Diagnostic test accuracy of dipstick urinalysis for diagnosing urinary tract infection in febrile infants attending the emergency department.

OBJECTIVE: To report the diagnostic test accuracy of dipstick urinalysis for the detection of urinary tract infections (UTIs) in febrile infants aged 90 days or less attending the emergency department (ED). DESIGN: Retrospective cohort study. PATIENTS: Febrile infants aged 90 days or less attending between 31 August 2018 and 1 September 2019. MAIN OUTCOME MEASURES: The sensitivity, specificity and predictive values of dipstick urinalysis in detecting UTIs defined as growth of ≥100 000 cfu/mL of a single organism and the presence of pyuria (>5 white blood cells per high-power field). SETTING: Eight paediatric EDs in the UK/Ireland. RESULTS: A total of 275 were included in the final analysis. There were 252 (92%) clean-catch urine samples and 23 (8%) were transurethral bladder catheter samples. The median age was 51 days (IQR 35-68.5, range 1-90), and there were 151/275 male participants (54.9%). In total, 38 (13.8%) participants had a confirmed UTI. The most sensitive individual dipstick test for UTI was the presence of leucocytes. Including 'trace' as positive resulted in a sensitivity of 0.87 (95% CI 0.69 to 0.94) and a specificity of 0.73 (95% CI 0.67 to 0.79). The most specific individual dipstick test for UTI was the presence of nitrites. Including trace as positive resulted in a specificity of 0.91 (95% CI 0.86 to 0.94) and a sensitivity of 0.42 (95% CI 0.26 to 0.59). CONCLUSION: Point-of-care urinalysis is moderately sensitive and highly specific for diagnosing UTI in febrile infants. The optimum cut-point to for excluding UTI was leucocytes (1+), and the optimum cut-point for confirming UTI was nitrites (trace). TRIAL REGISTRATION NUMBER: NCT04196192.

Validating clinical practice guidelines for the management of febrile infants presenting to the emergency department in the UK and Ireland.

OBJECTIVE: To report the performance of clinical practice guidelines (CPG) in the diagnosis of serious/invasive bacterial infections (SBI/IBI) in infants presenting with a fever to emergency care in the UK and Ireland. Two CPGs were from the National Institutes for Health and Care Excellence (NICE guidelines NG51 and NG143) and one was from the British Society for Antimicrobial Chemotherapy (BSAC). DESIGN: Retrospective multicentre cohort study. PATIENTS: Febrile infants aged 90 days or less attending between the 31 August 2018 to 1 September 2019. MAIN OUTCOME MEASURES: The sensitivity, specificity and predictive values of CPGs in identifying SBI and IBI. SETTING: Six paediatric Emergency Departments in the UK/Ireland. RESULTS: 555 participants were included in the analysis. The median age was 53 days (IQR 32 to 70), 447 (81%) underwent blood testing and 421 (76%) received parenteral antibiotics. There were five participants with bacterial meningitis (1%), seven with bacteraemia (1%) and 66 (12%) with urinary tract infections. The NICE NG51 CPG was the most sensitive: 1.00 (95% CI 0.95 to 1.00). This was significantly more sensitive than NICE NG143: 0.91 (95% CI 0.82 to 0.96, p=0.0233) and BSAC: 0.82 (95% 0.72 to 0.90, p=0.0005). NICE NG51 was the least specific 0.0 (95% CI 0.0 to 0.01), and this was significantly lower than the NICE NG143: 0.09 (95% CI 0.07 to 0.12, p<0.0001) and BSAC: 0.14 (95% CI 0.1 to 0.17, p<0.0001). CONCLUSION: None of the studied CPGs demonstrated ideal performance characteristics. CPGs should be improved to guide initial clinical decision making. TRIAL REGISTRATION NUMBER: NCT04196192.

Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study.

BACKGROUND: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection. DESIGN: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2-15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. RESULTS: 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). DISCUSSION: Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity. TRIAL REGISTRATION NUMBER: NCT0434740.

Fifteen-minute consultation: Apparent vaginal bleeding in the pre-pubertal girl.

A parent or carer's observation of blood in a child's nappy or underwear can be quite alarming for both parent and child and may indicate vaginal bleeding. At first glance, it may be difficult to ascertain whether the bleeding is from the skin, genital tract, urinary tract or anus. Confirmed vaginal bleeding in a pre-pubertal girl is rare but always abnormal and requires comprehensive assessment to determine the cause. Recognition of normal female pre-pubertal anatomy is essential to detect any abnormalities. Appropriate action should be taken according to findings on initial inspection of the ano-genital area. The possibility of child sexual abuse and the need for specialist paediatric sexual offences medicine examination by an FME (Forensic Medical Examiner) or specialist paediatrician should always be considered. This article offers a systematic approach to assessment in pre-pubertal girls with apparent vaginal bleeding which will benefit general paediatricians, emergency department practitioners and GPs.

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.

Loop-mediated isothermal amplification for the early diagnosis of invasive meningococcal disease in children.

BACKGROUND: Rapid molecular diagnostic testing has the potential to improve the early recognition of meningococcal disease (MD). The aim of this study was to report on the diagnostic test accuracy of point-of-care loop-mediated isothermal amplification (LAMP) in the diagnosis of MD. DESIGN: Data were collected prospectively from three UK emergency departments (ED) between November 2017 and June 2019. Consecutive children under 18 years of age attending the ED with features of MD were eligible for inclusion. The meningococcal LAMP test (index test) was performed on a dry swab of the child's oropharynx. Reference standard testing was the confirmation of invasive MD defined as positive N. meningitidis culture or PCR result from a sterile body site (blood or cerebrospinal fluid). RESULTS: There were 260 children included in the final analysis. The median age was 2 years 11 months and 169 (65%) children were aged 5 years or younger. The LAMP test was negative in 246 children and positive in 14 children. Of the 14 children with positive LAMP tests, there were five cases of invasive MD. Of the 246 children with negative LAMP tests, there were no cases of invasive MD. The sensitivity of LAMP testing was 1.00 and the specificity was 0.97. The negative and positive predictive values were 1.00 and 0.36, respectively. The positive likelihood ratio was 28.3. DISCUSSION: Non-invasive LAMP testing using oropharyngeal swabs provided an accurate fast and minimally invasive mechanism for predicting invasive MD in this study. TRIAL REGISTRATION NUMBER: NCT03378258.

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.

Emergency department attendance following 4-component meningococcal B vaccination in infants.

INTRODUCTION: In September 2015, the UK became the first country in the world to introduce the 4-component meningococcal B vaccine(4CMenB) into the routine vaccine schedule for infants. 4CMenB is known to cause fever in infants. Infants presenting with fever, particularly those under 3 months, have a significant risk of serious bacterial infection(SBI). METHOD: Between September 2015 and January 2016, we performed a prospective audit of management of infants between 30 and 180 days attending the regional paediatric emergency department(ED) in Northern Ireland, within 4 days of receiving 4CMenB. RESULTS: 35 ED attendances in infants aged 30-180 days were due to symptoms occurring after primary vaccinations including 4CMenB, representing an estimated 0.8% of the vaccinated population in the catchment area. 86% of infants presented after the first vaccine and parents reported giving paracetamol to 94% of infants. 80% of infants presented with fever. Blood tests were performed in 62% of infants and leucocytosis was present in 73%. All cultures taken were negative and 51% were admitted to hospital. 100% of final diagnoses were vaccine related (diagnosis made by exclusion). DISCUSSION: In this study, an estimated 0.8% of the vaccinated population in the catchment area attended ED with symptoms occurring after primary vaccinations including 4CMenB. Infants with fever have a higher risk of SBI, but infants with fever in the post-vaccination period may not have the same risk. Further data are essential to inform national guidelines on investigation and management of fever in infants following vaccination with 4CMenB, possibly incorporating a less-invasive approach.

The Croydon Assessment of Learning Study: prevalence and educational identification of mild mental retardation.

BACKGROUND: Mild mental retardation is an enduring and impairing condition. Its prevalence has varied widely across different studies from .5 to over 8%, with higher rates in completely ascertained samples. The current study estimates the prevalence of low IQ in the mental retardation range (intellectual disability) in a population sample and examines the factors that relate to educational identification. METHOD: A total of 2,730 children in school years 8 and 9 attending local authority schools were assessed in school with the group-administered Cognitive Abilities Test (CAT). A sample of 304 pupils at high, moderate and low risk of mild mental retardation was selected for in-depth study. This included the individually measured full-scale IQ (WISC-III(UK)), the Wechsler Quicktest of attainments, the Strengths and Difficulties Questionnaire from parents and teachers and an abbreviated version of the Social Communication Questionnaire. RESULTS: Of those selected for the in-depth study, 204 (67%) participated, with a greater proportion from the low risk group. A range of prevalence estimates were calculated using different imputation methods and assumptions about individuals not screened. Rates of pupils with WISC IQ < 70 varied from 5.8% to 10.6%. There were no significant gender differences. In contrast to the high prevalence estimates using the WISC, the proportion of pupils scoring in the lowest stanine on the CAT was as expected. Only 15% of those with IQ < 70 had a statement of special educational needs or attended a school for moderate learning difficulties. Behaviour, particularly social communication problems, predicted educational identification. CONCLUSIONS: The current study produced a high estimate of the prevalence of mild intellectual disability based on the WISC but not on the CAT. The findings highlight that the majority of mild intellectual disability in the UK would not be detected using registers. Cases that are detected by registers are more behaviourally disturbed than others.