In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided.ClinicalTrials.gov; No.: NCT02746185; URL: www.gov.

This review examines the recent progress in the initial management of pulmonary embolism (PE). Diagnostic strategies allowing the safe decrease of imaging testing have been proposed. New modalities of catheter-based interventions have emerged for hemodynamically unstable PE patients. For normotensive PE patients, direct oral anticoagulant treatment has become the new norm and a large proportion of patients are eligible for home treatment.

International audience; BACKGROUND: There is little data on major muscular hematomas and the little there is has mainly focused on patients exposed to oral anticoagulants. OBJECTIVE: To describe the clinical characteristics, management and outcomes of patients admitted to emergency department (ED) for major muscular hematoma associated with an antithrombotic agent, and to identify predictors of in-hospital mortality. PATIENTS AND METHODS: Over a three-year period, all consecutive cases of adult patients admitted to the ED of 5 tertiary care hospitals for major muscular hematoma while exposed to an antithrombotic agent were prospectively collected and medically validated. Clinical and biological data, therapeutic management of the bleeding event, and in-hospital mortality were collected from the medical records and compared across five groups of hematoma locations. Potential confounders were taken in account using a multivariate binomial regression model. RESULTS: Three hundred and seventy-five patients were included (mean age = 81.4 years): 271 were exposed to vitamin K antagonists, 58 to parenteral anticoagulants (heparin, LMWH, fondaparinux), 33 to antiplatelets, and 13 to direct oral anticoagulants. The muscular hematomas were located in the lower limbs (n = 198), the rectus sheath (n = 71), the iliopsoas (n = 45), the upper limbs (n = 33), or elsewhere (n = 28). Reversal therapy was prescribed for 48.5% of patients, red cell transfusions for 63.6%, surgery for 12.3% and embolization for 3.5%. For 84% of patients, hospitalization was required, with a median length of stay of 10 days. Overall, in-hospital mortality was 8.5%. Reversal therapy, the need for intensive care and mortality were significantly more frequent among patients with iliopsoas hematomas. The independent predictors of in-hospital mortality were: decrease in mean arterial pressure (RR = 1.84), decrease in hemoglobin level (RR = 1.37) and the iliopsoas location (RR = 3.06). CONCLUSION: Frail elderly patients with major muscular hematomas linked to antithrombotic agents risk substantial morbidity and in-hospital mortality. The iliopsoas location was the most life-threatening bleeding site. Close observation of this population is warranted to ensure better outcomes.

Pulmonary embolism (PE) remains a diagnostic challenge in 2021. As the pathology is potentially fatal and signs and symptoms are nonspecific, further investigations are classically required. Based on the Bayesian approach, clinical probability became the keystone of the diagnostic strategy to rule out PE in the case of a negative testing. Several clinical probability assessment methods are validated: gestalt, the Wells score, or the revised Geneva score. While the debate persists as to the best way to assess clinical probability, its assessment allows for the good interpretation of the investigation results and therefore directs the correct diagnostic strategy. The wide availability of computed tomography pulmonary angiography (CTPA) resulted in a major increase in investigations with a moderate increase in diagnosis, without any notable improvement in patient outcomes. This leads to a new challenge for PE diagnosis which is the limitation of the number of testing for suspected PE. We review different strategies recently developed to achieve this goal. The last challenge concerns the implementation in clinical practice. Two approaches are developed: simplification of the strategies versus the use of digital support tools allowing more sophisticated strategies. Artificial intelligence with machine-learning algorithms will probably be a future tool to guide the physician in this complex approach concerning acute PE suspicion.

IntroductionIn the context of the COVID-19 pandemic, early identification of patients who are likely to get worse is a major concern. Severity mainly depends on the development of acute respiratory distress syndrome (ARDS) with a predominance of subpleural lesions. Lung point-of-care ultrasonography (L-POCUS) is highly effective in detecting pulmonary peripheral patterns and may be appropriate for examining patients with COVID-19. We suggest that L-POCUS performed during the initial examination may identify patients with COVID-19 who are at a high risk of complicated treatment or unfavourable evolution.Methods and analysisPoint-of-care ultrasonography for risk stratification of non-critical COVID-19 patients on admission is a prospective, multicentre study. Adult patients visiting the emergency department (ED) of participating centres for suspected or confirmed COVID-19 are assessed for inclusion. Included patients have L-POCUS performed within 48 hours following ED admission. The severity of lung damage is assessed using the L-POCUS score based on 36 points for ARDS. Apart from the L-POCUS score assessment, patients are treated as recommended by the WHO. For hospitalised patients, a second L-POCUS is performed at day 5±3. A follow-up is carried out on day 14, and the patient’s status according to the Ordinal Scale for Clinical Improvement for COVID-19 from the WHO is recorded.The primary outcome is the rate of patients requiring intubation or who are dead from any cause during the 14 days following inclusion. We will determine the area under the ROC curve of L-POCUS.Ethics and disseminationThe protocol has been approved by the French and Belgian Ethics Committees and is carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study is funding by a grant from the French Health Ministry, and its findings will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberNCT04338100.

IMPORTANCE: The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain. OBJECTIVE: To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017. EXPOSURES: Acutely worsening respiratory symptoms in patients with COPD. MAIN OUTCOMES AND MEASURES: The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not. RESULTS: Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P

Diagnosis of pulmonary embolism (PE) relies on the sequential use of pretest probability (PTP), plasma D-dimer, and computed tomography pulmonary angiography. D-dimer

BACKGROUND: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method. RESEARCH QUESTION: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely? STUDY DESIGN AND METHODS: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment. RESULTS: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26). INTERPRETATION: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov.

IntroductionPatients with lower limb trauma requiring orthopaedic immobilisation may be at risk of venous thromboembolism but opinions differ about who may benefit from thromboprophylactic anticoagulant treatment.The aim of this CASTING study is to demonstrate the safety of thromboprophylaxis based on the Thrombosis Risk Prediction for patients with cast immobilisation (TRiP(cast) score with regards to the 3-month incidence of symptomatic venous thromboembolism events in low-risk patients not receiving thromboprophylaxis, as well as the usefulness of this strategy on the rate of patients receiving anticoagulant treatment in comparison to current practice.Methods and analysisCASTING will be a stepped-wedge cluster randomised controlled clinical trial, performed in 15 emergency departments in France and Belgium. With their informed consent, outpatients admitted to one of the participating emergency departments for a lower limb trauma requiring orthopaedic immobilisation without surgery will be included. All centres will begin the trial with the ‘observational period’ and, every 2 weeks, 1 centre will be randomly assigned to switch to the ‘interventional period’ and to apply the TRiP(cast) score, in which only patients with a score ≥7 will receive thromboprophylactic anticoagulant treatment. The primary endpoint is the rate of clinical thromboembolic events within 90 days following the inclusion of low-risk patients not receiving thromboprophylaxis.Ethics and disseminationThe protocol has been approved by the Comité de Protection des Personnes Sud I (Ethics Review ID-RCB: 2019-A01829-48) for France and the Comité d’éthique hôpital-facultaire Saint Luc (N° B403201941338) for Belgium. It is carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The findings of this study will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberNCT04064489.

Background: The diagnosis of pulmonary embolism (PE) in pregnant women represents an ongoing challenge. As in the general population, the first step in pregnant women with suspected PE consists of assessing clinical pre-test probability (PTP). However, no dedicated clinical decision rule has been developed in this population. Objective: To propose a new version of the Geneva score adapted to pregnant women with suspected PE. Methods: Data from a multicenter, prospective management outcome study including 395 women with suspected PE, in whom PTP was assessed using the Geneva score, were used. We first removed items which were present in none of the patients (cancer, age >65 years). Receiver operating characteristic (ROC) curve analysis was then performed for quantitative variables and the optimal threshold defined. The obtained Pregnancy-Adapted Geneva Score (PAG Score) comprised seven items, including an age 40 years or older and a heart rate >110 beats per minute. Results: The PAG Score showed a high discriminative power to identify patients with a low, intermediate, or high PTP, associated with increasing prevalence of PE, 2.3%, 11.6%, and 61.5%, respectively. The ROC curves showed an area under the curve of 0.795 for the PAG Score compared to 0.684 for the Geneva score. Conclusion: In pregnant women with suspected PE, the PAG Score shows a high discriminative power to identify patients at low, intermediate, or high PTP. It has the strength of being a fully objective decision rule, is clinically relevant, easy to compute, and should now be tested in a prospective outcome study.

Current guidelines for patients with suspected acute myocardial infarction are mainly based on troponin testing, commonly requiring an emergency department visit. HEAR score (History, Electrocardiogram, Age, and Risk factors) is a risk stratification tool validated in Europe, deduced from the HEART score (History, Electrocardiogram, Age, Risk factors, and Troponin), already implemented in clinical practice. We aimed to validate the HEAR score to rule out an acute myocardial infarction without needing biomarker testing.Retrospective cohort study at 15 emergency departments between May 2016 and December 2017. All adult encounters evaluated for possible acute myocardial infarction with a physician-documented HEART score for health plan members of Kaiser Permanente Southern California were included. Patients with an ST-segment elevation myocardial infarction, those under hospice care, or with a "do not resuscitate" status were excluded. HEAR scores from 0-8 were calculated for each encounter and used to report 30-day acute myocardial infarction or all-cause mortality for each score.There were 22,109 patient encounters included in the study. Overall, 30-day acute myocardial infarction or death occurred in 1.1% of patients. Among the 4106 patients (19%) with a HEAR score2, 3 died and 2 experienced an acute myocardial infarction within 30 days (0.1%; 95% confidence interval, 0.1-0.3). Sensitivity and specificity were 97.9% and 18.8%, respectively.A low HEAR score may accurately identify patients with a very low risk of 30-day acute myocardial infarction or death, representing a cohort of patients who might appropriately forego biomarker testing. Future research is warranted to assess the impact of implementing the HEAR score into routine clinical practice.

Introduction Methods for prognosis assessment and patient management in acute pulmonary embolism (PE) are much debated among physicians. We conducted an online survey to determine physician's attitudes and barriers towards the use of prognostic models when treating patients with acute PE. Method Physicians members of the French and the European scientific societies for emergency medicine or of a French thrombosis research network were reached by their respective scientific societies and invited to participate via email. The questionnaire was a mixture of close-ended with yes-no or multiple-choice options and a small number of open-ended questions. Results The survey included 461 respondents. The most commonly used prognostic tools were clinical judgment (36%) and prognostic models (29.5%). Prognostic models were used by 57% of respondents in more than half of all cases and prognostic indicators by 62% in addition to prognostic models. Affiliation group and type of hospital emerged as independent predictors for choosing prognostic models. Many (52%) reported lack of familiarity with the models and reported clinical judgment (60%) or hospital checklists (73%) as being as good as or better than prognostic models. The highest acceptable 30-day mortality rate limit for early discharge or outpatient management was deemed to be 1%, but few patients are discharged early or completely managed on an outpatient basis. Conclusions This survey provides new information for implementing knowledge translation strategies to improve prognostic risk assessment for acute PE patients, and highlights the need for considering the use of clinical judgment and hospital checklists in future clinical research.

International audience; Background - Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice. Methods and findings - A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013-2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (≤ 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors. Conclusion - The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication. Trial registration - NCT02886533.

International audience; D-dimer is a soluble fibrin degradation product deriving from the plasmin-mediated degradation of cross-linked fibrin. D-dimer can hence be considered a biomarker of activation of coagulation and fibrinolysis, and it is routinely used for ruling out venous thromboembolism (VTE). D-dimer is increasingly used to assess the risk of VTE recurrence and to help define the optimal duration of anticoagulation treatment in patients with VTE, for diagnosing disseminated intravascular coagulation, and for screening medical patients at increased risk of VTE. This review is aimed at (1) revising the definition of D-dimer; (2) discussing preanalytical variables affecting the measurement of D-dimer; (3) reviewing and comparing assay performance and some postanalytical variables (e.g. different units and age-adjusted cutoffs); and (4) discussing the use of D-dimer measurement across different clinical settings.

Summary Background The ability of the pulmonary embolism rule-out criteria (PERC) to exclude pulmonary embolism without further testing remains debated outside the USA, especially in the population with suspected pulmonary embolism who have a high prevalence of the condition. Our main objective was to prospectively assess the predictive value of negative PERC to rule out pulmonary embolism among European patients with low implicit clinical probability. Methods We did a multicentre, prospective, observational study in 12 emergency departments in France and Belgium. We included consecutive patients aged 18 years or older with suspected pulmonary embolism. Patients were excluded if they had already been hospitalised for more than 2 days, had curative anticoagulant therapy in progress for more than 48 h, or had a diagnosis of thromboembolic disease documented before admission to emergency department. Physicians completed a standardised case report form comprising implicit clinical probability assessment (low, moderate, or high) and a list of risk factors including criteria of the PERC rule. They were asked to follow international recommendations for diagnostic strategy, masked to PERC assessment. The primary endpoint was the proportion of patients with low implicit clinical probability and negative PERC who had venous thromboembolic events, diagnosed during initial diagnostic work-up or during 3-month follow-up, as externally adjudicated by an independent committee masked to the PERC and clinical probability assessment. The upper limit of the 95% CI around the 3-month thromboembolic risk was set at 3%. We did all analyses by intention to treat, including all patients with complete follow-up. This trial is registered with ClinicalTrials.gov, number NCT02360540. Findings Between May 1, 2015, and April 30, 2016, 1773 consecutive patients with suspected pulmonary embolism were prospectively assessed for inclusion, of whom 1757 were included. 1052 (60%) patients were classed as having low clinical probability, 49 (4·7%, 95% CI 3·5–6·1) of whom had a venous thromboembolic event. In patients with a low implicit clinical probability, 337 (32%) patients had negative PERC, of whom four (1·2%; 95% CI 0·4–2·9) went on to have a pulmonary embolism. Interpretation In European patients with low implicit clinical probability, PERC can exclude pulmonary embolism with a low percentage of false-negative results. The results of our prospective, observational study allow and justify an implementation study of the PERC rule in Europe. Funding French Ministry of Health.

