Myocardial Perfusion Reserve but not fibrosis predicts outcomes in initially asymptomatic patients with moderate to severe aortic stenosis : the PRognostic Importance of MIcrovascular Dysfunction in AS study- PRIMID AS

Peer reviewedPublisher PD

Accuracy of potential diagnostic indicators for coeliac disease:a systematic review protocol

INTRODUCTION: Coeliac disease (CD) is a systemic immune-mediated disorder triggered by gluten in genetically predisposed individuals. CD is diagnosed using a combination of serology tests and endoscopic biopsy of the small intestine. However, because of non-specific symptoms and heterogeneous clinical presentation, diagnosing CD is challenging. Early detection of CD through improved case-finding strategies can improve the response to a gluten-free diet, patients' quality of life and potentially reduce the risk of complications. However, there is a lack of consensus in which groups may benefit from active case-finding. METHODS AND ANALYSIS: We will perform a systematic review to determine the accuracy of diagnostic indicators (such as symptoms and risk factors) for CD in adults and children, and thus can help identify patients who should be offered CD testing. MEDLINE, Embase, Cochrane Library and Web of Science will be searched from 1997 until 2020. Screening will be performed in duplicate. Data extraction will be performed by one and checked by a second reviewer. Disagreements will be resolved through discussion or referral to a third reviewer. We will produce a narrative summary of identified prediction models. Studies, where 2×2 data can be extracted or reconstructed, will be treated as diagnostic accuracy studies, that is, the diagnostic indicators are the index tests and CD serology and/or biopsy is the reference standard. For each diagnostic indicator, we will perform a bivariate random-effects meta-analysis of the sensitivity and specificity. ETHICS AND DISSEMINATION: Results will be reported in peer-reviewed journals, academic and public presentations and social media. We will convene an implementation panel to advise on the optimum strategy for enhanced dissemination. We will discuss findings with Coeliac UK to help with dissemination to patients. Ethical approval is not applicable, as this is a systematic review and no research participants will be involved. PROSPERO REGISTRATION NUMBER: CRD42020170766

Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19 : protocol design of COVID-HEART-a UK, multicentre, observational study

Acknowledgements CB acknowledges British Heart Foundation support (RE/18/6134217). GPM is funded by a NIHR Research Professorship (RP‐2017‐08‐ST2‐007). CM is funded by a NIHR Clinician Scientist Award (CS‐2015‐15‐003). VMF and SN acknowledge the NIHR Oxford BRC for support of this study. CBD is in part supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. Additional support was provided by the NIHR Leicester Biomedical Research Centre and the NIHR Leeds Clinical Research Facility. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. We thank the patients and staff who have supported this project. Dr. Warren J. Manning served as a Guest Editor for this manuscript. Study Management and Recruitment centres: Grant applicants: JP Greenwood (chief investiga‐ tor), GP McCann, C Berry, M Dweck, J Moon, CM Miller, A Chiribiri, S Prasad, VM Ferreira, C Bucciarelli‐Ducci, D Dawson. Data repository and statistical analysis: Glasgow Clinical Trials Unit. Senior study statistician: Prof A McConnachie, GCTU. Local Principle Investigators and Recruitment Centres: Prof John Green‐ wood, Leeds Teaching Hospitals NHS Trust, UK; Prof Gerry McCann, Glenfield Hospital, Leicester, UK; Prof Dana Dawson, Aberdeen Royal Infirmary, UK; Prof Marc Dweck, Royal Infirmary of Edinburgh, UK; Prof Vanessa Ferreira, JohnRadcliffe Hospital, Oxford, UK; Prof Colin Berry, Queen Elizabeth University Hospital, Glasgow, UK; Dr Peter Swoboda, Pinderfields Hospital, Wakefield, UK; Dr Richard Steeds, Queen Elizabeth Hospital, Birmingham, UK; Prof James Moon, UCL Hospital London, UK; Dr Christopher Miller, Wythenshawe Hospital, Manchester, UK; Dr Timothy Fairbairn, Liverpool Heart and Chest Hospital, UK; Dr Andrew Flett, Southampton General Hospital, UK; Prof Marianna Fontana, Royal Free Hospital, London, UK; Dr Thomas Green, Northumbria NHS Trust, UK; Prof Amedeo Chiribiri, St Thomas’ Hospital, London, UK; Dr Chiara Bucciarelli‐Ducci, University Hospitals Bristol and Weston NHS Trust, UK; Dr Graham Cole, Hammersmith Hospital, London, UK; Prof Sanjay Prasad, Royal Brompton Hospital, London, UK; Dr Adam McDiarmid, Freeman Hospital, New‐ castle Upon Tyne, UK; Dr Nicholas Bunce, St Georges Hospital, London, UK; Dr Prathap Kanagala, Aintree University Hospital, Liverpool, UK; Prof Nicholas Bellenger, The Royal Devon and Exeter Hospital, UK; Dr Tishi Ninan, Swansea Bay University Hospital, UK; Dr Khaled Alfakih, Lewisham University Hospital, London, UK; Prof James Moon, St Bartholomew’s Hospital, London, UK. Funding COVID‐HEART is funded by the National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI) COVID‐19 Rapid Response Rolling Call (Grant Number COV0254), and sponsored by the University of Leeds, UK. The study has been endorsed by the British Society of Cardiovascular Magnetic Resonance (BSCMR) Research Group, and nationally prioritised, and received both BHF‐NIHR Cardiovascular Partnership Flagship Status, and the NIHR Urgent Public Health Group identified it as an Urgent Public Health (UPH) study. Funding for the translation of the patient information leaflets into non‐ English languages was provided by the West Yorkshire and Humber Clinical Research Network (CV070).Peer reviewedPublisher PD

Alcohol use among amateur sportsmen in Ireland

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to establish baseline data on alcohol consumption patterns, behaviours and harms among amateur sportsmen in the Republic of Ireland.</p> <p>Findings</p> <p>The study presents findings from the baseline survey for a cluster randomised controlled trial to evaluate the effectiveness of a community intervention programme to reduce problem alcohol use among a representative sample of Gaelic Athletic Association (GAA) clubs in two counties in the Republic of Ireland. Self reported alcohol use, prevalence of binge drinking, AUDIT scores and alcohol-related harms were assessed in amateur GAA sportsmen aged 16 years and over.</p> <p>Nine hundred and sixty (960) players completed questionnaires (72% response rate). Mean age was 24.0 years (S.D. 5.2). Of those aged 18 years or over, 75% had post-primary education; most (864, 90%) were current drinkers and 8.2% were regular smokers. The self-reported average yearly alcohol consumption was 12.5 litres. Almost one third (31%) of current drinkers reported drinking over the recommended limit of 21 standard drinks per week and just over half (54.3%) reported drinking 6 or more standard drinks in a row at least once a week (regular binge drinking). Of those who (self) completed the Alcohol Use Disorder Identification Test (AUDIT) questionnaire, three-quarters (74.7%) had a score of 8 or more; 11.5% had a score of 20 or above warranting referral for diagnostic evaluation and treatment. Almost all (87.6%) of the 864 drinkers reported experiencing at least one harm due to their drinking. These alcohol misuse outcomes were higher than those found in a nationally representative sample of males of a similar age. There were strong associations between regular binge drinking and reporting harms such as being in a fight (adjusted odds ratio (OR) 2.02, p < 0.001), missing time from work or college (adjusted OR 1.39, p = 0.04) or being in an accident (adjusted OR 1.78, p = 0.04).</p> <p>Conclusions</p> <p>These male amateur sportsmen reported high rates of alcohol consumption and alcohol-related harm.</p

"Half plate of rice to a male casual sexual partner, full plate belongs to the husband": Findings from a qualitative study on sexual behaviour in relation to HIV and AIDS in northern Tanzania

A thorough understanding of the contexts of sexual behaviour of the people who are vulnerable to HIV infection is an important component in the battle against AIDS epidemic. We conducted a qualitative study to investigate perceptions, attitudes and practices of sexually active people in three districts of northern Tanzania with the view of collecting data to inform the formulation of appropriate complementary interventions against HIV and AIDS in the study communities. We conducted 96 semi-structured interviews and 48 focus group discussions with sexually active participants (18-60 years of age) who were selected purposively in two fishing and one non-fishing communities. The study revealed a number of socio-economic and cultural factors which act as structural drivers of HIV epidemic. Mobility and migration were mentioned to be associated with the risk of HIV acquisition and transmission. Sexual promiscuous behaviour was common in all study communities. Chomolea, (a quick transactional sex) was reported to exist in fishing communities, whereas extramarital sex in the bush was reported in non-fishing community which was predominantly Christian and polygamous. Traditional practices such as Kusomboka (death cleansing through unprotected sex) was reported to exist. Other risky sexual behaviour and traditional practices together with their socio-economic and cultural contexts are presented in details and discussed. Knowledge of condom was low as some people mistook them for balloons to play with and as decorations for their living rooms. Acute scarcity of condoms in some remote areas such as vizingani (fishing islands) push some people to make their own condoms locally known as kondomu za pepsi using polythene bags. HIV prevention efforts can succeed by addressing sexual behaviour and its socio-economic and cultural contexts. More innovative, interdisciplinary and productive structural approaches to HIV prevention need to be developed in close collaboration with affected communities and be closely related to policy-making and implementation; to go beyond the limited success of traditional behavioural and biomedical interventions to particularly address the underlying social and structural drivers of HIV risk and vulnerability in the study communities

Aortic stiffness in aortic stenosis assessed by cardiovascular MRI: a comparison between bicuspid and tricuspid valves

Objectives To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). Methods MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57 ± 0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. Results The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p < 0.001), but there were no significant differences in AA distensibility (p = 0.099), DA distensibility (p = 0.498) or PWV (p = 0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. Conclusions In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. Key Points • Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I

Tackling gaps in developing life-changing treatments for dementia.

Since the G8 dementia summit in 2013, a number of initiatives have been established with the aim of facilitating the discovery of a disease-modifying treatment for dementia by 2025. This report is a summary of the findings and recommendations of a meeting titled "Tackling gaps in developing life-changing treatments for dementia", hosted by Alzheimer's Research UK in May 2018. The aim of the meeting was to identify, review, and highlight the areas in dementia research that are not currently being addressed by existing initiatives. It reflects the views of leading experts in the field of neurodegeneration research challenged with developing a strategic action plan to address these gaps and make recommendations on how to achieve the G8 dementia summit goals. The plan calls for significant advances in (1) translating newly identified genetic risk factors into a better understanding of the impacted biological processes; (2) enhanced understanding of selective neuronal resilience to inform novel drug targets; (3) facilitating robust and reproducible drug-target validation; (4) appropriate and evidence-based selection of appropriate subjects for proof-of-concept clinical trials; (5) improving approaches to assess drug-target engagement in humans; and (6) innovative approaches in conducting clinical trials if we are able to detect disease 10-15 years earlier than we currently do today

Effect of Information and Telephone-Guided Access to Community Support for People with Chronic Kidney Disease: Randomised Controlled Trial

Background: Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD. Methods and Findings: In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control. Conclusions: An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention