TITLE 1 The cost of diagnostic uncertainty : A prospective economic analysis of febrile children attending an 2 NHS Emergency

79 80 Background 81 Paediatric fever is a common cause of emergency department (ED) attendance. A lack of prompt and 82 definitive diagnostics makes it difficult to distinguish viral from potentially life-threatening bacterial 83 causes, necessitating a cautious approach. This may result in extended periods of observation, additional 84 radiography, and the precautionary use of antibiotics (ABs) to deal with bacterial foci. This study 85 examines resource use, service costs, and health outcomes. 86 87 Methods 88 We studied an all-year prospective, comprehensive, and representative cohort of 6,518 febrile children 89 (aged <16 years), attending Alder Hey Children’s Hospital, an NHS-affiliated paediatric care provider 90 in the North West of England, over a one-year period. Performing a time-driven and activity-based 91 micro-costing, we estimated the economic impact of managing paediatric febrile illness, with focus on 92 nurse/clinician time, investigations, radiography and inpatient stay. Using bootstrapped generalized 93 linear modelling (GLM, gamma, log), we identified the patient and healthcare provider characteristics 94 associated with increased resource use, applying retrospective case-note identification to determine 95 rates of potentially avoidable AB prescribing. 96 97 Results 98 Infants aged less than three months incurred significantly higher resource use than any other age-group, 99 at £1000.28 [95%CI £82.39-£2,993.37] per child, (p<0.001); while lesser experienced doctors exhibited 100 3.2-fold [95%CI 2.0-5.1-fold] higher resource use than consultants, (p<0.001). Approximately 32.4% 101 of febrile children received antibiotics and 7.1% were diagnosed with bacterial infections. Children 102 with viral illnesses for whom antibiotic prescription was potentially avoidable incurred 9.9-fold [95%CI 103 6.5-13.2-fold] cost increases compared to those not receiving antibiotics, equal to an additional 104 £1,352.10 per child; predominantly resulting from a 53.9 hour increase in observation and inpatient stay 105 (57.1 vs. 3.2 hours). Bootstrapped GLM suggested that infants aged below three months, those 106 prompting a respiratory rate “red flag”, treatment by lesser-experienced doctors and Manchester Triage 107 System (MTS) yellow or higher were statistically significant predictors of higher resource use in 100% 108 of bootstrap simulations. 109 110 Conclusion 111 The economic impact of diagnostic uncertainty when managing paediatric febrile illness is significant, 112 and the precautionary use of antibiotics is strongly associated with increased costs. The use of ED 113 resources is highest among infants (aged less-than-three months), and those infants managed by lesser 114 experienced doctors, independent of clinical severity. Diagnostic advances which could increase 115 confidence to withhold antibiotics, may yield considerable efficiency gains in these groups; where the 116 perceived risks of failing to identify potentially life-threatening bacterial infections are greatest. 117 118