| Summary: | Adherence to medication is a major issue in chronic illnesses in general and is of particular concern in children, who are often dependent on their parents/carers for medication administration. Adherence to the immunosuppressant mycophenolate in children with kidney transplant, which is poorly studied worldwide, was evaluated in the present research using a range of different measures for adherence assessment and triangulating the results. These methods were: measuring mycophenolic acid (MPA) concentration in plasma and dried blood spot (DBS) samples, patient self-report questionnaires, and pharmacy and prescriber records. MPA is the active form of mycophenolate in vivo. Factors which could influence patient adherence were explored via administration of questionnaires to patients and their carers including: the Beliefs about Medicines Questionnaire (BMQ), the Centre of Epidemiologic Studies Depression (CES-D) Scale, Paediatric Quality of Life Inventory (PedsQL™ Transplant Module) and consideration of demographical/medical information collected for each participating patient. Assay methods for the quantification of MPA in both DBS and plasma samples collected at outpatient clinics were developed using high performance liquid chromatography (HPLC) and validated according to international guidelines. Gradient elution HPLC with UV detection was utilised with the mobile phase consisting of a combination of phosphate buffer and acetonitrile; a C18 column acted as the stationary phase. A total of 33 children (8 to 18 years old) and their parents/guardians participated in the clinical study that followed. Adherence was assessed by applying the new assay methodology to determining MPA concentrations in paediatric samples and comparing these with predicted concentrations based on child parameters (weight, medication dose, co-medications) using population pharmacokinetic (PopPK) modelling simulations. This novel approach was found to be a useful in the assessment of patient adherence when combined with the other measures detailed above. Overall non-adherence to mycophenolate in the children with kidney transplant who participated in the research (n=33) was found to be 36.4%. Logistic regression analysis indicated that children who suffer from medication side effects were statistically more likely to be non-adherent. Although the adherence work formed the main body of the research presented in the thesis, two supplementary, supporting research projects were also included (i) A review of questions and answers raised in a patient online discussion forum for use by patients with kidney transplant and (ii) an online survey of paediatric clinical pharmacists on prioritising future research needs in the area of medicine use in children. In the discussion forum it was established that the concerns experienced by patients with kidney transplant could be categorised into three themes: concerns related to the clinical manifestations, concerns related to transplant management, and concerns about the transplant impact on daily life. Although the majority of users of the forum were adults, such concerns are expected to affect children with kidney transplant as they reach adulthood and could form a framework for the development of early interventions. The online survey of practicing paediatric pharmacists indicated that high priority should be given to new research in the areas of medication administration, pharmacokinetics, the use of extemporaneous formulations, pharmacovigilance of medicines, the use of ‘Specials’ and the use of off-label or unlicensed medicines in children. It is hoped that, when published, the priority list developed will act as a guide for prioritising new research projects on medicine use in children nationally and internationally.
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