Oral 11ß-HSD1 inhibitor AZD4017 improves wound healing and skin integrity in adults with type 2 diabetes mellitus: a pilot randomized controlled trial.

BACKGROUND: Chronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11ß-hydroxysteroid dehydrogenase type 1, 11ß-HSD1) impair wound healing. OBJECTIVES: Efficacy, safety, and feasibility of 11ß-HSD1 inhibition for skin function and wound healing. DESIGN: Investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial. METHODS: Single-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11ß-HSD1 inhibitor AZD4017 (n = 14) or placebo (n = 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized. RESULTS: Exploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h ex vivoskin 11ß-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: -3.4 to 5.5) but reduced systemic 11ß-HSD1 activity by 87% (69-104%). Wound diameter was 34% (7-63%) smaller with AZD4017 at day 2, and 48% (12-85%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9/month, 27/28, and 95.3%, respectively. CONCLUSION: A phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers. SIGNIFICANCE STATEMENT: Stress hormone activation by the enzyme 11ß-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11ß-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11ß-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11ß-HSD type 1 as a novel therapeutic target forchronic wounds.

Premature ovarian insufficiency: an International Menopause Society White Paper.

The aim of this International Menopause Society White Paper on premature ovarian insufficiency (POI) is to provide the latest information regarding this distressing condition. The impact of POI has far-reaching consequences due to its impact on general, psychological, and sexual quality of life, fertility prospects, and long-term bone, cardiovascular, and cognitive health. Progress in fully understanding the etiology, diagnosis, and optimal management options has been slow thus far due to the complexity of the condition and fragmented research. Recent advances in epidemiological and genetic research have improved our understanding of this condition and randomized prospective trials are being planned to determine the intervention strategies, which will optimize quality of life and long-term well-being. The International Menopause Society has commissioned a number of experts at the forefront of their specialty to define the state of the art in the understanding of this condition, to advise on practical management strategies, and to propose future research strategies. It is hoped that a global task force will subsequently be convened in order to formulate a consensus statement across key societies, to accelerate date collection and analysis of a global POI registry, and to facilitate progress in the key defined areas of research.

ESHRE Guideline: management of women with premature ovarian insufficiency.

STUDY QUESTION: What is the optimal management of women with premature ovarian insufficiency (POI) based on the best available evidence in the literature? SUMMARY ANSWER: The guideline development group (GDG) formulated 99 recommendations answering 31 key questions on the diagnosis and treatment of women with POI. WHAT IS KNOWN ALREADY: NA. STUDY DESIGN, SIZE, DURATION: This guideline was produced by a multidisciplinary group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to September 2014 and consensus within the guideline group on all recommendations. The GDG included a patient representative to ensure input from women with POI. After finalization of the draft, the European Society for Human Reproduction and Embryology (ESHRE) members and professional organizations were asked to review the guideline. PARTICIPANTS/MATERIALS, SETTING, METHODS: NA. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 17 recommendations on diagnosis and assessment of POI and 46 recommendations on the different sequelae of POI and their consequences for monitoring and treatment. Furthermore, 24 recommendations were formulated on hormone replacement therapy in women with POI, and two on alternative and complementary treatment. A chapter on puberty induction resulted in five recommendations. LIMITATIONS, REASONS FOR CAUTION: The main limitation of the guideline is that, due to the lack of data, many of the recommendations are based on expert opinion or indirect evidence from studies on post-menopausal women or women with Turner Syndrome. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limitations, the guideline group is confident that this document will be able to guide health care professionals in providing the best practice for managing women with POI given current evidence. Furthermore, the guideline group has formulated research recommendations on the gaps in knowledge identified in the literature searches, in an attempt to stimulate research on the key issues in POI. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the implementation of the guideline. The guideline group members did not receive payment. Dr Davies reports non-financial support from Novo Nordisk, outside the submitted work; the other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: NA.

Childhood obesity patterns and relation to middle-age sleep apnoea risk: the Bogalusa Heart Study.

BACKGROUND: Obese adults have a higher risk of obstructive sleep apnoea (OSA); however, the relationship between childhood obesity and adult OSA risk is unclear. Objectives This study aimed to examine overweight/obesity (OW) in childhood and risk of OSA in middle age. METHODS: Childhood OW status was classified as never OW, weight cycling, persistent OW and incident OW. After 35 years of follow-up, high risk for OSA was determined by a positive score in ≥2 domains on the Berlin Questionnaire with obesity removed from scoring. RESULTS: At initial assessment, mean (SD) age was 9.9 (2.9) years, and 23.9% were OW. Overall, 25.7% had scores indicating a high risk for OSA. Compared with participants who were never OW, those with persistent OW and incident OW were 1.36 (95%CI: 1.04-1.77) and 1.47 (1.11-1.96) times more likely to be high risk for OSA, after adjustment for multiple risk factors and adult OW status. Participants with an OW duration of 1-4 years, 5-8 years, and 8+ years were 0.96 (0.44-2.09), 1.20 (0.70-2.04) and 1.52 (1.22-1.90) times more likely to be high risk for OSA compared with those who were never OW (P for trend: 0.0002). CONCLUSIONS: These results suggest that childhood OW is associated with a high risk of OSA in middle age.

Nuclear changes in oral mucosa of alcoholics and crack cocaine users.

The effects of drugs of abuse on oral mucosa are only partly understood. The aims of the present study were to: (1) evaluate the frequency of nuclear changes in normal-appearing oral mucosa of alcoholics and crack cocaine users and (2) assess their association with cell proliferation rate. Oral smears were obtained from the border of the tongue and floor of the mouth of 26 crack cocaine users (24 males and 2 females), 29 alcoholics (17 males and 12 females), and 35 controls (17 males and 18 females). Histological slides were submitted to Feulgen staining to assess the frequency of micronuclei (MN), binucleated cells (BN), broken eggs (BE), and karyorrhexis (KR). A significant increase in the frequency of MN was observed in cells exfoliated from the tongue of crack cocaine users (p = 0.01), and alcoholics showed a higher frequency of KR in cells obtained from the floor of the mouth (p = 0.01). Our findings suggest that the use of crack cocaine induces clastogenic effects, whereas alcoholism is associated with higher degrees of keratinization in the floor of the mouth.

Which measures of adiposity predict subsequent left ventricular geometry? Evidence from the Bogalusa Heart Study.

BACKGROUND AND AIMS: Left ventricular (LV) hypertrophy increases the risk of future cardiovascular events. The relationship between obesity in young adulthood and later LV geometry is unknown. We examined the association between long-term changes in measures of adiposity and subsequent LV geometry among 1073 young adults from the Bogalusa Heart Study. METHODS AND RESULTS: Echocardiography-measured LV geometry was classified into normal (N = 796), concentric remodeling (N = 124), eccentric hypertrophy (N = 99), and concentric hypertrophy (N = 54) by integrating relative wall thickness and LV mass index. The mean age of our population was 38 years when the LV geometry was measured. Body mass index (BMI) increased by a mean of 4.9 kg/m(2) over a median of 20 years, waist circumference (WC) by 10.9 cm over 17 years, waist/hip ratio by 0.02 over 10 years, waist/height ratio by 0.06 over 17 years, abdominal height by 0.9 cm over 10 years, body fat (BF) percentage by 12.7% over 20 years, and Visceral Adiposity Index by 0.30 over 17 years. In polytomous logistic regression models corrected for multiple comparisons, participants with one-standard-deviation increases in BMI, WC, waist/height ratio, and BF had 2.00 (95% confidence interval (CI): 1.53-2.61), 1.33 (1.06-1.68), 1.35 (1.07-1.70), and 1.60 (1.26-2.03) times the risk of eccentric hypertrophy, respectively, after adjustment for demographic, lifestyle, metabolic risk factors, and follow-up time. Likewise, the rates of change in BMI, WC, waist/height ratio, and BF were associated with eccentric hypertrophy. There was no association with concentric remodeling or concentric hypertrophy. CONCLUSIONS: Our findings suggest that increases in BMI, WC, waist/height ratio, and BF were strong predictors of eccentric hypertrophy in middle age.

A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†.

BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR). RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation. CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups. TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

The prevalence of HIV in Pretoria's Medico-Legal Laboratory cases; RSA; in 2009

The purpose of this study was to determine the prevalence of Human Immunodeficiency Virus (HIV) amongst decedents admitted to the Pretoria Medico-Legal Laboratory (MLL). The study was designed as a cross sectional study. It is not standard procedure for the pathologist to do a HIV test at autopsy. Post mortem (PM) blood samples were obtained from all bodies admitted to the Pretoria MLL during one month in 2009. Analysis of the blood samples was performed using standardised laboratory procedures. Two hundred and thirty-eight PM blood samples were collected. In 43 cases (17); the test results were invalid. Of the 195 valid test samples; 51 (26.2) were HIV-positive. The prevalence of HIV in this study was 15 higher than that reported in a similar study done 10 years previously

The prevalence of HIV in Pretoria's Medico-Legal Laboratory cases; RSA; in 2009

The purpose of this study was to determine the prevalence of Human Immunodeficiency Virus (HIV) amongst decedents admitted to the Pretoria Medico-Legal Laboratory (MLL). The study was designed as a cross sectional study. It is not standard procedure for the pathologist to do a HIV test at autopsy. Post mortem (PM) blood samples were obtained from all bodies admitted to the Pretoria MLL during one month in 2009. Analysis of the blood samples was performed using standardised laboratory procedures. Two hundred and thirty-eight PM blood samples were collected. In 43 cases (17); the test results were invalid. Of the 195 valid test samples; 51 (26.2) were HIV-positive. The prevalence of HIV in this study was 15 higher than that reported in a similar study done 10 years previously

Hepcidin levels in diabetes mellitus and polycystic ovary syndrome.

AIM: Increased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load. METHODS: Serum concentrations of the active form of hepcidin (hepcidin-25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI, n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI, n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI, n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16). RESULTS: Participants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = -0.59, P < 0.05). CONCLUSION: Insulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin-resistant states.

Apples and oranges: a comparison of costing methods for obesity.

Obesity has escalated to epidemic proportions over the past 30 years resulting in increased disease burden and healthcare costs. The aim of this paper was to analyse different costing methods for obesity. Several databases have been searched to identify eligible literature estimating obesity cost. These were categorized into databases, patient-attributable fraction (PAF) and modelling studies. Studies from the United States were used to explore effects of study designs on cost outcomes. Our results show that cost outcomes are largely affected by underlying study designs, such as population size, age, cost categories (medical expenditure vs. total costs), length of the data collection and body mass index cut-offs. Three study types are likely to have an impact on reported costs, with modelling studies providing the most conservative estimates. Database studies can help to increase the overall awareness of the economic burden of obesity. PAF studies can make the obesity disease more tangible by drawing connections to diseases. Decision makers need to be aware of the different purposes and weaknesses of the studies when interpreting cost outcomes. Further research is needed to refine the existing methods and provide high-quality data accounting for the complexity of the disease.

The content validity of the Behaviour Support Plan Quality Evaluation tool (BSP-QEII) and its potential application in accommodation and day-support services for adults with intellectual disability.

BACKGROUND: The quality of support provided to people with disability who show challenging behaviour could be influenced by the quality of the behaviour support plans (BSPs) on which staff rely for direction. This study investigated the content validity of the Behaviour Support Plan Quality Evaluation tool (BSP-QEII), originally developed to guide the development of BSPs for children in school settings, and evaluated its application for use in accommodation and day-support services for adults with intellectual disability. METHOD: A three-round Delphi study involving a purposive sample of experienced behaviour support practitioners (n = 30) was conducted over an 8-week period. The analyses included deductive content analysis and descriptive statistics. RESULTS: The 12 quality domains of the BSP-QEII were affirmed as valid for application in adult accommodation and day-support service settings. Two additional quality domains were suggested, relating to the provision of detailed background on the client and the need for plans to reflect contemporary service philosophy. Furthermore, the results suggest that some issues previously identified in the literature as being important for inclusion in BSPs might not currently be a priority for practitioners. These included: the importance of specifying replacement or alternative behaviours to be taught, descriptions of teaching strategies to be used, reinforcers, and the specification of objective goals against which to evaluate the success of the intervention programme. CONCLUSIONS: The BSP-QEII provides a potentially useful framework to guide and evaluate the development of BSPs in services for adults with intellectual disability. Further research is warranted to investigate why practitioners are potentially giving greater attention to some areas of intervention practice than others, even where research has demonstrated these others areas of practice could be important to achieving quality outcomes.

Reliability and utility of the Behaviour Support Plan Quality Evaluation tool (BSP-QEII) for auditing and quality development in services for adults with intellectual disability and challenging behaviour.

BACKGROUND: Having an objective means of evaluating the quality of behaviour support plans (BSPs) could assist service providers and statutory authorities to monitor and improve the quality of support provided to people with intellectual disability (ID) who exhibit challenging behaviour. The Behaviour Support Plan Quality Evaluation Guide II (BSP-QEII) was developed to monitor and assess BSPs prepared by teachers to support children with disability in the school system. This study investigated the application of the BSP-QEII to the assessment of BSPs for adults with ID in community support services. METHOD: The inter-rater reliability of the BSP-QEII was assessed. The utility of the BPS-QEII was then investigated with reference to a time series study of matched pairs of BSPs, developed for the same clients over a period of approximately 3 years. Differences in plan quality measured across a number of service and systemic variables were also investigated. RESULTS: The BSP-QEII was found to have good inter-rater reliability and good utility for audit purposes. It was able to discriminate changes in plan quality over time. Differences in plan quality were also evident across different service types, where specialist staff had or had not been involved, and in some instances where a statutory format for the plan had or had not been used. There were no differences between plans developed by government and community sector agencies, nor were there any regional differences across the jurisdiction. CONCLUSIONS: The BSP-QEII could usefully be adopted as an audit tool for measuring the quality of BSPs for adults with ID. In addition to being used for research and administrative auditing, the principles underpinning the BSP-QEII could also be useful to guide policy and educational activities for staff in community based services for adults with ID.

Modelling obesity trends and related diseases in Eastern Europe.

Obesity has increased at an alarming rate across the world and, in turn, rates of non-communicable diseases have escalated. In Eastern Europe, this epidemic has probably occurred at a later stage than the West due to the economic transition following the demise of communism. Knowing how these trends will change is important. We used a micro-simulation model to project obesity trends and related incidence of coronary heart disease and stroke, cancer and type 2 diabetes 20 and 40 years into the future. Where nationally representative data were available, obesity levels were shown to increase with most prominent increases seen amongst men in Latvia and Estonia, and amongst women in Croatia and Latvia. The exception was Lithuania where a decrease in overweight and obesity was observed in both men and women. We showed that interventions effective in reducing obesity would have a significant impact upon the number of new cases of each disease. It is necessary to improve surveillance of obesity and disease incidence as well as implement policies that are effective in reducing body fat.

Maternal perception of the causes and consequences of sibling differences in eating behaviour.

BACKGROUND/OBJECTIVES: The aim of this study is to explore mothers' perceptions of differences between their children in the eating behaviour domain. SUBJECTS/METHODS: Twelve semistructured interviews were carried out with mothers who had at least two children aged between 6 and 15 years, to discuss feeding experiences, particularly around healthy eating. Interviews were recorded and transcribed verbatim and analysed using Framework Analysis. RESULTS: Mothers frequently identified differences in appetite and food preferences between their children, which they attributed largely to genetic factors. These sibling differences meant that although feeding goals might be common, the pathways to the goals varied depending on each child's appetitive characteristics. The overall pattern was one of flexible responsiveness to each child. In contrast to perceptions of their own children's eating behaviours, feeding difficulties in other families were usually attributed to lack of parental control. CONCLUSIONS: The feeding relationship is complex and interactive, resulting in parents modulating their feeding strategies to match each child's eating behaviour. Guidance to parents on healthy feeding needs to acknowledge the nuanced and interactive nature of feeding practices.

Associations between child weight and maternal feeding styles are mediated by maternal perceptions and concerns.

OBJECTIVE: To determine whether controlling parental feeding practices are associated with children's adiposity and test the hypothesis that any associations are mediated by maternal perception of their child's weight. METHOD: Children aged 7-9 years (n=405) were weighed and measured at school as part of the Physical Exercise and Appetite in CHildren Study (PEACHES). Adiposity was indexed with body mass index s.d. scores. The Child Feeding Questionnaire was completed by 53% of mothers of participating children (n=213). Mothers reported whether they thought their child was overweight, normal weight or underweight, and rated their concern about future overweight on a 5-point scale. RESULTS: Higher child adiposity was associated with lower 'pressure to eat' and higher 'restriction' scores. Restriction increased linearly with maternal concern about overweight, and maternal concern about overweight fully mediated the association between child adiposity and restriction. Use of pressure increased as mothers perceived their child to be thinner, but perceived weight did not mediate the association between child weight status and maternal pressure to eat. Monitoring was not associated with child adiposity, maternal perception of weight or concern about overweight. CONCLUSION: Restriction appears to be a consequence of mothers' concern about their child becoming overweight rather than a cause of children's weight gain. Pressure may be a more complex response that is influenced by the desire to encourage consumption of healthy foods as well as ensure adequate energy intake and appropriate weight gain.

Energy density of foods, but not beverages, is positively associated with body mass index in adult women.

BACKGROUND/OBJECTIVES: Energy density (kJ/g) may have a strong influence on energy balance. Although beverages are a considerable source of energy in the United States diet, rarely have studies among free-living populations investigated the energy density of foods (EDF) and the energy density of beverages (EDB) simultaneously. We examined the independent simultaneous associations of EDF and EDB on energy intake and body mass index (BMI) in adult women. SUBJECTS/METHODS: This cross-sectional design focused on 348 elementary school employees randomly selected at baseline of a worksite wellness trial in southeastern Louisiana. Two 24-h recalls were collected, and measured heights and weights were converted into BMI (kg/m(2)). RESULTS: Those in the highest EDF tertile consumed more energy and had higher BMIs than those in the lowest tertile (P<0.05). Employees in the highest EDB tertile consumed more energy than those in the lowest, yet there was no difference in BMIs between the two groups. Multivariate regression, with controls for demographic and health variables, confirmed the positive association between EDF and BMI; a 1 kJ/g increase in EDF was associated with a 0.39 kg/m(2) increase in BMI (P=0.038). Models that did not control for EDB gave estimates of EDF that were 8-10% lower. CONCLUSIONS: These findings suggest that EDF and EDB have important, yet distinct, functions in energy intake and BMI. Future studies should evaluate both types of energy density as independent predictors as our results suggest that EDB can confound the association of EDF with BMI.

Early predictors of anastomotic leaks after colectomy.

BACKGROUND: An anastomotic leak after colorectal surgery is associated with significant morbidity and decreased survival. Our aim was to identify the early predictors of anastomotic leaks. METHODS: The records of patients undergoing restorative resection for colorectal disease from January 2000 to November 2005 were reviewed. Demographics, clinical events, and laboratory parameters were recorded. RESULTS: A total of 311 patients were included. An anastomotic leak was identified in 25 patients (8%). A leak was suspected and diagnosis confirmed at a mean of 10+/-1 days postoperatively. More respiratory and neurological events occurred in patients with an anastomotic leak (p<0.001). These events occurred early in the postoperative course and were usually the first signs and symptoms of a leak. More patients with a leak had absence of bowel activity by postoperative day 6 compared to patients without a leak (p<0.0001). Elevations of the white blood cell count or temperature were a late finding. CONCLUSION: The earliest clinical predictors of an anastomotic leak are pulmonary and/or neurological. Awareness of these findings might help in early diagnosis and treatment of an anastomotic leak.

Eating behaviour and weight in children.

OBJECTIVE: To test the hypothesis that quantitative variation in eating behaviour traits shows a graded association with weight in children. DESIGN: Cross-sectional design in a community setting. SUBJECTS: Data were from 406 families participating in the Physical Exercise and Appetite in CHildren Study (PEACHES) or the Twins Early Development Study (TEDS). Children were aged 7-9 years (PEACHES) and 9-12 years (TEDS). MEASUREMENTS: Weights and heights were measured by researchers. Body mass index (BMI) s.d. scores were used to categorize participants into underweight, healthy weight, overweight and obese groups, with an additional division of the healthy weight group into higher and lower healthy weight at the 50th centile. Eating behaviour traits were assessed with the Child Eating Behaviour Questionnaire (CEBQ), completed by the parents on behalf of their child. Linear trend analyses compared CEBQ subscale scores across the five weight groups. RESULTS: Satiety Responsiveness/Slowness in Eating and Food Fussiness showed a graded negative association with weight, whereas Food Responsiveness, Enjoyment of Food, Emotional Overeating and Desire to Drink were positively associated. All effects were maintained after controlling for age, sex, ethnicity, parental education and sample. There was no systematic association with weight for Emotional Undereating. CONCLUSION: These results support the idea that approach-related and avoidance-related appetitive traits are systematically (and oppositely) related to adiposity, and not exclusively associated with obesity. Early assessment of these traits could be used as indicators of susceptibility to weight gain.