Fifteen-minute consultation: A guide to the paediatric primary survey.

It's 21:00 and you receive a stand-by call from the local ambulance service. Peter, a 9-year-old boy, was riding an electric scooter and has collided with a car. He has reduced consciousness, signs of shock and is hypoxic. How will you prepare your team? What are the possible injuries? Who will perform the primary survey? Injury is the leading cause of morbidity and mortality in the paediatric population accounting for approximately half of all attendances to paediatric emergency departments in the UK and Ireland. Major trauma can be distressing for patients, parents and physicians. Managing major trauma is challenging and it is vital to have a clear and organised approach. In this 15-minute guide we describe a structured approach to the primary survey that includes how to prepare before the child's arrival, the suggested roles of team members and the key components of the primary survey. We discuss life-threatening injuries, the life-saving bundle and the principles of resuscitation, and the role of imaging in the initial assessment of the injured child.

How to interpret cardiac biomarkers in children?

Cardiac biomarkers are used as first-line diagnostic tools in suspected myocardial injury and heart failure in adult patients. Their use in paediatric patients has been limited by variability caused by age, gender and the presence of an underlying congenital cardiac condition. There are established reference ranges for both NT-proBNP and troponin in healthy children, but these cannot be applied to all paediatric patients because of limited large studies focusing on children with congenital heart disease and/or cardiomyopathy.This article will focus on the pathophysiology of myocardial injury and heart failure in children and the subsequent cardiac biomarker correlation. It will explain how to interpret the biomarker assay levels obtained for both troponin and NT-proBNP and highlights the importance of a clear clinical question prior to requesting a cardiac biomarker assay level.Clinical cases outline scenarios that may prompt consideration of biomarker analysis in children and aims to equip the reader with an understanding of how to interpret the results.

Diagnostic value of mid-regional pro-Adrenomedullin as a biomarker of invasive bacterial infection in children: a systematic review.

BACKGROUND: Invasive bacterial infections (IBI) in children present a difficult clinical challenge. They are often life-threatening, however in the early stages they can be hard to differentiate from benign viral infections. This leaves clinicians with the risk of missing a serious IBI diagnosis or inappropriately using antimicrobials in a child with a viral infection- contributing to the ongoing development of increased antimicrobial resistance. Hence, biomarkers which could aid in early detection of IBI and differentiation from viral infections are desirable. Mid-Regional pro-Adrenomedullin (MR-proADM) is a biomarker which has been associated with IBI. The aim of this systematic review was to determine its diagnostic accuracy in identifying children with IBI. METHODS: A strategy was devised to search online databases MEDLINE, Embase, Web of Science and Scopus for human clinical trials reporting the accuracy of MR-proADM in children. Against predesigned inclusion and exclusion criteria full texts were selected for inclusion and data extraction. True positives, false positives, true negatives and false negatives were extracted from each included study to fill 2 × 2 tables. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool methodological quality of each study was assessed. RESULTS: A total of 501 articles were initially identified. After the removal of duplicates and abstract screening 11 texts were fully reviewed and four texts (totaling 1404 patients) were included in the systematic analysis. Only one study was of a high quality and that study accounted for the vast majority of patients. A single study reported the diagnostic accuracy of MR-proADM for invasive bacterial infection reporting an Area under the Curve of 0.69. The paucity of available studies made meta-analysis and studies of heterogeneity impossible. CONCLUSION: There is a paucity of research regarding the diagnostic accuracy of MR-proADM in the diagnosis of invasive bacterial infections in children. Initial results would suggest that MR-proADM testing alone is poor at identifying IBI in young children. It remains unclear if MR-proADM performs differently in older children or in children with signs and symptoms of IBI. TRIAL REGISTRATION: PROSPERO CRD42018096295 .

Periorbital and orbital cellulitis in children: a survey of emergency physicians and analysis of clinical practice guidelines across the PERUKI network.

BACKGROUND: Due to limited evidence to guide management of periorbital cellulitis (POC), we surveyed current practice and assessed quality and consistency of local clinical practice guidelines (CPGs) to highlight future research priorities. METHODS: A web-based survey was sent to a designated emergency physician (who clinically assesses children) at Paediatric Emergency Research United Kingdom and Ireland (PERUKI) sites between 23 November 2018 to 22 January 2019. A nominated site lead offered one response as a department-wide perspective on admission, severity assessment, treatment, disposition and specialty consultation request. Sites shared their CPG. These were compared using a standardised data collection tool, and quality assessed using Standardised Reporting Practice Guidelines in Healthcare (RIGHT) criteria. Survey responses were also compared against CPG recommendations. RESULTS: 83% (49/59) institutions invited submitted an individual survey response. 67% of responding sites had a CPG and 63% (31/49) submitted these. CPG quality was poor (mean 6.7/35 RIGHT criteria). 21 different severity markers were identified across CPGs. Most CPGS recommend investigations for severe disease, yet 23% (7/31) advise blood culture universally. 90% of CPGs advise discharge with oral antibiotics for milder cases, yet 86% of respondents reported departmental admission of all patients with POC. Nearly all respondents included proptosis, systemically unwell and visual disturbance as indications for admission but differed regarding importance of other signs. CONCLUSIONS: We demonstrated variation in practice across the PERUKI network in assessment of severity and management of POC. CPGs vary in recommendations, and clinical practice appears to differ from CPGs. Guidelines were generally of poor quality when compared against RIGHT standards.

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.

Secondary Attack Rate and Family Clustering of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children of Healthcare Workers With Confirmed Coronavirus Disease 2019 (COVID-19).

We measured serum SARS-CoV-2 antibodies in 215 children of healthcare workers to estimate secondary attack rates. Twenty-one families had a parent with confirmed COVID-19. There was strong evidence of family clustering (P < .001): 20/21 (95.2%) children were seropositive in 9 families and none of 23 children in 12 other families.

Diagnostic test accuracy of point-of-care procalcitonin to diagnose serious bacterial infections in children.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) have called for research into the role of biomarkers, and specifically procalcitonin (PCT), for the early diagnosis of serious bacterial infections (SBI) in children. The aim of this study was to compare the diagnostic test accuracy of C-reactive protein (CRP) and PCT for the diagnosis of SBI in children. METHODS: Data was collected prospectively from four UK emergency departments (ED) between November 2017 and June 2019. Consecutive children under 18 years of age with fever and features of possible sepsis and/or meningitis were eligible for inclusion. The index tests were PCT and CRP and the reference standard was the confirmation of SBI. RESULTS: 213 children were included in the final analysis. 116 participants (54.5%) were male, and the median age was 2 years, 9 months. Parenteral antibiotics were given to 100 (46.9%), three (1.4%) were admitted to a paediatric intensive care unit and there were no deaths. There were ten (4.7%) confirmed SBI. The area under the curve for PCT and CRP for the detection of SBI was identical at 0.70. CONCLUSIONS: There was no difference in the performance of PCT and CRP for the recognition of SBI in this cohort. TRIAL REGISTRATION: Registered at https://www.clinicaltrials.gov (trial registration: NCT03378258 ) on the 19th of December 2017.

Fifteen-minute consultation: How good is this test.

As technology evolves and cultural attitudes towards diagnosis change, there is an increasing move towards newer, faster and more accurate diagnostic testing. As new tests are developed, clinicians are increasingly required to appraise data from diagnostic test accuracy (DTA) studies.The accuracy of a test is fluid and changes depending on the population, setting, timing and position within the diagnostic pathway. This article attempts to provide a short guide to understanding diagnostic test accuracy and a simple approach to appraising DTA studies.

Fifteen-minute consultation: The limping child.

The limping child is a common presentation to paediatric services. In most instances the cause is benign with few, if any, investigations required. There is, however, always that concern that the limping child may have an underlying limb-threatening or life-threatening disease. This poses a challenge to clinicians, who must find that balance between correctly identifying disease early and avoiding the risks and harms of overinvestigation. In this article we discuss the diagnostic approach to the limping child and present a structure for assessment, investigation and risk management.

