27 research outputs found
Gaining consensus on expert rule statements for acute respiratory failure digital twin patient model in intensive care unit using a Delphi method
Digital twin technology is a virtual depiction of a physical product and has been utilized in many fields. Digital twin patient model in healthcare is a virtual patient that provides opportunities to test the outcomes of various interventions virtually without subjecting an actual patient to possible harm. This can serve as a decision aid in the complex environment of the intensive care unit (ICU). Our objective is to develop consensus among a multidisciplinary expert panel on statements regarding respiratory pathophysiology contributing to respiratory failure in the medical ICU. We convened a panel of 34 international critical care experts. Our group modeled elements of respiratory failure pathophysiology using directed acyclic graphs (DAGs) and derived expert statements describing associated ICU clinical practices. The experts participated in three rounds of modified Delphi to gauge agreement on 78 final questions (13 statements with 6 substatements for each) using a Likert scale. A modified Delphi process achieved agreement for 62 of the final expert rule statements. Statements with the highest degree of agreement included the physiology, and management of airway obstruction decreasing alveolar ventilation and ventilation-perfusion matching. The lowest agreement statements involved the relationship between shock and hypoxemic respiratory failure due to heightened oxygen consumption and dead space. Our study proves the utility of a modified Delphi method to generate consensus to create expert rule statements for further development of a digital twin-patient model with acute respiratory failure. A substantial majority of expert rule statements used in the digital twin design align with expert knowledge of respiratory failure in critically ill patients
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.
RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Métagénomique ciblée pour le diagnostic d’infection bactérienne.
Introduction: Le diagnostic d'une infection repose encore souvent sur les cultures conventionnelles de micro-organismes, ce qui entraîne un délai de résultat plus long et une faible sensibilité en cas d'utilisation antérieure d'antibiotiques ou de pathogène difficile à cultiver. Les méthodes moléculaires peuvent contourner les limitations ci-dessus en détectant directement l'ADN des micro-organismes dans un échantillon. La réaction en chaîne par polymérase (PCR) spécifique ou multiplex offre une alternative seulement si une idée prédéfinie du diagnostic a été faite. La PCR 16S suivie du séquençage Sanger a été utilisée comme méthode de diagnostic au cours des dernières décennies, mais en complément en cas de culture négative plus que comme technique alternative aux cultures. La limite principale du séquençage Sanger est qu’il ne peut détecter qu'une seule séquence à la fois, ce qui limite sa sensibilité et sa capacité à détecter plusieurs organismes par échantillon. En revanche, le séquençage nouvelle génération (NGS) peut amplifier des millions de fragments à la fois, permettant une détection plus sensible des pathogènes en particulier pour les échantillons négatifs en culture ou polymicrobiens. Objectif : Dans ce travail, nous évaluons 1) l’apport de l’implémentation du NGS dans les tests de routine et sa performances pour le diagnostic d'infection bactérienne dans les tissus et les liquides organiques provenant de sites normalement stériles; 2) l’utilisation du NGS pour l’identification des agents pathogènes dans le liquide synovial et le liquide de sonication de patients souffrant d'infections de prothèses articulaires (PJI); 3) l’utilisation du NGS pour le diagnostic microbiologique dans le sang et le plasma de patients atteints d'endocardite infectieuse (IE). Methodes : Nous nous sommes principalement concentrés sur une approche de métagénomique ciblée en utilisant l’amplification par PCR du gène de l'ARN ribosomal 16S, avant de séquencer l’ADN amplifié sur un outil de NGS, le MiSeqTM (Illumina). L’analyse bioinformatique a été faite sur RipSeq, Pathogenomix. Resultats : Dans les tissus et les liquides organiques, la sensibilité clinique de la métagénomique ciblée était plus élevée que celle des cultures, en particulier chez les patients ayant reçu un traitement antimicrobien préalable. Pour le diagnostic d’infection de prothèse ostéo-articulaire, la sensibilité de métagénomique ciblée dans le liquide synovial n’était pas augmentée par rapport à la sensibilité des cultures. Néanmoins, dans une étude portant sur 105 échantillons de liquide de sonication provenant de patient porteurs d’une prothèse totale de coude, la métagénomique ciblée avait une sensibilité clinique de 85 % contre 77 % pour les cultures. Dans le cas de l'endocardite infectieuse, un agent pathogène a été détecté dans 18/29 (62%) des IE à hemocultures