Heather Stirling

Impact of disordered puberty on bone density in β‐thalassaemia major

Summary. Reduction of bone density and its associated morbidity is recognized in young adults with β‐thalassaemia major, but the aetiology is not clear. This study used dual X‐ray absorptiometry (DXA) to look at bone mineral apparent density (BMAD) in children and young adults with thalassaemia in a predominantly Asian population, in the context of sexual maturation. Fifty‐five patients were scanned (mean age 13·8 years, range 5·9–37·5) and BMAD z‐scores were calculated using normal data from locally recruited control subjects. Eighteen patients had undergone bone marrow transplantation (BMT) and the remainder were on a transfusion/chelation regimen. BMAD z‐scores ranged from –3·3–1·6 with a mean of −0·92. No difference in BMAD was found between those patients treated conventionally and those who had undergone BMT. When comparing mean BMAD z‐score according to sexual maturation, there was a highly significant difference (P < 0·0001) between those whose pubertal maturation was age appropriate (mean z‐score −0·22), when compared with those who had disordered puberty (mean z‐score −1·82). We have shown that failure to progress normally through puberty is highly significant in the failure of adequate bone mineralization and achievement of peak bone mass in thalassaemic patients. The management of these patients should therefore be pro‐active to anticipate problems and facilitate normal sexual maturation.

Determination of formulation factors that affect oral medicines acceptability in a domiciliary paediatric population.

UNLABELLED Acceptability of medicines for children is a challenge, yet critical to ensure adherence to treatment. There is very little literature on formulation factors that influence acceptability of medicines, particularly in the domiciliary environment. This pragmatic study was conducted at University Hospital Coventry and Warwickshire (UHCW) with the aim of identifying the prevalence and nature of oral formulation-related barriers to medicines administration in children suffering from long-term conditions. This study used semi-structured face-to-face interviews with 221 parents/carers of children (0-18 years) and 57 young people (12-18 years). RESULT showed significant medicines refusal and manipulation in the domiciliary environment. Nearly one-third (71/232) of respondents reported medicines refusal. This was associated significantly with the age of child (p=0.016), socioeconomic status (IMD 2010 score) (p=0.002), taste (p<0.001), texture (p=0.017), and volume (of liquid/powder) or quantity (of solid dosage form) (p<0.001). 29% (74/252) of respondents reported manipulating medicines. P-values are based on multivariable statistical analysis models. This study has indicated that formulations prescribed to children with chronic conditions are not meeting the needs of a significant number of patients based on self-report. Age-appropriate medicines are required to provide suitable dose units with an acceptable taste for children. This study should aid pharmaceutical companies to prioritise paediatric formulation work.

Delayed visual maturation: pupillary responses implicate subcortical and cortical visual systems.

Vision in very early infancy is probably subserved by subcortical pathways, with many cortical processes only fully emerging by 3 months of age. The improvement of vision in delayed visual maturation (DVM) occurs around this time, and this has given rise to the Suggestion that the condition may have a subcortical basis that resolves with the appearance of cortical function. To explore further the role of cortical and subcortical visual systems in DVM we studied the visual development in identical twins, one of whom had type lb DVM. Two non‐invasive methods of investigating visual pathway function were employed: the acuity card procedure (a behavioural response) and luminance and grating pupillometry. While the former reflects both subcortical and cortical function and can be detected at birth, pupil responses to gratings reflect cortical activity alone and normally become measurable at 1 month of age. Development of both behavioural and pupillary responses was delayed in DVM, indicating that although the underlying defect is primarily subcortical, secondarily it delays the emergence of cortically mediated responses. The observed rapidity of improvement‐over a very few days and within a narrow age range ‐ suggests a discrete rather than a widespread structural abnormality, the improvement of which is closely linked to postmenstrual age.

G406(P) Oral formulation-related barriers to medicines administration in children with chronic conditions: views of parents and young people

Introduction Limited studies have explored oral formulation-related barriers to medicines administration in children, in narrow patient groups (e.g. HIV). Owing to the lack of licensed medicines suitable for use in children, often manipulation is required to either deliver a dose or to facilitate medicines administration. The need for more age-appropriate medicines has been well acknowledged [1]. Purpose This study adopted a pragmatic approach to determine the nature and prevalence of oral formulation-related barriers to medicines administration in children suffering from a wide range of chronic conditions. Problems reported by patients and their parents/carers about oral formulations were identified with the aim of informing future pharmaceutical development, thus improving future children’s medicines. Materials and methods Semi-structured face-to-face interviews were conducted with 278 parents/carers/young people at UHCW. Children (0- <18 y) were receiving prescribed medicines for a chronic condition (duration ≥1 month). Questions explored barriers to medicines administration, medicines refusal and manipulation. Ethical approval was granted. Results Medicines refusal 19% of all medicines were reported to be refused by childrenTaste was a problem reported for 64% of medicines that were refused. Medicines manipulation 19% of all medicines were reported to be manipulated 79% of manipulations were for the purpose of administering a specific dose (e.g. tablet segmented)26% of manipulations were to facilitate administration (e.g. mixed with foodstuffs). Oral formulation-related barriers to medicines administration: Taste was the most commonly reported (35% of all prescribed medicines) Drugs with highest incidence of taste issues were ranitidine liquid (82%), prednisolone soluble tablets (81%) and trimethoprim liquid (75%) of total usersIssues also reported (in descending order of prevalence) were: texture (8%), volume/quantity (5%), size/swallowing (5%), colour (2%) and smell (2%). Conclusions In total, 19% of medicines were reported to be refused by children. For administration to children, almost one fifth of medicines were reported to require manipulation. Taste was most the most frequently reported oral formulation-related barrier to medicines administration. Findings indicate that age-appropriate medicines should be developed to provide both suitable dose units and acceptable taste for paediatric patients. Reference 1. EMEA (2006) Reflection paper: formulations of choice for the paediatric population. London. EMEA/CHMP/PEG/194810/2005. p1–45. [Online] Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003782.pdf [Accessed on 17/05/2013].

How close is the dose? Manipulation of 10 mg hydrocortisone tablets to provide appropriate doses to children

ABSTRACT This study explores the methodology advised by healthcare professionals and the methods used by parents/carers to identify whether there is a best practice method for manipulation of 10mg hydrocortisone tablets to provide an accurate dose to children. Bespoke surveys were used to identify methods recommended and used in manipulation of tablets. Hydrocortisone tablets were manipulated to provide a specified dose by both naïve participants and parents/carers. The accuracy of manipulation was assessed using HPLC analysis. Competed surveys were received from 159 parent/carers reporting doses that ranged from 0.25 to 15mg. Parents/carers most commonly reported splitting the tablet and administering the solid fraction; however more than 30% of those reporting physically splitting tablets were preparing doses that were not simply halving or quartering tablets. In a naïve population the dose accuracy, defined as percent of doses within 20% of the theoretical dose ranged from 57 to 58% depending on the tablet brand and the method of manipulation used. Almost three‐quarters (74.1%) of parent/carers (n=27) were able to produce a dose within 20% of the theoretical value and the most accurate method was to split tablets and administer the solid fraction. This study shows that a lack of age‐appropriate medicines results in children being at risk of sub‐optimal dosing.

G219 Hydrocortisone tablets: human factors in manipulation and their impact on dosing accuracy

Background Exposure to deficient or excess glucocorticoids is associated with increased morbidity in patients with adrenal insufficiency. An age-appropriate low dose hydrocortisone formulation is not available and manipulation of adult medication is required with potential for inaccurate dosing. Licensed pharmaceutical products must contain ±10% of labelled drug content. Aims To assess the variability in manipulation procedures undertaken by parents/carers and to quantify the dose-variability in the manipulated product based on the method of preparation. Methods Parents of children with adrenal insufficiency completed a survey assessing the methods used to manipulate hydrocortisone 10 mg tablets. A sub-group were asked to manipulate a scored 10 mg hydrocortisone tablet (Auden Mackenzie brand) to provide the prescribed dose for their child as they would at home. Hydrocortisone content was analysed according to the current European Pharmacopoeial method. Results One hundred and twenty-nine parents completed the questionnaire. Overall 55% of parents break or cut the tablet and 43% suspend the tablet in water prior to administration. 34% are prescribed a dose indivisible by 2.5 mg of whom 33% break the tablet to acquire the dose. Twenty-seven parents/carers participated in the sub-study and the target doses they prepared ranged from 0.5–7.5 mg. Forty eight percent of the preparations were within 10% of the target dose; 74% were within 20% and 82% were within 30%. Based on this small sample size the most accurate method of tablet manipulation is to split the tablet along the score lines. However, this is only possible for doses divisible by 2.5 mg. Dispersion of the tablet in water and withdrawal of the relevant volume was associated with poor accuracy. Conclusions Children are at risk of suboptimal dosing when parents/carers are required to manipulate adult products to provide the appropriate dose to children. This risk is greatest when doses need to be prepared via dispersion of a tablet and calculation of the volume to withdraw. This may be related to the poor solubility of hydrocortisone which makes formation of a homogenous liquid difficult. There is a need for age-appropriate hydrocortisone products to be available to children. Acknowledgement This study was funded via an unrestricted research grant from Diurnal Ltd.

