Understanding who is and isn't involved and engaged in health research: capturing and analysing demographic data to diversify patient and public involvement and engagement.

BACKGROUND: Patient and public involvement and engagement (PPIE) can improve the relevance, quality, ethics and impact of research thus contributing to high quality research. Currently in the UK, people who get involved in research tend to be aged 61 years or above, White and female. Calls for greater diversity and inclusion in PPIE have become more urgent especially since the COVID-19 pandemic, so that research can better address health inequalities and be relevant for all sectors of society. Yet, there are currently no routine systems or requirements to collect or analyse the demographics of people who get involved in health research in the UK. The aim of this study was to develop to capture and analyse the characteristics of who does and doesn't take part in patient and public involvement and engagement (PPIE) activities. METHODS: As part of its strategic focus on diversity and inclusion, Vocal developed a questionnaire to assess the demographics of people taking part in its PPIE activities. Vocal is a non-profit organisation which supports PPIE in health research across the region of Greater Manchester in England. The questionnaire was implemented across Vocal activities between December 2018 and March 2022. In that time. Vocal was working with approximately 935 public contributors. 329 responses were received: a return rate of 29.3%. Analysis of findings and comparison against local population demographic data, and available national data related to public contributors to health research, was performed. RESULTS: Results show that it is feasible to assess the demographics of people who take part in PPIE activities, through a questionnaire system. Further, our emerging data indicate that Vocal are involving people from a wider range of ages and with a greater diversity of ethnic backgrounds in health research, as compared to available national data. Specifically, Vocal involves more people of Asian, African and Caribbean heritage, and includes a wider range of ages in its PPIE activities. More women than men are involved in Vocal's work. CONCLUSION: Our 'learn by doing' approach to assessing who does and doesn't take part in Vocal's PPIE activities has informed our practice and continues influence our strategic priorities for PPIE. Our system and learning reported here may be applicable and transferable to other similar settings in which PPIE is carried out. We attribute the greater diversity of our public contributors to our strategic priority and activities to promote more inclusive research since 2018.

Patient and public involvement and engagement (PPIE) can improve the relevance, quality, ethics and impact of research thus contributing to high quality research. Currently in the UK, people who get involved in research tend to be aged 61 years or above, White and female. Calls for greater diversity and inclusion in PPIE have become more urgent especially since the COVID-19 pandemic, so that research can better address health inequalities and be relevant for all sectors of society. Yet, there are currently no routine systems or requirements to collect or analyse the demographics of people who get involved in health research in the UK. Vocal is a non-profit organisation which supports PPIE in health research across the region of Greater Manchester in England. Since 2018, one of Vocal's strategic priorities has been to promote inclusive research by diversifying those who are engaged and involved in research, through the development of more inclusive ways of working together, including methods to understand who is (and isn't) currently involved in Vocal's PPIE activities. We find that it's feasible to capture and analyse demographic data related to PPIE. Further, our emerging data indicate that we are involving people from a wider range of ages and with a greater diversity of ethnic backgrounds in PPIE for health research, as compared to available national data. However, similarly to national trends, more women than men are involved in PPIE work.

Participating in innovative medicines initiative funded neurodegenerative disorder projects-An impact analysis conducted as part of the NEURONET project.

The European Commission's Innovative Medicines Initiative (IMI) has funded many projects focusing on neurodegenerative disorders (ND) that aimed to improve the diagnosis, prevention, treatment and understanding of NDs. To facilitate collaboration across this project portfolio, the IMI funded the "NEURONET" project between March 2019 and August 2022 with the aim of connecting these projects and promoting synergies, enhancing the visibility of their findings, understanding the impact of the IMI funding and identifying research gaps that warrant more/new funding. The IMI ND portfolio currently includes 20 projects consisting of 270 partner organizations across 25 countries. The NEURONET project conducted an impact analysis to assess the scientific and socio-economic impact of the IMI ND portfolio. This was to better understand the perceived areas of impact from those directly involved in the projects. The impact analysis was conducted in two stages: an initial stage developed the scope of the project, defined the impact indicators and measures to be used. A second stage designed and administered the survey amongst partners from European Federation of Pharmaceutical Industries and Associations (EFPIA) organizations and other partners (hereafter, referred to as "non-EFPIA" organizations). Responses were analyzed according to areas of impact: organizational, economic, capacity building, collaborations and networking, individual, scientific, policy, patient, societal and public health impact. Involvement in the IMI ND projects led to organizational impact, and increased networking, collaboration and partnerships. The key perceived disadvantage to project participation was the administrative burden. These results were true for both EFPIA and non-EFPIA respondents. The impact for individual, policy, patients and public health was less clear with people reporting both high and low impact. Overall, there was broad alignment between EFPIA and non-EFPIA participants' responses apart from for awareness of project assets, as part of scientific impact, which appeared to be slightly higher among non-EFPIA respondents. These results identified clear areas of impact and those that require improvement. Areas to focus on include promoting asset awareness, establishing the impact of the IMI ND projects on research and development, ensuring meaningful patient involvement in these public-private partnership projects and reducing the administrative burden associated with participation in them.

An explainable algorithm for detecting drug-induced QT-prolongation at risk of torsades de pointes (TdP) regardless of heart rate and T-wave morphology.

Torsade de points (TdP), a life-threatening arrhythmia that can increase the risk of sudden cardiac death, is associated with drug-induced QT-interval prolongation on the electrocardiogram (ECG). While many modern ECG machines provide automated measurements of the QT-interval, these automated QT values are usually correct only for a noise-free normal sinus rhythm, in which the T-wave morphology is well defined. As QT-prolonging drugs often affect the morphology of the T-wave, automated QT measurements taken under these circumstances are easily invalidated. An additional challenge is that the QT-value at risk of TdP varies with heart rate, with the slower the heart rate, the greater the risk of TdP. This paper presents an explainable algorithm that uses an understanding of human visual perception and expert ECG interpretation to automate the detection of QT-prolongation at risk of TdP regardless of heart rate and T-wave morphology. It was tested on a large number of ECGs (n=5050) with variable QT-intervals at varying heart rates, acquired from a clinical trial that assessed the effect of four known QT-prolonging drugs versus placebo on healthy subjects. The algorithm yielded a balanced accuracy of 0.97, sensitivity of 0.94, specificity of 0.99, F1-score of 0.88, ROC (AUC) of 0.98, precision-recall (AUC) of 0.88, and Matthews correlation coefficient (MCC) of 0.88. The results indicate that a prolonged ventricular repolarisation area can be a significant risk predictor of TdP, and detection of this is potentially easier and more reliable to automate than measuring the QT-interval distance directly. The proposed algorithm can be visualised using pseudo-colour on the ECG trace, thus intuitively 'explaining' how its decision was made, which results of a focus group show may help people to self-monitor QT-prolongation, as well as ensuring clinicians can validate its results.

Prospective study of change in liver function and fat in patients with colorectal liver metastases undergoing preoperative chemotherapy: protocol for the CLiFF Study.

INTRODUCTION: Preoperative chemotherapy in patients undergoing resection for colorectal liver metastases (CLM) improves oncological outcomes. However, chemotherapy-associated liver injury (occurring in two patterns: vascular and fat deposition) is a real clinical concern prior to hepatic resection. After major liver resection, regeneration of the residual liver is a prerequisite for recovery and avoidance of liver failure, but this regenerative capacity may be hindered by chemotherapy. Thus, there is a need to predict for this serious complication. Over the past two decades, several tests and derived indices have been developed, which have failed to achieve clinical utility, mainly as they were indirect measurements of liver function. Here, we will use a novel test of liver function (the liver maximum capacity (LiMAx) test), and measure liver fat using MRI. METHODS AND ANALYSIS: This prospective study will assess changes in liver function longitudinally, measured by the LiMAx test, and liver fat, measured by advanced MRI using both MR spectroscopy and the modified Dixon method, in up to 35 patients undergoing preoperative chemotherapy for CLM. The primary outcomes will be the changes in liver function and fat compared with baseline prechemotherapy measurements. Secondary outcome measures include: routinely measured liver function blood tests, anthropometric measurements, postoperative histology and digital quantification of fat, postoperative complications and mortality and quality of life. ETHICS AND DISSEMINATION: The study was approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences and the National Institute for Health Research network. Manuscripts will be published. TRIAL REGISTRATION NUMBER: This study is registered online at www.clinicaltrials.gov (registration number NCT03562234).

Innovating public engagement and patient involvement through strategic collaboration and practice.

BACKGROUND: Patient and public involvement and engagement is an important and expected component of health-related research activity in the UK. Specifically within the health research sphere, public engagement (usually defined as raising awareness of research) and patient involvement (usually defined as actively involving people in research) have traditionally been seen as separate but have much to gain from working together towards a common goal of better health outcomes for all. METHODS: This paper describes a unique approach taken by the Public Programmes Team: a small interdisciplinary team of public engagement specialists, with backgrounds in science, community development, public engagement and involvement, policy, ethics, communications, industry, museums and creative practice, embedded within translational research infrastructure and delivery in Manchester in the North West of England. We propose a new model of professional practice - a 'cycle' of engagement and involvement - innovating across the complementary fields of public engagement and patient involvement, and working inclusively and in partnership with people in health research. Further, our approach capitalises on strategic collaboration offering economies of scale and a joined up way of working. Our ambition is to boldly experiment, learn and reflect, responsibly and based on evidence and partnerships, using methods of engagement that address issues of social justice. RESULTS: Here, we report on preliminary case studies exemplifying the impact of our approach, and data relating to achievements and learning between April 2017 and March 2018. Informed by our findings, we propose that our approach has the potential to be replicated elsewhere. CONCLUSIONS: Our practice and the beginning of its evaluation lead us to believe that our way of working and model of professional practice - the 'cycle' of engagement and involvement - is effective in: addressing our vision of making health research relevant and inclusive for everyone; and embedding and joining up public involvement in a busy and fertile translational health research ecosystem.

What do young people with rheumatic conditions in the UK think about research involvement? A qualitative study.

BACKGROUND: Involving people of all ages in health research is now widely advocated. To date, no studies have explored whether and how young people with chronic rheumatic conditions want to be involved in influencing health research. This study aimed to explore amongst young people with rheumatic conditions, 1) their experiences of research participation and involvement 2) their beliefs about research involvement and 3) beliefs about how young people's involvement should be organized in the future. METHODS: Focus groups discussions with young people aged 11-24 years with rheumatic conditions across the UK. Data was analysed using a qualitative Framework approach. RESULTS: Thirteen focus groups were held involving 63 participants (45 F: 18 M, mean age 16, range 10 to 24 years) across the UK. All believed that young people had a right to be involved in influencing research and to be consulted by researchers. However, experience of research involvement varied greatly. For many, the current project was the first time they had been involved. Amongst those with experience of research involvement, awareness of what they had been involved in and why was often low. Those who had previously participated in research appeared more positive and confident about influencing research in the future. However, all felt that there were limited opportunities for them to be both research participants and to get involved in research as public contributors. CONCLUSIONS: These findings suggest that there is an on-going need to both increase awareness of research involvement and participation of young people in rheumatology as well as amongst young people themselves.

What do young people with rheumatic disease believe to be important to research about their condition? A UK-wide study.

BACKGROUND: The involvement of people of all ages including young people in research is now widely advocated but prioritisation of research topics is still driven largely by professional agendas. Evidence from adult literature has reported a mismatch between a researcher and patient generated list of research topics. There have been no studies to date exploring the priorities of young people with long term conditions other than in SLE. The study aimed to explore the research priorities of young people across the UK with respect to rheumatic conditions. METHODS: Focus groups were undertaken with young people aged 11-24 years with rheumatic conditions recruited across the UK via members of the Barbara Ansell National Network for Adolescent Rheumatology BANNAR and relevant national charities. Data was analysed using a Framework approach. Participants discussed their beliefs about what should be researched in: Basic Science; Clinical Medicine; Health Services, Psychosocial, and Public Health. They were then invited to prioritize these areas in terms of how much funding they should receive. RESULTS: Thirteen focus groups were held involving 63 participants (18 males: 45 females, mean age 16 years, range 10 to 24) in all four nations of the UK. Young people's research priorities were influenced by whether they felt research would achieve benefits for all or just some patients and long or short term goals. Another influence was whether participants felt that research areas were already well funded. Across all groups, Basic Science was a key priority and participants felt that psychosocial research should be prioritized more. Health Services Research was a lower priority, as the majority of participants were happy with their care. Clinical medicine was not a high priority as young people were happy with their medication or uncomfortable with trying new ones. Finally, for nearly all groups, Public Health was a low priority. Differences were also observed between the two age groups and across the geographically diverse focus groups. CONCLUSION: Understanding young people's research priorities is important to develop research that is in tune with their needs. The results highlight the importance of considering the whole age range of adolescence and young adulthood as well as geographical diversity. The findings from this work will inform the future research of the Barbara Ansell National Network for Adolescent Rheumatology BANNAR in the UK.