Optic Nerve Germinoma and Transient Spontaneous Regression-More Than Meets the Eye.

Infiltration of the optic pathway by germ cell tumors is exceptional and can lead to confusion with glioma or inflammatory conditions. We present the case of a 14-year-old girl with an optic nerve germinoma extending to the hypothalamus and manifesting as panhypopituitarism and visual loss. The patient experienced spontaneous regression of the lesion followed by secondary deterioration requiring treatment. Four other cases of spontaneously regressing intracranial germinoma followed by regrowth have been reported in the literature. This report highlights the importance of clinical and radiologic monitoring of intracranial germinoma, even in the event of initial spontaneous improvement.

Evaluation of patient-reported outcome measurements as a reliable tool to measure acceptability of the taste of paediatric medicines in an inpatient paediatric population.

OBJECTIVE: To evaluate the age appropriateness and suitability of patient-reported outcome measures to assess the acceptability of the taste of oral liquid medicines in children. DESIGN AND SETTING: An observational mixed-methods study involving children aged 2-16 years taking oral liquid medicine in paediatric inpatient wards across the West Midlands (UK). Assessment tools included patient-reported scores on the taste of medicines via a five-point Facial Hedonic Scale; a Visual Analogue Scale (VAS); a question, 'Did you think the medicine tasted OK?' and researcher observations of facial expressions and behaviours immediately before, during and after administration. RESULTS: 611 children participated. The percent unable to complete the scales was 7% (n=46) for the VAS; 2% (n=15) for the hedonic scale and 1% (n=7) for the question about taste. Significant correlations (Spearman's r) were observed between the patient-reported outcome measures: 0.80 and 0.78 for the taste question and hedonic and VAS, respectively, and 0.84 for the hedonic and VAS. Researcher observations demonstrated the ability of the patient to take the medicine as intended but did not provide sensitive measures of taste. 5% of administrations were not taken as intended by the children. Medicines known to have poor taste (clarithromycin and prednisolone) showed mean hedonic and VAS scores of ≥3.5 and >65 mm, respectively. CONCLUSIONS: Patient-reported outcome measures correlate with each other and are a useful means to assess the taste (and acceptability) of medicines. Hedonic scales are better understood by children and should be the first choice tool in the assessment of medicines taste.

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

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 10 mg 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 15 mg. 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.

COMPARISON OF HYDROCORTISONE 10†MG TABLETS: TABLET HARDNESS OPTIMISED FOR ADULT USE HAS NEGATIVE CONSEQUENCES FOR PAEDIATRIC USE.

BACKGROUND: Children's medicines are not always readily available as an age appropriate product and manipulation of adult products is often required. Recently the commercial manufacturing process for 10 mg hydrocortisone tablets has changed and the compression force increased due to tablets fracturing on removal from the blister pack. However, this change led to parents of children requiring hydrocortisone reporting that the tablets were more difficult to manipulate.This study evaluated 10 mg hydrocortisone tablets for their suitability for manipulation in order to deliver an appropriate dose to children (2 mg dose). The physical properties of tablets with the old and new compression force were compared as well as the accuracy of obtaining the paediatric dose. METHODS: The tablets compared were hydrocortisone Auden 10 mg tablets (Brand A, PL16876/002)-these are the newer, harder tablets- and hydrocortisone 10 mg tablets (Brand B, PL17507/0097). Tablet physical properties including friability (Copley FRV200) and tablet hardness (Copley TBF1000) were compared. The accuracy of split doses (halve and quarter tablets) were recorded on a Sartorius analytical balance. The accuracy of the 2 mg paediatric dosing was assessed by crushing the tablet, adding 10 mL of water and extracting 2 mL. The concentration was measured using UV analysis (Jenway Genova Plus) according to a calibration curve (wavelength=246 nm). Two devices were used to crush the tablets: a spoon onto a plate and a commercially available crushing device (Apothecary Ezy Crush Pill Crusher With Ergo Grip). RESULTS: As anticipated Brand A tablets were harder (51.85 ±5.1 N) compared to Brand B (30.99±4.1 N). Brand A tablets passed the friability testing with <1% weight loss whereas Brand B failed as 5 tablets broke during testing.The accuracy of split doses using the score lines to halve and quarter the tablets showed that Brand A were generally better with smaller ranges for both halves (Range for A=41-55%; B=29-70%) and quarters (Range for A=17-35%; B=12-42%) compared to Brand B.The 2 mg dosing accuracy was better for Brand B tablets compared to A and crushing tablets using a commercial device improved the accuracy of dosing for both brands of tablets. When crushing using a spoon the mean dose obtained was 1.3 mg for Brand A and 1.7 mg for Brand B; the commercial crushing device gave values of 1.9 mg for Brand A and 2.1 mg for Brand B. CONCLUSION: Parents or carers who are required to manipulate 10 mg hydrocortisone tablets to administer a dose to children dispersed in water should be advised to crush the tablet into a fine powder where possible to improve the likelihood of administering an accurate dose. This is particularly important since the introduction of new hydrocortisone Auden tablets which are known to be harder tablets and therefore more force is required to crush these. ACKNOWLEDGEMENTS: Some of the experimental work within this project was conducted by Andrew Hackett and Kameron Paul-Thaper whilst at the University of Birmingham on work experience from Arden Sixth Form, Station Rd, Knowle, Solihull, West Midlands, B93 0PT.

Barriers to administering non-oral formulations in a paediatric population: A semi-structured interview study.

There is a paucity of research exploring barriers to non-oral medicines administration in paediatric patients; however, these undoubtedly influence medicines adherence. Studies conducted with healthcare professionals have identified various issues with the administration and acceptance of non-oral medicines and devices (Venables et al., 2012; Walsh et al., 2015). EMA (2014) guidelines specify that formulation teams should demonstrate 'acceptability' of paediatric formulations when developing pharmaceutical formulations. Semi-structured interviews exploring barriers to administering non-oral medicines were conducted with young persons and the parents/legal guardians of children (0-17 years) with chronic conditions at the University Hospital of Coventry and Warwickshire, UK. 90 children prescribed a total of 148 non-oral medicines were recruited to the study; 88 barriers to administering non-oral medicines were reported. The most commonly reported barriers were: poor acceptance of face mask/difficulties with spacer for inhaled formulations (38% of reports); disliking parenteral/preferring alternative formulations (38% of reports); greasy texture of topical preparations; difficulty with administering an ocular ointment and the large dose volume of a nasal preparation. Formulation teams should consider the use of child-friendly, age-appropriate designs to improve usability and acceptance, thus medicines adherence. These findings should be used to inform future development of non-oral formulations and devices, suitable in terms of safety, efficacy and acceptability to paediatric patients.

Problems with oral formulations prescribed to children: a focus group study of healthcare professionals.

BACKGROUND: There is evidence to suggest that adherence with prescribed medication is lower amongst adolescents and children than in adults. Medication adherence rates between 11 and 93 % in paediatric patients have been reported. More research needs to be carried out in order to understand why medicines adherence is low and how adherence can be improved in children with long-term conditions. Personal communication with paediatricians in secondary care has highlighted that problems are most likely to be encountered by parents, carers, nurses and children themselves when administering medicines for prevalent long-term childhood conditions. OBJECTIVE: To explore problems with oral medicines prescribed to paediatric patients from the perspectives of medical practitioners, pharmacists and nurses. Setting Two NHS trusts in the West Midlands, UK. METHODS: Four focus groups (FG) were conducted. Five nurses, eight medical practitioners and six pharmacists participated in focus groups. The themes explored were problems experienced when prescribing, dispensing and administering oral medicines for children. Main outcome measure Themes evolving from Healthcare professionals reports on problems with administering medicines to paediatric patients. RESULTS: Two main themes: sensory and non-sensory emerged from the data. Included within these were taste, texture, colour, smell, size, swallowing, quantity, volume and manipulation with food. Taste was the most commonly reported barrier to medicines administration. Texture was reported to be a significant problem for the learning disability population. Medicines manipulation techniques 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. CONCLUSION: Organoleptic and physical properties of medicines are key barriers to medicines administration. A robust scientific evidence-based approach is warranted to inform standardised protocols guiding healthcare professionals to support safe and effective medicines manipulation across all settings. Pharmacists' knowledge of Specials medicines needs to be recognised as a valuable resource for doctors. Findings of this study should help to optimise paediatric prescribing and direct future formulation work.

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.

Impact of disordered puberty on bone density in beta-thalassaemia major.

Reduction of bone density and its associated morbidity is recognized in young adults with beta-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.