SummaryBackground-Although heart rate and respiratory rate are routinely measured in children in acute settings, current reference ranges are not evidence-based. The aim of this study is to derive new centile charts for heart rate and respiratory rate using systematic review data from existing studies, and to compare these with existing international ranges.

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Study selection Cohort studies including unselected groups of children and young adults presenting with new onset type 1 diabetes that distinguished between those who presented in diabetic ketoacidosis and those who did not and included a measurement of either pH or bicarbonate in the definition of diabetic ketoacidosis. There were no restrictions on language of publication.Results 46 studies involving more than 24 000 children in 31 countries were included. Together they compared 23 different factors. Factors associated with increased risk were younger age (for <2 years old v older, odds ratio 3.41 (95% confidence interval 2.54 to 4.59), for <5 years v older, odds ratio 1.59 (1.38 to 1.84)), diagnostic error (odds ratio 3.35 (2.35 to 4.79)), ethnic minority, lack of health insurance in the US (odds ratio 3.20 (2.03 to 5.04)), lower body mass index, preceding infection (odds ratio 3.14 (0.94 to 10.47)), and delayed treatment (odds ratio 1.74 (1.10 to 2.77)). Protective factors were having a first degree relative with type 1 diabetes at the time of diagnosis (odds ratio 0.33 (0.08 to 1.26)), higher parental education (odds ratios 0.4 (0.20 to 0.79) and 0.64 (0.43 to 0.94) in two studies), and higher background incidence of type 1 diabetes (correlation coefficient -0.715). The mean duration of symptoms was similar between children presenting with or without diabetic ketoacidosis (16.5 days (standard error 6.2) and 17.1 days (6.0) respectively), and up to 38.8% (285/735) of children who presented with diabetic ketoacidosis had been seen at least once by a doctor before diagnosis.Conclusions Multiple factors affect the risk of developing diabetic ketoacidosis at the onset of type 1 diabetes in children and young adults, and there is potential time, scope, and opportunity to intervene between symptom onset and development of diabetic ketoacidosis for both parents and clinicians.

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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...

Aims/hypothesisType 1 diabetes is the most frequent endocrine disease in children, with 65,000 children diagnosed worldwide every year. Up to 80% of these children present with diabetic ketoacidosis (DKA), which is associated with both short-term risks and long-term consequences. This study aimed to characterise the worldwide variation in presentation of type 1 diabetes to inform future interventions to reduce this excess morbidity and mortality.MethodsThis was a systematic review of studies indexed on PubMed, EMBASE, Web of Science, Scopus or CINAHL before March 2011 that included unselected groups of children presenting with new-onset type 1 diabetes, reported the proportion presenting with DKA and used a definition of DKA based on measurement of pH or bicarbonate.ResultsSixty-five studies of cohorts comprising over 29,000 children in 31 countries were included. The frequency of DKA at diagnosis ranged from 12.8% to 80%, with highest frequencies in the United Arab Emirates, Saudi Arabia and Romania, and the lowest in Sweden, the Slovak Republic and Canada. Multivariable modelling showed the frequency of DKA was inversely associated with gross domestic product, latitude and background incidence of type 1 diabetes.Conclusions/interpretationThis is the first description of the variation in frequency of DKA at presentation of type 1 diabetes in children across countries. It demonstrates large variations that may, at least in part, be explained by different levels of disease awareness and healthcare provision and suggests ways to decrease the excess morbidity and mortality associated with DKA at diagnosis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-012-2690-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

A gut feeling about the seriousness of illness in children is an instinctive response by clinicians to the concerns of the parents and the appearance of the children. It should trigger action such as seeking a second opinion or further investigations. The observed association between intuition and clinical markers of serious infection means that by reflecting on the genesis of their gut feeling, clinicians should be able to hone their clinical skills.

Objective To derive, cross validate, and externally validate a clinical prediction model that assesses the risks of different serious bacterial infections in children with fever at the emergency department.Design Prospective observational diagnostic study.Setting Three paediatric emergency care units: two in the Netherlands and one in the United Kingdom.Participants Children with fever, aged 1 month to 15 years, at three paediatric emergency care units: Rotterdam (n=1750) and the Hague (n=967), the Netherlands, and Coventry (n=487), United Kingdom. A prediction model was constructed using multivariable polytomous logistic regression analysis and included the predefined predictor variables age, duration of fever, tachycardia, temperature, tachypnoea, ill appearance, chest wall retractions, prolonged capillary refill time (>3 seconds), oxygen saturation <94%, and C reactive protein.Main outcome measures Pneumonia, other serious bacterial infections (SBIs, including septicaemia/meningitis, urinary tract infections, and others), and no SBIs.Results Oxygen saturation <94% and presence of tachypnoea were important predictors of pneumonia. A raised C reactive protein level predicted the presence of both pneumonia and other SBIs, whereas chest wall retractions and oxygen saturation <94% were useful to rule out the presence of other SBIs. Discriminative ability (C statistic) to predict pneumonia was 0.81 (95% confidence interval 0.73 to 0.88); for other SBIs this was even better: 0.86 (0.79 to 0.92). Risk thresholds of 10% or more were useful to identify children with serious bacterial infections; risk thresholds less than 2.5% were useful to rule out the presence of serious bacterial infections. External validation showed good discrimination for the prediction of pneumonia (0.81, 0.69 to 0.93); discriminative ability for the prediction of other SBIs was lower (0.69, 0.53 to 0.86).Conclusion A validated prediction model, including clinical signs, symptoms, and C reactive protein level, was useful for estimating the likelihood of pneumonia and other SBIs in children with fever, such as septicaemia/meningitis and urinary tract infections.