# Université de Rouen

• Mont-Saint-Aignan, Normandie, France
Recent publications
Objectif : Ce travail propose l’investigation des répercussions émotionnelles immédiates des annonces du troisième confinement en France. Afin de répondre à cet objectif, nous nous intéressons aux réactions émotionnelles exprimées sur le réseau social Twitter entre le 11 mars 2021 et le 08 avril 2021. Méthode : 481 601 tweets ont été récupérés via la bibliothèque rtweet du logiciel R. Une analyse automatisée du lexique émotionnel a été conduite en étudiant sur le contenu des tweets jours après jours. Les données ont donc été traitées selon deux approches : (i) l’une transversale et (ii) l’autre considérant longitudinalement l’aspect dynamique des émotions. Résultats : L’impact des annonces de confinement n’est pas anodin. Si des émotions positives peuvent être observées, l’impact reste majoritairement négatif et global. Sur l’ensemble de la période considérée, le mal-être est le ressenti dominant. Il s’illustre par un vécu de solitude, des sensations de tensions, de la souffrance et/ou de la frustration. Les affects dépressifs et la souffrance apparaissent également de manière prépondérante sur l’ensemble des tweets. Les analyses temporelles montrent que les émotions varient dans leur nature et dans leur diversité selon la date à laquelle les tweets ont été publiés. Les annonces de reconfinement sont ainsi principalement associées à la haine, mais n’apparaissent que de façons transitoires. Discussion : Les résultats sont discutés au regard des fonctions adaptatives que procurent des émotions. Conclusion : L'analyse des messages postés sur ce réseau social nous apporte une compréhension en temps réel des réactions émotionnelles en lien avec les annonces de reconfinement. Outre l’examen du type d’émotions mobilisées, une lecture dynamique de celles-ci a contribuera à faire émerger la signification personnelle que le confinement a pu avoir.
Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .
Background Liberating patients from mechanical ventilation (MV) requires a systematic approach. In the context of a clinical trial, we developed a simple algorithm to identify patients who tolerate assisted ventilation but still require ongoing MV to be randomized. We report on the use of this algorithm to screen potential trial participants for enrollment and subsequent randomization in the Proportional Assist Ventilation for Minimizing the Duration of MV (PROMIZING) study. Methods The algorithm included five steps: enrollment criteria, pressure support ventilation (PSV) tolerance trial, weaning criteria, continuous positive airway pressure (CPAP) tolerance trial (0 cmH 2 O during 2 min) and spontaneous breathing trial (SBT): on fraction of inspired oxygen (F i O 2 ) 40% for 30–120 min. Patients who failed the weaning criteria, CPAP Zero trial, or SBT were randomized. We describe the characteristics of patients who were initially enrolled, but passed all steps in the algorithm and consequently were not randomized. Results Among the 374 enrolled patients, 93 (25%) patients passed all five steps. At time of enrollment, most patients were on PSV (87%) with a mean (± standard deviation) F i O 2 of 34 (± 6) %, PSV of 8.7 (± 2.9) cmH 2 O, and positive end-expiratory pressure of 6.1 (± 1.6) cmH 2 O. Minute ventilation was 9.0 (± 3.1) L/min with a respiratory rate of 17.4 (± 4.4) breaths/min. Patients were liberated from MV with a median [interquartile range] delay between initial screening and extubation of 5 [1–49] hours. Only 7 (8%) patients required reintubation. Conclusion The trial algorithm permitted identification of 93 (25%) patients who were ready to extubate, while their clinicians predicted a duration of ventilation higher than 24 h .
