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/)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Correlation between processing conditions and fiber breakage during compounding of glass fiber-reinforced polyamide

International audienceThe inter-relationship between processing conditions and fiber breakage has been studied for glass fiber-reinforcedpolyamide 12, prepared using (i) an internal batch mixer, (ii) a laboratory scale corotating twin screw extruder, and (iii) an industrial scale twin screw extruder. The average fiber lengths and fiber length distributions were measured for various compounding conditions (screw or rotor speed, mixing time, feed rate). Experimental results have shown that fiber breakage depends on both screw speed and mixing time, the later being controlled, in an extruder, by the feed rate. For a given compounding system (batch mixer or twin screw extruder), the energy input (specific mechanical energy, SME) during the compounding process is found to be a reliable parameter, which governs fiber length (average, minimal, and maximal) evolution. Experimental data are correctly described with a model defining change in fiber length as a function of SM

Efficient profile-likelihood confidence intervals for capture-recapture models

International audienceIn a capture-recapture analysis, uncertainty in the parameter estimates is usually expressed by presenting classical Wald-type confidence intervals. This approach involves (1) the assumption that the maximum likelihood estimates are asymptotically normal and (2) numerical computation of the variance-covariance matrix of these estimates. When the sample size is small or when the estimates are on the boundary of their domain, a Wald confidence interval often performs badly. A natural alternative is to use profile-likelihood confidence intervals. In general, these intervals require a greater amount of computation. We propose a new implementation of this approach that is efficient, both in reducing the amount of computation and in coping with boundary estimates. We also show how profile-likelihood confidence intervals can be adjusted for overdispersion. Simulations were used to check whether nominal coverage levels were attained, and allowed us to compare this approach with the classical Wald procedure. We illustrate this work by considering a multi-state model for a sooty shearwater (Puffinus griseus) population

A Study of Fiber Breakage during Compounding in a Buss Kneader

International audienceThis paper is devoted to the study of fiber breakage during compounding with a polyamide matrix in a Buss kneader. Results showed a drastic decrease of glass fiber length during compounding, typically from 3500 to 350 mu m. Fiber breakage depended on processing conditions: it increased with screw speed, but the effect of feed rate was less clear. Fiber breakage increased also with the severity of the screw profile. Characterizations of fiber length evolution along the screw profile have also been performed after dead-stop experiments. Generally speaking, fiber length evolution can be described using a modified Shon-Liu-White model, in which either the number of turns or the specific energy is considered

Influence of extrusion conditions on fiber breakage along the screw profile during twin screw compounding of glass fiber-reinforced PA

International audienceIn the present study, Polyamide 12 was compounded with glass fibers in both laboratory and industrial twin screw extruders using various processing conditions (screw speed and feed rate). Dead-stop experiments were performed and samples were collected at different locations along the screws in order to determine the fiber length distribution and the extent of fiber breakage. Results show that significant fiber break-up occurs right after the addition of glass fibers to the molten matrix. Similarly fiber length distribution changes drastically at the first sampling location, near the glass fiber feeder. Processing conditions also influence the extent of degradation: it increases with screw speed and decreases with feed rate, which controls the residence time. Flow modelling has been used to calculate the flow conditions along the screw profile. It is shown that the modified Shon-Liu-White model previously proposed to describe the average fiber length evolution as function of specific energy is not able to correctly predict the evolution along the screw profile. In similar processing conditions, the large industrial extruder appears as less severe than the small laboratory on

Propriétés thermomécaniques et comportement élasto-(visco) plastique des matériaux composites bio-sourcés

International audienceIn this work, the nonlinear properties of bio-based composite materials are derived for a thermomechanical loading. The thermo-elastic problem of the composite is firstly solved by a micromechanics approach. It accounts for the material anisotropy through the morphological and topological textures. Next, the nonlinear response is established in the framework of the J2plasticity. The obtained algorithmic tangent operator for each constituent is used as uniformmodulus for homogenisation purpose. Numerical results are compared with data from the open literature. Applications, which are conducted on a flax fibres/polypropylene PP composite, highlight the influence of the strain rate, and the volume fraction as well as the temperature on the effective properties.Les propriétés non linéaires des composites bio-sourcés sous un chargement thermomécanique sont étudiées dans ce travail. L’approche, basée sur un formalisme micromécanique, dérive les propriétés thermoélastiques du bio-composite.Elle prend également en compte l’anisotropie du matériau par les textures morphologique et topologique de la microstructure. L’extension du modèle micromécanique au comportement non linéaire est obtenue de la linéarisation des équations constitutives locales. Celle-ci-est basée sur la théorie du J2en plasticité.Les modules tangents algorithmiques obtenus sont utilisés comme propriétés des phases dans d’homogénéisation micromécanique. Les résultats numériques sont comparés aux données de la littérature. Une application a été effectuée sur un composite de fibres de lin noyées dans une matrice polypropylène PP en fonction de la vitesse de déformation, la fraction volumique et la température

Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients

International audienceBackground: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. Method: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. Results: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 40,000) groups (HR = 0.327, CI95% [0.26–0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. Conclusion: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment