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Objective To collate all available evidence on the diagnostic value of laboratory tests for the diagnosis of serious infections in febrile children in ambulatory settings. Design Systematic review. Data sources Electronic databases, reference tracking, and consultation with experts. Study selection Studies were selected on six criteria: design (studies of diagnostic accuracy or deriving prediction rules), participants (otherwise healthy children and adolescents aged 1 month to 18 years), setting (first contact ambulatory care), outcome (serious infection), features assessed (in first contact care), and data reported (sufficient to construct a 2×2 table). Data extraction Quality assessment was based on the quality assessment tool of diagnostic accuracy studies (QUADAS) criteria. Meta-analyses were done using the bivariate random effects method and hierarchical summary receiver operating characteristic curves for studies with multiple thresholds. Data synthesis None of the 14 studies identified were of high methodological quality and all were carried out in an emergency department or paediatric assessment unit. The prevalence of serious infections ranged from 4.5% to 29.3%. Tests were carried out for C reactive protein (five studies), procalcitonin (three), erythrocyte sedimentation rate (one), interleukins (two), white blood cell count (seven), absolute neutrophil count (two), band count (three), and left shift (one). The tests providing most diagnostic value were C reactive protein and procalcitonin. Bivariate random effects meta-analysis (five studies, 1379 children) for C reactive protein yielded a pooled positive likelihood ratio of 3.15 (95% confidence interval 2.67 to 3.71) and a pooled negative likelihood ratio of 0.33 (0.22 to 0.49). To rule in serious infection, cut-off levels of 2 ng/mL for procalcitonin (two studies, positive likelihood ratio 13.7, 7.4 to 25.3 and 3.6, 1.4 to 8.9) and 80 mg/L for C reactive protein (one study, positive likelihood ratio 8.4, 5.1 to 14.1) are recommended; lower cut-off values of 0.5 ng/mL for procalcitonin or 20 mg/L for C reactive protein are necessary to rule out serious infection. White blood cell indicators are less valuable than inflammatory markers for ruling in serious infection (positive likelihood ratio 0.87-2.43), and have no value for ruling out serious infection (negative likelihood ratio 0.61-1.14). The best performing clinical decision rule (recently validated in an independent dataset) combines testing for C reactive protein, procalcitonin, and urinalysis and has a positive likelihood ratio of 4.92 (3.26 to 7.43) and a negative likelihood ratio of 0.07 (0.02 to 0.27). Conclusion Measuring inflammatory markers in an emergency department setting can be diagnostically useful, but clinicians should apply different cut-off values depending on whether they are trying to rule in or rule out serious infection. Measuring white blood cell count is less useful for ruling in serious infection and not useful for ruling out serious infection. More rigorous studi...

PracticeWhy read this summary? Although urinary tract infection affects at least 3.6% of boys and 11% of girls, establishing the diagnosis is difficult in early childhood owing to the lack of specific urinary symptoms, difficulty in urine collection, and contamination of samples. Most children have a single episode and recover promptly. Current imaging, prophylaxis, and prolonged follow-up strategies place a heavy burden on patients, families, and NHS resources and carry risks without evidence of benefit. This article summarises the most recent guidance from the National Institute for Health and Clinical Excellence (NICE) on how to provide consistent clinically and cost effective practice for the diagnosis, treatment, and further management of urinary tract infection in childhood.

Background Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. Methods The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. Findings The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent ( p < 0.01), whereas altered consciousness/confusion were more frequent ( p < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. Interpretation Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40. Funding Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.