Multiphase flow is a challenging area of computational fluid dynamics (CFD) due to their potential large topological change and close coupling between the interface and fluid flow solvers. As such, Lagrangian meshless methods are very well suited for solving such problems. In this paper, we present a new fully explicit incompressible Smoothed Particle Hydrodynamics approach (EISPH) for solving multiphase flow problems. Assuming that the change in pressure between consecutive time-steps is small, due to small time steps in explicit solvers, an approximation of the pressure for following time-steps is derived. To verify the proposed method, several test cases including both single-phase and multi-phase flows are solved and compared with either analytical solutions or available literature. Additionally, we introduce a novel kernel function, which improves accuracy and stability of the solutions, and the comparison with a well-established quintic spline kernel function is discussed. For the presented benchmark problems, results show very good agreements in velocity and pressure fields and the interface-capturing with those in the literature. To the best knowledge of the authors, the EISPH method is presented for the first time for multiphase flow simulations.
We consider macroscopic systems in mild contact with boundary reservoirs and under the action of external fields. We present an explicit formula for the Hamiltonian of such systems, from which we deduce the equation of motions, the action functional, the hydrodynamic equation for the adjoint dynamics, and a formula for the quasi-potential. We examine the case in which the external forcing depends on time and drives the system from one nonequilibrium state to another. We extend the results presented in Bertini (J. Statist. Phys. 149: 773-802, 2012) on thermodynamic transformations for systems in strong contact with boundary reservoirs to the present situation. In particular, we propose a natural definition of renormalized work, and show that it satisfies a Clausius inequality, and that quasi-static transformations minimize the renormalized work. In addition, we connect the renormalized work to the quasi-potential describing the fluctuations in the stationary nonequilibrium ensemble.
This article deals with two min-max regret covering problems: the min-max regret Weighted Set Covering Problem (min-max regret WSCP) and the min-max regret Maximum Benefit Set Covering Problem (min-max regret MSCP). These problems are the robust optimization counterparts, respectively, of the Weighted Set Covering Problem and of the Maximum Benefit Set Covering Problem. In both problems, uncertainty in data is modeled by using an interval of continuous values, representing all the infinite values every uncertain parameter can assume. This study has the following major contributions: (i) a proof that MSCP is Σp2-Hard, (ii) a mathematical formulation for the min-max regret MSCP, (iii) exact and (iv) heuristic algorithms for the min-max regret WSCP and the min-max regret MSCP. We reproduce the main exact algorithms for the min-max regret WSCP found in the literature: a Logic-based Benders decomposition, an extended Benders decomposition and a branch-and-cut. In addition, such algorithms have been adapted for the min-max regret MSCP. Moreover, five heuristics are applied for both problems: two scenario-based heuristics, a path relinking, a pilot method and a linear programming-based heuristic. The goal is to analyze the impact of such methods on handling robust covering problems in terms of solution quality and performance.
Infantile (fetal and neonatal) megakaryocytes have a distinct phenotype consisting of hyperproliferation, limited morphogenesis, and low platelet production capacity. These properties contribute to clinical problems that include thrombocytopenia in neonates, delayed platelet engraftment in recipients of cord blood stem cell transplants, and inefficient ex vivo platelet production from pluripotent stem cell-derived megakaryocytes. The infantile phenotype results from deficiency of the actin-regulated coactivator, MKL1, which programs cytoskeletal changes driving morphogenesis. As a strategy to complement this molecular defect, we screened pathways with potential to affect MKL1 function and found that Dyrk1a kinase inhibition dramatically enhanced megakaryocyte morphogenesis in vitro and in vivo. Dyrk1 inhibitors rescued enlargement, polyploidization, and thrombopoiesis in human neonatal megakaryocytes. Megakaryocytes derived from induced pluripotent stem cells responded in a similar manner. Progenitors undergoing Dyrk1 inhibition demonstrated filamentous actin assembly, MKL1 nuclear translocation, and modulation of MKL1 target genes. Loss of function studies confirmed MKL1 involvement in this morphogenetic pathway. Ablim2, a stabilizer of filamentous actin, increased with Dyrk1 inhibition, and Ablim2 knockdown abrogated the actin, MKL1, and morphogenetic responses to Dyrk1 inhibition. These results thus delineate a pharmacologically tractable morphogenetic pathway whose manipulation may alleviate clinical problems associated with the limited thrombopoietic capacity of infantile megakaryocytes.
Contexte La connaissance des bases moléculaires des troubles du spectre autistique (TSA) est un enjeu pour le développement de médicaments pouvant compléter les thérapies comportementales actuelles. Sur la base des essais médicamenteux déclarés en vue de traiter les symptômes les plus handicapants des TSA infantiles, cette étude visait à reconstituer les voies biologiques manifestement en cause. Méthodes Des essais médicamenteux ont été recherchés sur ClinicalTrials.gov. N'ont pas été inclus les essais : i) sur des adultes (>18 ans); ii) avec un statut « retiré » ou « suspendu », iii) n'impliquant pas de médicaments. Une fouille de texte et l'utilisation de « DrugBank » ont permis d'homogénéiser les noms de molécules. Leurs cibles biologiques ont été identifiées avec la base de données « Drug Gene Interaction database ». Les principales voies biologiques ciblées ont été caractérisées via une analyse d'enrichissement fonctionnel avec « Reactome Pathway database ». Résultats Les 179 essais retenus ont impliqué 91 médicaments différents. Ces essais se mènent principalement aux Etats-Unis (97 %). Les principales voies biologiques sous-jacentes aux protéines ciblées par les médicaments ont concerné : Fonctionnement neuronal (e.g. canaux K+); Développement du système nerveux (e.g. Interactions NCAM1); Transduction du signal (e.g. Récepteur Tyrosine-kinase); Système immunitaire (e.g. Cytokines); Expression génique (e.g. TP53). Parmi les médicaments testés, seules l'Aripriprazole et la Rispéridone ont reçu une approbation de la FDA pour les TSA infantiles (Réduction de l'irritabilité et des comportements agressifs). Des essais émergents incluaient le Cannabidiol ou le Bumétanide. Discussion/Conclusion Cette étude propose une nouvelle approche intégrative ayant permis d'identifier cinq voies biologiques à partir des potentiels médicaments contre les TSA infantiles. Elle assure une vue d'ensemble susceptible d’éclairer autant les enquêtes étiologiques que la découverte de molécules et surtout le repositionnement de médicaments au profit d'autres conditions complexes analogues aux TSA. Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêts.
Introduction: Cage impactions (CI) of Oblique Lumbar Interbody Fusion (OLIF) appear to be a frequent mechanical complication with a potential functional impact. Objectives: To determine the rate of CI occurrence, their risk factors and clinical implications in the case of combined single-level arthrodesis. Method: A retrospective analysis of prospectively collected data was performed. All our patients with degenerative spondylolisthesis initially underwent OLIF combined with pedicle screw fixation (PSF). Intraoperative control with an image intensifier and a standard radiograph in the immediate postoperative period made it possible to assess the occurrence of CI, depending on the position of the implant. Secondary subsidence was sought on the standing radiological examination using EOS biplanar radiography during follow-up. The pelvic parameters were analyzed, as well as the occurrence of bone fusion. The clinical evaluation was made at ≥1 year, by the Oswestry Disability Index (ODI), the walking distance (WD) and the Visual Analogue Scale (VAS). Results: 130 patients out of the 131 included were analyzed. A CI occurred in 25.3% (n=33) of cases and of these, 94% (n=32) occurred intraoperatively. Postmenopausal women had more CI with an Odds Ratio (OR) of 5.8 (p=0.034). The "CI" group had a 9.5% lower ODI score than the "non-CI" group (p=0.0040), but both provided excellent ODI gains of 30.8±16 and 32.9±15.5% (p<0.0001). An "anterior" position of the implant allowed a greater gain in lumbar lordosis (p<0.001) but was associated with greater CI occurrence (p<0.001), with an OR of 6.75 (p=0.0018). Conclusion: The occurrence of intraoperative cage impaction is a frequent event when performing OLIF. Postmenopausal women have an approximately 6 times greater risk of impaction than men, and patients with an "anterior" implant placement have a 7 times greater risk than with central placement. The negative impact of cage impactions on the clinical score (ODI) was significant after one year of follow-up. Level of evidence: IV, non-comparative cohort study
Radiation-induced embrittlement of nuclear steels is one of the main limiting factors for safe long-term operation of nuclear power plants. In support of accurate and safe reactor pressure vessel (RPV) lifetime assessments, we developed a physics-based model that predicts RPV steel hardening and subsequent embrittlement as a consequence of the formation of nano-sized clusters of minor alloying elements. This model is shown to provide reliable assessments of embrittlement for a very wide range of materials, with higher accuracy than industrial correlations. The core of our model is a multiscale modelling tool that predicts the kinetics of solute clustering, given the steel chemical composition and its irradiation conditions. It is based on the observation that the formation of solute clusters ensues from atomic transport driven by radiation-induced mechanisms, differently from classical nucleation-and-growth theories. We then show that the predicted information about solute clustering can be translated into a reliable estimate for radiation-induced embrittlement, via standard hardening laws based on the dispersed barrier model. We demonstrate the validity of our approach by applying it to hundreds of nuclear reactors vessels from all over the world.
We study quantum circuits composed of a sequence of CNOT\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\texttt {CNOT}$$\end{document} gates between distant qubits of a n-qubit system. We present some results concerning two important topics related to these circuits: circuit optimization and emergence of entanglement. Regarding the optimization problem, we first describe the group structure underlying quantum circuits generated by CNOT\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\texttt {CNOT}$$\end{document} gates (group isomorphism, group presentation), then we apply these mathematical results to the description of heuristics to reduce the number of gates in these circuits and we also propose an optimization algorithm for circuits of a few qubits. Concerning entanglement, we show how to create some useful entangled states when a circuit of CNOT\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\texttt {CNOT}$$\end{document} gates acts on a fully factorized state. In the case of a 3-qubit system, we prove that a CNOT\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\texttt {CNOT}$$\end{document} circuit acting on a fully factorized state can create all types of entanglement and we propose a method to evaluate the reliability of the implementation of a SLOCC\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathtt {SLOCC}$$\end{document}-equivalent to the state |W3⟩\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$|\mathtt {W}_3\rangle$$\end{document} in a quantum machine by computing the value of the hyperdeterminant. In the case of a 4-qubit system, we propose a circuit to compute a generic entangled state and a (computer-assisted) proof of the impossibility of creating a SLOCC\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathtt {SLOCC}$$\end{document}-equivalent to the state |W4⟩\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$|\mathtt {W}_4\rangle$$\end{document} from a circuit of CNOT\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\texttt {CNOT}$$\end{document} gates acting on a factorized state
Pemphigus is a life-threatening auto-immune blistering disease of the skin and mucous membrane that is caused by the production of auto-antibodies (auto-Abs) directed against adhesion proteins: desmoglein 1 and 3. We demonstrated in the “Ritux3” trial, the high efficacy of rituximab, an anti-CD20 recombinant monoclonal antibody, as the first-line treatment for pemphigus. However, 25% of patients relapsed during the six-month period after rituximab treatment. These early relapses were associated with a lower decrease in anti-desmoglein auto-Abs after the initial cycle of rituximab. The N-glycosylation of immunoglobulin-G (IgG) can affect their affinity for Fc receptors and their serum half-life. We hypothesized that the extended half-life of Abs could be related to modifications of IgG N-glycans. The IgG N-glycome from pemphigus patients and its evolution under rituximab treatment were analyzed. Pemphigus patients presented a different IgG N-glycome than healthy donors, with less galactosylated, sialylated N-glycans, as well as a lower level of N-glycans bearing an additional N-acetylglucosamine. IgG N-glycome from patients who achieved clinical remission was not different to the one observed at baseline. Moreover, our study did not identify the N-glycans profile as discriminating between relapsing and non-relapsing patients. We report that pemphigus patients present a specific IgG N-glycome. The changes observed in these patients could be a biomarker of autoimmunity susceptibility rather than a sign of inflammation.
Purpose To describe the management of the discovery of a retropharyngeal carotid artery in the context of a cervical dislocation. Description of the case A 68-year-old female presented acute neck pain and incomplete tetraplegia following a fall on the stairs. Radiographs, contrast-enhanced computed tomography scan and magnetic resonance of the cervical spine revealed a C5–C6 bi-articular dislocation. A detailed preoperative assessment of the images discovered a medialization of the left common carotid artery. An external reduction and a left anterior cervical approach allowed a careful management of the vascular variation and an anterior C5–C6 arthrodesis. At six months, a full neurological recovery was assessed and radiographs demonstrated successful fusion of the cervical arthrodesis. Discussion/conclusion Anatomical features such as medialization of the common carotid artery may affect patients with traumatic cervical spine injuries. The severity of the traumatic bone lesions should not overshadow the preoperative analysis of the adjacent anatomical structures encountered during the surgical approach, even in an emergency situation.
Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov , NCT01926249
Background: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. Objective: Our objective was to develop a predictive model combining clinical scores and imaging. Methods: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual valuesResults:Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p < 0.001). The models that added imaging features enhanced the performances: with T1w (R2 = 0.65 and 0.76, p < 0.001) and with R2* (R2 = 0.60 and 0.72, p < 0.001). Conclusion: These results suggest that modeling is potentially a simple way to estimate dopa-sensitivity, but requires confirmation in a larger population, including patients with dopa-sensitivity < 30.
Quantification of DNA and RNA biomarkers via isothermal amplification technologies can significantly simplify biosensing and clinical diagnostics. However, highly sensitive and wash‐free assay formats based on time‐resolved Förster resonance energy transfer (TR‐FRET) have been limited to terbium (Tb) based FRET pairs and their application on specialized clinical instruments. Here, we present the implementation of rolling circle amplification (RCA)‐FRET to europium‐dye (Eu‐ATTO620) FRET pairs and its application on standard benchtop fluorescence plate readers. Eu‐ATTO620 RCA‐FRET was used to quantify microRNA‐21 (miR‐21) in a 1 to 100 pM concentration range on a SPARK multimode plate reader system. Detection limits down to 120±20 fM (18±3 attomol of miR‐21) and quantification of endogenous miR‐21 from the plasma of ovarian cancer patients using a KRYPTOR clinical plate reader demonstrated the broad applicability and clinical relevance of Eu‐dye‐based RCA‐FRET. The extension to both Eu and Tb based TR‐FRET and to standard bioanalytical laboratory instruments has the potential to significantly broaden the application and versatility of RCA‐FRET for simple, highly‐sensitive, and multiplexed bioanalysis.
Background Ventilator-associated lower respiratory tract infections (VA-LRTI) are common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between corticosteroid adjuvant administration and the incidence of VA-LRTI. Methods Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 hours for a SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VA-LRTI diagnosis required strict definition with clinical, radiological and microbiological documentation. We assessed the association of VA-LRTI with corticosteroid administration using univariate and multivariate cause-specific Cox’s proportional hazard models with adjustment on prespecified confounders. Results 545 patients were included, of whom 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VA-LRTI was violated (p=0.018) indicating that this effect varied during the ICU stay. We found a lower risk of VA-LRTI for corticosteroid treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time dependent coefficients, the association between corticosteroids and the incidence of VA-LRTI was not significant (overall effect p=0.068), with time-dependent hazard ratios (95% confidence interval) of 0.45 (0.18 to 1.10) at day 2, 0.89 (0.62 to 1.27) at day 7, 1.38 (0.99 to 1.92) at day 14 and 1.80 (1.08 to 2.98) at day 21. Conclusions No significant association was found between corticosteroid adjuvant therapy and the incidence of VA-LRTI, although a significant time-varying effect of corticosteroids was identified along the 28-day follow-up.
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