Hereditary ataxias and paediatric neurology: new movers and shakers enter the field

Over 25 autosomal dominant and autosomal recessive spinocerebellar ataxias have been isolated over the last decade. The recognition of paediatric ataxia phenotypes and, in addition, other movement disorders including hereditary choreiform and parkinsonian syndromes, has improved our knowledge of these diseases. Advances in molecular genetics has allowed fuller delineation and better recognition of these diseases. (C) 2003 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The Utility of Cardiopulmonary Exercise Testing in Difficult Asthma

Background: Unexplained persistent breathlessness in patients with difficult asthma despite multiple treatments is a common clinical problem. Cardiopulmonary exercise testing (CPX) may help identify the mechanism causing these symptoms, allowing appropriate management.

Methods: This was a retrospective analysis of patients attending a specialist-provided service for difficult asthma who proceeded to CPX as part of our evaluation protocol. Patient demographics, lung function, and use of health care and rescue medication were compared with those in patients with refractory asthma. Medication use 6 months following CPX was compared with treatment during CPX.

Results: Of 302 sequential referrals, 39 patients underwent CPX. A single explanatory feature was identified in 30 patients and two features in nine patients: hyperventilation (n = 14), exercise-induced bronchoconstriction (n = 8), submaximal test (n = 8), normal test (n = 8), ventilatory limitation (n = 7), deconditioning (n = 2), cardiac ischemia (n = 1). Compared with patients with refractory asthma, patients without “pulmonary limitation” on CPX were prescribed similar doses of inhaled corticosteroid (ICS) (median, 1,300 µg [interquartile range (IQR), 800-2,000 µg] vs 1,800 µg [IQR, 1,000-2,000 µg]) and rescue oral steroid courses in the previous year (median, 5 [1-6] vs 5 [1-6]). In this group 6 months post-CPX, ICS doses were reduced (median, 1,300 µg [IQR, 800-2,000 µg] to 800 µg [IQR, 400-1,000 µg]; P < .001) and additional medication treatment was withdrawn (n = 7). Patients with pulmonary limitation had unchanged ICS doses post CPX and additional therapies were introduced.

Conclusions: In difficult asthma, CPX can confirm that persistent exertional breathlessness is due to asthma but can also identify other contributing factors. Patients with nonpulmonary limitation are prescribed inappropriately high doses of steroid therapy, and CPX can identify the primary mechanism of breathlessness, facilitating steroid reduction.

Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials.

Objectives: To investigate the knowledge and views of a range of healthcare professionals (consultant paediatricians, general practitioners (GPs), community pharmacists and paediatric nurses) regarding the use of unlicensed/off-label medicines in children and the participation of children in clinical trials.

Methods: A regional study in which a survey instrument with 39 items was issued to 500 randomly selected GPs, all community pharmacists (n?=?512), 50 hospital consultants and 150 paediatric nurses in Northern Ireland.

Results: Approximately half (46.5%) of the 1,212 healthcare professionals approached responded to the questionnaire. The majority of respondents indicated their familiarity with the term unlicensed (82.9%) or off-label (58.6%) prescribing with the most frequently quoted reason for such prescribing being younger age (33.6%). Apart from community pharmacists, most respondents reported having gained their knowledge through personal experience. Even though a large percentage of respondents expressed concerns about the safety (77.8%) or efficacy (87.9%) of unlicensed/off-label prescribing in children, only 30.7% reported informing parents/guardians of these concerns on the use of such medicines in children. In addition, only 56% of respondents believed that unlicensed/off-label medicines should undergo clinical trials in children. Overall, 28.4% of respondents (20.1% of GPs, 41.4% of community pharmacists, 27.7% of paediatric nurses and 94% of consultant paediatricians) indicated their willingness to be actively involved in, and recruit their patients for paediatric clinical research.

Conclusion: The use of unlicensed and off-label medicines remains a major issue in paediatric medicine. Until such times as more licensed medicines are available for children, clear guidance should be developed to allow consistency in practice across the spectrum of healthcare professionals who are involved with such medicines in their routine practice.

Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant

Importance of the field: Tacrolimus is the most commonly used immunosuppressive agent following solid-organ transplantation in children. Its clinical use, however, is complicated by side effects (mainly nephrotoxicity), narrow therapeutic index and pharmacokinetic variability which can result in an increased risk of treatment failure or toxicity. Studies examining inter-individual differences in the expression of the ABCB1 (ATP-binding cassette, subfamily B, member 1) gene (which encodes the drug transporter, P-gp) and its genetic polymorphisms have attempted to elucidate variations in tacrolimus response and disposition in children.

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis.

Objective To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. Methods Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the “gold standard measure,” chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. Results The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. Conclusion We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.

An interprofessional approach to improving paediatric medication safety.

BACKGROUND: Safe drug prescribing and administration are essential elements within undergraduate healthcare curricula, but medication errors, especially in paediatric practice, continue to compromise patient safety. In this area of clinical care, collective responsibility, team working and communication between health professionals have been identified as key elements in safe clinical practice. To date, there is limited research evidence as to how best to deliver teaching and learning of these competencies to practitioners of the future.

METHODS: An interprofessional workshop to facilitate learning of knowledge, core competencies, communication and team working skills in paediatric drug prescribing and administration at undergraduate level was developed and evaluated. The practical, ward-based workshop was delivered to 4th year medical and 3rd year nursing students and evaluated using a pre and post workshop questionnaire with open-ended response questions.

RESULTS: Following the workshop, students reported an increase in their knowledge and awareness of paediatric medication safety and the causes of medication errors (p < 0.001), with the greatest increase noted among medical students. Highly significant changes in students' attitudes to shared learning were observed, indicating that safe medication practice is learnt more effectively with students from other healthcare disciplines. Qualitative data revealed that students' participation in the workshop improved communication and teamworking skills, and led to greater awareness of the role of other healthcare professionals.

CONCLUSION: This study has helped bridge the knowledge-skills gap, demonstrating how an interprofessional approach to drug prescribing and administration has the potential to improve quality and safety within healthcare.