Correlation between unproven therapies and delayed return-to-work for COVID-19-infected healthcare workers.

The objective of this study is to investigate factors influencing the time to return to work (RTW) of HealthCare Workers (HCW) infected with COVID-19 during the initial wave of the pandemic in a southern French university hospital. Data collection of 170 HCW (between March 16 to June 1, 2020) included demographic and professional information, clinical profiles, comorbidities, medical management, therapies and RT-PCR results. The mean time to RTW was 15.6 days. Multivariate analyses revealed that the time to RTW was shorter among laboratory and emergency workers, while it was longer for HCW aged 40 to 49 years, at higher risk of severe illness, with a delayed negative SARS-CoV-2 PCR or those treated with azithromycin and/or hydroxychloroquine. This study highlights diverse factors affecting HCW RTW post-COVID-19 infection, underscoring the importance of exercising caution in administering unproven therapies to HCW during the early stages of a novel infectious pandemic.

[Translation into French and republication of: "Home treatment for patients with cancer-associated venous thromboembolism"]. / Traduction et republication de : « Traitement à domicile des patients atteints de maladie veineuse thromboembolique associée au cancer ¼.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Operator Formulation of Feynman Path Centroid Dynamics for Rotations.

An operator formulation of centroid molecular dynamics (CMD) for rotational degrees of freedom is presented. The quasi-density operator concept was introduced by Jang and Voth [J. Chem. Phys 111, 2357 (1999)] and is used to obtain a phase-space mapping without the need for discretized path integrals. The approach allows the calculation of approximate Kubo-transformed time correlation functions. The particle on a ring is chosen as an illustrative example. Numerical results demonstrate that the proposed approach leads to accurate results when compared with exact diagonalization calculations for linear operators. At very low temperatures, it is found that rotational CMD yields results that are in exact agreement with the quantum dynamics of a spin-1 system.

Pulmonary embolism risk stratification: external validation of the 4-level Clinical Pretest Probability Score (4PEPS).

Background: The 4-level clinical pretest probability score (4PEPS) was recently introduced as a clinical decision rule for the diagnosis of pulmonary embolism (PE). Based on the score, patients are classified into clinical pretest probability categories (c-PTP). The "very low" category aims at excluding PE without further testing; "low" and "moderate" categories require D-dimer testing with specific thresholds, while patients with a "high" pretest directly proceed to imaging. Objectives: To provide further external validation of the 4PEPS model. Methods: The 4PEPS was applied to a previously collected prospective database of 756 patients with clinically suspected PE enrolled from European emergency departments in 2002 to 2003. The safety threshold for the failure rate in our study was calculated at 1.95% based on a 26% prevalence of PE in our study, as per the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee guidance. Results: Patients were classified as follows: 90 (12%) in the very low c-PTP group, of whom 5 (5.6%; 95% CI, 2.4%-12.4%) had PE; 363 (49%) in the low c-PTP group, of whom 34 had PE (9.4%); 246 (34%) in the moderate c-PTP group, of whom 124 (50%) had PE; and 35 (5%) in the high c-PTP group of whom 30 (86%) had PE. Overall, the failure rate of the 4PEPS was 9/734 (1.2%; 95% CI, 0.59%-2.23%) Overall, 9 out of 734 patients (1.2%; 95% CI, 0.59%-2.23%) were diagnosed with PE despite a negative 4PEPS rule; 5 (5.6%) from the very low c-PTP group, 3 (1.4%) in the low c-PTP group, and 1 (3.2%) in the moderate c-PTP group. Conclusion: We provide external validation data of the 4PEPS. In this high-prevalence cohort (26% prevalence), PE prevalence in the very low-risk group was higher than expected. A prospective validation study is needed before implementing the 4PEPS model in routine clinical practice.

Quantum criticality in chains of planar rotors with dipolar interactions.

In this work, we perform a density matrix renormalization group study of chains of planar rotors interacting via dipolar interactions. By exploring the ground state from weakly to strongly interacting rotors, we find the occurrence of a quantum phase transition between a disordered and a dipole-ordered quantum state. We show that the nature of the ordered state changes from ferroelectric to antiferroelectric when the relative orientation of the rotor planes varies and that this change requires no modification of the overall symmetry. The observed quantum phase transitions are characterized by critical exponents and central charges, which reveal different universality classes ranging from that of the (1 + 1)D Ising model to the 2D classical XY model.

Outpatient management of cancer-associated pulmonary embolism: A post-hoc analysis from the HOME-PE trial.

INTRODUCTION: Cancer-related pulmonary embolism (PE) is associated with poor prognosis. Some decision rules identifying patients eligible for home treatment categorize cancer patients at high risk of complications, precluding home treatment. We sought to assess the effectiveness and the safety of outpatient management of patients with low-risk cancer-associated PE. METHODS: In the HOME-PE trial, hemodynamically stable patients with symptomatic PE were randomized to either triaging with Hestia criteria or sPESI score. We analyzed 3 groups of low-risk PE patients: 47 with active cancer treated at home (group 1), 691 without active cancer treated at home (group 2), and 33 with active cancer as the only sPESI criterion qualifying them for hospitalization (group 3). The main outcome was the composite of recurrent venous thromboembolism, major bleeding, and all-cause death within 30 days after randomization. RESULTS: Patients treated at home had composite outcome rates of 4.3 % (2/47) for those with cancer vs. 1.0 % (7/691) for those without (odds ratio (OR) 4.98, 95%CI 1.15-21.49). Patients with cancer had rates of complications of 4.3 % when treated at home vs. 3.0 % (1/33) when hospitalized (OR 1.19, 95%CI 0.15-9.47). In multivariable analysis, active cancer was associated with an increased risk of complications for patients treated at home (OR 7.95; 95%CI 1.48-42.82). For patients with active cancer, home treatment was not associated with the primary outcome (OR 1.19, 95%CI 0.15-9.74). CONCLUSIONS: Among patients treated at home, active cancer was a risk factor for complications, but among patients with active cancer, home treatment was not associated with adverse outcomes.

Targeted prophylactic anticoagulation based on the TRiP(cast) score in patients with lower limb immobilisation: a multicentre, stepped wedge, randomised implementation trial.

BACKGROUND: Prophylactic anticoagulation in emergency department patients with lower limb trauma requiring immobilisation is controversial. The Thrombosis Risk Prediction for Patients with Cast Immobilisation-TRiP(cast)-score could identify a large subgroup of patients at low risk of venous thromboembolism for whom prophylactic anticoagulation can be safely withheld. We aimed to prospectively assess the safety of withholding anticoagulation for patients with lower limb trauma at low risk of venous thromboembolism, defined by a TRiP(cast) score of less than 7. METHODS: CASTING was a stepped-wedge, multicentre, cluster-randomised trial with blinded outcome assessment. 15 emergency departments in France and Belgium were selected and randomly assigned staggered start dates for switching from the control phase (ie, anticoagulation prescription according to the physician's usual practice) to the intervention phase (ie, targeted anticoagulation according to TRiP(cast) score: no prescription if score <7 and anticoagulation if score was ≥7). Patients were included if they presented to a participating emergency department with lower limb trauma requiring immobilisation for at least 7 days and were aged 18 years or older. The primary outcome was the 3-month cumulative rate of symptomatic venous thromboembolism during the intervention phase in patients with a TRiP(cast) score of less than 7. The targeted strategy was considered safe if this rate was less than 1% with an upper 95% CI of less than 2%. The primary analysis was performed in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT04064489). FINDINGS: Between June 16, 2020, and Sept 15, 2021, 15 clusters and 2120 patients were included. Of the 1505 patients analysed in the intervention phase, 1159 (77·0%) had a TRiP(cast) score of less than 7 and did not receive anticoagulant treatment. The symptomatic venous thromboembolism rate was 0·7% (95% CI 0·3-1·4, n=8/1159). There was no difference between the control and the intervention phases in the cumulative rate of symptomatic venous thromboembolism or in bleeding rates. INTERPRETATION: Patients with a TRiP(cast) score of less than 7 who are not receiving anticoagulation have a very low risk of venous thromboembolism. A large proportion of patients with lower limb trauma and immobilisation could safely avoid thromboprophylaxis. FUNDING: French Ministry of Health.

Derivation and validation of a risk-stratification model for patients with probable or proven COVID-19 in EDs: the revised HOME-CoV score.

BACKGROUND: The HOME-CoV (Hospitalisation or Outpatient ManagEment of patients with SARS-CoV-2 infection) score is a validated list of uniquely clinical criteria indicating which patients with probable or proven COVID-19 can be treated at home. The aim of this study was to optimise the score to improve its ability to discriminate between patients who do and do not need admission. METHODS: A revised HOME-CoV score was derived using data from a previous prospective multicentre study which evaluated the original Home-CoV score. Patients with proven or probable COVID-19 attending 34 EDs in France, Monaco and Belgium between April and May 2020 were included. The population was split into a derivation and validation sample corresponding to the observational and interventional phases of the original study. The main outcome was non-invasive or invasive ventilation or all-cause death within 7 days following inclusion. Two threshold values were defined using a sensitivity of >0.9 and a specificity of >0.9 to identify low-risk and high-risk patients, respectively. The revised HOME-CoV score was then validated by retrospectively applying it to patients in the same EDs with proven or probable COVID-19 during the interventional phase. The revised HOME-CoV score was also tested against original HOME-CoV, qCSI, qSOFA, CRB65 and SMART-COP in this validation cohort. RESULTS: There were 1696 patients in the derivation cohort, of whom 65 (3.8%) required non-invasive ventilation or mechanical ventilation or died within 7 days and 1304 patients in the validation cohort, of whom 22 (1.7%) had a progression of illness. The revised score included seven clinical criteria. The area under the curve (AUC) was 87.6 (95% CI 84.7 to 90.6). The cut-offs to define low-risk and high-risk patients were <2 and >3, respectively. In the validation cohort, the AUC was 85.8 (95% CI 80.6 to 91.0). A score of <2 qualified 73% of patients as low risk with a sensitivity of 0.77 (0.55-0.92) and a negative predictive value of 0.99 (0.99-1.00). CONCLUSION: The revised HOME-CoV score, which does not require laboratory testing, may allow accurate risk stratification and safely qualify a significant proportion of patients with probable or proven COVID-19 for home treatment.

Overcrowding in the Dispatching Centre During the COVID-19 Crisis: Are Medical Students a Resource?

INTRODUCTION: In February, the emergence of COronaVIrus Disease 2019 (COVID - 19) in France made it necessary to rapidly adapt emergency and SAMU services in order to take care of many infected patients. To respond to the increase in the number of calls in the dispatch centers, reinforcements were necessary on the fronts of the Medical Regulation Assistants (ARM). The aim of this study was to assess the relevance of medical students' responses to first calls exclusively concerning COVID-19. METHODS: This prospective, observational cohort study was carried out at the University Hospital Centre (CHU) in Angers. Twenty medical students mostly in the 5th year were voluntarily enrolled in the first line COVID-19 call taker team. Calls on the 1st, 3rd, and 5th starting day for each medical student, and randomly selected calls from the experienced first-line call taker were listened to by a medical expert to assess the adequate level of prioritization and orientation (emergency physician or general practitioner). The percentage of agreement between the expert, students, and experienced first-line call handlers were assessed. All participants gave their free consent to participate. The study was approved by the Ethics Committee of Angers (N° 2020-48). RESULTS: From March 18 to April 23, 2020, 302 calls from medical students (n = 20 students) and 40 calls from experienced first-line call handlers were analyzed. The average prioritization agreement rate between the expert and students was 76.16% (95% Confidence Interval: 71.04 to 80.62%) (n = 230/302) compared to 87.50% (95% CI: 73.9 to 94.5%) (n = 45/50) for the experienced first-line call handlers (P = 0.15). Medical students took more time per call with an absolute difference of 2 minutes 16 seconds (P < 0.001). CONCLUSION: The lessons to be observed from this COVID-19 crisis are that in the early days of increasing calls heralding a strain on the healthcare system, support by medical students must be considered.

Home treatment for patients with cancer-associated venous thromboembolism.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Obesity as a Predictor for Pulmonary Embolism and Performance of the Age-Adjusted D-Dimer Strategy in Obese Patients with Suspected Pulmonary Embolism.

INTRODUCTION: Obesity is a risk factor for venous thromboembolism, but studies evaluating its association with pulmonary embolism (PE) in patients with suspected PE are lacking. OBJECTIVES: To evaluate whether body mass index (BMI) and obesity (i.e., BMI ≥30 kg/m2) are associated with confirmed PE in patients with suspected PE and to assess the efficiency and safety of the age-adjusted D-dimer strategy in obese patients. METHODS: We conducted a secondary analysis of a multinational, prospective study, in which patients with suspected PE were managed according to the age-adjusted D-dimer strategy and followed for 3 months. Outcomes were objectively confirmed PE at initial presentation, and efficiency and failure rate of the diagnostic strategy. Associations between BMI and obesity, and PE were examined using a log-binomial model that was adjusted for clinical probability and hypoxia. RESULTS: We included 1,593 patients (median age: 59 years; 56% women; 22% obese). BMI and obesity were not associated with confirmed PE. The use of the age-adjusted instead of the conventional D-dimer cut-off increased the proportion of obese patients in whom PE was considered ruled out without imaging from 28 to 38%. The 3-month failure rate in obese patients who were left untreated based on a negative age-adjusted D-dimer cut-off test was 0.0% (95% confidence interval: 0.0-2.9%). CONCLUSION: BMI on a continuous linear scale and obesity were not predictors of confirmed PE among patients presenting with a clinical suspicion of PE. The age-adjusted D-dimer strategy appeared safe in ruling out PE in obese patients with suspected PE.

Pulmonary embolism rule-out decision-making tools for patients aged 35 years or younger in hospital emergency departments: a post-hoc analysis of performance in 3 prospective cohorts. / Capacidad de diferentes reglas de decisión clínica para descartar tromboembolismo pulmonar en pacientes de 35 o menos años atendidos en servicios de urgencias: análisis post-hoc de tres cohortes prospectivas.

OBJECTIVES: To assess the performance of the Pulmonary Embolism Rule-out Criteria (PERC) and the age-modified PERC-35 tool in hospital emergency departments (EDs) for evaluating patients aged 35 years or younger. A secondary aim was to assess other decision-making criteria. MATERIAL AND METHODS: Post-hoc analysis of 3 European cohort studies. We included data for patients aged 35 years or younger suspected of PE who were followed for 3 months. The safety and efficacy of applying the PERC and PERC-35 were assessed with the diagnostic error rate (failure to detect PE) and the proportion of patients in whom a diagnosis of PE was ruled out. We also assessed the safety and efficacy of applying the YEARS and PEGeD criteria. RESULTS: Data for 1235 patients aged 35 years or younger were analyzed. Twenty-two (1.8%; 95% CI, 1.2%-2.7%) PE cases were diagnosed at 3 months. Six (1.0%; 95% CI, 0.5%-2.2%) and 5 (0.9%; 95% CI, 0.4%-2.1%) PE cases were not diagnosed by the PERC and PERC-35 tools, respectively. These tools allowed PE to be ruled out in 591 (48.2%; 95% CI, 45.4%-51.0%) and 554 (46.2%; 95% CI, 43.4%-49.0%) cases, respectively. The error rates of the YEARS and PEGeD criteria, respectively, were 0.4% (95% CI, 0.1%-1.1%) and 0.5% (95% CI, 0.2%-1.2%); their efficacy was similar. CONCLUSION: The safety and efficacy profiles of the PERC and PERC-35 algorithms were similar in patients aged 35 years or younger. However, the large confidence intervals we report do not allow us to confirm the safety of using the tools in patients in this age group.

OBJETIVO: Evaluar la capacidad de la regla PERC (Pulmonary Embolism Rule-out Criteria) y la regla modificada por edad (PERC-35) para descartar tromboembolia pulmonar (TEP) en servicios de urgencias hospitalarios (SUH) en pacientes 35 años. El objetivo secundario fue analizar otras reglas de decisión clínica. METODO: Análisis post-hoc de 3 estudios de cohorte europeos (PROPER, PERCEPIC y MODIGLIANI). Se incluyeron pacientes 35 años con sospecha de TEP en SUH y con seguimiento a 3 meses. La seguridad y eficacia de PERC y PERC-35 se evaluaron con su tasa de error -no detectar TEP- y la proporción de pacientes con diagnóstico de TEP descartado. Se evaluó la seguridad y eficacia de las reglas YEARS y PEGeD. RESULTADOS: Se analizaron 1.235 pacientes 35 años. Hubo 22 (1,8%, IC 95%: 1,2-2,7) TEP diagnosticados a los 3 meses. Hubo 6 (1,0%, IC 95%: 0,5-2,2) y 5 (0,9%, IC 95%: 0,4-2,1) TEP no diagnosticados con las reglas PERC y PERC-35 respectivamente. Estas reglas permitieron descartar TEP en 591 (48,2%, IC 95%: 45,4- 51,0) y 554 (46,2%, IC 95%: 43,4- 49,0) respectivamente. La tasa de error de YEARS y PEGeD fue del 0,4% (IC 95%: 0,1- 1,1) y 0,5% (IC 95%: 0,2-1,2), con una eficacia similar. CONCLUSIONES: En pacientes 35 años, las reglas PERC y PERC-35 mostraron perfiles de seguridad y eficacia similares. Sin embargo, el amplio intervalo de confianza comunicado en este estudio no permite confirmar su seguridad.

Capacidad de diferentes reglas de decisión clínica para descartar tromboembolismo pulmonar en pacientes de 35 o menos años atendidos en servicios de urgencias: análisis post-hoc de tres cohortes prospectivas / Pulmonary embolism rule-out decision-making tools for patients aged 35 years or younger in hospital emergency departments: a post-hoc analysis of performance in 3 prospective cohorts

Objetivos: Evaluar la capacidad de la regla PERC (Pulmonary Embolism Rule-out Criteria) y la regla modificada por edad (PERC-35) para descartar tromboembolia pulmonar (TEP) en servicios de urgencias hospitalarios (SUH) en pacientes # 35 años. El objetivo secundario fue analizar otras reglas de decisión clínica. Método: Análisis post-hoc de 3 estudios de cohorte europeos (PROPER, PERCEPIC y MODIGLIANI). Se incluyeron pacientes # 35 años con sospecha de TEP en SUH y con seguimiento a 3 meses. La seguridad y eficacia de PERC yPERC-35 se evaluaron con su tasa de error -no detectar TEP- y la proporción de pacientes con diagnóstico de TEP descartado. Se evaluó la seguridad y eficacia de las reglas YEARS y PEGeD. Resultados: Se analizaron 1.235 pacientes # 35 años. Hubo 22 (1,8%, IC 95%: 1,2-2,7) TEP diagnosticados a los 3 meses. Hubo 6 (1,0%, IC 95%: 0,5-2,2) y 5 (0,9%, IC 95%: 0,4-2,1) TEP no diagnosticados con las reglas PERC y PERC-35 respectivamente. Estas reglas permitieron descartar TEP en 591 (48,2%, IC 95%: 45,4- 51,0) y 554 (46,2%, IC 95%: 43,4- 49,0) respectivamente. La tasa de error de YEARS y PEGeD fue del 0,4% (IC 95%: 0,1- 1,1) y 0,5% (IC 95%: 0,2-1,2), con una eficacia similar. Conclusiones: En pacientes # 35 años, las reglas PERC y PERC-35 mostraron perfiles de seguridad y eficacia similares. Sin embargo, el amplio intervalo de confianza comunicado en este estudio no permite confirmar su seguridad. (AU)

Objectives: To assess the performance of the Pulmonary Embolism Rule-out Criteria (PERC) and the age-modified PERC-35 tool in hospital emergency departments (EDs) for evaluating patients aged 35 years or younger. A secondary aim was to assess other decision-making criteria. Method: Post-hoc analysis of 3 European cohort studies. We included data for patients aged 35 years or younger suspected of PE who were followed for 3 months. The safety and efficacy of applying the PERC and PERC-35 were assessed with the diagnostic error rate (failure to detect PE) and the proportion of patients in whom a diagnosis of PE was ruled out. We also assessed the safety and efficacy of applying the YEARS and PEGeD criteria. Results: Data for 1235 patients aged 35 years or younger were analyzed. Twenty-two (1.8%; 95% CI, 1.2%-2.7%) PE cases were diagnosed at 3 months. Six (1.0%; 95% CI, 0.5%-2.2%) and 5 (0.9%; 95% CI, 0.4%-2.1%) PE cases were not diagnosed by the PERC and PERC-35 tools, respectively. These tools allowed PE to be ruled out in 591 (48.2%; 95% CI, 45.4%-51.0%) and 554 (46.2%; 95% CI, 43.4%-49.0%) cases, respectively. The error rates of the YEARS and PEGeD criteria, respectively, were 0.4% (95% CI, 0.1%-1.1%) and 0.5% (95% CI, 0.2%-1.2%); their efficacy was similar. Conclusions: The safety and efficacy profiles of the PERC and PERC-35 algorithms were similar in patients aged 35 years or younger. However, the large confidence intervals we report do not allow us to confirm the safety of using the tools in patients in this age group. (AU)

Tailoring elastic and inelastic collisions of relativistic antiferromagnetic domain walls.

Soliton-based computing relies on their unique properties for transporting energy and emerging intact from head-on collisions. Magnetic domain walls are often referred to as solitons disregarding the strict mathematical definition requiring the above scattering property. Here we demonstrate the conditions of elastic and inelastic scattering for spin-orbit torque-induced dynamics of relativistic domain walls on the technologically relevant Mn[Formula: see text]Au antiferromagnetic material. We show that even domain walls with opposite winding numbers can experience elastic scattering and we present the corresponding phase diagram as a function of the spin-orbit field strength and duration. The elastic collision requires minimum domain walls speed, which we explain assuming an attractive potential created by domain wall pair. On the contrary, when the domain walls move at lower speeds, their collision is inelastic and results in a dispersing breather. Our findings will be important for the development of soliton-based computing using antiferromagnetic spintronics and we discuss their prospects for building NOT and XOR gates.

[Point-of-care testing for D-dimer in the exclusion of venous thromboembolism: a critical analysis]. / Les dispositifs délocalisés de dosage des D-dimères dans l'exclusion de la maladie thromboembolique veineuse : une analyse critique.

Point-of-care testing (POCT) for D-dimer is an alternative to -laboratory testing for the exclusion of venous thromboembolism (VTE). This critical review by the "CEC et biologie délocalisée" working group of the "Société Française de Thrombose et d'Hémostase" (French Society of -Thrombosis and Haemostasis) aims to present the characteristics of six POCT D-dimer assays available in France in 2023. The article highlights the need to define VTE -exclusion thresholds specific to each technique and validated by clinical studies. There is insufficient data to validate the use of cut off suggested by manufacturers, and age-adjusted thresholds. The article discusses the role of laboratories in justifying and prescribing POCT D-dimer, according to objective criteria, such as the availability and turnaround time of classical laboratory tests. They should also encourage rational prescribing, limited to patients with low risk of venous thromboembolism, following an assessment of clinical probability according to national and international guidelines.

Pulmonary embolism diagnostic strategies in patients with COPD exacerbation: Post-hoc analysis of the PEP trial.

BACKGROUND: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined. AIMS: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD. METHOD: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy. RESULTS: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to -32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %). CONCLUSION: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased VTE diagnosis failure rate that exceeds the safety threshold. Further studies are needed to improve diagnostic management in this population.

The electron-centric approach to the exchange-correlation energy.

The Kohn-Sham theory addresses the challenge of representing the kinetic energy by re-quantizing density functional theory at a level of non-interacting electrons. It transforms the many-electron problem into a fictitious non-interacting electron problem, with the many-electron effects concealed within the exchange-correlation (XC) energy, which is expressed in terms of the electron density ρ(r). Unlike the wave function, ρ(r) can be viewed as a classical quantity, and expressing the XC energy in terms of it circumvents the need for correlated wave functions. In this work, we once again employ the re-quantization strategy and determine the XC energy using a local one-particle Schrödinger equation. The ground-state eigenfunction of the corresponding Hamiltonian is a reference point (r) dependent orbital φr,σ(u, σ') which is subsequently used to generate the XC hole and the XC energy. The spin coordinate is denoted by σ and u is the electron-electron separation. The one-particle equation for φr,σ(u, σ') includes a local potential vr,σ(u, σ') that we approximate using two simple physical constraints. We assess the approximation by applying it to the helium iso-electronic series, the homogeneous electron gas, and the dissociation of the hydrogen molecule.

Transcriptional regulation of the mouse EphA4, Ephrin-B2 and Ephrin-A3 genes by the circadian clock machinery.

Circadian rhythms originate from molecular feedback loops. In mammals, the transcription factors CLOCK and BMAL1 act on regulatory elements (i.e. E-boxes) to shape biological functions in a rhythmic manner. The EPHA4 receptor and its ligands Ephrins (EFN) are cell adhesion molecules regulating neurotransmission and neuronal morphology. Previous studies showed the presence of E-boxes in the genes of EphA4 and specific Ephrins, and that EphA4 knockout mice have an altered circadian rhythm of locomotor activity. We thus hypothesized that the core clock machinery regulates the gene expression of EphA4, EfnB2 and EfnA3. CLOCK and BMAL1 (or NPAS2 and BMAL2) were found to have transcriptional activity on distal and proximal regions of EphA4, EfnB2 and EfnA3 putative promoters. A constitutively active form of glycogen synthase kinase 3ß (GSK3ß; a negative regulator of CLOCK and BMAL1) blocked the transcriptional induction. Mutating the E-boxes of EphA4 distal promoter sequence reduced transcriptional induction. EPHA4 and EFNB2 protein levels did not show circadian variations in the mouse suprachiasmatic nucleus or prefrontal cortex. The findings uncover that core circadian transcription factors can regulate the gene expression of elements of the Eph/Ephrin system, which might contribute to circadian rhythmicity in biological processes in the brain or peripheral tissues.

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. REGISTRATION: PROSPERO ID 89366.