Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).
To standardise clinical care across the country, clinical practice guidelines are being used. Local hospitals rely on a mixture of locally produced guidelines alongside national guidelines. This study aims to review the range of existing local guidelines, across London hospitals, relating to the management of infants with a fever and how these guidelines vary from each other and from NICE 'Fever in under 5s' guideline.1
Methods
As a sub-project of Febrile Infants Regional Evaluation (FIRE), all London hospitals with an emergency department were asked which guidelines they use when looking after febrile infants. Of those that responded, 13 use the NICE fever guideline, whereas 9 have their own local guideline. Guidelines were reviewed by 2 independent researchers, and quality was ascertained using AGREE II tool. Data was extracted from local guidelines for comparison with their NICE guideline compliance. Specific areas that were explored include: risk stratification, indications for C-reactive protein (CRP), lumbar puncture (LP), antibiotics and admission. The AGREE II tool was used to ascertain the quality of local and national guidelines.2
Results
Amongst the 9 local guidelines all are following the NICE risk stratification 'traffic light system', and all agree with NICE on the indication for CRP. In regards to indication for LP, 3 of the local guidelines agree with NICE advice, whereas, 6 recommend to consider LP in infants presenting with 'amber' features which is not a recommendation by NICE. There was more variation between guidelines in regards to the use of empirical parenteral antibiotics. Lastly, admission criteria of 7 local guidelines was in accordance with NICE. (compliance of 9 local trusts with NICE in table 1). All local guidelines scored lower on quality, as per the AGREE II tool, when compared to the NICE guideline.
Conclusion
Most London trusts use NICE fever guidelines for management of young febrile infants. Local guidelines are more cautious in comparison to the NICE guideline in respect to the need for lumbar puncture, potentially having a significant impact on variation of care between local hospitals. The FiRE study, a retrospective multicentre observational study, is currently collecting data to investigate variations in management of febrile infants at risk of serious bacterial infections when compared to the gold-standard NICE guideline.
References
Fever in under 5s: assessment and initial management, National Institute for Health and Care Excellence, 7 November 2019. Appraisal of Guidelines for REsearch and Evaluation (AGREE) II Instrument, AGREE Next Steps Consortium, December 2017.
A recent editorial discusses how the FEAST trial, 1 the only phase III randomised controlled trial assessing fluid bolus therapy (FBT) in severely ill African children, had little impact on guidelines despite the increased mortality risk in children receiving FBT.
Abstract Background The use of point of care (POC) tests varies across Europe, but research into what drives this variability is lacking. Focusing on CRP POC tests, we aimed to understand what factors contribute to high versus low adoption of the tests, and also to explore whether they are used in children. Methods We used a comparative qualitative case study approach to explore the implementation of CRP POC tests in the Netherlands and England. These countries were selected because although they have similar primary healthcare systems, the availability of CRP POC tests in General Practices is very different, being very high in the former and rare in the latter. The study design and analysis were informed by the non-adoption, abandonment, spread, scale-up and sustainability (NASSS) framework. Data were collected through a review of documents and interviews with stakeholders. Documents were identified through a scoping literature review, search of websites, and stakeholder recommendation. Stakeholders were selected purposively initially, and then by snowballing. Data were analysed thematically. Results Sixty-five documents were reviewed and 21 interviews were conducted. The difference in the availability of CRP POC tests is mainly because of differences at the wider national context level. In the two countries, early adopters of the tests advocated for their implementation through the generation of robust evidence and by engaging with all relevant stakeholders. This led to the inclusion of CRP POC tests in clinical guidelines in both countries. In the Netherlands, this mandated their reimbursement in accordance with Dutch regulations. Moreover, the prevailing better integration of health services enabled operational support from laboratories to GP practices. In England, the funding constraints of the National Health Service and the prioritization of alternative and less expensive antimicrobial stewardship interventions prevented the development of a reimbursement scheme. In addition, the lack of integration between health services limits the operational support to GP practices. In both countries, the availability of CRP POC tests for the management of children is a by-product of the test being available for adults. The tests are less used in children mainly because of concerns regarding their accuracy in this age-group. Conclusions The engagement of early adopters combined with a more favourable and receptive macro level environment, including the role of clinical guidelines and their developers in determining which interventions are reimbursed and the operational support from laboratories to GP practices, led to the greater adoption of the tests in the Netherlands. In both countries, CRP POC tests, when available, are less used less in children. Organisations considering introducing POC tests into primary care settings need to consider how their implementation fits into the wider health system context to ensure achievable plans.
Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.
Objectives To describe the incidence of new onset paediatric diabetes mellitus, clinical characteristics and patterns of presentation to emergency departments (ED) during the COVID-19 pandemic, and to assess whether this increase was associated with SARS-CoV-2 infection. Design Retrospective medical record review. Setting Forty nine paediatric EDs across the UK and Ireland. Patients All children aged 6 months to 16 years presenting to EDs with (1) new onset diabetes or (2) pre-existing diabetes with diabetic ketoacidosis (DKA), during the COVID-19 pandemic (1 March 2020–28 February 2021) and the preceding year (1 March 2019–28 February 2020). Results There were increases in new onset diabetes (1015 to 1183, 17%), compared with background incidence of 3%–5% in the UK over the past 5 years. There were increases in children presenting with new onset diabetes in DKA (395 to 566, 43%), severe DKA (141 to 252, 79%) and admissions to intensive care (38 to 72, 89%). Increased severity was reflected in biochemical and physiological parameters and administration of fluid boluses. Time to presentation from symptom onset for children presenting with new onset diabetes and DKA were similar across both years; healthcare seeking delay did not appear to be the sole contributing factor to DKA during the pandemic. Patterns of presentation changed in the pandemic year and seasonal variation was lost. Children with pre-existing diabetes presented with fewer episodes of decompensation. Conclusions There were increases in new onset diabetes in children and a higher risk of DKA in the first COVID pandemic year.
Objectives To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED). Methods Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n=219) or the control group (usual care; n=220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for "pneumonia" and "other SBI". Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses' compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs. Results The decision model had good discriminative ability for both pneumonia (n=33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n=22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value<0.05) and more urine-dipstick testing (71% vs. 61%, p-value<0.05). Conclusions In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing. Trial Registration Nederlands Trial Register NTR2381
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