Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 � 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 �103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7) were included in the primary analysis (median interquartile range age, 62 50-71 years; 237 42.2% women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% 95% CI,-6.6% to 9.8%; odds ratio, 1.06 95% CI, 0.76-1.48; P =.70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% 1-sided 97.5% CI,-� to 3.4%; odds ratio, 1.83 1-sided 97.5% CI, 0.00-5.93), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% 95% CI, 0.4%-3.8%; P =.01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. © 2021 American Medical Association. All rights reserved

Fluid structure interaction (FSI) based wind load modeling for dynamic analysis of overhead transmission lines

Electricity is a crucial form of energy in our societies, and transmission lines are key elements to ensure the reliability of electric power grids. Continuity of service is the main preoccupation of electric utilities, and this continuity may be disrupted by a large variety of sources and accidents. Transmission lines, by their intrinsic topology, remain the grid components that are the most exposed to climatic sources of disruption.The most common and important source of dynamic loads on transmission lines results from wind effects on the towers and conductors. Conductors are particularly sensitive to wind effects as they are long and relatively flexible (compared to their supports) and are literally wind-catching structures in the power grid infrastructure. In cold climates, wind and ice have compounding effects on lines and give rise to the most severe design loading conditions. Therefore, accurate prediction of the wind pressure on overhead conductors is essential to conduct a reliable assessment of the line response, in terms of both electrical clearances and conductor loads transferred to supports. Spatial randomness of wind loads on overhead lines has already been addressed by stochastic analysis methods and is now taken into account in design with the use of so-called span factors. Further gains in wind load accuracy can be obtained by examining the physics of wind effects on conductors, in both non-iced and iced conditions, with improved predictions of lift and drag forces determined from fluid-structure interaction (FSI) analysis.The traditional design method to apply wind load on transmission lines is to convert the design wind speed to a static pressure through Bernoulli's equation where the pressure is proportional to the air density and the squared wind speed. In this approach the fluid-structure interaction of wind and line components is ignored: wind is considered as a quasi-static load on conductors and supports, while special instability effects due to particular wind conditions such as vortex shedding (Aeolian vibrations) and flutter (cable galloping) are accounted for separately with specific mitigation solutions if necessary.In gusty wind conditions with high turbulence intensity, conductors may experience large horizontal displacements that affect their surrounding wind flow. A physically accurate wind load evaluation on conductors is possible by computational wind-structure interaction analysis. To date, largely due to its high computational cost and the lack of experimental data to validate computational models, an advanced fluid-structure analysis framework for wind-cable interaction has not been developed. In this study a new approach based on FSI analysis to evaluate equivalent wind loads on conductors is developed. The first step in such an approach is accurate evaluation of wind pressure on conductor. For this purpose the FSI analysis is carried out in two dimensions where the detailed bare and iced conductor section geometry and surrounding air flow are modeled, considering a given incident wind speed. The conductor cross section is assumed to be supported on flexible supports to study the interaction between the conductor motion and the air flow. FSI analysis yields both the fluid and structure response. Of particular interest is the wind pressure field on the conductor section, which allows the computation of the resultant drag and lift forces. This process is repeated for several cross sections along the span and the resulting forces provide the effective span wise wind load distribution on the conductor. This wind loading is then used as input in a separate 3-D computational nonlinear dynamic analysis model to predict the line response. This dynamic analysis of the line section can be detailed to represent very realistic line sections including conductors, suspension links and supporting towers.Nos sociétés sont fortement dépendantes de l'électricité, et il ne fait pas de doute que la fonctionnalité des lignes de transport est déterminante pour assurer la fiabilité des réseaux électriques modernes. En effet, la continuité de l'approvisionnement en électricité reste la préoccupation majeure de toutes les compagnies d'électricité, et cette continuité du service peut être compromise par une