Prevalence of being underweight and overweight and obesity at diagnosis in UK patients with childhood acute lymphoblastic leukaemia 1985-2002.

BACKGROUND: Being underweight or overweight and obesity at diagnosis may all worsen prognosis in childhood acute lymphoblastic leukaemia (ALL), although no studies have estimated the prevalence of an unhealthy weight status at diagnosis in large representative samples using contemporary definitions of weight status based on body mass index (BMI) for age. METHODS: The present study comprised a retrospective study that aimed to estimate prevalence of being underweight and overweight and obesity at diagnosis for patients with childhood ALL on three successive UK treatment trials: UKALL X (1985-1990; n = 1033), UKALL XI (1990-1997; n = 2031), UKALL 97/99 (1997-2002; n = 898).The BMI for age was used to define weight status with both UK 1990 BMI for age reference data and the Cole-International Obesity Task Force (IOTF) definitions. RESULTS: The prevalence of being underweight was 6% in the most recent trial for which data were available. The prevalence of being overweight and obesity was 35% in the most recent trial when expressed using Cole-IOTF definitions and 41% when expressed relative to UK 1990 reference data. CONCLUSIONS: Even with highly conservative estimates, >40% of all UK patients with ALL were underweight, overweight or obese at diagnosis in the most recent trial for which UK data are available (UKALL 97/99, 1997-2002).

Development of bioelectrical impedance-derived indices of fat and fat-free mass for assessment of nutritional status in childhood.

OBJECTIVES: (1) To develop a method of manipulating bioelectrical impedance (BIA) that gives indices of lean and fat adjusted for body size, using a large normative cohort of children. (2) To assess the discriminant validity of the method in a group of children likely to have abnormal body composition. DESIGN: Two prospective cohort studies. SETTING: Normative data: Avon Longitudinal Study of Parents and Children (ALSPAC), population based cohort; proof of concept study: tertiary feeding clinic and special needs schools. SUBJECTS: Normative data: 7576 children measured aged between 7.25 and 8.25 (mean 7.5) (s.d.=0.2) years; proof of concept study: 29 children with either major neurodisability or receiving artificial feeding, or both, mean age 7.6 (s.d.=2) years. MEASURES: Leg-to-leg (Z (T)) and arm-to-leg (Z (B)) BIA, weight and height. Total body water (TBW) was estimated from the resistance index (RI=height(2)/Z), and fat-free mass was linearly related to TBW. Fat mass was obtained by subtracting fat-free mass from total weight. Fat-free mass was log-transformed and the reciprocal transform was taken for fat mass to satisfy parametric model assumptions. Lean and fat mass were then adjusted for height and age using multiple linear regression models. The resulting standardized residuals gave the lean index and fat index, respectively. RESULTS: In the normative cohort, the lean index was higher and fat index lower in boys. The lean index rose steeply to the middle of the normal range of body mass index (BMI) and then slowly for higher BMI values, whereas the fat index rose linearly through and above the normal range. In the proof of concept study, the children as a group had low lean indices (mean (s.d.) -1.5 (1.7)) with average fat indices (+0.21 (2.0)) despite relatively low BMI standard deviation scores (-0.60 (2.3)), but for any given BMI, individual children had extremely wide ranges of fat indices. The lean index proved more stable and repeatable than BMI. CONCLUSIONS: This clinical method of handling BIA reveals important variations in nutritional status that would not be detected using anthropometry alone. BIA used in this way would allow more accurate assessment of energy sufficiency in children with neurodisability and may provide a more valid identification of children at risk of underweight or obesity in field and clinical settings.

Neonatal nephrocalcinosis: long term follow up.

AIMS: To assess the spontaneous resolution of neonatal nephrocalcinosis and its long term effects on renal function. METHODS: Fourteen very low birthweight preterm babies with nephrocalcinosis were followed up at 5-7 years of age; 14 controls were matched for sex, gestation, and birth weight. Height, weight, blood pressure, and renal symptomatology were recorded, and a renal ultrasound scan was performed. Early morning urine osmolality and creatinine ratios of albumin, phosphate, calcium, oxalate and beta microglobulin were determined. Urea and electrolytes in the study group were determined, and glomerular filtration rate (GFR) and TmP/GFR (tubular reabsorption of phosphate per GFR) were calculated. Statistical analysis was performed on a group basis using the Mann-Whitney confidence interval. RESULTS: Mean age was 6.9 years (range 5.81-7.68). An early morning urine osmolality >700 mOsm/kg was achieved in all cases. In two cases and four controls, the calcium/creatinine ratio was >0.7 mmol/mmol. In all cases, the GFR was normal (median 132.6 ml/min/1.73 m(2) (range 104.1-173.1)). Median TmP/GFR was 1.22 mmol/l (0.73-1.61), with two having levels below the normal range. These did not have persisting nephrocalcinosis. Nephrocalcinosis was found in three of the 12 cases scanned and one control. There were no significant differences in urine biochemistry. CONCLUSIONS: Resolution of nephrocalcinosis occurred in 75% of cases. No evidence was found to suggest that nephrocalcinosis is associated with renal dysfunction in the long term. There was evidence of hypercalciuria in the cases and controls, suggesting that prematurity may be a risk factor.

Statistical issues in the analysis of neuroimages.

Statistical issues in the analysis of neuroimages are reviewed. These include biological questions of interest, basic problems of measurement and experimental design, normalisation, standardisation and transformation, and statistical methodology. Finally, three data sets are reviewed to illustrate some of the issues raised in the report.

Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) using topical delta-aminolevulinic acid (delta-ALA) is an effective treatment for Bowen disease and certain basal cell carcinomas (BCCs), but its place in clinical practice remains to be established. Patients with large and/or multiple lesions of Bowen disease or BCC can represent a considerable therapeutic challenge. We suggest that delta-ALA PDT may be of particular benefit in such patients. OBSERVATION: In an open study, 35 (88%) of 40 large patches of Bowen disease, all with a maximum diameter greater than 20 mm, cleared following 1 to 3 treatments of delta-ALA PDT, although 4 patches recurred within 12 months. delta-Aminolevulinic acid PDT was also used to treat 40 large BCCs, with an identical 88% initial clearance (after 1-3 treatments), with 4 recurrences within 34 months (range, 12-60 months). In 10 further patients with multiple (> or =3) patches of Bowen disease, 44 (98%) of 45 patches cleared following delta-ALA PDT, although 4 lesions recurred over 12 months. In 3 patients with multiple BCCs, PDT cleared 52 (90%) of 58 lesions, with 2 recurrences during 41 months (range, 12-52 months). Treatments were well tolerated, with only 5 patients with solitary large lesions requiring local anesthesia. CONCLUSIONS: delta-Aminolevulinic acid PDT is an effective tissue-sparing modality achieving good cosmesis. We propose that delta-ALA PDT be considered as a first-line therapy for large and/or multiple areas of Bowen disease and superficial BCCs.

Nephrocalcinosis in preterm babies.

OBJECTIVES: To determine prospectively the incidence and cause of nephrocalcinosis in preterm infants. STUDY DESIGN: Inborn babies of gestation less than 32 weeks or birth weight less than 1500 g were eligible to be entered into a prospective observational study. Two renal ultrasound scans were performed, the first at 1 month postnatal age and the second at term or discharge. Data were collected on gestation, birth weight, sex, race, family history of renal calculi, oliguria on first day, respiratory support (ventilation, steroid, and oxygen dependency), and use of nephrotoxic drugs (gentamicin, vancomycin, and frusemide). Intake of fluid, calcium, and phosphate and plasma urea, creatinine, calcium, and phosphate were recorded for the first 6 weeks of life. Random urinary calcium/creatinine, oxalate/creatinine, and urate/creatinine ratios and tubular absorption of phosphate were measured once at term. RESULTS: A total of 101 preterm infants were studied. Twenty three (23%) had abnormal ultrasound scans. Sixteen (16%) had nephrocalcinosis. On univariate analysis, gestational age, male sex, duration of ventilation, oxygen dependency, duration and frequency of gentamicin treatment, toxic gentamicin/vancomycin levels, and postnatal dexamethasone were significantly associated with nephrocalcinosis. In addition, babies with nephrocalcinosis had a lower intake of fluid, calcium, and phosphate, longer duration of total parenteral nutrition, and higher urinary oxalate/creatinine and urate/creatinine ratios than infants who did not have the condition. There was also a significant association with plasma urea and creatinine but not with plasma calcium or phosphate or urinary calcium. Multivariate analysis showed that the strongest predictors of nephrocalcinosis were duration of ventilation, toxic gentamicin/vancomycin levels, low fluid intake, and male sex. CONCLUSION: 16% of babies born at less than 32 weeks gestation developed nephrocalcinosis. The multifactorial origin, in particular, the association with extreme prematurity and severity of respiratory disease, is confirmed. In addition, an association with male sex, frequency and duration of gentamicin use, and high urinary oxalate and urate excretion is shown.

Statistical methods in neuroimaging with particular application to emission tomography.

We review statistical methods being applied in four key areas connected with PET and SPECT neuroimaging: (i) image reconstruction (briefly); (ii) tracer-kinetic, or compartmental, modelling; (iii) inference from region-of-interest data; (iv) inference at the pixel or voxel level. Under the last heading, we pay particular attention to the analysis of data from serial scans. We conclude by identifying some topics for future statistical research.

Protein energy supplements in unwell elderly patients--a randomized controlled trial.

BACKGROUND: To determine whether oral protein energy supplements, prescribed during hospitalization to elderly medical admissions, affect nutritional status and if baseline nutritional state influences this status. We also considered the effects on mortality, length of hospital stay, functional recovery, and institutionalization. METHODS: A prospective randomized controlled trial with no placebo. Consenting patients were stratified in 3 nutritional categories, and patients from each stratum were randomized into treatment or control. Observers were blinded to randomization. The participants were emergency admissions from home to a Medicine for the Elderly Unit in a Scottish hospital. The inclusion criteria were as follows: no known malignancy, the ability to swallow, and nonobesity (BMI < 75th percentile). The intervention was a prescription of 120 mL sip feed, 3 times daily (540 kcal, 22.5 g protein per day) throughout hospitalization, using the medicine prescription chart. The trial was powered to detect change in mean percentage weight. The following outcomes were also considered: anthropometry; mortality, length of hospital stay, functional recovery, and rates of institutionalization. RESULTS: Included in the trial were 381 patients. Nutritional supplementation was associated with significantly better energy intake (p = .001) and weight gain (p = .003) pooled across all nutritional categories. In the most poorly nourished patients, the intervention was associated with reduced mortality (5/34 versus 14/40, p < .05) and more patients improved functionally (17/25 versus 11/28, p < .04). Overall mortality results were 21/186 versus 33/195, odds ratio (OR) 0.62, 95% confidence interval (CI) 0.35, 1.13. CONCLUSIONS: Prescribing sip feed supplements in the medicine prescription chart during hospital stay reduces weight loss. Our data also support other evidence for a reduction in mortality noted in elderly patients on nutritional supplementation. There were suggestions of other clinical benefits.

Cognitive functioning in people with epilepsy plus severe learning disabilities: a systematic analysis of predictors of daytime arousal and attention.

In spite of the high prevalence of epilepsy and the importance of preserving cognitive function in people with learning disabilities, this population has received relatively little research attention. This study sets out systematically to investigate possible predictive factors of inter-ictal states of arousal and attention. The daytime function of 28 people with epilepsy and severe learning disabilities was assessed by performance on a two-choice reaction time vigilance task, behavioural analysis of time-sampled video recordings taken in naturalistic settings, and carer ratings on visual analogue scales. This methodology yielded eight discrete functional measures, from which two further index measures were derived after principal components analysis. A range of clinical and psychosocial assessments was completed and subjects had 36 hour ambulatory EEG and sleep EEG monitoring. Regression models identified significant predictors of cognitive function from a range of potential explanatory variables i.e. demographic, clinical, pharmacological, background EEG rhythms and sleep parameters. Results indicated that greater severity of learning disability, longer bedtime periods, poor sleep efficiency, frequent seizures and antiepileptic drug polytherapy were significant predictor variables. Explained variance (adjusted R2) was greater than 50% for six of 10 outcome variables (range up to 85%). Furthermore, significant regression equations (P < 0.05) were obtained for all but one variable. Thus, these results appear reasonably robust. Results support an interactional model of daytime arousal and attention in people with epilepsy plus severe learning disabilities. Inter-ictal cognitive function appears to be mediated by a combination of organic, circadian (sleep wake), clinical and pharmacological factors.

Sleep studies of adults with severe or profound mental retardation and epilepsy.

Sleep patterns of people with mental retardation have received little research attention. This is an important gap in knowledge because understanding the relation between sleep and wakefulness may be critical to care provision. Descriptive sleep information on 28 people with severe or profound mental retardation and epilepsy was presented here. Sleep EEG data, studied both conventionally and by means of a neural network-based sleep analysis system suggest atypical sleep stages with significant depletion of REM sleep and a predominance of "indiscriminate" non-REM sleep. Sleep diaries completed by caregivers reveal lengthy sleep period times, especially among those with profound mental retardation. Possible explanations for these results and their implications were discussed.

The use of removable orthodontic appliances in the General Dental Service.

One hundred and fifty removable appliance cases consecutively sampled by the Scottish Dental Practice Board were analysed using the PAR index. The cases were assessed as being suited or unsuited to the removable appliance approach based on the presenting features previously shown to be effectively treated by removable appliances. Using chi-squared tests of association, suitable cases were characterised as being in the mixed dentition, had one feature treated and one appliance used. Suitable cases on average showed 3-4 PAR points more improvement as a result of treatment than equivalent unsuitable cases; regression equations are given. Because of the wide variability within the sample it proved impossible to predict accurately the expected duration of treatment in the General Dental Service.

Home nebuliser use in children with asthma in two Scottish Health Board Areas.

OBJECTIVE: To audit the use of home nebulisers in children with asthma. DESIGN: Postal questionnaire. SETTING: Two Health Board Areas in Central Scotland--one large industrialised city, one mixed urban and rural. SUBJECTS: 297 children with asthma. MEASURES EVALUATED: Initial supply and technical support for the compressor. EDUCATION: Pattern of drug usage. SYMPTOM CONTROL: Monitoring and treatment of acute attacks. RESULTS: The full burden of the home nebulised therapy is not being met by the NHS. Supply and servicing arrangements for home nebuliser therapy were poorly organised. Chronic asthma symptoms did not appear to be optimally controlled on present medication, with 61% reporting sleep disturbance in the previous three months. About 20% of parents admitted that they would give nebulised bronchodilator therapy more frequently than the recommended 3 to 4 hourly. CONCLUSION: Re-organisation of resources and arrangements could improve the service and bring it in line with recognised standards of care.

Effect of socioeconomic status on objectively measured physical activity.

BACKGROUND: A socioeconomic gradient in childhood obesity is known to be present by the age of school entry in the UK. The origin of this gradient is unclear at present, but must lie in socioeconomic differences in habitual physical activity, sedentary behaviour, or dietary intake. AIMS: To test the hypothesis that habitual physical activity and/or sedentary behaviour are associated with socioeconomic status (SES) in young Scottish children. METHODS: Observational study of 339 children (mean age 4.2 years, SD 0.3) in which habitual physical activity and sedentary behaviour were measured by accelerometry over six days (study 1). In a second study, 39 pairs of children of distinctly different SES (mean age 5.6 years, SD 0.3) were tested for differences in habitual physical activity and sedentary behaviour by accelerometry over seven days. RESULTS: In study 1, SES was not a significant factor in explaining the amount of time spent in physical activity or sedentary behaviour once gender and month of measurement were taken into account. In study 2, there were no significant differences in time spent in physical activity or sedentary behaviour between affluent and deprived groups. CONCLUSION: Results do not support the hypothesis that low SES in young Scottish children is associated with lower habitual physical activity or higher engagement in sedentary behaviour.

Use of the PAR index in assessing the effectiveness of removable orthodontic appliances.

The dental study casts of 150 consecutively completed removable appliance cases were examined before and after orthodontic treatment using the PAR index. Eighty-nine per cent were classified either as 'improved' or 'greatly improved'. Of the 16 cases classified as 'worse, no different', six were mixed dentition cases with limited treatment objectives (which were successfully achieved) and three were permanent dentition cases where only one tooth was being aligned. Using predefined criteria removable appliances were shown to be most effective in treating cross-bites, ectopic tooth position, anterior spacing, and overjet, and less effective in treating crowding, rotations, and molar relationships.

A method of measuring the apical base.

The maxillary and mandibular apical base areas were measured, using a gnathograph, on the study casts of 156 adults and children representing Class II division 1, Class II division 2 and Class III malocclusions. There were significant differences between the groups at each age. The maxillary apical base areas tended to be smaller for the adults than for the children in all three occlusal classes. By contrast, the mandibular apical base areas tended to be larger for the adults than for the children, except in Class II division 1 malocclusion. Following a logarithmic transformation to stabilize the variance, regression lines were fitted to relate the size of the maxillary and mandibular apical bases to one another, for the malocclusion groups within each age group. The method gives additional information regarding the degree of apical base discrepancy in a given case, but more work is required before it can be used as a diagnostic tool.

Factors associated with the standard and duration of orthodontic treatment.

The pretreatment and post-treatment study casts and records of 156 completed fixed appliance and removable appliance cases were analysed, and the influence of various factors on the standard of result, as measured by the change in PAR score produced by treatment and the duration of treatment, was assessed. For the purpose of analysis the sample was divided into two groups; a two-arch fixed appliance group (n = 81) and a removable/mini fixed appliance group (n = 75). Multiple regression procedures were carried out separately for both groups, first, with all gathered data and, secondly, with only information which would be known at the start of treatment. For fixed appliances the initial PAR score was consistently an influential variable on change in PAR score and duration of treatment. Patient compliance, the need to extract a permanent first molar and the presence of an anterior crossbite were also important. The initial PAR score also explained much of the variation in change in PAR for removable/mini fixed appliances, but generally, regression models for this group were less well fitting.

Differentiation between cleft lip with or without cleft palate and isolated cleft palate using parental cephalometric parameters.

OBJECTIVE: The purpose of this study was to identify and compare lateral cephalometric measurements in noncleft parents of children with cleft palate (CP) and cleft lip (CL), and cleft lip and palate (CLP). The hypothesis was that discriminant analysis would enable identification of morphometric features that predispose to orofacial clefting and that differ for CP, CL, and CLP and are unevenly distributed within parental pairs. DESIGN: This was a prospective, parametric analysis. SETTING: The study was conducted by the Department of Dental Health, University of Dundee, and the Department of Statistics, University of Glasgow, Scotland. SUBJECTS: From a completely ascertained sample of 286 children with cleft lip and/or palate born in the West of Scotland between January 1, 1980, and December 31, 1984, a sample of 83 parents of children with non-syndromic clefts volunteered for lateral cephalometric examination. METHODS: Thirty-seven cranial and 99 facial landmarks were identified and 37 linear, angular, and area parameters were used to describe the craniofacial skeleton. Analysis of variance was used for a three-way comparison of CL/CLP/CP, and stepwise discriminant analysis was used to determine which variables discriminate best between cleft lip with or without cleft palate [CL(P)] and isolated cleft palate (CP) parents. RESULTS: There were no significant differences whatsoever in the craniofacial morphology between the parents of children with CL and CLP, but differences were found between the CL(P) and CP groups. The most significant of these were in mandibular length, ramus length, mandibular area, and cranial area. Mandibular ramus length alone discriminated between the two groups in 71.4% of CP and in 62.5% of CL(P) cases, while separate analysis of fathers and mothers showed that ramus length and cranial height together reliably distinguish between mothers in 75% of CP and 80% of CL(P) cases. CONCLUSIONS: Previous studies suggests that unaffected parents with non-syndromic children with cleft lip and/or palate have differences in their craniofacial morphology when compared to the general population. This study indicates that these morphologic features differ for CP and CL(P).

Orthodontic treatment with fixed appliances in the General Dental Service in Scotland.

The records of 128 subjects treated by orthodontic specialists with fixed appliances in the General Dental Service in Scotland were randomly selected from the Scottish Dental Practice Board for analysis. The results of the study revealed that: (1) Mean post-treatment Peer Assessment Rating was 7.8 +/- 4.6 PAR points. (2) Mean reduction in PAR score was 14.9 +/- 10.6 PAR points. (3) Mean percentage reduction in PAR was 59 per cent. (4) Twenty-eight per cent of the cases were 'greatly improved', 15 per cent of the cases were made 'worse or no different'. (5) Median duration of treatment was 15 months, with a range of 2-41 months. (6) Multiple regression analysis showed that 82 per cent of the variability of PAR change could be predicted by the pretreatment PAR scores and the number of arches treated. Post-treatment PAR scores and duration of treatment could not be predicted with adequate reliability. It was concluded that although about 75 per cent of the cases were treated to at least acceptable alignment and occlusion, the modest average percentage reduction in PAR score could be explained by the low average initial PAR score and the borderline need for treatment in many cases.

Breakage incidence with direct-bonded lingual retainers.

This study examined the effects of a number of patient and clinical variables on the breakage of bonded retainers, and consisted of a retrospective review of the survival of 200 bonded retainers. Data was collected from two clinical centres between November 1996 and February 1997. The subjects comprised 198 patients of both sexes divided into three age groups. Retainers at both centres were made in 018-inch co-axial wire with Relyabond and Helioprogress adhesives used at each respective centre. The effects on time to first breakage of adhesive, patient sex, and arch (upper/lower) were considered using Kaplan Meier survival graphs and in Log Rank Tests. Finally, a Cox Proportional Hazard Model was used to examine the joint effects of these factors and the patients' ages. Breakage over a 5-year period with Relyabond was 38.8 per cent upper, 22.1 per cent lower, and with Helioprogress 75 per cent upper and 23.2 per cent lower. Breakage appears to be unrelated to the materials used or to the age and sex of the patients. Upper retainers break more often than lowers (P = 0.016) and early breakage is more likely to occur at an adhesive pad than at a wire (9.6 versus 2.5 per cent within 6 months).