To develop standards and recommendations for transitional care for young people (YP) with juvenileonset rheumatic and musculoskeletal diseases ( jRMD). The consensus process involved the following: (1) establishing an international expert panel to include patients and representatives from multidisciplinary teams in adult and paediatric rheumatology; (2) a systematic review of published models of transitional care in jRMDs, potential standards and recommendations, strategies for implementation and tools to evaluate services and outcomes; (3) setting the framework, developing the process map and generating a first draft of standards and recommendations; (4) further iteration of recommendations; (5) establishing consensus recommendations with Delphi methodology and (6) establishing standards and quality indicators. The final consensus derived 12 specific recommendations for YP with jRMD focused on transitional care. These included: high-quality, multidisciplinary care starting in early adolescence; the integral role of a transition coordinator; transition policies and protocols; efficient communications; transfer documentation; an open electronic-based platform to access resources; appropriate training for paediatric and adult healthcare teams; secure funding to continue treatments and services into adult rheumatology and the need for increased evidence to inform best practice. These consensus-based recommendations inform strategies to reach optimal outcomes in transitional care for YP with jRMD based on available evidence and expert opinion. They need to be implemented in the context of individual countries, healthcare systems and regulatory frameworks.

Purpose: The aim of this study was to define the pharmacokinetics of carboplatin in children and use the data to develop a pediatric dose formula. It was anticipated that renal function would be a major determinant of carboplatin disposition and the relationship between carboplatin clearance and glomerular filtration rate (GFR) was examined in detail.Patients and Methods: Plasma carboplatin pharmacokinetics were measured as ultrafiltrable platinum in 22 patients (5 to 63 kg) following 200 to 1,000 mg/m2 of carboplatin. GFR was measured by the plasma clearance of chromium 51-edathamil ( treatment of neuroblastoma, pediatric brain tumors, and germ cell tumors, and the use of the drug in these diseases is increasing.'3 Studies in adults have shown that the pharmacokinetics of carboplatin have a major impact on the toxicity of the drug and also, probably, on its activity. Thus, a number of investigations have shown a relationship between carboplatin exposure, expressed as the area under the plasma carboplatin concentration versus time curve (AUC), and tolerance to the drug, in particular thrombocytopenia. 6The work reported by Horwich et al 7 with testicular teratoma patients suggests that inadequate carboplatin exposure (AUC < 4 mg/mL-min) may compromise activity in this chemotherapy-curable disease. Similarly, a retrospective analysis reported by Jodrell et al 8 implied that ovarian cancer patients who received carboplatin at doses calculated to have produced AUC values less than 4 mg/ mL* min were less likely to achieve a response than those calculated to have experienced exposures greater than 4 mg/mL, min. Finally, preliminary results from a randomized study in ovarian cancer of an AUC of 6 mg/ mL* min administered every 4 weeks for six courses vs an AUC of 12 mg/mL-min administered every 4 weeks for four courses, suggests that the complete response rate is higher in the high AUC arm. 9In adults, for a given surface area-based dose of carboplatin, the AUC achieved varies over a twofold to

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Summary The purpose of the study was to evaluate the incidence, risk factors and changes in severity with time of cisplatin nephrotoxicity in children. A total of 35 children underwent measurement of glomerular filtration rate (GFR) and tubular function after completion of cisplatin chemotherapy. No child received ifosfamide. A clinically relevant 'nephrotoxicity score' was derived from GFR and serum magnesium. Followup studies were performed in 16 children at 1 year and in 15 at 2 years after cisplatin. Considerable interpatient variability in nephrotoxicity was observed. Treatment was modified in three patients because of nephrotoxicity. GFR was low in 18 out of 31 patients. Proximal nephron toxicity caused hypomagnesaemia in ten patients and hypocalcaemia in five patients. Elevated urinary N-acetylglucosaminidase excretion was seen in 22 out of 30 children, indicating subclinical tubular toxicity. Nephrotoxicity was less severe in children who received cisplatin courses at a dose rate of 40 mg m-2 dar' than in those who received higher dose rates (P < 0.005), but there was no correlation with total dose received. Follow-up studies revealed partial recovery of GFR (P < 0.05). Glomerular and proximal nephron toxicity are common in children treated with cisplatin, and more severe at higher dose rates. Despite partial recovery of GFR, the long-term outcome of nephrotoxicity remains unknown and careful monitoring of chronic toxicity is necessary.Keywords: cisplatin; nephrotoxicity; children The use of combination chemotherapy has led to dramatic improvements in the survival rates from many childhood malignancies during the last three decades. However, cytotoxic drugs may also cause severe and chronic side-effects, leading to permanent ill-health, disability or even premature death (Morris Jones and Craft, 1990). The development of effective strategies to prevent these adverse events depends on careful evaluation of toxicity both during and after treatment.In view of its established efficacy, cisplatin has retained an important role in the treatment of several childhood solid tumours, including neuroblastoma, osteosarcoma, hepatic and brain tumours, despite the increasing use of its apparently less nephrotoxic analogue carboplatin. Indeed, recent evidence has suggested that cisplatin may be more active than carboplatin in some germ cell tumours in adolescents and adults (Bajorin et al, 1993). However, even with the use of hyperhydration and other protective measures, nephrotoxicity is still a common and potentially serious adverse effect of cisplatin in both adults (Madias and Harrington, 1978;Schilsky et al, 1982;Daugaard and Abildgaard, 1989) and children (Womer et al, 1985;Brock et al, 1991). Despite numerous publications concerning cisplatin nephrotoxicity in adults, there is less information and no clear consensus on the importance of patient-and treatment-related risk factors for the development of nephrotoxicity in children. Furthermore, as there are few data concerning the long-term outcome of cisplatin nep...

1 Cyclophosphamide pharmacokinetics were measured in 38 children with cancer. 2 A high degree of inter-patient variation was seen in all pharmacokinetic parameters. Cyclophosphamide half-life varied between 1.1 and 16.8 h, clearance varied between 1.2 and 10.61 h-l m P 2 and volume of distribution varied between 0.26 and 1.48 1 kg-'. 3 The half-life of cyclophosphamide was prolonged at high dose levels (P = 0.008). 4 Children who had received prior treatment with dexamethasone showed a mean increase in clearance of 2.5 1 h-l m P 2 (P=O.OOl) presumably as a result of CYP450 enzyme induction. 5 Treatment with allopurinol or chlorpromazine was associated with a significant increase in cyclophosphamide half-life (P < 0.001 in both cases). 6 Dose and concurrent treatment may influence cyclophosphamide metabolism in vivo and thus potentially alter the drugs therapeutic effect.