Background Sepsis management in the Emergency Department remains a daily challenge. The Surviving Sepsis Campaign (SSC) has released three-hour bundle. The implementation of these bundles in European Emergency Departments remains poorly described. The main objective was to assess the compliance with the Severe Sepsis Campaign 3-h bundle (blood culture, lactate dosage, first dose of antibiotics and 30 ml/kg fluid challenge). Secondary objectives were the analysis of the delay of severe sepsis recognition and description of the population. Methods In accordance with STROBE statement, we performed a retrospective study in two French University Hospital Emergency Departments from February to August 2015. Patients admitted during the study period were screened using the electronic files of the hospital databases. Patient’s files were reviewed and included in the study if they met severe sepsis criteria. Demographics, comorbities, treatments were recorded. Delays from admission to severe sepsis diagnosis, fluid loading onset and antibiotics administration were calculated. Results One hundred thirty patients were included (76 men, mean age 71 ± 14 years). Blood culture, lactate dosage, antibiotics and 30 ml/kg fluid loading were performed within 3 hours in % [95% confidence interval] 100% [96–100%], 62% [54–70%], 49% [41–58%] and 19% [13–27%], respectively. 25 patients out of 130 (19% [13–27%]) fulfilled each criteria of the 3-h bundle. The mean fluid loading volume was 18 ± 11 ml/kg. Mean delay between presentation and severe sepsis diagnosis was 200 ± 263 min, from diagnosis to fluid challenge and first antibiotic dose, 10 ± 27 min and 20 ± 55 min, respectively. Conclusion Compliance with SSC 3-h bundle and delay between admission and sepsis recognition have to be improved. If confirmed by other studies, an improvement program might be deployed.

International audience; Bleeding represents the most recognized and feared complications of antithrombotic drugs including oral anticoagulants. Previous studies showed inconsistent results on the safety profile. Among explanations, bleeding definition could vary and classification bias exists related to the lack of medical evaluation. To quantify the risk of major haemorrhagic event and event-free survival associated with antithrombotic drugs (vitamin K antagonist [VKA], non-VKA anticoagulant [NOAC], antiplatelet agent, parenteral anticoagulant) in 2012–2015, we linked the French nationwide Health Insurance database (SNIIRAM) with a local ‘emergency database’ (clinical and biological data collected in clinical records). In the VKA-NOAC comparison, a Cox regression analysis will be used to estimate the hazard ratio of major haemorrhagic event adjusted on gender, modified HAS-BLED score and comorbidities. A distinction on the type of major haemorrhagic event (intracranial, gastrointestinal and other haemorrhagic events) was made. We present here the study protocol and the database linkage results. Using six linkage keys, among 3 837 557 hospital visits identified in SNIIRAM, 5264 have been matched with a major haemorrhagic event identified in the ‘emergency database’, thus clinically confirmed. The 1090 unmatched haemorrhagic events could be explained by the fact that patients were not extracted in the SNIIRAM database (patients living in accommodation establishment with internal use of pharmacy, military people with specific insurance…). We showed the value of SNIIRAM enrichment with a clinical database, a necessary step to categorize haemorrhagic events by a clinically relevant definition and medical validation; it will allow to estimate more accuracy each type of haemorrhagic event.

Falls in older adults are a frequent reason for admission to the emergency department, associated with greater morbidity and mortality risks, and justify specialized geriatric expertise. Our objective was to determine i) the number of older fallers admitted to the emergency department for a serious fall, and ii) the proportion of those who were referred to a geriatrician in the following 12 months.We included all patients aged 75 and over admitted to the emergency department of the University hospital of Angers, France, for a fall between 1st October and 1st November 2015. The consensual criteria proposed by the French national authority for health (2009) were used to define serious falls.Of the 214 older fallers admitted to the emergency department, 213 (99.5%) had at least one severity criterion for the fall. Only 40 older patients (18.7%) were referred to a geriatrician during the following 12 months. They exhibited more frequently a post-fall syndrome (p=0.007), more than 3 fall risk factors (p0.001), and took more often an anticoagulant (p=0.032) than those who had not been referred to a geriatrician.Although almost all older fallers admitted to the emergency room had experienced a serious fall, only a minority of them received a geriatric assessment in the following year.

Comparison of the Wells score and the revised Geneva score as a tool to predict pulmonary embolism in outpatients over 65 years of age.The incidence and mortality of pulmonary embolism (PE) is high in the elderly. The Wells score (SW) and the revised Geneva score (RGS) have been validated in patient populations with a large age range. The aim of this study was to compare the predictive accuracy of these two scores in diagnosis of PE in patients over 65 years of age.A prospective multicentre study (nine French and three Belgian centres) was conducted at the same time as the PERCEPIC study. A total of 1757 patients admitted with suspected PE were included and divided into two groups according to age (≥65 years or65 years). The pre-test probability of PE was assessed prospectively for the RGS. The SW was calculated retrospectively. The predictive accuracy of the two scores was compared by the area under the curve (AUC) of the ROC curves.The overall prevalence of PE was 11.3%. The prevalence among patients aged ≥65 in the low, moderate and high pre-test probability groups, evaluated using the WS and was respectively 13.5% (CI 95%: CI 9.9-17.3), 28.2% (CI 22.1-34.3), 50% (CI 26-74) and 8.1% (CI 3.2-12.9), 22.3% (CI 18.2-26.3), 43.7% (CI 25.6-61.9) using the RGS. The AUC for the WS and RGS for patients aged ≥65 was 0.632 (CI 0.574-0.691) and 0.610 (CI 0.555-0.666). The difference between the AUCs was not statistically significant (p = .441).In the population for this study, the WS and RGS have the same PE diagnostic accuracy in patients over age 65. This result should be validated in a prospective study that directly compares these scores.

Key Points Question Can a pretest probability score make it possible to rule out pulmonary embolism solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing? Findings In this study, the 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) was derived and validated using databases from 3 merged management studies. The safety and the efficacy of the 4PEPS strategy was confirmed in 2 external validation cohorts (false-negative rates: 0.71% and 0.89%; absolute reductions in imaging testing: −19% and −22%, respectively). Meaning The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected pulmonary embolism., This study derives and validates a 4-level pretest probability rule that makes it possible to rule out pulmonary embolism solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected pulmonary embolism., Importance In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern. Objective To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE. Design, Setting, and Participants This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019. Main Outcomes and Measures The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing. Results Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from −2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were −22% (95% CI, −26 to −19) and −19% (95% CI, −22 to −16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing. Conclusions and Relevance The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.

Summary Background Clear guidelines for the investigation of occult malignancy after unprovoked venous thromboembolism are not yet available. 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT could serve as a comprehensive screening strategy for occult malignancy in this context. We aimed to compare a screening strategy based on 18 F-FDG PET/CT with a limited screening strategy for detection of malignant disease in patients with unprovoked venous thromboembolism. Methods In an open-label, multicentre, randomised study we enrolled patients from four French university hospitals. Patients aged 18 years or older, diagnosed with unprovoked venous thromboembolism (not provoked by a major inherited or acquired risk factor) were invited to participate. Patients were randomly assigned in a 1:1 ratio to a limited screening strategy (physical examination, usual laboratory tests, and basic radiographs) or a screening strategy consisting of the limited strategy plus an 18 F-FDG PET/CT scan. Randomisation was done with a dedicated central web-based randomisation system, in block sizes of six, stratified by centre, and concealed from the investigators. Patients and investigators were not masked to study group assignment. Patients were followed up for 2 years. The primary outcome was the proportion of patients with a cancer diagnosis in each group after the initial screening assessment. Analyses were conducted in modified intention-to-test and per-protocol populations. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275. Findings Between March 3, 2009, and Aug 18, 2012, we enrolled and randomly assigned 399 patients; five withdrew consent, leaving 197 in each group for the modified intention-to-test analysis. After initial screening assessment, cancer was diagnosed in 11 (5·6%) patients in the 18 F-FDG PET/CT group and four (2·0%) patients in the limited screening group (absolute risk difference 3·6%, 95% CI −0·4 to 7·9; p=0·07). At the initial screening assessment, seven (64%) of the 11 cancers diagnosed in the 18 F-FDG PET/CT group were early-stage compared with two of four cancers diagnosed in the limited screening group (p=1·00). One (0·5%) occult malignancy was detected in 186 patients who had negative initial screening in the 18 F-FDG PET/CT group, compared with nine (4·7%) in 193 patients in the limited screening group (absolute risk difference 4·1%, 95% CI 0·8 to 8·4, p=0·01). Overall, five (42%) of the 12 cancers diagnosed in the 18 F-FDG PET/CT group were advanced stage, compared with seven (54%) of the 13 cancers diagnosed in the limited screening group (p=0·70). 16 patients died during follow-up, eight (4·1%) in each group. Two (1·0%) patients in the 18 F-FDG PET/CT group and five (2·5%) in the limited screening group had cancer-related deaths. Interpretation A strategy including limited screening and a 18 F-FDG PET/CT was not associated with a significantly higher rate of cancer diagnosis after unprovoked venous thromboembolism. The risk of subsequent cancer diagnosis was, however, lower in patients who had negative initial screening that included 18 F-FDG PET/CT than in patients who had negative initial limited screening. Whether or not 18 F-FDG PET/CT might be useful in a more selected population of patients with a high risk of cancer remains to be determined. Funding Programme Hospitalier de Recherche Clinique (French Department of Health).

Introduction Unprovoked venous thromboembolism (VTE) may be the first manifestation of an undiagnosed cancer. We assessed the cost-effectiveness of 18F-Fluorodesoxyglucose Positron Emission/Computed Tomography (FDG PET/CT) plus limited screening and limited screening strategies in patients with unprovoked VTE from the perspectives of the Ontario (Canada) and French health care systems. Methods We conducted a cost-effectiveness analysis based on a published randomized controlled trial of 394 patients aged 18 years or older who were diagnosed with unprovoked VTE. We obtained data with respect to efficacy and health care utilization from the published trial. The primary measure of effectiveness was the number of avoided cases of delayed cancer diagnosis and the secondary measure of effectiveness was the quality adjusted life year (QALY) at the end of the study in each group. We used generalized linear models to estimate incremental cost-effectiveness ratios (ICER) while controlling for patient demographic and clinical characteristics. Results were presented as the incremental cost to avoid one case of delayed cancer diagnosis and the incremental cost per QALY gained. The 95% confidence intervals (CIs) were estimated using bootstrap re-sampling procedures with 5000 iterations. Results Compared to a limited screening strategy, the ICER of limited strategy plus FDG PET/CT scan was C$ 26,840.19 (95% CI: C$ 24,046.51; C$ 34,581.53) per one avoided case of delayed cancer diagnosis from the Ontario health system perspective and €16,370.45 (95% CI: € 9904.48; € 39,578.91) per one avoided case of delayed cancer diagnosis from the French health system perspective. The probabilities that addition of FDG PET/CT to limited screening is cost-effective rose with increasing willingness to pay values. Compared with the limited screening, the extensive screening was associated with C$ 3412.85 per QALY gained (95% CI: 1463.89; −13,935.88) from the Ontario health system perspective and €2162.83 per QALY gained (95% CI 958.78; −10,544.42) from the French health system perspective. Conclusion Addition of a FDG PET/CT for occult cancer diagnosis was associated with better health outcomes (fewer cases of delayed cancer diagnosis and greater QALYs) and a higher cost from the perspective of publicly funded health care systems; the cost-effectiveness results are however highly uncertain.

International audience; BACKGROUND: This study aimed to determine the failure rate of a combination of the PERC and the YEARS rules for the diagnosis of pulmonary embolism (PE) in the emergency department (ED).METHODS: We performed a retrospective analysis of two European cohorts of emergency patients with low gestalt clinical probability of PE (PROPER and PERCEPIC). All patients we included were managed using a conventional strategy (D-dimer test, followed, if positive, by computed tomographic pulmonary angiogram (CTPA). We tested a diagnostic strategy that combined PERC and YEARS to rule out PE. The primary endpoint was a thromboembolic event diagnosed in the ED or at 3-months follow-up. Secondary endpoints included a thromboembolic event at baseline in the ED and a CTPA in the ED. Ninety-five percent confidence intervals (CIs) of proportions were calculated with the use of Wilson's continuity correction.RESULTS: We analyzed 1,951 patients (mean±SD age= 47±18years, 56% women) with an overall proportion of patients with PE of 3.5%. Both PERC and YEARS strategies were associated with 11 missed PE in the ED: failure rate 0.57 (95% CI= 0.32-1.02). At 3-month follow-up, the overall failure rate was 0.83% (95% CI= 0.51-1.35). Among the 503 patients who underwent a CTPA (26%), the use of the PERC-YEARS combination would have ruled out PE without CTPA in 249 patients (50% [95%CI= 45%-54%], absolute reduction13% (95% CI= 11%-14%]).CONCLUSION: The combination of PERC then YEARS was associated with a low risk of PE diagnostic failure and would have resulted in a relative reduction of almost half of CTPA.

Summary Background Remote ischaemic preconditioning (RIPC) protects tissues against ischaemia-reperfusion (I/R) injury, a common occurrence in several clinical settings. Aims To evaluate whether RIPC has a beneficial impact on walking disability in arterial intermittent claudication. Methods A total of 20 patients with proven intermittent claudication underwent two treadmill walking tests with a 7-day interval in between; they were randomized according to the order in which they received either RIPC or a control procedure before the first treadmill test, with a crossover at the second test. Patients received three cycles of alternating 5-minute inflation and 5-minute deflation of blood-pressure cuffs on both arms, with inflation to a pressure of 200 mmHg in the RIPC procedure or 10 mmHg in the control procedure. Walking distances and limb oxygenation data, assessed with transcutaneous oximetry and near infrared spectroscopy measurements, were obtained during both RIPC and control procedures in all patients. Results Similar exercise intensities were achieved after the control and RIPC procedures. Walking distances did not significantly differ after the control and RIPC procedures (204 [141–259] m vs 215 [162–442] m, respectively; P = 0.22). Similarly, no difference was observed in terms of transcutaneous oxygen pressure change and near infrared spectroscopy measurements during exercise between the two procedures. Conclusion RIPC did not improve walking distance or limb ischaemia variables in patients with peripheral artery disease and intermittent claudication.

Beside scores, doctor–patient relationship still key to assess individual benefit of extended anticoagulationhttp://ow.ly/uWaL303tb77

In patients consulting in the Emergency Department for chest pain, a HEART score ≤ 3 has been shown to rule out an acute coronary syndrome (ACS) with a low risk of major adverse cardiac event (MACE) occurrence. A negative CARE rule (≤ 1) that stands for the first four elements of the HEART score may have similar rule-out reliability without troponin assay requirement. We aim to prospectively assess the performance of the CARE rule and of the HEART score to predict MACE in a chest pain population. Prospective two-center non-interventional study. Patients admitted to the ED for non-traumatic chest pain were included, and followed-up at 6 weeks. The main study endpoint was the 6-week rate of MACE (myocardial infarction, coronary angioplasty, coronary bypass, and sudden unexplained death). 641 patients were included, of whom 9.5% presented a MACE at 6 weeks. The CARE rule was negative for 31.2% of patients, and none presented a MACE during follow-up [0, 95% confidence interval: (0.0-1.9)]. The HEART score was ≤ 3 for 63.0% of patients, and none presented a MACE during follow-up [0% (0.0-0.9)]. With an incidence below 2% in the negative group, the CARE rule seemed able to safely rule out a MACE without any biological test for one-third of patients with chest pain and the HEART score for another third with a single troponin assay.

18F-Fluorodesoxyglucose Positron-Emission-Tomography combined with Computed-Tomography (FDG PET/CT) might be an attractive tool for cancer screening in patients with venous thromboembolism (VTE), allowing non-invasive whole-body imaging. One of the frequent criticisms to the use of FDG PET/CT for screening is the potential for false positive results leading to unnecessary/invasive investigations. Our aim was to compare the frequency and invasiveness of additional testing following extensive and limited screening strategies for occult malignancy in patients with unprovoked VTE. We analysed patients included in the MVTEP study, a randomized trial that compared a screening strategy based on FDG-PET/CT with a limited screening strategy for occult malignancy diagnosis in patients with unprovoked VTE. All additional diagnostic procedures following screening were recorded and classified as invasive or non-invasive. A total of 394 patients were analysed. Additional diagnostic procedures realized in patients of each group consisted of 59 tests in patients of the FDG PET/CT group versus 53 tests among the patients from the limited screening group (p=0.65). Overall, 45 (22.8%) patients in the FDG PET/CT group underwent additional diagnostic tests, versus 32 (16.2%) in the limited screening group (absolute risk difference+6.6%, 95% CI -1.3 to +14.4%, p=0.13). Sixteen (8.1%) patients in the FDG PET/CT group underwent invasive procedures, versus 6 (3%) in the limited screening group (absolute risk difference+5.1%, 95% CI +0.5 to +10.0%, p=0.03). We found no statistical difference in the number of additional procedures following each screening strategy. However, a higher number of invasive tests were performed in the FDG PET/CT group.

International audience; Despite clear potential benefits of outpatient care, most patients suffering from pulmonary embolism (PE) are currently hospitalized due to the fear of possible adverse events. Nevertheless, some teams have increased or envisage to increase outpatient treatment or early discharge.We performed a narrative systematic review of studies published on this topic. We identified three meta-analyses and 23 studies, which involved 3671 patients managed at home (n = 3036) or discharged early (n = 535). Two main different approaches were applied to select patients eligible for outpatient in recent prospective studies, one based on a list of pragmatic criteria as the HESTIA rule, the other adding severity criteria (i.e. risk of death) as the Pulmonary Embolism Severity Criteria (PESI) or simplified PESI. In all these studies, a specific follow-up was performed for patients managed at home involving a dedicated team. The overall early (i.e. between 1 to 3 months) complication rate was low, Outpatient management appears to be feasible and safe for many patients with PE.In the coming years, outpatient treatment may be considered as the first line management for hemodynamically stable PE patients, subject to the respect of simple eligibility criteria and on the condition that a specific procedure for outpatient care is developed in advance.

International audience; IMPORTANCE: D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients. OBJECTIVE: To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE. DESIGN, SETTINGS, AND PATIENTS: A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013. INTERVENTIONS: All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period. MAIN OUTCOMES AND MEASURES: The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result. RESULTS: Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings. CONCLUSIONS AND RELEVANCE: Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01134068.

IntroductionThis study protocol describes a trial designed to investigate whether antihistamine alone in patients with acute urticaria does not increase the 7-day Urticaria Activity Score (UAS7) in comparison with an association of antihistamine and glucocorticoids and reduces short-term relapses and chronic-induced urticaria.Methods and analysisThis is a prospective, double-blind, parallel-group, multicentre non-inferiority randomised controlled trial. Two-hundred and forty patients with acute urticaria admitted to emergency department will be randomised in a 1:1 ratio to receive levocetirizine or an association of levocetirizine and prednisone. Randomisation will be stratified by centre. The primary outcome will be the UAS7 at day 7. The secondary outcomes will encompass recurrence of hives and/or itch at day 7; occurrence of spontaneous hives or itch for >6 weeks; patients with angioedema at day 7, and 2, 6, 12 and 24 weeks; new emergency visits for acute urticaria recurrences at days 7 and 14, and 3 months; Dermatology Life Quality Index at days 7 and 14, and 3 and 6 months; and Chronic Urticaria Quality of Life Questionnaire at 6 weeks.Ethics and disseminationThe protocol has been approved by the Comité de Protection des PersonnesSud-Méditerranée II and will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. A steering committee will oversee the progress of the study. Findings will be disseminated through national and international scientific conferences and publication in peer-reviewed journals.Trial registration numberNCT03545464

We sought to derive a parsimonious predictive model to identify a subgroup of patients that will experience a low number of adverse events within 14 days of the diagnosis of pulmonary embolism. Retrospective cohort study of adult patients with acute pulmonary embolism at the Ottawa Hospital between 2007 and 2012. Primary outcome was defined as the composite of all-cause mortality, recurrent venous thromboembolism and major bleeding within 14 days. Multivariate logistic regression models were fit to model the occurrence of the primary outcome so as to guide either outpatient therapy or early discharge after initial admission. Calibration and discrimination were assessed in both the derivation and internal validation cohorts. 1143 patients were included, of whom 42% were treated as outpatients. At pulmonary embolism diagnosis, final score to predict the primary outcome included age, malignancy, intravenous drug or oxygen requirement and systolic blood pressure

BACKGROUND:Misuse of thromboprophylaxis may increase preventable complications for hospitalized medical patients. OBJECTIVES:To assess the net clinical benefit of a multifaceted intervention in emergency wards (educational lectures, posters, pocket cards, computerized clinical decision support systems and, where feasible, electronic reminders) for the prevention of venous thromboembolism. PATIENTS/METHODS:Prospective cluster-randomized trial in 27 hospitals. After a pre-intervention period, centers were randomized as either intervention (n = 13) or control (n = 14). All patients over 40 years old, admitted to the emergency room, and hospitalized in a medical ward were included, totaling 1,402 (712 intervention and 690 control) and 15,351 (8,359 intervention and 6,992 control) in the pre-intervention and intervention periods, respectively. RESULTS:Symptomatic venous thromboembolism or major bleeding (primary outcome) occurred at 3 months in 3.1% and 3.2% of patients in the intervention and control groups, respectively (adjusted odds ratio: 1.02 [95% confidence interval: 0.78-1.34]). The rates of thromboembolism (1.9% vs. 1.9%), major bleedings (1.2% vs. 1.3%), and mortality (11.3% vs. 11.1%) did not differ between the groups. Between the pre-intervention and intervention periods, the proportion of patients who received prophylactic anticoagulant treatment more steeply increased in the intervention group (from 35.0% to 48.2%: +13.2%) than the control (40.7% to 44.1%: +3.4%), while the rate of adequate thromboprophylaxis remained stable in both groups (52.4% to 50.9%: -1.5%; 49.1% to 48.8%: -0.3%). CONCLUSIONS:Our intervention neither improved adequate prophylaxis nor reduced the rates of clinical events. New strategies are required to improve thromboembolism prevention for hospitalized medical patients. TRIAL REGISTRATION:ClinicalTrials.gov NCT01212393.

International audience; IntroductionPERC rule was created to rule out pulmonary embolism (PE) without further exams, with residual PE risk < 2%. Its safety is currently not confirmed in high PE prevalence populations even when combined with low clinical probability assessed by revised Geneva score (RGS). As PERC rule and RGS are 2 similar explicit rules with many redundant criteria, we hypothesized that the combination of PERC rule with gestalt clinical probability could resolve this limitation. Methods We collected prospectively documented clinical gestalt assessments and retrospectively calculated PERC rules and RGS from a prospective study of PE suspected patients. We analyzed performance of combinations of negative PERC with low clinical probability assessed by both methods in high overall PE prevalence population. Results Among the final study population (n = 959), the overall PE prevalence was 29.8%. Seventy-four patients (7.7%) were classified as PERC negative and among them, 4 patients (5.4%) had final diagnosis of PE. When negative PERC was combined with low pretest probability assessed by RGS or gestalt assessment, PE prevalence was respectively 6.2% and 0%. This last combination reaches threshold target of 2% and unnecessary exams could easily have been avoided in this subgroup (6%). However, it confidence interval was still wide (0%; CI 0–5). Conclusions PERC rule combined with low gestalt probability seems to identify a group of patients for whom PE could easily be ruled out without additional test. A larger study is needed to confirm this result and to ensure safety.

To assess the sensitivity and specificity of emergency physicians in detecting anxiety and depression in patients requiring admission to the emergency department (ED) observation care unit for complementary investigations/treatment.339 consecutive patients admitted to the emergency observation care unit of 14 EDs were interviewed with standardised questionnaires. The characteristics of the patients, EDs and attending ED physicians were collected. Patients' anxiety and depression were identified using the Hospital Anxiety and Depression Scale (HADS), a self-administered questionnaire. ED physicians were blind to the HADS score and were asked to declare whether they perceived anxiety and depression in each patient. The judgement of ED physicians and the HADS score were compared using sensitivity, specificity, positive and negative likelihood ratios.The HADS questionnaire was correctly completed by 310 patients who comprised the study population. HADS detected symptoms of anxiety in 148 patients (47%) and symptoms of depression in 70 patients (23%). ED physicians determined the presence or absence of anxiety with a sensitivity of 48% (95% CI 40% to 56%) and a specificity of 69% (95% CI 61% to 75%). Positive and negative likelihood ratios were 1.54 (95% CI 1.16 to 2.06) and 0.75 (95% CI 1.28 to 3.28) for anxiety. They detected the presence or absence of depression with a sensitivity of 39% (95% CI 28% to 51%) and a specificity of 78% (95% CI 72% to 83%). Positive and negative likelihood ratios were 1.75 (95% CI 1.20 to 2.56) and 0.78 (95% CI 1.26 to 3.87) for depression.Although patients presenting to the ED often experience anxiety and depression, these symptoms are poorly detected by ED physicians.