Diagnosing serious infections in acutely ill children in ambulatory care (ERNIE 2 study protocol, part A): diagnostic accuracy of a clinical decision tree and added value of a point-of-care C-reactive protein test and oxygen saturation

Background: Acute illness is the most common presentation of children to ambulatory care. In contrast, serious infections are rare and often present at an early stage. To avoid complications or death, early recognition and adequate referral are essential. In a recent large study children were included prospectively to construct a symptom-based decision tree with a sensitivity and negative predictive value of nearly 100%. To reduce the number of false positives, point-of-care tests might be useful, providing an immediate result at bedside. The most probable candidate is C-reactive protein, as well as a pulse oximetry. Methods: This is a diagnostic accuracy study of signs, symptoms and point-of-care tests for serious infections. Acutely ill children presenting to a family physician or paediatrician will be included consecutively in Flanders, Belgium. Children testing positive on the decision tree will get a point-of-care C-reactive protein test. Children testing negative will randomly either receive a point-of-care C-reactive protein test or usual care. The outcome of interest is hospital admission more than 24 hours with a serious infection within 10 days. Aiming to include over 6500 children, we will report the diagnostic accuracy of the decision tree (+/- the point-of-care C-reactive protein test or pulse oximetry) in sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values. New diagnostic algorithms will be constructed through classification and regression tree and multiple logistic regression analysis. Discussion: We aim to improve detection of serious infections, and present a practical tool for diagnostic triage of acutely ill children in primary care. We also aim to reduce the number of investigations and admissions in children with non-serious infections

Nitrate in upper groundwater on farms under tillage as affected by fertilizer use, soil type and groundwater table

Indicators are needed to check whether policies on protection of groundwater are effective and if regulations are complied with. We evaluated various indicators at different scales, both in space and in time, and at different degrees of complexity. Groundwater was sampled on 34 arable farms for 3 years. Nitrate concentration in upper groundwater was low on clay soil. On sandy soil, peat layers reduced the nitrate concentration with about 80 mg/l on average. Sandy soils with high groundwater tables had nitrate concentrations that were less than half of those at sandy soils with low groundwater tables. The relationship between different fertilization variables and nitrate in groundwater was investigated for sandy soils without peat layers. N surplus poorly correlated with nitrate concentrations in groundwater when individual sampling points were studied, but clearly increased when data were averaged at the farm level. Soil mineral nitrogen correlated best with nitrate concentrations in groundwater. The relationships show that especially on well drained soil drastic measures will be inevitable to reach good water quality

Optimizing antibiotic prescribing for acutely ill children in primary care (ERNIE2 study protocol, part B): a cluster randomized, factorial controlled trial evaluating the effect of a point-of-care C-reactive protein test and a brief intervention combined with written safety net advice

Background: Despite huge public campaigns, there is still overconsumption of antibiotics in children with self-limiting diseases. Possible explanations may be the physicians’ and parents’ uncertainty about the gravity of the disease and inadequate communication between physicians and parents leading to lack of reassurance for the parents. In this paper we describe the design and methods of a trial aiming to rationalize antibiotic prescribing by decreasing this uncertainty and parental anxiety. Methods/Design: Acutely ill children without suspected serious disease consulting their family physician will be consecutively included in a four-armed cluster randomized factorial controlled trial. The intervention will consist a Point-of-Care C-reactive protein test and/or a brief intervention with safety net advice. The control group will receive usual care. We intend to include 2560 patients in 88 family practices. Patients will be followed up until cure. The primary outcome measure is the immediate antibiotic prescribing rate. Secondary outcomes are: comparison between groups of speed of clinical recovery, parental concern, parental perception of the quality of the communication, parental satisfaction, use of medication, use of diagnostic tests and medical services during the illness episode, and cost-effectiveness of the interventions. Besides this, we will observationally analyse data of the children included in the large ERNIE2-trial, but excluded in the cluster randomized trial, namely children suspected of serious disease presenting in primary care and children who initially present at the out-patient paediatric clinic or emergency department. We will search for predictors of antibiotic prescribing, speed of clinical recovery, parental concern, parental perception of communication, parental satisfaction, use of medication, diagnostic tests and medical services. Discussion: This is a unique multifaceted intervention, in that it targets both physicians and parents by aiming specifically at their uncertainty and concerns during the consultation. Both interventions are easy to implement without special training. When proven effective, they could offer a feasible way to decrease inappropriate antibiotic prescribing for children in family practice and thus avoid emergence of bacterial resistance, side effects and unnecessary healthcare costs. Moreover, the observational part of the study will increase our insight in the course, management and parent’s concern of acute illness in children. Trial registration: ClinicalTrials.gov Identifier: NCT02024282. </p

Reducing inappropriate antibiotic prescribing for children in primary care: a cluster randomised controlled trial of two interventions

Background: Antibiotics are overprescribed for non-severe acute infections in children in primary care. Aim: To explore two different interventions that may reduce inappropriate antibiotic prescribing for non-severe acute infections. Design and setting: A cluster randomised, factorial controlled trial in primary care, in Flanders, Belgium. Method: Family physicians (FPs) enrolled children with non-severe acute infections into this study. The participants were allocated to one of four intervention groups according to whether the FPs performed: (1) a point-of-care C-reactive protein test (POC CRP); (2) a brief intervention to elicit parental concern combined with safety net advice (BISNA); (3) both POC CRP and BISNA; or (4) usual care (UC). Guidance on the interpretation of CRP was not provided. The main outcome was the immediate antibiotic prescribing rate. A mixed logistic regression was performed to analyse the data. Results: In this study 2227 non-severe acute infections in children were registered by 131 FPs. In comparison with UC, POC CRP did not influence antibiotic prescribing, (adjusted odds ratio [AOR] 1.01, 95% confidence interval [CI] = 0.57 to 1.79). BISNA increased antibiotic prescribing (AOR 2.04, 95% CI = 1.19 to 3.50). In combination with POC CRP, this increase disappeared. Conclusion: Systematic POC CRP testing without guidance is not an effective strategy to reduce antibiotic prescribing for non-severe acute infections in children in primary care. Eliciting parental concern and providing a safety net without POC CRP testing conversely increased antibiotic prescribing. FPs possibly need more training in handling parental concern without inappropriately prescribing antibiotics.</p

Diagnosing serious infections in acutely ill children in ambulatory care (ERNIE 2 study protocol, part A): diagnostic accuracy of a clinical decision tree and added value of a point-of-care C-reactive protein test and oxygen saturation

Background: Acute illness is the most common presentation of children to ambulatory care. In contrast, serious infections are rare and often present at an early stage. To avoid complications or death, early recognition and adequate referral are essential. In a recent large study children were included prospectively to construct a symptom-based decision tree with a sensitivity and negative predictive value of nearly 100%. To reduce the number of false positives, point-of-care tests might be useful, providing an immediate result at bedside. The most probable candidate is C-reactive protein, as well as a pulse oximetry. Methods: This is a diagnostic accuracy study of signs, symptoms and point-of-care tests for serious infections. Acutely ill children presenting to a family physician or paediatrician will be included consecutively in Flanders, Belgium. Children testing positive on the decision tree will get a point-of-care C-reactive protein test. Children testing negative will randomly either receive a point-of-care C-reactive protein test or usual care. The outcome of interest is hospital admission more than 24 hours with a serious infection within 10 days. Aiming to include over 6500 children, we will report the diagnostic accuracy of the decision tree (+/− the point-of-care C-reactive protein test or pulse oximetry) in sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values. New diagnostic algorithms will be constructed through classification and regression tree and multiple logistic regression analysis. Discussion: We aim to improve detection of serious infections, and present a practical tool for diagnostic triage of acutely ill children in primary care. We also aim to reduce the number of investigations and admissions in children with non-serious infections. Trial Registration: ClinicalTrials.gov Identifier: NCT02024282 </p

Point-of-care C reactive protein to identify serious infection in acutely ill children presenting to hospital: prospective cohort study

Objective; Acute infection is the most common presentation of children to hospital. A minority of these infections are serious, but early recognition and adequate management are essential. We aimed to develop improved tools to assess children attending ambulatory hospital care, integrating clinical features with point-of-care C reactive protein (CRP). Design; Prospective observational diagnostic study. Setting and patients; 5517 acutely ill children (1 month–16 years) presenting to 106 paediatricians at six outpatient clinics and six emergency departments in Belgium. Index test; Point-of-care CRP alongside vital signs and objective symptoms measurements. Main outcome; Hospital admission for >24 hours with a serious infection <5 days after presentation. Results; An algorithm was developed consisting of clinical features and CRP. This achieved 97.1% (95% CI 94.3% to 98.7%) sensitivity and 99.6% (95% CI 99.2% to 99.8%) negative predictive value, excluding serious infections in 36.4% of children. It stratifies patients into three groups based on CRP level: high-risk group with CRP >75 mg/L (26.8% risk of infection), intermediate-risk group with CRP 20–75 mg/L and at least one of seven clinical features (8.1%), and lower risk group with CRP <20 mg/L with at least one of the 11 features (3.8%). Children in intermediate-risk or low-risk groups with normal clinical assessment have 0.6% and 0.4% risk of serious infections, respectively. Conclusions; Conducting a CRP test may first enable children to be stratified into three risk groups, guiding assessment of clinical features that could be performed by junior doctors or nurses. In one-third of acutely ill children, the algorithm could exclude serious infection. Prospective validation of the algorithm is needed. Clinical trial registration; NCT02024282 (post-results)

Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial

BACKGROUND: Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment. METHODS: Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12-30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L. RESULTS: Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8-82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP &lt; 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP &lt; 5 mg/L. CONCLUSIONS: CRP testing should be restricted to children at higher risk after clinical assessment. A CRP &lt; 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals

CRP-test alleen bij acuut zieke kinderen met hoger risico

Inleiding Een CRP-sneltest via een vingerprik zou de huisarts kunnen helpen bij het uitsluiten van een ernstige infectie bij kinderen. Wij onderzochten of we de sneltest bij alle kinderen moeten aanbieden of alleen bij kinderen met klinische risicofactoren. Methode We voerden een clustergerandomiseerd onderzoek uit onder acuut zieke kinderen die zich aanmeldden bij 133 huisartsen in 78 huisartspraktijken in België (3147 ziekte-episodes). We randomiseerden praktijken om een CRP-sneltest uit te voeren bij alle kinderen of alleen bij kinderen met klinische risicofactoren (kortademigheid, temperatuur ≥ 40 °C, diarree bij kinderen tussen 12 tot 30 maanden of een niet-pluisgevoel van de arts). De uitkomstmaat was ziekenhuisopname met een ernstige infectie binnen vijf dagen. Resultaten Als kinderen een CRP-test krijgen op basis van klinische risicofactoren, is zo’n test slechts nodig bij 20% van de kinderen. Er was tussen de twee onderzoeksgroepen geen verschil in het aantal kinderen met een ernstige infectie dat de huisartsen dadelijk naar het ziekenhuis verwezen (0,16% versus 0,14%, p = 0,88), of misten bij het eerste contact (0,29% versus 0,14%, p = 0,35). Elf kinderen hadden een ernstige infectie, van hen hadden er zes een CRP van minder dan 20 mg/L. Slechts een kind met een CRP ≺ 5 mg/L had een ziekte die een opname rechtvaardigde. Conclusie De CRP-sneltest is alleen nuttig bij kinderen met klinische risicofactoren. Een CRP ≺ 5 mg/L sluit een ernstige infectie uit en kan de huisarts helpen om onnodige verwijzingen te vermijden. Het klinische oordeel van de arts blijft essentieel, zelfs als een lage CRP-waarde een ernstige infectie lijkt uit te sluiten.</p

Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial

BACKGROUND: Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment. METHODS: Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12-30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L. RESULTS: Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8-82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP &lt; 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP &lt; 5 mg/L. CONCLUSIONS: CRP testing should be restricted to children at higher risk after clinical assessment. A CRP &lt; 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals