Paediatric uveitis: a Sydney clinic experience

PURPOSE: The aim of this study was to retrospectively review uveitis cases at The Children's Hospital at Westmead, Sydney, since its inception in 1997 to 2001, including patients presenting at the Camperdown, Sydney, campus between 1989 and 1997 attending Westmead for further care. Comparison is made with international centres. METHODS: Information was obtained from medical records. RESULTS: Forty patients (53 eyes) presented, of whom 23 (57.5%) were female and 17 (42.5%) were male (mean age 6.7 years). Of 53 eyes, 35 (66%) had anterior uveitis, three (5.7%) intermediate uveitis, seven (13.2%) posterior uveitis and eight (15.1%) panuveitis. Twenty-seven (67.5%) patients had disease unilaterally and 13 (32.5%) bilaterally. Twenty-four (60%) cases were idiopathic. Seven (17.5%) cases were associated with juvenile rheumatoid arthritis, three (7.5%) with herpes zoster, two (5%) with herpes simplex, two (5%) with toxocara, one (2.5%) with toxoplasma, and one (2.5%) with ulcerative colitis. Complications included cataract in 14 (26.4%) eyes; band keratopathy in four (7.5%) eyes; macular scarring in three (5.7%) eyes; and glaucoma in four (7.5%) eyes. Last measured acuity was 6/6 for 19 (35.8%) eyes, < or =6/18 for 15 (28.3%) eyes and <6/60 for eight (15.1%) eyes. CONCLUSIONS: Despite small numbers, the comparisons of this study with some international studies, and its contrasts with other studies, are due to similarities and differences amongst these studies with respect to factors of referral bias, and the aetiological basis of disease.     

Frequency and characteristics of hospital admissions associated with drug-related problems in paediatrics

AIM: To determine the frequency of paediatric hospital admissions associated with drug-related problems (DRPs) at two Australian hospitals. METHODS: The investigator and ward pharmacists prospectively screened eligible patients. A multidisciplinary panel reviewed data and established causality, preventability and clinical significance classifications. RESULTS: Over 22 weeks of data collection, a total of 11,564 patients were admitted, 2933 met eligibility criteria. Of those eligible, 127 [4.3%, 95% confidence interval (CI) 3.6, 5.0] were judged to have hospital admissions associated with DRPs. Direct costs associated with DRPs identified totalled pounds 100,707. Of the 81 cases assessed for preventability, 46.9% were deemed preventable. CONCLUSIONS: This research has provided information on the nature and characteristics of paediatric DRPs associated with hospital admissions.     

Portfolios for assessment of paediatric specialist registrars

INTRODUCTION: In 1997 the Royal College of Paediatrics and Child Health introduced portfolios to guide and monitor the learning of specialist registrars. We studied their value for assessment. METHODS: Using Bigg's SOLO criteria we devised a marking scheme based on 6 domains of competence: clinical, communication, teaching and learning, ethics and attitudes, management and evaluation, and creation of evidence. We rated portfolios according to quality of evidence presented and expectations by year of training. We similarly assessed trainee performance in the annual record of in-training assessment (RITA) interview. Specific advice based on the results of the first portfolio assessments was circulated to all trainees, instructing them to increase the structure and decrease the bulk of portfolios. A second sample of portfolios was reviewed a year later, using similar evaluations, to determine the effects. RESULTS: A total of 76 portfolios were assessed in year 1 by a single rater; 30 portfolios were assessed in year 2 by 2 independent raters. The quality of documentation improved from year 1 to year 2 but there was no significant increase in portfolio scores. The inter-rater correlation coefficient of the portfolio assessment method was 0.52 (Cohen's kappa 0.35). The inter-rater correlation coefficient of the RITA interview was 0.71 (Cohen's kappa 0.38). There was moderate inter-assessment correlation between portfolios and RITA interviews (kappa 0.26 in year 1 and 0.29 in year 2). Generalisability analysis suggested that 5 successive ratings by a single observer or independent ratings by 4 observers on the same occasion would be needed to yield a generalisability coefficient > 0.8 for overall portfolio rating. CONCLUSIONS: This method of portfolio assessment is insufficiently reliable as a sole method for high stakes, single-instance assessment, but has a place as part of a triangulation process. Repeated portfolio assessment by paired observers would increase reliability. Longer term studies are required to establish whether portfolio assessment positively influences learner behaviour.     

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.     

Population pharmacokinetics and dose simulation of carvedilol in paediatric patients with congestive heart failure

Aims

To investigate the ontogeny of carvedilol pharmacokinetics and to develop an age-appropriate carvedilol dosing strategy for paediatric patients.

