The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation.

Background: Low levels of testosterone cause male hypogonadism, which is associated with sexual dysfunction, tiredness and reduced muscle strength and quality of life. Testosterone replacement therapy is commonly used for ameliorating symptoms of male hypogonadism, but there is uncertainty about the magnitude of its effects and its cardiovascular and cerebrovascular safety. Aims of the research: The primary aim was to evaluate the safety of testosterone replacement therapy. We also assessed the clinical and cost-effectiveness of testosterone replacement therapy for men with male hypogonadism, and the existing qualitative evidence on men's experience and acceptability of testosterone replacement therapy. Design: Evidence synthesis and individual participant data meta-analysis of effectiveness and safety, qualitative evidence synthesis and model-based cost-utility analysis. Data sources: Major electronic databases were searched from 1992 to February 2021 and were restricted to English-language publications. Methods: We conducted a systematic review with meta-analysis of individual participant data according to current methodological standards. Evidence was considered from placebo-controlled randomised controlled trials assessing the effects of any formulation of testosterone replacement therapy in men with male hypogonadism. Primary outcomes were mortality and cardiovascular and cerebrovascular events. Data were extracted by one reviewer and cross-checked by a second reviewer. The risk of bias was assessed using the Cochrane Risk of Bias tool. We performed one-stage meta-analyses using the acquired individual participant data and two-stage meta-analyses to integrate the individual participant data with data extracted from eligible studies that did not provide individual participant data. A decision-analytic Markov model was developed to evaluate the cost per quality-adjusted life-years of the use of testosterone replacement therapy in cohorts of patients of different starting ages. Results: We identified 35 trials (5601 randomised participants). Of these, 17 trials (3431 participants) provided individual participant data. There were too few deaths to assess mortality. There was no difference between the testosterone replacement therapy group (120/1601, 7.5%) and placebo group (110/1519, 7.2%) in the incidence of cardiovascular and/or cerebrovascular events (13 studies, odds ratio 1.07, 95% confidence interval 0.81 to 1.42; p = 0.62). Testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups. In the testosterone replacement therapy group, serum testosterone was higher while serum cholesterol, triglycerides, haemoglobin and haematocrit were all lower. We identified several themes from five qualitative studies showing how symptoms of low testosterone affect men's lives and their experience of treatment. The cost-effectiveness of testosterone replacement therapy was dependent on whether uncertain effects on all-cause mortality were included in the model, and on the approach used to estimate the health state utility increment associated with testosterone replacement therapy, which might have been driven by improvements in symptoms such as sexual dysfunction and low mood. Limitations: A meaningful evaluation of mortality was hampered by the limited number of defined events. Definition and reporting of cardiovascular and cerebrovascular events and methods for testosterone measurement varied across trials. Conclusions: Our findings do not support a relationship between testosterone replacement therapy and cardiovascular/cerebrovascular events in the short-to-medium term. Testosterone replacement therapy improves sexual function and quality of life without adverse effects on blood pressure, serum lipids or glycaemic markers. Future work: Rigorous long-term evidence assessing the safety of testosterone replacement therapy and subgroups most benefiting from treatment is needed. Study registration: The study is registered as PROSPERO CRD42018111005. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/68/01) and is published in full in Health Technology Assessment; Vol. 28, No. 43. See the NIHR Funding and Awards website for further award information.

Testosterone is a hormone which is vital for sexual activity, bone growth and muscle development in men. Men with low testosterone levels may experience problems with erections and may suffer from brittle bones (osteoporosis), weakness, feeling down (low mood) and tiredness. The manifestations of low testosterone can be treated with testosterone replacement therapy. However, there is current uncertainty about the positive effects of testosterone replacement therapy and its safety. We brought together results from all available medical studies that looked at the use of testosterone replacement therapy in men with low testosterone and contacted the doctors who led these studies to gather further information on their participants. We found 35 studies (5601 participants) conducted in different countries, 17 of which provided additional information on their participants. We did not find any evidence to show that testosterone replacement therapy increases the risk of heart problems, or any evidence to show that some men who take testosterone replacement therapy benefit more than others. Men with low testosterone reported having low mood, poor concentration and lack of energy; however, medical studies often failed to prove that these manifestations improved with testosterone replacement therapy. Most medical studies were conducted among white men in North America using questionnaires designed specifically for them; therefore, the results may not reflect the experiences of men in other countries and from more diverse ethnic backgrounds. There is too much uncertainty about the benefits of testosterone replacement therapy to accurately estimate its value for money for the NHS. We think our findings offer some reassurance to doctors and patients that testosterone replacement therapy does not increase the risk of heart problems. New studies are needed to find out whether some groups of men (such as older or younger men) are more likely to benefit from testosterone replacement therapy more than others. It is also important to develop tools which better reflect the experience of men from a diverse range of social and ethnic backgrounds. To inform men with low testosterone about our findings, we are creating a website with dedicated YouTube video clips.

Effect of nonmeat, high-protein supplementation on quality of life and clinical outcomes in older residents of care homes: a systematic review and meta-analysis.

Context: Care home residents are at risk of malnutrition owing to reduced food intake, anabolic resistance in aging muscle, and a high prevalence of medical morbidity and functional dependency. There has been limited consensus regarding the effectiveness of a high-protein diet on quality of life or clinical outcomes in care home residents. Objective: The aim of this review was to evaluate the effectiveness of nonmeat, high-protein supplementation on health-related quality of life (HRQOL) and relevant clinical and nutritional outcomes in older people in a care home setting. Data Sources: The following databases were searched (to February 2018) for randomized controlled trials: Embase, AMED, CINAHL, MEDLINE, the Cochrane Central Registry of Controlled Trials, OpenGrey, clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, the ISRCTN registry, and the NIHR Clinical Research Network Portfolio. Study Selection: Trials were selected if they assessed a nonmeat, high-protein dietary intervention provided to care home residents who were aged 65 years or older. Data Extraction: Data from included trials were extracted if they assessed care home residents aged 65 years or older and compared those residents who received protein supplementation with those who did not. Trial quality was assessed using the Cochrane risk-of-bias tool. Meta-analysis was undertaken when appropriate. Results: Seventeen studies with 1246 participants fulfilled the inclusion criteria. All studies were of low or moderate quality. There was no evidence of improved HRQOL when the Short Form 36 (SF-36) was used to assess outcomes (standardized mean difference [SMD] = -0.10; 95%CI, -0.51 to 0.31; P = 0.62), although significant improvement was seen in the 1 trial that used the EQ-5D instrument (SMD = 2.58; 95%CI, 2.05-3.10; P < 0.00001). Conclusions: Nonmeat, high-protein oral supplements can improve markers of nutritional status in care home residents. However, there is insufficient high-quality evidence to determine the effect of such supplements on HRQOL in older adults in care homes. Systematic Review Registration: PROSPERO registration number: CRD42015029313.

An application of partial least squares for identifying dietary patterns in bone health.

In a large cohort of older women, a mechanism-driven statistical technique for assessing dietary patterns that considers a potential nutrient pathway found two dietary patterns associated with lumbar spine and femoral neck bone mineral density. A "healthy" dietary pattern was observed to be beneficial for bone mineral density. INTRODUCTION: Dietary patterns represent a broader, more realistic representation of how foods are consumed, compared to individual food or nutrient analyses. Partial least-squares (PLS) is a data-reduction technique for identifying dietary patterns that maximizes correlation between foods and nutrients hypothesized to be on the path to disease, is more hypothesis-driven than previous methods, and has not been applied to the study of dietary patterns in relation to bone health. METHODS: Women from the Aberdeen Prospective Osteoporosis Screening Study (2007-2011, n = 2129, age = 66 years (2.2)) provided dietary intake using a food frequency questionnaire; 37 food groups were created. We applied PLS to the 37 food groups and 9 chosen response variables (calcium, potassium, vitamin C, vitamin D, protein, alcohol, magnesium, phosphorus, zinc) to identify dietary patterns associated with bone mineral density (BMD) cross-sectionally. Multivariable regression was used to assess the relationship between the retained dietary patterns and BMD at the lumbar spine and femoral neck, adjusting for age, body mass index, physical activity level, smoking, and national deprivation category. RESULTS: Five dietary patterns were identified, explaining 25% of the variation in food groups and 77% in the response variables. Two dietary patterns were positively associated with lumbar spine (per unit increase in factor 2: 0.012 g/cm2 [95% CI: 0.006, 0.01]; factor 4: 0.007 g/cm2 [95% CI: 0.00001, 0.01]) and femoral neck (factor 2: 0.006 g/cm2 [95% CI: 0.002, 0.01]; factor 4: 0.008 g/cm2 [95% CI: 0.003, 0.01)]) BMD. Dietary pattern 2 was characterized by high intakes of milk, vegetables, fruit and vegetable juices, and wine, and low intakes of processed meats, cheese, biscuits, cakes, puddings, confectionary, sweetened fizzy drinks and spirits while dietary pattern 4 was characterized by high intakes of fruits, red and white meats, and wine, and low intakes of vegetables and sweet spreads. CONCLUSION: Our findings using a robust statistical technique provided important support to initiatives focusing on what constitutes a healthy diet and its implications.

Longitudinal study of weight, energy intake and physical activity change across two decades in older Scottish women.

BACKGROUND: The perimenopausal and postmenopausal periods are times of pronounced physiological change in body mass index (BMI), physical activity and energy intake. Understanding these changes in middle age could contribute to formation of potential public health targets. METHOD: A longitudinal cohort of 5119 perimenopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) recruited between 1990 and 1994, with follow-up visits at 1997-1999 and 2009-2011. At each visit, participants were weighed, measured and completed socioeconomic and demographic questionnaires. Participants at the first visit were asked to recall body weights at 20, 30 and 40 years of age. We assessed trends in BMI, physical activity and energy intake across and within visits. RESULTS: Over 2 decades, obesity prevalence doubled from 14% to 28% of the participants, with 69% of participants being categorised as overweight or obese. Greater than 70% of participants gained >5% of their baseline BMI with weight gain occurring across all weight categories. Energy intake and physical activity levels (PALs) did not change during the 2 decades after menopause (p trend=0.06 and 0.11, respectively), but, within the second visit, energy intake increased concomitantly with a decrease in physical activity across increasing quartiles of BMI (p trend <0.001 for all). CONCLUSIONS: Overweight and obesity increased by over 50% over the course of 20 years. Weight gain occurred across the adult life course regardless of starting weight. The marked increase in dietary intake and decrease in PALs in middle age suggest a potential critical period for intervention to curb excess weight gain.

Moving to Capture Children's Attention: Developing a Methodology for Measuring Visuomotor Attention.

Attention underpins many activities integral to a child's development. However, methodological limitations currently make large-scale assessment of children's attentional skill impractical, costly and lacking in ecological validity. Consequently we developed a measure of 'Visual Motor Attention' (VMA)-a construct defined as the ability to sustain and adapt visuomotor behaviour in response to task-relevant visual information. In a series of experiments, we evaluated the capability of our method to measure attentional processes and their contributions in guiding visuomotor behaviour. Experiment 1 established the method's core features (ability to track stimuli moving on a tablet-computer screen with a hand-held stylus) and demonstrated its sensitivity to principled manipulations in adults' attentional load. Experiment 2 standardised a format suitable for use with children and showed construct validity by capturing developmental changes in executive attention processes. Experiment 3 tested the hypothesis that children with and without coordination difficulties would show qualitatively different response patterns, finding an interaction between the cognitive and motor factors underpinning responses. Experiment 4 identified associations between VMA performance and existing standardised attention assessments and thereby confirmed convergent validity. These results establish a novel approach to measuring childhood attention that can produce meaningful functional assessments that capture how attention operates in an ecologically valid context (i.e. attention's specific contribution to visuomanual action).

Patterns of weight change after the diagnosis of type 2 diabetes in Scotland and their relationship with glycaemic control, mortality and cardiovascular outcomes: a retrospective cohort study.

OBJECTIVES: To determine weight change patterns in Scottish patients 2 years after diagnosis of type 2 diabetes and to examine these in association with medium-term glycaemic, mortality and cardiovascular outcomes. SETTING: Using a retrospective cohort design, ethical approval was obtained to link the Scottish diabetes care database to hospital admission and mortality records. PARTICIPANTS: 29 316 overweight/obese patients with incident diabetes diagnosed between 2002 and 2006 were identified with relevant information for ≥2 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Weight records over time provided intrapatient weight change and variation and glycated haemoglobin (HbA1c) gave measures of glycaemic control. These characteristics and demographic variables at diagnosis were linked with notifications of death (2-5 years after diagnosis) and cardiovascular events (0-5 year after diagnosis). RESULTS: By 2 years, 36% of patients had lost ≥2.5% of their weight. Increasing age, being female and a higher body mass index at diagnosis were associated with larger proportions of weight lost (p<0.001). Multivariable modelling showed that inadequate glycaemic control at 2 years was associated with being younger at baseline, being male, having lower levels of obesity at diagnosis, gaining weight or being weight stable with weight change variability, and starting antidiabetic medication. While weight change itself was not related to mortality or cardiovascular outcomes, major weight variability was independently associated with poorer survival and increased cardiovascular outcome risks, as was deprivation. CONCLUSIONS: Our results suggest that weight loss or being weight stable with little weight variability early after diabetes diagnosis, are associated with better glycaemic control and we identified groups less able to lose weight. With respect to mortality and cardiovascular outcomes, although weight change at 2 years was a weak predictor, major weight variability appeared to be the more relevant factor.

A Brief Educational Intervention Increases Knowledge of the Sugar Content of Foods and Drinks but Does Not Decrease Intakes in Scottish Children Aged 10-12 Years.

OBJECTIVE: To assess the effectiveness of an educational intervention to improve children's knowledge of the sugar content of food and beverages. METHODS: Cluster-randomized, controlled trial with 268 children (aged 10-12 years) from 14 primary schools in Aberdeen, Scotland. The intervention group received 2 interactive classroom sessions about sugar. A questionnaire to assess knowledge was completed at baseline and 4, 10, and 34 weeks postintervention. Dietary intake was assessed by food frequency questionnaire at baseline and on weeks 10 and 34. RESULTS: After the intervention, the intervention group demonstrated greater knowledge of sugar than did the control group (P < .001), which was sustained at week 34 (P < .001). Dietary intakes of sugar did not change postintervention. Pre-intervention children underestimated the sugar content of fruit-based beverages. CONCLUSIONS AND IMPLICATIONS: Children's knowledge of sugar in food and beverages is limited but can be improved through a simple educational intervention. Further intervention would be needed to encourage a change in dietary intake.

Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk.

Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997-2000 (n 3237, mean age 54·8 (SD 2·2) years). Participants (n 2130, mean age 66·0 (SD 2·2) years) returned during 2007-11 for follow-up. Diet was assessed by FFQ (n 1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past 'prudent' dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern; P= 0·002 and P= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the 'prudent' dietary pattern (P= 0·030 and P= 0·006, respectively). hs-CRP concentration increased across the quintiles of a 'meat-dominated' dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (P< 0·001 for hs-CRP and IL-6, and P= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised ß for prudent component: -0·053, 95% CI -0·102, -0·003; carotenoid component: -0·183, 95% CI -0·233, -0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit and vegetable consumption) and a serum carotenoid profile characteristic of a fruit and vegetable-rich diet are associated with lower concentrations of intermediary markers that are indicative of CVD risk reduction.

The monitoring of longer term prescriptions of antidepressants: observational study in a primary care setting.

BACKGROUND: There is little evidence to guide the frequency of review for patients taking antidepressants in the longer term. OBJECTIVES: To measure the frequency with which patients on longer term courses of antidepressants have their treatment monitored in primary care and to identify patient characteristics associated with the frequency of monitoring. METHODS: A cohort of patients who were receiving antidepressants continuously for at least two years was identified from four general practices. Data were collected from patients' general medical records. The dates of all GP consultations and whether they included a documented review of antidepressant therapy were recorded, along with patient characteristics hypothesized to influence the frequency of monitoring. RESULTS: The frequency of antidepressant review consultations and proportion of participants being reviewed during a specific year of antidepressant therapy decreased with increasing year of antidepressant therapy. Individuals who receive antidepressants for an overt mental health reason; undergo more dose and drug changes; and who are referred to the community mental health team have their antidepressant therapy reviewed more often during the first five years of antidepressant therapy. CONCLUSION: As many patients on longer term courses of antidepressants are not being appropriately reviewed, a 'chronic disease management approach' to depression in primary care is advocated.

Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis.

Sepsis is a massive inflammatory response mediated by infection, characterized by oxidative stress, release of cytokines, and mitochondrial dysfunction. Melatonin accumulates in mitochondria, and both it and its metabolites have potent antioxidant and anti-inflammatory activities and may be useful in sepsis. We undertook a phase I dose escalation study in healthy volunteers to assess the tolerability and pharmacokinetics of 20, 30, 50, and 100 mg oral doses of melatonin. In addition, we developed an ex vivo whole blood model under conditions mimicking sepsis to determine the bioactivity of melatonin and the major metabolite 6-hydroxymelatonin at relevant concentrations. For the phase I trial, oral melatonin was given to five subjects in each dose cohort (n = 20). Blood and urine were collected for measurement of melatonin and 6-hydroxymelatonin, and symptoms and physiological measures were assessed. Validated sleep scales were completed. No adverse effects after oral melatonin, other than mild transient drowsiness with no effects on sleeping patterns, were seen, and no symptoms were reported. Melatonin was rapidly cleared at all doses with a median [range] elimination half-life of 51.7 [29.5-63.2] min across all doses. There was considerable variability in maximum melatonin levels within each dose cohort, but 6-hydoxymelatonin sulfate levels were less variable and remained stable for several hours. For the ex vivo study, blood from 20 volunteers was treated with lipopolysaccharide and peptidoglycan plus a range of concentrations of melatonin/6-hydroxymelatonin. Both melatonin and 6-hydroxymelatonin had beneficial effects on sepsis-induced mitochondrial dysfunction, oxidative stress, and cytokine responses at concentrations similar to those achieved in vivo.

Diet behaviour among young people in transition to adulthood (18-25 year olds): a mixed method study.

Background: Young people (18-25 years) during the adolescence/adulthood transition are vulnerable to weight gain and notoriously hard to reach. Despite increased levels of overweight/obesity in this age group, diet behaviour, a major contributor to obesity, is poorly understood. The purpose of this study was to explore diet behaviour among 18-25 year olds with influential factors including attitudes, motivators and barriers. Methods: An explanatory mixed method study design, based on health Behaviour Change Theories was used. Those at University/college and in the community, including those Not in Education, Employment or Training (NEET) were included. An initial quantitative questionnaire survey underpinned by the Theory of Planned Behaviour and Social Cognitive Theory was conducted and the results from this were incorporated into the qualitative phase. Seven focus groups were conducted among similar young people, varying in education and socioeconomic status. Exploratory univariate analysis was followed by multi-staged modelling to analyse the quantitative data. 'Framework Analysis' was used to analyse the focus groups. Results: 1313 questionnaires were analysed. Self-reported overweight/obesity prevalence was 22%, increasing with age, particularly in males. Based on the survey, 40% of young people reported eating an adequate amount of fruits and vegetables and 59% eating regular meals, but 32% reported unhealthy snacking. Based on the statistical modelling, positive attitudes towards diet and high intention (89%), did not translate into healthy diet behaviour. From the focus group discussions, the main motivators for diet behaviour were 'self-appearance' and having 'variety of food'. There were mixed opinions on 'cost' of food and 'taste'. Conclusion: Elements deemed really important to young people have been identified. This mixed method study is the largest in this vulnerable and neglected group covering a wide spectrum of the community. It provides evidence base to inform tailored interventions for a healthy diet within this age group.

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: a 1-year double-blind RCT in postmenopausal women.

Few year-long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25-dihydroxyvitamin D[1,25(OH)2 D], N-terminal propeptide of type 1 collagen [P1NP], C-terminal telopeptide of type I collagen [CTX], and fibroblast growth factor-23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25-hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored.

Physical activity attitudes, intentions and behaviour among 18-25 year olds: a mixed method study.

BACKGROUND: Young people (18-25 years) during the adolescence/adulthood transition are vulnerable to weight gain and notoriously hard to reach. Despite increased levels of overweight/obesity in this age group, physical activity behaviour, a major contributor to obesity, is poorly understood. The purpose of this study was to explore physical activity (PA) behaviour among 18-25 year olds with influential factors including attitudes, motivators and barriers. METHODS: An explanatory mixed method study design, based on health Behaviour Change Theories was used. Those at university/college and in the community, including those Not in Education, Employment or Training (NEET) were included. An initial self reported quantitative questionnaire survey underpinned by the Theory of Planned Behaviour and Social Cognitive Theory was conducted. 1313 questionnaires were analysed. Results from this were incorporated into a qualitative phase also grounded in these theories. Seven focus groups were conducted among similar young people, varying in education and socioeconomic status. Exploratory univariate analysis was followed by multi staged modelling to analyse the quantitative data. 'Framework Analysis' was used to analyse the focus groups. RESULTS: Only 28% of 18-25 year olds achieved recommended levels of PA which decreased with age. Self-reported overweight/obesity prevalence was 22%, increasing with age, particularly in males. Based on the statistical modelling, positive attitudes toward PA were strong predictors of physical activity associated with being physically active and less sedentary. However, strong intentions to do exercise, was not associated with actual behaviour. Interactive discussions through focus groups unravelled attitudes and barriers influencing PA behaviour. Doing PA to feel good and to enjoy themselves was more important for young people than the common assumptions of 'winning' and 'pleasing others'. Further this age group saw traditional health promotion messages as 'empty' and 'fear of their future health' was not a motivating factor to change current behaviour. CONCLUSION: 18-25 year olds are a difficult group to reach and have low levels of PA. Factors such as, 'enjoyment', 'appearance 'and 'feeling good' were deemed important by this specific age group. A targeted intervention incorporating these crucial elements should be developed to improve and sustain PA levels.

Analysis of the UK recommendations on obesity based on a proposed implementation framework.

BACKGROUND: There is considerable expertise in the obesity field in identifying, appraising, and synthesising evidence to develop guidelines and recommendations for policy and practice. The recommendations, while based on evidence, are not formulated in a way that readily leads to implementation. This paper analyses the recent UK recommendations on obesity using a proposed implementation framework. METHODS: Two bibliographic databases (Medline and Embase) and various health related and government websites were systematically searched for obesity recommendations published between 1996 and 2007. All the documents published on recommendations for either prevention or treatment of obesity in the UK were assessed. A proposed implementation framework was developed for the purpose of this review. All the UK recommendations were critically appraised and results summarised according to the criteria used within the framework. Cross-country applicability of the proposed framework was assessed using the Swedish policy recommendations on obesity. RESULTS: Most recommendations on obesity while demonstrating their basis in evidence, fail to meet the implementation standards. They tend to be non-specific in identifying who is responsible for implementation and monitoring, and often no timescale is indicated. The costs of implementation are rarely estimated and those responsible for such funding are not specified. There are some notable exemptions to the general pattern emanating from more operational and locally based groups. The Swedish policy details 79 proposals with responsibility clearly identified and costs are presented for 20 of them. This policy satisfied most of the framework criteria but failed to give details on evaluation, monitoring and the timeframe for implementation. CONCLUSIONS: Public health has developed skills in appraising evidence and formulating recommendations based on appropriate evidence but these are often not implemented. Different skills are required to translate these recommendations into actions. Public health clearly needs to develop the implementation skills to a level comparable to the ability to synthesise evidence.

Influences of weight loss on long-term diabetes outcomes.

Increasing rates of type 2 diabetes (T2DM) follow the obesity 'epidemic', with 86% of patients with T2DM being overweight and over half being obese. Literature has highlighted that being overweight or obese increases the risk of diabetes. Weight loss for obese patients is associated with clinical improvements, although this evidence is mostly from short-term studies. As part of a Health Technology Assessment systematic review the long-term (> or =2 years) effects of weight loss on change in diabetes-related outcome measures for those with diabetes, or risk of developing diabetes for those without diabetes, was investigated in obese individuals. Eleven studies published between 1966 and 2001 fulfilled the inclusion criteria (Caucasian, BMI >28 kg/m2, adults, no eating disorders, weight loss and changes in diabetes-outcome measures). Results of these studies indicated that intentional weight loss reduces the risk of developing diabetes in the long term and those participants with T2DM often have reduced clinical symptoms and mortality risk. These results have been verified and enhanced by literature published since this review. A similar systematic review was conducted as part of a six-phase project, the PRevent Obesity GRowing Economic Synthesis Study. This review excluded BMI >34 kg/m2 and was restricted to lifestyle interventions (or intentional weight loss). Limited information relating to diabetes was gained, with only a non-significant increasing trend for mortality from diabetes for severe weight cycling practices being suggested. Other results indicated a relationship between weight loss and fasting plasma glucose, but because of the heterogeneity of participation groups and lack of definition in relation to diabetes this relationship was not formalised. In summary, weight loss is beneficial for long-term diabetes outcomes for overweight, obese and morbidly-obese participants. There is little research evidence for those individuals who are overweight or just obese, indicating areas of future research in terms of prevention of both obesity and diabetes.

Nutritional status and subsequent all-cause mortality in men and women aged 75 years or over living in the community.

We prospectively investigated relationships between blood markers of Fe, vitamin B12, folate, vitamin C and vitamin D status and subsequent all-cause mortality in 208 men and 191 women aged 75 years or over living in the community in Aberdeen, Scotland. The participants had been recruited for a cross-sectional study in 1999-2000 when they completed health and lifestyle questionnaires and had blood samples taken for analysis of serum ferritin, serum vitamin B12, erythrocyte folate, plasma vitamin C and serum 25-hydroxycholecalciferol. Mortality was ascertained on national databases up to December 2005, with a median time of follow up of 69.2 (range 1.0-79.9) months. Participants were divided into sex-specific quintiles of baseline levels for each nutrient, and hazard ratios were estimated with Cox proportional hazard models adjusted for age and sex with the significance of linear trends in the associations assessed by logistic regression. There was no significant association between blood markers of Fe, vitamin B12 or folate status at baseline and mortality, but vitamin D status at baseline was inversely related to mortality (P for trend < 0.001). For vitamin C there was no evidence of a linear trend but participants in the lowest quintile of plasma levels had a significantly higher risk of death than those in the highest quintile. Randomized controlled trials of lifestyle changes which improve vitamin status are needed to assess whether these associations could be causal.

tRNA properties help shape codon pair preferences in open reading frames.

Translation elongation is an accurate and rapid process, dependent upon efficient juxtaposition of tRNAs in the ribosomal A- and P-sites. Here, we sought evidence of A- and P-site tRNA interaction by examining bias in codon pair choice within open reading frames from a range of genomes. Three distinct and marked effects were revealed once codon and dipeptide biases had been subtracted. First, in the majority of genomes, codon pair preference is primarily determined by a tetranucleotide combination of the third nucleotide of the P-site codon, and all 3 nt of the A-site codon. Second, pairs of rare codons are generally under-used in eukaryotes, but over-used in prokaryotes. Third, the analysis revealed a highly significant effect of tRNA-mediated selection on codon pairing in unicellular eukaryotes, Bacillus subtilis, and the gamma proteobacteria. This was evident because in these organisms, synonymous codons decoded in the A-site by the same tRNA exhibit significantly similar P-site pairing preferences. Codon pair preference is thus influenced by the identity of A-site tRNAs, in combination with the P-site codon third nucleotide. Multivariate analysis identified conserved nucleotide positions within A-site tRNA sequences that modulate codon pair preferences. Structural features that regulate tRNA geometry within the ribosome may govern genomic codon pair patterns, driving enhanced translational fidelity and/or rate.

Weight change in adult life and health outcomes.

OBJECTIVE: To investigate the relationship between weight change in adult life and subsequent mortality and cancer incidence in women. RESEARCH METHODS AND PROCEDURES: In 1994 to 1995, all women (age range, 42 to 81) still under general practitioner observation in the United Kingdom's Royal College of General Practitioners Oral Contraception Study (n = 12,303) were sent a health survey asking about health and lifestyle issues, including current weight and weight at age 30. The main outcome measures were 6-year all-cause mortality and cancer incidence among different weight change deciles. Cox regression was used to calculate hazard ratios that were adjusted for: social class at recruitment, BMI at age 30, and age group, parity, smoking status, and hormone replacement therapy status in 1995. RESULTS: Women who had been obese at age 30 were more likely to die and significantly more likely to develop cancer in the 6 years after the health survey than non-obese respondents. Women reporting weight gains between age 30 and 1995 were significantly less likely to die during the 6 years after the health survey than those with a stable weight, whereas those with weight loss did not fare any better than those in the stable-weight group. DISCUSSION: Although obesity at young age was associated with subsequent mortality and cancer incidence, weight gain over a time period of 12 to 51 years appeared to be beneficial when compared with women with stable weight over the same time period. Further research is needed to confirm or refute our findings and to allow detailed examination of potential explanations for them.