NIHRDataInsights/HRCSData huggingface dataset:
Title: Centre for Precision Cell Therapy for the Liver
Funder: Chief Scientist Office, Scotland

Abstract: We aim to bring new products for the treatment of liver diseases and Type I diabetes to patients and boost our ability to perform liver related clinical trials in Scotland. Since 1970, deaths due to liver disease have quadrupled and it is the biggest cause of death in people aged 35 to 49. It is a disease of inequalities, unfairly affecting the poorest and the most vulnerable in society. People who live in more deprived areas are up to six times more likely to die of liver disease than those who live in wealthier areas. Chronic liver disease often results in liver cirrhosis, but there are currently no specific medical treatments for liver cirrhosis. Liver transplantation is a cure but only for a small number of patients. It is limited by the supply of suitable organs and a global shortage of donor organs means that many patients die waiting for a transplant. Liver transplants cannot meet the numbers of Scottish patients with liver failure or end-stage liver disease, therefore alternative treatments are urgently needed. As many patients with chronic liver disease are diagnosed at an advanced stage, there is a need to develop better therapies for patients with advanced liver disease. Because of the different causes of liver damage, each condition has different disease processes, so a different ‘precision medicine’ approach is required for each specific liver disease. Cell and gene therapies (known as Advanced Therapy Medicinal Products, ATMPs) offer the ability to precisely fix biological defects in damaged organs and are now providing cures in previously untreatable diseases (e.g. CAR-T cell therapy for cancer). We will use funding from CSO to build on our outstanding existing skills and facilities to create a ‘Centre for Precision Medicine for the Liver’. We will use precise advanced therapies to target the liver to treat severe liver disease, reduce liver mortality and morbidity and the need for liver transplantation. This will involve different forms of cell therapy that we have shown are effective in model systems and in one type of cell therapy safe in patients with cirrhosis. This funding will allow investment in critical staff and expertise in key “bottleneck areas” within Scottish National Blood Transfusion Service, pharmacy and advanced therapy trial management. This will serve the Scottish population and be a platform for the delivery of these novel therapies.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: ORAL AND GASTROINTESTINAL
Title: 2020 Doctoral Fellowship: TRaditional or minimal intervention Endodontics For managing caRiOus teeth with syMptomatic pulpitis (REFORM): A pragmatic randomised clinical trial in general dental practice setting in N. Ireland
Funder: Public Health Agency, NI

Abstract: Teeth with deep caries diagnosed with irreversible pulpits (IP) are traditionally treated with root canal treatment (RCTx), a destructive, technically challenging, time consuming and expensive process involving removal of the entire dental pulp. Recent United Kingdom (UK) data highlights that a large proportion of RCTx performed in general dental practice (GDP) are technically inadequate, with a high prevalence of associated apical infection. A key aim of contemporary minimally invasive (MI) endodontics is preservation of vital pulp using biologically based therapies. Two MI therapies being suggested for managing IP are complete coronal pulpotomy (Cp) and partial coronal pulpotomy (Pp). Cp involves removal of entire coronal pulp leaving the radicular pulp intact, whilst in Pp only 2-3 mm of the coronal pulp is removed. In both Cp and Pp the residual pulp is dressed with biomaterial to promote healing. Success of these treatments is dependent on a good understanding of the extent of injury to the dental pulp, including the intensity of bacterial infection and the inflammatory responses taking place. The challenge for practitioners is that the clinical quantification of the inflammatory processes, which influences the outcome, relies on unreliable subjective symptoms and weak diagnostic and assessment tools. Aim: To investigate the utility of minimal intervention approaches for managing carious teeth with symptoms of irreversible pulpitis in general dental practice (GDP) in Northern Ireland (NI). A subsidiary aim is to test the feasibility of using biomarkers for pulpal diagnosis and subsequent treatment needs. Objectives: (1) Evaluate the evolving scientific evidence for minimally invasive endodontics procedures and scope dentists’ and users’ perception of this approach. (2) Conduct a threearm single blinded randomised trial to assess the incidence of pain following RCTx, Cp and Pp at day 1-3 post-operatively in the management of IP in permanent posterior teeth. (3) Measure inflammatory biomarkers in pulpal blood samples collected from teeth undergoing RCTx, Pp or Cp using multiplex cytokines arrays and to correlate the level of biomarkers with pre- and post-operative pain measures to validate their use as diagnostic and prognostic markers. Outcome and impact: The outcome of this study if successful will change the way in which, teeth with IP will be managed in GDP and will provide evidence for the utility of biomarkers in case selection for MI endodontics


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: ORAL AND GASTROINTESTINAL
Title: A speech recognition application as a communication aid for critical care patients with tracheostomies: a feasibility trial
Funder: Public Health Agency, NI

Abstract: Background. Tracheostomy is a common procedure performed in critically ill patients requiring prolonged mechanical ventilation with approximately 10,000 patients undergoing a tracheostomy annually in the UK alone. Many patients with tracheostomies are unable to communicate verbally and loss of speech is a frightening experience. Patients often rely on facial expressions, gestures and writing to communicate, but these are often ineffective and result in frustration, agitation, anxiety, and fear for the patient. A Speech Recognition Application for the Voice Impaired (SRAVI) has been developed for lip reading and may provide a useful alternative communication aid for tracheostomy patients. Aim.The overall aim of this project is to undertake a feasibility trial of SRAVI. Methods. The following methods will be used to address the aim:1. A survey of critical care unit (CCU) (intensive care unit and high dependency unit) healthcare professionals to collect information on what they say is current practice in aiding communication.2. A feasibility randomised clinical trial in multi-centre CCUs to compare two forms of communication service provision: (1) Usual Care which includes the use of communication boards, writing, gesturing, head nods and speaking valves (as defined in aim 1); (2) Usual Care plus access to SRAVI. 3. Interviews with critical care patients, significant others and critical care multi-disciplinary (MDT) staff to obtain views on satisfaction with the randomised communication service provision. Outcomes. The primary outcome is the acceptability and usability of SRAVI. Additional outcomes are the feasibility of recruiting for, and conducting, a larger trial powered to detect cognitive and psychological impairment three months following discharge from critical care.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: ORAL AND GASTROINTESTINAL
Title: Doctoral Fellowship - Suzanne Lester - PREhabilitation for Patients Awaiting liveR transplantation: development and feasibility testing of a remote multicomponent prEhabilitation intervention: PREPARE
Funder: Public Health Agency, NI

Abstract: Background: Sarcopenia (a reduction in muscle mass, muscle strength and physical function) in patients with end stage liver disease is very common. Up to 70% of patients will be affected, with a two fold increase in the presence of sarcopenia in end stage liver disease in comparison to any other chronic condition due to the altered metabolic process of a cirrhotic liver. Interventions aimed at preventing or minimising sarcopenia could increase physical funciton, increase muscle strength and muscle mass, and improve patient well being.A remote multicomponent prehabilitation intervention that aims to improve sarcopenia prior to liver transplantation has the potential to reduce overall hospital length of stay and reduce waiting list mortality whilst resulting in improved post-surgical outcomes. Aim: To develop and test the feasibility of a remote multicomponent prehabilitation intervention for patients with end stage liver disease awaiting liver transplantation to prevent or minimise post-operative complications through increased physical activity and function. Methods: This study will use a range of methods: 1. A scoping review to map the available evidence around prehabilitation and remote intervention delivery in patients awaiting liver transplantation. 2. Focus groups with patients awaiting liver transplantation or who have had a transplantation and their family/caregivers, expert liver disease clinicians, and clinicians involved in the delivery of prehabilitation, to explore opinions, experiences, facilitators, and barriers to a remote multicomponent prehabilitation intervention. 3.Co-design workshops to develop a remote multicomponent prehabilitation intervention in partnership with patients awaiting liver transplantation. 4. A Feasibility study in a single liver unit to test the intervention, its delivery, fidelity, recruitment rates, and outcomes. Benefits:This study will demonstrate if the delivery of a remote multicomponent prehabilitation intervention for patients with end stage liver disease awaiting transplantation is feasible in a UK centre. It will inform the design of a larger definitive trial to determine clinical and cost effectiveness of such an intervention compared to standard care in this patient group.


Research activity codes: 6.4 SURGERY;7.1 INDIVIDUAL CARE NEEDS
Health categories: ORAL AND GASTROINTESTINAL
Title: Determinants of microbe-host responses in the gut across life
Funder: Biotechnology and Biological Sciences Research Council

Abstract: To probe specific mechanistic aspects of the gut microbiome's positive influence on health throughout life, we have developed a systems-level experimental approach. We will use innovative in vivo, in vitro, and in silico tools/models in tandem with a key longitudinal cohort (pregnancy and early life) to define and refine novel intervention strategies that will promote gut health. Our multi-disciplinary research theme managed by QIB and university research leaders, maps to three objectives. These objectives will determine how microbes (bacterial, viral, fungal) establish and maintain a balanced community that modulates host homeostatic cross-talk within the gut._x000D__x000D_ This theme involves a 250-particpant longitudinal population study of pregnancy mothers and their infants, up to 2 years of age. _x000D__x000D_ Theme 1 focusses on the gut during the very first stages of life, and in the elderly, and will seek to unravel: (i) how pioneer/keystone microbial species facilitate healthy development (ii) which microbial mediators modulate microbe-microbe and microbe-host cross-talk and (iii) bi-directional immune system-microbiota interactions within the gut._x000D__x000D_ Theme 1 Outputs _x000D__x000D_ â€¢ identification of critical pre- and post-natal periods for establishing a healthy intestinal microbiome and the contribution that host and environmental factors play_x000D__x000D_ â€¢ define molecular mediators of microbe-microbe and microbe-host crosstalk important in microbial ecology and establishing tolerance_x000D__x000D_ Our integrated plan of work will ultimately determine microbiome- and host-associated pathways that could represent key targets for lifestyle changes and therapies that reduce the incidence and burden of infectious, metabolic, and immune-mediated conditions.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: ORAL AND GASTROINTESTINAL
Title: Modulation of the gut microbes to promote health throughout life
Funder: Biotechnology and Biological Sciences Research Council

Abstract: This theme focuses on the translational aspect of the Gut Microbes and Health programme, which will pursue ongoing applied work within the programme but will also identify additional targets based on the output of basic research outlined in themes 1 and 2, to strengthen and further develop strategies to promote health throughout life. Specifically, these will focus on developing bifidobacterial-based probiotics for infant supplements as well as lactic acid bacteria for animal feed to reduce the pathogen load in the food chain to reduce the incidents of food poisoning in humans. _x000D__x000D_ _x000D__x000D_ Gut commensal organisms capable of efficient expression of specific enzyme and antimicrobial peptides to inhibit pathogens such as C. difficile, which affects the elderly, will be developed and tested. We also propose to identify carbohydrate-based mucosal barrier protectors as well as gut commensals and their products as therapeutics and for development of vaccines to promote gut health. We will explore strategies for modulation of the structure and function of the gut microbiome, including the application of faecal microbiota transplant, phage therapy and exploitation of the gut commensal eukaryotes (yeast and fungi) for restoration of gut microbiota homeostasis. We will utilise in-house facilities of tissue and organ cultures, in vitro colon models, animal models (including germ free mice) as well as human intervention studies to conduct proof-of-concept studies and demonstrate efficacy of the strategies developed.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: ORAL AND GASTROINTESTINAL
Title: Translation of an innovative microgel technology for improving swallowing in the elderly
Funder: Economic and Social Research Council

Abstract: Ultimate goal: to scale up and commercialise a novel, marketable health product (a food-grade, non-lipidic lubricant) for patients suffering from dry mouth. Objectives: 1) Building a wide portfolio of saliva substitute formats, 2) Manufacturing a safety- and regulatory-compliant prototype, in a range of formats, 3) Further capturing real-word user input into product design.

Lay abstract: Dry mouth, due to a reduction/absence of salivary flow/lubricity, affects at least 10 million people in the UK, predominantly elders. Largely driven by age-related chronic/neurogenerative diseases and polypharmacy, oral dryness significantly increases the risk of dental caries, periodontal diseases, candidiasis, oral ulceration, and dysphagia - all of which adversely impact the nutritional status and quality of life of elderly people. Numerous salivary replacers are commercially available, but none offers long-lasting relief due to their poor lubrication properties, thus forcing sufferers to use mouth spray repeatedly all day long to be able to eat. Subsequent malnutrition, which affects 1.3 million over-65s, results in a £7.3 billion annual loss. We have recently patented an innovative, highly lubricating saliva substitute for dry mouth sufferers, which offers 95% more effective lubrication and a 50% longer relief period than both currently marketed saliva-replacing products and the naturally lubricating human saliva. Our technology forms a viscous fluid film that moistens/lubricates the mouth (lubricity-improving hydration thanks to the water-encapsulating biopolymeric hydrogel) and stays adsorbed onto the human tongue/palate following ingestion (long-lasting hydration thanks to the efficiently adsorbing proteinaceous microgel). Besides technical development, we have demonstrated up-scaling feasibility and regulatory compliance. Our novel lubricant will overcome the bottleneck of the sub-optimal performance of marketed aqueous lubricants, and will surely contribute to addressing the long-standing swallowing issues faced by elders. This award will allow conducting further proof-of-principle work, including manufacturing a safety compliant medical device, assessing its cost, and building a robust business case.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: ORAL AND GASTROINTESTINAL
Title: Treatment outcomes of periodontal regenerative procedures. A cross-sectional, observational study.
Funder: Barts Charity

Abstract: Gum disease is caused by bacteria that accumulate at the gum line progressively destroying the gum and bone surrounding the tooth. Its treatment includes oral hygiene instructions, deep cleaning and gum surgery. In some cases dentists can attempt to surgically ?regenerate?/regrow the tissues lost. Previous studies have shown that when conditions are favourable regenerative surgery can be successful[3]. However, these results come from studies where ideal conditions and experienced surgeons are involved. Indeed the success of regenerative surgeries performed by specialists in training in a NHS teaching Hospital is not known. The aim of this study is to assess the results of regenerative surgery in patients with gum disease treated in an NHS teaching hospital. An initial analysis of clinical data of patients that received gum surgery will be undertaken followed by a recall appointment for a gum check-up to assess success of treatment over a longer period of time.


Research activity codes: 6.4 SURGERY
Health categories: ORAL AND GASTROINTESTINAL
Title: Validating the Prognostic Utility of Vascular Adhesion Protein 1 in Primary ScleRosing Cholangitis: The VAPoR Study
Funder: PSC Support

Abstract: Dr Trivedi will draw on the UK-PSC data set (to which many UK patients have already given blood samples) to: Yield a robust, validated biomarker for patients, which is linked to the underlying disease process and accurately predicts prognosis in PSC. Improve understanding of the features that define high versus lower risk groups. Provide a better evidence base to identify those most in need of new treatments, and consequently refine the criteria that determine clinical trial eligibility.

Lay abstract: as per abstract

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: Investigation of Infliximab Pharmacokinetics in Acute Severe UC
Funder: Crohn's & Colitis UK

Abstract: Treatment outcomes for rescue therapy with infliximab (IFX) in ASUC remain suboptimal with up to 30% of patients requiring emergency surgery, which is associated with increased morbidity and mortality. Preliminary evidence suggests that IFX pharmacokinetics (PK) may be altered in some ASUC patients due to disease severity and accelerated clearance though there has never been a detailed evaluation in the acute severe setting. Most studies investigating IFX PK have been conducted in chronic ambulatory UC which is distinct from ASUC. We aim to conduct a prospective multi-centre observational study to systematically analyse IFX PK in ASUC to (i) determine the role of various disease co-variates which influence IFX PK and (ii) determine threshold IFX values associated with response and avoidance of colectomy. We also aim to validate a point-of-care IFX assay to enable real time decision making for clinicians. This will form the basis for individualised therapy and improving outcomes in ASUC.

Lay abstract: Acute severe Ulcerative Colitis (ASUC) is a life-threatening condition that requires urgent treatment with steroids. But, 40% of people do not respond to the steroid treatment and need further rescue treatment with infliximab or cyclosporin to avoid emergency surgery to remove their bowel (colectomy). Unfortunately, 30% of people also fail to respond to infliximab and go on to need an emergency colectomy. Emergency surgery results in more complications and deaths than planned surgery, so if it can be avoided it will result in much better outcomes for the patient. The way infliximab is absorbed, distributed and excreted from the body, a process known as pharmacokinetics, is different in people with ASUC compared to people with less severe Ulcerative Colitis. There are a number of reasons for this: There is more inflammation in ASUC - this acts as a sponge to soak up the infliximab and clear it from the body more quickly. More infliximab is lost in the stools due to the ‘leakiness’ of the large bowel caused by the severe inflammation. Infliximab needs to bind to a protein in the blood called albumin and people with ASUC have less albumin in their blood. This research project will investigate the pharmacokinetics of infliximab in people with ASUC. Researchers will take blood and stool samples and measure the amount of infliximab at different time points after treatment. They will compare this to how severe the patient’s Ulcerative Colitis is by measuring their clinical symptoms and markers of inflammation. This will allow the researchers to find the minimum amount of infliximab that needs to be in the blood to make sure the treatment works. The researchers will use this information to create a new test that can be used in the clinic.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: Faecal volatile organic compounds in children with eosinophilic oesophagitis potential as non-invasive biomarkers
Funder: Guts UK

Abstract: Eosinophilic oesophagitis (EoE) is a chronic inflammation of the oesophageal mucosa, resulting in moderate or severe inability to swallow fluids and food, which can lead to food bolus impaction and strictures if untreated (1). First diagnosed in the 90’s, EoE has rapidly rising pooled prevalence of 34/100,000 and incidence of 6.6/100,000 children per year (2). Until now, diagnosis and regular monitoring depend on upper endoscopy (OGD) under general anaesthetic with multiple biopsies from the oesophagus, which can result in more than 10 and more endoscopies during the paediatric patient journey to achieve sustained remission with elimination diets (3) and has a profound impact on health-related quality of life (Auth MKH, 2021). EoE results from pathological activation of eosinophilic leukocytes to food proteins by dendritic cell antigen update enhanced Treg differentiation, Th2 response, leading to migrating from the intestinal lymphatic nodes (hosting 70% of immune-competent cells) to the oesophagus via eotaxin-3 signals. Experts in EoE, oesophageal diseases, and allergies have shown that a loss of protective commensal bacteria (caused by caesarean section, formula feeding, antibiotics and PPI exposure, diet and other medication) results in dysbiosis of the gut microbiome (4,5), which can be measured by changes in the gut metabolome (5), and risk of allergy development (4). According to the epithelial barrier hypothesis, exposure to barrier damaging agents leads to inflammation in the epithelium and barrier damage, colonisation of opportunistic pathogens, microbial dysbiosis, decreased biodiversity, translocation of microbiota into subepithelial spaces, and an immune response via Th2/Treg mediated eosinophilic recruitment into other epithelial spaces by means of mucosal surfaces communicating with each other (6,7, Furuta GT, 2021).


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL