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Title: Adverse drug reactions in hospitalised children
Author: Thiesen, S.
ISNI:       0000 0004 6422 5305
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2016
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Adverse Drug Reactions (ADRs) are a global health problem and a leading cause of death, illness and injury in economically developed countries. Therapeutic response, as well the occurrence of undesired effects, can differ significantly between children and adults and many drugs have not been sufficiently studied in the paediatric population. Existing studies on ADRs in children differ widely in study design and outcome reporting, and many are methodically problematic. The incidence and characteristics of ADRs in hospitalised children and factors associated with an increased risk of experiencing and ADR, were assessed in a large, prospective, observational study. 17.7% of all children experienced at least one ADR. Opiate analgesia and drugs used in general anaesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Less than 1% of ADRs caused permanent harm or required admission to a higher level of care. Children post GA were more than six times more likely to experience an ADR than children who had not received a GA (HR 6.38; 95%CI 5.3-7.7). Other risk factors identified were increasing age (HR 1.05 for each year; 95%CI 1.04-1.07), increasing number of medicines (HR 1.25 for each additional medicine; 95%CI 1.22-1.28) and being an oncology patient (HR 1.89; 95%CI 1.36-2.63). The proportion of ADRs caused by GA agents and opiate analgesia has previously been underestimated. The cost of excess bed days due to ADRs, has been estimated to be £2 Million per year for a 400-bed adult hospital. The cost of excess bed days in our study was only £35,000 per year for a 300-bed hospital. Other parameters and methods might need to be considered when assessing the financial impact of ADRs in children. Cisplatin is used in cancer treatment and causes irreversible hearing loss in 42-88% of children. Cathechol-O-Methyltransferase (COMT) and Thiopurine-S-Methyltransferase (TPMT) genetic variants have been associated with hearing loss in paediatric patients, but findings from subsequent studies are contradictory. The occurrence of COMT and TPMT genetic variants in a UK population was examined in a retrospective, multicentre cohort study. Known risk factors for ototoxicity were confirmed; increasing cumulative dose of cisplatin younger age (p< 0.01), cranial radiotherapy (p <0.028) and exposure to vincristine p< 0.091). The association with COMT and TPMT genetic polymorphisms could not be replicated. ADRs in children are common and improving medicines safety in children remains a vital aspect of clinical care. New assessment tools are aiming to address some of the challenges faced by clinicians and researchers. Our knowledge of pharmacokinetics and pharmacodynamics in children is still limited, but advances in the field of paediatric pharmacogenomics are beginning to translate into improved medicines safety and efficacy for children. Further work about non-Oncology ADRs would benefit from a focus on high impact events that are described in this thesis.
Supervisor: Turner, M. ; Pirmohamed, M. ; Smyth, R. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral