Matthew J Thompson

Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review

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 studies are needed, including studies in primary care, to assess the value of laboratory tests alongside clinical diagnostic measurements, including vital signs.

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Risk score to stratify children with suspected serious bacterial infection: observational cohort study

Objectives To derive and validate a clinical score to risk stratify children presenting with acute infection. Study design and participants Observational cohort study of children presenting with suspected infection to an emergency department in England. Detailed data were collected prospectively on presenting clinical features, laboratory investigations and outcome. Clinical predictors of serious bacterial infection (SBI) were explored in multivariate logistic regression models using part of the dataset, each model was then validated in an independent part of the dataset, and the best model was chosen for derivation of a clinical risk score for SBI. The ability of this score to risk stratify children with SBI was then assessed in the entire dataset. Main outcome measure Final diagnosis of SBI according to criteria defined by the Royal College of Paediatrics and Child Health working group on Recognising Acute Illness in Children. Results Data from 1951 children were analysed. 74 (3.8%) had SBI. The sensitivity of individual clinical signs was poor, although some were highly specific for SBI. A score was derived with reasonable ability to discriminate SBI (area under the receiver operator characteristics curve 0.77, 95% CI 0.71 to 0.83) and risk stratify children with suspected SBI. Conclusions This study demonstrates the potential utility of a clinical score in risk stratifying children with suspected SBI. Further work should aim to validate the score and its impact on clinical decision making in different settings, and ideally incorporate it into a broader management algorithm including additional investigations to further stratify a childs risk.

Which early 'red flag' symptoms identify children with meningococcal disease in primary care?

BACKGROUNDnSymptoms are part of the initial evaluation of children with acute illness, and are often used to help identify those who may have serious infections. Meningococcal disease is a rapidly progressive infection that needs to be recognised early among children presenting to primary care.nnnAIMnTo determine the diagnostic value of presenting symptoms in primary care for meningococcal disease.nnnDESIGN OF STUDYnData on a series of presenting symptoms were collected using a parental symptoms checklist at point of care for children presenting to a GP with acute infection. Symptom frequencies were compared with existing data on the pre-hospital features of 345 children with meningococcal disease.nnnSETTINGnUK primary care.nnnMETHODnThe study recruited a total of 1212 children aged under 16 years presenting to their GP with an acute illness, of whom 924 had an acute self-limiting infection, including 407 who were reported by parents to be febrile. Symptom frequencies were compared with those reported by parents of 345 children with meningococcal disease. Main outcome measures were diagnostic characteristics of individual symptoms for meningococcal disease.nnnRESULTSnFive symptoms have clinically useful positive likelihood ratios (LR+) for meningococcal disease: confusion (LR+ = 24.2, 95% confidence interval [CI] = 11.5 to 51.3), leg pain (LR+ = 7.6, 95% CI = 4.9 to 11.9), photophobia (LR+ = 6.5, 95% CI = 3.8 to 11.0), rash (LR+ = 5.5, 95% CI = 4.3 to 7.1), and neck pain/stiffness (LR+ = 5.3, 95% CI = 3.5 to 8.3). Cold hands and feet had limited diagnostic value (LR+ = 2.3, 95% CI = 1.9 to 3.0), while headache (LR+ = 1.0, 95% CI = 0.8 to 1.3), and pale colour (LR+ = 0.3, 95% CI = 0.2 to 0.5) did not discriminate meningococcal disease in children.nnnCONCLUSIONnThis study confirms the diagnostic value of classic red flag symptoms of neck stiffness, rash, and photophobia, but also suggests that the presence of confusion or leg pain in a child with an unexplained acute febrile illness should also usually prompt a face-to-face assessment to exclude meningococcal disease. Telephone triage systems and primary care clinicians should consider these as red flags for serious infection.

Evaluation of temperature–pulse centile charts in identifying serious bacterial illness: observational cohort study

Background Distinguishing serious bacterial infection (SBI) from milder/self-limiting infections is often difficult. Interpretation of vital signs is confounded by the effect of temperature on pulse and respiratory rate. Temperature–pulse centile charts have been proposed to improve the predictive value of pulse rate in the clinical assessment of children with suspected SBI. Objectives To assess the utility of proposed temperature–pulse centile charts in the clinical assessment of children with suspected SBI. Study design and participants The predictive value for SBI of temperature–pulse centile categories, pulse centile categories and Advanced Paediatric Life Support (APLS) defined tachycardia were compared among 1360 children aged 3 months to 10 years presenting with suspected infection to a hospital emergency department (ED) in England; and among 325 children who presented to hospitals in the UK with meningococcal disease. Main outcome measure SBI. Results Among children presenting to the ED, 55 (4.0%) had SBI. Pulse centile category, but not temperature–pulse centile category, was strongly associated with risk of SBI (p=0.0005 and 0.288, respectively). APLS defined tachycardia was also strongly associated with SBI (OR 2.90 (95% CI 1.60 to 5.26), p=0.0002). Among children with meningococcal disease, higher pulse and temperature–pulse centile categories were both associated with more severe disease (p=0.004 and 0.041, respectively). Conclusions Increased pulse rate is an important predictor of SBI, supporting National Institute for Health and Clinical Excellence recommendations that pulse rate be routinely measured in the assessment of febrile children. Temperature–pulse centile charts performed more poorly than pulse alone in this study. Further studies are required to evaluate their utility in monitoring the clinical progress of sick children over time.

Which symptoms and clinical features correctly identify serious respiratory infection in children attending a paediatric assessment unit

Objective Parent-reported symptoms are frequently used to triage children, but little is known about which symptoms identify children with serious respiratory infections. The authors aimed to identify symptoms and triage findings predictive of serious respiratory infection, and to quantify agreement between parent and nurse assessment. Design Prospective diagnostic cohort study. Setting Paediatric Assessment Unit, University Hospitals Coventry and Warwickshire NHS Trust. Patients 535 children aged between 3 months and 12 years with suspected acute infection. Methods Parents completed a symptom questionnaire on arrival. Children were triaged by a nurse, who measured routine vital signs. The final diagnosis at discharge was used as the outcome. Symptoms and triage findings were analysed to identify features diagnostic of serious respiratory infection. Agreement between parent and triage nurse assessment was measured and kappa values calculated. Results Parent-reported symptoms were poor indicators of serious respiratory infection (positive likelihood ratio (LR+) 0.56–1.93) and agreed poorly with nurse assessment (kappa 0.22–0.56). The best predictor was clinical assessment of respiratory distress (LR+ 5.04). Oxygen saturations <94% were highly specific (specificity 95.1%) but had poor sensitivity (35.6%). Tachypnoea (defined by current Advanced Paediatric Life Support standards) offered little discriminatory value. Conclusion Parent-reported symptoms were unreliable discriminators of serious respiratory infection in children with suspected acute infection, and did not correlate well with nurse assessment. Using symptoms to identify higher risk children in this setting is unreliable. Nurse triage assessment of respiratory distress and some vital signs are important predictors.