Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome.

Down's syndrome (DS) is a genetic disorder caused by full or partial trisomy of human chromosome 21 and presents with many clinical phenotypes including a reduced incidence of solid tumours. Recent work with the Ts65Dn model of DS, which has orthologues of about 50% of the genes on chromosome 21 (Hsa21), has indicated that three copies of the ETS2 (ref. 3) or DS candidate region 1 (DSCR1) genes (a previously known suppressor of angiogenesis) is sufficient to inhibit tumour growth. Here we use the Tc1 transchromosomic mouse model of DS to dissect the contribution of extra copies of genes on Hsa21 to tumour angiogenesis. This mouse expresses roughly 81% of Hsa21 genes but not the human DSCR1 region. We transplanted B16F0 and Lewis lung carcinoma tumour cells into Tc1 mice and showed that growth of these tumours was substantially reduced compared with wild-type littermate controls. Furthermore, tumour angiogenesis was significantly repressed in Tc1 mice. In particular, in vitro and in vivo angiogenic responses to vascular endothelial growth factor (VEGF) were inhibited. Examination of the genes on the segment of Hsa21 in Tc1 mice identified putative anti-angiogenic genes (ADAMTS1and ERG) and novel endothelial cell-specific genes, never previously shown to be involved in angiogenesis (JAM-B and PTTG1IP), that, when overexpressed, are responsible for inhibiting angiogenic responses to VEGF. Three copies of these genes within the stromal compartment reduced tumour angiogenesis, explaining the reduced tumour growth in DS. Furthermore, we expect that, in addition to the candidate genes that we show to be involved in the repression of angiogenesis, the Tc1 mouse model of DS will permit the identification of other endothelium-specific anti-angiogenic targets relevant to a broad spectrum of cancer patients.

Psychosocial support for children and families requiring renal replacement therapy.

Chronic kidney disease (CKD) and the need for renal replacement therapy (RRT) can place a great strain on the child and family. As well as the medical and nutritional prescription, each child and family requires an individual psychosocial prescription that requires input from multiprofessional team members. The information needs of each child and family need to be constantly evaluated as well as the choice of therapy in relation to social, psychological and economic factors. Many tertiary units lack adequate "time" to deliver such assessments and coordinate the support and respite care for those on long-term dialysis, especially when significant numbers of children are now accepted onto RRT programmes with co-morbidities. National and international standards are needed for the staffing of comprehensive tertiary paediatric renal units as well as studies evaluating supportive care to families.

Adherence to transition guidelines in European paediatric nephrology units.

BACKGROUND: There is increasing focus on the problems involved in the transition and transfer of young adult patients from paediatric to adult renal units. This situation was addressed by the 2011 International Pediatric Nephrology Association/International Society of Nephrology (IPNA/ISN) Consensus Statement on transition. METHODS: We performed a survey of transition practices of 15 paediatric nephrology units across Europe 2 years after publication of the consensus statement. RESULTS: Two thirds of units were aware of the guidelines, and one third had integrated them into their transition practice. Forty-seven per cent of units transfer five or fewer patients with chronic kidney disease (CKD) stage 5 per year to a median of five adult centres, with higher numbers of CKD stages 2-4 patients. Seventy-three per cent of units were required by the hospital or government to transfer patients by a certain age. Eighty per cent of units commenced transition planning after the patient turned 15 years of age and usually within 1-2 years of the compulsory transfer age. Forty-seven per cent of units used a transition or transfer clinic. Prominent barriers to effective transition were patient and parent attachment to the paediatric unit and difficulty in allowing the young person to perform self-care. CONCLUSIONS: Whereas awareness of the consensus statement is suboptimal, it has had some impact on practice. Adult nephrologists receive transferred patients infrequently, and the process of transition is introduced too late by paediatricians. Government- and hospital-driven age-based transfer policies distract focus from the achievement of competencies in self care. Variable use of transition clinics, written patient information and support groups is probably due to economic and human-resource limitations. The consensus statement provides a standard for evolving and evaluating transition policies jointly agreed upon by paediatric and adult units.

Encapsulating peritoneal sclerosis in children on chronic PD: a survey from the European Paediatric Dialysis Working Group.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) that is associated with significant morbidity and mortality in adults. There are scarce data for children. We performed a 10-year survey to determine the prevalence, risk factors and outcome for EPS in children. METHODS: Chronic PD patients in 14 dialysis units participating in the European Paediatric Dialysis Working Group between January 2001 and December 2010 were included in this study. RESULTS: Twenty-two cases of EPS were reported (prevalence 1.5%; 8.7 per 1000 patient-years on PD). Median PD vintage was 5.9 (1.6-10.2) in EPS and 1.7 (0.7-7.7) years in the remainder of the PD population (P<0.0001). EPS patients had a significantly higher peritonitis rate than non-EPS patients (P=0.2). EPS was diagnosed while the child was on PD in 17 (77%), after conversion to haemodialysis (HD) in 3 and after transplantation in 2. Fifteen of 17 (88%) developed ultrafiltration (UF) failure. The median interval between UF failure and presentation with bowel obstruction was 2.8 (0.02-5.8) months. Twenty (91%) had clinical and radiological signs of bowel obstruction. Enterolysis was performed in 14 and 19 received immunosuppression or tamoxifen. Nine required parenteral nutrition. At final follow-up 4.8 (1.3-8.7) years after EPS diagnosis, 3 patients died, 11 had a functioning transplant and 8 were on HD. CONCLUSIONS: The prevalence of EPS in European children on PD is comparable with that of adult PD patients, but mortality from paediatric EPS is significantly lower. A high index of suspicion is required for the diagnosis of EPS in children with longer dialysis duration, a high peritonitis rate and UF failure.

Clinical practice recommendations for the care of infants with stage 5 chronic kidney disease (CKD5).

BACKGROUND: To provide recommendations for the care of infants with stage 5 chronic kidney disease (CKD5). SETTING: European Paediatric Dialysis Working Group. DATA SOURCES: Literature on clinical studies involving infants with CKD5 (end stage renal failure) and consensus discussions within the group. RECOMMENDATIONS: There has been an important change in attitudes towards offering RRT (renal replacement therapy) to both newborns and infants as data have accumulated on their improved survival and long-term outcomes. The management of this challenging group of patients differs in a number of ways from that of older children. The authors have summarised the basic recommendations for treating infants with CKD5 in order to support the multidisciplinary teams who endeavour on this difficult task.

Factors influencing choice of renal replacement therapy in European paediatric nephrology units.

BACKGROUND: Many factors may impact upon choice of renal replacement therapy (RRT) for children and adolescents, including patient and family choice, patient size and distance from the renal centre as well as logistic issues such as facilities and staffing at the unit. We report a survey of factors influencing treatment choice in 14 European paediatric nephrology units. METHODS: A questionnaire was developed by consensus and completed by 14 members of the European Paediatric Dialysis Working Group on facilities, staffing and family assessments impacting on choice of therapy as well as choice of therapy for 97 patients commencing initial RRT in 2011. RESULTS: All units offered all modalities of RRT, but there were limitations for pre-emptive transplantation (PET) and largely adult surgical dependence for creation of arteriovenous fistulae and transplantation. The average waiting time for a deceased donor kidney was 18.5 (range 3-36) months. Full time dietetic support was available in six of the 14 units. There was no social worker, psychology, play therapy or teaching support in three, two, seven and four units, respectively. Assessment by other members of the multidisciplinary team and home visits before choice of therapy was carried out in 50 % of units, and although all patients were discussed at team meetings, the medical opinion predominated. In terms of types of RRT, 50 % of patients were commenced on chronic peritoneal dialysis (PD), 34 % on haemodialysis (HD) and 16 % underwent pre-emptive transplantation (PET). Chronic PD predominated in patients aged <5 years and HD predominated in those aged >10 years. Patient and family choice and age or size of patient were predominant factors in choice of therapy with a predictable decline in renal function favouring PET and social factors HD. CONCLUSIONS: Chronic peritoneal dialysis predominated as primary choice of RRT, especially in younger children. The PET rates remain low. The influence of surgeons predominanted, and national transplant rules may be significant. Most units had insufficient multiprofessional support, which may impact upon initial choice of therapy as well as sustaining families through RRT.

Unilateral multicystic dysplastic kidney: does initial size matter?

BACKGROUND: We report the long-term follow-up of children with antenatally detected unilateral multicystic dysplastic kidney (MCDK) who were followed between 1985 and 2009. METHODS: Involution rates were documented over time based on the initial size of the MCDK, as documented on postnatal ultrasound (USS), as well as long-term complications and renal function. RESULTS: In 323 patients (182 male), 10 % of MCDK had involuted, as evidenced on the first postnatal USS, with survival function analysis showing the probability of complete involution to be 35 % in 249 patients by 2 years of age, 47 % in 180 patients by 5 years of age and 62 % in 94 patients by 10 years of age. There was a significant difference in the involution rates of MCKD at the 10-year follow-up between MCDK with an initial size of >5 cm versus MCDK with an initial size of ≤5 cm (p < 0.0001). No patients in the whole cohort developed sustained hypertension or malignancy during a median follow-up of 10.1 years (range 0.3-15.4 years). Median estimated glomerular filtration rate (eGFR) in 76 patients (7 at 5 years, 69 at 10 years) was 93 ml/min/1.73 m(2) (range 46-175 ml/min/1.73 m(2)), with 40 (53%) having an eGFR of between 90 and 140 ml/min/1.73 m(2). Twenty-three (30 %) of the 76 patients at 10 years had normal eGFR (90-140 ml/min/1.73 m(2)) as well as complete involution of the MCDK, compensatory hypertrophy of the contralateral kidney, no proteinuria and no hypertension. CONCLUSIONS: Larger MCDK at birth are less likely to involute during the first decade of life. However, conservative management remains justified due to the lack of complications. A minority of patients fulfil current criteria for discharge from specialty follow-up at 10 years.

Vascular access: choice and complications in European paediatric haemodialysis units.

BACKGROUND: European and U.S. guidelines emphasise that permanent vascular access in the form of arteriovenous fistulae (AVF) or grafts (AVG) are preferable to central venous catheters (CVC) in paediatric patients on long-term haemodialysis. We report vascular access choice and complication rates in 13 European paediatric nephrology units. METHODS: A survey of units participating in the European Pediatric Dialysis Working Group requesting data on type of vascular access, routine care and complications in patients on chronic haemodialysis between March 2010 and February 2011. RESULTS: Information was complied on 111 patients in 13 participating centres with a median age of 14 (range 0.25-20.2) years. Central venous catheters were used in 67 of 111 (60%) patients, with 42 patients (38%) having an AVF and two patients (2%) having an AVG. Choice of vascular access was significantly related to patient age, with patients with AVF/AVG having a median age of 16 years compared to 12 years for patients with CVCs (p < 0.001). Routine CVC exit site care and catheter lock solution use differed between centres. CVC infections requiring intravenous antibiotics were reported at a rate of 1.9 and exit site infections at a rate of 1.8 episodes/1000 catheter days. Overall infective complications necessitating CVC change occurred at a rate of 0.9 episodes/1000 catheter days. No infective complications were reported in patients with AVF/AVG access. The rate of CVC infections requiring intravenous antibiotics was significantly lower in patients in whom CVC exit sites were cleaned weekly as opposed to every dialysis session (relative risk with every session cleaning vs. weekly cleaning 2.58, 95% confidence interval 1.17-5.69). Catheter malfunction (inadequate blood flow) was a more prevalent complication necessitating 22.4 thrombolytic interventions/1000 catheter days and 2.1 CVC changes/1000 catheter days. CONCLUSIONS: Central venous catheters remain the predominant choice of vascular access in Europe despite problems of malfunction and infection. AVF/AVG were predominantly used in adolescents without reported complications. More regular exit site cleaning may predispose to CVC infection, but this observation requires prospective evaluation.

Growth in very young children undergoing chronic peritoneal dialysis.

Very young children with chronic kidney disease often have difficulty maintaining adequate nutrition, which contributes to the high prevalence of short stature in this population. Characteristics of the dialysis prescription and supplemental feeding via a nasogastric (NG) tube or gastrostomy may improve growth, but this is not well understood. Here, we analyzed data from 153 children in 18 countries who commenced chronic peritoneal dialysis at <24 months of age. From diagnosis to last observation, 57 patients were fed on demand, 54 by NG tube, and 10 by gastrostomy; 26 switched from NG to gastrostomy; and 6 returned from NG to demand feeding. North American and European centers accounted for nearly all feeding by gastrostomy. Standardized body mass index (BMI) uniformly decreased during periods of demand feeding and increased during NG and gastrostomy feeding. Changes in BMI demonstrated significant regional variation: 26% of North American children were obese and 50% of Turkish children were malnourished at last observation (P < 0.005). Body length decreased sharply during the first 6 to 12 months of life and then tended to stabilize. Time fed by gastrostomy significantly associated with higher lengths over time (P < 0.001), but adjustment for baseline length attenuated this effect. In addition, the use of biocompatible peritoneal dialysate and administration of growth hormone independently associated with improved length, even after adjusting for regional factors. In summary, growth and nutritional status vary regionally in very young children treated with chronic peritoneal dialysis. The use of gastrostomy feeding, biocompatible dialysis fluid, and growth hormone therapy associate with improved linear growth.

