Gamma-glutamyl-transferase is associated with incident hip fractures in women and men ≥ 50 years: a large population-based cohort study.

The association of serum gamma-glutamyl-transferase (GGT) with hip fracture risk has not been examined in women and men ≥ 50 years. We show that elevated GGT was associated with increased hip fracture risk, particularly in men. GGT could be a candidate serum marker of long-term hip fracture risk in the elderly. INTRODUCTION: We herein examined a possible relation between serum levels of GGT and hip fracture risk in women and men aged ≥ 50 years, which has not been investigated before. METHODS: In this population-based prospective cohort study, approximately 41,000 women and nearly 33,000 men ≥ 50 years participating in a medical prevention program 1985-2005 in western Austria were followed up for the occurrence of osteoporotic hip fractures during 2003-2013. ICD-10 based discharge diagnoses for hip fracture included S72.0, S72.1, and S72.2 available from all regional hospitals. GGT-related hip fracture risk was ascertained at each participant´s first and last examination during the prevention program. In a subset of 5445 participants, alcohol consumption could be included as a covariate. RESULTS: In men, hip fracture risk rose significantly by 75% and 86% for every tenfold increase of GGT measured at the first and last examination, respectively, and in women, hip fracture risk rose by 22% from the last examination. Elevated GGT (≥ 36 U/l in women, ≥ 56 U/l in men) at the first examination was associated with increased hip fracture risk only in men (HR 1.51, 95% CI 1.25-1.82), and at the last examination in both women (HR 1.14, 95% CI 1.02-1.28) and men (HR 1.61, 95% CI 1.33-1.95). Alcohol consumption had no significant influence on GGT-mediated hip fracture risk in women and men. CONCLUSIONS: Our findings identified an association of elevated GGT and hip fracture in women and men ≥ 50 years and suggest GGT as a candidate serum marker of long-term hip fracture risk in an elderly population.

Statins, diabetes mellitus and prognosis of amyotrophic lateral sclerosis: data from 501 patients of a population-based registry in southwest Germany.

BACKGROUND AND PURPOSE: A wide variety of metabolic changes, including an increased incidence of diabetes mellitus (DM) and dyslipidaemia, has been described in amyotrophic lateral sclerosis (ALS). The aim of this study was to investigate the associations of statin use and history of DM with onset of disease and survival in patients with ALS. METHODS: In all, 501 patients (mean age 65.2 ± 10.9 years; 58.5% male) from the ALS Registry Swabia recruited between October 2010 and April 2016 were included in this prospective cohort study. Data were collected using a standardized questionnaire. RESULTS: Statin use (n = 65) was not associated with overall survival (P = 0.62). Age of ALS onset in patients with DM was 4.2 years later (95% confidence interval 1.3-7.2 years) than in patients without DM (P < 0.01). The overall survival of patients with high body mass index at study entry (>27.0 kg/m2 , upper quartile, n = 127) was prolonged by more than 5 months compared to patients with low body mass index (<22.0 kg/m2 , lower quartile, n = 123; P = 0.04). CONCLUSIONS: This study supports the view that statin use is not associated with overall survival of ALS patients, suggesting that statins are not harmful and should not be discontinued in ALS. Furthermore, the delayed onset of ALS in patients with DM may mirror the potentially protective metabolic profile associated with type 2 DM. Consistently, this study provides further evidence that high body mass index is a positive prognostic factor in ALS.

The effect of age on the shape of the BMI-mortality relation and BMI associated with minimum all-cause mortality in a large Austrian cohort.

BACKGROUND: It is unclear if the body mass index (BMI) associated with minimum all-cause mortality is constant throughout adult life or increasing with age. METHODS: We applied multivariable fractional polynomials to the data of the Vorarlberg Health Monitoring and Prevention Program to quantify the BMI associated with minimum mortality over age. The analysis included data of 129,904 never-smoking women and men (mean age: 45.4 years) who were followed for a median of 18.6 years. RESULTS: Optimum BMI in women increased with age, lying within the normal BMI category (according to the World Health Organization definition) from the age of 20 years (23.3 kg m(-2), 95% confidence interval (CI): 22.2-24.3) to the age of 54 years and in the lower half of the overweight category from the age of 55 years onwards, reaching 26.2 kg m(-2) (95% CI: 25.1-27.3) at the age of 69 years. In men, optimum BMI increased slightly from 23.7 kg m(-2) (95% CI: 22.1-25.2) at the age of 20 years until the age of 59 years, reaching a BMI of 25.4 kg m(-2) (95% CI: 24.8-26.0) and decreased afterwards to 22.7 kg m(-2) (95% CI: 20.9-24.6) at the age of 80 years. CONCLUSIONS: Our results indicate that BMI associated with minimum all-cause mortality changes with age and that patterns differ by sex. Sex- and age-independent BMI recommendations might therefore be inappropriate. Further studies using flexible methods instead of predefined categories are necessary to revise BMI recommendations.

Asthma phenotypes identified by latent class analysis in the ISAAC phase II Spain study.

BACKGROUND: Classification of respiratory symptoms may help to identify different underlying asthma phenotypes reflecting differences in aetiology and prognosis of wheezing disease among children. OBJECTIVE: To determine childhood asthma phenotypes based on respiratory symptoms from a widely used questionnaire to further classify phenotypes in international settings. METHODS: Between 2000 and 2002 cross-sectional studies were performed in four centres in Spain. Parental questionnaires were used to collect information on allergic diseases in more than 4000 children aged 8-12 years. In addition, objective markers for allergic sensitization and bronchial hyperresponsiveness (BHR) were measured. Latent class analyses (LCA) were applied to identify subgroups of children according to respiratory symptoms, and then the association of these groups with relevant clinical features such as concomitant allergic disease symptoms, atopy and BHR was studied. RESULTS: We found seven classes, one corresponding to healthy children, three classes related to wheeze and three other classes mainly related to congestion and coughed-up phlegm. These tentative phenotypes differed in severity of symptoms and also in clinical correlates such as BHR and allergic sensitization. Atopy was more predominant in the 'wheeze phenotypes' whereas concomitant 'allergic' symptoms were most frequent in two of the 'wheeze phenotypes' and one of the 'cough phenotypes'. CONCLUSIONS: LCA on reported symptoms in a cross-sectional survey allowed different subgroups with meaningful clinical correlates to be defined. It remains to be investigated to what extent these groups also have different aetiologies, prognoses and therapeutic needs.

Influence of Mediterranean diet on asthma in children: a systematic review and meta-analysis.

BACKGROUND: There is epidemiological evidence that Mediterranean diet exposure is associated with lower asthma prevalence in children. We aimed to summarize the available data and to know whether the Mediterranean setting modifies this association. METHODS: The literature search, up to May 2012, was on epidemiological studies in the general population of children assessing whether adherence to Mediterranean diet (measured as a score) was associated with the prevalence of 'current wheeze'; 'current severe wheeze'; or 'asthma ever'. Odds ratios (OR) of the eight included studies compared the highest tertile of the score with the lowest. Random-effects meta-analyses for the whole group of studies and stratified by Mediterranean setting (centers <100 Km from the Mediterranean coast) were performed. Differences between strata were assessed using the Q test. RESULTS: For 'current wheeze', there was a negative significant association with the highest tertile of Mediterranean diet score (OR 0.85, 95% CI 0.75-0.98; p = 0.02), driven by Mediterranean centers (0.79, 0.66-0.94, p = 0.009), although the difference with the non-Mediterranean centers (0.91, 0.78-1.05, p = 0.18) was not significant. The results for 'current severe wheeze' were as follows: 0.82, 0.55-1.22, p = 0.330 (all); 0.66, 0.48-0.90, p = 0.008 (Mediterranean); and 0.99, 0.79-1.25, p = 0.95 (non-Mediterranean); with the difference between regions being significant. For 'asthma ever', the associations were as follows: 0.86, 0.78-0.95, p = 0.004 (all); 0.86, 0.74-1.01, p = 0.06 (Mediterranean); 0.86, 0.75-0.98; p = 0.027 (non-Mediterranean); with the difference between regions being negligible. CONCLUSIONS: Adherence to the Mediterranean diet tended to be associated with lower occurrence of the three respiratory outcomes. For current and current severe wheeze, the association was mainly driven by the results in Mediterranean populations.

18†Engaging with young people to improve research, services and workforce development: eye-YPAG and 'visually' workshops.

Involving children and young people (CYP) in service and research design improves quality and accessibility. Running events in schools to invite CYP to volunteer and explore careers in the NHS may contribute to uptake of training posts and developing the NHS workforce.Here we evaluate two activities with CYP, our Young Person's Advisory Group for research (eye-YPAG) and our workshop for secondary schools, 'visually'.We evaluated eye-YPAG in focus groups and online surveys with group members, parents/carers, researchers, facilitators and funders. We conducted thematic analysis and descriptive statistics. To evaluate 'visually', we monitored the numbers of workshops and young people applying for volunteering roles. We asked those who started working with us about their experience.eye-YPAG members valued social and creative aspects as well as learning about research and developing skills and confidence. Researchers reported that CYP gave novel suggestions, modifying research plans, and that their different perspective was helpful in making research more relevant for children and families.Over 6 months, we held 15 'visually' workshops in secondary schools. Ninety students applied for volunteering roles, and 20 have completed the Human Resources onboarding process. Young volunteers report that this work has increased their confidence and that they have gained insights into how a hospital works. One is considering training to become an orthoptist.Both eye-YPAG and 'visually' are available to all eye researchers and units in the UK and can facilitate outreach activities.

Metabolic risk factors and skin cancer in the Metabolic Syndrome and Cancer Project (Me-Can).

BACKGROUND: Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). OBJECTIVES: To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). METHODS: During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. RESULTS: Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04-1·31 and HR 1·18, 95% CI 1·03-1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58-3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P-trend 0·02) and there was a trend with triglyceride concentration (P-trend 0·09). CONCLUSION: These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.

Metabolic syndrome and rare gynecological cancers in the metabolic syndrome and cancer project (Me-Can).

BACKGROUND: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. MATERIALS AND METHODS: The Metabolic syndrome and Cancer project cohort includes 288,834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. RESULTS: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). CONCLUSION: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors.

Lack of evidence for a protective effect of prolonged breastfeeding on childhood eczema: lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

BACKGROUND: Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease. OBJECTIVES: To investigate whether exclusive breastfeeding protects against childhood eczema. METHODS: Study subjects comprised 51,119 randomly selected 8- to 12-year-old schoolchildren in 21 countries. Information on eczema and breastfeeding was gathered by parental questionnaire. Children were also examined for flexural eczema and underwent skin prick testing. Odds ratios (ORs) were calculated for each study centre and then pooled across populations. RESULTS: There was a small increase in the risk of reported 'eczema ever' in association with 'breastfeeding ever' and breastfeeding < 6 months [pooled adjusted OR 1·11, 95% confidence interval (CI) 1·00-1·22 and OR 1·10, 95% CI 1·02-1·20, respectively]. There was no significant association between reported 'eczema ever' and breastfeeding > 6 months (pooled adjusted OR 1·09, 95% CI 0·94-1·26). Risk estimates were very similar for exclusive breastfeeding < 2 months, 2-4 months and > 4 months and for eczema symptoms in the past 12 months and eczema on skin examination. As for more severe eczema, breastfeeding per se conveyed a risk reduction on sleep disturbed eczema (pooled adjusted OR 0·71, 95% CI 0·53-0·96), but this effect was lost where children had been exclusively breastfed for > 4 months (pooled adjusted OR 1·02, 95% CI 0·67-1·54). Allergic sensitization and a history of maternal allergic disease did not modify any of these findings. CONCLUSIONS: Although there was a protective effect of ever having been breastfed on more severe disease, we found no evidence that exclusive breastfeeding for 4 months or longer protects against eczema. Our results are consistent with findings from a recent systematic review of prospective studies. The U.K. breastfeeding guidelines with regard to eczema should be reviewed. Intervention studies are now required to explore how and when solids should be introduced alongside breastfeeding to aid protection against eczema and other allergic diseases.

Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.

International variations in associations of allergic markers and diseases in children: ISAAC Phase Two.

BACKGROUND: Circulating allergen-specific IgE (sIgE) and skin prick tests (SPT) are used to define atopy. Downregulation of local inflammatory responsiveness has been proposed to explain a low prevalence of positive SPTs in less affluent countries. We analysed the association between SPTs, total and allergen-specific IgE and their relationships to allergic symptoms in centres with diverse living conditions. METHODS: Cross-sectional studies of stratified random samples of 8 to 12-year-old children (n = 7461) used the standardized methodology of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema were ascertained by parental questionnaires. Skin examination, hypertonic saline bronchial challenge, six aeroallergen SPTs and measurements of serum total IgE and sIgE were performed. RESULTS: In nonaffluent countries, a higher proportion of children with positive SPT had no detectable sIgE (range 37-61%) than in affluent countries (0-37%). Total serum IgE was associated with all disease outcomes among children with both positive SPT and sIgE (P < 0.001), but only with self-reported eczema in children with negative SPTs and negative sIgE. CONCLUSIONS: The international pattern of discordance between SPT and sIgE results did not support the downregulation hypothesis. Among children with no evidence of sensitization to common aeroallergens, increased total IgE contributes little to the risk of wheeze and rhinitis in the general population but may play a role in eczema.

Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study.

OBJECTIVE: Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and are increased in the mucosa of patients with ulcerative colitis. The aim of this investigation was to conduct the first prospective cohort study investigating if a high dietary intake of linoleic acid increases the risk of developing incident ulcerative colitis. DESIGN AND SETTING: Dietary data from food frequency questionnaires were available for 203 193 men and women aged 30-74 years, resident in the UK, Sweden, Denmark, Germany or Italy and participating in a prospective cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). These participants were followed up for the diagnosis of ulcerative colitis. Each case was matched with four controls and the risk of disease calculated by quartile of intake of linoleic acid adjusted for gender, age, smoking, total energy intake and centre. RESULTS: A total of 126 participants developed ulcerative colitis (47% women) after a median follow-up of 4.0 years (range, 1.7-11.3 years). The highest quartile of intake of linoleic acid was associated with an increased risk of ulcerative colitis (odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.23 to 5.07, p = 0.01) with a significant trend across quartiles (OR = 1.32 per quartile increase, 95% CI = 1.04 to 1.66, p = 0.02 for trend). CONCLUSIONS: The data support a role for dietary linoleic acid in the aetiology of ulcerative colitis. An estimated 30% of cases could be attributed to having dietary intakes higher than the lowest quartile of linoleic acid intake.

Serum triglyceride concentrations and cancer risk in a large cohort study in Austria.

BACKGROUND: Blood lipid levels as part of the metabolic syndrome are thought to be linked to cancer risk. Few epidemiological studies have addressed the association between serum triglyceride (STG) concentrations and cancer risk. METHODS: Serum triglyceride concentrations were collected in a health investigation (1988-2003). The analyses included 156 153 subjects (71 693 men and 84 460 women), with 5079 incident cancers in men and 4738 cancers in women, and an average of 10.6 years of follow-up. All malignancies were ascertained from the population cancer registry. Multivariate Cox proportional hazard models stratified by age and sex were used to determine adjusted cancer risk estimates and 95% confidence interval (95% CI). RESULTS: In men and women combined, higher STG concentrations were associated with increased risk of lung (4th vs 1st quartile: HR, 1.94; 95% CI, 1.47-2.54), rectal (HR, 1.56; 95% CI, 1.00-2.44), and thyroid cancer (HR, 1.96; 95% CI, 1.00-3.84). Serum triglyceride concentrations were inversely associated with non-Hodgkin's lymphoma. In men, STG concentrations were inversely associated with prostate cancer and positively with renal cancer. In women, STG concentrations were positively associated with gynaecological cancers. Stratification by BMI revealed a higher risk of gynaecological cancers in overweight than in normal weight women. No other associations were found. CONCLUSIONS: Our findings support the hypothesis that STG concentrations are involved in the pathogenesis of lung, rectal, thyroid, prostate, and gynaecological cancers.

Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II.

The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires. Data from 54,000 randomly selected school children (aged 8-12 yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function. Random effect models for meta-analysis were applied to calculate combined odds ratios (ORs). Any breastfeeding was associated with less wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI) 0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries. In contrast, breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only (mean ratio 1.11, 95% CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic wheeze, which becomes particularly evident in nonaffluent countries. Overall, breastfeeding was not related to any measure of allergy. These findings may explain some of the controversy regarding breastfeeding, since the direction of the association with breastfeeding depends on the predominating wheeze phenotype (e.g. atopic, nonatopic).

CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to cytokine-activated endothelial cells.

Neutrophil adherence to cytokine-activated endothelial cell (EC) monolayers depends on the expression of the endothelial leukocyte adhesion molecule-1 (ELAM-1). The ligand for ELAM-1 is the sialylated Lewis-x antigen (SLe(x)) structure. The selectin LAM-1 (or LECAM-1) has been described as one of the SLe(x)-presenting glycoproteins involved in neutrophil binding to ELAM-1. Other presenter molecules have not yet been described. Our data demonstrate that the carcinoembryonic antigen (CEA)-like surface molecules on neutrophils--known as the nonspecific cross-reacting antigens (NCAs)--are involved in neutrophil adherence to monolayers of IL-1-beta-activated EC. The NCAs are recognized by CD66 (NCA-160 and NCA-90) and CD67 (NCA-95). Because NCA-95 and NCA-90 have previously been found to be phosphatidylinositol (PI)-linked, paroxysmal nocturnal hemoglobinuria (PNH) neutrophils (which lack PI-linked surface proteins) were tested as well. PNH neutrophils showed a diminished binding to activated EC. CD66 (on PNH cells still recognizing the transmembrane NCA-160 form) still inhibited the adherence of PNH cells to IL-1-beta-activated EC, but to a limited extent. Soluble CEA(-related) antigens inhibited normal neutrophil adherence as well, whereas neutrophil transmigration was unaffected. Sialidase-treatment as well as CD66 preclearing abolished the inhibitory capacity of the CEA(-related) antigens. The binding of soluble CEA antigens to IL-1-beta-pretreated EC was blocked by anti-ELAM-1. These soluble antigens, as well as the neutrophil NCA-160 and NCA-90, both recognized by CD66 antibodies, presented the SLe(x) determinant. Together, these findings indicate that the CD66 antigens (i.e., NCA-160/NCA-90) function as presenter molecules of the SLe(x) oligosaccharide structures on neutrophils that bind to ELAM-1 on EC.

Lazy Sundays: role of day of the week and reactivity on objectively measured physical activity in older people.

BACKGROUND: The aim of this study was to assess the effect of day of the week and wearing a device (reactivity) on objectively measured physical activity (PA) in older people. METHODS: Walking duration as a measure for PA was recorded from 1333 German community-dwelling older people (≥65 years, 43.8% women) over 5 days using accelerometers (activPAL). Least-square means of PA with 95%-confidence intervals (95%-CI) from multi-level analysis were calculated for each day of the week and each measurement day (days after sensor attachment). RESULTS: Walking duration on Sundays was significantly lower compared to working days (Sunday vs. Monday-Friday: - 12.8 min (95%-CI: - 14.7; - 10.9)). No statistically significant difference compared to working days was present for Saturdays. The linear slope for measurement day and walking duration was marginal and not statistically significant. CONCLUSIONS: Studies using PA sensors in older people should assess Sundays and working days to adequately determine the activity level of the participants.

Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II).

BACKGROUND: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent. OBJECTIVES: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries. METHODS: Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi-centre cross-sectional study of 840 children aged 9-12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end-points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen-specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure. RESULTS: Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29-0.96) for endotoxin levels per m(2) of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64-0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever. CONCLUSION: These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.

Phenylketonuria. The in vivo hydroxylation rate of phenylalanine into tyrosine is decreased.

In phenylketonuria (PKU), the enzyme phenylalanine hydroxylase is deficient, resulting in a decreased conversion of phenylalanine (Phe) into tyrosine (Tyr). The severity of the disease is expressed as the tolerance for Phe at 5 yr of age. In PKU patients it is assumed that the decreased conversion of Phe into Tyr is directly correlated with the tolerance for Phe. We investigated this correlation by an in vivo stable isotope study. The in vivo residual hydroxylation was quantitated using a primed continuous infusion of L-[ring- 2H5]Phe and L-[1-13C]Tyr and the determination of the isotopic enrichments of L-[ring-2H5]Phe, L-[ring-2H4]Tyr, and L-[1-13C]Tyr in plasma. Previous reports by Thompson and coworkers (Thompson, G.N., and D. Halliday. 1990. J. Clin. Invest. 86:317-322; Thompson, G.N., J.H. Walter, J.V. Leonard, and D. Halliday. 1990. Metabolism. 39:799-807; Treacy, E., J.J. Pitt, K. Seller, G.N. Thompson, S. Ramus, and R.G.H. Cotton. 1996. J. Inherited Metab. Dis. 19:595- 602), applying the same technique, showed normal in vivo hydroxylation rates of Phe in almost all PKU patients. Therefore, our study was divided up in two parts. First, the method was re-evaluated. Second, the correlation between the in vivo hydroxylation of Phe and the tolerance for Phe was tested in seven classical PKU patients. Very low (0.13- 0.95 micromol/kg per hour) and normal (4.11 and 6.33 micromol/kg per hour) conversion rates were found in patients and controls, respectively. Performing the infusion study twice in the same patient and wash-out studies of the labels at the end of the experiment in a patient and control showed that the method is applicable in PKU patients and gives consistent data. No significant correlation was observed between the in vivo hydroxylation rates and the tolerances. The results of this study, therefore, showed that within the group of patients with classical PKU, the tolerance does not depend on the in vivo hydroxylation.

Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women.

OBJECTIVE: The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: The population are 2109 women who were control subjects in a case-control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch. RESULTS: Serum IGF-I levels were positively related to protein intake (P(trend)<0.001), but not related to energy, fat or carbohydrate intake. Positive relationships were observed with the intake of milk (P(trend)=0.007), calcium (P(trend)<0.001), magnesium (P(trend)=0.003), phosphorus (P(trend)<0.001), potassium (P(trend)=0.002), vitamin B6 (P(trend)=0.03), vitamin B2 (P(trend)=0.001) and inverse relationships with vegetables (P(trend)=0.02) and beta-carotene (P(trend)=0.02). IGFBP-3 was not related with most of the nutrients and foods in this study. CONCLUSIONS: In this population, circulating IGF-I is modestly related with the intake of protein and minerals, and with milk and cheese, while IGFBP-3 does not appear to be related with diet.