Cost-effectiveness of radioguided occult lesion localization using 125I seeds versus hookwire localization before breast-conserving surgery for non-palpable breast cancer.

BACKGROUND: The aim was to determine the cost-effectiveness of radioguided occult lesion localization using 125I-labelled seeds (125I seeds) versus hookwire localization in terms of incremental cost per reoperation avoided for women with non-palpable breast cancer undergoing breast-conserving surgery. METHODS: This study was based on a multicentre RCT with eight study sites comprising seven public hospitals and one private hospital. An Australian public health system perspective was taken. The primary effectiveness outcome for this study was reoperations avoided. Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to explore uncertainty. The willingness to pay (additional cost of localization using 125I seeds justified by reoperation cost avoided) was set at the weighted, top-down cost of reoperation. Costs were in 2019 Australian dollars ($1 was equivalent to €0.62). RESULTS: The reoperation rate was 13.9 (95 per cent confidence interval 10.7 to 18.0) per cent for the 125I seed group and 18.9 (14.8 to 23.8) per cent for the hookwire localization group. The ICER for 125I seed versus hookwire localization was $4474 per reoperation averted. The results were most sensitive to uncertainty around the probability of reoperation. Accounting for transition probability and cost uncertainty for 125I seed localization, there was a 77 per cent probability that using 125I seeds would be cost-effective, with a willingness to pay of $7693 per reoperation averted. CONCLUSION: Radioguided occult lesion localization using 125I seeds is likely to be cost-effective, because the marginal (additional) cost compared with hookwire localization is less than the cost of reoperations avoided.

Pathways into and out of overweight and obesity from infancy to mid-childhood.

OBJECTIVES: To investigate whether high weight in infancy predicts obesity in childhood. METHOD: Data from two UK cohorts (Newcastle Growth and Development N = 795, Gateshead Millennium N = 393) and one Finnish (Tampere N = 1262) were combined. Z scores of weight at 3 and 12 months and body mass index (BMI) at 5 and 8 years were categorized as raised/overweight (1 to <2 SD) or high/obese (≥2 SD). RESULTS: The majority of infants with raised or high weight at birth tended to revert to normal by 3 months and to track in the same category from 3 to 12 months. Although infants with high weight were five times more likely to have BMI ≥ 2 SD at 8 years (p < 0.001), only 22% went on to have BMI ≥ 2 SD, while 64% of infants with raised weight had normal BMI at 8 years. Of children with BMI ≥ 2 SD aged 8 years, only 22% had raised weight in infancy and half had BMI ≥ 2 SD for the first time at that age. CONCLUSIONS: Infants with raised weight in infancy tend to remain so, but most children who go on to have BMI ≥ 2 SD were not unusually heavy infants and the majority of infants with high weight reverted to overweight or normal weight in childhood.

'Now I understand': consulting parents on chart design and parental information for the UK-WHO child growth charts.

BACKGROUND: Regular assessment of growth is an important part of child health surveillance in the UK and most parents are very interested in their child's growth. UK parents are given a personal child health record (PCHR), including growth charts, which are plotted during baby clinic visits. Parents were consulted as part of the process of designing new UK charts to incorporate the World Health Organization growth standard. This paper describes the main themes that emerged and how they influenced the final design. METHOD: Three sets of consultations with 47 parents were conducted to collect preliminary information, and to evaluate proposed chart designs, instructions and written information for parents. RESULTS: At every consultation, the impact of the depiction of the 50th centile line in bold was mentioned spontaneously by parents. They also found aspects of the charts unclear, including the implications of a recorded weight on any particular centile, the difficulty of understanding existing text about charts in the PCHR, their preference for using pounds and ounces rather than metric weights and confusion about how frequently babies should be weighed. This led to the production of parental information including explanation of these issues which were then tested in two further sets of focus groups. CONCLUSION: Involving parents in the process of designing growth charts and information influenced the finished design and the text in the PCHR. Ensuring information meets parents' needs is important to ensure successful growth monitoring.

Screening for activating EGFR mutations in surgically resected nonsmall cell lung cancer.

The clinical applicability of screening surgically resected nonsmall cell lung cancer (NSCLC) tumour tissue and serum for activating epidermal growth factor receptor (EGFR) mutation is unknown. Furthermore, the comparative accuracy of inexpensive EGFR mutation tests, mutant-enriched (ME)-PCR and high-resolution melt (HRM) has not been determined. Lung tumour DNA from 522 surgically resected stage I-IV NSCLC and matched serum DNA from a subset of 64 subjects was analysed for EGFR mutations in exons 19 and 21 using ME-PCR and HRM. Additionally, 97 subjects had previous EGFR DNA sequencing data available for comparison. ME-PCR and HRM detected EGFR mutations in 5% (27 out of 522) of tumour samples. Compared to DNA sequencing, ME-PCR had a sensitivity of 100% and specificity of 99%, while HRM had 100% sensitivity and specificity. Six subjects with EGFR mutation tumours had matched serum, where ME-PCR detected mutations in three samples and HRM in two samples. In the cohort of never-smoker subjects, those with EGFR mutated tumours had worse survival compared with wild-type tumours (30 versus 49 months; p=0.017). ME-PCR and HRM have similar accuracy in detecting EGFR mutations but the prognostic implications of the mutations in resected NSCLC warrants further study.

When do mothers think their child is overweight?

OBJECTIVE: To quantify how overweight children have to be for their mothers to classify them as overweight and to express concern about future overweight, and to investigate the adiposity cues in children that mothers respond to. DESIGN: Cross-sectional. SUBJECTS: A total of 531 children from the Gateshead Millennium Study cohort at 6-8 years and their mothers. MEASUREMENTS: In the mother: responses to two questions concerning the child's adiposity; height; weight; educational qualifications; and economic status. In the child: height; weight; waist circumference; skinfold thicknesses; bioelectrical impedance; and bone frame measurements. RESULTS: The body mass index (BMI) at which half the mothers classify their child as overweight was 21.3 (in the obese range for children of this age). The BMI at which half the mothers were concerned about their child becoming overweight in the future was 17.1 (below the overweight range). Waist circumference and skinfolds contributed most to mothers' responses. Although BMI and fat scores were important predictors individually, they did not contribute independently once waist circumference and skinfolds (their most visible manifestations) were included in the regression equations. Mothers were less likely to classify girls as overweight. Mothers with higher BMIs were less likely to classify their child as overweight, but were more likely to be concerned about future overweight. CONCLUSION: Health promotion efforts directed at parents of young primary school children might better capitalise on their concern about future overweight in their child than on current weight status, and focus on mothers' response to more visible characteristics than the BMI.

Tracking of obesity and body fatness through mid-childhood.

OBJECTIVES: To explore how fat, lean and body mass index (BMI) track in childhood and how this relates to parental obesity. DESIGN AND SETTING: Prospective population-based cohort study: Avon Longitudinal Study of Parents and Children, UK. METHOD: Height, weight and leg-to-leg bioelectrical impedance (BIA) were collected at ages 7 and 11 years, as well as pre-pregnancy parental heights and weights. For BMI International Obesity Task Force thresholds of obesity and overweight were used. Impedance data were expressed as separate lean and fat z scores, internally standardised for gender, height and age and a child was defined as over-fat if fat z score was >85th and very over-fat if >95th internal centile. RESULTS: Data were available for 7723 and 7252 children at ages 7 and 11 years, respectively (6066 at both time points). Of those obese at age 7, 75% were still obese at age 11, while of those who had been overweight 16% had become obese and 20% now had normal BMI. Both fat and lean z scores showed moderate levels of tracking (correlation coefficients 0.70 and 0.73, respectively). Children with one or two obese parents had higher fat z scores at age 7 and showed greater increases in fat thereafter. They were more likely to be very over-fat at age 7 and, of these, 69% remained so at age 11 compared to only 45% with non-obese parents (p <0.001). CONCLUSIONS: Children of obese parents already have high fat levels at age 7 and are more likely to remain very over-fat.

Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in nonsmall cell lung cancer.

Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P(450), family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association of CYP1A1 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate three CYP1A1 variants, CYP1A1*2A (rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)), CYP1A1*2C (rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) and CYP1A1*4 (rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods. The CYP1A1*2A and CYP1A1*2C variants were significantly over-represented in NSCLC cases compared with controls, whereas the CYP1A1*4 variant was under-represented. CYP1A1 haplotypes (in allele order CYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population. The present study has identified risk haplotypes for CYP1A1 in NSCLC and confirmed that CYP1A1 polymorphisms are a minor risk factor for NSCLC.

Family history? The forgotten question in high-risk colorectal cancer patients.

AIM: The aim of the study was to investigate the frequency and detail of family history recorded for patients diagnosed with potentially high-risk colorectal cancer, and to determine the proportion of these patients referred to a high-risk assessment clinic. METHOD: Medical records of patients diagnosed with colorectal cancer under the age of 50 admitted to a major Sydney teaching hospital were reviewed. The proportion of records containing information about family history was calculated. Associations between recording of family history and demographic and clinical characteristics of patients were investigated. Logistic regression modelling was performed to identify significant, independent predictors of study outcomes. RESULTS: Of 113 patients with colorectal cancer diagnosed under the age of 50 years, 61 (54%, 95% CI: 44-63%) had an entry in their hospital medical record about family history. Family history was significantly less likely to be recorded for females, for those admitted via the Emergency Department, and for those with shorter lengths of stay. A significant family history was found in 51% of the 61 patients who had a family history recorded. Records of patients attending specialist colorectal surgeons were significantly more likely to contain information about family history than those who attended other specialists (P = 0.04). Only 14 patients (12%, 95% CI: 7-20%) were formally referred for further genetic assessment. CONCLUSION: These results suggest that family history is still being neglected in routine clinical practice, and high-risk assessment services are underutilized, implying the need for further dissemination of guidelines with regard to the recognition and management of hereditary colorectal cancer.

Childhood growth and dental caries.

OBJECTIVES: The aim of the study was to examine whether the removal of carious teeth affected children's growth relative to that of a standard population. DESIGN: Longitudinal prospective observational study. SETTING: Manchester Dental Hospital (MDH), U.K. PARTICIPANTS: Five- and six-year-old children who attended for extraction of carious teeth under general anaesthesia. MAIN OUTCOME MEASURE: Change in height, weight and BMI standard deviation scores during the six months after extraction of carious teeth. METHODS AND MATERIALS: The children's dental caries levels, weight and height were measured prior to extraction using standard criteria and a single trained examiner and they were then re-measured six months later. The body mass index of the children was calculated and all measurements were converted to standard deviation scores (SDS) using the U.K. 1990 growth reference. Changes in growth SDS during the six months subsequent to the extractions were then calculated. RESULTS: Two hundred and eighteen children, mean (range) age 5.9 (5-6) were examined initially, of whom 131 were successfully followed up a mean 7.1 (0.13) months later. The participants had a mean dmft of 7.18 (SD 3.27) at baseline and were not shorter than expected (8.3% <10th percentile), or more underweight (6.9% <10th percentile for weight). At follow up children showed a statistically significant gain in BMI SDS (mean (SD) 0.26 (37) p < 0.001) and a small gain in height SDS (0.05 (0.38) p = 0.05). CONCLUSION: This study suggests that the extraction of carious teeth in five and six year old children promotes weight gain and possibly growth.

Targeting health visitor care: lessons from Starting Well.

BACKGROUND: UK child health promotion guidelines expect health visitors to assess family needs before new babies are aged 4 months and offer targeted care on that basis thereafter. Data from an intensive family support programme were used to assess how accurately family needs can be predicted at this stage. DESIGN: A population based cohort of 1202 families with new babies receiving an intensive health visiting programme. Analysis of routinely recorded data. SETTING: Starting Well project, Glasgow, UK. PREDICTORS: Health visitor rating of family needs. MAIN OUTCOME MEASURES: Families receiving high visiting rates or referred to social work services. RESULTS: Of 302 families rated high need, only 143 (47%) were identified by age 4 months. Visiting rates in the first year for those initially rated high need were nearly double those for the remainder, but around two thirds of those with high contact rates/referred to social work were not initially rated high need. Six family characteristics (no income, baby born preterm, multiple pregnancy, South Asian, prior social work/criminal justice involvement, either parent in care as a child) were identified as the commonest/strongest predictors of contact rates; 1003 (83%) families had one such characteristics and/or lived in a highly deprived area, including 228 (93%) of those with high contact rates and 157 (96%) of those referred to social work. CONCLUSIONS: Most families at risk will not be identified on an individual basis in the early weeks. Most families in deprived areas need continued input if the most vulnerable families are to be reliably identified.

The detection of early weight faltering at the 6-8-week check and its association with family factors, feeding and behavioural development.

AIMS: To identify infants with early weight faltering at the 6-8-week check and examine their family circumstances, feeding and behavioural development. METHODS: Over a 2-year period, the weight gain of all infants born in an area of North East England was screened. z Scores for weights at birth and at 6-8 weeks were used to calculate a "thrive index" (z score for weight gain). In a nested case-control study within the larger cohort, infants below the fifth centile on the thrive index were identified. 74 cases and 86 controls were followed up. Their development was assessed at 4 and 9 months using the Bayley Scales and their mothers interviewed. RESULTS: Of 1996 infants, weights at birth and at 6-8 weeks were available for 1880 (94%), and 6.1% of term-born infants were identified as weight faltering over the first 6-8 weeks. These infants had more feeding problems and showed some developmental delay as assessed using the Bayley Scales (at 4 months, mean difference and 95% CI -3.5, -0.6 to -6.4 for the Mental Developmental Index (MDI) and -3.6, -0.2 to - 6.9 for the Psychomotor Developmental Index (PDI); at 9 months -2.3, 1.3 to -5.8 for MDI and -2.2, 2.5 to -7.0 for PDI). Their families were not significantly different from those of controls on any economic or educational measure. CONCLUSION: Infants whose early weight gain is slow show more feeding problems than controls, and some developmental delay. They can be identified using a thrive index at the 6-8-week check.

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.

Association between systemic calcified atherosclerosis and bone density.

Both atherosclerosis and osteoporosis are responsible for significant morbidity and mortality, are independent predictors of cardiovascular disease (CVD) events, and may share common regulatory mechanisms as well as histopathology. Multiple reports of weak or null relationships between traditional CVD risk factors and calcified atherosclerosis have heightened interest in novel predictors of arterial calcium. One such hypothesis is for an inverse relationship between bone mineral density (BMD) and calcified coronary atherosclerosis. Although contrary findings have been reported, the majority of cross-sectional and all prospective studies have demonstrated a significant inverse association between arterial calcium deposits and BMD. The few studies that include men are equivocal, and, to date, no study has investigated the relationship between BMD and systemic arterial calcium. The aim of this study was to test the hypothesis that lumbar BMD is significantly associated with the presence of arterial atherosclerotic calcium in the carotid, coronary, and iliac vascular beds as well as the aorta.

Failure to thrive: the prevalence and concurrence of anthropometric criteria in a general infant population.

BACKGROUND: Failure to thrive (FTT) in early childhood is associated with subsequent developmental delay and is recognised to reflect relative undernutrition. Although the concept of FTT is widely used, no consensus exists regarding a specific definition, and it is unclear to what extent different anthropometric definitions concur. OBJECTIVE: To compare the prevalence and concurrence of different anthropometric criteria for FTT and test the sensitivity and positive predictive values of these in detecting children with "significant undernutrition", defined as the combination of slow conditional weight gain and low body mass index (BMI). METHODS: Seven criteria of FTT, including low weight for age, low BMI, low conditional weight gain and Waterlow's criterion for wasting, were applied to a birth cohort of 6090 Danish infants. The criteria were compared in two age groups: 2-6 and 6-11 months of life. RESULTS: 27% of infants met one or more criteria in at least one of the two age groups. The concurrence among the criteria was generally poor, with most children identified by only one criterion. Positive predictive values of different criteria ranged from 1% to 58%. Most single criteria identified either less than half the cases of significant undernutrition (found in 3%) or included far too many, thus having a low positive predictive value. Children with low weight for height tended to be relatively tall. CONCLUSIONS: No single measurement on its own seems to be adequate for identifying nutritional growth delay. Further longitudinal population studies are needed to investigate the discriminating power of different criteria in detecting significant undernutrition and subsequent outcomes.

Dietary and social characteristics of children with severe tooth decay.

BACKGROUND AND AIMS: Dental decay remains a major public health problem in Scottish children. The aim of this study was to investigate the relationship between diet, bowel habit, social class, and body mass index (BMI) in children with severe tooth decay. CHILDREN AND METHODS: A cross sectional study of 165 children aged 3 -11 years attending Glasgow Dental Hospital for extraction of teeth under dental general anaesthesia (DGA), was undertaken. A structured questionnaire was used to obtain information from each child on diet, bowel habit, and social status of their parents. Fibre and sugar scores were calculated from the frequency of consumption of a range of relevant foods. RESULTS: The children (mean age 5.7 (SD1.8) years) had between 1 and 20 decayed, missing or filled primary teeth (dmft) with a mean dmft of 7.9 (SD 3.5). 37% ate a chocolate bar daily, and 29% regularly drank a sugary drink after brushing their teeth. An excess of children were from the most deprived parts of the city and they had the worst decay. Children with the worst decay were also significantly thinner. No relationship was found between tooth decay and bowel habit. CONCLUSIONS: In this selected group of children with poor dental health, those from deprived families were over-represented and had significantly more decay. Severe dental decay was also associated with underweight.

Physical and emotional development, appetite and body image in adolescents who failed to thrive as infants.

BACKGROUND: Previous studies suggest that failure to thrive in infancy may be associated with adverse sequelae in childhood. Although cognitive abilities have been extensively investigated, little systematic research is available on other aspects of development. METHODS: Eighty-nine children who failed to thrive as infants and 91 controls were followed up when twelve years old and examined using anthropometric measurement, self-ratings of appetite and body image, the Dutch Eating Behaviour Questionnaire, the Self-perception Profile for Children, The Revised Children's Manifest Anxiety Scale, the parent and child form of the Mood and Feelings Questionnaire and the parent and teacher's form of the Child Behavior Checklist. RESULTS: The children who failed to thrive were significantly shorter and lighter at twelve and had significantly lower BMIs, but they did not go into puberty any later. They were more likely to rate their appetite as lower than their best friend's, were generally more satisfied with their body shape, and had significantly lower restraint score on the Dutch Eating Behaviour Questionnaire. They were not significantly different from controls on any of the measures reflecting anxiety, depression or low self-esteem. CONCLUSIONS: Failure to thrive in infancy is not associated with adverse emotional development in childhood.

Unilateral visual impairment and neurodevelopmental performance in preschool children.

BACKGROUND: Unilateral visual impairment (UVI) as a result of amblyopia or refractive error is common in childhood, but its functional significance remains largely unexplored. AIM: To investigate the influence of visual acuity and stereoacuity on the performance of preschool children on tasks requiring visuomotor skills and visuospatial ability. METHODS: Children with normal (6/6) visual acuity (VA) in both eyes and children with UVI ranging from 6/9 to 6/60, with no strabismus and normal vision in the fellow eye, were assessed on a neurodevelopmental test battery of visually guided tasks. RESULTS: 50 children (mean age (SD): 52.4 (5.7) months; median (range) VA: 6/9 (6/6 to 6/60); median (range) stereoacuity: 70 seconds arc (40-absent)) completed the test battery. UVI and stereoacuity correlated moderately (Pearson's r = 0.537, p < 0.001) but seven of 28 children with impaired VA had normal stereoacuity (< 70 seconds arc) while five of 22 with normal VA had abnormal stereoacuity. Stereoacuity correlated with performance on a task requiring fine hand-eye coordination and a task measuring visuomotor integration. UVI did not correlate with performance on any test battery items. CONCLUSIONS: UVI itself does not appear to relate to visuomotor actions, except when associated with reduced stereoacuity. Stereoacuity appears to have an influential role in fine visuomotor actions and spatial representation in preschool children.

The influence of maternal socioeconomic and emotional factors on infant weight gain and weight faltering (failure to thrive): data from a prospective birth cohort.

AIMS: To study the influence of maternal socioeconomic and emotional factors on infant weight gain and weight faltering (failure to thrive) in the first year of life. METHODS: The Gateshead Millennium Baby Study is a population birth cohort in northeast England studied prospectively from birth, via parental questionnaires and a health check aged 13 months. Data were collected on maternal education, deprivation, eating attitudes, and depression, using the Edinburgh Post Natal Depression Scale (EPDS) at 3 months. Weight gain was assessed using change in weight SD score, conditional on birth weight (Thrive Index); weight faltering was defined as conditional weight gain below the 5th centile. RESULTS: Of 923 eligible infants born at term, 774 (84%) had both weight and questionnaire data. Replicating a previous finding, both the highest and the lowest levels of deprivation were associated with weight faltering; this was independent of the type of milk feeding. No relation was found with maternal educational status. Maternal eating restraint was unrelated to weight gain. Infants of mothers with high depression symptom scores (EPDS >12) had significantly slower weight gain and increased rates of weight faltering up to 4 months (relative risk 2.5), especially if they came from deprived families, but by 12 months they were no different from the remainder of the cohort. CONCLUSIONS: In this setting, social and maternal characteristics had little influence on infants' weight gain, apart from a strong, but transient effect of postnatal depression.