NIHRDataInsights/HRCSData huggingface dataset:
Title: Investigation of JAK2 targets in haematological malignancy
Funder: Chief Scientist Office (Scotland)

Abstract: The myeloproliferative neoplasms (MPN) are haematological disorders with significant complications, particularly vascular events and inflammatory responses linked to increased risk of thrombosis. The JAK/STAT pathway is important for normal haemopoiesis and inflammatory responses. Activation of JAK2, especially via the V617F mutation, is a common occurrence in MPN. This laboratory-based, in vitro study will use CD34+ cells to generate induced pluripotent stem cells to investigate how V617F JAK2 affects primitive HSC and more differentiated haemopoietic progenitors. To complement this, FDCP Mix progenitor cell models expressing wild-type and V617F JAK2 will also be generated. This will enable detailed gene expression studies (Fluidigm technology) and protein activity (Western blotting, flow cytometry, immunofluorescence), of transcription factors involved in the maintenance of MPN. Of particular interest will be the effects of V617F JAK2 on the inflammatory response, especially alterations in IFN response genes and the transcriptional regulator PML, which forms transcriptionally active centres in nuclear bodies. These cell models will provide sufficient material to investigate epigenetic (ChIPSeq), nuclear proteins (Western blotting) and protein-protein interactions (co-immunoprecipitation). Using these models, the effects of pharmacological inhibition of JAK2 (AT9283, TG101209 and ruxolitinib) can be evaluated through changes in gene expression, metabolic activity, cell viability/apoptosis, cell cycle analysis and colony forming cell assays. Overall this study will identify new targets involved in MPN and determine why current small molecules inhibitors of JAK2 are ineffective in controlling MPN. If new therapeutic targets can be identified these patients could benefit hugely from reduction of disease burden, the associated symptoms and complications.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Development of a measurement guided medicine intervention to optimise
Funder: Chief Scientist Office (Scotland)

Abstract: Background Inadequate prescribing of analgesic medication by health care professionals and inaccurate use of the medication by patients are important causes for suboptimal pain control among cancer patients. Objectives 1. To explore whether accurate patient-generated measurements of pain levels and analgesic adherence and could: i. be used to overcome barriers to effective management of cancer pain ii. be gathered and timeously communicated to health professionals iii. enable health professionals to optimise cancer pain management 2. To develop a measurement guided medication management intervention for health professionals to receive accurate patient-generated measurements pain levels and analgesic adherence to act upon to optimise cancer pain management 3. To conduct an early stage feasibility study of the intervention Design Based on MRC’s framework for development and evaluation of complex interventions: 1. Rapid literature review with narrative synthesis 2. Interviews and focus groups with stakeholders 3. Intervention development and software testing 4. Feasibility testing among patients and professionals Outcomes An acceptable, feasible intervention that capitalizes on innovative technologies to address the major caveats in current cancer pain management. Key facilitators and barriers to large-scale evaluation of the intervention will have been determined. At least three scientific publications will be delivered which will disseminate the results and inform a subsequent application for funding a large-scale evaluation of its effectiveness and cost-effectiveness.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: The experiences of community health professionals following their involvement in providing palliative care to a child with cancer within the family home.
Funder: Department of Health (England)

Abstract: The proposed study aims to compare the perceived role of the GP in providing palliative care for the child with cancer with the perceptions of bereaved families.The key aims are to identify; discrepancies between family and GP perceptions, areas where the GP role could be enhanced through education and training, findings that could be transferable to palliative care generally and ways of enhancing the role of the Macmillan team in supporting GPs in this arena. Data collection methods include semi-structured interviews and Q-methodology.The findings will have a direct impact on my role as a paediatric Macmillan nurse, informing practice through an increased awareness of the family’s experience and identifying, and addressing, areas where practice could be enhanced.In addition the lectureship will provide me with an opportunity to build on my research knowledge and experience and further develop my clinical skills.


Research activity codes: 7.2 END OF LIFE CARE
Health categories: CANCER AND NEOPLASMS
Title: Development of a tool to assess the benefit versus adverse effects ratio in modern radiotherapy for common cancers
Funder: Department of Health (England)

Abstract: More people who have had a common cancer are surviving. Radiotherapy is contributing to this success but treatment has long term consequences. There is a complex relationship between radiotherapy benefits and risks. We will use physics and mathematical methods to describe this via software which will calculate radiation dose through the whole body, not just the treated region. The radiation doses will be related to adverse effects such as second cancers following radiotherapy, and effects on the heart. The output will be a benefit versus risk information tool for patients and healthcare professionals.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Assessing dysphagia in laryngectomy and the effect of different voice prostheses on swallowing and voice.
Funder: Department of Health (England)

Abstract: This research will investigate Fiberopic Endoscopic Evaluation of Swallowing (FEES) in patients with laryngectomy and examine how voice prostheses affect swallowing and voice.Using prospective observational designs, the efficacy of FEES as an assessment tool will be compared to videofluroscopy and the impact of different voice prostheses will be studied in the same group of patients. It is hypothesised that FEES is a viable tool for investigating dysphagia, that swallow and voice will differ according to prosthesis, and that amount of neopharyngeal residue predicts dysphagia.Since dysphagia causes significant distress to these patients, this work will improve quality of life.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Understanding the experiences and support needs of patients with melanoma and their carers: Charting changes over time
Funder: Department of Health (England)

Abstract: Melanoma is increasing in incidence. The complex treatment pathway can cause physical, emotional and financial difficulties for patients and their carers, yet exploration of their support needs is limited. This research aims to explore the changing experiences and support needs of patients with melanoma and their carers throughout the disease process via Co-constructed Inquiry derived from Grounded Theory methodology. Patients, carers and healthcare professionals will be interviewed for one to three years. Where patient and carer experiences may be improved by changes to care, guidelines for best practice will be produced in conjunction with participants.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: NCI Health Economics Fellowship 2010: dr Mary Dallat
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: This is a four year fellowship in health economics with a focus on cancer, leading to a PhD degree in health economics, obtained through Queens University, Belfast. Its overall aim is to increase capacity in health economics in Northern Ireland by encouraging successful candidates to pursue a career in health economics. The first year includes ten months of coursework in health economics, cancer prevention and health policy, based in Northern Ireland/UK, as well as a 4 week cancer prevention course at the National Cancer Institute (NCI), Bethesda, USA. Years two and three are spent at the NCI in Europe or the USA where candidates are allocated an NCI mentor and finally in year four candidates return to Northern Ireland for a final year of mentored research. In terms of funding, fellows are provided with an annual studentship of £25,000 for four years. Their student fees, any equipment costs, costs associated with travel and the cost of health insurance for the duration of their stay in Europe or the USA are covered. Funds are also available for fellows to attend at least one scientific conference per research year and any relevant training courses in health economics. As fellows will be PhD students of Queens University it is also possible for them to attend any relevant lectures and/or seminars at the university that they feel may enhance their research.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: CANCER AND NEOPLASMS
Title: Career Development Fellowship: Investigating the impact of incidental medication use on cancer progression in patients with common cancers
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Background: In the UK, there are, on average, 300,000 individuals diagnosed with cancer each year and over 150,000 deaths from cancer. Cancer patients are increasingly exposed to a wide range of prescription medications but the effect of these medications on the progression of their cancer is largely unknown. Aims: The aim of this fellowship is to conduct a series of robust evaluations of the effect of specific medications to identify whether they could inhibit cancer progression or promote cancer progression in patients with common cancer (breast, colorectal, prostate and lung cancer). The drug types of interest, because of their mechanism or empirical evidence for their effect on cancer, are: ACE-inhibitors, antiplatelets, NSAIDs, statins and diabetes medications. Methods: Annonymised patient data will be used from two large administrative health datasets, the UK General Practice Research Database (a large database of general practice records) and the NI-COIS-EPD dataset (a Northern Ireland database based upon links between the cancer registry, oncology unit patient records and prescription records). In these datasets, cohorts of patients with common cancers (breast, colorectal, lung and prostate) will be identified. The risk of death from cancer and the risk of cancer recurrence will be compared between individuals taking specific medications to a suitable non-user comparison group. Advanced statistical methods will be applied to produce the best estimates of treatment effect. Potential: This research has the potential to benefit patients by identifying new uses for existing medications in the prevention of cancer progression which could then be tested in clinical trials. It could also benefit patients by identifying medications with accelerate cancer progression which could result in the amendment of clinical guidelines leading to restricted use of these drugs in cancer patients.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Textural analysis of multimodality imaging data for the detection of recurrent prostate cancer
Funder: Prostate Cancer UK

Abstract: Over 2,000 men each year in the UK are diagnosed with recurrent prostate cancer following previous radiotherapy. Whole-gland salvage treatment is associated with a high incidence of serious long term toxicity and is infrequently performed. Focal salvage, where only the region of recurrence is treated, may be more acceptable to men. However, conventional imaging analysis methods lack the extreme accuracy needed to define the exact pattern of recurrent disease. New PET and MR technologies produce a myriad of quantitative biomarkers that assess a host of physiological and biochemical tumour characteristics. Hitherto, only the most simplistic attempts have been made to combine these parameters to improve our ability to distinguish aggressive prostate cancer from indolent disease. In this project, each patient will be evaluated by the most advanced PET and MRI techniques currently available. The vast quantity of multiparametric data will be analysed in an entirely new way with the hope of achieving a degree of understanding of the nature of the recurrent tumour that has never been possible before. Not only will textural analysis optimise the selection of patients for salvage therapy but will also have ramifications for the assessment of prostate cancer at all stages of the disease.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Influence of stage and therapy on the NKG2D axis in prostate cancer
Funder: Prostate Cancer UK

Abstract: Treatment of advanced prostate cancer with chemotherapy can be toxic in a generally elderly population. Immunotherapy, with potentially fewer side effects has recently gained renewed interest. Our laboratory has investigated the receptor NKG2D on NK cells and gamma delta T cells. This receptor can be activated by cells expressing NKG2D ligands, found on prostate cancer cells but only in limited amounts on healthy cells. We have shown that patients with prostate cancer receiving concomitant therapies display a significant impairment in the NKG2D pathway, although this potentially can be boosted, suggesting therapeutic application. Aim and objectives This project will explore the NKG2D pathway as part of the lymphoid stress surveillance in prostate cancer. The following questions will be addressed: 1) Is there evidence that the NKG2D pathway varies with tumour stage in patients with prostate cancer? 2) Is there evidence that the NKG2D pathway varies with concomitant therapy in patients with prostate cancer and is this correlated with altered killing potential? 3) Are we able to influence to variability of PBMC responses to NKG2D ligand + targets? Methods Experimental set up includes gene expression analysis on prostate cancer tissue examining components of the NKG2D axis. Patient blood samples to monitor the NKG2D pathway during various therapies. Flow cytometry for phenotypical and functional analysis. Co-culture experiments with peripheral blood mononuclear cells and NKG2D ligand + cell lines will be used in order to optimise the NKG2D pathway. Scientific and medical opportunities Exploration of the NKG2D-ligand interaction under various tumour and host conditions will help our understanding of this axis as a target for immune therapy, which ultimately could benefit patients.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Can a negative Faecal Immunochemical Test for haemoglobin (FIT) avoid the need for routine surveillance colonoscopy in patients at increased risk of colorectal cancer?
Funder: Chief Scientist Office (Scotland)

Abstract: The British Society of Gastroenterology guidelines recommend routine surveillance colonoscopy for individuals at moderate/high risk of colorectal cancer. Colonoscopy has a small but significant risk of complication. Local audit reveals surveillance colonoscopy is normal in 70%. A non-invasive test to determine the likelihood of an adenoma / cancer would be preferable. Faecal Immunochemical Testing for haemoglobin (FIT) detects human haemoglobin in stool; levels rise in proportion to size of the neoplastic colorectal lesion. In this pilot study, we will ask all attending routine surveillance colonoscopy to complete a FIT test before colonoscopy. Patients would have the colonoscopy as planned. Feasibility and acceptability of FIT testing will be assessed. The FIT results would be matched with colonoscopy findings to determine a cut-off level which predicts a negative colonoscopy. If successful, funding for a larger validation study will be sought.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Risk of Hospitalisation and death following prostatic biopsy in Scotland: retrospective cohort study
Funder: Chief Scientist Office (Scotland)

Abstract: Screening for prostate cancer using the prostate-specific antigen (PSA) test is a source of controversy. Because prostate cancer accounts for only a relatively small proportion of overall mortality, a trial with all cause mortality as the end-point would require an unfeasibly large study population. So, even though screening has been shown to reduce disease-specific mortality in some studies, there are concerns that the adverse consequences of screening and treatment may outweigh any benefits. One such adverse consequence is the morbidity and mortality associated with prostate biopsy. However, there is limited information available on the extent of these in unselected populations. We plan to assess the adverse consequences of prostate biopsy using linked hospital discharge, cancer registration and mortality records covering the whole of Scotland.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Improving quality of life and swallowing function in patients with head and neck cancer: development and feasibility of a swallowing intervention package (SIP)
Funder: Chief Scientist Office (Scotland)

Abstract: Due to increasing incidence, more intensive treatment and improved survival, a growing number of head and neck cancer (HNC) survivors experience long-term swallowing difficulties, profoundly affecting eating/drinking, increasing feeding tube dependence and risk of aspiration (food/fluid entering the airway) and significantly reducing quality of life. Some evidence suggests that swallowing exercises can improve outcomes in HNC patients undergoing chemo-radiotherapy. However, many questions remain about the timing, selection and duration of exercises as well as their practicality and feasibility in the UK. This study will develop a practical Swallowing Intervention Package (SIP), including adherence and fidelity measures, in partnership with patients and speech and language therapists. Focus groups and consensus workshops will be followed by a feasibility study using qualitative and quantitative methods to examine treatment fidelity, adherence to and impact of the SIP on quality of life, swallowing outcomes and service use, in order to inform a future trial.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: CANCER AND NEOPLASMS
Title: Impact of Post-Operative Wound Complications on long-term survival from Breast Cancer: Population-based retrospctive cohort study in Scotland
Funder: Chief Scientist Office (Scotland)

Abstract: There is evidence that some of the factors involved in wound healing can stimulate tumour growth factors. A previous study has shown a higher risk of systemic disease recurrence in patients with post-operative wound complications following surgery for breast cancer. However, the study was based on a single hospital series of just over 1,000 patients, and was too small to examine survival as an outcome. Using linked hospital discharge, cancer registration, and mortality records in Scotland, we propose to study the survival outcome of a large, population-based cohort of patients with and without wound complications following surgery for breast cancer.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: CANCER AND NEOPLASMS
Title: The Scottish Cervical Cancer Prevention Programme: Assessing and modelling the impact of HPV 16/18 immunisation on the performance of current cervical screening performance and the effectiveness of alternative cervical screening strategies to optimise cancer prevention in the HPV immunisation era.
Funder: Chief Scientist Office (Scotland)

Abstract: In Scotland, HPV vaccination of females aged 12 to 13 years starts, by a school immunisation programme, on 1 September 2008 along side a ‘catch up campaign’ to target up to age 18. Scotland now moves from the Scottish Cervical Screening Programme to a Scottish Cervical Cancer Prevention Programme with the aim of further reducing cervical cancer mortality by primary prevention with HPV immunisation and secondary prevention with screening. Health Protection Scotland (HPS) is co-ordinating the introduction of this new immunisation programme and establishing an HPV Immunisation Project to monitor its impact. Many new questions need to be investigated to inform NHS policy urgently on future service delivery for cervical screening and the immunisation programme; disease reduction and prevention. Scotland is in a unique position to lead on new research as 16-17 year olds will be immunised in 2008 and become eligible for cervical screening from September 2010. Our proposal combines routinely collected data on screening and disease detection with research generated data on HPV genotyping and screening test performance to model future screening performance. Scotland’s networks of researchers, HPS and our excellent data linkage facilities can collaborate effectively with a single population health intervention for cancer prevention to provide evidence to improve health outcomes in Scotland and provide evidence on changes required for the cervical screening programme in the future.


Research activity codes: 4.4 POPULATION SCREENING;3.4 VACCINES
Health categories: CANCER AND NEOPLASMS
Title: Working together to support active living and well being (ActWell) in the health promoting health service - feasibility trial to reduce breast cancer risk factors.
Funder: Chief Scientist Office (Scotland)

Abstract: Background It is estimated that 42% of breast cancer in post-menopausal women could be prevented by increased physical activity and decreases in alcohol and body fatness. It is notable that (at any BMI) weight gain in adult life is associated with greater risk of the disease (e.g increase of 2-10 kg after age 50 years is associated with a 30% increased risk). Aims The proposed study will finalise a protocol for a minimal contact, weight management intervention initiated within the breast cancer screening setting, to inform the design of a definitive randomised control trial (RCT). Methods Phase One will involve focus group discussions and interviews with the target population, screening and cancer charity staff to explore acceptability and development of the prototype intervention. Phase two (feasibility trial) will assess recruitment, early retention and indicative outcomes. Process measures will be undertaken to assess implementation time, cost, fidelity and acceptability of procedures.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: CANCER AND NEOPLASMS