Realizing the Potential of Adolescence to Prevent Transgenerational Conditioning of Noncommunicable Disease Risk: Multi-Sectoral Design Frameworks.

Evidence from the field of Developmental Origins of Health and Disease (DOHaD) demonstrates that early life environmental exposures impact later-life risk of non-communicable diseases (NCDs). This has revealed the transgenerational nature of NCD risk, thus demonstrating that interventions to improve environmental exposures during early life offer important potential for primary prevention of DOHaD-related NCDs. Based on this evidence, the prospect of multi-sectoral approaches to enable primary NCD risk reduction has been highlighted in major international reports. It is agreed that pregnancy, lactation and early childhood offer significant intervention opportunities. However, the importance of interventions that establish positive behaviors impacting nutritional and non-nutritional environmental exposures in the pre-conceptual period in both males and females, thus capturing the full potential of DOHaD, must not be overlooked. Adolescence, a period where life-long health-related behaviors are established, is therefore an important life-stage for DOHaD-informed intervention. DOHaD evidence underpinning this potential is well documented. However, there is a gap in the literature with respect to combined application of theoretical evidence from science, education and public health to inform intervention design. This paper addresses this gap, presenting a review of evidence informing theoretical frameworks for adolescent DOHaD interventions that is accessible collectively to all relevant sectors

Adolescents as agents of healthful change through scientific literacy development: A school-university partnership program in New Zealand.

BACKGROUND: Scientific literacy development is widely emphasized as the overarching goal of science education. It encompasses development of understanding of the nature of science as well as knowledge, attitudes, and values that contribute to empowering adolescents to engage with and make evidence-based decisions about socioscientific issues. Scientific literacy development is enhanced when learning is contextualized in exploration of socioscientific issues.Noncommunicable diseases (NCDs) associated with a combination of obesity and adverse environmental exposures are examples of pressing health-related SSIs facing the world today. Evidence emerging from the field of Developmental Origins of Health and Disease (DOHaD) has identified adolescence as a key life-phase where population-wide education-based interventions that empower teens to engage in science-based health-promoting behaviors could significantly change the course of this epidemic. To achieve this, learning resources that support scientific and health literacy development contextualized in issues linking NCD risk and DOHaD are required.The Healthy Start to Life Education for Adolescents Project is a school-university partnership program designed to support scientific and health literacy development, knowledge translation, and participant-led actions relating to NCD risk prevention. This study assesses the impact of program participation in a cohort of 11-14-year-olds in New Zealand. Evaluation comprised analysis of individually matched questionnaires, pre-, 3 months, and 12 months post-intervention (n = 201) and 6 months post-intervention interviews (n = 40). RESULTS: Positive engagement in science learning occurred. Positive changes in health-related awareness and attitudes 3 months post-intervention were sustained to 12 months. Adolescents reporting pre-intervention dietary behaviors associated with increased obesity risk reported sustained positive behavior changes (p < .001). Qualitative evidence revealed that these changes resulted from application of scientific and health literacy. This has the potential to improve long-term health outcomes for adolescents and their future offspring. Furthermore, feedback from parents demonstrated that adolescents became science communicators within their families. CONCLUSIONS: We demonstrated that contextualized learning promoting scientific and health literacy development facilitated knowledge translation. This allowed adolescents to decide if, and how, to use scientific evidence in relation to their current and future wellbeing. Exploration of the transferability of scientific and health literacy capabilities, and impacts on future health would enhance understanding of the value of the intervention

Exercise for depression

Background Depression is a common and important cause of morbidity and mortality worldwide. Depression is commonly treated with antidepressants and/or psychotherapy, but some people may prefer alternative approaches such as exercise. There are a number of theoretical reasons why exercise may improve depression. Objectives To determine the effectiveness of exercise in the treatment of depression. Search strategy We searched Medline, Embase, Sports Discus, PsycINFO, the Cochrane Controlled Trials Register, and the Cochrane Database of Systematic Reviews for eligible studies in March 2007. In addition, we hand-searched several relevant journals, contacted experts in the field, searched bibliographies of retrieved articles, and performed citation searches of identified studies. We also searched www.controlled-trials.com in May 2008. Selection criteria Randomised controlled trials in which exercise was compared to standard treatment, no treatment or a placebo treatment in adults (aged 18 and over) with depression, as defined by trial authors. We excluded trials of post-natal depression. Data collection and analysis We calculated effect sizes for each trial using Cohen's method and a standardised mean difference (SMD) for the overall pooled effect, using a random effects model. Where trials used a number of different tools to assess depression, we included the main outcome measure only in the meta-analysis. Main results Twenty-eight trials fulfilled our inclusion criteria, of which 25 provided data for meta-analyses. Randomisation was adequately concealed in a minority of studies, most did not use intention to treat analyses and most used self-reported symptoms as outcome measures. For the 23 trials (907 participants) comparing exercise with no treatment or a control intervention, the pooled SMD was -0.82 (95% CI -1.12, -0.51), indicating a large clinical effect. However, when we included only the three trials with adequate allocation concealment and intention to treat analysis and blinded outcome assessment, the pooled SMD was -0.42 (95% CI -0.88, 0.03) i.e. moderate, nonsignificant effect. The effect of exercise was not significantly different from that of cognitive therapy. There was insufficient data to determine risks and costs. Authors' conclusions Exercise seems to improve depressive symptoms in people with a diagnosis of depression, but when only methodologically robust trials are included, the effect sizes are only moderate and not statistically significant. Further, more methodologically robust trials should be performed to obtain more accurate estimates of effect sizes, and to determine risks and costs. Further systematic reviews could be performed to investigate the effect of exercise in people with dysthymia who do not fulfil diagnostic criteria for depression. This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2010, Issue 1. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.</p

Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review

Background: Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture. Methods: We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age. Results: The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful. Conclusion: Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation

Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

BACKGROUND: Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. METHOD: To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75(th )centile) to those of lower birth weight (5-25(th )centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. RESULTS: We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. CONCLUSION: These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk

Susceptibility of Clostridium difficile isolates of varying antimicrobial resistance phenotypes to SMT19969 and 11 comparators.

We determined the in vitro activity of SMT19969 and 11 comparators, including metronidazole, vancomycin and fidaxomicin, against 107 C. difficile isolates of different antimicrobial resistance phenotypes. Fidaxomicin and SMT19969 were most active. Geometric mean fidaxomicin and SMT19969 MICs were highest in ribotypes known to show multiple resistance. Co-resistance to linezolid and moxifloxacin was evident in ribotypes 001, 017, 027 and 356. High-level ceftriaxone resistance in ribotypes 356 and 018 was location-linked

Exposure of neonatal rats to maternal cafeteria feeding during suckling alters hepatic gene expression and DNA methylation in the insulin signalling pathway

Nutrition in early life is a determinant of lifelong physiological and metabolic function. Diseases that are associated with ageing may, therefore, have their antecedents in maternal nutrition during pregnancy and lactation. Rat mothers were fed either a standard laboratory chow diet (C) or a cafeteria diet (O) based upon a varied panel of highly palatable human foods, during lactation. Their offspring were then weaned onto chow or cafeteria diet giving four groups of animals (CC, CO, OC, OO n=9-10). Livers were harvested 10 weeks post-weaning for assessment of gene and protein expression, and DNA methylation. Cafeteria feeding post-weaning impaired glucose tolerance and was associated with sex-specific altered mRNA expression of peroxisome proliferator activated receptor gamma (PPARg) and components of the insulin-signalling pathway (Irs2, Akt1 and IrB). Exposure to the cafeteria diet during the suckling period modified the later response to the dietary challenge. Post-weaning cafeteria feeding only down-regulated IrB when associated with cafeteria feeding during suckling (group OO, interaction of diet in weaning and lactation P=0.041). Responses to cafeteria diet during both phases of the experiment varied between males and females. Global DNA methylation was altered in the liver following cafeteria feeding in the post-weaning period, in males but not females. Methylation of the IrB promoter was increased in group OC, but not OO (P=0.036). The findings of this study add to a growing evidence base that suggests tissue function across the lifespan a product of cumulative modifications to the epigenome and transcriptome, which may be both tissue and sex-specific

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

Vision and visual history in elite-/near-elite level cricketers and rugby-league players

Background: The importance of optimal and/or superior vision for participation in high-level sport remains the subject of considerable clinical research interest. Here we examine the vision and visual history of elite/near-elite cricketers and rugby-league players. Methods: Stereoacuity (TNO), colour vision, and distance (with/without pinhole) and near visual acuity (VA) were measured in two cricket squads (elite/international-level, female, n=16; near-elite, male, n=23) and one professional rugby-league squad (male, n=20). Refractive error was determined, and details of any correction worn and visual history were recorded. Results: Overall, 63% had their last eye-examination within 2 years. However, some had not had an eye examination for 5 years, or had never had one (near-elite-cricketers: 30%; rugby-league players: 15%; elite-cricketers: 6%). Comparing our results for all participants to published data for young, optimally-corrected, non-sporting adults, distance VA was ~1 line of letters worse than expected. Adopting α=0.01, the deficit in distance-VA deficit was significant, but only for elite-cricketers (p0.02 for all comparisons). On average, stereoacuity was better than in young adults, but only in elite-cricketers (p<0.001; p=0.03, near-elite-cricketers; p=0.47, rugby-league -players). On-field visual issues were present in 27% of participants, and mostly (in 75% of cases) comprised uncorrected ametropia. Some cricketers (near-elite: 17.4%; elite: 38%) wore refractive correction during play but no rugby-league player did. Some individuals with prescribed correction choose not to wear it when playing. Conclusion: Aside from near stereoacuity in elite-cricketers, these basic visual abilities were not better than equivalent, published data for optimally-corrected adults. 20-25% exhibited sub-optimal vision, suggesting that the clearest possible vision might not be critical for participation at the highest levels in the sports of cricket or rugby-league. Although vision could be improved in a sizeable proportion of our sample, the impact of correcting these, mostly subtle, refractive anomalies on playing performance is unknown