Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome.

OBJECTIVE: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution. METHODS: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells. RESULTS: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1-4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups. CONCLUSIONS: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose.

Fit to WHO weight standard of European infants over time.

OBJECTIVES: The 2006 WHO growth charts were created to provide an international standard for optimal growth, based on healthy, breastfed populations, but it has been suggested that Northern European children fit them poorly. This study uses infant weight data spanning 50 years to determine how well-nourished preschool children from different eras fit the WHO standard, and discuss the implications of deviations. DESIGN: Four longitudinal datasets from the UK and one from Finland were used comprising over 8000 children born between 1959 and 2003. Weights from birth to 2 years were converted to age-sex-adjusted Z scores using the WHO standard and summarised using Generalized Additive Models for Location, Scale and Shape. RESULTS: Weights showed a variable fit to the WHO standard. Mean weights for all cohorts were above the WHO median at birth, but dipped by up to 0.5 SD to a nadir at 8 weeks before rising again. Birth weights increased in successive cohorts and the initial dip became slightly shallower. By age 1 year, cohorts were up to 0.75 SD above the WHO median, but there was no consistent pattern by era. CONCLUSIONS: The WHO standard shows an acceptable, but variable fit for Northern European infants. While birth weights increased over time, there was, unexpectedly, no consistent variation by cohort beyond this initial period. Discrepancies in weight from the standard may reflect differences in measurement protocol and trends in infant feeding practice.

Assessment of adult body composition using bioelectrical impedance: comparison of researcher calculated to machine outputted values.

OBJECTIVES: To explore the usefulness of Bioelectrical Impedance Analysis (BIA) for general use by identifying best-evidenced formulae to calculate lean and fat mass, comparing these to historical gold standard data and comparing these results with machine-generated output. In addition, we explored how to best to adjust lean and fat estimates for height and how these overlapped with body mass index (BMI). DESIGN: Cross-sectional observational study within population representative cohort study. SETTING: Urban community, North East England PARTICIPANTS: Sample of 506 mothers of children aged 7-8 years, mean age 36.3 years. METHODS: Participants were measured at a home visit using a portable height measure and leg-to-leg BIA machine (Tanita TBF-300MA). MEASURES: Height, weight, bioelectrical impedance (BIA). OUTCOME MEASURES: Lean and fat mass calculated using best-evidenced published formulae as well as machine-calculated lean and fat mass data. RESULTS: Estimates of lean mass were similar to historical results using gold standard methods. When compared with the machine-generated values, there were wide limits of agreement for fat mass and a large relative bias for lean that varied with size. Lean and fat residuals adjusted for height differed little from indices of lean (or fat)/height(2). Of 112 women with BMI >30 kg/m(2), 100 (91%) also had high fat, but of the 16 with low BMI (<19 kg/m(2)) only 5 (31%) also had low fat. CONCLUSIONS: Lean and fat mass calculated from BIA using published formulae produces plausible values and demonstrate good concordance between high BMI and high fat, but these differ substantially from the machine-generated values. Bioelectrical impedance can supply a robust and useful field measure of body composition, so long as the machine-generated output is not used.

Effects of a beverage rich in (poly)phenols on established and novel risk markers for vascular disease in medically uncomplicated overweight or obese subjects: A four week randomized placebo-controlled trial.

OBJECTIVE: To determine if (poly)phenols alter cardiovascular risk factors, we assessed the potential of a high (poly)phenol beverage drink, rich in hydroxycinnamates and flavonoids, to modify vascular function in middle aged, overweight or obese subjects without medical co-morbidity in a randomized placebo controlled pilot study. METHODS: Randomly assigned active 250 ml beverages containing 361 mg of (poly)phenols and 120 mg of vitamin C or placebo (no polyphenol/vitamin C) were taken twice daily for 4 weeks. Both beverages contained 40 kcals/250 ml. The primary end-points were pulse wave velocity (PWV) and cutaneous microvascular responses to sodium nitroprusside (SNP) and acetyl choline (ACh) laser doppler iontophoresis. A range of established and novel plasma markers were also measured. RESULTS: Twenty subjects received active beverage and 19 placebo; all completed the study. There was no difference in cutaneous vascular response to either SNP or ACh with mean group differences (logΔ area under perfusion curve) of 0.30 (-0.65, 1.26) and 0.35 (-0.11, 0.81) respectively. Nor was there evidence of a change in log PWV with a mean group difference of 0.029 m/s (-0.042, 0.10). No significant differences were seen in plasma leptin, apolipoproteins, cystatin C, insulin, adiponectin, CRP, ICAM-1, E-Selectin or t-PA, but IL-6 increased in active versus placebo recipients (0.32 vs - 0.18 pg/ml; p=0.010). CONCLUSION: There was no evidence for a short-term beneficial effect of (poly)phenol intervention on microcutaneous vascular response or pulse wave velocity, and no evidence for a benefit on established or novel risk factors in overweight or obese subjects. Our results do not support a short-term benefit of (poly)phenol supplementation on cardiometabolic risk. REGISTRATION: Clinical Trials.gov (NCT00795834).

National Adolescent Treatment Trial for Obesity in Kuwait (NATTO): project design and results of a randomised controlled trial of a good practice approach to treatment of adolescent obesity in Kuwait.

BACKGROUND: Few randomised controlled trials (RCTs) of interventions for the treatment of adolescent obesity have taken place outside the western world. This RCT tested whether a simple 'good practice' intervention for the treatment of adolescent obesity would have a greater impact on weight status and other outcomes than a referral to primary care (control) in adolescents in Kuwait City. METHODS: We report on an assessor-blinded RCT of a treatment intervention in 82 obese 10- to 14-year-olds (mean age 12.4, SD 1.2 years), randomised to a good practice treatment or primary care control group over 6 months. The good practice intervention was intended as relatively low intensity (6 hours contact over 24 weeks, group-based), aiming to change sedentary behaviour, physical activity, and diet. The primary outcome was a change in body mass index (BMI) Z score; other outcomes were changes in waist circumference and blood pressure. RESULTS: The retention of subjects to follow up was acceptable (n = 31 from the intervention group, and n = 32 from the control group), but engagement with both the intervention and control treatment was poor. Treatment had no significant effect on BMI Z score relative to control, and no other significant benefits to intervention were observed. CONCLUSIONS: The trial was feasible, but highlights the need to engage obese adolescents and their families in the interventions being trialled. The trial should inform the development of future adolescent obesity treatment trials in the Gulf States with the incorporation of qualitative assessment in future intervention trials. TRIAL REGISTRATION: RCT Registered as National Adolescent Treatment Trial for Obesity in Kuwait (NATTO): http://www.controlled-trials.com/ISRCTN37457227, 1 December 2009.

Prognostic significance of being overweight and obese at diagnosis in children with acute lymphoblastic leukemia.

This study tested the hypothesis that being overweight/obese at diagnosis of childhood ALL was related to risk of relapse. In a national cohort of 1033 patients from the UK, there was no evidence that weight status at diagnosis was related significantly to risk of relapse: log-rank test (P=0.90) with overweight and obesity as the exposure (n=917); individual (P=0.42) and stepwise (P=0.96) proportional hazards models, with BMI Z score as the exposure. The study does not support the hypothesis that being overweight/obese at diagnosis impairs prognosis in childhood ALL in the UK.

Effects of a physical education intervention on cognitive function in young children: randomized controlled pilot study.

BACKGROUND: Randomized controlled trials (RCT) are required to test relationships between physical activity and cognition in children, but these must be informed by exploratory studies. This study aimed to inform future RCT by: conducting practical utility and reliability studies to identify appropriate cognitive outcome measures; piloting an RCT of a 10 week physical education (PE) intervention which involved 2 hours per week of aerobically intense PE compared to 2 hours of standard PE (control). METHODS: 64 healthy children (mean age 6.2 yrs SD 0.3; 33 boys) recruited from 6 primary schools. Outcome measures were the Cambridge Neuropsychological Test Battery (CANTAB), the Attention Network Test (ANT), the Cognitive Assessment System (CAS) and the short form of the Connor's Parent Rating Scale (CPRS:S). Physical activity was measured habitually and during PE sessions using the Actigraph accelerometer. RESULTS: Test- retest intraclass correlations from CANTAB Spatial Span (r 0.51) and Spatial Working Memory Errors (0.59) and ANT Reaction Time (0.37) and ANT Accuracy (0.60) were significant, but low. Physical activity was significantly higher during intervention vs. control PE sessions (p < 0.0001). There were no significant differences between intervention and control group changes in CAS scores. Differences between intervention and control groups favoring the intervention were observed for CANTAB Spatial Span, CANTAB Spatial Working Memory Errors, and ANT Accuracy. CONCLUSIONS: The present study has identified practical and age-appropriate cognitive and behavioral outcome measures for future RCT, and identified that schools are willing to increase PE time. TRIAL REGISTRATION NUMBER: ISRCTN70853932 (http://www.controlled-trials.com).

Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian Childhood Obesity Treatment Trial (MASCOT).

CONTEXT: Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. AIM: To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. METHODS: Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). RESULTS: The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. CONCLUSIONS: Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes.

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA.

BACKGROUND: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. METHODS/DESIGN: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted.A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken. TRIAL REGISTRATION NUMBER: UKCRN5045.

Age- and sex-standardised lean and fat indices derived from bioelectrical impedance analysis for ages 7-11 years: functional associations with cardio-respiratory fitness and grip strength.

Indices for lean and fat mass adjusted for height derived from bioelectrical impedance for children aged 7 years have been published previously and their usefulness in the clinical assessment of undernutrition has been demonstrated. However, there is a need for norms that cover a wider age range and to explore their functional significance. The aim of the present study is to derive lean and fat indices for children aged 7-11 years and investigate associations with objective measures of cardio-respiratory fitness and grip strength. Subjects were 9574 children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Bioelectrical impedance analysis (BIA) data collected longitudinally between ages 7 and 11 were used to derive lean and fat indices using the method of standardised residuals. Cardio-respiratory fitness (CRF) (9 years) and grip strength (11 years) were also measured. Correlation coefficients and 95 % CI were calculated to assess the strength of association between lean index, fat index and CRF and grip strength. Equations for calculating lean and fat indices in children aged 7-11 years relative to the ALSPAC population are presented. Lean index was linearly associated with CRF (rboys 0.20 (95 % CI 0.15, 0.25), rgirls 0.26 (95 % CI 0.22, 0.30)) and grip strength (rboys 0.29 (95 % CI 0.26, 0.32), rgirls 0.26 (95 % CI 0.23, 0.29)). BMI showed slightly weaker associations, while fat index was unrelated to either CRF or grip strength. Lean indices relate to muscle function and fitness while fat index does not.

Randomized, controlled trial of a best-practice individualized behavioral program for treatment of childhood overweight: Scottish Childhood Overweight Treatment Trial (SCOTT).

OBJECTIVE: The objective of this study was to determine whether a generalizable best-practice individualized behavioral intervention reduced BMI z score relative to standard dietetic care among overweight children. METHODS: The design consisted of an assessor-blinded, randomized, controlled trial involving 134 overweight children (59 boys, 75 girls; BMI > or = 98th centile relative to United Kingdom 1990 reference data for children aged 5-11 years) who were randomly assigned to a best-practice behavioral program (intervention) or standard care (control). The intervention used family-centered counseling and behavioral strategies to modify diet, physical activity, and sedentary behavior. BMI z score, weight, objectively measured physical activity and sedentary behavior, fat distribution, quality of life, and height z score were recorded at baseline and at 6 and 12 months. RESULTS: The intervention had no significant effect relative to standard care on BMI z score from baseline to 6 months and 12 months. BMI z score decreased significantly in both groups from baseline to 6 and 12 months. For those who complied with treatment, there was a significantly smaller weight increase in those in the intervention group compared with control subjects from baseline to 6 months. There were significant between-group differences in favor of the intervention for changes in total physical activity, percentage of time spent in sedentary behavior, and light-intensity physical activity. CONCLUSIONS: A generalizable, best-practice individualized behavioral intervention had modest benefits on objectively measured physical activity and sedentary behavior but no significant effect on BMI z score compared with standard care among overweight children. The modest magnitude of the benefits observed perhaps argues for a longer-term and more intense intervention, although such treatments may not be realistic for many health care systems.

Does vitamin D stop inpatients falling? A randomised controlled trial.

BACKGROUND: Vitamin D deficiency is common in older people and may increase risk of falls and fracture. Hospital inpatients are at particular risk of falling. Previous studies suggest that vitamin D improves neuromuscular function and reduces falls. OBJECTIVE: To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are inpatients. DESIGN: Randomised, double-blind, controlled study. PARTICIPANTS: two hundred and five acute admissions >65 years to a geriatric medical unit. METHODS: Patients were randomised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg, until discharge or death. RESULTS: Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days (IQR 14.75-71.00). In a pre-selected sub-group (54/205 participants), median admission vitamin D level = 22.00 nmol/l (IQR 15.00-30.50). This did not significantly increase in the treatment versus control group. Median study drug adherence = 88%, with no significant difference between study groups (Mann-Whitney: P = 0.711). Although there were fewer fallers in the vitamin D cohort, this did not reach statistical significance (vitamin D: calcium = 36:45 fallers; RR 0.82 (CI 0.59-1.16). Neither the mean number of falls (vitamin D: calcium = 1.040:1.155; Mann-Whitney P = 0.435) or time to first fall (Log-rank test P = 0.377) differed between groups. CONCLUSIONS: In a population of geriatric hospital inpatients, vitamin D did not reduce the number of fallers. Routine supplementation cannot be recommended to reduce falls in this group.

Physical activity to prevent obesity in young children: cluster randomised controlled trial.

OBJECTIVE: To assess whether a physical activity intervention reduces body mass index in young children. DESIGN: Cluster randomised controlled single blinded trial over 12 months. SETTING: Thirty six nurseries in Glasgow, Scotland. PARTICIPANTS: 545 children in their preschool year, mean age 4.2 years (SD 0.2) at baseline. INTERVENTION: Enhanced physical activity programme in nursery (three 30 minute sessions a week over 24 weeks) plus home based health education aimed at increasing physical activity through play and reducing sedentary behaviour. MAIN OUTCOME MEASURE: Body mass index, expressed as a standard deviation score relative to UK 1990 reference data. Secondary measures were objectively measured physical activity and sedentary behaviour; fundamental movement skills; and evaluation of the process. RESULTS: Group allocation had no significant effect on the primary outcome measure at six and 12 months or on measures of physical activity and sedentary behaviour by accelerometry. Children in the intervention group had significantly higher performance in movement skills tests than control children at six month follow-up (P=0.0027; 95% confidence interval 0.3 to 1.3) after adjustment for sex and baseline performance. CONCLUSIONS: Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36363490.

Renal transplant biopsy specimen adequacy in a paediatric population.

Updated guidelines on the diagnosis of acute allograft rejection including criteria for biopsy specimen adequacy were published in 1999. We sought to determine the adequacy of specimens in paediatric transplant patients and identify factors influencing adequacy. All renal transplant biopsies performed between 1998 and 2003 were classified as adequate (n =25), minimal (n =19) or inadequate (n =27) in accordance with the Banff 97 criteria, and the histological diagnoses were documented. The effect on specimen adequacy of grade of operator, method of sedation, age of child, needle gauge, number of cores and total core length was then investigated. Overall, a minimal or adequate specimen was obtained in 62% of cases. No histological diagnosis could be made in 30% of all specimens, just over half of which were inadequate. Higher rates of rejection were found in adequate (52%) than inadequate (33%) samples. The grade of operator (p =0.498), the age of the child at the time of biopsy (p =0.815) and type of sedation (p =0.188) did not affect adequacy. More than one core was obtained in 38 (54%) cases, and this was significantly associated with specimen adequacy (p <0.0005) as was longer total core length (p =0.002). Clinical features in isolation are not sufficient for the diagnosis of acute allograft rejection. Renal biopsy remains the gold standard and relies on adequate specimen collection. Our data shows that specimen adequacy according to the Banff 97 guidelines is achievable in children and that more than one core at the time of sampling significantly improves this achievement. Adequate sampling reduces the risk of an inconclusive histological diagnosis.

Vascular access survival in children and young adults receiving long-term hemodialysis.

BACKGROUND: The delivery of long-term hemodialysis therapy in children is complicated by smaller vascular caliber and the potential lifelong requirement for hemodialysis access. Various factors have resulted in the increased use of cuffed central venous catheters (CVLs) in preference to autologous arteriovenous fistulae (AVFs) and arteriovenous synthetic grafts (AVGs). The aim of this study is to compare CVL, AVF, and AVG survival and determine factors affecting their survival. METHODS: A 20-year retrospective study was undertaken of pediatric patients receiving long-term hemodialysis therapy. Age, height, weight, body mass index, and sex were noted at each procedure, in addition to the presence of hypoalbuminemia, underlying diagnosis, type and site of vascular access, and effect of previous access surgery. The grade of operator also was noted. RESULTS: Three hundred four vascular access procedures were performed on 114 patients, with a median age at initial access formation of 12.0 years (range, 4 weeks to 21.9 years). The most common procedure was CVL insertion (182 procedures) and then AVF formation (107 procedures), with only 15 AVGs created. Median censored survival was 3.14 years (95% confidence interval, 1.22 to 5.06) for AVFs and 0.6 years (95% confidence interval, 0.20 to 1.00) for CVLs. Factors adversely affecting vascular access survival were younger age, trainee operator, presence of hypoalbuminemia, and type of access undertaken, with AVF better than CVL. CONCLUSION: This study shows increased survival of AVFs over CVLs and AVGs. Vascular access in children and adolescents may impact on future dialysis accessibility and should be undertaken by those most experienced in each technique.

Urinary citrate in preterm and term babies.

OBJECTIVES: (1) To determine a normal range for urinary citrate for term babies. (2) To compare urinary citrate measured in ex preterm babies at term with this normal range. (3) To evaluate whether urinary citrate was related to presence of nephrocalcinosis (NC) and chronic Lung Disease (CLD) in these ex preterm babies. STUDY DESIGN: Urinary citrate was measured in 38 healthy term babies (mean birth weight 3.52 kg, mean gestation 41 weeks) at a mean postnatal age of 3 days (1-5 days) and in 53 ex preterm babies (<32 weeks gestation at birth) at term. These preterm babies were part of a larger study on NC in which two renal ultrasound scans were performed at 1 month and term. RESULTS: The normal range for urinary citrate in term babies was 0.025-2.97 (mean 1.03) mmol/l and citrate/creatinine ratio 0.0011-0.852 (mean 0.27). In the ex-preterm urinary citrate was not significantly different (mean 1.1 vs. 1.03, p=0.7232) but urine citrate/creatinine ratio was significantly higher (mean 1.27 vs. 0.27, p=0.0005). There was no significant difference in urinary citrate or ratios of citrate/creatinine and calcium/citrate in the 11 (20.7%) with NC or in the 17 (32%) babies with CLD. There was no significant relationship found between duration of TPN and urinary citrate measured at term. CONCLUSION: We have determined a normal range for urinary citrate in healthy term babies in the first week of life. The range was very wide. Ex preterm babies had similar values at term and there was no association between urinary citrate and NC or CLD.

Urinary citrate in preterm and term babies.

OBJECTIVES: (1) To determine a normal range for urinary citrate for term babies. (2) To compare urinary citrate measured in ex preterm babies at term with this normal range. (3) To evaluate whether urinary citrate was related to presence of nephrocalcinosis (NC) and chronic Lung Disease (CLD) in these ex preterm babies. STUDY DESIGN: Urinary citrate was measured in 38 healthy term babies (mean birth weight 3.52 kg, mean gestation 41 weeks) at a mean postnatal age of 3 days (1-5 days) and in 53 ex preterm babies (<32 weeks gestation at birth) at term. These preterm babies were part of a larger study on NC in which two renal ultrasound scans were performed at 1 month and term. RESULTS: The normal range for urinary citrate in term babies was 0.025-2.97 (mean 1.03) mmol/l and citrate/creatinine ratio 0.0011-0.852 (mean 0.27). In the ex-preterm urinary citrate was not significantly different (mean 1.1 vs. 1.03, p=0.7232) but urine citrate /creatinine ratio was significantly higher (mean 1.27 vs. 0.27, p=0.0005). There was no significant difference in urinary citrate or ratios of citrate/creatinine and calcium/citrate in the 11 (20.7%) with NC or in the 17 (32%) babies with CLD. There was no significant relationship found between duration of TPN and urinary citrate measured at term. CONCLUSION: We have determined a normal range for urinary citrate in healthy term babies in the first week of life. The range was very wide. Ex preterm babies had similar values at term and there was no association between urinary citrate and NC or CLD.

Comparison of prosthetic valve hydrodynamic function: objective testing using statistical multilevel modeling.

BACKGROUND AND AIM OF THE STUDY: The performance of novel prosthetic heart valves is assessed using in-vitro hydrodynamic function tests. The study aim was to examine the problem of objective discrimination of hydrodynamic performance to determine significant differences between valve designs, and illustrate proposed methodology using data collected from five different polyurethane tri-leaflet valve designs. METHODS: Two engineering designs were manufactured with leaflets of the same polyurethane (GE, LE); design L was manufactured using three further leaflet materials of differing material modulus (LL, L4, L5). Six valves were made in each design, each tested at five flow rates in a standard hydrodynamic test rig, with five test replications for each valve. The data were analyzed using multilevel statistical modeling methods, allowing simultaneous comparison of multiple regression lines describing valve performance. The multilevel model is hierarchical in structure, in this case with two levels of data, describing individual valves at level 2 and test replicates at level 1. In all cases, the multilevel model uses the hydrodynamic function measure of interest, e.g. mean pressure gradient or leakage, with logarithmic transformation as required as the dependent variable, Y. The independent variable, X, is, in all cases, the natural logarithm of the RMS flow measured through the valve. RESULTS: The two-design multilevel model enabled quantitative discrimination of designs GE and LE, showing that design GE had significantly better hydrodynamic function overall than design LE in this case (mean pressure gradient was estimated as 0.93 mmHg lower at low cardiac output, 14.74 mmHg lower at 9.6 l/min). The five-design multilevel model showed clearly the relatively poor hydrodynamic performance of designs L4 and L5 compared with others. The procedure was straightforward, and produced a statistical comparison among valve designs that is not easily achieved by other means. CONCLUSION: This methodology provides a useful means of objective assessment of valve function for valve developers. Variance estimates provided by the analysis also provide a basis for quality control of valve production and testing.

Can prescription of sip-feed supplements increase energy intake in hospitalised older people with medical problems?

A blinded randomised controlled trial of prescribed oral sip-feed supplements compared with routine hospital practice was undertaken in acute admissions to a geriatric medicine department. Patients were eligible for inclusion if they were admitted from home, were not obese (BMI>75th percentile), had no swallowing difficulties and were not deemed to be in the terminal stage of illness. On admission they were stratified by nutritional status (BMI<5th, >5th to <25th, >25th to <75th percentile) and randomised. The intervention group received 120 ml oral sip-feed supplement prescribed three times per d in the medicine prescription chart (22.5 g protein, 2260 kJ (540 kcal) energy/d) distributed at medication rounds for the duration of hospital stay. The control group received routine hospital care. Outcomes were patient compliance with supplement, total energy intake and nursing staff views of the method. Patients were randomised to receive supplements (n 186 of total n 381). Half had full compliance and three-quarters at least moderate compliance. Total energy intake was significantly increased, on average, in the intervention group (P=0.001). The proportion of patients meeting estimated minimum energy requirements was significantly increased (P=0.023), but was still <50 % for the sample of patients in the intervention group. The present study suggests this method is acceptable to patients and staff and improves total energy intake. However, the amount prescribed did not ensure minimum energy requirements were met in all cases.

Glomerular basement membrane thickness in children: a stereologic assessment.

BACKGROUND: Stereologic methods have emerged as the technique of choice in assessing glomerular basement membrane (GBM) thickness, following conceptual modeling comparing the stereologic technique of harmonic mean of the orthogonal intercept estimation (Th) with the model based method of arithmetic mean estimation (ATH), with no direct comparison undertaken. We undertook to establish the gold standard for GBM estimation and use this technique to establish a range for GBM thickness in children. METHODS: Intra-observer and inter-glomerular variation was estimated in 34 cases with (presumed) normal GBM thickness, using Th, ATH and a rapid direct measurement technique, with intra-observer variation measured in 35 cases with GBM attenuation. A total of 34,011 measurements were undertaken to establish a range for Th in children on 212 biopsies from 199 patients (127 male) demonstrating minimal change nephropathy (N = 153), focal segmental glomerulosclerosis (24), no abnormality (24), and acute tubular necrosis (8), which were used as surrogates for normals. RESULTS: Th demonstrated less variation than ATH in both the normal and attenuated groups. GBM thickness increased throughout childhood, from 194 +/- 6.5 nm (mean +/- SE) at one year to 297 +/- 6.0 nm at 11 years, with a reduced rate of increase after age 11 years. CONCLUSION: Stereologic methods are superior to model based techniques in estimating GBM thickness and should be regarded as the technique of choice in this area. GBM thickness was observed to increase during childhood with no gender effect demonstrable as a main effect or interaction.