Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: study protocol for the international, multicenter, randomized PLUSS trial.

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if: (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), potential systemic side effects of corticosteroids, cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity). DISCUSSION: Combining budesonide with surfactant for intratracheal administration is a simple intervention that may reduce BPD in extremely preterm infants and translate into health benefits in later childhood. The PLUSS trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants regardless of their initial mode of respiratory support. Should intratracheal budesonide mixed with surfactant increase survival free of BPD, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au ), ACTRN12617000322336. First registered on 28th February 2017.

Energy-Aware Dynamic DU Selection and NF Relocation in O-RAN Using Actor-Critic Learning.

Open radio access network (O-RAN) is one of the promising candidates for fulfilling flexible and cost-effective goals by considering openness and intelligence in its architecture. In the O-RAN architecture, a central unit (O-CU) and a distributed unit (O-DU) are virtualized and executed on processing pools of general-purpose processors that can be placed at different locations. Therefore, it is challenging to choose a proper location for executing network functions (NFs) over these entities by considering propagation delay and computational capacity. In this paper, we propose a Soft Actor-Critic Energy-Aware Dynamic DU Selection algorithm (SA2C-EADDUS) by integrating two nested actor-critic agents in the O-RAN architecture. In addition, we formulate an optimization model that minimizes delay and energy consumption. Then, we solve that problem with an MILP solver and use that solution as a lower bound comparison for our SA2C-EADDUS algorithm. Moreover, we compare that algorithm with recent works, including RL- and DRL-based resource allocation algorithms and a heuristic method. We show that by collaborating A2C agents in different layers and by dynamic relocation of NFs, based on service requirements, our schemes improve the energy efficiency by 50% with respect to other schemes. Moreover, we reduce the mean delay by a significant amount with our novel SA2C-EADDUS approach.