Malrotation and Fibroblast Growth Factor Receptor-2-Associated Craniosynostosis: An Underrecognized Association and Management Pathway.

INTRODUCTION: Feeding difficulties are common and multifactorial in children with Fibroblast Growth Factor Receptor-2 (FGFR-2) mutations. Intestinal rotation anomalies have been demonstrated to occur more frequently in animals with FGFR-2 mutations. This study aims to describe intestinal rotation anomalies, surgical management, and feeding assistance in children with FGFR-2 mutations who have undergone upper gastrointestinal (UGI) contrast studies. METHODS: Retrospective data were collected of children born between 1988 and 2020 in a UK quaternary craniofacial unit with FGFR-2-associated craniosynostosis. A consultant survey of approach to malrotation was undertaken. RESULTS: Thirty-four children were included, 17 (50%) female. Six (18%) had UGI symptoms, which included bilious vomiting (n=2), nonbilious vomiting (n=5), retching (n=1), feed intolerance (n=3), and failure to thrive (n=3). Nine had a gastrostomy in situ. Intestinal rotation anomalies occurred in 4 (12%) children, 3 of whom underwent a Ladd procedure and two third required gastrojejunal feeding postoperatively. Consultants agreed that all children with FGFR-2 mutation and UGI symptoms should undergo UGI contrast study, as should children requiring a gastrostomy. DISCUSSION: Intestinal rotation anomalies in children with FGFR-2 mutations occur more frequently than the general population. Prompt consideration of UGI contrast in symptomatic children with FGFR-2 mutation is recommended to enable early surgical management of children with malrotation.

Our experience of a paediatrician-led clinic for the medical management of children with obstructive sleep-disordered breathing.

BACKGROUND: Obstructive sleep-disordered breathing (OSDB) is very common in children. Adenotonsillectomy is usually curative, but there is emerging evidence that topical nasal steroids can also be effective for some children and may avoid the need for surgery. The number of children referred for assessment of OSDB is increasing and in some departments, waiting times are long. We established a paediatrician-led clinic for assessment and initial medical management of OSDB and in this study we report the proportion of children who avoided the need for surgery. METHOD: Referral letters to the otolaryngology department were screened and those with suspected OSDB and no significant co-morbidities were diverted to the paediatrician-led clinic. We recorded data for a consecutive series of children seen in this clinic with suspected OSDB over a 3-month period. Parents completed a 5-item subset of questions from the OSA-11 questionnaire before and after treatment with 6 weeks of topical nasal steroids. RESULTS: In the 3-month study period, 103 children were seen, with a mean age of 6 (range 1-16). Six (5.8%) had improved spontaneously before clinic attendance. Of the 97 children who were still symptomatic, 17 (17.5%) were referred directly for surgery on the basis of the severity of their symptoms, or because of other coexisting conditions that required surgical treatment (such as recurrent tonsillitis or otitis media). Three declined intranasal steroids. Seventy-seven had a trial of intranasal steroids, of whom 34 (35%) reported enough improvement to avoid surgery, and 29 (28%) failed to improve and were referred for surgery. Fourteen (14%) failed to attend after the trial of steroids: of these, 5 (5%) were contactable by phone and confirmed improvement after topical steroids. OSA-5 scores were significantly improved following intranasal steroids. DISCUSSION: A paediatrician-led clinic can be an effective way to ease the workload of an over-stretched otolaryngology service, and judicious use of topical nasal steroids can help around 40% of children with OSDB avoid surgery.

Transanastomotic tubes reduce the cost of nutritional support in neonates with congenital duodenal obstruction.

PURPOSE: To determine the impact of intra-operative Trans-anastomotic Tube (TAT) placement on the cost of post-operative nutrition in infants with congenital duodenal obstruction (CDO). METHODS: A retrospective analysis of patients undergoing corrective surgery for CDO, with birth-weight over 1.5 kg over a 10-year period. Data are presented as median (inter-quartile range) and analysed with Mann-Whitney U test and Fisher's exact test as appropriate. RESULTS: 59 patients were included. There was no difference between TAT and non-TAT groups for baseline characteristics, age at operation and abnormality. In the TAT group there was a significant reduction in the duration of post-operative parenteral nutrition (PN) [6 (0-11) vs 12 (8-19) days, p = 0.006], the cost of PN [£750 (0-1375) vs £1500 (1000-2375), p = 0.006] and the total cost of nutrition [£765.26 (38.36-1404) vs £1387.52 (1008.23-2363.08), p = 0.015], thereby demonstrating a median cost saving of £622.26 per patient. 14% experienced TAT displacement but no other TAT complications were encountered. CONCLUSION: The use of a TAT is a safe and effective way to reduce the duration of PN required in patients with CDO. This infers a significant cost saving per patient, a factor that cannot be overlooked in this period of austerity.

Gram-negative organisms in peritoneal dialysis peritonitis: an early indication for surgery in patients with haemolytic uraemic syndrome?

PURPOSE: Haemolytic uraemic syndrome (HUS) is the commonest childhood cause of acute renal failure. Peritoneal dialysis peritonitis (PDP) is a well-recognised complication, with some children requiring surgical intervention (SI). The aim of this study is to determine whether the presence of enteric organisms in cases of PDP might predict the need for SI. METHODS: Retrospective, 5-year (2009-2014) case note review of all HUS cases requiring PD presenting to a single centre. Mann-Whitney U test was used for continuous non-parametric data and χ (2) for categorical data. RESULTS: 48 children required PD for HUS, 18/48 (38 %) developed PDP and of these 5/18 (28 %) required SI (subtotal colectomy n = 4, small bowel resection n = 1). Peritoneal fluid was cultured as part of the work-up for PDP. The presence of enteric organisms was associated with a 10.4 fold relative risk of requiring surgery (p = 0.02, 95 % CI 1.5-71.9), with 4/5 of these patients requiring surgery (median 17 days post-culture result). Only 1/13 patients not requiring surgery grew gram-negative bacteria. CONCLUSION: The presence of enteric bacteria in patients with PDP significantly decreases the chances of successful conservative management. In these patients early involvement of the surgical team is essential with a low threshold for SI.

Validation of the Manchester Cosmetic Clinician-Reported Outcomes Questionnaire (MCCRO-Q).

Patient-reported outcome measures (PROM) are collected pre- and post-operatively following cosmetic surgery. Clinicians assess their own outcomes following surgery, but without a validated clinician-reported outcome measure (CROM), there is no way to compare the clinical results among clinicians or compare these to PROM. Assessment of clinical outcomes is important to address the patients' expectations in the consenting process and to provide recommendations to patients preoperatively to improve post-operative appearance. To address the lack of validated CROM for cosmetic surgery, the Manchester Cosmetic Clinical Reported Outcome Questionnaire (MCCRO-Q) was developed. This study assessed the inter-rater reliability of assessors using the four-point scale pre- and post-operative MCCRO-Q questionnaires. Fifteen assessors reviewed photos from pre- and post-operative assessments in the UK between July 2016 and February 2020. Ninety-five patients were included in this validation study, with each patient assessed by a minimum of 3 assessors. MCCRO-Q showed consistency between reviewers, with all intra-class coefficient averages >0.5 for pre- and post-operative assessments. Moreover, 26% of preoperative assessments demonstrated perfect agreement, 56% had a maximum one-point difference and 18% had a two-point difference to the median score. Furthermore, 1% of postoperative assessments demonstrated perfect agreement, 36% had a one-point difference and 63% had a maximum point difference of 2 to the median score. The inter-rate agreement showed that MCCRO-Q is a reliable tool when used with 3 or more assessors to judge patient appearance clinically, preoperatively and post-operatively, concerning abdominoplasty.

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.

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.

Association of a device-based remote management heart failure pathway with outcomes: TriageHF Plus real-world evaluation.

AIMS: Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device-derived risk scores to augment and organize care. TriageHF Plus is a device-based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization. We aimed to evaluate the impact of TriageHF Plus on hospitalizations and describe the associated workforce burden. METHODS AND RESULTS: TriageHF Plus was a multi-site, prospective study that compared outcomes for patients recruited between April 2019 and February 2021. All alert-triggered assessments were analysed to determine the appropriateness of the alert and the workload burden. A negative-binomial regression with inverse probability treatment weighting using a time-matched usual care cohort was applied to estimate the effect of TriageHF Plus on non-elective hospitalizations. A post hoc pre-COVID-19 sensitivity analysis was also performed. The TriageHF Plus cohort (n = 443) had a mean age of 68.8 ± 11.2 years, 77% male (usual care cohort: n = 315, mean age of 66.2 ± 14.5 years, 65% male). In the TriageHF Plus cohort, an acute medical issue was identified following an alert in 79/182 (43%) cases. Fifty assessments indicated acute HF, requiring clinical action in 44 cases. At 30 day follow-up, 39/66 (59%) of initially symptomatic patients reported improvement, and 20 (19%) initially asymptomatic patients had developed new symptoms. On average, each assessment took 10 min. The TriageHF Plus group had a 58% lower rate of hospitalizations across full follow-up [incidence relative ratio: 0.42, 95% confidence interval (CI): 0.23-0.76, P = 0.004]. Across the pre-COVID-19 window, hospitalizations were 31% lower (0.69, 95% CI: 0.46-1.04, P = 0.077). CONCLUSIONS: These data represent the largest real-world evaluation of a DHFP based on multi-parametric risk stratification. The TriageHF Plus clinical pathway was associated with an improvement in HF symptoms and reduced all-cause hospitalizations.

Does time to theater matter in simple gastroschisis?

Objective: A recent publication has suggested that expedited time to theater in gastroschisis results in higher rates of primary closure and decreases the length of stay (LOS). This study primarily aims to assess the impact of time to first management of neonates with gastroschisis on the LOS. Methods: Neonates admitted between August 2013 and August 2020 with gastroschisis were included. Data were collected retrospectively, and neonates with complex gastroschisis were excluded. Variables including gestation, birth weight, time of first management, primary/delayed closure and use of patch were evaluated as possible confounding variables. The outcome measures were time to full feeds, time on parenteral nutrition (PN) and LOS. Univariate and multivariate linear regression analyses were performed. P<0.05 was regarded as significant. Results: Eighty-six neonates were identified, and 16 were then excluded (eight patients with complex gastroschisis, eight patients with time to first management not documented). The median LOS for those who underwent primary closure was 21 days (interquartile range (IQR) =16-29) and for those who underwent silo placement and delayed closure was 59 days (IQR=44-130). The mean time to first management was 473 min (standard deviation (SD) =146 min), with only 20% of these infants being operated on at less than 6 hours of age. Univariate and multivariate analyses demonstrated no relationship between time to first management and LOS (r2=0.00, p=0.82) but did demonstrate a consistent positive association between time to first feed and LOS and delayed closure, resulting in a longer time to full feeds and a longer time on PN. Conclusions: The time to first management was not associated with a change in LOS in these data. Further prospective evaluation of the impact of reducing the time to first feed on the LOS is recommended. Level of evidence: IV.

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.

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.

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.

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.

Bibliography of published COVID-19 in children literature.

BACKGROUND: The COVID-19 pandemic is the biggest worldwide health challenge in this century. Research concerning the role of children in the spread of SARS-CoV-2, and investigating the clinical effects of infection in children, has been vital. This paper describes the publication trend for pertinent scientific literature relating to COVID-19 in children during the first 6 months of the pandemic. METHODS: A comprehensive search of preprint and published literature was conducted daily across four databases (PubMed, Scopus, Ovid-Embase and MedRXiv) between 1 January 2020 and 30 June 2020. Titles and abstracts were screened against predefined inclusion and exclusion criteria. FINDINGS: Over the study period, a total of 45 453 papers were retrieved, of which 476 met our inclusion criteria. The cumulative number of children described in included publications totalled (at most) 41 396. The median number of children per paper was 6 (IQR 1-33). Nearly one-third of papers (30.2%) reported on a single child, and a further 28.3% reported on between 1 and 9 children. Half of all the publications originated from Asia. INTERPRETATION: Our prospective bibliographic analysis of paediatric COVID-19 publications demonstrated a steady increase in the number of papers over time. Understanding and policy evolved with new information that was gathered over the course of the study period. However, over half of publications were individual case reports or small case series, which may have had a limited contribution to advancement of knowledge. During a pandemic, literature should be interpreted with great caution, and clinical/policy decisions should be continually reviewed in light of emerging evidence.

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.

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.

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.

Routine evaluation of vesico-ureteric reflux in children with anorectal malformation does not reduce the rate of urinary tract infection.

OBJECTIVE: Children with anorectal malformations (ARM) have a high rate of renal anomalies and increased risk of urinary tract infection (UTI). We aimed to determine whether using routine Micturating Cystourethrogram (MCUG) to detect VUR is effective in reducing the incidence of UTI or renal scarring in children with ARM. METHODS: A retrospective study of consecutive children diagnosed with ARM in two centres with a minimum of 3 years follow-up was performed, excluding those with cloaca or an MCUG prior to ARM repair. Univariate and multivariate logistic regression analysis was used to determine variables which were associated with VUR, UTI and renal scarring. Associations are described as Odd's Ratio (OR), 95% Confidence Interval. Significance was taken as p<0.05. RESULTS: 344 children were included with a median age of 8 years (IQR 5-11 years). 150 (44%) were female. 89 (26%) had renal anomalies and 101 (29%) had spine anomalies. 148 patients had routine MCUG and VUR was found in 62 (42%) of these children. Univariate analysis did not correlate any of the assessed variables with VUR or renal scarring. However, abnormal renal ultrasound - OR 6.18 (95% CI 2.99-13.07, p 0.0001) was associated with UTI whilst abnormal spine - OR 0.27 (95% CI 0.10-0.62, p 0.009), low ARM - OR 0.30 (CI 0.14-0.63, p 0.006) and intermediate ARM - OR 0.35 (CI 0.17-0.70, p 0.01) were associated with a reduced risk of UTI. On multivariate analysis, only abnormal renal USS retained a significant association with UTI (p<0.0001). CONCLUSIONS: VUR is common in patients with ARM. Children with an abnormal R-USS are at increased risk of UTI. Performing routine MCUG does not reduce the risk of UTI in children with ARM.

A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process.

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a novel condition that was first reported in April, 2020. We aimed to develop a national consensus management pathway for the UK to provide guidance for clinicians caring for children with PIMS-TS. A three-phase online Delphi process and virtual consensus meeting sought consensus over the investigation, management, and research priorities from multidisciplinary clinicians caring for children with PIMS-TS. We used 140 consensus statements to derive a consensus management pathway that describes the initial investigation of children with suspected PIMS-TS, including blood markers to help determine the severity of disease, an echocardiogram, and a viral and septic screen to exclude other infectious causes of illness. The importance of a multidisciplinary team in decision making for children with PIMS-TS is highlighted throughout the guidance, along with the recommended treatment options, including supportive care, intravenous immunoglobulin, methylprednisolone, and biological therapies. These include IL-1 antagonists (eg, anakinra), IL-6 receptor blockers (eg, tocilizumab), and anti-TNF agents (eg, infliximab) for children with Kawasaki disease-like phenotype and non-specific presentations. Use of a rapid online Delphi process has made it possible to generate a national consensus pathway in a timely and cost-efficient manner in the middle of a global pandemic. The consensus statements represent the views of UK clinicians and are applicable to children in the UK suspected of having PIMS-TS. Future evidence will inform updates to this guidance, which in the interim provides a solid framework to support clinicians caring for children with PIMS-TS. This process has directly informed new PIMS-TS specific treatment groups as part of the adaptive UK RECOVERY trial protocol, which is the first formal randomised controlled trial of therapies for PIMS-TS globally.