Feasibility study and pilot cluster randomised controlled trial of the GoActive Intervention aiming to promote physical activity among adolescents: outcomes and lessons learnt

$\textbf{Objectives:}$ Assess the feasibility of implementing the GoActive intervention in secondary schools, to identify improvements, test study procedures, determine preliminary effectiveness to increase moderate-to-vigorous physical activity (MVPA), and inform power calculations to establish programme effectiveness. $\textbf{Setting:}$ Feasibility study (1 school) and pilot CRCT (2 intervention;1 control school(s)) $\textbf{Participants:}$ 460 participants (46.6% female; 13.2(0.4) years-old). $\textbf{Interventions:}$ 8-week intervention (2013) involved: classes choosing weekly activities encouraged by Mentors (older adolescents) and in-class peer-leaders. Students gain points for trying activities which are entered into an intra-mural competition. $\textbf{Primary and secondary outcome measures:}$ Planned quantitative (questionnaire) and qualitative (focus groups) process evaluation addressed enjoyment, confidence, participation, suggested improvements. Outcomes were assessed at baseline and follow-up (week 8) in pilot CRCT and included: accelerometer-assessed MVPA; adolescent-reported activity type, wellbeing, peer-support, shyness, sociability. ANCOVA was used to assess preliminary effectiveness as change in MVPA adjusted for baseline. $\textbf{Results:}$ All Year 9 students in intervention schools were exposed to the intervention; over all schools 77% of eligible students were measured. 71% boys and 74% girls found GoActive ‘fun’; 38% boys and 32% girls said it increased confidence and 64% boys and 59% girls said they would continue with a GoActive activity. Suggested improvements included more Mentorship; improved training; streamlined points recording. Pilot results indicated potential effectiveness ((adjusted mean difference (95%CI)p-value) (MVPA mins) 5.1(1.1,9.2)p=0.014)) and suggest recruitment of 16 schools (2400 adolescents) for a full trial. Compared to control, intervention students reported greater peer support 0.5(0.1,0.9)p=0.03, wellbeing 1.8(0.1, 3.4)p=0.04 but no difference in shyness/sociability. Participation in activity types approached significance (intervention group 2.3(-0.2,4.7)p=0.07 more activity types). $\textbf{Conclusions:}$ Results suggest feasibility and indicate potential effectiveness of GoActive to increase MVPA and support a fully-powered evaluation of effectiveness and cost-effectiveness. Process evaluation data was used to refine GoActive prior to a full trial. $\textbf{Trial Registration:}$ ISRCTN registry ISRCTN31583496.Funding for this study and the work of all authors was supported, wholly or in part, by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence (RES-590-28-0002). Funding from the British Heart Foundation, Department of Health, Economic and Social Research Council, Medical Research Council, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The work of Kirsten Corder, Helen Brown and Esther M F van Sluijs was supported by the Medical Research Council (MC_UU_12015/7)

Engaging stakeholders and target groups in prioritising a public health intervention: the Creating Active School Environments (CASE) online Delphi study

$\textbf{Objectives}$ Stakeholder engagement and public involvement are considered as integral to developing effective public health interventions and is encouraged across all phases of the research cycle. However, limited guidelines and appropriate tools exist to facilitate stakeholder engagement—especially during the intervention prioritisation phase. We present the findings of an online ‘Delphi’ study that engaged stakeholders (including young people) in the process of prioritising secondary school environment-focused interventions that aim to increase physical activity. $\textbf{Setting }$ Web-based data collection using an online Delphi tool enabling participation of geographically diverse stakeholders. $\textbf{Participants }$ 37 stakeholders participated, including young people (age 13–16 years), parents, teachers, public health practitioners, academics and commissioners; 33 participants completed both rounds. $\textbf{Primary and secondary outcome measures}$ Participants were asked to prioritise a (short-listed) selection of school environment-focused interventions (eg, standing desks, outdoor design changes) based on the criteria of ‘reach’, ‘equality’, ‘acceptability’, ‘feasibility’, ‘effectiveness’ and ‘cost’. Participants were also asked to rank the criteria and the effectiveness outcomes (eg, physical activity, academic achievement, school enjoyment) from most to least important. Following feedback along with any new information provided, participants completed round 2 4 weeks later. $\textbf{Results }$ The intervention prioritisation process was feasible to conduct and comments from participants indicated satisfaction with the process. Consensus regarding intervention strategies was achieved among the varied groups of stakeholders, with ‘active lessons’ being the favoured approach. Participants ranked ‘mental health and well-being’ as the most important outcome followed by ‘enjoyment of school’. The most important criteria was ‘effectiveness’, followed by ‘feasibility’. $\textbf{Conclusions }$ This novel approach to engaging a wide variety of stakeholders in the research process was feasible to conduct and acceptable to participants. It also provided insightful information relating to how stakeholders prioritise interventions. The approach could be extended beyond the specific project to be a useful tool for researchers and practitioners.This report is independent research commissioned and funded by the Department of Health Policy Research Programme (opportunities within the school environment to shift the distribution of activity intensity in adolescents, PR-R5-0213-25001). This work was also supported by the Medical Research Council (unit programme number: MC_UU_12015/7). The work was undertaken under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which is funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust (MR/K023187/1)

Bronchial artery embolization for management of massive cryptogenic hemoptysis: a case series

<p>Abstract</p> <p>Introduction</p> <p>Hemoptysis constitutes a common and urgent medical problem. Swift and effective management is of crucial importance, especially in severe, life-threatening cases. In cases of idiopathic hemoptysis, in which no underlying pulmonary pathology can be identified, treatment is challenging. We report our experience with bronchial artery embolization in the treatment of massive idiopathic hemoptysis.</p> <p>Cases presentation</p> <p>We report three consecutive cases of acute severe idiopathic hemoptysis. Our patients (two men aged 51 and 56 years and one woman aged 46 years), were of Caucasian ethnicity. We discuss the results and management of the patients, and review the literature. All three patients were treated safely and successfully with transcatheter embolization of the bronchial arteries using tris-acryl gelatin microspheres. Hemoptysis was controlled. All cases were followed up for 12 months, and there was no recurrence of bleeding.</p> <p>Conclusion</p> <p>Bronchial artery embolization is an effective tool for the evaluation and treatment of massive idiopathic hemoptysis.</p

Gallbladder Cancer Predisposition: A Multigenic Approach to DNA-Repair, Apoptotic and Inflammatory Pathway Genes

Gallbladder cancer (GBC) is a multifactorial disease with complex interplay between multiple genetic variants. We performed Classification and Regression Tree Analysis (CART) and Grade of Membership (GoM) analysis to identify combinations of alleles among the DNA repair, inflammatory and apoptotic pathway genetic variants in modifying the risk for GBC. We analyzed 16 polymorphisms in 8 genes involved in DNA repair, apoptotic and inflammatory pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were XRCC1, OGG1, ERCC2, MSH2, CASP8, TLR2, TLR4 and PTGS2. Single locus analysis by logistic regression showed association of MSH2 IVS1+9G>C (rs2303426), ERCC2 Asp312Asn (rs1799793), OGG1 Ser326Cys (rs1052133), OGG1 IVS4-15C>G (rs2072668), CASP8 -652 6N ins/del (rs3834129), PTGS2 -1195G>A (rs689466), PTGS2 -765G>C (rs20417), TLR4 Ex4+936C>T (rs4986791) and TLR2 –196 to –174del polymorphisms with GBC risk. The CART analysis revealed OGG1 Ser326Cys, and OGG1 IVS4-15C>G polymorphisms as the best polymorphic signature for discriminating between cases and controls. In the GoM analysis, the data was categorized into six sets representing risk for GBC with respect to the investigated polymorphisms. Sets I, II and III described low intrinsic risk (controls) characterized by multiple protective alleles while sets IV, V and VI represented high intrinsic risk groups (GBC cases) characterized by the presence of multiple risk alleles. The CART and GoM analyses also showed the importance of PTGS2 -1195G>A polymorphism in susceptibility to GBC risk. In conclusion, the present multigenic approach can be used to define individual risk profiles for gallbladder cancer in North Indian population

A Randomised controlled trial of Energetic Activity for Depression in Young people (READY): A multi-site feasibility trial protocol

Background: Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery. Methods: The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13–17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a ‘healthy living’ behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness. Discussion: UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression. Trial registration: ISRCTN, ISRCTN66452702. Registered 9 April 2020

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

BACKGROUND: Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown. METHODS: We performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm(2), n = 319) and high (> 1.11 g/cm(2), n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections. RESULTS: Based on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm(2)) and 138 females with high (>1.04 g/cm(2)) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD. CONCLUSION: This study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis

Impact of Flavonoids on Cellular and Molecular Mechanisms Underlying Age-Related Cognitive Decline and Neurodegeneration

Purpose of Review This review summarises the most recent evidence regarding the effects of dietary flavonoids on age-related cognitive decline and neurodegenerative diseases. Recent Findings Recent evidence indicates that plant-derived flavonoids may exert powerful actions on mammalian cognition and protect against the development of age-related cognitive decline and pathological neurodegeneration. The neuroprotective effects of flavonoids have been suggested to be due to interactions with the cellular and molecular architecture of brain regions responsible for memory. Summary Mechanisms for the beneficial effects of flavonoids on age-related cognitive decline and dementia are discussed, including modulating signalling pathways critical in controlling synaptic plasticity, reducing neuroinflammation, promoting vascular effects capable of stimulating new nerve cell growth in the hippocampus, bidirectional interactions with gut microbiota and attenuating the extracellular accumulation of pathological proteins. These processes are known to be important in maintaining optimal neuronal function and preventing age-related cognitive decline and neurodegeneration