Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial

background acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. however, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. methods the personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. the primary endpoint is all-cause mortality at day 90. secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). after a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. discussion PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. trial registration the PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344)

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

As prerrogativas contratuais unilaterais

Le contrat, traditionnellement le temple de la bilatéralité, subit depuis de nombreuses années l’influence d’un mouvement insufflant davantage d’unilatéralisme à son contenu. L’acceptation de cet unilatéralisme, contemporaine de la revalorisation de l’individu au sein de la société, a eu lieu de manière graduelle. Initialement confiné à des clauses périphériques, l’unilatéralisme a pris une place de plus en plus importante jusqu’à gagner le cœur des échanges entre les parties. La diversification du modèle contractuel, fondé au départ exclusivement sur l’échange établi sur la vente et englobant aujourd’hui d’autres opérations économiques obéissant notamment à une logique de coopération, apparaît comme essentielle à la compréhension de cette évolution. La logique sous-jacente à l’opération économique du contrat, un échange ou une coopération, guidera la compréhension des limites de l’unilatéralisme au sein de l’instrument contractuel.Une fois l’unilatéralisme admis au cœur des échanges, les limites du pouvoir unilatéral restent à définir. La mise en œuvre de l’unilatéralisme nécessite un encadrement rigoureux afin d’éviter tout débordement et notamment l’abus dans l’utilisation des prérogatives contractuelles unilatérales. Certains mécanismes ont été prévus par le législateur afin de contrôler la mise en œuvre de l’unilatéralisme. C’est le cas notamment de l’obligation de motivation. D’autres outils, inspirés notamment du droit brésilien, pourraient contribuer au renforcement de ce contrôle. L’évolution du droit des contrats, le travail de la doctrine et de la jurisprudence détermineront les limites de l’unilatéralisme reconnu par le législateur.The contract, an institution usually endorsed by at least two people, has now undergone for many years the influence of a movement instilling more of what French authors call unilatéralisme, meaning more unilateral powers to only one of the contractors. The influence of unilatéralisme over the contract, contemporary to the more and more significant place of the individual in society, took place gradually. Initially confined to peripheral clauses of the contract such as termination clauses, unilateralism took an increasingly important place until it reached the very heart of the exchanges between the parties. The diversification of the economic model of the contract, which was initially based on the exchange established by the sale of goods and which encompasses today other economic operations based on the cooperation between the parties, is essential to understand this evolution. The logic underlying the economic operation of the contract, an exchange or a cooperation, will guide the understanding of the limits of the unilateralism.Once unilateralism has been accepted at the heart of the exchanges, the limits of the unilateral power remain to be defined. The enforcement of unilateral powers requires a rigorous framework to avoid any misuse and abuse of the unilateral power. The legislator provided a few mechanisms to perform this control of the use of unilateral powers, for example the duty to give reasons. Other tools, inspired by Brazilian law, could also contribute to strengthening this control. The evolution of contract law, the work of doctrine and case-law will determine the limits of the unilateralism.Tradicionalmente visto como o “templo da bilateralidade”, o contrato vem sofrendo nos últimos anos a influência de um movimento de valorização das chamadas prerrogativas unilaterais. A aceitação da influência do que a doutrina francesa convencionou chamar de “unilatéralisme” encontra eco na valorização recente do indivíduo dentro da sociedade, característica do pós-modernismo. Se, inicialmente, a influência das prerrogativas individuais só podia ser observada em cláusulas ditas “marginais” do contrato, como as cláusulas resolutivas, hoje as prerrogativas unilaterais fazem parte também do conteúdo central do instrumento contratual. O aumento da importância das prerrogativas unilaterais pode ser explicado pelo movimento da “diversificação” do modelo contratual. Inicialmente visto como tão somente uma troca entre os contratantes, como o que ocorre no contrato de compra e venda, o contrato hoje deve levar em conta diversas outras operações econômicas, muitas vezes numa lógica de cooperação entre as partes (distribuição, franquia, entre outros). No entanto, a multiplicação desse tipo de cláusula apresenta um risco para o equilíbrio contratual. Sem um controle rigoroso, a execução dessas cláusulas pode dar margem a abuso. Assim, a presente tese propõe alguns limites para as cláusulas que conferem um poder unilateral, evitando o abuso no uso das mesmas. Alguns dos mecanismos de controle são diretamente inspirados do direito brasileiro. Outros, fazem parte da realidade contratual do direito francês. Os verdadeiros limites dessas cláusulas serão estabelecidos pela evolução do direito dos contratos e pela influência da doutrina e da jurisprudência

Annos academicos, S. Paulo, 1860-1864 /

Includes index.Mode of access: Internet

New General Discrete-Time Scheduling Model for Multipurpose Batch Plants

This work deals with the optimal short-term scheduling of general multipurpose batch plants, considering multiple operational characteristics such as sequence-dependent changeovers, temporary storage in the processing units, lots blending, and material flows traceability. A novel Mixed Integer Linear Programming (MILP) discrete-time formulation based on the State-Task Network (STN) is proposed, with new types of constraints for modeling changeovers and storage. We also propose some model extensions for addressing changeovers start; nonpreemptive lots; lots start and sizes; alternative task-unit and task-unit-layout assignments. Computational tests have shown that the proposed model is more effective than a similar model based on the Resource-Task Network (RTN)

Optimizing the Design and Planning of a Sugar-Bioethanol Supply Chain under Uncertain Market Conditions

In today’s society, the so-called green consciousness about environmental issues has triggered an intense search for renewable energy sources. Bioenergy, obtained by transformation processes of biomass such as castor bean or sugar cane, plays a decisive role in this context, providing much of the energy used in the electricity production, heat supply, and transport sector. Sugar cane, in particular, has assured considerable economic relevance due to its multiple applications. It is commonly employed as fodder for animal feed or as raw material for producing electricity, bioethanol, sugar, molasses, and other bioproducts. Currently, the integrated management of all stages of the transformation processes of this biomass has become a major challenge due to the complex interactivity and exchanges between all the actors present in the logistics chain. In this work, a scenario-based approach built upon a mixed-integer linear programming (MILP) formulation is proposed aiming at designing and planning, under demand uncertainty, a sugar-bioethanol supply chain network whose harvesting, production, storage, and distribution activities are integrated. The model’s optimization objective is to maximize the expected net present value (ENPV) when deciding on the location, size, and technologies of industrial parks and storage sites, the size of truck fleets, which markets to serve, and inventory levels, among other important issues. The adequacy and efficiency of the MILP model are illustrated through a case study based on the Brazilian sugar-bioethanol industry

Solution Methodology for Scheduling Problems in Batch Plants

This paper proposes a solution methodology for the production scheduling of batch plants. The methodology is defined by an integrated approach that simultaneously considers the representation of the scheduling problem, the optimization model, and the decision-making process. A problem representation and a mixed integer linear programing (MILP) model are developed and applied to solve a real world scheduling problem from the chemical–pharmaceutical industry. The main advantage of this approach is that it includes a general process representation that can be used across several departments of the company. Moreover, we also discuss development and implementation challenges of optimization methods for the process industry, and we provide some guidelines to mitigate existing problematic issues in this domain

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines

: Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable