Evaluation of Phoenix Sepsis Score Criteria: Exploratory Analysis of Characteristics and Outcomes in an Emergency Transport PICU Cohort From the United Kingdom, 2014-2016.

Objectives: To assess characteristics and outcomes of children with suspected or confirmed infection requiring emergency transport and PICU admission and to explore the association between the 2024 Phoenix Sepsis Score (PSS) criteria and mortality.

Design: Retrospective analysis of curated data from a 2014-2016 multicenter cohort study.

Setting: PICU admission following emergency transport in South East England, United Kingdom, from April 2014 to December 2016.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

Longer-term survival, quality of life, and cost-effectiveness of conservative versus liberal oxygenation targets in critically ill children: a pre-specified analysis from Oxy-PICU, a multicentre, open, parallel-group, randomised controlled trial.

Background: Peripheral oxygen saturation (SpO) above 94% is typical in children in paediatric intensive critical care units (PICUs) who are receiving invasive ventilation and supplemental oxygen. In a previous report from the Oxy-PICU trial, we showed that lower (conservative) oxygenation targets (SpO 88-92%) are beneficial, showing small but statistically significant differences in duration of organ support and large but non-significant cost reductions at 30 days. In this pre-specified analysis of the Oxy-PICU trial, we compare longer-term outcomes and cost-effectiveness of conservative versus liberal (SpO >94%) oxygenation targets in children with emergency PICU admission.

High-flow nasal cannula is an expensive and clunky placebo: myth or maxim?

High-flow nasal cannula (HFNC) is now a commonly used noninvasive method of providing respiratory support to children and young people. Its rapid spread into varied clinical applications has often left assessment of the evidence of its mechanism of action and clinical benefit lagging behind its uptake. This review will discuss the proposed mechanisms of action of HFNC, review the evidence base for its use, cover its applications in paediatrics and outline its limitations.

Cost-effectiveness of high flow nasal cannula therapy versus continuous positive airway pressure for non-invasive respiratory support in paediatric critical care.

Background: High flow nasal cannula therapy (HFNC) and continuous positive airway pressure (CPAP) are two widely used modes of non-invasive respiratory support in paediatric critical care units. The FIRST-ABC randomised controlled trials (RCTs) evaluated the clinical and cost-effectiveness of HFNC compared with CPAP in two distinct critical care populations: acutely ill children ('step-up' RCT) and extubated children ('step-down' RCT). Clinical effectiveness findings (time to liberation from all forms of respiratory support) showed that HFNC was non-inferior to CPAP in the step-up RCT, but failed to meet non-inferiority criteria in the step-down RCT.

Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children.

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls.

Contribution of ethnicity, area level deprivation and air pollution to paediatric intensive care unit admissions in the United Kingdom 2008-2021.

Background: There is emerging evidence on the impact of social and environmental determinants of health on paediatric intensive care unit (PICU) admissions and outcomes. We analysed UK paediatric intensive care data to explore disparities in the incidence of admission according to a child's ethnicity and the degree of deprivation and pollution in the child's residential area.

Methods: Data were extracted on children <16 years admitted to UK PICUs between 1st January 2008 and 31st December 2021 from the Paediatric Intensive Care Audit Network (PICANet) database.

Transport of critically ill children to paediatric intensive care units in the UK and Ireland: 2013-2022.

Objective: To explore the trends and changes in the transport of children to paediatric intensive care units (PICUs) between 2013 and 2022.

Design: Retrospective analysis of routinely collected data.

Patients: Children transported for care in a PICU in the UK and Ireland aged<16 years.

Ethnicity and Observed Oxygen Saturations, Fraction of Inspired Oxygen, and Clinical Outcomes: A Post-Hoc Analysis of the Oxy-PICU Trial of Conservative Oxygenation.

Objectives: A conservative oxygenation strategy, targeting peripheral oxygen saturations (Sp o2 ) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Sp o2 greater than 94% in our recent Oxy-PICU trial. Sp o2 monitors may overestimate arterial oxygen saturation (Sa o2 ) in patients with higher levels of skin pigmentation compared with those with less skin pigmentation. We investigated if ethnicity was associated with changes in distributions of Sp o2 and F io2 and outcome.

Effectiveness of high flow nasal Cannula (HFNC) therapy compared to standard oxygen therapy (SOT) and continuous positive airway pressure (CPAP) in bronchiolitis.

High Flow Nasal Cannula therapy (HFNC) is a form of respiratory support for bronchiolitis. Recent evidence confirms HFNC reduces the risk of treatment escalation by nearly half (45%) compared to standard oxygen therapy (SOT), although most patients (75%) with mild-moderate respiratory distress manage well on SOT. The majority of children (60%) failing SOT respond well to HFNC making rescue use of HFNC a more cost-effective approach compared to its first-line use.

Framework for Research Gaps in Pediatric Ventilator Liberation.

Background: The 2023 International Pediatric Ventilator Liberation Clinical Practice Guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, because of the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence.

Research Question: What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines?

Study Design And Methods: We conducted systematic reviews of the literature in eight predefined Population, Intervention, Comparator, Outcome (PICO) areas related to pediatric ventilator liberation to generate recommendations.

Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children.

Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children.

Clinical practice, decision-making, and use of clinical decision support systems in invasive mechanical ventilation: a narrative review.

Invasive mechanical ventilation is a key supportive therapy for patients on intensive care. There is increasing emphasis on personalised ventilation strategies. Clinical decision support systems (CDSS) have been developed to support this.

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

Objectives: Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care.

Can critical care transport be safely reduced in children intubated during emergency management of status epilepticus in the United Kingdom: a national audit with case-control analysis.

Objective: This study describes the baseline clinical characteristics, predictors of successful extubation at referring hospitals and short-term outcomes of children intubated for status epilepticus and referred to United Kingdom (UK) paediatric critical care transport teams (PCCTs).

Design: Multicentre audit with case-control analysis, conducted between 1 September 2018 and 1 September 2020.

Setting: This study involved 10 UK PCCTs.

Using healthcare systems data for outcomes in clinical trials: issues to consider at the design stage.

Background: Healthcare system data (HSD) are increasingly used in clinical trials, augmenting or replacing traditional methods of collecting outcome data. This study, PRIMORANT, set out to identify, in the UK context, issues to be considered before the decision to use HSD for outcome data in a clinical trial is finalised, a methodological question prioritised by the clinical trials community.

Methods: The PRIMORANT study had three phases.

Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

Background: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care.

Hospital admissions linked to SARS-CoV-2 infection in children and adolescents: cohort study of 3.2 million first ascertained infections in England.

Objective: To describe hospital admissions associated with SARS-CoV-2 infection in children and adolescents.

Design: Cohort study of 3.2 million first ascertained SARS-CoV-2 infections using electronic health care record data.

Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children: A Systematic Review and Network Meta-Analysis.

Importance: Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown.

Objective: To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT).

Emergency Inter-Hospital Transfer of Children to PICUs in the United Kingdom: Qualitative Exploration of Parents' Experiences of Retrieval Teams.

Objectives: Each year in the United Kingdom there are around 5,000 inter-hospital transfers of critically ill children into PICUs. There are few published descriptions of what this experience is like for parents. The objective was to describe parents' experiences of the inter-hospital transfer of their critically ill child to a PICU.

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.

Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort.