UK Health Research Research Articles

Prospective longitudinal evaluation of AI-ECG in newly diagnosed heart failure (PLANE-HF)

Abstract Background * In the United Kingdom, there are one million people suffering from heart failure (HF), with more than 60,000 new cases annually (1). * Monitoring for declining left ventricular ejection fraction (LVEF) could optimise treatment approaches and avert healthcare episodes. * Easy home-based tracking of cardiac function would be transformative. * Previous studies have validated the capability of artificial intelligence-enabled electrocardiogram (AI-ECG) to correlated with changes in LVEF (2). * We hypothesize that longitudinal changes in AI-ECG probability score is associated with changes in the left ventricular (LV) function. Method * A prospective multicentre longitudinal study recruiting newly diagnosed HF with reduced ejection fraction (HFrEF) cases to investigate application of AI-ECG using longitudinal single-lead ECG recordings via patient-administered smart ECG-stethoscope examination – Figure 1. * A total of 36 patients were included in the analysis, with invitation to return for repeat echocardiography at 6-8 weeks. * Adjusted logistic regression was performed to analyze changes in LVEF by 10% as the outcome variable, investigating the relationship with the trajectory of AI-ECG probability scores. This study was approved by the UK Health Research Authority (reference 22/LO/0701). Result * Out of 36 patients, 19 patients had ischaemic and 17 had a non-ischaemic HF. * The mean age was 56.3 years, 97.2% patients were male and 46.6% were White. * 328 longitudinal single-lead ECGs were captured and used in the analysis. * 12 (33.3%) patients had an increase of their LVEF by 10%; preceding AI-ECGs was predictive of this recovery (OR 1.36; 95% CI, 1.05 – 1.65, p value = 0.016 – Table 1) Clinical Importance: * Individualised predictions of deterioration and improvement * Proactive medication adjustment * Enhanced triage for echocardiography Conclusion * AI-ECG designed to identify left ventricular systolic dysfunction (LVSD) can predict changes in LVEF% among newly diagnosed HFrEF patients. * Such results can place AI-ECG as a remote monitoring tool to track improvement or deterioration in patients’ LVEF%, which facilitate a proactive management and prevention strategies.

Long-term clinical outcomes informed by artificial intelligence-enabled single-lead ECG detection of reduced ejection fraction

Abstract Background * Reduced left ventricular ejection fraction (LVEF) is linked to poor clinical outcomes (1, 2). * Despite its increasing prevalence, reduced LVEF is often undetected due to resource-limited echocardiography and lack of suitable point-of-care diagnostic tools. * Previous studies have shown that an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm can accurately identify patients with reduced LVEF, but may also offer novel insights on long-term prognosis (3, 4). Purpose We aimed to determine if an AI-ECG algorithm designed for detecting reduced LVEF can also independently predict 2-year major adverse cardiovascular events (MACE) and all-cause mortality. Method * A retrospective multicentre observational study investigating the ability of AI-ECG to predict long-term clinical outcomes (i.e. over two years' follow up). * Analysis included a total of 1,007 consecutive unselected patients attending for routine echocardiography, with a single-lead ECG recording performed at the same time. * An AI-ECG algorithm, designed to identify impaired LVEF, was applied to each single-lead ECG. * Occurrence of MACE and all-cause mortality associated with AI-ECG results (Figure 1) was investigated using Cox regression; evaluating performance of AI-ECG results as a classifier (0 or 1) and as a probability score (0 to 1). * The study was approved by the UK Health Research Authority (reference 21/LO/0051). Results * The mean age was 62.3 years. 52.4% of patients were male and 57.5% of patients were White. * Appropriately, patients with a positive AI-ECG had a higher MACE rate compared to those with a negative AI-ECG (34.2% vs. 11.9%; adjusted hazard ratio (aHR) 2.02; 95% CI, 1.46 – 2.81; p < 0.005), primarily driven by increased mortality (23% vs. 9.6%; p < 0.0001; aHR 1.65; 95% CI, 1.12 – 2.43) and heart failure hospitalization (14.5% vs. 1%; p < 0.0001) – Figure 2. * AI-ECG probability score (per 10% increase) was significantly associated with MACE (aHR 1.17; 95% CI, 1.09 – 1.25; p < 0.005) and all-cause mortality (aHR 1.11; 95% CI, 1.02 – 1.20; p = 0.01). * Importantly, sub-analysis of AI-ECG for those who have a normal LVEF (i.e. ≥50%) continued to show association between positive AI-ECG and MACE (27.2% vs. 11.9%; p < 0.0001; aHR 1.70, 95% CI 1.17 – 2.48) and all-cause mortality (20.4% vs. 9.6%; p < 0.0001; aHR 1.53, 95% CI 1.00 – 2.36). Conclusion An AI-ECG algorithm designed to identify impaired LVEF can identify patients at risk of MACE and all-cause mortality from single-lead ECG screening – regardless of their LVEF. Such results may enable further risk stratification for cardiovascular investigations through the simple addition of single-lead ECG recording.

Evaluating the impact of a ward environment with 20 single occupancy rooms and two four-bedded bays on patient and staff experiences and outcomes in an acute NHS Trust: a mixed-methods study protocol

IntroductionTraditionally, wards in acute care hospitals consist predominately of multioccupancy bays with some single rooms. There is an increasing global trend towards a higher proportion of single rooms in hospitals,...

HAP-FAST: a feasibility study incorporating qualitative, mechanistic and costing sub-studies alongside a randomised pilot trial comparing chest x-ray to low-dose CT scan and empirical antibiotics to antibiotics guided by the BIOFIRE® FILM ARRAY® pneumonia plus panel in adults with suspected non-ventilator-associated hospital-acquired pneumonia

IntroductionNon-ventilator-associated hospital-acquired pneumonia (nv-HAP) is the most common healthcare-associated infection (HCAI), is associated with high mortality and morbidity and places a major burden on healthcare systems. Diagnosis currently relies on...

Effect of synthetic CT on dose-derived toxicity predictors for MR-only prostate radiotherapy.

Toxicity-driven adaptive radiotherapy (RT) is enhanced by the superior soft tissue contrast of magnetic resonance (MR) imaging compared with conventional computed tomography (CT). However, in an MR-only RT pathway synthetic CTs (sCT) are required for dose calculation. This study evaluates 3 sCT approaches for accurate rectal toxicity prediction in prostate RT. Thirty-six patients had MR (T2-weighted acquisition optimized for anatomical delineation, and T1-Dixon) with same day standard-of-care planning CT for prostate RT. Multiple sCT were created per patient using bulk density (BD), tissue stratification (TS, from T1-Dixon) and deep-learning (DL) artificial intelligence (AI) (from T2-weighted) approaches for dose distribution calculation and creation of rectal dose volume histograms (DVH) and dose surface maps (DSM) to assess grade-2 (G2) rectal bleeding risk. Maximum absolute errors using sCT for DVH-based G2 rectal bleeding risk (risk range 1.6% to 6.1%) were 0.6% (BD), 0.3% (TS) and 0.1% (DL). DSM-derived risk prediction errors followed a similar pattern. DL sCT has voxel-wise density generated from T2-weighted MR and improved accuracy for both risk-prediction methods. DL improves dosimetric and predicted risk calculation accuracy. Both TS and DL methods are clinically suitable for sCT generation in toxicity-guided RT, however, DL offers increased accuracy and offers efficiencies by removing the need for T1-Dixon MR. This study demonstrates novel insights regarding the effect of sCT on predictive toxicity metrics, demonstrating clear accuracy improvement with increased sCT resolution. Accuracy of toxicity calculation in MR-only RT should be assessed for all treatment sites where dose to critical structures will guide adaptive-RT strategies. Patient data were taken from an ethically approved (UK Health Research Authority) clinical trial run at Guy's and St Thomas' NHS Foundation Trust. Study Name: MR-simulation in Radiotherapy for Prostate Cancer. ClinicalTrials.gov Identifier: NCT03238170.

Online survey exploring researcher experiences of research funding processes in the UK: the effort and burden of applying for funding and fulfilling reporting requirements

ObjectiveTo explore researchers’ experiences of funding processes, the effort and burden involved in applying for funding, obtaining funding and/or fulfilling reporting requirements with a UK health and social care research...

A study protocol to investigate if acipimox improves muscle function and sarcopenia: an open-label, uncontrolled, before-and-after experimental medicine feasibility study in community-dwelling older adults

IntroductionSarcopenia is the age-associated loss of muscle mass and strength. Nicotinamide adenine dinucleotide (NAD) plays a central role in both mitochondrial function and cellular ageing processes implicated in sarcopenia. NAD...

Sphingomyelinase Regulates the Release of Protumoral Mitochondria Containing-Vesicles from AML Cells

Mitochondrial transfer from bone marrow stromal cells to acute myeloid leukaemia (AML) blasts is protumoral (Marlein et al., 2017; Moschoi et al., 2016) . We have previously shown that this was through a NADPH oxidase-2 (Nox2) dependent mechanism which increases AML fitness both in vitro and in vivo. Furthermore, we recently have shown that AML cells export mitochondria in vesicles which are subsequently phagocytosed by bone marrow macrophages (Moore et al., 2022) . Next, we have investigated how the release of mitochondria-containing vesicles is regulated and how this process contributes to the fitness of AML blasts. Sphingolipids are a component of the cell membrane which impact the stability and curvature of the membrane. They have been shown to play a role in the biogenesis of vesicles and a number of the enzymes involved in sphingolipid metabolism are dysregulated in AML, therefore we investigated the role of sphingolipids in mitochondrial exocytosis via vesicle formation. To understand the role of vesicles in regulating AML fitness, we used primary human AML (collected with approval on the East of England - Cambridgeshire and Hertfordshire Research Ethics Committee and the UK Health Research Authority, IRAS Project ID - 33753) and mouse syngeneic AML models (MN1 and HOXA9/Meis). We find that the myosin inhibitor blebbistatin inhibits vesicle release and results in an increased mitochondrial mass and increased apoptosis. In order to investigate the involvement of one of the major sphingolipids, ceramide, we targeted neutral sphingomyelinase (GW4869) which is responsible for ceramide synthesis. We treated the AML cells in vitro with GW4869 for 24 h which induced a large increase in vesicle release. Using the mitochondrial stain Mitotracker Green (MTG) we confirm that these vesicles contain mitochondria. The vesicles were isolated, DNA was extracted, and RT-qPCR performed which confirms increased mitochondrial DNA content. Others have previously shown that low levels of cellular reactive oxygen species (ROS) are associated with leukaemic stem cells (LSCs). DCF staining of AML treated with GW4869 shows low levels of cellular ROS. To assess how this process might impact the stemness of AML, we performed in vivo experiments. Pretreatment of MN1 cells with GW4869 accelerated engraftment in C57Bl/6 animals which corresponded with a decrease in cellular ROS. In summary, we have demonstrated the mechanism of mitochondrial exocytosis is important for AML fitness and that by disrupting sphingolipid metabolism, dysregulation of this process leads to increased tumour burden.

Sting Activation in Bone Marrow Macrophages Targets AML Blasts for Phagocytosis in an ICAM-1 Dependent Mechanism

The initiation and proliferation of acute myeloid leukaemia (AML) is in part regulated by the bone marrow microenvironment. Previous work by our group has shown that the stimulator of interferon genes (STING) pathway is activated in macrophages in the AML bone marrow microenvironment (Moore et al., 2022) . We found that AML-derived mitochondrial damage-associated molecular patterns were processed by bone marrow macrophages (BMMs) via LC3-associated phagocytosis (LAP). Furthermore, activation of STING resulted in a suppression of AML growth through an LAP dependent mechanism. Here we have investigated how the activation of STING in bone marrow macrophages increases macrophage phagocytic activity and in turn supresses the growth of AML. To understand the role of STING activation in bone marrow derived macrophages (BMDMs) in AML we used various STING agonists including DMXAA, 2'3'-cGAMP, and CpG oligonucleotides. We showed STING activation was induced through these agonists by measuring the upregulation of STING related genes ( Gbp2, Irf7 and Ifit3). We demonstrated that STING activation caused increased phagocytic clearance of live MN1 cells (mouse AML cell line) in an in vitro phagocytosis assay. In order to investigate how STING activation increases the phagocytic clearance of AML cells by BMDMs, we used three complementary methods. First, we performed a receptor tyrosine kinase array to measure the phosphorylation of mouse kinases following STING activation. Second, we investigated the transcriptomic changes resulting from STING activation with mRNA-sequencing. Third, after combining these results we identified an upregulation of key phagocytic pathways that specifically led us to focus on the adhesion molecules, in particular ICAM-1. Further investigation using an anti-ICAM-1 blocking antibody showed a reduction in the phagocytic potential of the BMDMs demonstrating the role of ICAM-1 in the phagocytic clearance of AML. Next, we activated human macrophages (derived from peripheral blood monocytes collected from healthy donors with approval of the East of England - Cambridgeshire and Hertfordshire Research Ethics Committee and the UK Health Research Authority, IRAS Project ID 33753) through STING which depleted AML in vitro confirming the results obtained using the mouse system. To investigate the in vivo significance of these findings, we treated C57Bl/6 animals with DMXAA and observed a significantly decreased tumour burden and increased survival following engraftment with MN1 cells. Cytotoxic T cell activity and number in the bone marrow was unchanged by STING activation in this model. In summary, we have shown that the activation of STING in bone marrow macrophages directly supresses the growth and proliferation of AML by stimulating the phagocytic activity of the macrophages, and the clearance of the leukaemic cells.

How is ethnicity reported, described, and analysed in health research in the UK? A bibliographical review and focus group discussions with young refugees

BackgroundThe ethnicity data gap pertains to 3 major challenges to address ethnic health inequality: 1) Under-representation of ethnic minorities in research; 2) Poor data quality on ethnicity; 3) Ethnicity data not being meaningfully analysed. These challenges are especially relevant for research involving under-served migrant populations in the UK. We aimed to review how ethnicity is captured, reported, analysed and theorised within policy-relevant research on ethnic health inequities.MethodsWe reviewed a selection of the 1% most highly cited population health papers that reported UK data on ethnicity, and extracted how ethnicity was recorded and analysed in relation to health outcomes. We focused on how ethnicity was obtained (i.e. self reported or not), how ethnic groups were categorised, whether justification was provided for any categorisation, and how ethnicity was theorised to be related to health.We held three 1-h-long guided focus groups with 10 young people from Nigeria, Turkistan, Syria, Yemen and Iran. This engagement helped us shape and interpret our findings, and reflect on.1) How should ethnicity be asked inclusively, and better recorded?2) Does self-defined ethnicity change over time or context? If so, why?ResultsOf the 44 included papers, most (19; 43%) used self-reported ethnicity, categorised in a variety of ways. Of the 27 papers that aggregated ethnicity, 13 (48%) provided justification. Only 8 of 33 papers explicitly theorised how ethnicity related to health.The focus groups agreed that 1) Ethnicity should not be prescribed by others; individuals could be asked to describe their ethnicity in free-text which researchers could synthesise to extract relevant dimensions of ethnicity for their research; 2) Ethnicity changes over time and context according to personal experience, social pressure, and nationality change; 3) Migrants and non-migrants’ lived experience of ethnicity is not fully inter-changeable, even if they share the same ethnic category.ConclusionsEthnicity is a multi-dimensional construct, but this is not currently reflected in UK health research studies, where ethnicity is often aggregated and analysed without justification. Researchers should communicate clearly how ethnicity is operationalised for their study, with appropriate justification for clustering and analysis that is meaningfully theorised. We can only start to tackle ethnic health inequity by treating ethnicity as rigorously as any other variables in our research.

An in-depth exploration of researcher experiences of time and effort involved in health and social care research funding in the UK: The need for changes.

The need to reform the way in which research is undertaken is clear, with reducing research bureaucracy and waste at the forefront of this issue for the UK government, funding organisations, higher education institutions and wider research community. The aim of this study was to describe researchers' experiences of the time, effort and burden involved in funding processes-namely applying for research funding and fulfilling reporting requirements. This was an in-depth qualitative study using semi-structured interviews with researchers who had experience applying for funding and/or completing reporting requirements for a UK health and social care research funder between January 2018 and June 2021. Following thematic analysis, five key themes were identified describing researcher experiences of key issues around time, efforts and burden associated with funding processes. These themes encompassed (1) issues with the current funding model for health and social care research, (2) time and effort involved in funding processes, (3) the need for a streamlined end-to-end process, (4) implications for work-life balance, and (5) addressing the need for better support and communication. The findings from this study describe researcher experiences of tasks in the research pathway that currently take considerable time and effort. It was clear that whilst some of this time and effort is considered necessary, some is exacerbated by inefficient and ineffective processes, such as perceived under-funding of research or lack of clarity with regards to funder expectations. This in turn contributes to unnecessary researcher burden, research waste and negative research culture. Better investment in health and social care research and in the researchers themselves who design and deliver the research, alongside improvements in transparency, streamlining and research support could ensure a more positive research culture, and improve the quality of funded research.

A Diagnostic Accuracy Study to Evaluate Standard Rapid Diagnostic Test (RDT) Alone to Safely Rule Out Imported Malaria in Children Presenting to UK Emergency Departments.

Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs). UK-based, multi-center, retrospective, diagnostic accuracy study. Included: any child <16 years presenting to ED with history of fever and travel to a malaria-endemic country, between 01/01/2016 and 31/12/2017. Diagnosis: microscopy for malarial parasites (clinical reference standard) and RDT (index test). UK Health Research Authority approval: 20/HRA/1341. There were 47 cases of malaria out of 1,414 eligible cases (prevalence 3.3%) in a cohort of children whose median age was 4 years (IQR 2-9), of whom 43% were female. Cases of Plasmodium falciparum totaled 36 (77%, prevalence 2.5%). The sensitivity of RDT alone to detect malaria infection due to any Plasmodium species was 93.6% (95% CI 82.5-98.7%), specificity 99.4% (95% CI 98.9-99.7%), positive predictive value 84.6% (95% CI 71.9-93.1%) and negative predictive value 99.8% (95% CI 99.4-100.0%). Sensitivity of RDT to detect P. falciparum infection was 100% (90.3-100%), specificity 98.8% (98.1-99.3%), positive predictive value 69.2% (54.9-81.2%, n = 46/52) and negative predictive value 100% (99.7-100%, n = 1,362/1,362). RDTs were 100% sensitive in detecting P. falciparum malaria. However, lower sensitivity for other malaria species and the rise of pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions in the P. falciparum parasite mandate the continued use of microscopy for diagnosing malaria.

Can artificial intelligence accelerate the diagnosis of inherited retinal diseases? Protocol for a data-only retrospective cohort study (Eye2Gene)

IntroductionInherited retinal diseases (IRD) are a leading cause of visual impairment and blindness in the working age population. Mutations in over 300 genes have been found to be associated with...

Minding the gap: The importance of active facilitation in moving boundary objects from in-theory to in-use as a tool for knowledge mobilisation

The Health Inequalities Assessment Toolkit (HIAT) was developed to support those involved in health research to integrate a focus on health inequalities. Our study focuses on bringing together the concepts of boundary objects (BO) and brokers-as-bricoleurs to explain the implementation of the HIAT within a research capacity building programme. Exploring the extent to which (i) the HIAT operated as a BO and (ii) the ideal conditions to nurture and enhance its effectiveness during knowledge mobilisation. We employed a qualitative approach to analyse: semi-structured focus groups and telephone interviews; secondary data from an evaluation of the wider research programme within which the capacity building was situated. Data was thematically analysed incorporating the properties of a BO: meaningfulness, convergence, resonance and authenticity. Four main themes identified: (1) Generating convergence through creating a focus (2) Reconciling differences to create a common language (3) Workshop facilitators: boundary brokers-as-bricoleurs, (4) Thoughts into action. The HIAT operated as a BO, enabling individuals across the different project teams to galvanise around the issue of health inequalities, explore collaboratively and incorporate equity within service evaluations. Highlighting the importance of involving brokers with an ability to improvise and mobilise around the HIAT, using their expertise to translate and interpret across boundaries and emphasise shared goals. Reflecting on this, a modified tool with additional resources beyond socio-economic causes has been launched as a forum to consider health inequalities from diverse perspectives for use beyond UK health and social care research.

Safety and efficacy of an artificial intelligence-enabled decision tool for treatment decisions in neovascular age-related macular degeneration and an exploration of clinical pathway integration and implementation: protocol for a multi-methods validation study

IntroductionNeovascular age-related macular degeneration (nAMD) management is one of the largest single-disease contributors to hospital outpatient appointments. Partial automation of nAMD treatment decisions could reduce demands on clinician time. Established...

Research priority setting in UK podiatric surgery

Evidence-based practice provides the foundation for high quality patient care, and in the NHS, research is seen as vital to enable service transformation and improve outcomes. Research is one of the four pillars of enhanced and advanced clinical practice and is therefore a fundamental part of podiatric surgery services. In order to meet the UK health research strategies, the most recent being ‘Saving and Improving Lives: The Future of UK Clinical Research Delivery’ (2021), the Faculty of Podiatric Surgery in the UK agreed to support the development of research priorities in order to inform a future research strategy.The Podiatric Surgery Research Strategy Group was set up and embarked on a project with the aim of engaging its members in formulating and agreeing national research priorities. The initial stage included a national research scoping survey to identify key themes, topic, and research questions. The final stage consisted of developing and enabling a live consensus vote conducted at the 2022 national Faculty of Podiatric Surgery Conference. At the end of the vote, the top five research topics that met the agreement criteria were: 1. Surgical treatment – forefoot, 2. Patient reported outcome measures, 3. Post-operative management, 4. Surgical treatment – midfoot and 5. Service delivery. The top five research questions that met the criteria were1. How does quality of life improve following elective foot surgery? 2. How does podiatric surgery benefit the health of the population? 3. How does podiatric surgery benefit the health of the population in the at-risk foot? 4. What is the most effective Lapidus fixation option? and 5. What is the benefit of utilising PASCOM-10 to improve large scale outcome data? These will inform the initial UK podiatric surgery research priorities in the next three to five years.

Quantitative myocardial blood flow as a prognostic marker for cardiovascular outcomes in patients with Type 2 Diabetes Mellitus: a multicentre study

Abstract Introduction: Patients with Type 2 Diabetes Mellitus (T2DM) are at increased risk of cardiovascular disease, including epicardial coronary heart disease, silent myocardial infarction (MI), and coronary microvascular dysfunction (CMD) [1]. All of these can be assessed and quantified using cardiac magnetic resonance (CMR), including most recently quantitative myocardial blood flow (MBF). We aimed to determine the prognostic relevance of MBF in patients with T2DM and test the hypothesis that impaired stress MBF and myocardial perfusion reserve (MPR) have independent prognostic value over standard clinical and imaging parameters. Methods A 4-centre study of patients with T2DM who underwent quantitative perfusion assessment using CMR. Diagnosis of T2DM was based on Hba1c &amp;gt;48mmol/l or a known diagnosis of T2DM. Image analysis was performed automatically using an artificial intelligence approach deriving global MBF and MPR [2]. Cox proportional hazard models adjusting for comorbidities and CMR parameters sought associations between stress MBF and MPR with death and major adverse cardiovascular events (MACE), including MI, non-fatal stroke, heart failure hospitalisation and death. Results A total of 630 patients with T2DM were included with a median follow-up of 722 days (interquartile range 493) days. There were 27 (4.3%) deaths and 76 MACE events in 62 (12.1%) patients. Patient data was represented into groups depending on threshold stress MBF values of 1.94ml/g/min and MPR thresholds of 1.96 using validated data from invasive coronary physiology [3]. Patient demographics and CMR data are seen in table 1. Kaplan-Meier curves are seen in figure 1. Stress MBF was associated with mortality and MACE after adjusting for age, LV ejection fraction and HbA1c. The stress MBF adjusted hazard ratios for all cause death and death and MACE were 0.35 (95% CI, 0.13–0.95, P=0.04) and 0.54 (95% CI, 0.30–0.96, P=0.04), respectively. MPR was not significantly associated with death and MACE after adjusting for age, LV ejection fraction and HbA1c; hazard ratio for all cause death and death and MACE was 0.83 (95% CI, 0.41–1.69, P=0.60) and 0.81 (95% CI, 0.53–1.23, p=0.32) respectively. Conclusion In patients with T2DM, reduced stress MBF measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcome. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): 1. REC ID 14/EE/0007 (Barts Heart Centre funding). 2. For PREDICT (Leicester data) ethical approval was provided by the UK Health Research Authority Research Ethics Committee (reference 17/WM/0192). 3. MATCH Study, Leeds - British Heart Foundation - 17/YH/0300. 4. LEAN-DM, Leeds - British Heart Foundation - 18/YH/01685. CEED, Leeds: British Heart Foundation - REC reference - 18/YH/0190

367. RANDOMISED CONTROLLED TRIAL (FEASIBILITY STUDY) OF PROPHYLACTIC PYLORIC BALLOON DILATATION DURING IVOR LEWIS ESOPHAGECTOMY TO PREVENT DELAYED GASTRIC EMPTYING

Abstract Early delayed gastric emptying (DGE) occurs in up to 37% of patients following esophagectomy. This can contribute to increased anastomotic leak and respiratory infection rates. Although the treatment of DGE in the form of pyloric balloon dilatation (PBD) post-operatively is well established, there is no consensus on the optimal approach in the prevention of DGE. The aim is to carry out a randomised control trial to determine the efficacy of prophylactic PBD in the prevention of DGE following esophagectomy. This presentation details the protocol, recruitment strategy and potential timeline for a feasibility study addressing this. We detail the rationale, objectives, design, and methods of this study. Patients will be recruited over a three to six-month period (starting in January 2022) and randomised to either a control group (no intervention) or a treatment group (prophylactic PBD). The Chief Investigator has obtained approval from the UK Health Research Authority (HRA) and Research Ethics Committee (REC) on 01/12/21 (IRAS project ID: 287659). As a feasibility study, the objectives will be to ascertain the following: Number of patients approached; Number of patients who agreed to be randomised; Number of patients successfully randomised; Number of patients who dropped out; Successful measurement of outcome measures (delayed gastric emptying, pneumonia, anastomotic leak). Prophylactic pyloric balloon dilatation is potentially a safe and effective procedure which can significantly improve outcomes in patients after an esophagectomy. This protocol describes details for the feasibility study to be carried out which will allow important learning points for the main randomised controlled trial.

New Horizons: the value of UK Biobank to research on endocrine and metabolic disorders.

UK Biobank is an intensively characterized prospective study of 500 000 men and women, aged 40 to 69 years when recruited, between 2006 and 2010, from the general population of the United Kingdom. Established as an open-access resource for researchers worldwide to perform health research that is in the public interest, UK Biobank has collected (and continues to collect) a vast amount of data on genetic, physiological, lifestyle, and environmental factors, with prolonged follow-up of heath conditions through linkage to administrative electronic health records. The study has already demonstrated its unique value in enabling research into the determinants of common endocrine and metabolic diseases. The importance of UK Biobank, heralded as a flagship project for UK health research, will only increase over time as the number of incident disease events accrue, and the study is enhanced with additional data from blood assays (such as whole-genome sequencing, metabolomics, and proteomics), wearable technologies (including physical activity and cardiac monitors), and body imaging (magnetic resonance imaging and dual-energy X-ray absorptiometry). This unique research resource is likely to transform our understanding of the causes, diagnosis, and treatment of many endocrine and metabolic disorders.

MET-PREVENT: metformin to improve physical performance in older people with sarcopenia and physical prefrailty/frailty – protocol for a double-blind, randomised controlled proof-of-concept trial

IntroductionSkeletal muscle dysfunction is central to both sarcopenia and physical frailty, which are associated with a wide range of adverse outcomes including falls and fractures, longer hospital stays, dependency and...