A Study of Safety and Effectiveness of Evicel Fibrin Sealant as an Adjunctive Hemostat in Pediatric Surgery.

INTRODUCTION: Data on the use of fibrin sealants to control intraoperative bleeding in children are scarce. Evicel Fibrin Sealant (Ethicon Inc., Raritan, New Jersey, United States) was found safe and effective in clinical trials of adults undergoing various surgery types. We evaluated the safety and efficacy of Evicel versus Surgicel Absorbable Hemostat (Ethicon Inc.) as adjunctive topical hemostats for mild/moderate raw-surface bleeding in pediatric surgery. METHODS: A phase III randomized clinical trial was designed as required by the European Medicines Agency's Evicel Pediatric Investigation Plan: 40 pediatric subjects undergoing abdominal, retroperitoneal, pelvic, or thoracic surgery were randomized to Evicel or Surgicel, to treat intraoperative mild-to-moderate bleeding. Descriptive analyses included time-to-hemostasis and rates of treatment success (4, 7, 10 minutes), intraoperative treatment failure, rebleeding, and thromboembolic events. RESULTS: Forty of 130 screened subjects aged 0.9 to 17 years were randomized 1:1 to Evicel or Surgicel. Surgeries were predominantly open abdominal procedures. The median bleeding area was 4.0 cm2 for Evicel and 1.0 cm2 for Surgicel. The median time-to-hemostasis was 4.0 minutes for both groups. The 4-, 7-, and 10-minute treatment success rates were 80.0% versus 65.0%, 100.0% versus 80.0%, and 95.0% versus 90.0%, whereas treatment failure rates were 5.0% versus 25.0%, for Evicel and Surgicel, respectively. No deaths or thrombotic events occurred. Re-bleeding occurred in 5.0% of Evicel and 10.0% of Surgicel subjects. CONCLUSIONS: In accordance with adult clinical trials, this randomized study supports the safety and efficacy of Evicel for controlling mild-to-moderate surgical bleeding in a broad range of pediatric surgical procedures.

Impact of the COVID-19 pandemic on the clinical management trends for acute appendicitis among the under-25s: a retrospective study.

OBJECTIVE: To describe the COVID-19 pandemic's impact on acute appendicitis management on children and young people (CYP). DESIGN: Retrospective cohort study. SETTING: All English National Health Service hospitals. PATIENTS: Acute appendicitis admissions (all, simple, complex) by CYP (under-5s, 5-9s, 10-24s). EXPOSURE: Study pandemic period: February 2020-March 2021. Comparator pre-pandemic period: February 2015-January 2020. MAIN OUTCOME MEASURES: Monthly appendicectomy and laparoscopic appendicectomy rate trends and absolute differences between pandemic month and the pre-pandemic average. Proportions of appendicitis admissions comprising complex appendicitis by hospital with or without specialist paediatric centres were compared. RESULTS: 101 462 acute appendicitis admissions were analysed. Appendicectomy rates fell most in April 2020 for the 5-9s (-18.4% (95% CI -26.8% to -10.0%)) and 10-24s (-28.4% (-38.9% to -18.0%)), driven by reductions in appendicectomies for simple appendicitis. This was equivalent to -54 procedures (-68.4 to -39.6) and -512 (-555.9 to -467.3) for the 5-9s and 10-24s, respectively. Laparoscopic appendicectomies fell in April 2020 for the 5-9s (-15.5% (-23.2% to -7.8%)) and 10-24s (-44.8% (-57.9% to -31.6%) across all types, which was equivalent to -43 (-56.1 to 30.3) and -643 (-692.5 to -593.1) procedures for the 5-9s and 10-24s, respectively. A larger proportion of complex appendicitis admissions were treated within trusts with specialist paediatric centres during the pandemic. CONCLUSIONS: For CYP across English hospitals, a sharp recovery followed a steep reduction in appendicectomy rates in April 2020, due to concerns with COVID-19 transmission. This builds on smaller-sized studies reporting the immediate short-term impacts.

Defining treatment success in children with surgical conditions.

OBJECTIVES: Develop a score summarising how successfully a child with any surgical condition has been treated, and test the clinical validity of the score. DESIGN: Discrete choice experiment (DCE), and secondary analysis of data from six UK-wide prospective cohort studies. PARTICIPANTS: 253 people with lived experience of childhood surgical conditions, 114 health professionals caring for children with surgical conditions and 753 members of the general population completed the DCE. Data from 1383 children with surgical conditions were used in the secondary analysis. MAIN OUTCOME MEASURES: Normalised importance value of attribute (NIVA) for number/type of operations, hospital-treated infections, quality of life and duration of survival (reference attribute). RESULTS: Quality of life and duration of survival were the most important attributes in deciding whether a child had been successfully treated. Parents, carers and previously treated adults placed equal weight on both attributes (NIVA=0.996; 0.798 to 1.194). Healthcare professionals placed more weight on quality of life (NIVA=1.469; 0.950 to 1.987). The general population placed more weight on survival (NIVA=0.823; 95% CI 0.708 to 0.938). The resulting score (the Children's Surgery Outcome Reporting (CSOR) Treatment Success Score (TSS)) has the best possible value of 1, a value of 0 describes palliation and values less than 0 describe outcomes worse than palliation. CSOR TSSs varied clinically appropriately for infants whose data were included in the UK-wide cohort studies. CONCLUSIONS: The CSOR TSS summarises how successfully children with surgical conditions have been treated, and can therefore be used to compare hospitals' observed and expected outcomes.

Systematic Review and Meta-analysis to Compare the Short- and Long-term Outcomes of Non-operative Management With Early Operative Management of Simple Appendicitis in Children After the COVID-19 Pandemic.

BACKGROUND: Non-operative management (NOM) of simple appendicitis is becoming an increasingly researched treatment option. This systematic review aims to describe the short and long-term failure rates of NOM and the complication rate of appendicectomy in children with simple appendicitis. METHODS: The systematic review was registered a priori (CRD42022322149). Study inclusion criteria are: participants aged ≤ 18 years of age; groups undergoing both NOM and appendicectomy for simple appendicitis; outcomes including one or more of: NOM failure rate at 30 days or 1 year and beyond; study design: RCT or case control study. Four databases were searched and 3 reviewers determined study eligibility and data extraction. Risk of bias was assessed and meta-analysis was performed using Stata. RESULTS: The database search identified 2731 articles, 14 studies met the inclusion criteria; 4 RCTs and 10 case controlled studies. All studies had moderate-serious risk of bias. There were no deaths in either group in any study. Meta-analysis demonstrated a 30 day failure rate of 20 % (95 % CI 11-29 %) and 11 studies reported failure rate at 1 year or beyond at 32 % (95 % CI 25-38 %). Rates of significant complications of appendicectomy was 1 % (95 % CI 0-1 %). CONCLUSIONS: Non-operative management of simple appendicitis in children is safe, with moderate early success. The failure rate increases over time, resulting in eventual appendicectomy in a third of the children diagnosed with appendicitis. These data will enable clinicians to have an informed discussion with children and their parents about their treatment options for simple appendicitis. LEVEL OF EVIDENCE: II.

Quantifying acute kidney injury in an Ischaemia-Reperfusion Injury mouse model using deep-learning-based semantic segmentation in histology.

This study focuses on ischaemia-reperfusion injury (IRI) in kidneys, a cause of acute kidney injury (AKI) and end-stage kidney disease (ESKD). Traditional kidney damage assessment methods are semi-quantitative and subjective. This study aims to use a convolutional neural network (CNN) to segment murine kidney structures after IRI, quantify damage via CNN-generated pathological measurements, and compare this to conventional scoring. The CNN was able to accurately segment the different pathological classes, such as Intratubular casts and Tubular necrosis, with an F1 score of over 0.75. Some classes, such as Glomeruli and Proximal tubules, had even higher statistical values with F1 scores over 0.90. The scoring generated based on the segmentation approach statistically correlated with the semiquantitative assessment (Spearman's rank correlation coefficient=0.94). The heatmap approach localised the intratubular necrosis mainly in the outer stripe of the outer medulla, while the tubular casts were also present in more superficial or deeper portions of the cortex and medullary areas. This study presents a CNN model capable of segmenting multiple classes of interest, including acute IRI-specific pathological changes, in a whole mouse kidney section and can provide insights into the distribution of pathological classes within the whole mouse kidney section.

Pediatric Hospitalizations and ICU Admissions Due to COVID-19 and Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 in England.

Importance: Investigating how the risk of serious illness after SARS-CoV-2 infection in children and adolescents has changed as new variants have emerged is essential to inform public health interventions and clinical guidance. Objective: To examine risk factors associated with hospitalization for COVID-19 or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) among children and adolescents during the first 2 years of the COVID-19 pandemic and change in risk factors over time. Design, Setting, and Participants: This population-level analysis of hospitalizations after SARS-CoV-2 infection in England among children and adolescents aged 0 to 17 years was conducted from February 1, 2020, to January 31, 2022. National data on hospital activity were linked with data on SARS-CoV-2 testing, SARS-CoV-2 vaccination, pediatric intensive care unit (PICU) admissions, and mortality. Children and adolescents hospitalized with COVID-19 or PIMS-TS during this time were included. Maternal, elective, and injury-related hospitalizations were excluded. Exposures: Previous medical comorbidities, sociodemographic factors, and timing of hospitalization when different SARS-CoV-2 variants (ie, wild type, Alpha, Delta, and Omicron) were dominant in England. Main Outcomes: PICU admission and death within 28 days of hospitalization with COVID-19 or PIMS-TS. Results: A total of 10 540 hospitalizations due to COVID-19 and 997 due to PIMS-TS were identified within 1 125 010 emergency hospitalizations for other causes. The number of hospitalizations due to COVID-19 and PIMS-TS per new SARS-CoV-2 infections in England declined during the second year of the COVID-19 pandemic. Among 10 540 hospitalized children and adolescents, 448 (4.3%) required PICU admission due to COVID-19, declining from 162 of 1635 (9.9%) with wild type, 98 of 1616 (6.1%) with Alpha, and 129 of 3789 (3.4%) with Delta to 59 of 3500 (1.7%) with Omicron. Forty-eight children and adolescents died within 28 days of hospitalization due to COVID-19, and no children died of PIMS-TS (PIMS-S data were limited to November 2020 onward). Risk of severe COVID-19 in children and adolescents was associated with medical comorbidities and neurodisability regardless of SARS-CoV-2 variant. Results were similar when children and adolescents with prior SARS-CoV-2 exposure or vaccination were excluded. Conclusions: In this study of data across the first 2 years of the COVID-19 pandemic, risk of severe disease from SARS-CoV-2 infection in children and adolescents in England remained low. Children and adolescents with multiple medical problems, particularly neurodisability, were at increased risk and should be central to public health measures as further variants emerge.

The transition zone in Hirschsprung's bowel contains abnormal hybrid ganglia with characteristics of extrinsic nerves.

The aganglionic bowel in short-segment Hirschsprung's disease is characterized both by the absence of enteric ganglia and the presence of extrinsic thickened nerve bundles (TNBs). The relationship between the TNBs and the loss of enteric ganglia is unknown. Previous studies have described decreasing numbers of ganglia with increasing density of TNBs within the transition zone (TZ) between ganglionic and aganglionic gut, and there is some evidence of spatial contact between them in this region. To determine the cellular interactions involved, we have analysed the expression of perineurial markers of TNBs and enteric ganglionic markers for both neural cells and their ensheathing telocytes across four cranio-caudal segments consisting of most proximal ganglionic to most distal aganglionic from pull-through resected colon. We show that in the TZ, enteric ganglia are abnormal, being surrounded by perineurium cells characteristic of TNBs. Furthermore, short processes of ganglionic neurons extend caudally towards the aganglionic region, where telocytes in the TNB are located between the perineurium and nerve fibres into which they project telopodes. Thus, enteric ganglia within the TZ have abnormal structural characteristics, the cellular relationships of which are shared by the TNBs. These findings will help towards elucidation of the cellular mechanisms involved in the aetiology of Hirschsprung's disease.

National consensus to develop core outcomes for the evaluation of complications from excess weight (CEW) clinics: results of a national Delphi process.

OBJECTIVE: In 2021, centres across all seven NHS-England regions were selected to develop pilot clinics with the aim of treating children and young people (CYP) living with complications relating to excess weight (CEW). We led a process to develop core outcomes to enable the evaluation of these clinics. METHODS: A two-round Delphi process, virtual steering group meetings and two patient representation workshops were used to agree the most important outcomes for both clinicians/allied professionals and representative prospective service users. RESULTS: A total of 119 clinicians/allied professionals were invited to contribute to the Delphi process: 62 (52%) agreed and completed round 1 and 47 of these (76%) went on to complete round 2. Six young people (age range 13-17 years) and six parents were involved in two patient representation workshops and their experiences fed into virtual steering group meetings, via a representative.There were 44 outcomes assessed in round 1 and 21 outcomes assessed in round 2. There were 16 core outcomes selected: anthropometric, glucose tolerance/insulin resistance/type 2 diabetes, blood pressure, lipid profile, breathing problems, identification of aetiology, non-alcoholic fatty liver disease, idiopathic intracranial hypertension, anxiety, depression, self-esteem, quality of life, school attendance, dietary habits including disordered eating, exercise and activity habits. CONCLUSIONS: Use of an online Delphi process, patient representation workshops and virtual steering group meetings has enabled the development of core outcomes for clinical obesity services with eight physical health, five mental health and three self-management outcomes. Further work is needed to develop outcome measures to complete a core outcome set. These will be used to guide the evaluation of novel regional clinics for the treatment of complications of excess weight.

Lateral flow test performance in children for SARS-CoV-2 using anterior nasal and buccal swabbing: sensitivity, specificity, negative and positive predictive values.

OBJECTIVE: To determine if the sensitivity of the lateral flow test is dependent on the viral load and on the location of swabbing in the respiratory tract in children. DESIGN: Phase 1: Routinely performed reverse transcriptase PCR (RT-PCR) using nose and throat (NT) swabs or endotracheal (ET) aspirates were compared with Innova lateral flow tests (LFTs) using anterior nasal (AN) swabs. Phase 2: RT-PCR-positive children underwent paired AN RT-PCR and LFT and/or paired AN RT-PCR and buccal LFT. SETTING: Tertiary paediatric hospitals. PATIENTS: Children under the age of 18 years. Phase 1: undergoing routine testing, phase 2: known SARS-CoV-2 positive. RESULTS: Phase 1: 435 paired swabs taken in 431 asymptomatic patients resulted in 8 positive RT-PCRs, 9 PCR test failures and 418 negative RT-PCRs from NT or ET swabs. The test performance of AN LFT demonstrated sensitivity: 25% (4%-59%), specificity: 100% (99%-100%), positive predictive value (PPV): 100% (18%-100%) and negative predictive value (NPV): 99% (97%-99%).Phase 2: 14 AN RT-PCR-positive results demonstrated a sensitivity of 77% (50%-92%) of LFTs performed on AN swabs. 15/16 paired buccal LFT swabs were negative. CONCLUSION: The NPV, PPV and specificity of LFTs are excellent. The sensitivity of LFTs compared with RT-PCR is good when the samples are colocated but may be reduced when the LFT swab is taken from the AN. Buccal swabs are not appropriate for LFT testing. Careful consideration of the swabbing reason, the tolerance of the child and the requirements for test processing (eg, rapidity of results) should be undertaken within hospital settings. TRIAL REGISTRATION NUMBER: NCT04629157.

Risk of paediatric multisystem inflammatory syndrome (PIMS-TS) during the SARS-CoV-2 alpha and delta variant waves: National observational and modelling study, 2020-21, England.

Objectives: Paediatric Multisystem Inflammatory Syndrome (PIMS-TS) is a rare life-threatening complication that typically occurs several weeks after SARS-CoV-2 infection in children and young people (CYP). We used national and regional-level data from the COVID-19 pandemic waves in England to develop a model to predict PIMS-TS cases. Methods: SARS-CoV-2 infections in CYP aged 0-15 years in England were estimated using the PHE-Cambridge real-time model. PIMS-TS cases were identified through the British Paediatric Surveillance Unit during (March-June 2020) and through Secondary Uses Services (SUS) from November 2020. A predictive model was developed to estimate PIMS-TS risk and lag times after SARS-CoV-2 infections. Results: During the Alpha wave, the model accurately predicted PIMS-TS cases (506 vs. 502 observed cases), with a median estimated risk of 0.038% (IQR, 0.037-0.041%) of paediatric SARS-CoV-2 infections. For the Delta wave, the median risk of PIMS-TS was significantly lower at 0.026% (IQR, 0.025-0.029%), with 212 observed PIMS-TS cases compared to 450 predicted by the model. Conclusions: The model accurately predicted national and regional PIMS-TS cases in CYP during the Alpha wave. PIMS-TS cases were 53% lower than predicted during the Delta wave. Further studies are needed to understand the mechanisms of the observed lower risk with the Delta variant.

Impact of rectal dissection technique on primary-school-age outcomes for a British and Irish cohort of children with Hirschsprung disease.

BACKGROUND: This prospective cohort study compared primary-school-aged outcomes between children with Hirschsprung disease (HD) following Soave, Duhamel or Swenson procedures. METHODS: Children with histologically proven HD were identified in British/Irish paediatric surgical centers (01/10/2010-30/09/2012). Parent/clinician outcomes were collected when children were 5-8 years old and combined with management/early outcomes data. Propensity score/covariate adjusted multiple-event-Cox and multivariable logistic regression analyses were used. RESULTS: 277 (91%) of 305 children underwent a pull-through (53% Soave, 37% Duhamel, 9% Swenson). Based upon 259 children (94%) with complete operative data, unplanned reoperation rates (95% CI) per-person year of follow-up were 0.11 (0.08-0.13), 0.34 (0.29-0.40) and 1.06 (0.86-1.31) in the Soave/Duhamel/Swenson groups respectively. Adjusted Hazard Ratios for unplanned reoperation compared with the Soave were 1.50 (95% CI 0.66-3.44, p = 0.335) and 7.57 (95% CI 3.39-16.93, p < 0.001) for the Duhamel/Swenson respectively. Of 217 post-pull-through children with 5-8 year follow-up, 62%, 55%, and 62% in Soave/Duhamel/Swenson groups reported faecal incontinence. In comparison to Soave, Duhamel was associated with lower risk of faecal incontinence (aOR 0.34,95%CI 0.13-0.89,p = 0.028). Of 191 children without a stoma, 42%, 59% and 30% in Soave/Duhamel/Swenson groups required assistance to maintain bowel movements; compared to Soave, the Duhamel group were more likely to require assistance (aOR 2.61,95% CI 1.03-6.60,p = 0.043). CONCLUSIONS: Compared with Soave, Swenson was associated with increased risk of unplanned reoperation, whilst Duhamel was associated with reduced risk of faecal incontinence, but increased risk of constipation at 5-8 years of age. The risk profiles described can be used to inform consent discussions between surgeons and parents. LEVEL OF EVIDENCE: Level II.

Impact of COVID-19 on outpatient appointments in children and young people in England: an observational study.

OBJECTIVES: To describe the impact of the COVID-19 pandemic on outpatient appointments for children and young people. SETTING: All National Health Service (public) hospitals in England. PARTICIPANTS: All people in England aged <25 years. OUTCOME MEASURES: Outpatient department attendance numbers, rates and modes (face to face vs telephone) by age group, sex and socioeconomic deprivation. RESULTS: Compared with the average for January 2017 to December 2019, there was a 3.8 million appointment shortfall (23.5%) for the under-25 population in England between March 2020 and February 2021, despite a total rise in phone appointments of 2.6 million during that time. This was true for each age group, sex and deprivation fifth, but there were smaller decreases in face to face and total appointments for babies under 1 year. For all ages combined, around one in six first and one in four follow-up appointments were by phone in the most recent period. The proportion of appointments attended was high, at over 95% for telephone and over 90% for face-to-face appointments for all ages. CONCLUSIONS: COVID-19 led to a dramatic fall in total outpatient appointments and a large rise in the proportion of those appointments conducted by telephone. The impact that this has had on patient outcomes is still unknown. The differential impact of COVID-19 on outpatient activity in different sociodemographic groups may also inform design of paediatric outpatient services in the post-COVID period.

Impact of COVID-19 on primary care contacts with children and young people in England: longitudinal trends study 2015-2020.

BACKGROUND: The NHS response to COVID-19 altered provision and access to primary care. AIM: To examine the impact of COVID-19 on GP contacts with children and young people (CYP) in England. DESIGN AND SETTING: A longitudinal trends analysis was undertaken using electronic health records from the Clinical Practice Research Datalink (CPRD) Aurum database. METHOD: All CYP aged <25 years registered with a GP in the CPRD Aurum database were included. The number of total, remote, and face-to-face contacts during the first UK lockdown (March to June 2020) were compared with the mean contacts for comparable weeks from 2015 to 2019. RESULTS: In total, 47 607 765 GP contacts with 4 307 120 CYP were included. GP contacts fell 41% during the first lockdown compared with previous years. Children aged 1-14 years had greater falls in total contacts (≥50%) compared with infants and those aged 15-24 years. Face-to-face contacts fell by 88%, with the greatest falls occurring among children aged 1-14 years (>90%). Remote contacts more than doubled, increasing most in infants (over 2.5-fold). Total contacts for respiratory illnesses fell by 74% whereas contacts for common non-transmissible conditions shifted largely to remote contacts, mitigating the total fall (31%). CONCLUSION: During the COVID-19 pandemic, CYP's contact with GPs fell, particularly for face-to-face assessments. This may be explained by a lower incidence of respiratory illnesses because of fewer social contacts and changing health-seeking behaviour. The large shift to remote contacts mitigated total falls in contacts for some age groups and for common non-transmissible conditions.

Murine models of renal ischemia reperfusion injury: An opportunity for refinement using noninvasive monitoring methods.

BACKGROUND: Renal ischemia reperfusion injury (R-IRI) can cause acute kidney injury (AKI) and chronic kidney disease (CKD), resulting in significant morbidity and mortality. To understand the underlying mechanisms, reproducible small-animal models of AKI and CKD are needed. We describe how innovative technologies for measuring kidney function noninvasively in small rodents allow successful refinement of the R-IRI models, and offer the unique opportunity to monitor longitudinally in individual animals the transition from AKI to CKD. METHODS: Male BALB/c mice underwent bilateral renal pedicle clamping (AKI) or unilateral renal pedicle clamping with delayed contralateral nephrectomy (CKD) under isoflurane anesthetic. Transdermal GFR monitoring and multispectral optoacoustic tomography (MSOT) in combination with statistical analysis were used to identify and standardize variables within these models. RESULTS: Pre-clamping anesthetic time was one of the most important predictors of AKI severity after R-IRI. Standardizing pre-clamping time resulted in a more predictably severe AKI model. In the CKD model, MSOT demonstrated initial improvement in renal function, followed by significant progressive reduction in function between weeks 2 and 4. Performing contralateral nephrectomy on day 14 enabled the development of CKD with minimal mortality. CONCLUSIONS: Noninvasive monitoring of global and individual renal function after R-IRI is feasible and reproducible. These techniques can facilitate refinement of kidney injury models and enable the degree of injury seen in preclinical models to be translated to those seen in the clinical setting. Thus, future therapies can be tested in a clinically relevant, noninvasive manner.

Which children and young people are at higher risk of severe disease and death after hospitalisation with SARS-CoV-2 infection in children and young people: A systematic review and individual patient meta-analysis.

BACKGROUND: We aimed to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in hospitalised children and young people (CYP), within a systematic review and individual patient meta-analysis. METHODS: We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies published between 1st January 2020 and 21st May 2021 which included all CYP admitted to hospital with ≥ 30 CYP with SARS-CoV-2 or ≥ 5 CYP with PIMS-TS or MIS-C. Eligible studies contained (1) details of age, sex, ethnicity or co-morbidities, and (2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted groupings of co-morbidities were eligible for narrative review. We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).PROSPERO: CRD42021235338. FINDINGS: 83 studies were included, 57 (21,549 patients) in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years (reference group), infants (aged <1 year) had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).The number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a step-wise fashion. Compared with CYP without comorbidity, odds ratios for critical care admission were: 1.49 (1.45-1.53) for 1 comorbidity; 2.58 (2.41-2.75) for 2 comorbidities; 2.97 (2.04-4.32) for ≥3 comorbidities. Corresponding odds ratios for death were: 2.15 (1.98-2.34) for 1 comorbidity; 4.63 (4.54-4.74) for 2 comorbidities and 4.98 (3.78-6.65) for ≥3 comorbidities. Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. IPD analysis demonstrated that, compared to children without co-morbidity, the risk difference of admission to critical care was increased in those with 1 comorbidity by 3.61% (1.87-5.36); 2 comorbidities by 9.26% (4.87-13.65); ≥3 comorbidities 10.83% (4.39-17.28), and for death: 1 comorbidity 1.50% (0.00-3.10); 2 comorbidities 4.40% (-0.10-8.80) and ≥3 co-morbidities 4.70 (0.50-8.90). INTERPRETATION: Hospitalised CYP at greatest vulnerability of severe disease or death with SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions. FUNDING: RH is in receipt of a fellowship from Kidney Research UK (grant no. TF_010_20171124). JW is in receipt of a Medical Research Council Fellowship (Grant No. MR/R00160X/1). LF is in receipt of funding from Martin House Children's Hospice (there is no specific grant number for this). RV is in receipt of a grant from the National Institute of Health Research to support this work (grant no NIHR202322). Funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript.

Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year.

Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective interventions. To address this question, we used data for all hospitalizations in England among 0-17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020-2021); hospitalizations due to all other non-traumatic causes in 2020-2021; hospitalizations due to all non-traumatic causes in 2019-2020; and hospitalizations due to influenza in 2019-2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15-17 year olds compared to 1-4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies.

Deaths in children and young people in England after SARS-CoV-2 infection during the first pandemic year.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP, <18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally infected with the virus, we undertook a clinical review of all CYP deaths with a positive SARS-CoV-2 test from March 2020 to February 2021. The predominant SARS-CoV-2 variants were wild-type and Alpha. Here we show that, of 12,023,568 CYP living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to coronavirus disease 2019-the clinical disease associated with SARS-CoV-2 infection-and 3 were due to pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. In total, 99.995% of CYP with a positive SARS-CoV-2 test survived. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths. These results are important for guiding decisions on shielding and vaccinating children. New variants might have different mortality risks and should be evaluated in a similar way.

NHS 111 Clinical Assessment Services: paediatric consultations.

Around the UK, commissioners have different models for delivering NHS 111, General Practice (GP) out-of-hours and urgent care services, focusing on telephony to help deliver urgent and emergency care. During the (early phases of the) COVID-19 pandemic, NHS 111 experienced an unprecedented volume of calls. At any time, 25%-30% of calls relate to children and young people (CYP). In response, the CYP's Transformation and Integrated Urgent Care teams at NHS England and NHS Improvement (NHSE/I) assisted in redeploying volunteer paediatricians into the integrated urgent care NHS 111 Clinical Assessment Services (CAS), taking calls about CYP. From this work, key stakeholders developed a paediatric 111 consultation framework, as well as learning outcomes, key capabilities and illustrations mapped against the Royal College of Paediatrics and Child Health (RCPCH) Progress curriculum domains, to aid paediatricians in training to undertake NHS 111 activities. These learning outcomes and key capabilities have been endorsed by the RCPCH Curriculum Review Group and are recommended to form part of the integrated urgent care service specification and workforce blueprint to improve outcomes for CYP.