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BMJ | 2011

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

A Van den Bruel; Matthew J Thompson; T Haj-Hassan; Richard L. Stevens; Henriëtte A. Moll; Monica Lakhanpaul; David Mant

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.


The Lancet | 2010

Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review.

Ann Van den Bruel; T Haj-Hassan; Matthew Thompson; Frank Buntinx; David Mant

BACKGROUND Our aim was to identify which clinical features have value in confirming or excluding the possibility of serious infection in children presenting to ambulatory care settings in developed countries. METHODS In this systematic review, we searched electronic databases (Medline, Embase, DARE, CINAHL), reference lists of relevant studies, and contacted experts to identify articles assessing clinical features of serious infection in children. 1939 potentially relevant studies were identified. Studies were selected on the basis of six criteria: design (studies of diagnostic accuracy or prediction rules), participants (otherwise healthy children aged 1 month to 18 years), setting (ambulatory care), outcome (serious infection), features assessed (assessable in ambulatory care setting), and sufficient data reported. Quality assessment was based on the Quality Assessment of Diagnostic Accuracy Studies criteria. We calculated likelihood ratios for the presence (positive likelihood ratio) or absence (negative likelihood ratio) of each clinical feature and pre-test and post-test probabilities of the outcome. Clinical features with a positive likelihood ratio of more than 5.0 were deemed red flags (ie, warning signs for serious infection); features with a negative likelihood ratio of less than 0.2 were deemed rule-out signs. FINDINGS 30 studies were included in the analysis. Cyanosis (positive likelihood ratio range 2.66-52.20), rapid breathing (1.26-9.78), poor peripheral perfusion (2.39-38.80), and petechial rash (6.18-83.70) were identified as red flags in several studies. Parental concern (positive likelihood ratio 14.40, 95% CI 9.30-22.10) and clinician instinct (positive likelihood ratio 23.50, 95 % CI 16.80-32.70) were identified as strong red flags in one primary care study. Temperature of 40 degrees C or more has value as a red flag in settings with a low prevalence of serious infection. No single clinical feature has rule-out value but some combinations can be used to exclude the possibility of serious infection-for example, pneumonia is very unlikely (negative likelihood ratio 0.07, 95% CI 0.01-0.46) if the child is not short of breath and there is no parental concern. The Yale Observation Scale had little value in confirming (positive likelihood ratio range 1.10-6.70) or excluding (negative likelihood ratio range 0.16-0.97) the possibility of serious infection. INTERPRETATION The red flags for serious infection that we identified should be used routinely, but serious illness will still be missed without effective use of precautionary measures. We now need to identify the level of risk at which clinical action should be taken. FUNDING Health Technology Assessment and National Institute for Health Research National School for Primary Care Research.


British Journal of General Practice | 2012

When and how do GPs record vital signs in children with acute infections? A cross-sectional study

Claire Blacklock; T Haj-Hassan; Matthew Thompson

BACKGROUND NICE recommendations and evidence from ambulatory settings promotes the use of vital signs in identifying serious infections in children. This appears to differ from usual clinical practice where GPs report measuring vital signs infrequently. AIM To identify frequency of vital sign documentation by GPs, in the assessment of children with acute infections in primary care. DESIGN AND SETTING Observational study in 15 general practice surgeries in Oxfordshire and Somerset, UK. METHOD A standardised proforma was used to extract consultation details including documentation of numerical vital signs, and words or phrases used by the GP in assessing vital signs, for 850 children aged 1 month to 16 years presenting with acute infection. RESULTS Of the children presenting with acute infections 31.6% had one or more numerical vital signs recorded (269, 31.6%), however GP recording rate improved if free text proxies were also considered: at least one vital sign was then recorded in over half (54.1%) of children. In those with recorded numerical values for vital signs, the most frequent was temperature (210, 24.7%), followed by heart rate (62, 7.3%), respiratory rate (58, 6.8%), and capillary refill time (36, 4.2%). Words or phrases for vital signs were documented infrequently (temperature 17.6%, respiratory rate 14.6%, capillary refill time 12.5%, and heart rate 0.5%), Text relating to global assessment was documented in 313/850 (36.8%) of consultations. CONCLUSION GPs record vital signs using words and phrases as well as numerical methods, although overall documentation of vital signs is infrequent in children presenting with acute infections.


Health Technology Assessment | 2012

Systematic review and validation of prediction rules for identifying children with serious infections in emergency departments and urgent-access primary care.

Matthew Thompson; A Van den Bruel; J.Y. Verbakel; Monica Lakhanpaul; T Haj-Hassan; Richard L. Stevens; Henriëtte A. Moll; Frank Buntinx; Marjolein Y. Berger; Bert Aertgeerts; Rianne Oostenbrink; David Mant


The Lancet | 2014

Israel-Gaza conflict

T Haj-Hassan; Tony McShane; Imran Mahmud; Peter Watkinson; Christopher Conlon; Terence Hope; David A. Lloyd; Nick Maynard


Archive | 2012

Characteristics of variables included in the data sets used to validate clinical prediction rules

Matthew Thompson; A Van den Bruel; J.Y. Verbakel; Monica Lakhanpaul; T Haj-Hassan; Richard L. Stevens; Henriëtte A. Moll; F Buntinx; Marjolein Y. Berger; Bert Aertgeerts; Rianne Oostenbrink; David Mant


Archive | 2012

Details of clinical features and cut-off values in prediction rules included in Chapter 6

Matthew Thompson; A Van den Bruel; J.Y. Verbakel; Monica Lakhanpaul; T Haj-Hassan; Richard L. Stevens; Henriëtte A. Moll; F Buntinx; Marjolein Y. Berger; Bert Aertgeerts; Rianne Oostenbrink; David Mant


Archive | 2012

Results of systematic review of clinical features

Matthew Thompson; A Van den Bruel; J.Y. Verbakel; Monica Lakhanpaul; T Haj-Hassan; Richard L. Stevens; Henriëtte A. Moll; F Buntinx; Marjolein Y. Berger; Bert Aertgeerts; Rianne Oostenbrink; David Mant


Archive | 2012

Results of external validation of clinical prediction rules

Matthew Thompson; A Van den Bruel; J.Y. Verbakel; Monica Lakhanpaul; T Haj-Hassan; Richard L. Stevens; Henriëtte A. Moll; F Buntinx; Marjolein Y. Berger; Bert Aertgeerts; Rianne Oostenbrink; David Mant


Archive | 2012

Results of the systematic review of laboratory tests for serious infections

Matthew Thompson; A Van den Bruel; J.Y. Verbakel; Monica Lakhanpaul; T Haj-Hassan; Richard L. Stevens; Henriëtte A. Moll; F Buntinx; Marjolein Y. Berger; Bert Aertgeerts; Rianne Oostenbrink; David Mant

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Bert Aertgeerts

Catholic University of Leuven

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J.Y. Verbakel

Katholieke Universiteit Leuven

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Henriëtte A. Moll

Erasmus University Rotterdam

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F Buntinx

Katholieke Universiteit Leuven

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