Stand Out in Class: restructuring theclassroom environment to reducesedentary behaviour in 9–10-year-olds—study protocol for a pilot clusterrandomised controlled trial

Background: Sedentary behaviour (sitting) is a highly prevalent negative health behaviour, with individuals of allages exposed to environments that promote prolonged sitting. Excessive sedentary behaviour adversely affects health inchildren and adults. As sedentary behaviour tracks from childhood into adulthood, the reduction of sedentary time inyoung people is key for the prevention of chronic diseases that result from excessive sitting in later life. The sedentaryschool classroom represents an ideal setting for environmentalchange, through the provision of sit-stand desks. Whilstthe use of sit-stand desks in classrooms demonstrates positiveeffects in some key outcomes, evidence is currently limitedby small samples and/or short intervention durations, withfewstudiesadoptingrandomisedcontrolledtrial(RCT)designs. This paper describes the protocol of a pilot cluster RCT of a sit-stand desk interventioninprimaryschoolclassrooms.Methods/Design:A two-arm pilot cluster RCT will be conducted in eight primary schools (four intervention, four control)with at least 120 year 5 children (aged 9–10 years). Sit-stand desks will replace six standard desks in the interventionclassrooms. Teachers will be encouraged to ensure all pupils are exposed to the sit-stand desks for at least 1 h/dayon average using a rotation system. Schools assigned to the control arm will continue with their usual practice, noenvironmental changes will be made to their classrooms. Measurements will be taken at baseline, beforerandomisation, and at the end of the schools’academic year. In this study, the primary outcomes of interest will beschool and participant recruitment and attrition, acceptability of the intervention, and acceptability and complianceto the proposed outcome measures (including activPAL-measured school-time and school-day sitting, accelerometer-measured physical activity, adiposity, blood pressure, cognitive function, academic progress, engagement, andbehaviour) for inclusion in a definitive trial. A full process evaluation and an exploratory economic evaluation willalso be conducted to further inform a definitive tria

Metacognitive therapy home-based self-help for cardiac rehabilitation patients experiencing anxiety and depressive symptoms : study protocol for a feasibility randomised controlled trial (PATHWAY Home-MCT)

BACKGROUND: Anxiety and depression are common among patients attending cardiac rehabilitation services. Currently available pharmacological and psychological interventions have limited effectiveness in this population. There are presently no psychological interventions for anxiety and depression integrated into cardiac rehabilitation services despite emphasis in key UK National Health Service policy. A new treatment, metacognitive therapy, is highly effective at reducing anxiety and depression in mental health settings. The principal aims of the current study are (1) to evaluate the acceptability of delivering metacognitive therapy in a home-based self-help format (Home-MCT) to cardiac rehabilitation patients experiencing anxiety and depressive symptoms and conduct a feasibility trial of Home-MCT plus usual cardiac rehabilitation compared to usual cardiac rehabilitation; and (2) to inform the design and sample size for a full-scale trial. METHODS: The PATHWAY Home-MCT trial is a single-blind feasibility randomised controlled trial comparing usual cardiac rehabilitation (control) versus usual cardiac rehabilitation plus home-based self-help metacognitive therapy (intervention). Economic and qualitative evaluations will be embedded within the trial. Participants will be assessed at baseline and followed-up at 4 and 12 months. Patients who have been referred to cardiac rehabilitation programmes and have a score of ≥ 8 on the anxiety and/or depression subscales of the Hospital Anxiety and Depression Scale will be invited to take part in the study and written informed consent will be obtained. Participants will be recruited from the National Health Service in the UK. A minimum of 108 participants will be randomised to the intervention and control arms in a 1:1 ratio. DISCUSSION: The Home-MCT feasibility randomised controlled trial will provide evidence on the acceptability of delivering metacognitive therapy in a home-based self-help format for cardiac rehabilitation patients experiencing symptoms of anxiety and/or depression and on the feasibility and design of a full-scale trial. In addition, it will provide provisional point estimates, with appropriately wide measures of uncertainty, relating to the effectiveness and cost-effectiveness of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03129282 , Submitted to Registry: 11 April 2017

A genomic approach to therapeutic target validation identifies a glucose-lowering <i>GLP1R</i> variant protective for coronary heart disease

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process