Methods

Data were derived from a prospective, nonplacebo-controlled study of carvedilol for the treatment of paediatric patients with congestive heart failure and analysed using a nonlinear mixed-effects modelling approach (NONMEM, Version V 1.1). The population pharmacokinetic model was further utilized for simulations of different carvedilol dosing strategies.

Results

Four hundred and eighty carvedilol plasma concentrations of 41 patients (0.1–19.3 years; median 3.5) were included in the analysis. A two-compartment model with first-order absorption and absorption lag served as structural model. Weight and age were the most important covariates for carvedilol pharmacokinetics. The weight-adjusted clearance was highest for the younger patients with 2.7 l h⁻¹ kg⁻¹ for a 1-year-old patient compared with 0.7 l h⁻¹ kg⁻¹ for a 19.3-year-old patient. Dose simulations revealed that the area under the plasma concentration–time curve (AUC) as a measure of drug exposure increased with age despite constant doses with respect to body weight. For infants (28 days to 23 months), children (2–11 years) and adolescents (12–15 years) daily doses of 3, 2 and 1 mg kg⁻¹, administered in two or three discrete doses, were necessary to reach an exposure comparable to adults receiving 0.7 mg kg⁻¹ day⁻¹.

Conclusion

The ontogeny of carvedilol pharmacokinetics in paediatric patients depends on age and weight. Dose simulations revealed that younger patients have to be treated with higher doses with respect to body weight to reach the same exposure as adults.

What is already known about this subject

• Applying in silico tools such as population pharmacokinetic analysis and simulation will help to find adequate dosing strategies and increase the probability of success for a randomized controlled trial.
• Up to now, for carvedilol in paediatric patients with congestive heart failure (CHF) the dose has been linearly extrapolated from adults, but the results with this dosing strategy are ambiguous.
• Further trials are necessary to establish carvedilol for paediatric patients with CHF.

What this study adds

• Carvedilol pharmacokinetics in paediatric patients with CHF depends on the weight and age of the patient.
• Therefore, the drug exposure differs substantially between patients of different ages receiving the same dose with respect to body weight.
• Simulations revealed that an age-adjusted carvedilol dosing strategy with higher doses for younger patients with respect to body weight is preferable to a uniform one.

     

An adapted walking intervention for a child with Pitt Hopkins syndrome*

Purpose: To investigate the effects of a community-based adapted walking intervention on a child with Pitt Hopkins syndrome (PTHS).

Methods: A four-year old boy with PTHS participated in a 12-week intervention comprising five one-hour long walking sessions per week at a local daycare. Walking sessions used the Upsee mobility device (Firefly by Leckey Ltd., Ireland). Outcome measures included Goal Attainment Scaling and the Mobility Ability Participation Assessment.

Results: Parental and caregiver goals for social interaction, physical activity and physical health surpassed expectations by post-testing. Gains were not sustained at three months follow-up. The participant’s ability and mobility may have increased following the intervention.

Conclusions: Participants with PTHS may benefit from regular physical activity and early intervention. The Upsee mobility device is a feasible and fun way to promote inclusive community-based physical activity and social engagement in a young child with PTHS. Further research into the health benefits of physical activity and the Upsee for children with PTHS may be warranted.

• Implications for Rehabilitation

• Physical activity may be beneficial for a child with Pitt Hopkins syndrome, a rare genetic disorder.

• New design, implementation of mobility intervention for a child with neurodevelopmental disabilities.

• The Upsee mobility device may offer physical benefits for a child with a neurodevelopmental disability.

• The Upsee mobility device may offer social benefits for a child with a neurodevelopmental disability.

     

The most difficult clinical situations: a survey of Victorian general paediatricians

OBJECTIVE: To identify which clinical situations are the most difficult to manage for general paediatricians in Victoria, Australia. METHODS: Self-administered questionnaires were sent to general paediatricians in Victoria. They were asked their opinions regarding what were the most difficult and the most dangerous clinical situations with which they deal. RESULTS: The response rate was 64% (63 out of 98 questionnaires sent). The general paediatricians surveyed believed that behavioural, developmental and psychosocial conditions were the most difficult to deal with; conduct disorder was the most nominated clinical category (26% of respondents). The 'dangerous' cases nominated were predominately traditional medical cases. The most commonly nominated category was sepsis and shock (21% of respondents). The most difficult and dangerous clinical situations overall for general paediatricians in Victoria appear to be in the areas of sepsis, child protection, paediatric and neonatal resuscitation, depression and suicide, raised intracranial pressure, intravenous fluid management, and communication with parents and adolescents. CONCLUSIONS: The present survey provides useful information to help with training-programme design and it gives trainee paediatricians an idea of what experienced paediatricians find difficult. Severe behavioural, family and social difficulties, as well as neonatal and childhood resuscitation, severe sepsis, raised intracranial pressure, and intravenous fluid management were the clinical situations most frequently described as difficult.