G434(P) Improving prescribing for children: Healthcare professionals’ understanding of children’s medicines

Introduction and purpose One in ten prescriptions for children in primary care is for an unlicensed or off-label medicine which can lead to an unsuitable formulation. Manufacture of “specials” is a major issue with significant cost implications. Doctors and health care professionals at all levels of training are often unaware of the licensing requirements for paediatric drugs and the implications of these, but there is little information assessing their knowledge. Method Health care professionals attending a paediatric continuing professional development afternoon were invited to complete a questionnaire at the start of the session. The participants were asked to provide five definitions related to the prescribing of children’s medicines: 1) Off-licence, 2) Off-label 3) Specials, 4) NICE approved and 5) Marketing authorisation. The answers were analysed as to whether they were correct, partly correct or incorrect/unknown according to standard definitions. Ethics approval was not necessary. Results 36 questionnaires were distributed and 32 (89%) were returned from 12 paediatric consultants, 9 paediatric trainee doctors, 4 senior paediatric nurses and 7 pharmacists. Participants were asked to provide 5 definitions each, giving a total of 160 potentially correct answers. Correct Partly correct Incorrect/unknown Paediatric consultants 33/60 (55%) 9/60 (15%) 18/60 (30%) Paediatric trainees 3/45 (7%) 7/45 (16%) 35/45 (77%) Paediatric nurses 5/20 (25%) 5/20 (25%) 10/20 (50%) Pharmacists 23/35 (66%) 7/35 (20%) 5/35 (14%) There were also differences in the ability to define the definitions. There was particularly poor understanding of the term “special”. 50% of consultants were able to define it adequately, yet no doctors in training were. The pharmacists had the best understanding. Conclusion There is limited knowledge regarding paediatric prescribing amongst all levels of doctors, but most worryingly the junior doctors who do not understand when they are prescribing off -label or off-licence drugs. They are unlikely to be aware when they are prescribing a “special” and therefore unaware of the problems the child and family may have obtaining it, the variations in the formulations’ pharmacokinetics, and the cost. The paediatric consultants fared a little better, but have gaps in understanding. Doctors’ lack of knowledge regarding paediatric prescribing needs to be addressed. The strength of paediatric pharmacists’ knowledge could be utilised more to guide doctors in prescribing the most suitable and cost-effective formulations for children.

G413(P) Problems with the administration of oral formulations to children: Perspectives of medical practitioners, pharmacists and nurses

Introduction There is limited evidence regarding healthcare professionals (HCP)s knowledge of issues with medicines administration in paediatric patients with chronic conditions. The few studies that have been conducted have included HCPs working in disease-specific groups1, 2 and those investigating knowledge on the use of unlicensed medicines.3, 4 Purpose The objective was to explore problems with medicines administration in children suffering from chronic conditions from the perspectives of medical practitioners, pharmacists and nurses, and additionally to identify common and unique themes of problems with oral medicines prescribed to children. Materials and methods Four focus groups (FG) were conducted at two NHS trusts. FG1 (n = 5): neonatal nurse practitioners, nurse practice educator, community paediatric nurses. FG2 (n = 8): GP, general paediatric consultants, specialist paediatric consultants, paediatric registrar. FG3 (n = 2): paediatric pharmacist, specialist pharmacist. FG4 (n = 4): paediatric pharmacists. Themes explored problems experienced when prescribing, dispensing and administering medicines for children. Ethical approval was granted. Results Themes identified included taste, texture, colour, smell, size/swallowing, quantity/volume and manipulation with food. Taste was the most commonly reported oral-formulation related barrier to medicines administration across the groups. Flucloxacillin solution was discussed with regard to its poor palatability in all groups. Texture was reported to be a significant problem for the learning disability population across the groups. Medicines manipulation techniques (e.g. mixing with foodstuffs) were revealed across the groups, yet there was limited knowledge regarding the evidence base for such activity. Problems surrounding the supply of Specials medicines were discussed in-depth by the pharmacists. Conclusions Taste was perceived to be the major barrier to medicines administration in children. Further organoleptic and physical properties of medicines were also identified as barriers to medicines administration and should not be overlooked. A robust scientific evidence-base approach is warranted to inform standardised protocols guiding HCPs to support safe and effective medicines manipulation in both domiciliary (i.e. by parents/carers) and hospital (i.e. by nurses) settings. Pharmacists should collaborate with prescribers and provide advice on Specials prescribing owing to their increased knowledge. Findings of this study should help to optimise paediatric prescribing and also direct future formulation work.

Thyroxine: Cause and cure for headache: Correspondence section

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