Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE) : A multicentre observational study

Funding Information: This project has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No. 668303. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors no sources of funding were declared. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all research nurses for their help in collecting data, and Anda Nagle (Riga) and the Institute of Microbiology at University Medical Centre Ljubljana for their help in collecting data on antimicrobial resistance. Members of the PERFORM consortium are listed in S11 Text. Publisher Copyright: Copyright: © 2020 Hagedoorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. Methods and findings Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. Conclusions In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.publishersversionPeer reviewe

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

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

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