How to use clinical signs of meningitis.

Meningitis is a critical diagnosis not to miss in children presenting with fever. Since the early 20th century, classical clinical signs have been used to aid the diagnosis of meningitis. These classical signs are nuchal rigidity, Kernig's sign and Brudzinski's sign. Each of these relies on the principle that stretching the inflamed meningeal membranes causes clinically detectable irritation. Several primary studies have quantified the diagnostic performance of clinical examination in detecting meningitis in children. The results of these studies vary significantly due to methodological differences, clinical heterogeneity and interobserver variability. However, their findings demonstrate that positive meningitic signs increase the likelihood of a diagnosis of meningitis, and the absence of meningitic signs reduces this probability. These signs have greatest utility when combined with other features in the history and examination to contribute to a comprehensive clinical assessment.

Fifteen-minute consultation: Symptoms and signs of meningococcal disease.

Meningococcal disease remains a leading cause of meningitis, sepsis and death in children worldwide and in the UK. Successful vaccination programmes in the UK have, however, significantly reduced the burden of disease in children. Unfortunately, despite vaccination, a significant number of children are still diagnosed with invasive meningococcal disease each year.As the prevalence of meningococcal disease falls, it is important that we maintain awareness of the symptoms and signs of meningococcal disease because the prompt recognition of this life-threatening infection improves outcomes.In this article we discuss the pathology, epidemiology and recognition of invasive meningococcal disease in children. The aim is to maintain awareness of this rare but life-threatening infection.

A systematic review of the diagnostic accuracy of Loop-mediated-isothermal AMPlification (LAMP) in the diagnosis of invasive meningococcal disease in children.

BACKGROUND: The early recognition of meningococcal disease in children is vital. During the prodrome however, meningococcal infection presents similarly to many self-limiting viral infections. This mandates a cautious approach with many children receiving unnecessary broad-spectrum parenteral antibiotics. Advances in nucleic acid amplification techniques mean that it is now possible to test for Neisseria meningitidis DNA using Loop-mediated-isothermal AMPlification (LAMP). This technique is quicker than traditional PCR techniques and can be performed using simple equipment. METHODS: Prior to performing this systematic review, a protocol was developed adhering to PRISMA P standards and underwent full external peer review. This systematic review was registered with PROSPERO (CRD42017078026). The index test assessed was LAMP for Neisseria meningitidis and the reference standard was culture or qPCR of a sterile site detecting Neisseria meningitidis. RESULTS: We identified 95 records in total: 94 records from the electronic databases and 1 additional study from the grey literature. After removal of duplicates, 36 studies were screened, and 31 studies excluded based on the title/abstract. Five full text studies underwent full text review and three studies, including 2243 tests on 1989 patients aged between 7 days and 18 years were included in the final systematic review. In all studies the LAMP assay and qPCR primers were directed against the ctrA region of the Neisseria meningitidis bacteria. The diagnostic accuracy of LAMP testing for invasive meningococcal disease was reported as high (sensitivity 0.84-1.0 and specificity 0.94-1.0) in all studies irrespective of the sample tested (CSF, Blood, Swab). CONCLUSIONS: We included three studies with 2243 tests on 1989 patients using CSF, blood samples or naso/oropharyngeal swabs. The studies were all of a high quality and deemed at low risk of bias. Results show that LAMP testing on blood and CSF was highly accurate when compared to qPCR/culture. LAMP testing for Neisseria meningitidis is fast and highly accurate and therefore has the potential to be used to rapidly rule in/out meningococcal disease in children. Given the life-threatening nature of meningococcal infection further research is required to demonstrate the safety and efficacy of using LAMP testing for Neisseria meningitidis as a rule in/out test. TRIAL REGISTRATION: This systematic review was registered prospectively with PROSPERO on the 29/11/2017 (CRD42017078026).

How to write an Interpretation.

Every day we interpret examination findings and clinical tests with the aim of coming to a diagnosis. But how well do we interpret these tests? Whether it is a traditional examination technique used by doctors for centuries or a new cutting edge biomarker, the diagnostic landscape shifts over time. The aim of interpretations is to produce a library of evidence-based resources directing the use of clinical tests including examination techniques. In this article we discuss how best to tackle writing an interpretation. Interpretations are succinct evidence-based summaries that draw together research findings to provide practical answers for clinicians.

Fifteen-minute consultation: Preseptal and orbital cellulitis.

'It is midnight and you are called to see a thirteen-year-old boy who has been brought to the paediatric emergency department with a 24-hour history of swelling and redness of his left eye. He has had a 'runny nose' for a couple of days. He is systemically well. His upper and lower lids are red and swollen such that his eye is not open fully, though you elicit normal eye movements when you open his eye. Pupils are equal and reactive with no afferent pupillary defect. Visual acuity and colour vision are normal on examination.' In this article, we consider the approach to preseptal and orbital cellulitis in children including the initial assessment and management options.

How to use C-reactive protein.

A 3-month-old baby is brought to the paediatric emergency department by their parents because of a fever. You decide to check their inflammatory markers. Their C-reactive protein (CRP) level comes back as 20 mg/L. Does this affect whether or not you start antibiotic therapy? Does it influence your decision to admit or discharge the patient? CRP is a commonly used biochemical test and yet its use is constantly debated and challenged. We look at the current evidence and suggest the best way to use this test in clinical practice.

Point-of-care testing for procalcitonin in identifying bacterial infections in young infants: a diagnostic accuracy study.

BACKGROUND: The primary objective of this study was to report on the diagnostic accuracy of point-of-care testing (POCT) for procalcitonin (PCT) in identifying invasive bacterial infections in young infants. Invasive bacterial infection was defined as the isolation of a bacterial pathogen in blood or cerebrospinal fluid culture. METHODS: This was a prospective observational diagnostic accuracy study. Young infants less than 90 days of age presenting to the Royal Belfast Hospital for Sick Children with signs of possible bacterial infection were eligible for inclusion. Eligible infants underwent point-of-care testing for procalcitonin in the emergency department. Testing was performed by clinical staff using 0.5 ml of whole blood. Results were available within 20 min. RESULTS: 126 children were included over a 5-month period between September 2017 and January 2018. There were 14 children diagnosed with bacterial infections (11.1%). Of these 4 children were diagnosed with invasive bacterial infections (3.2%). POCT procalcitonin demonstrated an excellent diagnostic accuracy for identifying children with invasive bacterial infection area under the curve (AUC) of 0.97(95% CI, 0.94 to 1.0). At a cut-off value of 1.0 ng/ml is highly accurate at identifying infants at risk of invasive bacterial infection with a sensitivity and specificity of 1.00 and 0.92 respectively. CONCLUSIONS: Point-of-care procalcitonin can be performed quickly in the emergency department and demonstrates an excellent diagnostic accuracy for the identification of young infants with invasive bacterial infections. TRIAL REGISTRATION: NCT03509727 Retrospectively registered on 26th April 2018.

The "Petechiae in children" (PiC) study: evaluating potential clinical decision rules for the management of feverish children with non-blanching rashes, including the role of point of care testing for Procalcitonin & Neisseria meningitidis DNA - a study protocol.

BACKGROUND: Children commonly present to Emergency Departments (ED) with a non-blanching rash in the context of a feverish illness. While most have a self-limiting viral illness, this combination of features potentially represents invasive serious bacterial infection, including meningococcal septicaemia. A paucity of definitive diagnostic testing creates diagnostic uncertainty for clinicians; a safe approach mandates children without invasive disease are often admitted and treated with broad-spectrum antibiotics. Conversely, a cohort of children still experience significant mortality and morbidity due to late diagnosis. Current management is based on evidence which predates (i) the introduction of meningococcal B and C vaccines and (ii) availability of point of care testing (POCT) for procalcitonin (PCT) and Neisseria meningitidis DNA. METHODS: This PiC study is a prospective diagnostic accuracy study evaluating (i) rapid POCT for PCT and N. meningitidis DNA and (ii) performance of existing clinical practice guidelines (CPG) for feverish children with non-blanching rash. All children presenting to the ED with a history of fever and non-blanching rash are eligible. Children are managed as normal, with detailed prospective collection of data pertinent to CPGs, and a throat swab and blood used for rapid POCT. The study is running over 2 years and aims to recruit 300 children. PRIMARY OBJECTIVE: Report on the diagnostic accuracy of POCT for (i) N. meningitidis DNA and (ii) PCT in the diagnosis of early MD Report on the diagnostic accuracy of POCT for PCT in the diagnosis of Invasive bacterial infection Secondary objectives: Evaluate the performance accuracy of existing CPGs Evaluate cost-effectiveness of available diagnostic testing strategies Explore views of (i) families and (ii) clinicians on research without prior consent using qualitative methodology Report on the aetiology of NBRs in children with a feverish illness DISCUSSION: The PiC study will provide important information for policy makers regarding the value of POCT and on the utility and cost of emerging diagnostic strategies. The study will also identify which elements of existing CPGs may merit inclusion in any future study to derive clinical decision rules for this population. TRIAL REGISTRATION: NCT03378258 . Retrospectively registered on December 19, 2017.

How to interpret malaria tests.

There are over 300 new cases of imported paediatric malaria in the UK each year and this has been increasing over the last 20 years. Malaria in children is particularly difficult to diagnose because the initial presenting features are subtler than in adults and do not display the classical presenting features. However, they are also more likely to deteriorate rapidly and to develop severe malaria. The 'gold standard' for ruling out the diagnosis of malaria if clinically suspected is three negative thin and thick blood films, which require serial phlebotomy and the availability of trained technicians. There are now a range of other tests, including rapid diagnostic tests and PCR, as well as clinical features that make the diagnosis more or less likely. We explore the different tests available and whether these might replace the three negative blood films currently needed. We also look at whether we are able to use clinical features to aid the tests used for a diagnosis of imported malaria.

How to interpret mast cell tests.

Mast cell tryptase (tryptase) is an enzyme produced almost exclusively by mast cells that is easy to measure using a widely available test. In this article we discuss the physiology of the mast cell and how that relates to IgE-mediated anaphylaxis and mastocytosis. We also describe the technical aspects of testing tryptase and the reported normal ranges in health. Finally we explore the diagnostic performance of serum mast cell tryptase measurements, when used to confirm anaphylaxis, estimate future anaphylaxis risk and in diagnosing/monitoring leukaemia.

Role of diagnostic tests for sepsis in children: a review.

Paediatric sepsis has a significant global impact and highly heterogeneous clinical presentation. The clinical pathway encompasses recognition, escalation and de-escalation. In each aspect, diagnostics have a fundamental influence over outcomes in children. Biomarkers can aid in creating a larger low-risk group of children from those in the clinical grey area who would otherwise receive antibiotics 'just in case'. Current biomarkers include C reactive protein and procalcitonin, which are limited in their clinical use to guide appropriate and rapid treatment. Biomarker discovery has focused on single biomarkers, which, so far, have not outperformed current biomarkers, as they fail to recognise the complexity of sepsis. The identification of multiple host biomarkers that may form a panel in a clinical test has the potential to recognise the complexity of sepsis and provide improved diagnostic performance. In this review, we discuss novel biomarkers and novel ways of using existing biomarkers in the assessment and management of sepsis along with the significant challenges in biomarker discovery at present. Validation of biomarkers is made less meaningful due to methodological heterogeneity, including variations in sepsis diagnosis, biomarker cut-off values and patient populations. Therefore, the utilisation of platform studies is necessary to improve the efficiency of biomarkers in clinical practice.