NIHRDataInsights/HRCSData huggingface dataset:
Title: Human Papillomavirus integration events and cervical disease progression post-vaccination
Funder: Tenovus Cancer Care

Abstract: Cervical cancer is the second most common cancer among women worldwide with an estimated 500,000 cases and 250,000 deaths worldwide due to cervical cancer per annum. Infection with Human Papillomavirus (HPV) is essential but not the only contributing factor in cervical cancer development. High Risk (HR) HPV DNA integration into the human genome is one of the key stages in the onset of malignant progression in cervical cancer and is a potential positive predictive biomarker of invasive disease. The HPV vaccination programme will target HPV16 and HPV18 infections and associated neoplasias are expected to decline [8]. However, cervical disease associated with non-vaccine targeted HR HPV types will still be a concern. New methods are therefore required to differentiate between the residual HPV infections in the population that are likely to progress and cause cancer in a population of vaccinated women. Recent data on the type specific risk for cervical cancer development in a cytologically screened population from a case-control study of 262 invasive cervical cancers and 8,428 controls who attended for routine screening investigated the HR HPV types with oncogenic potential [9]. The odds ratio for infection with HPV16 and HPV18 was significant (2770 and 950 respectively), followed by types HPV 45 and HPV 33 (386 and 188 respectively). Integration methods targeting HPV16, HPV18, HPV33 and HPV45 have been established with the HPV Research Group, Cardiff University. The focus of this PhD studentship will be to develop further integration methods for detection of HR HPV types: 31, 39, 51, 56 and 58, all of which had an odds ratio above 70 (adjusted for age) [9]. The key methods to be explored include: Restriction Site PCR (RS-PCR) and Detection of Integrated Papillomavirus Sequences (DIPS). Results from the different methodologies will be compared and the potential use of these techniques within the cervical screening programme will be assessed. This PhD studentship will apply the novel DNA HPV integration methods to a previously characterised sample cohort: Baseline HPV 2009. This cohort includes many non 16/18 infections with 80 cases positive for HPV31, 52 cases HPV39 positive, 114 cases HPV51 positive, 54 cases HPV56 positive and 50 cases positive for HPV59. Investigation of integration status in these clinical specimens will allow us to address several questions including how HPV integration events relate to disease progression, the importance of fragile sites in the host genome and the potential for hot spots for integration and their links with disease progression. Studies into HPV integration events linked with non 16/18 HPV infections has not previously been investigated and this PhD studentship will start to analyse potential differences between integration events for individual HR HPV genotypes.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: INFECTION
Title: Effectiveness of testing for treatment of hard-to-reach groups for latent tuberculosis, hepatitis B virus and hepatitis C virus in England: The HALT Study
Funder: Department of Health (England)

Abstract: Hard-to-reach groups, such as homeless persons, substance misusers and exprisoners, have difficulty accessing, and remaining engaged with, healthcare services as a result of a variety of lifestyle factors. The same factors render them susceptible to a range of infectious diseases, such as TB and hepatitis. To examine the effectiveness and cost-effectiveness of two key methods to prevent the transmission of infection in the hard-to-reach: a) testing for LTBI, chronic HBV and HCV, b) supported HBV/HCV treatment among those with diagnosed infection. This will be in addition to assessing barriers to the success of HBV community vaccination programmes. Finally, determine whether side effects really should prohibit treatment of LTBI in individuals over 35 years of age. Research plan and methods of investigation: Hard-to-reach individuals will be screened in the community for LTBI, HBV and HCV infection. Individuals identified with chronic HCV and HBV will be randomly assigned to either peer supported assessment and, if indicated, the treatment or routine referral. HBV vaccination levels amongst this population will be assessed, together with the reasons for incomplete immunity. Additionally, individuals with LTBI who are over 35 years of age will be recruited from London TB clinics and will be supported through treatment with careful liver function monitoring in order to determine if prophylaxis is viable in this group. Outcomes: 1. Full clinical diagnosis of HCV/HBV in the hard-to-reach and supported treatment of chronic infection. 2. Supported treatment of LTBI in those over 35 years of age. 3. The effectiveness (quality adjusted life years gained) and cost-effectiveness (incremental cost-effectiveness ratios) of these control of these control interventions. Research team: multi-disciplinary (clinical, epidemiology, health economics, statistics), with experience of TB and hepatitis research, working with the hard-to-reach and evaluating service provision for these groups. Potential impact/influence on the relevant policy field, users and wider stakeholders: Improved access to and uptake of diagnosis and treatment services for hard-to-reach groups that could be adapted into commissioning policy in major conurbations, thus potentially reducing transmission. Better understanding of the impact of changing policy to promote LTBI treatment in the over 35s.


Research activity codes: 4.3 INFLUENCES AND IMPACT;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;3.4 VACCINES
Health categories: INFECTION
Title: Evaluation of TB Control Interventions in the Community and Emergency Medicine D
Funder: Department of Health (England)

Abstract: Background: Control of infectious diseases requires prompt, effective identification and treatment to safeguard health and prevent transmission. Identifying those in high risk groups, evaluating signs and symptoms and referring individuals for testing and management are key to control efforts. Tuberculosis (TB) causes significant morbidity in the UK. Early treatment may have the greatest impact by interrupting transmission. Between 2000-9, TB cases in England rose from 12.4 to 16 per 100,000 with over 8000 cases diagnosed annually, mostly among individuals from identified risk groups. In London A&E accounts for 20% Mtb cases diagnosed and 49% from primary care overall. Aim: Research plan and methods Work Package 1: Determining the prevalence of latent TB infection and active TB disease and cost effectiveness of testing high risk groups attending A&E departments. An observational study, which prospectively recruits participants for latent TB testing, combined with health economics modelling will be performed. The prevalence of latent and active TB will be measured by approaching attendees at 3 A&E Departments in England. The study areas have been chosen to include: areas with a high burden of TB; sites in and outside London; sites with high throughput and numbers of cases in recent years; as well as those willing to participate. The areas also have a concentration of high levels of socioeconomic deprivation and ethnic diversity reflecting the population of TB cases nationally. All study sites will be coordinated from the HPA in Colindale. Work Package 2: Assess the effectiveness and cost effectiveness of health protection service developments aimed at improving the diagnosis and management of tuberculosis in high risk groups. We will utilise the collection of observation data from each project and undertake epidemiological analysis to assess the effectiveness of contact tracing around large incidents, screening for latent tuberculosis in primary care in North West London and pre-entry screening for active TB. Incremental cost effectiveness analysis will be undertaken for each intervention. In addition, we will evaluate the structure, process and impact of the following health protection service developments aimed at improving TB control: Improving the coordination of tuberculosis control in Birmingham; whole system service reviews in Yorkshire and North West London; and supporting cohort reviews. Potential to influence policy: The package of interventions to be evaluated in this proposal cover a wide spectrum of areas critical to current national TB control policy.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS;4.4 POPULATION SCREENING
Health categories: INFECTION
Title: Evaluating the Pilot Implementation of Vaccinating Healthy School-Aged Children Against Seasonal Influenza
Funder: Department of Health (England)

Abstract: BACKGROUND Based on recommendations from the Joint Committee on Vaccination and Immunisations, the Department and Health and Public Health England have commissioned seven pilot sites to implement vaccination among school-aged children using the nasal spray vaccine Fluenz. With some variations in the staff groups to be used, six of the pilot sites are adopting school-based programmes, with one site using local pharmacies as an alternative. Although there is some relevant research from the US, evidence directly relevant to the UK is required to inform important decisions at a national level concerning the roll-out of this policy and at a local level concerning planning, communications and operational arrangements. Given that plans for the pilots are still being finalised, it has not been possible to develop a research protocol that sufficiently accounts for the details of the implementation at each site or to incorporate the perspectives of parents, young people, school based staff or NHS staff to our research design. Aims and objectives We aim to inform future policy and implementation in this area by i) evaluating the different approaches that are being adopted by pilot sites; ii) understanding the facilitators and barriers to successful implementation; iii) assess the preferences, attitudes and experiences of parents and children. We will do this by 1) conducting and sharing with pilot sites a synthesis of existing literatures; 2) assessing the design of the pilots in terms of the resource implications, information sharing and operational arrangements; 3) developing protocols for evaluating the processes adopted, outcomes achieved and costs incurred in two 'flu seasons and for assessing the attitudes of staff and parents. METHODS By spring 2014 we will have used a mix of research approaches including literature review and synthesis, operational research modelling and information systems analysis to provide early insights to pilots. We will also form a stakeholder advisory group and, with their assistance, develop full research protocols for: i) a quantitative assessment of outcomes achieved and costs incurred by pilot sites and the Department of Health in delivering these vaccination programmes; ii) a multi-level organisational process evaluation of the inter and intra-organisational barriers and facilitators to implementation based on interviews with key informants; iii) a mixed methods assessment of parental preferences, attitudes and experiences of the vaccination programmes based on discrete choice experiments, qualitative and quantitative analysis of questionnaires and on interviews. Impact Our work will inform important decisions at a national level concerning the expansion of programmes to vaccinate healthy school-aged children against seasonal influenza. Also, we will provide valuable evidence on the challenges faces, costs incurred and outcomes achieved through different approaches to vaccination.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Production of Annual Report on Research and Development Work Relating To Equipment for Disabled People
Funder: Department of Health (England)

Abstract: Background Information will be gathered about activity in development and evaluation of assistive technologies funded by the relevant funding bodies as specified in the tender document. This will be conducted alongside FAST's existent data compilation activity covering Section 22 funded projects and also projects in the charitable and commercial sectors. The essential features of the data compilation process will be: a) Data will be input in a format whereby it can be meaningfully extracted by users b) Use of other relevant databases will be maximised c) Minimal time required on the part of contributors d) Information will reach the database manager in as input-ready state as possible e) Updating procedure will be as efficient as possible. Aims HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Plan of Investigation HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Potential Impact HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Policy Relevance Unknown


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFECTION
Title: Scoping Paper on Horizon Scanning For Diagnostics of Relevance to AMR
Funder: Department of Health (England)

Abstract: Aims and Scope: The report will provide an overview of diagnostic technologies relevant to improving the appropriate prescribing of antibiotics. The focus of the report will be on point-of-care technologies and will include technologies currently available, as well as identifying relevant technologies currently in development where possible. Format of the Report: We will carry out a broad and comprehensive literature search using several databases (including Medline, Embase, the Cochrane Library) to identify the relevant literature, and will search conference abstracts, trial registries, patents and relevant news media. We will also contact industry representatives to identify technologies in development which are very close to market. The report will include point-of-care technologies relevant to decreasing the inappropriate use of antibiotics, including pathogen detection and markers of host response (e.g. distinguishing between viral and bacterial infection). For each technology, the report will provide a concise 1-page overview of the technology consisting of the following elements: 1. The technology, it’s application and the setting in which it would be used 2. A brief evidence synopsis describing studies relevant to the device and its use in relation to anti-microbial resistance. This will include test properties (e.g. sensitivity, specificity, predictive value, etc.) We will use the CEBM levels of evidence (www.cebm.net/ocebm-levels-of-evidence/; see appendix 1) to determine the study type and the clinical question addressed. 3. A summary of the implications for practice with regard to anti-microbial resistance 4. Requirements for further research 5. Conclusions regarding the application of the technology and any cautions. For each technology, two clinicians will use the McMaster Online Rating of Evidence (MORE) criteria to rate the technologies for clinical relevance and newsworthiness to clinical practice - based on a scale of 1 to 7 (see appendix 2). The report will also provide a summative overview highlighting the overall findings and implications with regard to implementation and further research. Output: Formal final report to the Department of Health to be delivered by 31 October 2014.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Asymptomatic clostridium difficile infection among acute geriatric hospital admissions; frequency, risk factors and transmission to prevent C. difficile associated diarrhoea
Funder: The Dunhill Medical Trust

Abstract: Clostridium difficile associated diarrhoea (CDAD) causes expense to hospitals and both suffering and death for patients. Current infection control practices focus on stopping transmission from patients with proven CDAD and have only been partially successful. To successfully stop C. difficile transmission in hospitals it is necessary to address transmission from patients who have the organism in their stool without symptoms of diarrhoea. Patients with such ‘asymptomatic infection’ are not currently identified for infection control purposes and their role in transmission has not been established. We will conduct a prospective observational study on the geriatric unit of a large teaching hospital to 1) determine how commonly elderly patients have asymptomatic C. difficile infection, 2) what the risk factors are for asymptomatic C. difficile infection 3) whether molecular testing could be used to identify such patients and 4) estimate the contribution of asymptomatic infection to transmission of C. difficile in hospital.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: INFECTION
Title: Talking about HPV-related cancer: development and testing of scripted consultations
Funder: Division for Social Care and Health Research (Wales)

Abstract: HPV is a group of viruses, some of which are involved in all cases of cervical cancer and varying proportions of other gynaecological, anal, penile and head and neck cancers. HPV-related cancers are on the increase. They respond to different treatments and have different prognoses to those that are not HPV-related. Doctors need to be able to communicate this information effectively to their patients in order to help them make informed treatment decisions. The development from HPV infection to disease is complex (making it difficult to explain) and the high-risk types found in these cancers are sexually transmitted (making it a sensitive issue). Our previous research has shown that people worry about having an STI, blame themselves, worry about passing it on, and find it difficult to confide in anyone. In HPVrelated neoplasia, this comes on top of having received a cancer diagnosis. We will work with patients, clinicians and our public and patient representatives, in a series of interviews using different techniques, to develop scripts for doctors that aim to effectively convey messages that are important to patients. In the first phase, patients will help us identify and prioritise messages; in the second phase other patients will help us reword them in language that can be easily understood and in ways that are meaningful to patients. Then we will set the messages in scripts for doctors and nurses, backed up by brief information sheets for patients to take home that give the same key messages clearly and readably. Different versions will be tailored for patients with different types of cancer. We will then test the scripts with a third group. Final versions will be ready for testing in future trials for effectiveness in helping patients to feel less anxious, understand their diagnosis and make informed treatment choices.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFECTION
Title: 2005 RRG 9.41 - Skin bacteria as a source of surgical infections: molecular epidemiology and prevention in wound contamination
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: A recent study of spinal surgery at Queen's University Belfast showed that nearly 30% of operative wounds contained bacteria of the normal skin microbiota, despite pre-operative treatment of the patient's skin with the antiseptic povidone-iodine (PVI); however, as peropertive antibiotic prophylaxis was successful, these patients did not have post-surgical infection. The rise in antibiotic resistance, typified by methicillin resistant Staphylococcus aureus (MRSA), will inevitably result in an increase in life threatening post-operative wound infection, potentially to the 30% level of wound contamination observed in the QUB study. It is therefore proposed to pre-empt such a scenario by addressing the current procedures for skin antisepsis prior to surgery. Chlorhexidine gluconate (CHG) and PVI are skin disinfection antiseptics with different modes of bacterial killing; however, there have been no randomised controlled trials to determine if CHG used in addition to PVI reduces wound contamination in the operative setting. It is therefore proposed to determine if the sequential pre-operative treatment of patient skin with antiseptic CHG and PVI, will reduce wound contamination in a randomised controlled trial of patients undergoing orthopaedic surgery. Wound contamination will be determined by total viable bacterial count and bacteria will be tracked using methods such as multilocus sequence typing. The antibiotic and antiseptic resistance of isolates will be determined, as will the presence of key antibiotic resistance genes. This study will enable us to determine if by using both CHG and PVI it will be possible to counter the potential rise in post-operative infection arising from antibiotic resistant bacteria.


Research activity codes: 6.4 SURGERY
Health categories: INFECTION
Title: The role of microvesicle in the spread of rhinovirus infections
Funder: The Dunhill Medical Trust

Abstract: Rhinovirus is a small RNA-containing non-enveloped picornavirus that infects human airway epithelium resulting in inflammatory responses that cause the common cold and acute exacerbations of asthma or COPD. Over 150 antigenically distinct serotypes of rhinovirus are capable of circulating in human populations and despite years of research no effective vaccine or antiviral therapeutic has been developed. Epithelial cell infection by rhinovirus results in virus replication, interferon production and the release of pro-inflammatory cytokines. Although rhinovirus does not contain a membrane envelope we suspect that the infection of cells triggers the release of small membrane enclosed microvesicles that can regulate inflammatory responses and the spread of virus infection by potentially carrying rhinovirus. We wish to characterise the kinetics, structure and contents of the microvesicles released following rhinovirus infection and to determine their role in the spread of rhinovirus infections. This research could lead to potential novel therapeutic strategies for rhinovirus infections


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: PIVOT Trial
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: A long-term strategy study sponsored by the Medical Research Council (MRC) in the UK reported low rates of serious complications and the potential to reduce drug costs. However, more than a third of people on the ritonavir-boosted PI monotherapy group had viral load rebound compared to only 3% of people on standard combination therapy. The PIVOT study randomised 587 UK patients who already had an undetectable viral load on stable treatment to either PI/r monotherapy or triple therapy. It included four years of follow up (median 44 months, maximum 59 months) and the primary endpoints was loss of future treatment options based on development of drug resistance.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION