NIHRDataInsights/HRCSData huggingface dataset:
Title: Developing a prototype device for point-of-care non-alcoholic fatty liver disease diagnostics
Funder: Innovate UK

Abstract: Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation in the liver and affects 20-30% of adults globally, ˜20% of whom progress to a more serious condition called non-alcoholic steatohepatitis (NASH). NASH-related liver damage is reversible, but only if diagnosed early. However, NASH diagnosis rates are extremely low, and for most patients diagnosis occurs too late for intervention. New tests are needed that allow more patients to be tested for NASH, resulting in earlier diagnosis and treatment. Given that NASH is common, these tests ideally need to be provided by a GP and, therefore, must be low-cost and require little equipment. Existing tests and those in development do not meet these requirements, and there is a need for innovative approaches that fill this gap. This proposal addresses this need using Rosa Biotech's sensing platform, Pandra, which can detect NASH in patient blood samples with high accuracy. Pandra detects disease using the principle of olfaction (the sense of smell). The olfactory system uses arrays of protein receptors that bind to odorants as they enter the nose. The brain recognises patterns of receptor stimulation and interprets the pattern as a smell. When applied to biosensing, this principle is called differential sensing. It allows small changes in a sample's total contents to be analysed, without relying on pre-identified markers of disease. Rather than olfactory receptors, which are challenging to work with, Rosa's sensing technology, Pandra, uses arrays of designed proteins that bind coloured dyes. Exposing the array to samples containing fats displaces the dyes from the proteins to different extents, resulting in colour changes across the array. This produces a unique 'fingerprint' for the sample. An artificial intelligence (AI) algorithm is trained to recognise differences between fingerprints associated with disease in known samples. The algorithm is then used to detect disease in unknown samples. Pandra is cheap to produce, usable by non-experts, and sensitive to small changes in fat composition. This makes it well-suited to NASH diagnostics. This project aims to produce an early prototype Pandra sensor that could be deployed at the point-of-care in a GPs surgery. This would provide clinicians with an invaluable new tool for initially assessing high-risk patients for NASH and deciding the best referral route. Ultimately, it will result in a new test that will enable more patients to be tested for NASH, reducing the number progressing to more severe liver disease, cancer, and death.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: University of Southampton and Glaxosmithkline Consumer Healthcare (UK) Trading Limited
Funder: Innovate UK

Abstract: To investigate the efficacy of oral health formulations for dentine hypersensitivity with emphasis on novel 3D imaging methodologies to assess tubule occlusion and mineralisation of human dentine.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL
Title: Developing and validating a computational model of the gut microbiota-mucosa interactions to replace and reduce animal experiments
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Many recent discoveries revealed the fascinating and important effects that the bacteria living in our gut have on our health. For example, they train our immune system, affect weight gain and even our mood and behaviour. As a consequence, the number of studies of gut bacteria has risen sharply. As many of these studies use animal experiments, more and more animals are being used.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: ORAL AND GASTROINTESTINAL
Title: Combining a fully synthetic hydrogel with human intestinal organoids to model pathological matrix remodelling in Inflammatory Bowel Disease (IBD)
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Overview: Human intestinal organoids (hIO) formed from induced pluripotent stem cells (iPSC) are increasingly replacing mouse models of inflammatory bowel disease (IBD), but Matrigel, which is required to support hIO cultures, is created from a mouse tumour, and its undefined composition precludes controlled studies on gut pathological matrix remodelling. Here, we aim to establish, validate, and demonstrate the utility of an hIO-synthetic hydrogel tool to study matrix remodelling in the gut that can replace murine and Matrigel-supported hIO models of IBD.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: ORAL AND GASTROINTESTINAL
Title: An Artificial Intelligence tool for improved liver tumor detection and segmentation
Funder: The Academy of Medical Sciences

Abstract: Liver tumor ultrasound scanning is recently becoming more recommended as a first diagnosis option for early prediction of response to chemotherapy treatment. Visual assessment of tumor response to chemotherapy is very challenging without monitoring the time series of tumor development. The quantitative ultrasound parameters can facilitate for a personalised cancer therapy to evaluate the cancer response to treatment non-invasively. However, the analytical complexity of the statistical model generalizations could still limit its practical application in tumor tissue segmentation, while simplified models can overlook some of the important aspects of the statistics of the envelope detected echo. Thus there is a need to balance the trade-off between simplicity and effective characterization to render the approach significant for clinical applications. Moreover, given the increasing number of patients admitted to hospitals, and given the limited resources in hospitals and clinics in Jordan, clinicians are faced with increased burden of working under stressed conditions for delivering the medical reports in a timely manner. On the other hand, an automated decision system can assist in maintaining consistency for the perceived patterns, and reduce the time for clinical management decisions in choosing the appropriate treatment procedure. Local parametric fractal features extracted via maximum likelihood estimation for different statistical models will be used for liver tumor texture segmentation. A multimodal computer aided diagnosis system would be developed for an automated detection and diagnosis of liver tumor relying on the radio-frequency (RF) parametric signal for improved quantitative tumor analysis. The approach will try to relate the locally extracted fractal characteristics of the tissue scatterers to the underlying statistical properties derived from the RF envelope-detected signal. Various RF backscatter models (e.g. Nakagami, Rayleigh, Rician, K-distribution) would be adaptively employed locally for an improved characterisation of the heterogeneous tumor tissue. The main objective would be to demonstrate the efficacy in modeling the underlying tumor physiological changes from ultrasound parametric images of scatterer tissue properties, and hence improved tumor segmentation. Tumor tissue scatterer characterization is a challenging task due to the disease chaotic behaviour.Therefore, the issue of tumor depth and size variation will be addressed, and the best statistical model that can better characterise tumor texture complexity will be investigated.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL
Title: Repurposing Sirolimus in Cirrhosis: Assessing Response with Magnetic Resonance Imaging (MRI)
Funder: The Academy of Medical Sciences

Abstract: Aim To compare the changes in quantitative MRI measures of hepatic structure and splanchnic haemodynamics with changes in liver histology and portal pressure in patients with cirrhosis. Objectives • To correlate the changes in MRI measures of liver fibrosis with histological changes following treatment with Sirolimus. • To explore the MRI parameters at baseline that predict treatment response to Sirolimus. • To evaluate if changes in quantitative MRI measures reflect changes in portal pressure following Sirolimus treatment. Background Liver biopsy remains the gold standard test to assess the degree of liver fibrosis. However, liver biopsy is invasive, associated with rare but life-threatening complications and prone to sampling errors. We have previously showed that novel non-invasive quantitative MRI parameters provide a surrogate measure of liver fibrosis and portal pressure. A proof-of-concept study to evaluate Sirolimus as an anti-fibrotic in patients with cirrhosis (RESUS) will soon commence. In the RESUS study, patients with cirrhosis will be randomised to 6-month treatment of Sirolimus versus placebo with histological end-points. Study design and Methodology This will be a prospective study nested as a sub-study of RESUS; 30 participants will undergo non-invasive MRI within 2 weeks of liver biopsy at baseline and at the end of treatment. The changes in the MR parameters will be correlated to the changes in liver histology. Clinical Impact MRI can be performed serially to assess progression or regression of liver fibrosis. This will allow risk stratification of patients and therapeutic intervention targeted accordingly, paving the way for personalised-medicine.

Lay abstract: Scarring in the liver can lead to liver failure and premature death. The current method to measure the amount of liver scarring is a liver biopsy. This technique is invasive and could lead to complications including bleeding and injury to other organs. We have recently shown that we can measure liver scarring using magnetic resonance imaging (MRI), which is completely non-invasive and patient-friendly. There is a current study of a medication called Sirolimus, in slowing down liver scarring (RESUS study). Thirty patients will be given Sirolimus or a dummy drug (placebo) randomly, and they will have liver biopsy as part of this study to assess the effect of this medication. In this proposal, we aim to perform MRI scans on the patients of the RESUS study. This is a unique opportunity which allows us to compare the changes on liver biopsy with the changes on the MRI scan. If the changes are comparable, MRI can be used to monitor patients with chronic liver disease in the future. Patients with progressive scarring and at risk of life-threatening complications can be easily identified and potential treatment can be targeted at these patients.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: A closer examination of dietary information in permanent teeth: comparing stable isotope data from co-forming deciduous and permanent teeth where diet and medical history is known.
Funder: The British Academy

Abstract: The first 1000 days of life are a critical period in the development and lifelong health of humans. I am in search of biomarkers for perinatal stress: teeth offer the only "window on the womb" extant in a child (both modern and archaeological) who survives infancy. My research uses temporal changes in chemicals from the diet recorded in deciduous (milk tooth) collagen, (including tissue formed in utero) to investigate diet and physiology. Archaeological studies generally use permanent teeth resulting in lower temporal resolution and potential errors in interpretation of the important maternal/infant period. This grant would allow me to compare deciduous dentine data with co-forming permanent teeth from the same modern infants with known medical histories and diet, using the currently applied method and trialling the novel method developed at the University of Bradford by Curtis et al. (submitted) of microsampling along developmental landmarks to improve temporal resolution and interpretation.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: An evaluation of an eReferral Management & Triage System for Minor Oral Surgery referrals from primary care dentists.
Funder: Department of Health (England)

Abstract: The 2010 King’s fund report stated a need to address and manage demand for services within dentistry. It concluded that a whole systems approach to service redesign was needed. Consequently the introduction of intelligent centralised referral management within oral surgery (and Dentistry as a whole) will be inevitable within the NHS.A pilot study carried out in Greater Manchester has demonstrated the potential for centralised referral management to improve the quality of referrals and reduce oral surgery waiting lists for acute trusts. However the full impact on costs and quality of care are currently unknown. There is therefore a need to carry out a robust evaluation in order for the NHS to understand the risks and benefits of introducing this type of intervention. NHS Sefton currently has no comprehensive referral management system in place for oral surgery and offers a useful mix of acute trusts: a teaching hospital (University Dental Hospital) a large foundation trust (Aintree Hospital) and a district general (Ormskirk). Sefton is therefore an ideal site in which to conduct a full and comprehensive evaluation of the impact of introducing a new referral management system.Within the outline bid there were five main areas of research described. The first piece is preparatory in nature and involves a diagnostic test accuracy study. The main study is an interrupted time series design and will fully evaluate a new remote centralised referral management system for Oral Surgery.•How efficient is remote centralised referral assessment and triage?•How does remote centralised referral management (RCRM) impact on GDP referral behaviour and practice?•How does RCRM management impact on secondary care providers?•How does RCRM impact on patients?•How does RCRM impact on the NHS?A mixed methods study (interrupted time series designcombined with qualitative analysis) will be carried over a period of 36 months. This period of time is necessary in order to:a) Year 1; Collect baseline data taking into account possible seasonal variation in the number of referrals received by secondary care providersb) Year 2; To look at the potential impact of centralised electronic referral management and triage system and to gather information and intelligence so that appropriate specialist primary care services can be informed and commissioned prior to full implementationc) Year 3; To assess the impact of full implementation of the new intervention


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: ORAL AND GASTROINTESTINAL
Title: Novel Antimicrobial Restorative Materials to Manage Dental Disease
Funder: Division for Social Care and Health Research (Wales)

Abstract: Disease of living part of the tooth (dental pulp / pulpal disease) and infection of the root canals of teeth (endodontic infection) are significant causes of viable tooth loss. Retention of teeth is important for aesthetic and social reasons, as well as function and nutrition. A common reason for tooth loss in adults is recurrent dental decay forming around dental fillings. Current research indicates more than 50% of fillings placed are replaced within 10 years. Tooth decay forming around fillings leads to abscess formation and requirement for further, deeper fillings or root canal treatments at significant cost to the NHS (approx. £200M) or patient directly. Management of such scenarios is difficult, particularly in adults with other medical conditions often resulting in premature tooth loss. This leads to reduced chewing forces, poor dietary choices and poorer nutritional status. Complete dentures increase the risks of fungal infections. Treatment of pulpal disease is limited due to complications of effectively removing the multi-bacterial infection and root canal treatments are necessary. Such endodontic treatments leave the tooth vulnerable to secondary infections, resulting in failure of the restoration and tooth loss and some 28% of root canal treatments fail. Systemic antibiotics are not effective in treating pulpal infection or failed root canal treatments due to the mixed bacterial population and also due to careful management of antibiotic treatments so there is a requirement to develop new antimicrobial treatments. This project will develop a novel dental filling with antimicrobial capability, which will have potential to limit the formation bacterial infection in the dental pulp and tooth root canals reducing associated problems including abscess formation, thus decreasing the likelihood of tooth loss. The action of this material would make it superior to existing dental filling materials as currently used restorative materials tend to be inert and no antimicrobial filling material is available for clinical use to manage this chronic condition.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL
Title: COmparison of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT)
Funder: Division for Social Care and Health Research (Wales)

Abstract: Ulcerative colitis (UC) is a chronic disease with many unanswered questions regarding causes course treatment and outcome. It can present as an acute severe illness requiring intravenous steroids but some patients are steroid resistant. In the past emergency surgery to remove the colon was then the only option.Infliximab and ciclosporin are drugs that offer hope for treating steroid resistant UC. There is evidence that they are effective in the short term but evidence about their clinical effectiveness and cost effectiveness is lacking. The overall aim of this study is to compare the clinical effectiveness and cost effectiveness of these drugs in this situation and a key objective is to establish long-term data collection to enable answers to further research questions regarding progress and outcome following treatment with steroids infliximab ciclosporin or surgery. This study funded by NIHR Health Technology Assessment programme is a pragmatic randomised controlled trial (RCT) involving 40 UK centres. Inpatients with acute severe UC who fail to respond to intravenous steroids but do not require immediate surgery will be randomised to either infliximab or ciclosporin (480 patients).The primary outcome measure will be Quality of Life. Secondary outcomes measures will be emergency and planned colectomy additional medical therapy mortality quality adjusted survival disease activity readmissions length of remission incidence of malignancies incidence of serious infections incidence of renal disorders incidence of new symptoms total NHS costs and patient borne costs. Patient interviews will be undertaken to investigate the views of patients regarding therapies for acute severe UC.Study data will be collected using a web-based clinical information system and record linkage of electronically held routine data. Research data collection will continue for two years; clinical data collection and record linkage will then continue for the following eight years.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL
Title: Seal or Varnish? A randomised trial to determine the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay
Funder: Division for Social Care and Health Research (Wales)

Abstract: Dental caries (tooth decay) remains a significant source of morbidity in children particularly those from deprived backgrounds where levels of decay are three times higher than in better off areas. In the worst affected areas 69% of 12 year olds have decay in their permanent teeth. The majority of this (84%) is located on the biting surface of the first molars which erupt at age six. We know that the application of pit and fissure sealants to the biting surface is effective in preventing tooth decay. This treatment consists of a plastic coating that occludes the rough biting surface which harbour decay-causing bacteria. The application at six-monthly intervals of fluoride varnish containing high levels of fluoride is also known to prevent decay.This works by strengthening the tooth enamel making it more decay resistant. What is not known is which of these two modes of treatment works best and which is the most cost-effective. It is also not know which of these treatments are most acceptable from the perspective of children and their parents. Fissure sealant application requires an involved dental intervention (use of rotary brush tooth surface preparation to make the sealant stick use of a sucker to keep the tooth dry). Varnish application simply involves painting the tooth surface. This trial will examine the relative clinical and cost effectiveness of these treatments and investigate their acceptability to children and their parents.The study will take the form of a randomised trial in which children will receive either fissure sealants on their first permanent molars or fluoride varnish. We will determine the success of the study by comparing the proportion of children who receive the alternative treatments who are caries-free in their first molar teeth after three years. We will also look at the cost effectiveness and patient acceptability of the treatments. The findings from this study will be applicable across the NHS particularly in areas of high need with greatest health inequalities.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: ORAL AND GASTROINTESTINAL
Title: The clinical effectiveness and cost-effectiveness of STeroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2x2 factorial randomised controlled trial
Funder: Department of Health (England)

Abstract: In the UK the mortality rate from alcoholic liver disease is rising rapidly and so STOPAH is considered as a vitally important study being more than 10x larger than any previous study in this patient population. Since 1971 there have been 13 randomised studies and 4 meta-analyses investigating the role of corticosteroid therapy for this condition. Despite this apparent wealth of evidence controversy persists and there remains deep division with regard to the use of corticosteroidsPentoxifylline (PTX) has also recently been studied in the treatment of alcoholic hepatitis. It is believed to act in part by inhibiting the synthesis of the pro-inflammatory cytokine tumour necrosis factor alpha. There has been one randomised controlled trial which showed significant benefit.On review of the published studies none of these reach an adequate statistical power to make a statement with 80% confidence. The two most recent meta-analyses of all of the available trials demonstrated that although there was a trend of benefit with steroids the results were either not statistically significant or impossible to interpret due to the heterogeneity of the incorporated studies. However a re-analysis of the 3 largest studies indicated a significant benefit from corticosteroid. In this meta-analysis patients with a discriminant function (DF) greater than or equal to 32 treated with prednisolone had 28 day mortality of 15% as opposed to a mortality of 35% amongst placebo-treated patients (p=0.001). Only one study has demonstrated the benefit of pentoxifylline (PTX) in alcoholic hepatitis. No study has compared the effects of prednisolone and PTX directly nor has any study compared the combination of these treatments with corticosteroid monotherapy.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL