Hospitalisation after birth of infants:cross sectional analysis of potentially avoidable admissions across England using hospital episode statistics

Abstract Background Admissions of infants in England have increased substantially but there is little evidence whether this is across the first year or predominately in neonates; and for all or for specific causes. We aimed to characterise this increase, especially those admissions that may be avoidable in the context of postnatal care provision. Methods A cross sectional analysis of 1,387,677 infants up to age one admitted to English hospitals between April 2008 and April 2014 using Hospital Episode Statistics and live birth denominators for England from Office for National Statistics. Potentially avoidable conditions were defined through a staged process with a panel. Results The rate of hospital admission in the first year of life for physiological jaundice, feeding difficulties and gastroenteritis, the three conditions identified as potentially preventable in the context of postnatal care provision, increased by 39% (39.55 to 55.33 per 1000 live births) relative to an overall increase of 6% (334.97 to 354.55 per 1000 live births). Over the first year the biggest increase in admissions occurred in the first 0–6 days (RR 1.26, 95% CI 1.24 to 1.29) and 85% of the increase (12.36 to 18.23 per 1000 live births) in this period was for the three potentially preventable conditions. Conclusions Most of the increase in infant hospital admissions was in the early neonatal period, the great majority being accounted for by three potentially avoidable conditions especially jaundice and feeding difficulties. This may indicate missed opportunities within the postnatal care pathway and given the enormous NHS cost and parental distress from hospital admission of infants, requires urgent attention

Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020

Background: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland. Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. Findings: there were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 serology. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died. Interpretation: the strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-T

Point-of-care testing in paediatric settings in the UK and Ireland: A cross-sectional study

Background: Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. Methods: A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). Results: In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. Conclusion: This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT

Structural, Morphological and Cytotoxic Analysis of NixZ1-xFe2O4(x=0.00, 0.03, 0.07) Nanoparticles

Nickel doped zinc ferrite compounds with the formula NixZn1-xFe2O4 (ZNFO) were prepared by using co-precipitation method.  The X-ray diffraction patterns confirm the synthesis of single crystalline NixZn1-xFe2O4 ferrite nanoparticles. The lattice parameter decreases whereas crystallite size increases with the increase in nickel ion concentration. The structure of nanoparticles was studied using X-ray diffraction pattern. The band gap energy for normal zinc ferrite is found to be 1.77.  Whereas the bandgap energy decreases to 1.03 eV  and 1.02 for Nix Zn1-xFe2O4 with x = 0.03 and 0.07 respectively. FTIR will help to study the functional groups present in the nanoparticles, so this technique is used for qualitative analysis of materials. The microstrain decreases as nickel ion concentration increases. The obtained results revealed that NixZn1- xFe2O4[x = 0.03] nanoparticles obtained by us in a model of actinomycetes exhibit lower cytotoxicity, which was confirmed in cytotoxic assay and with high LC50 value. From safety point of view, a careful cytotoxicity analysis of ZNFO (0.03) nanoparticles with concentration up to 50µg/mL can be used for biomedical applications

Vitamin D status of children with Paediatric Inflammatory Multisystem Syndrome Temporally associated with Severe acute respiratory syndrome coronavirus 2 (PIMS-TS).

Coronavirus disease 2019 (COVID-19), has caused mild illness in children, until the emergence of the novel hyperinflammatory condition PIMS-TS: Paediatric Inflammatory Multisystem Syndrome Temporally associated with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PIMS-TS is thought to be a post- SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the United Kingdom (U.K), due to its postulated role in cytokine regulation and immune response. Eighteen children [median (range) age 8.9 (0.3 to 14.6) years, male=10] met the case definition. Majority were of Black, Asian and Minority Ethnic (BAME) origin [89%, 16/18]. Positive SARS-CoV-2 IgG antibodies were present in 94% (17/18) and RNA by PCR in 6% (1/18). 72% of the cohort were vitamin D deficient (<30nmol/L). The mean 25OHD concentration was significantly lower when compared to the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4-10 years) [24 vs 54nmol/L (95% CI: -38.6, -19.7); p<0.001]. The PICU group had lower mean 25OHD concentrations compared to the non-PICU group, but this was not statistically significant [19.5 vs 31.9 nmol/L; p=0.11]. The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the U.K BAME population has been long overdue

Paediatric Inflammatory Multisystem Syndrome: Temporally Associated with SARS-CoV-2 (PIMS-TS): Cardiac Features, Management and Short-Term Outcomes at a UK Tertiary Paediatric Hospital.

Children were relatively spared during COVID-19 pandemic. However, the recently reported hyperinflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome-"Paediatric Inflammatory Multisystem Syndrome-temporally associated with SARS-CoV-2" (PIMS-TS) has caused concern. We describe cardiac findings and short-term outcomes in children with PIMS-TS at a tertiary children's hospital. Single-center observational study of children with PIMS-TS from 10th April to 9th May 2020. Data on ECG and echocardiogram were retrospectively analyzed along with demographics, clinical features and blood parameters. Fifteen children with median age of 8.8 (IQR 6.4-11.2) years were included, all were from African/Afro-Caribbean, South Asian, Mixed or other minority ethnic groups. All showed raised inflammatory/cardiac markers (CRP, ferritin, Troponin I, CK and pro-BNP). Transient valve regurgitation was present in 10 patients (67%). Left Ventricular ejection fraction was reduced in 12 (80%), fractional shortening in 8 (53%) with resolution in all but 2. Fourteen (93%) had coronary artery abnormalities, with normalization in 6. ECG abnormalities were present in 9 (60%) which normalized in 6 by discharge. Ten (67%) needed inotropes and/or vasopressors. None needed extracorporeal life support. Improvement in cardiac biochemical markers was closely followed by improvement in ECG/echocardiogram. All patients were discharged alive and twelve (80%) have been reviewed since. Our entire cohort with PIMS-TS had cardiac involvement and this degree of involvement is significantly more than other published series and emphasizes the need for specialist cardiac review. We believe that our multi-disciplinary team approach was crucial for the good short-term outcomes

The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL6 may be preferable to IL1 or TNF-α . We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease

Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome.

Background During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance. Methods Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test. Results Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses. Conclusions Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups