Rachel M. Taylor

Wilson's disease in children: 37‐Year experience and revised King's score for liver transplantation

Wilsons disease (WD) is a rare liver‐based disorder of copper metabolism. Prognostic criteria described by our group in 1986 to predict death without transplantation have not been universally validated. The clinical features of 88 children were reviewed, retrospectively in 74 and prospectively in 14. Data from the retrospectively recruited patients that died or survived on long‐term chelation were used to evaluate the validity of our old scoring system and to devise a new prognostic index, then assessed in the 14 prospectively recruited patients. Using the old scoring system, 5 children scoring ≥ 7, the cutoff value for death without transplantation, survived, whereas 4 scoring ≤ 7 died (sensitivity 87% and specificity 90%). A new index based on serum bilirubin, international normalized ratio, aspartate aminotransferase (AST), and white cell count (WCC) at presentation identified a cutoff score of 11 for death and proved to be 93% sensitive and 98% specific, with a positive predictive value of 88%. When the new index was evaluated prospectively in 14 patients, it predicted the need for transplantation in only the 4 who required it, although 1 child with a score of 11 survived on medical treatment. In conclusion, the new Wilson Index is more sensitive and specific in predicting mortality without transplantation than the old scoring system, but needs to be validated in a larger number of patients. (Liver Transpl 2005;11:441–448.)

The experience of living with a chronic illness during adolescence: a critical review of the literature.

AIMS To identify and critique literature on the adolescent lived experience of chronic illness; describe the lived experience; and to make recommendations for clinical practice. BACKGROUND Young people with chronic illness have the same developmental issues as those who are healthy. However, development can be disrupted by treatment and repeated hospitalisation. While the physical consequences of chronic illness on development have been established, the subjective personal experience is less known. DESIGN Literature review. METHODS Electronic databases and hand searches were made of the literature published between January 1990-September 2007. Literature was eligible for inclusion if it involved adolescents between 10-19 years, and published in English and used qualitative methods of data collection. Methodological quality was assessed using the criteria described by Cesario et al. [Journal of Obstetrics, Gynaecology and Neonatal Nursing 31 (2002) 31]. CONCLUSIONS Twenty studies were identified involving young people with a wide variety of chronic illnesses. The study quality was variable, however, generally the majority was assessed as being good or fair. Seven common themes were found between the identified studies: developing and maintaining friendships; being normal/getting on with life; the importance of family; attitude to treatment; experiences of school; relationship with the healthcare professionals; and the future. RELEVANCE TO PRACTICE As there was commonality in themes between studies strategies to lessen the burden of chronic illness during adolescence do not necessarily need to be disease specific. Nurses need to focus on treating the young person rather than their illness.

Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure

Acute liver failure (ALF) carries a high mortality in children. N‐acetylcysteine (NAC), an antioxidant agent that replenishes mitochondrial and cytosolic glutathione stores, has been used in the treatment of late acetaminophen‐induced ALF and non‐acetaminophen‐induced ALF. In our unit, NAC was introduced as additional treatment for non‐acetaminophen‐induced ALF in 1995. The aim of this study was to evaluate the safety and efficacy of NAC in children with ALF not caused by acetaminophen poisoning. A retrospective review of medical records of 170 children presenting with nonacetaminophen‐induced ALF between 1989 and 2004 was undertaken. ALF was defined as either international normalized ratio of prothrombin time (INR) > 2 and abnormal liver function or INR >1.5 with encephalopathy and abnormal liver function. Children were divided into the following groups: Group 1 (1989‐1994), standard care (n = 59; 34 [58%] male; median age 2.03 yr, range 0.003‐15.8 yr); and Group 2 (1995‐2004), standard care and NAC administration (n = 111; 57 [51%] male; median age 3.51 yr, range 0.005‐17.4 yr). NAC was administered as a continuous infusion (100 mg/kg/24 hours) until INR < 1.4, death, or liver transplantation (LT). The median duration of NAC administration in Group 2 was 5 (range, 1‐77) days. Complications were noted in 8 (10.8%) children: rash in 3, arrhythmia in 3, and dizziness and peripheral edema in 1. One child had an allergic reaction (bronchospasm) and NAC was stopped. A total of 41 (71%) children in Group 1 vs. 85 (77%) in Group 2 required admission to intensive care, P = not significant (ns). The length of intensive care stay was 6 (range, 1‐58) days in Group 1 vs. 5 (range, 1‐68) days in Group 2, P = ns and length of hospital stay was 25 (range, 1‐264) days vs. 19 (range, 1‐201) days, P = 0.05. The 10‐yr actuarial survival was 50% in Group 1 compared to 75% in Group 2, P = 0.009. Survival with native liver occurred in 13 (22%) in Group 1 vs. 48 (43%) in Group 2, P = 0.005; 15 (25%) in Group 1 died without transplant vs. 21 (19%) in Group 2, P = ns; and LT was performed in 32 (54%) vs. 42 (38%), P = ns. Death after transplantation occurred in 15 (39%) in Group 1 vs. 8 (16%) in Group 2, P = 0.02. In conclusion, NAC is safe in non‐acetaminophen‐induced ALF. In this retrospective study NAC was associated with a shorter length of hospital stay, higher incidence of native liver recovery without transplantation, and better survival after transplantation. Liver Transpl, 2007.

A critical review of the health-related quality of life of children and adolescents after liver transplantation

We critically examined research on health‐related quality of life (HRQL) in children and adolescents after liver transplantation. The specific aims were to identify research studies on HRQL after liver transplantation, to critique the methodological quality of the studies, to estimate overall HRQL after transplant, and to make recommendations for future research. Databases searched included Medline, Cumulative Index to Nursing and the Allied Health Literature, PsycINFO, EMBASE, Allied and Complementary Medicine, Institute for Scientific Information Web of Science, and Applied Social Sciences Index and Abstracts. Searches also were made on related Web sites and proceedings of transplantation and associated conferences. Eligible studies involved children between birth and 18 years of age who received isolated orthotopic, auxiliary, or living related liver transplantation. HRQL was assessed through 2 or more of the domains of physical health, psychological functioning, social functioning, family functioning, or general well‐being. Eligible studies were abstracted, assessed for methodological quality, and synthesized using the sign test to provide an indication of the effect of liver transplantation on each HRQL domain. The synthesis of findings suggested an improvement in HRQL in comparison with pretransplant status; there was a trend toward a worse HRQL in comparison with the healthy population and better than those with other chronic illnesses. In conclusion, liver transplantation in childhood has a negative impact on some aspects of HRQL. However, this finding is tentative because of the small number of studies and variable study quality found. (Liver Transpl 2005;11:51–60.)

Mutations in the RP2 Gene Cause Disease in 10% of Families with Familial X-Linked Retinitis Pigmentosa Assessed in This Study

We wish to thank Dr. Wolfgang Berger for kindly providing the primer sequences 2 wk prior to publication. The authors also wish to thank all the clinicians and participating families who have supported our research over the years; Dr. Kamal Dulai for invaluable computer support; and Ilaria Zito for running SSCP gels. This research was supported by The Wellcome Trust (grant 051733/Z/97 to A.J.H.), the Guide Dogs for the Blind Association (grant 95-52A to D.L.T.), and the British RP Society.

Nutritional support in critically ill children.

BACKGROUND & AIMS Enteral nutrition is the feeding method of choice during critical illness, but in some cases as few as 25% are fed appropriately. The aim was to retrospectively review the administration of nutrition to critically ill children. METHODS The notes of 95 children over the age of 1 year who were in PICU>or=3 days were reviewed and information related to the delivery of nutrition was obtained. RESULTS Fifty-nine per cent were fed within 24h of admission. Enteral nutrition was administered 54% of the time, 10% required parenteral nutrition and 9.5% received no nutritional support. Children only received a median 58.8 (range 0-277)% of their energy requirements, which could not be optimised until the 10th intensive care day. Energy intake was greater when supplemented with parenteral nutrition. Parenteral nutrition administration was interrupted 3 times while enteral nutrition was stopped 264 times, mainly to allow other clinical procedures to take place. For 75% of the study time, children had abnormal bowel patterns. Seventy-nine per cent were constipated for 3-21 days and 43% had diarrhoea of unknown aetiology. CONCLUSION This was a retrospective study to describe the efficiency of nutritional support in critically ill children. We have shown that it is possible to administer enteral nutrition safely. However, the difference between desirable intake and actual intake achieved suggests that a more pro-active approach should be adopted.

Can energy expenditure be predicted in critically ill children

Objective To determine whether critically ill children are hypermetabolic and to calculate whether predictive equations are appropriate for critically ill children. Design Prospective, clinical study. Setting Pediatric intensive care unit. Patients A total of 57 children (39 boys) aged 9 months to 15.8 yrs. Interventions None. Measurements and Main Results The median resting energy expenditure measurement measured by indirect calorimetry was 37.2 (range, 11.9–66.6) kcal·kg−1·day−1. This was significantly lower than would be predicted using either the Schofield (42.7 [26.9–65.4] kcal·kg−1·day−1) or Fleisch equations (42.8 [20.9–66.2] kcal·kg−1·day−1, p < .001) but significantly higher than the White equation developed specifically for pediatric intensive care units (26.2 [8.5–70.1] kcal·kg−1·day−1, p < .0001). Methods comparison analysis showed the limits of agreement were −484 to 300, −461 to 319, and −3.2 to 854 kcal/day, respectively. Multivariate analysis indicated the following factors contribute to hypometabolism and hypermetabolism: age (p = .006), sex (p = .034), time spent in the pediatric intensive care unit (p = .001), diagnosis (p = .015), weight (p = .009), temperature (p = .04), continuous infusion for sedation (p = .04), and neuromuscular blockade (p = .03). Conclusions Children do not become hypermetabolic during critical illness. These data suggest that agreement between resting energy expenditure and the predictive equations are so broad that they are inappropriate for use in critically ill children.

Autosomal dominant cone-rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase

OBJECTIVE To describe the clinical features of autosomal dominant cone-rod retinal dystrophy (CRD) in a British family mapping to chromosome 17p12-p13 (CORD6), with a heterozygous mutation (Glu837Asp/ Arg838Ser) of GUCY2D. DESIGN A prospective, clinical family survey. PATIENTS Ten affected members of a family with autosomal dominant CRD. METHODS Full clinical examinations were undertaken. Selected affected family members underwent electrophysiologic evaluation, scotopic static perimetry, dark adaptometry, and color vision assessment. MAIN OUTCOME MEASURES Clinical appearance and electroretinographic responses. RESULTS Typical clinical and electroretinographic features of childhood-onset CRD were recorded. In addition, moderate myopia and pendular nystagmus were seen in affected individuals. Color vision assessment in the youngest affected individual showed no color discrimination on a tritan axis, but retention of significant red-green discrimination. Electronegative electroretinogram responses were seen on electrophysiology in the only young family member examined. CONCLUSIONS The phenotype associated with GUCY2D CRD is clinically distinct from that associated with other dominant CRD loci. Unusual electroretinographic responses may indicate that this mutation of GUCY2D is associated with early defects in photoreceptor synaptic transmission to second-order neurons.

Study of the Factors Affecting Health-Related Quality of Life in Adolescents After Liver Transplantation

The aim of the study was to identify factors affecting health‐related quality of life (HRQL) in adolescents after liver transplantation. HRQL was measured using the CHQ‐CF87 in 55 adolescents, aged 12–18 years. Factors associated with HRQL included allograft morbidity, psychological and family‐related variables measured through standardized questionnaires. The domains of the CHQ‐CF87 were reduced using factor analysis to give physical, psychological and social domains. Impacting factors were identified through stepwise, multiple regression analysis. Adolescents had significantly lower HRQL in every domain except for role/social‐behavior and family cohesion compared to the general population. Adolescents experienced median 18 (range 4–31) symptoms related to immunosuppression, 40(75%) had one or more chronic illnesses related to immunosuppression and 12(22%) had a history of emotional difficulties. Self‐esteem and emotional health were similar to the general population but behavior and aspects of family function were lower. Following regression analysis, the factors associated with HRQL were: age at transplant, secondary chronic illness, symptom distress, headaches, history of emotional difficulties, self‐esteem and family conflict. These explained 57% of the variance in physical function, 61% of psychological function and 39% of social function. HRQL is significantly reduced in adolescents after transplantation, which could be related to immunosuppression and psychosocial factors.

Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation

Renal dysfunction of variable severity is being increasingly recognized as a major complication of calcineurin inhibitors (CI), in some patients even necessitating renal transplantation. Close and effective monitoring of the renal function is indicated. Current methods for this monitoring are calculation of the glomerular filtration rate (GFR) based on creatinine or exogenous substances like 51Cr‐EDTA. The first method is unreliable in children and the second is expensive and cumbersome. Cystatin C has been shown to be an accurate marker of glomerular filtration but has not been evaluated in a large cohort of pediatric patients before and after liver transplantation (LT). We evaluated the accuracy of cystatin C in 62 children (30 male) with LT, who had their 51Cr‐EDTA measured on 40 occasions prior to LT and on 47 occasions after LT. The reciprocal of cystatin C correlated better with 51Cr‐EDTA GFR (r = .78) than the reciprocal of creatinine (r = .40). Diagnostic accuracy in the identification of reduced GFR was assessed by ROC analysis. Cystatin C yielded the highest area under the ROC curve (AUC) in all groups assessed. From these data a cutoff level of cystatin C predicting 51Cr‐EDTA GFR < 80 ml/min/1.73m2 was calculated. A level of 1.06 mg/L was found to have a sensitivity of 91% and a specificity of 81%. Applying this cutoff level in our patient group would have avoided 51Cr‐EDTA GFR estimation in 43 of the 87 estimations. In conclusion, the use of this simple test could be recommended as screening of renal dysfunction in children with liver disease and after LT. (Liver Transpl 2005;11:344–349.)