positives et 5/6 (83%) des IE à hémocultures négatives.Conclusion:. Nous avons démontré l’utilité de la métagénomique ciblée pour la détection d’agents pathogènes sur les tissus et liquides biologiques en examen de routine, ainsi que dans le diagnostic d’infection de prothèses ostéo-articulaires et de l’endocardite infectieuse. Nos résultats ouvrent la perspective d’une application technique en routine, indépendante des cultures et avec une meilleure sensibilité que ces dernières dans un temps imparti théorique de 48h.Introduction : Diagnosis of infection still oftentimes relies on conventional cultures of microorganisms, resulting in longer result delay and poor sensitivity in case of previous use of antibiotics difficult-to-grow pathogens. Molecular methods may circumvent the above limitations by detecting microorganism DNA in samples. Next generation sequencing (NGS) can amplify millions of DNA fragments at once, and thus makes a perfect candidate for diagnostic, especially for culture-negative specimens and polymicrobial samples.Objectives : In this work, 1) we evaluate the additional value of 16S rRNA gene-based PCR followed by Sanger sequencing or NGS in routine testing and its performance for diagnostic of bacterial infection in tissues and body fluids from normally sterile sites. Then, 2) we investigated its use for pathogen identification in synovial fluid and sonicate fluid from patients suffering from Prosthetic Joint Infections (PJI), as well as 3) in blood and plasma in patients with Infective Endocarditis (IE). Methods : We focus on a targeted metagenomics approach using 16S rRNA gene-based PCR as an amplification step before performing NGS on a MiSeqTM (Illumina). Bioinformatics analysis was done using Ripseq, Pathogenomix software. Results : In tissues and body fluids the clinical sensitivity of targeted metagenomics was higher than cultures especially in patients who had received antimicrobial therapy. For diagnosis of PJI, tNGS was not superior to cultures in synovial fluid. However, in a study on 105 sonicate fluids from elbow arthroplasty failures, targeted metagenomics had a clinical sensitivity of 85% compared to 77% for cultures. In IE, pathogens were detected in whole blood and plasma, in 18 out of 29 (62%) blood culture-positive cases and 5 out of 6 (83%) BCNE.Conclusion : tNGS is useful for bacterial diagnosis in routine microbiology as well as in PJI and IE, especially in culture-negative infection and patients who had received antimicrobial therap
Li, B and Be Contents of Harzburgites from the Dramala Complex (Pindos Ophiolite, Greece): Evidence for a MOR-type Mantle in a Supra-subduction Zone Environment
The Pindos ophiolite represents oceanic lithosphere obducted during the Jurassic. The Dramala mantle section mainly consists of highly depleted spinel harzburgite and minor plagioclase-bearing harzburgite. Textural observations and major element compositions of minerals indicate that the harzburgites experienced impregnation by a mafic, depleted melt and subsequent high-temperature (high-T) hydration and cooling (>750°C) forming pargasite and edenitic hornblende. During further cooling (from 350–400°C to µg/g) are slightly elevated. The bulk Li contents (0•5–1•1 µg/g) are in the upper range of values for unmetasomatized mantle, whereas B contents (µg/g) are variable and slightly elevated compared with the unmetasomatized mantle as a result of serpentinization. Beryllium abundances in all minerals are very low (µg/g), except for pargasite, where a maximum Be content of 0•012 µg/g was measured. The selective addition of Li to clinopyroxene can be related to the interaction with a depleted melt, and/or to partitioning of Li into clinopyroxene upon cooling. During high-T hydration and cooling, the fluid calculated to be in equilibrium with the pargasite or edenitic hornblende (based on Li, Be and B) could have been reaction-modified seawater. Low-T hydration may have led to a very minor increase in bulk B content of most samples and to the formation of serpentine with highly variable B contents (0•1–28 µg/g). Low-T hydration decreased the Li content of orthopyroxene, and Li was probably leached from some samples. The lack of correlation between degree of serpentinization and bulk B contents as well as the presence of high- and low-B serpentine can be explained by low fluid–rock ratios, decreasing T during serpentinization and lack of equilibrium as a result of fast obduction–exhumation. The low light-element contents of primary minerals and whole-rock samples clearly argue against a supra-subduction zone (SSZ) origin of the Dramala mantle section, and against the previous hypothesis of hydrous melting of the Pindos mantle above a subduction zone. We therefore conclude that the Dramala harzburgites represent a mid-ocean ridge (MOR)-type mantle, and not an SSZ-type mantle, juxtaposed with MOR-type and SSZ-type oceanic crust, either in a back-arc or in an intra-oceanic subduction zone setting