multitude d'incidents ou d'accidents sur l'ensemble du réseau. Parmi toutes les sources possibles de charges dynamiques sollicitant les lignes de transport, celles provenant des effets du vent sur les pylônes et les conducteurs restent les plus fréquentes. Les conducteurs de lignes sont particulièrement vulnérables aux effets du vent car les portées sont longues et flexibles (comparé aux pylônes) et leur présence physique dans le réseau en font des structures exposées à toutes les intempéries qui peuvent survenir sur le territoire couvert. Cette vulnérabilité est encore plus grande dans les climats nordiques où les effets combinés du givrage atmosphérique et du vent créent des scénarios de charges de conception parmi les plus critiques et donc susceptibles de contrôler la conception finale des lignes. Il nous apparaît donc essentiel de comprendre la dynamique des fluides des effets du vent pour prédire avec réalisme et un degré de précision raisonnable la pression du vent exercée sur les conducteurs. Une meilleure évaluation des charges dues au vent permettrait par le fait même des prédictions plus réalistes de la réponse des lignes aux charges de vent, non seulement en terme de déplacements et dégagements électriques mais aussi en terme des charges nettes transférées aux pylônes par les conducteurs. La nature aléatoire des effets du vent sur les conducteurs a déjà fait l'objet de nombreuses études scientifiques et les méthodes d'analyse stochastique modernes permettent de cerner la question : les méthodes de conception simplifiées qui sont suggérées dans les normes et guides tiennent compte de ces effets en utilisant un coefficient de portée global qui ajuste à la baisse les efforts calculés au pylône sous des charges supposées synchrones et uniformes le long des conducteurs. Cette recherche ne concerne pas cet aspect de la question. Nous croyons que des gains de précision appréciables dans la prédiction des charges de vent sur les lignes sont possibles par une meilleure modélisation de la physique des effets du vent sur les conducteurs, dans les conditions givrées ou non, en utilisant les techniques d'analyse qui tiennent compte des interactions dynamiques fluide-structure. Ces interactions sont ignorées dans les méthodes d'analyse conventionnelles qui consistent simplement à calculer une pression statique proportionnelle à la vitesse carrée du fluide selon l'équation classique de Bernoulli. Bien sûr, les concepteurs ne négligent pas la considération des vibrations éoliennes ou du galop des conducteurs, mais ces phénomènes sont traités séparément et n'influencent pas le calcul des charges sur les pylônes. Dans cette recherche, nous nous intéressons aux conditions de vent de rafale avec grande turbulence qui caractérisent les tempêtes de vent. Ces vents forts et turbulents créent de grands déplacements des conducteurs qui modifient les conditions d'écoulement d'air. Une évaluation plus précise de ces conditions est possible par analyse computationnelle des interactions vent-conducteur.Les bases théoriques de la physique des phénomènes en présence sont connues mais aucun cadre d'application numérique n'a été proposé jusqu'à maintenant, en partie à cause des coûts numériques élevés mais aussi dû au manque de données expérimentales pouvant valider ces modèles computationnels.Nous avons développé un tel cadre d'analyse computationnelle dans cette recherche et l'avons illustré dans un cycle complet, du calcul des charges au calcul de la réponse d'une section de ligne, avec plusieurs exemples pratiques à chacune des étapes de développemen

Fluid Structure Interaction (FSI) Based Wind Load Modelingfor Dynamic Analysis of Overhead Transmission Lines

Note:Electricity is a crucial form of energy in our societies, and transmission lines are key elements to ensure the reliability of electric power grids. Continuity of service is the main preoccupation of electric utilities, and this continuity may be disrupted by a large variety of sources and accidents. Transmission lines, by their intrinsic topology, remain the grid components that are the most exposed to climatic sources of disruption. The most common and important source of dynamic loads on transmission lines results from wind effects on the towers and conductors. Conductors are particularly sensitive to wind effects as they are long and relatively flexible (compared to their supports) and are literally wind-catching structures in the power grid infrastructure. In cold climates, wind and ice have compounding effects on lines and give rise to the most severe design loading conditions. Therefore accurate prediction of the wind pressure on overhead conductors is essential to conduct a reliable assessment of the ine response, in terms of both electrical clearances and conductor loads transferred to supports. Spatial randomness of wind loads on overhead lines has already been addressed by stochastic analysis methods and is now taken into account in design with the use of so-called span factors. Further reasonable gains in wind load accuracy can be obtained by examining the physics of wind effects on conductors, in both non-iced and iced conditions, with improved predictions of lift and drag forces determined from fluid-structure interaction (FSI) analysis. The traditional design method to apply wind load on transmission lines is to convert the design wind speed to a static pressure through Bernoulli 's equation where the pressure is proportional to the air density and the squared wind speed. In this approach the fluid-structure interaction of wind and line components is ignored: wind is considered as a quasi-static load on conductors and supports, while special instability effects due to particular wind conditions suc as vortex shedding (Aeolian vibrations) and flutter (cable galloping) are accounted for separately with specific mitigation solutions if necessary. In gusty wind conditions with high turbulence intensity, conductors may experience large horizontal displacements that affect their surrounding wind flow. A physically accurate wind load evaluation on conductors is possible by computational wind-structure interaction analysis. To date, largely due to its high computational cost and the lack of experimental data to validate computational models, an advanced fluid-structure analysis framework for wind-cable interaction has not been developed. In this study a new approach based on FSI analysis to evaluate equivalent wind loads on conductors is developed. The first step in such an approach is accurate evaluation of wind pressure on conductor. For this purpose the FSI analysis is carried in two dimensions where the detailed bare and iced conductor section geometry and surrounding air flow are modeled, considering a gi en incident wind speed. The conductor cross section is assumed to be supported on flexible supports to study the interaction between the conductor motion and the air flow. FSI analysis yields both the fluid and structure response. Of particular interest is the wind pressure field on the conductor section, which allows the computation of the resultant drag and lift forces. This process is repeated for several cross sections along the span and the resulting forces provide the effective span wise wind load distribution on the conductor. This wind loading is then used as input in a separate 3-D computational nonlinear dynamic analysis model to predict the line response. This dynamic analysis of the line section can be detailed to represent very realistic line sections including conductors, suspension links and supporting towers. It should be emphasized that the author does not advocate the "complexification" of overhead line wind analysis with the introduction of FSI and dynamic computational simulations in engineering offices. It is rather proposed to use these advanced computational methods, in a research and development context, to evaluate and possibly improve current wind analysis methods. Another very interesting application of this computational technique relates to optimized cross-sectional design of conductors, in terms of geometry and surface roughness. Detailed FSI analysis also enables the evaluation of aerodynamic damping of various cable geometries. As many Canadian utilities are reassessing the reliability levels of their transmission infrastructure and making difficult investment decisions, a more realistic wind loading model could be of high value. Key words: Overhead transmission line wind loading; fluid-structure interactions; computational fluid dynamics; conductor lift and drag coefficients; interactive wind and ice effects; overhead line conductorsNos societes sont fortement dependantes de l'electricite, et il ne fait pas de doute que la fonctionnalite des !ignes de transport est determinante pour assurer la fiabilite des reseaux electriques modemes. En effet, la continuite de l'approvisionnement en electricite reste la preoccupation majeure de toutes les compagnies d'electricite, et cette continuite du service peut etre compromise par une multitude d'incidents ou d'accidents sur !'ensemble du reseau. Les !ignes de transport sont toutefois les composants du reseau qui sont les plus exposes aux charges climatiques ou environnementales susceptibles de declencher des pannes. Parmi toutes les sources possibles de charges dynamiques sollicitant les !ignes de transport, celles provenant des effets du vent sur les pylones et les conducteurs restent les plus frequentes. Les conducteurs de !ignes sont particulierement vulnerables aux effets du vent car les portees sont longues et flexibles (compare aux pylones) et leur presence physique dans le reseau en font ds structures exposees a toutes les intemperies qui peuvent survenir sur le territoire couvert. Cette vulnerabilite est encore plus grande dans les climats nordiques ou les effets combines du givrage atmospherique et du vent creent des scenarios de charges de conception parmi les plus critiques et done susceptibles de controler la conception finale des !ignes. Il nous apparait done essentiel de comprendre la dynamique des fluides des effets du vent pour predire avec realisme et un degre de precision raisonnable la pression du vent exercee sur les conducteurs. Une meilleure evaluation des charges dues au vent permettrait par le fait meme des predictions plus realistes de la reponse des lignes aux charges de vent, non seulement en terme de deplacements et degagements electriques mais aussi en terme des charges nettes transferees aux pylones par les conducteurs. La nature aleatoire des effets du vent sur les conducteurs a deja fait l'objet de nombreuses etudes scientifiques et les methodes d'analyse stochastique modemes permettent de cemer la question: les methodes de conception simplifiees qui sont suggerees dans les normes et guides tiennent compte de ces effets en utilisant un coefficient de portee global qui ajuste a la baisse les efforts calcules au pylone sous des charges supposees synchrones et uniformes le long des conducteurs. Cette recherche ne conceme pas cet aspect de la question. Nous croyons que des gains de precision appreciables dans la prediction des charges de vent sur les lignessont possibles par une meilleure modelisation de la physique des effets du vent sur les conducteurs, dans les conditions givrees ou non, en utilisant les techniques d'analyse qui tiennent compte des interactions dynamiques fluide-structure. Ces interactions sont ignorees dans les methodes d'analyse conventionnelles qui consistent simplement a calculer une pression statique proportionnelle a la vitesse carree du fluide selon l' equation classique de Bemouilli. Bien sur, les concepteurs ne negligent pas la consideration des vibrations eoliennes ou du galop des conducteurs, mais ces phenomenes sont traites separement et n'influencent pas le calcul des charges sur les pyl6nes. Dans cette recherche, nous nous interessons aux conditions de vent de rafale avec grande turbulence qui caracterisent les tempetes de vent. Ces vents forts et turbulents creent de grands deplacements des conducteurs qui modifient les conditionsd'ecoulement d' air. Une evaluation plus precise de ces conditions est possible par analyse computationnelle des interactions vent-conducteur. Les bases theoriques de la physique des phenomenes en presence sont connues mais aucun cadre d'application numerique n'a ete propose a date, en partie a cause des couts numeriques eleves mais aussi du au manque de donnees experimentales pouvant valider ces modeles computationnels. Nous avons developpe un tel cadre d' analyse computationnelle dans cette recherche et 1' avons illustre dans un cycle complet, du calcul des charges au calcul de la reponse d'une section de ligne, avec plusieurs exemples pratiques a chacune des etapes de developpement. L'etape initiate consiste a determiner precisement le champ des pressions exercees a la surface d 'un conducteur de ligne a partir de modeles en deux dimensions qui rendent la reponse detaillee d 'une section de conducteur sur supports flexibles dans un ecoulement d'air a vitesse de vent incidente donnee. Une analyse CFD (dynamique des fluides computationnelle) du domaine fluide, l'air en mouvement entourant le conducteur, procede interactivement avec une analyse des deplacements de la section de conducteur, pour determiner les forces nettes (trainee et portance) agissant a !'interface airconducteur. Le processus est repete a volonte pour differentes conditions de support duconducteur ( correspondant a diverses positions le long de la portee) et pour une serie temporelle de conditions de vitesse de vent incident. Au final, on peut ainsi calculer un historique des forces dues au vent sur une portion tributaire de la portee jugee representative et utiliser ces forces comme des charges extemes sur des modeles d'analyse dynamique non lineaire de sections de lignes en trois dimensions. Ces analyses peuvent etre detaillees a souhait pour determiner la reponse dynamique des conducteurs, accessoires d'attache et pylones sous vents turbulents. Nous insistons sur le fait que nous ne suggerons pas une complexification de !'analyse des !ignes de transport sous les effets du vent dans les bureaux d'etudes a !'aide de modeles dynamiques sophistiques combinant les interactions des domaines fluides et solides. Nous proposons plutot d' utiliser le cadre computationnel mis a l'epreuve danscette recherche dans un contexte de recherche et developpement pour evaluer et possiblement ameliorer les methodes statiques conventionnelles. Une autre application interessante conceme la conception optimisee de la geometrie des conducteurs de lignes en termes de proprietes aerodynamiques. Mots cles: vent sur les !ignes aeriennes de transmission; interactions fluide-structure ; dynamique des fluides computationnelle ; coefficients de trainee et de portance des conducteurs ; interactions vent et givre

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial

BACKGROUND: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. METHODS: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. RESULTS: In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p $_{interaction}$ = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (OR$_{ordinal}$: 0.64, 95% CI: 0.41-1.01, p = 0.05). CONCLUSION: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508)