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Introduction: Childhood critical illness impacts the entire family of the critically ill patient. Disruptions to usual family rhythms and routines, established relationships, physical relocations or shifts in caregivers, and the uncertainty about the patient's well-being can have significant impacts on siblings and other connected children in the family. Promoting and facilitating family interactions and engaging younger family members in the hospital experience have been shown to reduce patient and family anxiety, enhance family adaptation, and improve child and family outcomes. The critical care team can implement evidence-informed approaches to address and mitigate challenges for families and provide developmentally aligned support to impacted siblings., Aim: This conceptual paper describes the potential impacts of a critical illness hospitalization on siblings, approaches to supporting siblings, and practical interventions drawn from a synthesis of the current literature and the author's practice experience caring for critically ill children and their families., Data Sources: A traditional review and narrative analysis moderated by the authors and supported by lived experience., Conclusions: There is a range of impacts of a critical illness hospitalization on siblings and young family members of the patient. Providing consistent, transparent, and supportive child, sibling, and whole family-centered care can improve the experience and outcomes for the child and family., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Dryden-Palmer, Shinewald and O'Leary.)

Pediatric intensive care is a rapidly developing medical specialty and with evolving understanding of pediatric pathophysiology and advances in technology, most children in the developed world are now surviving to intensive care and hospital discharge. As mortality rates for children with critical illness continue to improve, increasing PICU survivorship is resulting in significant long-term consequences of intensive care in these vulnerable patients. Although impairments in physical, psychosocial and cognitive function are well documented in the literature and the importance of establishing follow-up programs is acknowledged, no standardized or evidence-based approach to long-term follow-up in the PICU exists. This narrative review explores pediatric post-intensive care syndrome and summarizes the multifactorial deficits and morbidity that can occur in these patients following recovery from critical illness and subsequent discharge from hospital. Current practices around long-term follow-up are explored with discussion focusing on gaps in research and understanding with suggested ways forward and future directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Quadir, Festa, Gilchrist, Thompson, Pride and Basu.)

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation., Competing Interests: JC-C speaker for Novamed and Tecnoquimicas; received financial travel support from BAGO to attend the Colombian Congress of Pediatrics; participated in an Advisory Board for ZambonColombia; acted as an investigator in phase 2 and 3 clinical trials of Merck Sharp and Dhome drugs (antibiotics and monoclonal antibodies) that do not interfere in the course of this study. JL stock options in MERCK and MODERNA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor “CFO” declared a past co-authorship with the authors “NK & MOW”. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Kortz, Mediratta, Smith, Nielsen, Agulnik, Gordon Rivera, Reeves, O’Brien, Lee, Abbas, Attebery, Bacha, Bhutta, Biewen, Camacho-Cruz, Coronado Muñoz, deAlmeida, Domeryo Owusu, Fonseca, Hooli, Wynkoop, Leimanis-Laurens, Nicholaus Mally, McCarthy, Mutekanga, Pineda, Remy, Sanders, Tabor, Teixeira Rodrigues, Yuee Wang, Kissoon, Takwoingi, Wiens and Bhutta.)

Background: In pediatric intensive care units, extubation failure following invasive mechanical ventilation poses significant health risks. Determining readiness for extubation in children can minimize associated morbidity and mortality. This study investigates the potential role of renal near-infrared spectroscopy (RrSO2) in predicting extubation failure in pediatric patients., Methods: A total of 84 patients aged between 1 month and 18 years, mechanically ventilated for at least 24 h, were included in this prospective study. RrSO2 levels were measured using near-infrared spectroscopy before and during an extubation readiness test (ERT). The primary outcome measure was extubation failure, defined as a need for reintubation within 48 h., Results: Of the 84 patients, 71 (84.6%) were successfully extubated, while 13 (15.4%) failed extubation. RrSO2 was found to be lower in the failed extubation group, also decrease in RrSO2 values during ERT was significantly greater in patients with extubation failure. ROC analysis indicated a decrease in ΔRrSO2 of more than 6.15% from baseline as a significant predictor of extubation failure, with a sensitivity of 0.984 and a specificity of 0.889., Conclusion: Monitoring changes in RrSO2 values may serve as a helpful tool to predict extubation failure in pediatric patients. Further multi-center research is warranted to improve the generalizability and reliability of these findings., Competing Interests: GC worked at Hamilton Medical AG in the Department of Medical Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Colak, Ceylan, Topal, Sarac Sandal, Atakul, Soydan, Sarı, Hepduman, Karaarslan and Ağın.)

Background: Spinal Muscular Atrophy (SMA) type 1 is a debilitating condition with a poor prognosis, though therapeutic advances are promising. Long-term ventilation is a common management strategy as respiratory function deteriorates. Without consensus on best practice respiratory management, the decision to initiate invasive LTV (I-LTV) for this group of young children involves many ethical considerations. Understanding the main influencing factors on a clinician's likelihood to initiative I-LTV for a child with chronic critical illness is important to maintain transparency and trust with the family during this challenging time., Methods: A factorial survey was used to identify the factors that influence a clinician to support initiation of I-LTV for children with SMA type 1. Factorial survey content was based on literature and evidence-based practice and the content was subject to extensive pretesting and pilot testing. An anonymous survey was disseminated (Oct 2021-Jan 2022), via eight international professional organisations, to clinicians with experience caring for children at the time of initiation of I-LTV., Results: 251 participants answered 514 vignettes on SMA type 1. The greatest influencing factor on clinician's likelihood to initiate I-LTV was parental agreement with the need to initiate I-LTV. Additional qualitative comments from participants support this finding. Clinicians also highlighted the important role of innovative therapies as well as the availability of supports for families when considering initiation however these findings were context based., Conclusions: The factorial survey approach provides a valuable way of identifying influencers on decision-making in sensitive situations. The findings demonstrate the acceptance of the centrality of parental influence in decisions on care delivery. Effective communication with the child's family is key to ensuring shared understanding and agreement of goals of care. More international research is needed on the long-term effects of novel treatments, as well as impact on quality of life and influence of geographical location, to inform decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Quirke, Cassidy, Alexander, Walsh, Hill, Masterson, Flynn and Brenner.)

Introduction: Mortality rates in infancy and childhood are lower in females than males. However, for children admitted to Paediatric Intensive Care Units (PICU), mortality has been reported to be lower in males, although males have higher admission rates. This female mortality excess for the subgroup of children admitted in intensive care is not well understood. To address this, we carried out a systematic literature review to summarise the available evidence. Our review studies the differences in mortality between males and females aged 0 to <18 years, while in a PICU, to examine whether there was a clear difference (in either direction) in PICU mortality between the two sexes, and, if present, to describe the magnitude and direction of this difference., Methods: Any studies that directly or indirectly reported the rates of mortality in children admitted to intensive care by sex were eligible for inclusion. The search strings were based on terms related to the population (those admitted into a paediatric intensive care unit), the exposure (sex), and the outcome (mortality). We used the search databases MEDLINE, Embase, and Web of Science as these cover relevant clinical publications. We assessed the reliability of included studies using a modified version of the risk of bias in observational studies of exposures (ROBINS-E) tool. We considered estimating a pooled effect if there were at least three studies with similar populations, periods of follow-up while in PICU, and adjustment variables., Results: We identified 124 studies of which 114 reported counts of deaths by males and females which gave a population of 278,274 children for analysis, involving 121,800 (44%) females and 156,474 males (56%). The number of deaths and mortality rate for females were 5,614 (4.61%), and for males 6,828 (4.36%). In the pooled analysis, the odds ratio of female to male mortality was 1.06 [1.01 to 1.11] for the fixed effect model, and 1.10 [1.00 to 1.21] for the random effects model., Discussion: Overall, males have a higher admission rate to PCU, and potentially lower overall mortality in PICU than females., Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=203009, identifier (CRD42020203009)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Almossawi, Friend, Palla, Feltbower, Sardo-Infirri, O'Brien, Harron, Nadel, Saunders and De Stavola.)

Tetralogy of Fallot (ToF) is one of the most common congenital cyanotic heart lesions and can present to a variety of health care professionals, including teams working in pediatric intensive care. Pediatric intensive care teams may care for a child with ToF pre-operatively, peri-operatively, and post-operatively. Each stage of management presents its own unique challenges. In this paper we discuss the role of pediatric intensive care in each stage of management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Hammett and Griksaitis.)

Objective: The Surviving Sepsis Campaign recommends systematic screening for sepsis. Although many sepsis screening tools include parent or healthcare professional concern, there remains a lack of evidence to support this practice. We aimed to test the diagnostic accuracy of parent and healthcare professional concern in relation to illness severity, to diagnose sepsis in children., Design: This prospective multicenter study measured the level of concern for illness severity as perceived by the parent, treating nurse and doctor using a cross-sectional survey. The primary outcome was sepsis, defined as a pSOFA score >0. The unadjusted area under receiver-operating characteristic curves (AUC) and adjusted Odds Ratios (aOR) were calculated., Setting: Two specialised pediatric Emergency Departments in Queensland., Patients: Children aged 30 days to 18 years old that were evaluated for sepsis., Intervention: None., Main Results: 492 children were included in the study, of which 118 (23.9%) had sepsis. Parent concern was not associated with sepsis (AUC 0.53, 95% CI: 0.46-0.61, aOR: 1.18; 0.89-1.58) but was for PICU admission (OR: 1.88, 95% CI: 1.17-3.19) and bacterial infection (aOR: 1.47, 95% CI: 1.14-1.92). Healthcare professional concern was associated with sepsis in both unadjusted and adjusted models (nurses: AUC 0.57, 95% CI-0.50, 0.63, aOR: 1.29, 95% CI: 1.02-1.63; doctors: AUC 0.63, 95% CI: 0.55, 0.70, aOR: 1.61, 95% CI: 1.14-2.19)., Conclusions: While our study does not support the broad use of parent or healthcare professional concern in isolation as a pediatric sepsis screening tool, measures of concern may be valuable as an adjunct in combination with other clinical data to support sepsis recognition., Clinical Trial Registration: ACTRN12620001340921., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Sever, Schlapbach, Gilholm, Jessup, Phillips, George, Gibbons and Harley.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Failure to recognize and respond to clinical deterioration in a timely and effective manner is an urgent safety concern, driving the need for early identification systems to be embedded in the care of children in hospital. Pediatric early warning systems (PEWS) or PEW scores alert health professionals (HPs) to signs of deterioration, trigger a review and escalate care as needed. PEW scoring allows HPs to record a child's vital signs and other key data including parent concern., Aim: This study aimed to explore the experiences and perceptions of parents about the acceptability of a newly implemented electronic surveillance system (the DETECT surveillance system), and factors that influenced acceptability and their awareness around signs of clinical deterioration and raising concern., Methods: Descriptive, qualitative semi-structured telephone interviews were undertaken with parents of children who had experienced a critical deterioration event (CDE) ( n = 19) and parents of those who had not experienced a CDE (non-CDE parents) ( n = 17). Data were collected between February 2020 and February 2021., Results: Qualitative data were analyzed using generic thematic analysis. Analysis revealed an overarching theme of trust as a key factor that underpinned all aspects of children's vital signs being recorded and monitored. The main themes reflect three domains of parents' trust: trust in themselves, trust in the HPs, and trust in the technology., Conclusion: Parents' experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic pediatric early warning system (The DETECT system) were positive; they found it acceptable and welcomed the use of new technology to support the care of their child., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saron, Carter, Siner, Preston, Peak, Mehta, Lane, Lambert, Jones, Hughes, Harris, Evans, Dee, Eyton-Chong, Carrol and Sefton.)

Background and Aims: Intracranial Hypertension (ICH) is a life-threatening complication of brain injury. The invasive measurement of intracranial pressure (ICP) remains the gold standard to diagnose ICH. Measurement of Optic Nerve Sheath Diameter (ONSD) using ultrasonography is a non-invasive method for detecting ICH. However, data on paediatric brain injury are scarce. The aim of the study was to determine the performance of the initial ONSD measurement to predict ICH occurring in children with severe brain injury and to describe the ONSD values in a control group., Methods: In this cross-sectional study, ONSD was measured in children aged 2 months-17 years old with invasive ICP monitoring: before placement of ICP probe and within the 60 min after, and then daily during 3 days. ONSD was also measured in a control group., Results: Ninety-nine patients were included, of whom 97 were analysed, with a median (IQR) age of 8.7 [2.3-13.6] years. The median (IQR) PIM 2 score was 6.6 [4.4-9.7] and the median (IQR) PELOD score was 21 [12-22]. Aetiologies of brain injury were trauma ( n = 72), infection ( n = 17) and stroke ( n = 8). ICH occurred in 65 children. The median (IQR) ONSD was 5.58 mm [5.05-5.85]. ONSD performed poorly when it came to predicting ICH occurrence within the first 24 h (area under the curve, 0.58). There was no significant difference between the ONSD of children who presented with ICH within the first 24 h and the other children, with a median (IQR) of 5.6 mm [5.1-5.9] and 5.4 mm [4.9-5.8], respectively. Infants aged less than 2 years had a median (IQR) ONSD of 4.9 mm [4.5-5.2], significantly different from children aged more than 2 years, whose median ONSD was 5.6 mm [5.2-5.9]. Age, aetiology or ICP levels did not change the results. Thirty-one controls were included, with a median age of 3.7 (1.2-8.8) years. The median (IQR) of their ONSD measurement was 4.5 mm [4.1-4.8], significantly lower than the patient group., Conclusion: In a paediatric severe brain injury population, ONSD measurement could not predict the 24 h occurrence of ICH. Severity of patients, timing and conditions of measurements may possibly explain these results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cour-Andlauer, Portefaix, Wroblewski, Rabilloud, Bordet, Cogniat, Didier, Pouyau, Valla, Kassai-Koupai, Siméon, Ginhoux, Courtil-Teyssedre and Javouhey.)

Background: The Post Intensive Care Syndrome (PICS) describes new impairments of physical, cognitive, social, or mental health after critical illness. In recent years, prevention and therapy concepts have been developed. However, it is unclear whether and to what extent these concepts are known and implemented in hospitals in German-speaking countries., Methods: We conducted an anonymous online survey in German-speaking pediatric intensive care units on the current state of knowledge about the long-term consequences of intensive care treatment as well as about already established prevention and therapy measures. The request to participate in the survey was sent to the heads of the PICUs of 98 hospitals., Results: We received 98 responses, 54% of the responses came from nurses, 43% from physicians and 3% from psychologist, all working in intensive care. As a main finding, our survey showed that for only 31% of the respondents PICS has an importance in their daily clinical practice. On average, respondents estimated that about 42% of children receiving intensive care were affected by long-term consequences after intensive care. The existence of a follow-up outpatient clinic was mentioned by 14% of the respondents. Frequent reported barriers to providing follow-up clinics were lack of time and staff. Most frequent mentioned core outcome parameters were normal developmental trajectory (59%) and good quality of life (52%)., Conclusion: Overall, the concept of PICS seems to be underrepresented in German-speaking pediatric intensive care units. It is crucial to expand knowledge on long-term complications after pediatric critical care and to strive for further research through follow-up programs and therewith ultimately improve long-term outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Von Borell, Engel, Neunhoeffer, Hoffmann and Michel.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction: Clinical research within Paediatric Intensive Care (PICU) is necessary to reduce morbidity and mortality associated within this resource-intensive environment. With UK PICUs encouraged to be research-active there was a drive to understand how centres support research delivery., Aim: To identify the research workforce available within UK/Ireland PICUs to support clinical research delivery., Method: An electronic survey, endorsed by the Paediatric Critical Care Society (PCCS), was designed and reported in accordance with CHERRIES guidelines. The survey was distributed by email to all UK/Ireland Nurse Managers and Medical/ Nursing Research leads, aiming for one response per site during the period of April-June 2021. Only one response per site was included in analysis., Results: 44 responses were received, representing 24/30 UK/Ireland sites (80% response rate). Responses from n = 21/30 units are included (three excluded for insufficient data). 90% ( n = 19/21) units were research active, although only 52% ( n = 11) had permanent research roles funded within their staffing establishment. The majority of units ( n = 18, 86%) had less than two WTE research nurses. Resources were felt to be sufficient for current research delivery by 43% of units ( n = 9), but this confidence diminished to 19% ( n = 4) when considering their ability to support future research. The top barriers to research conduct were insufficiently funded/unfunded studies (52%; n = 11), clinical staff too busy to support research activity (52%; n = 11) and short-term/fixed-term contracts for research staff (38%; n = 8)., Conclusion: Despite the perceived importance of research and 90% of responding UK/Ireland PICUs being research active, the majority have limited resources to support research delivery. This has implications for their ability to participate in future multi-centre trials and opportunities to support the development of future medical/nursing clinical academics. Further work is required to identify optimum models of clinical research delivery., Competing Interests: JM is a National Institute for Health Research (NIHR) Senior Nurse and Midwife Research Leader. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Menzies, Jennings and Marshall.)

Background: Infections represent one of the most common complications in patients managed on Extracorporeal Membrane Oxygenation (ECMO) and are associated with poorer outcomes. Clinical signs of infection in patients on ECMO are non-specific. We assessed the diagnostic accuracy of Procalcitonin (PCT), C-reactive protein (CRP) and White cell count (WCC) to diagnose infection on ECMO., Methods: Retrospective single center observational study including neonates and children <18 years treated with ECMO in 2015 and 2016. Daily data on PCT, CRP and WCC were assessed in relation to microbiologically confirmed, and clinically suspected infection on ECMO using operating characteristics (ROC) curves., Results: Sixty-five ECMO runs in 58 patients were assessed. CRP had the best accuracy with an area under the ROC curve (AUC) of 0.79 (95%-CI 0.66-0.92) to diagnose confirmed infection and an AUC of 0.72 (0.61-0.84) to diagnose confirmed and suspected infection. Abnormal WCC performed slightly worse with an AUC of 0.70 (0.59-0.81) for confirmed and AUC of 0.66 (0.57-0.75) for confirmed and suspected infections. PCT was non-discriminatory., Conclusion: The diagnosis of infections acquired during ECMO remains challenging. Larger prospective studies are needed that also include novel infection markers to improve recognition of infection in patients on ECMO., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Doo, Staub, Mattke, Haisz, Seidler, Alphonso and Schlapbach.)

Introduction: Paediatric post sepsis syndrome is poorly defined and causes physical, neurocognitive, psychosocial morbidity, and family dysfunction. Families of sepsis survivors report unmet needs during care. Worldwide, the provision of post sepsis care is in its infancy with limited evidence to design clinical support pathways. Perspective: The Queensland Paediatric Sepsis Program (QPSP) developed a family support structure (FSS) to improve care during all stages of childhood sepsis. It was designed in partnership with consumers guided by information from consumers and it is partly delivered by consumers. Key areas include online, multimodal education for families and the ability to connect with other families affected by sepsis. The FSS is delivered by a multidisciplinary team (MDT) acting with clinicians local to the child. Families can join the FSS registry at any stage of their sepsis journey which connects them to our MDT team and opens opportunities to participate in future research and other initiatives. Improving public awareness is a critical outcome for our consumers and they have co-designed media and digital campaigns. Discussion: The ideal FSS for post sepsis syndrome management is a clinical pathway designed in partnership with consumers of interventions proven to improve outcomes from sepsis that meets their requirements. The QPSP FSS is novel as it is co-designed with, and partly delivered by, consumers with interventions aimed to improve the entire spectrum of morbidities suffered by survivors and their families, not just physical sequelae. Evaluation is embedded in the program and outcomes will guide evolution of the FSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Raman, English, O'Keefe, Harley, Steele, Minogue, Weller, Long, Irwin and Lister.)

Introduction: The prevalence of rare diseases is very important for health care research. According to the European Surveillance of Congenital Anomalies (EUROCAT) registers, the live prevalence for exstrophy and/or epispadias (grades 1-3) is reported with 1:23,255 (95% CI: 1:26,316; 1:20,000). A Europe-wide prevalence evaluation based on reports from excellence centers estimates a prevalence for exstrophies of 1:32,200 and for isolated epispadias of 1:96,800 in 2010. However, the frequency of exstrophy [International Statistical Classification of Diseases and Related Health Problems revision 10 (ICD-10): Q64.1] and epispadias (ICD-10: Q64.0) treated in different age groups in Germany remains unclear. Material and Method: Public health insurance data from 71 million people (approximately 87% of the population) were provided by the German Institute for Medical Documentation and Information (DIMDI) in accordance to the German Social Insurance Code for this research purpose. DIMDI analyzed the data source for the ICD diagnoses exstrophy and epispadias between 2009 and 2011. As provided data were robust over the years, averaged data are mentioned. Detailed subgroup analysis of small numbers was forbidden due to privacy protection. Results: Annually, 126 persons of all ages with epispadias and 244 with exstrophy are treated as inpatients. In the observed population, 34 infants (<1 year of age) with epispadias and 19 with exstrophy (58% male) are treated as outpatients each year. This corresponds to an estimated live prevalence of 1:11,000 (95% CI: 1:14,700; 1:8,400) for EEC (exstrophy-epispadias complex), more specifically a prevalence of 1:17,142 for epispadias and of 1:30,675 for exstrophy. The male-to-female ratio for exstrophy is 1.4:1 for infants and 1.6:1 for all minors. In children and adolescents, 349 epispadias and 393 exstrophies (up to the age of 17) are treated annually, whereas adults with exstrophy and even more with epispadias make comparatively less use of medical care. Conclusion: With the help of DIMDI data, the live prevalence of bladder exstrophy and epispadias in Germany could be estimated. The prevalence of epispadias was higher than in previous reports, in which milder epispadias phenotypes (grade 1 or 2) may not have been included. These analyses might enlighten knowledge about nationwide incidence and treatment numbers of rare diseases such as the EEC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors HR, NZ, and EJ., (Copyright © 2021 Ebert, Zwink, Reutter and Jenetzky.)

Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe form associated with SARS-CoV-2 infection in children. To reduce the spread of SARS-CoV-2 at the population level, educational setting closure have been implemented in many countries. However, the direct benefit of school closure on the MIS-C burden remains to be explored. We aimed to assess the role of educational settings in SARS-CoV-2 transmission among children with MIS-C. Methods: We conducted a French national prospective surveillance of MIS-C, coordinated by Public Health France, from April 2020 to March 2021. During this period, we included all children with MIS-C fulfilling the WHO definition who were reported to Public Health France. For each child, we traced the source of SARS-CoV-2 transmission. The main outcome was the proportion of children with MIS-C, with educational setting-related SARS-CoV-2 infection, during the period of school opening. Results: We included 142 children fulfilling WHO criteria for MIS-C: 104 (70%) cases occurred during school opening periods. In total, 62/104 children (60%, 95%CI [50; 69]) had been contaminated by a household contact and 5/104 in educational settings (5%, 95%CI [2; 11]). Among children with MIS-C occurring during school closure periods, the proportion of household transmission remained similar (66%, 25/38). Conclusion: Children with MIS-C were mainly infected by SARS-CoV-2 within their family environment, and the educational setting played a marginal role in this transmission. This suggests that mitigating school attendance may not reduce substantially the burden of MIS-C., Competing Interests: EJ reported receiving grants from CSL Behring. CL reported receiving grants from GlaxoSmithKline, Merck Sharp & Dohme, and Sanofi and personal fees from Pfizer and Merck. RC reported receiving personal fees from GlaxoSmithKline, Pfizer, Sanofi, and Merck Sharp & Dohme. NO report travel grants from GSK, Pfizer and Sanofi, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guenver, Oualha, Levy, Antona, Madhi, Toubiana, Lachaume, Javouhey, Lorrot, Yang, Levy, Caseris, Galeotti, Ovaert, Wiedemann, Girardin, Rybak, Cohen, Belot, Angoulvant and Ouldali.)

Background: It has been suggested that children and infants can develop multisystem inflammatory syndrome in children (MIS-C) in response to a SARS-CoV-2 infection and that Black children are overrepresented among cases. The aim of the current study was to quantify the association between Black, Asian, or other non-White genetic background and COVID-19-related MIS-C in children and infants. Methods: Eight different research groups contributed cases of MIS-C, potentially related to SARS-CoV-2 infection. Several sensitivity analyses were performed, including additional data available from the literature. Analyses were stratified by geographical region. Results: Seventy-three cases from nine distinct geographical regions were included in the primary analyses. In comparison to White children, the relative risk for developing MIS-C after SARS-CoV-2 infection was 15 [95% confidence interval (CI): 7.1 to 32] for Black children, 11 (CI: 2.2 to 57) for Asian, and 1.6 (CI: 0.58 to 4.2) for other ethnic background. Conclusion: Pediatricians should be aware of the fact that the risk of COVID-19-related MIS-C is severely increased in Black children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Middelburg, Crijnen, D'Antiga, Verdoni, Chikermane, Garg, Acharyya, Pruccoli, Schnapp, Rauf and Middelburg.)

Background: Suspected early-onset sepsis (EOS) is the main reason for antibiotic therapy at the start of life. Prolonged antibiotic therapy for culture-negative sepsis is often reported. Antibiotic stewardship is mandatory due to the potential negative effects of unnecessary antibiotics. Procalcitonin (PCT)-guided therapy is one possible strategy with published evidence to shorten antibiotic therapy. The aim of this study is to analyze the feasibility and the performance of the published PCT-algorithm in the clinical setting without study support. Methods: This is a retrospective, population-based study regarding duration of antibiotic therapy for suspected EOS in Central Switzerland between 2014 and 2018. All neonates >34 0/7 weeks of gestational age started on antibiotic therapy for suspected EOS within the first 3 calendar days of life were included. The Procalcitonin-guided algorithm according to the NeoPInS study was used as strategy to determine duration of antibiotic therapy. Results: In a population-based cohort of 35,642 life born neonates, the duration of antibiotic therapy of 879 neonates (2.5% of the cohort) treated for suspected EOS was 4 calendar days (median, IQR 2-5). We observed a statistically significant reduction from 4 (median, IQR 3-6) to 3 calendar days (median, IQR 2-4) from 2014 to 2018. Duration of antibiotic therapy was independent of gestational age (late-preterm vs. term neonates), of the presence of risk factors or clinical signs, but dependent on the presence of abnormal laboratory measurements (C-reactive protein > 10 mg/l or leukocytopenia <5 Giga/l) before start of antibiotic therapy ( p < 0.01). Conclusions: PCT-guided therapy using the NeoPInS algorithm is feasible and may lead to reduced duration of antibiotic therapy for suspected EOS as reported in the original study. We observed a learning curve to the new algorithm which may be explained as change process. The use of biomarker to guide duration of antibiotic therapy for suspected EOS may have unintended consequences with prolongation of antibiotic therapy in some cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zihlmann-Ji, Braun, Buettcher, Hodel, Lehnick and Stocker.)

Background: The use and perceived value of transcranial Doppler (TCD) scope in paediatric critical care medicine has not been extensively documented. Objective: To describe the use of TCD to assess non-traumatic brain injury in patients admitted to four paediatric intensive care units (PICUs) in France. Methods: We prospectively included all children (aged under 18) assessed with inpatient TCD between November 2014 and October 2015 at one of the four PICUs. The physicians completed a questionnaire within 4 h of performing TCD. Results: 152 children were included. The primary diagnosis was neurological disease in 106 patients (70%), including post ischemic-anoxic brain insult ( n = 42, 28%), status epilepticus ( n = 19, 13%), and central nervous system infection/inflammation ( n = 15, 10%). TCD was the first-line neuromonitoring assessment in 110 patients (72%) and was performed within 24 h of admission in 112 patients (74%). The most common indications for TCD were the routine monitoring of neurological disorders ( n = 85, 56%) and the detection of asymptomatic neurological disorders ( n = 37, 24). Concordance between the operator's interpretation of TCD and the published normative values was observed for 21 of the 75 (28%) TCD abnormal findings according to the published normative values. The physicians considered that TCD was of value for the ongoing clinical management of 131 (86%) of the 152 patients. Conclusion: TCD is commonly used in French PICUs and tends to be performed early after admission on patients with a broad range of diseases. The physicians reported that the TCD findings often helped their clinical decision making. In view of the subjectivity of bedside interpretation, true TCD contribution to clinical care remains to be determined. Objective studies of the impact of TCD on patient management and clinical outcomes are therefore warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rollet-Cohen, Sachs, Léger, Merchaoui, Rambaud, Berteloot, Kossorotoff, Mortamet, Dauger, Tissieres, Renolleau and Oualha.)

Introduction: Septic shock in children still carries substantial mortality and morbidity. While resuscitation with 40-60 mL/kg intravenous fluid boluses remains a cornerstone of initial resuscitation, an increasing body of evidence indicates potential for harm related to high volume fluid administration. We hypothesize that a protocol on early use of inotropes in children with septic shock is feasible and will lead to less fluid bolus use compared to standard fluid resuscitation. Here, we describe the protocol of the Early Resuscitation in Paediatric Sepsis Using Inotropes - A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED). Methods and analysis: The RESPOND ED study is an open label randomised controlled, two arm, multicentre pilot study conducted at four specialised paediatric Emergency Departments. Forty children aged between 28 days and 18 years treated for presumed septic shock will be randomized in a 1:1 ratio to early inotropes vs. standard fluid resuscitation. Early inotrope treatment is defined as the commencement of a continuous intravenous adrenaline infusion after 20 mL/kg fluid bolus resuscitation. Standard fluid resuscitation is defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to commencement of inotropes. In addition to feasibility outcomes, survival free of organ dysfunction censored at 28 days will be assessed as the main clinical outcome. The study cohort will be followed up at 28 days, and at 6 months post enrolment to assess quality of life and functional status. Biobanking nested in the study cohort will be performed to enable ancillary biomarker studies. Ethics and dissemination: The trial has ethical clearance (Children's Health Queensland, Brisbane, HREC/18/QCHQ/49168) and is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619000828123). Enrolment commenced on July 21st, 2019. The primary manuscript will be submitted for publication in a peer-reviewed journal. Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12619000828123., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Harley, George, King, Phillips, Keijzers, Long, Gibbons, Bellomo and Schlapbach.)

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce. Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing. Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance. Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation. Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schlapbach, Andre, Grazioli, Schöbi, Ritz, Aebi, Agyeman, Albisetti, Bailey, Berger, Blanchard-Rohner, Bressieux-Degueldre, Hofer, L'Huillier, Marston, Meyer Sauteur, Pachlopnik Schmid, Perez, Rogdo, Trück, Woerner, Wütz, Zimmermann, Levin, Whittaker, Rimensberger and the PIMS-TS working group of the Interest Group for Pediatric Neonatal Intensive Care (IGPNI) of the Swiss Society of Intensive Care and the Pediatric Infectious Diseases Group Switzerland (PIGS).)

Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy ("metabolic resuscitation") in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU). Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers. Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version : V1.8 22/7/20., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schlapbach, Gibbons, Ridolfi, Harley, Cree, Long, Buckley, Erickson, Festa, George, King, Singh, Raman, Bellomo and the RESPOND PICU study investigators and the Australian New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG).)

Sepsis and septic shock in newborns causes mortality and morbidity depending on the organism and primary site. ECMO provides cardiorespiratory support to allow adequate organ perfusion during the time for antibiotics and source control surgery (if needed) to occur. ECMO mode and cannulation site vary depending on support required and local preference. Earlier and more aggressive use of ECMO can improve survival., (Copyright © 2020 Butt and Chiletti.)

Objective: To explore the characteristics of mechanical ventilation parameters and the arterial partial pressure of oxygen in neonatal respiratory distress syndrome (RDS) at high altitude. Methods: From the 1st May 2017 to the 31st December 2018, we recruited 33 neonates with severe RDS who were undergoing mechanical ventilation in the NICU of Naqu People's Hospital in Tibet (4,580 m above sea level); these neonates formed a plateau observation group. We also recruited a non-plateau control group: 66 neonates with severe RDS undergoing mechanical ventilation of Shengjing Hospital in Liaoning (51 m above sea level). Various ventilation parameters and the arterial partial pressure of oxygen were then compared between the two groups, between the survivors of the two groups, and between those who died and survived in the plateau group. Results: In terms of initial ventilator parameters, peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), and the fraction of inspired oxygen (FiO2) in the plateau group were significantly higher than those in the non-plateau group ( P < 0.01). PIP, PEEP, and FiO2 in the survivors from the plateau group were also significantly higher than those in the non-plateau group ( P < 0.01). In addition, the arterial partial pressure of oxygen in the non-plateau group was higher ( P < 0.05) than that in the plateau group during the early postnatal period, and the arterial partial pressure of oxygen at 6 and 12 h was lower than that in the plateau group ( P < 0.05). Conclusion: Mechanical ventilation can effectively improve the arterial oxygen partial pressure and reduce the mortality of newborns with RDS in a plateau environment. It was clearly evident that ventilation parameters are closely related to altitude. It is therefore not advisable to apply mechanical ventilation parameters used in a non-plateau area as a guide for the treatment of newborns with RDS in plateau areas., (Copyright © 2019 Chen, Liu and Li.)

Background: Congenital heart disease (CHD) is one of the main causes of morbidity and mortality in children. Microcirculatory changes in CHD patients have previously been investigated using a variety of techniques. Handheld videomicroscopy enables non-invasive direct visualization of the microcirculatory bed. The aim of our study was to determine if there are microcirculatory differences among CHD patients based on age and the presence of cyanosis. Methods: A prospective observational study was carried out. Patients with CHD undergoing corrective surgery were evaluated after anesthetic induction prior to surgery. Microcirculation was evaluated using sidestream dark field (SDF) imaging. Hemodynamics and respiratory, biochemical, and tissue perfusion parameters were analyzed. Results: A total of 30 patients were included, of whom 14 were classified as cyanotic and 16 as non-cyanotic. Cyanotic patients had a higher total vessel density (TVD) ( p = 0.016), small vessel density ( p = 0.004), and perfused small vessel density ( p = 0.013), while their microvascular flow index (MFI) was lower ( p = 0.013). After adjustment for age and PaO 2 , cyanotic patients showed increased TVD ( p = 0.023), and small vessel density ( p = 0.025) compared to non-cyanotic patients but there were no differences on the MFI. Age was directly correlated with total MFI (spearman's rho = 0.499, p = 0.005) and small vessel MFI (spearman's rho = 0.420, p = 0.021). After adjustment for the type of CHD (cyanotic vs. non-cyanotic) patients with MFI and small MFI vessels <3 were younger than those with values ≥3 ( p = 0.033 and p = 0.037). Conclusions: SDF-based evaluation of microcirculation in CHD patients showed that patients with cyanotic defects had higher vascular density, as compared to patients with non-cyanotic defects. Younger patients were more likely to have a low MFI regardless of their type of CHD.

The recently revised Sepsis-3 definitions were based on criteria that were derived and validated in adult patient databases from high income countries. Both sepsis and septic shock continue to account for a substantial proportion of mortality globally, especially amongst children in low-and-middle income country settings. It is therefore urgent to develop and validate standardized criteria for sepsis that can be applied to pediatric populations in different settings, including in- and outside intensive care, both in high- and low/middle- income countries. This will be a pre-requisite to evaluate the impact of sepsis treatment strategies to improve clinical outcomes.

Infection with the meningococcus is one of the main causes of meningitis and septicaemia worldwide. Humans are the only natural reservoir for the meningococcus which is found primarily as a commensal inhabitant in the nasopharynx in ~10% of adults, and may be found in over 25% of individuals during adolescence. Prompt recognition of meningococcal infection and early aggressive treatment are essential in order to reduce mortality, which occurs in up to 10% of those with invasive meningococcal disease (IMD). This figure may be significantly higher in those with inadequate or delayed treatment. Early administration of effective parenteral antimicrobial therapy and prompt recognition and appropriate management of the complications of IMD, including circulatory shock and raised intracranial pressure (ICP), are critical to help improve patient outcome. This review summarizes clinical features of IMD and current treatment recommendations. We will discuss the evidence for immunization and effects of vaccine strategies, particularly following implementation of effective vaccines against Group B meningococcus.

Sepsis is a leading cause of morbidity and mortality in children with a worldwide prevalence in pediatric intensive care units of approximately 8%. Fluid bolus therapy (FBT) is a first line therapy for resuscitation of septic shock and has been a recommendation of international guidelines for nearly two decades. The evidence base supporting these guidelines are based on limited data including animal studies and case control studies. In recent times, evidence suggesting harm from fluid in terms of morbidity and mortality have generated interest in evaluating FBT. In view of this, studies of fluid restrictive strategies in adults and children have emerged. The complexity of studying FBT relates to several points. Firstly, the physiological and haemodynamic response to FBT including magnitude and duration is not well described in children. Secondly, assessment of the circulation is based on non-specific clinical signs and limited haemodynamic monitoring with limited physiological targets. Thirdly, FBT exists in a complex myriad of pathophysiological responses to sepsis and other confounding therapies. Despite this, a greater understanding of the role of FBT in terms of the physiological response and possible harm is warranted. This review outlines current knowledge and future direction for FBT in sepsis.

Background: In septic shock, both oxygen delivery (DO 2 ) and oxygen consumption (VO 2 ) are dysfunctional. The current therapeutic regimens are geared to normalize global oxygen delivery (DO 2 ) to tissues via goal directed therapies but mortality remains high at 10-20%. Methods: We studied cardiac index (CI), systemic vascular resistance index (SVRI), central venous oxygen saturation (ScvO2), central venous pressure (CVP), peripheral oxygen saturation (SpO2), mean blood pressure (MBP), body temperature, blood lactate, base excess and hemoglobin concentration (Hb) in a cohort of children admitted in "fluid-refractory" severe septic shock to pediatric intensive care, over 4.5-years. We calculated their 6 h global oxygen delivery (DO2) and global oxygen consumption (VO2) over the first 42 h and looked at factors associated with VO2/DO2 ratio (i.e., global oxygen extraction, gO2ER) and 28-day mortality. Results: Sixty-two children mean age (SD) 7.19 (5.44) years were studied. Fifty-seven (93%) children were sedated and mechanically ventilated and all received adrenaline or noradrenaline or both and added milrinone in 6 (9.6%). At 28 days, 9 (14.5%) were dead. The global oxygen extraction ratio (gO2ER) was consistently lower amongst the survivors and independently predicted mortality (ROC AUC = 0.75). A lactate level of 4 mmol/l or above, when associated with a concurrent metabolic acidosis predicted mortality with a sensitivity of 100% (95% CI 90.5-100) and a specificity of 67.7% (95% CI 62.2-72.9). A gO2ER of 0.48 or above on admission to the PICU was associated with death with a 66.7% sensitivity (95%CI 29.9-92.5) and 90.5% specificity (95%CI 79.3-96.8). A global O2ER of >0.48 combined with a concurrent blood lactate >4.0 mmol/l at any time within the first 42 h of therapy predicted death with a sensitivity of 63.9% (95% CI, 46.2-79.1) and specificity of 97.8% (95% CI, 95.7-99.0). A radar plot identified MBP-CVP difference, and CI as additional goals of therapy that may offer a survival benefit. Conclusions: Global O2ER of >0.48 with a concurrent blood lactate >4.0 mmol/l in children with metabolic acidosis was an independent factor associated with death in fluid resistant septic shock. Trends of gO2ER seem useful to recognize survivors and non-survivors early in the illness.

Background: Blood cultures are essential for the diagnosis and further appropriate treatment in children with suspected sepsis. In most hospitals, children will be empirically treated or closely monitored for at least 48 h awaiting results of blood cultures. Several studies have challenged the optimal duration of empiric treatment in the era of continuously monitored blood culture systems. The aim of our study was to investigate time-to-positivity (TTP) of blood cultures in children with proven sepsis. Methods: The Swiss Pediatric Sepsis Study prospectively enrolled children 0-16 years of age with blood culture positive sepsis between September 2011 and October 2015. TTP was prospectively assessed in six participating academic pediatric hospitals by fully automated blood culture systems. Results: In 521 (93%) of 562 bacteremia episodes (493 children, median age 103 days, range 0 days-16.9 years) a valid TTP was available. Median TTP was 12 h (IQR 8-17 h, range 0-109 h). By 24, 36, and 48 h, 460 (88%), 498 (96%), and 510 (98%) blood cultures, respectively, were positive. TTP was independent of age, sex, presence of comorbidities, site of infection and severity of infection. Median TTP in all age groups combined was shortest for group B streptococcus (8.7 h) and longest for coagulase-negative staphylococci (16.2 h). Conclusion: Growth of bacteria in blood cultures is detectable within 24 h in 9 of 10 children with blood culture-proven sepsis. Therefore, a strict rule to observe or treat all children with suspected sepsis for at least 48 h is not justified.

Radiological assessment of the head is a routine part of the management of traumatic brain injury. This assessment can help to determine the requirement for invasive intracranial pressure (ICP) monitoring. The radiological correlates of elevated ICP have been widely studied in adults but far fewer specific pediatric studies have been conducted. There is, however, growing evidence that there are important differences in the radiological presentations of elevated ICP between children and adults; a reflection of the anatomical and physiological differences, as well as a difference in the pathophysiology of brain injury in children. Here in, we review the radiological parameters that correspond with increased ICP in children that have been described in the literature. We then describe the future directions of this work and our recommendations in order to develop non-invasive and radiological markers of raised ICP in children.

Objective: To assess the impact of service improvements implemented because of latent threats (LTs) detected during in situ simulation., Design: Retrospective review from April 2008 to April 2015., Setting: Paediatric Intensive Care Unit in a specialist tertiary hospital., Intervention: Service improvements from LTs detection during in situ simulation. Action plans from patient safety incidents (PSIs)., Main Outcome Measures: The quantity, category, and subsequent service improvements for LTs. The quantity, category, and subsequent action plans for PSIs. Similarities between PSIs and LTs before and after service improvements., Results: 201 Simulated inter-professional team training courses with 1,144 inter-professional participants. 44 LTs were identified (1 LT per 4.6 courses). Incident severity varied: 18 (41%) with the potential to cause harm, 20 (46%) that would have caused minimal harm, and 6 (13%) that would have caused significant temporary harm. Category analysis revealed the majority of LTs were resources (36%) and education and training (27%). The remainder consisted of equipment (11%), organizational and strategic (7%), work and environment (7%), medication (7%), and systems and protocols (5%). 43 service improvements were developed: 24 (55%) resources/equipment; 9 (21%) educational; 6 (14%) organizational changes; 2 (5%) staff communications; and 2 (5%) guidelines. Four (9%) service improvements were adopted trust wide. 32 (73%) LTs did not recur after service improvements. 24 (1%) of 1,946 PSIs were similar to LTs: 7 resource incidents, 7 catastrophic blood loss, 4 hyperkalaemia arrests, 3 emergency buzzer failures, and 3 difficulties contacting staff. 34 LTs (77%) were never recorded as PSIs., Conclusion: An in situ simulation program can identify important LTs which traditional reporting systems miss. Subsequent improvements in workplace systems and resources can improve efficiency and remove error traps.

[This corrects the article on p. 205 in vol. 5, PMID: 28993802.].

Introduction: A strong association exists between hyperglycemia and outcome in pediatric traumatic brain injury (TBI). Herein, we describe observations of serum markers of glucose metabolism in a cohort of pediatric TBI patients and how these variables are related to parameters of intracranial pathophysiology., Methods: A retrospective analysis was performed on pediatric severe TBI patients admitted to Addenbrookes Hospital Paediatric Intensive Care Unit (PICU) between January 2001 and December 2013. Demographic, outcome, systemic physiological, and cerebral autoregulatory data were extracted for patients who had received continuous invasive monitoring (ICM+, Cambridge Enterprise, Cambridge, UK). Data were analyzed using a mixed linear model., Results: Forty-four patients with an average age of 12.2 years were admitted to the PICU with a TBI requiring invasive neurosurgical monitoring. Thirty-two patients (73%) survived, with favorable outcomes in 62%. The mean (SD) intracranial pressure (ICP) was 17.6 + 9.0 mmHg, MAP was 89.7 + 9.0 mmHg, and pressure-reactivity index (PRx) was -0.01 + 0.23 a.u. The mean (SD) serum lactate was 2.2 (3.3) mmol/L. and the mean (SD) serum glucose was 6.1 (1.6) mmol/L. Early hyperglycemia was strongly associated with both PRx (Pearson correlation 0.351, p  < 0.001) and ICP (Pearson correlation 0.240, p  = 0.002) death ( p  = 0.021) and impaired cerebral autoregulation ( p  = 0.02). There was a strong association between ICP and serum lactate ( p  = 0.001)., Conclusion: Increases in systemic glucose are associated with impaired cerebrovasular autoregulation after severe pediatric TBI. Moreover, deranged blood glucose is a marker of poor prognosis. Further studies are required to delineate putative mechanisms of hyperglycemia induced cerebral harm.

Extracorporeal life support (ECLS) is an important device in the management of children with severe refractory cardiac and or pulmonary failure. Actually, two forms of ECLS are available for neonates and children: extracorporeal membrane oxygenation (ECMO) and use of a ventricular assist device (VAD). Both these techniques have their own advantages and disadvantages. The intra-aortic balloon pump is another ECLS device that has been successfully used in larger children, adolescents, and adults, but has found limited applicability in smaller children. In this review, we will present the "state of art" of ECMO in neonate and children with heart failure. ECMO is commonly used in a variety of settings to provide support to critically ill patients with cardiac disease. However, a strict selection of patients and timing of intervention should be performed to avoid the increase in mortality and morbidity of these patients. Therefore, every attempt should be done to start ECLS "urgently" rather than "emergently," before the presence of dysfunction of end organs or circulatory collapse. Even though exciting progress is being made in the development of VADs for long-term mechanical support in children, ECMO remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation. With the increase in familiarity with ECMO, new indications have been added, such as extracorporeal cardiopulmonary resuscitation (ECPR). The literature supporting ECPR is increasing in children. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS have reduced in the last 5 years and many centers support patients with functionally univentricular circulations. Improved results have been recently achieved in this complex subset of patients.