Propylene glycol intake from medications used on paediatric intensive care

Background: There are increasing reports of propylene glycol (PG) toxicity, which is used in many medications as a solvent for water-insoluble drugs. Polypharmacy may increase PG exposure in vulnerable PICU patients who may accumulate PG due to compromised liver and renal function. The study aim was to quantify PG intake in PICU patients and attitudes of clinicians towards PG. Methods: A snapshot of 50 patients’ medication intake was collected. Other data collected included age, weight, diagnosis, lactate levels and renal function. Manufacturers were contacted for PG content and then converted to mg/kg. Excipients in formulations that compete with the PG metabolism pathway were recorded. The Intensivists opinions on PG intake was sought via e-survey. Results: The 50 patients were prescribed 62 drugs and 83 formulations, 43/83 (52 %) were parenteral formulations. Sixteen formulations contained PG, 2/16 were parenteral, 6/16 unlicensed preparations. Thirty-eight patients received drugs with PG. PG intake ranged from 0.002 mg/kg/day to 250 mg/kg/day, with 29/38 receiving formulations with concomitant pathway competing excipients. The total amount could not be quantified in two cases due to lack of availability of information from the manufacturer. Four commonly used formulations contributed to higher intakes of PG. Only 1/16intensivists was aware of PG content in drugs, 16/16 would actively change therapy if intake was above European Medicines Agency recommendations. Conclusions: Certain formulations used on PICU can considerably increase PG exposure to patients. These should be highlighted to the clinician to make an informed decision regarding risks versus benefits in continuing that drug or formulation.

Developing multidimensional metrics for evaluating paediatric neurodevelopmental disorders

Healthy brain functioning depends on efficient communication of information between brain regions, forming complex networks. By quantifying synchronisation between brain regions, a functionally connected brain network can be articulated. In neurodevelopmental disorders, where diagnosis is based on measures of behaviour and tasks, a measure of the underlying biological mechanisms holds promise as a potential clinical tool. Graph theory provides a tool for investigating the neural correlates of neuropsychiatric disorders, where there is disruption of efficient communication within and between brain networks. This research aimed to use recent conceptualisation of graph theory, along with measures of behaviour and cognitive functioning, to increase understanding of the neurobiological risk factors of atypical development. Using magnetoencephalography to investigate frequency-specific temporal dynamics at rest, the research aimed to identify potential biological markers derived from sensor-level whole-brain functional connectivity. Whilst graph theory has proved valuable for insight into network efficiency, its application is hampered by two limitations. First, its measures have hardly been validated in MEG studies, and second, graph measures have been shown to depend on methodological assumptions that restrict direct network comparisons. The first experimental study (Chapter 3) addressed the first limitation by examining the reproducibility of graph-based functional connectivity and network parameters in healthy adult volunteers. Subsequent chapters addressed the second limitation through adapted minimum spanning tree (a network analysis approach that allows for unbiased group comparisons) along with graph network tools that had been shown in Chapter 3 to be highly reproducible. Network topologies were modelled in healthy development (Chapter 4), and atypical neurodevelopment (Chapters 5 and 6). The results provided support to the proposition that measures of network organisation, derived from sensor-space MEG data, offer insights helping to unravel the biological basis of typical brain maturation and neurodevelopmental conditions, with the possibility of future clinical utility.

An evaluation of paediatric medicines reconciliation at hospital discharge into the community

OBJECTIVE: A UK national survey of primary care physicians has indicated that the medication information on hospital discharge summary was incomplete or inaccurate most of the time. Internationally, studies have shown that hospital pharmacist's interventions reduce these discrepancies in the adult population. There have been no published studies on the incidence and severity of the discrepancies of the medication prescribed for children specifically at discharge to date. The objectives of this study were to investigate the incidence, nature and potential clinical severity of medication discrepancies at the point of hospital discharge in a paediatric setting. METHODS: Five weeks prospective review of hospital discharge letters was carried out. Medication discrepancies between the initial doctor's discharge letter and finalised drug chart were identified, pharmacist changes were recorded and their severity was assessed. The setting of the review was at a London, UK paediatric hospital providing local secondary and specialist tertiary care. The outcome measures were: - incidence and the potential clinical severity of medication discrepancies identified by the hospital pharmacist at discharge. KEY FINDINGS: 142 patients (64 female and 78 males, age range 1 month - 18 years) were discharged on 501 medications. The majority of patients were under the care of general surgery and general paediatric teams. One in three discharge letters contained at least one medication discrepancy and required pharmacist interventions to rectify prior to completion. Of these, 1 in 10 had the potential for patient harm if undetected. CONCLUSIONS: Medicines reconciliation by pharmacist at discharge may be a good intervention in preventing medication discrepancies which have the potential to cause moderate harm in paediatric patients.