Transition from pediatric to adult renal services: a consensus statement by the International Society of Nephrology (ISN) and the International Pediatric Nephrology Association (IPNA).

The transfer of young patients from pediatric to adult renal care takes place after a transition process which involves both sides. It is important that it is individualized for each young person, focusing on self-management skills as well as assessing support structures. The consensus statement has been developed by the panel of adult and pediatric nephrologists and endorsed by the councils of both ISN and IPNA. It is hoped that the statement will provide a basis for the development of locally appropriate recommendations for clinical practice.

Endothelial alpha3beta1-integrin represses pathological angiogenesis and sustains endothelial-VEGF.

Integrin alpha3beta1 is a major receptor for laminin. The expression levels of laminins-8 and -10 in the basement membrane surrounding blood vessels are known to change during tumor angiogenesis. Although some studies have suggested that certain ligands of alpha3beta1 can affect angiogenesis either positively or negatively, either a direct in vivo role for alpha3beta1 in this process or its mechanism of action in endothelial cells during angiogenesis is still unknown. Because the global genetic ablation of alpha3-integrin results in an early lethal phenotype, we have generated conditional-knockout mice where alpha3 is deleted specifically in endothelial cells (ec-alpha3-/-). Here we show that ec-alpha3-/- mice are viable, fertile, and display enhanced tumor growth, elevated tumor angiogenesis, augmented hypoxia-induced retinal angiogenesis, and increased vascular endothelial growth factor (VEGF)-mediated neovascularization ex vivo and in vivo. Furthermore, our data provide a novel method by which an integrin may regulate angiogenesis. We show that alpha3beta1 is a positive regulator of endothelial-VEGF and that, surprisingly, the VEGF produced by endothelial cells can actually repress VEGF-receptor 2 (Flk-1) expression. These data, therefore, identify directly that endothelial alpha3beta1 negatively regulates pathological angiogenesis and implicate an unexpected role for low levels of endothelial-VEGF as an activator of neovascularization.

Deficiency of bone marrow beta3-integrin enhances non-functional neovascularization.

beta3-Integrin is a cell surface adhesion and signalling molecule important in the regulation of tumour angiogenesis. Mice with a global deficiency in beta3-integrin show increased pathological angiogenesis, most likely due to increased vascular endothelial growth factor receptor 2 expression on beta3-null endothelial cells. Here we transplanted beta3-null bone marrow (BM) into wild-type (WT) mice to dissect the role of BM beta3-integrin deficiency in pathological angiogenesis. Mice transplanted with beta3-null bone marrow show significantly enhanced angiogenesis in subcutaneous B16F0 melanoma and Lewis lung carcinoma (LLC) cell models and in B16F0 melanoma lung metastasis when compared with tumours grown in mice transplanted with WT bone marrow. The effect of bone marrow beta3-integrin deficiency was also assessed in the RIPTAg mouse model of pancreatic tumour growth. Again, angiogenesis in mice lacking BM beta3-integrin was enhanced. However, tumour weight between the groups was not significantly altered, suggesting that the enhanced blood vessel density in the mice transplanted with beta3-null bone marrow was not functional. Indeed, we demonstrate that in mice transplanted with beta3-null bone marrow a significant proportion of tumour blood vessels are non-functional when compared with tumour blood vessels in WT-transplanted controls. Furthermore, beta3-null-transplanted mice showed an increased angiogenic response to VEGF in vivo when compared with WT-transplanted animals. BM beta3-integrin deficiency affects the mobilization of progenitor cells to the peripheral circulation. We show that VEGF-induced mobilization of endothelial progenitor cells is enhanced in mice transplanted with beta3-null bone marrow when compared with WT-transplanted controls, suggesting a possible mechanism underlying the increased blood vessel density seen in beta3-null-transplanted mice. In conclusion, although BM beta3-integrin is not required for pathological angiogenesis, our studies demonstrate a role for BM beta3-integrin in VEGF-induced mobilization of bone marrow-derived cells to the peripheral circulation and for the functionality of those vessels in which BM-derived cells become incorporated.

Karyomegalic-like nephropathy, Ewing's sarcoma and ifosfamide therapy.

Karyomegalic interstitial nephropathy has been reported as a rare interstitial nephritis in adult patients. Histology shows atypical epithelial cells and large abnormal hyperchromatic nuclei with irregular outlines. We report 3 adolescent patients who all recovered from their initial treatment for Ewing's sarcoma but developed a tubulopathy attributed to ifosfamide therapy. Renal impairment resulted in biopsy, which showed features of karyomegalic nephropathy in all 3. One patient has progressed to haemodialysis. Recognition of the pathology may be important in similar patients. It is surmised that the unusual histological findings in these patients stem from a common pathogenesis which may be related to chemotherapeutic agent related nuclear damage. At present there is no specific treatment to prevent progressive renal impairment.

Self-reported quality of life in children and young people with chronic kidney disease.

Chronic kidney disease (CKD) would be expected to impact upon the quality of life (QoL) of children and young people; therefore, it is important that they are given the means to express their opinions about how they perceive their own QoL. We used the Generic Children's Quality of Life Measure (GCQ) in 225 paediatric renal patients (118 male, mean age 13.6 years, range 6.2-18.9 years) from seven UK centres. Of these, 47 were on dialysis (23 on haemodialysis), 128 were post-transplant (47 pre-emptive) and 49 had advanced CKD. A comparison between the 124 renal patients (65 male, mean age 11.2 years) in the same age range as the general population (6-14 years) showed a higher GCQ QoL score for the renal patients (p = 0.02). Analysis of the whole group of renal patients (n = 225) revealed no significant difference between the mean GCQ scores of participants in various treatment modalities (p = 0.26) and no significant differences between gender (p = 0.90) and age group (p = 0.44). The results indicate that young people can perceive their QoL as good despite living with what others may perceive as severe limitations. This may seem counter-intuitive, but QoL is a subjective measure and thus may be difficult to predict from observable limitations (health status). The GCQ is an ideal measure for use in annual departmental audits of generic paediatric QoL and may help to individualise the work of psychosocial teams with each patient.

Renal biopsies in children: current practice and audit of outcomes.

BACKGROUND: There is considerable variation in the way that children are prepared for and the techniques employed in a renal biopsy. There was national agreement between UK paediatric renal centres to review current practice and audit outcomes METHODS: An initial questionnaire survey was undertaken and a 12-month prospective audit performed of renal biopsies against agreed standards for the number of needle passes, adequacy of biopsy material and complication rates. RESULTS: Eleven of 13 centres participated. Information leaflets are sent pre-biopsy in five centres with only one using play preparation. Six of 11 routinely perform biopsies as day-case (DC) procedures and 6 use general anaesthesia (GA). Real-time ultrasound is the favoured method in eight centres. Biopsies are performed by nephrologists only in four centres, nephrologists with radiologists in five and radiology alone in two. Of 531 biopsies (352 native), 31% were performed as a DC with 49% being done under GA. The standard for the number of passes of native kidneys (95%). The major complication rate was higher than the standard of

Cutaneous warts in children before and after renal transplantation.

Cutaneous warts occur in 3.9-4.9% of children in the UK. The incidence is increased in organ transplant recipients and may be increased in patients with chronic kidney disease (CKD), since uraemia reduces the immune system's function. We surveyed the records from our CKD and renal transplant clinic to ensure patients with warts were identified and appropriately treated. Data were collected by questionnaire. The presence of warts, location, treatment, levels of pain and emotional upset were recorded. Nine of 49 (18.4%) pre-transplantation patients (33 male, median age 12.1 years) were currently suffering from warts compared with 17 of 60 (28.3%) post-transplantation patients (34 male, median age 13.9 years). A further 14 pre-transplantation and 16 post-transplantation patients had previously suffered from warts which had resolved. Forty-one patients had sought treatment for warts, mainly from primary care. Five patients, all having received transplants, were seen by a dermatologist. Self-rated levels of pain and emotional upset were generally low, apart from those of four adolescent patients who expressed significant emotional upset. We concluded that cutaneous warts are more common among CKD patients. Appropriate information and treatment are required before and after transplantation. The majority of warts can be treated in primary care, but selected patients with extensive warts that cause distress need early referral for dermatology opinion.

Core competencies for clinical ethics committees.

Clinical ethics committees (CECs) are increasing in number in the UK and have mostly developed in response to local interest, as opposed to being mandated as in the USA. However, there is no regulatory framework for UK CECs with no defined educational requirements or specification of core competencies for their members. The UK Clinical Ethics Network has consulted extensively with its members to set out, for the first time in the UK, the core competencies necessary for the provision of clinical ethics support. Recommendations for educational and membership requirements for CECs have also been made. Given the appropriate resources the standards proposed can be appropriately evaluated and are consistent with principles of ethical governance.

Continuous venovenous hemofiltration with or without extracorporeal membrane oxygenation in children.

OBJECTIVES: We report the frequency of usage, patient demographics, and outcomes in children treated with continuous venovenous hemofiltration (CVVH) in three pediatric intensive care units (PICUs), with one unit providing combined extracorporeal membrane oxygenation (ECMO) and CVVH. DESIGN: Prospective database analysis. SETTING: Three regional PICUs in the Trent Haemofiltration Network with two general PICUs admitting 450-500 patients annually and the other providing regional cardiac support and a supraregional service for ECMO (600-650 admissions annually with 50 ECMO patients). PATIENTS: Children who underwent CVVH alone or in combination with ECMO or other therapies between January 2000 and December 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 115 children (58 male) treated, with a median age of 18 months (range 1 day to 17 yrs) and median weight of 12 kg (range 1.8-119 kg). In the two PICUs without ECMO, CVVH was undertaken in 2.5% of admissions annually compared with 3% of annual admissions to the PICU with an ECMO service. Fifty-five patients received CVVH alone (group 1), while 53 patients underwent CVVH in conjunction with ECMO (group 2). In addition, five patients received plasmafiltration followed by CVVH, and two patients were treated with combined CVVH and molecular adsorbents recirculating system. Mean duration of therapy in group 1 was 142 hrs (1-840 hrs) and in group 2,231 hrs (3-1104 hrs). Overall patient survival was 43% with 29 of 55 (53%) CVVH patients surviving and 18 of 53 (34%) of those treated with ECMO plus CVVH. CONCLUSIONS: Performing CVVH in a heterogeneous population with large age and weight ranges poses significant clinical and technical challenges. The low frequency of CVVH use, as well as the use of other extracorporeal therapies, also raises problems with maintaining nursing skills. Objective clinical and biochemical markers for commencing CVVH alone or in combination with ECMO remain to be defined.

Preparation of chldren undergoing nuclear medicine procedures.

OBJECTIVES: To re-evaluate implementation of standards developed for children undergoing nuclear medicine procedures and the effect of introducing cannulation by the day case coordinating nurse. METHODS: A prospective audit was undertaken of 177 children undergoing day case nuclear medicine procedures in a teaching hospital department used for paediatric and adult patients. Audit proformas were completed by both ward and nuclear medicine staff at the time of procedure over a 15 month period and the results compared to a previously published audit. RESULTS: Standards were met for providing families with relevant information and giving them sufficient notice about scan dates. Most children were offered surface analgesia for venepuncture and play preparation before the procedure. The day case coordinating nurse successfully performed 89 per cent of cannulations with the percentage performed by the SHOs falling from 71 per cent to six per cent between 2003 and 2006. Sixty-four per cent and 95 per cent of children were successfully cannulated after one and a total of three attempts respectively. Only two per cent of children were sedated. The percentage of children scanned within 0-20 minutes of the scheduled time improved over three years from 71 per cent to 97 per cent. CONCLUSIONS: The development of the day case coordinating nurse's role to include cannulation has had a positive effect on the efficiency of radionuclide procedures due to an increased success rate of cannulation and quicker transfer of the children from the ward to the nuclear medicine department. Improved standards have ensured that the patient pathway involving preparation, information and support for children and families has been enhanced. The audit standards could be used for comparison between units.