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      The cost of diagnostic uncertainty: a prospective economic analysis of febrile children attending an NHS emergency department

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          Abstract

          Background

          Paediatric fever is a common cause of emergency department (ED) attendance. A lack of prompt and definitive diagnostics makes it difficult to distinguish viral from potentially life-threatening bacterial causes, necessitating a cautious approach. This may result in extended periods of observation, additional radiography, and the precautionary use of antibiotics (ABs) prior to evidence of bacterial foci. This study examines resource use, service costs, and health outcomes.

          Methods

          We studied an all-year prospective, comprehensive, and representative cohort of 6518 febrile children (aged < 16 years), attending Alder Hey Children’s Hospital, an NHS-affiliated paediatric care provider in the North West of England, over a 1-year period. Performing a time-driven and activity-based micro-costing, we estimated the economic impact of managing paediatric febrile illness, with focus on nurse/clinician time, investigations, radiography, and inpatient stay. Using bootstrapped generalised linear modelling (GLM, gamma, log), we identified the patient and healthcare provider characteristics associated with increased resource use, applying retrospective case-note identification to determine rates of potentially avoidable AB prescribing.

          Results

          Infants aged less than 3 months incurred significantly higher resource use than any other age group, at £1000.28 [95% CI £82.39–£2993.37] per child, ( p < 0.001), while lesser experienced doctors exhibited 3.2-fold [95% CI 2.0–5.1-fold] higher resource use than consultants ( p < 0.001). Approximately 32.4% of febrile children received antibiotics, and 7.1% were diagnosed with bacterial infections. Children with viral illnesses for whom antibiotic prescription was potentially avoidable incurred 9.9-fold [95% CI 6.5–13.2-fold] cost increases compared to those not receiving antibiotics, equal to an additional £1352.10 per child, predominantly resulting from a 53.9-h increase in observation and inpatient stay (57.1 vs. 3.2 h). Bootstrapped GLM suggested that infants aged below 3 months and those prompting a respiratory rate ‘red flag’, treatment by lesser experienced doctors, and Manchester Triage System (MTS) yellow or higher were statistically significant predictors of higher resource use in 100% of bootstrap simulations.

          Conclusion

          The economic impact of diagnostic uncertainty when managing paediatric febrile illness is significant, and the precautionary use of antibiotics is strongly associated with increased costs. The use of ED resources is highest among infants (aged less than 3 months) and those infants managed by lesser experienced doctors, independent of clinical severity. Diagnostic advances which could increase confidence to withhold antibiotics may yield considerable efficiency gains in these groups, where the perceived risks of failing to identify potentially life-threatening bacterial infections are greatest.

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          Most cited references24

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          Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study

          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.
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            Oral versus initial intravenous therapy for urinary tract infections in young febrile children.

            The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy. In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by 99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days. Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was approximately 8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously ($3577 vs $1473) compared with those treated orally. Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures.
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              Systematic review and validation of prediction rules for identifying children with serious infections in emergency departments and urgent-access primary care.

              Although the vast majority of children with acute infections are managed at home, this is one of the most common problems encountered in children attending emergency departments (EDs) and primary care. Distinguishing children with serious infection from those with minor or self-limiting infection is difficult. This can result in misdiagnosis of children with serious infections, which results in a poorer health outcome, or a tendency to refer or admit children as a precaution; thus, inappropriately utilising secondary-care resources.
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                Author and article information

                Contributors
                +44 7503 955 592 , Simon.leigh@liverpool.ac.uk
                Alison.grant@alderhey.nhs.uk
                Nicolarosemurray@doctors.org.uk
                Brian.faragher@lstmed.ac.uk
                HenalDesai@hotmail.com
                Samatha.dolan@boltonft.nhs.uk
                nmo.cabdi@gmail.com
                James.murray2@uhb.nhs.uk
                yasmin.rejaei@midyorks.nhs.uk
                Stephanie.Stewart@nhs.net
                Karl.Edwardson@alderhey.nhs.uk
                Jason.Dean@alderhey.nhs.uk
                bimal.mehta@nhs.net
                Shunmay.yeung@lshtm.ac.uk
                Coenen@liverpool.ac.uk
                Louis.Niessen@lstmed.ac.uk
                edcarrol@liv.ac.uk
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                6 March 2019
                6 March 2019
                2019
                : 17
                : 48
                Affiliations
                [1 ]ISNI 0000 0004 1936 8470, GRID grid.10025.36, Institute of Infection and Global Health, , University of Liverpool, ; 8 West Derby St, Liverpool, L69 7BE UK
                [2 ]ISNI 0000 0004 0421 1374, GRID grid.417858.7, Infectious Diseases Department, , Alder Hey Children’s NHS Foundation Trust, ; Eaton Road, Liverpool, L12 2AP UK
                [3 ]ISNI 0000 0004 0421 1374, GRID grid.417858.7, Alder Hey Children’s NHS Foundation Trust, ; Eaton Road, Liverpool, L12 2AP UK
                [4 ]ISNI 0000 0004 0417 2395, GRID grid.415970.e, The Royal Liverpool University Hospital, ; Prescot St, Liverpool, L7 8XP UK
                [5 ]ISNI 0000 0004 1936 9764, GRID grid.48004.38, Medical Statistics Unit, Department of Clinical Sciences, , Liverpool School of Tropical Medicine, ; Pembroke Place, Liverpool, L3 5QA UK
                [6 ]ISNI 0000 0004 0400 0219, GRID grid.413619.8, Royal Derby Hospital, ; Uttoxeter Road, Derby, DE22 3NE UK
                [7 ]ISNI 0000 0004 0399 766X, GRID grid.414534.3, Royal Bolton Hospital, ; Minerva Road, Farnworth, BL4 0JR UK
                [8 ]ISNI 0000 0004 1936 8470, GRID grid.10025.36, School of Medicine, , University of Liverpool, ; Cedar House, Liverpool, L69 3GE UK
                [9 ]ISNI 0000 0001 2177 007X, GRID grid.415490.d, Queen Elizabeth Hospital, ; Mindelsohn Way, Birmingham, B15 2TH UK
                [10 ]ISNI 0000 0004 0398 5474, GRID grid.413702.3, Pinderfields District General Hospital, ; Aberford Road, Wakefield, WF1 4DG UK
                [11 ]GRID grid.449813.3, Wirral University Teaching Hospital, ; Arrowe Park Road, Wirral, CH49 5PE UK
                [12 ]ISNI 0000 0004 0421 1374, GRID grid.417858.7, Information Department, , Alder Hey Children’s NHS Foundation Trust, ; Eaton Road, Liverpool, L12 2AP UK
                [13 ]ISNI 0000 0004 0421 1374, GRID grid.417858.7, Finance Department, , Alder Hey Children’s NHS Foundation Trust, ; Eaton Road, Liverpool, L12 2AP UK
                [14 ]ISNI 0000 0004 0421 1374, GRID grid.417858.7, Emergency Department, , Alder Hey Children’s NHS Foundation Trust, ; Eaton Road, Liverpool, L12 2AP UK
                [15 ]ISNI 0000 0004 0425 469X, GRID grid.8991.9, Department of Clinical Research, MARCH Centre for Maternal, Adolescent, Reproductive and Child Health, , London School of Hygiene and Tropical Medicine, ; Keppel Street, London, WC1E 7HT UK
                [16 ]ISNI 0000 0004 1936 8470, GRID grid.10025.36, Department of Computer Science, , University of Liverpool, ; Ashton Building, Ashton Street, Liverpool, L693BX UK
                [17 ]ISNI 0000 0004 1936 9764, GRID grid.48004.38, Department of International Public Health and Clinical Sciences, , Liverpool School of Tropical Medicine and University of Liverpool, ; Liverpool, UK
                [18 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of International Health, , Johns Hopkins Bloomberg School of Public Health, ; Baltimore, MA USA
                Author information
                http://orcid.org/0000-0002-6843-6447
                Article
                1275
                10.1186/s12916-019-1275-z
                6402102
                30836976
                da137833-17ee-41a1-9d93-8dc1aee488b3
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 October 2018
                : 30 January 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100007601, Horizon 2020;
                Award ID: 668303
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Medicine
                febrile,fever,pyrexia,children,health economics,cost of illness,antibiotics,united kingdom
                Medicine
                febrile, fever, pyrexia, children, health economics, cost of illness, antibiotics, united kingdom

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