The predictive value of the NICE "red traffic lights" in acutely ill children

Objective: Early recognition and treatment of febrile children with serious infections (SI) improves prognosis, however, early detection can be difficult. We aimed to validate the predictive rule-in value of the National Institute for Health and Clinical Excellence (NICE) most severe alarming signs or symptoms to identify SI in children. Design, Setting and Participants: The 16 most severe ("red") features of the NICE traffic light system were validated in seven different primary care and emergency department settings, including 6,260 children presenting with acute illness. Main Outcome Measures: We focussed on the individual predictive value of single red features for SI and their combinations. Results were presented as positive likelihood ratios, sensitivities and specificities. We categorised "general" and "disease-specific" red features. Changes in pre-test probability versus post-test probability for SI were visualised in Fagan nomograms. Results: Almost all red features had rule-in value for SI, but only four individual red features substantially raised the probability of SI in more than one dataset: "does not wake/stay awake", "reduced skin turgor", "non-blanching rash", and "focal neurological signs". The presence of ≥3 red features improved prediction of SI but still lacked strong rule-in value as likelihood ratios were below 5. Conclusions: The rule-in value of the most severe alarming signs or symptoms of the NICE traffic light system for identifying children with SI was limited, even when multiple red features were present. Our study highlights the importance of assessing the predictive value of alarming signs in clinical guidelines prior to widespread implementation in routine practice

Addressing model discrepancy in a clinical model of the oxygen dissociation curve

Many mathematical models suffer from model discrepancy, posing a significant challenge to their use in clinical decision-making. In this article, we consider methods for addressing this issue. In the first approach, a mathematical model is treated as a black box system, and model discrepancy is defined as an independent and additive term that accounts for the difference between the physical phenomena and the model representation. A Gaussian Process (GP) is commonly used to capture the model discrepancy. An alternative approach is to construct a hybrid grey box model by filling in the incomplete parts of the mathematical model with a neural network. The neural network is used to learn the missing processes by comparing the observations with the model output. To enhance interpretability, the outputs of this non-parametric model can then be regressed into a symbolic form to obtain the learned model. We compare and discuss the effectiveness of these approaches in handling model discrepancy using clinical data from the ICU and the Siggaard–Andersen oxygen status algorithm. This article is part of the theme issue ‘Uncertainty quantification for healthcare and biological systems (Part 2)’

Haemodynamic changes with paracetamol in critically-ill children.

PURPOSE: Paracetamol has been associated with a reduction in blood pressure, especially in febrile, critically-ill adults. We hypothesised that blood pressure would fall following administration of paracetamol in critically-ill children and this effect would be greater during fever and among children with a high body surface area to weight ratio. METHODS: A 12-month prospective observational study of children (0-16years) admitted to paediatric intensive care, who underwent pulse contour analysis and received paracetamol concurrently. RESULTS: Mean arterial blood pressure decreased significantly by 4.7% from baseline (95% CI 1.75-8.07%) in 31 children following 148 doses of paracetamol. The nadir was 2-hour post-dose. The effect was pronounced in children with fever at baseline (6.4%, 95% CI 2.8-10%), although this was not statistically significant. There was no simple relationship between this effect and body surface area to weight ratio. The association between a change in blood pressure and changes in heart rate or measured stroke volume was poor; therefore it was likely that a change in the systemic vascular resistance contributes most to this effect. CONCLUSION: There is a significant but modest reduction in blood pressure post-paracetamol in critically-ill children. This is likely related to a change in systemic vascular resistance

SEAL: Sealed-Bid Auction without Auctioneers

We propose the first auctioneer-free sealed-bid auction protocol with a linear computation and communication complexity O(c), c being the bit length of the bid price. Our protocol, called Self-Enforcing Auction Lot (SEAL), operates in a decentralized setting, where bidders jointly compute the maximum bid while preserving the privacy of losing bids. In our protocol, we do not require any secret channels between participants. All operations are publicly verifiable; everyone including third-party observers is able to verify the integrity of the auction outcome. Upon learning the highest bid, the winner comes forward with a proof to prove that she is the real winner. Based on the proof, everyone is able to check if there is only one winner or there is a tie. While our main protocol works with the first-price sealed-bid, it can be easily extended to support the second-price sealed-bid (also known as the Vickrey auction), revealing only the winner and the second highest bid, while keeping the highest bid and all other bids secret. To the best of our knowledge, this work establishes to date the best computation and communication complexity for sealed-bid auction schemes without involving any auctioneer

The use of physiologic markers of anemia intolerance to guide transfusion practice in pediatric intensive care units: an international survey

Objectives: To explore how red blood cell (RBC) transfusion practice of pediatric intensivists is modulated by physiologic markers of anemia intolerance, in addition to the hemoglobin (Hb) concentration. Background: Most research to date has tested transfusion policies based on Hb threshold alone. Use of physiologic parameters to guide RBC transfusion in pediatric intensive care units (PICU) is not well described. Methods/materials: Scenario-based self-administered survey among pediatric intensivists in tertiary-care PICUs in Belgium, Canada, France, Japan and United Kingdom. Pediatric intensivists were approached through national networks and by e-mail. Five case scenarios were developed for non-bleeding critically ill children who were hemodynamically stable at baseline. Respondents were asked to select a Hb threshold for each scenario and indicate how alternative thresholds of different physiologic parameters would modify their baseline hemoglobin (Hb) threshold. Results: One hundred thirty-two participant responses were received (response rate 56%). Findings indicate that pediatric intensivists do incorporate physiologic parameters when deciding to transfuse RBCs. The most significant determinants of RBC transfusion, in addition to Hb threshold, were baseline co-morbidity (cyanotic cardiac vs. other patients), ScvO2, blood lactate, increasing inotrope or vasoactive-inotropic score, and a drop ≥ 3 g/dL in the Hb concentration. Conclusions: Stated transfusion practice by pediatric intensivists involves physiologic parameters, in addition to Hb concentration. Both static and dynamic parameters (single value and trend over time) were considered by clinicians. The striking variation in practice pattern reported strongly supports the need for further studies that would identify and assess the impact of physiologic biomarkers for RBC transfusion in PICU

Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions

Background: Renovascular hypertension (RenoVH) is a cause of hypertension in children. A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin–angiotensin–aldosterone axis, often leading to cardiac remodelling. This longitudinal observational study aims to describe occurrence of cardiovascular changes secondary to RenoVH and also any improvement in cardiac remodelling after successful endovascular and/or surgical intervention. Methods: All patients with RenoVH referred to our centre, who received ≥ 1 endovascular intervention (some had also undergone surgical interventions) were included. Data were collected by retrospective database review over a 22-year period. We assessed oscillometric blood pressure and eight echocardiographic parameters pre- and post-intervention. Results: One hundred fifty-two patients met inclusion criteria and had on average two endovascular interventions; of these children, six presented in heart failure. Blood pressure (BP) control was achieved by 54.4% of patients post-intervention. Average z-scores improved in interventricular septal thickness in diastole (IVSD), posterior Wall thickness in diastole (PWD) and fractional shortening (FS); left ventricular mass index (LVMI) and relative wall thickness (RWT) also improved. PWD saw the greatest reduction in mean difference in children with abnormal (z-score reduction 0.25, p < 0.001) and severely abnormal (z-score reduction 0.23, p < 0.001) z-scores between pre- and post-intervention echocardiograms. Almost half (45.9%) had reduction in prescribed antihypertensive medications, and 21.3% could discontinue all antihypertensive therapy. Conclusions: Our study reports improvement in cardiac outcomes after endovascular + / − surgical interventions. This is evidenced by BP control, and echocardiogram changes in which almost half achieved normalisation in systolic BP readings and reduction in the number of children with abnormal echocardiographic parameters. Graphical abstract: [Figure not available: see fulltext.]

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Paediatric Intensive Care

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Spo2) target of 88-92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Spo2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Spo2 target of more than 94% or a conservative Spo2 target of 88-92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals

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. DESIGN: Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. SETTING: Eighteen PICUs across the United Kingdom. PATIENTS: Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. INTERVENTIONS: Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). CONCLUSIONS: Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals