NIHRDataInsights/HRCSData huggingface dataset:
Title: Determination of hantaviruses as a cause of clinical disease in England
Funder: Department of Health (England)

Abstract: Hantaviruses are a common cause of zoonotic disease across the globe, particularly in parts of Northern Europe. Recent evidence suggest that hantaviruses may be an important cause of disease in the UK. At least nine acute severe cases have been detected and several seroprevalence studies indicate continued exposure. The objective of this study is to develop and implement a sensitive diagnostic assay into the HPA’s special pathogens reference unit as a future service for suspected hantavirus cases. As proven in European studies, rapid and sensitive diagnosis improves patient outcome, reduces the likelihood of invasive and unnecessary treatment and overall reduces the cost to the NHS.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: INFECTION;RENAL AND UROGENITAL
Title: An exploration of post-transplantation gamma-delta T cell phenotype and function.
Funder: Medical Research Council

Abstract: Solid organ transplantation is curative surgery for end-stage organ dysfunction. The immunosuppression required to prevent allorejection, however, causes substantial morbidity and mortality. A granular description of tolerogenic and alloreactive cell populations within the human immune system is necessary to develop targeted immunotherapies. Gamma-delta T cells are a highly conserved lymphocyte subpopulation characterised by innate and adaptive properties. They initiate, propagate, and modulate immune responses, and have been associated with operational tolerance and a reduced cancer risk following renal transplant. I aim to investigate the gamma-delta T cell compartment in transplantation and identify therapeutic opportunities that capitalise on their unique identity and function. My fellowship comprises three objectives: 1. define the cell surface, transcriptomic, and functional signatures of gamma-delta T cell subsets. This will be achieved using bulkRNAseq and flow cytometry of human blood to identify immunoregulatory signatures. 2. investigate the impact of autologous regulatory T cell therapy on peripheral and infiltrating gamma-delta populations in human renal transplant recipients. I will utilise single cell RNAseq and multiplexed transcriptomic profiling of our unique biobank from renal transplant recipients to probe for tolerising signatures associated with successful immunosuppression withdrawal. 3. assess the efficacy of gamma-delta subsets in preventing skin graft rejection using an in vivo model of transplantation. I will generate data assessing the therapeutic potential of autologous and allogeneic immunoregulatory gamma-delta T cells. My fellowship proposal is an exciting opportunity to generate insights into unconventional lymphocyte biology and investigate their therapeutic potential for transplant recipients, in addition to a personal opportunity to receive world-class research training in bioinformatics and single cell sequencing.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION;RENAL AND UROGENITAL
Title: Are prophylactic antibiotics necessary before laparoscopic living kindey donation? A randomised, controlled trial.
Funder: Department of Health (England)

Abstract: Background Two-thirds of kidney transplants in the UK are from living donors, with most performed laparoscopically. Donors are selected, healthy individuals, with an uninfected surgical field, yet there is a significant incidence of wound and urinary infections after surgery, at around 10-15%. There is no data on whether prophylactic perioperative antibiotics would prevent infections after this surgery and national guidelines have identified the need for a trial. Avoiding unnecessary antibiotics may be beneficial due to fewer side effects and less antibiotic resistance as well as reducing costs. However, preventable infections increase hospital stay and readmissions, and treble costs. This study is a randomised, double-blind study of prophylactic antibiotics for laparoscopic living kidney donation. Aims We aim to determine whether a single dose of prophylactic intravenous antibiotic prior to laparoscopic living kidney donation leads to -Fewer wound infections within 30 days of surgery -A decrease in other infectious complications within 30 days of surgery -A lower mean hospital stay and readmission rate -An increase in side effects including antibiotic associated diarrhoea -A quicker return to work/normal activities for donors -A reduction in costs Plan of Investigation This study is a randomised, double blind, controlled trial in which patients are randomly allocated to one of two study arms: Group 1- patients undergoing laparoscopic living kidney donation who will receive a single dose of 1.2g of co-amoxiclav intravenously on induction of anaesthesia. Group 2- patients undergoing laparoscopic living kidney donation who will receive a single dose of placebo intravenously on induction of anaesthesia. Data will be collected by a researcher blinded to the patients' treatment. Outcome measures will include a primary endpoint of all infections within 30 days of surgery, and secondary endpoints will include hospital stay and readmissions, potential antibiotic associated side effects, time before returning to work and overall healthcare associated costs. Potential Impact This study has the potential to change clinical practice in living kidney donation. Currently the use of prophylactic antibiotics is inconsistent and is not guided by evidence. This study will provide the evidence to determine whether antibiotics should be used, and may results in: -Fewer infectious complications or antibiotic associated side effects -Shorter hospital stay and lower readmission rates -Reduced costs -A quicker recovery for donors This study will provide an evidence base for transplant teams throughout the UK and beyond, as no trial exists in this group of patients. It may also influence the management of patients undergoing nephrectomy for other reasons, since there is also no evidence for the use of antibiotics in this group.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: INFECTION;RENAL AND UROGENITAL
Title: Responding to COVID-19 impacts through clinical study and commercialisation in renal dialysis line securement
Funder: Innovate UK

Abstract: Intravenous cannulas are the most commonly used patient device in modern medicine. The majority of COVID-19 patients will receive an IV cannula to administer drugs, fluids and antibiotics. IV cannula insertion takes 20 minutes of HCW time. However, up to 50% of devices fail before meeting their clinical need. Patients admitted to intensive care routinely undergo cannulation of the radial artery. These cannulas also frequently fail and need replacing. If the majority of the UK population is affected by COVID-19, cannula failures could lead to millions of reinsertions, unnecessary HCW exposure and PPE use. An SME is developing a low-cost device that is worn by patients to protect and secure cannulas in order to reduce failure rates, improve care, reduce waste and minimise unnecessary HCW exposure to COVID-19. Due to the impacts of COVID-19, a range of opportunities exist to develop the device for application in community and home dialysis settings thereby presenting multiple avenues for commercialisation.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: INFECTION;RENAL AND UROGENITAL;CARDIOVASCULAR
Title: In Their Own Voices: Vulnerabilities & Abilities of Women, Children, & Families in Health Research
Funder: Medical Research Council

Abstract: Efforts surrounding the Millennium Development and Sustainable Development Goals have brought much needed attention to lessening the burden of disease shouldered by women and children, which is most severe in low-income countries. Lasting advances in women’s and children’s health will require improvement of health systems, environment, education, improved access to effective health interventions, including better ways to deliver care in rural, low-income settings. Innovations in each of these areas will require clinical, social science and implementation research. However, many of these women and children are considered to be vulnerable to harms, coercion or exploitation, making inclusion in even potentially beneficial research ethically concerning. While significant strides have been made to develop research ethics guidance for those working with vulnerable populations, critical gaps remain in our understanding of specific vulnerabilities in context, accompanying abilities, the role of social support in mitigating vulnerability, and individuals’ own perceptions of vulnerabilities and abilities. To address these gaps and to improve support and guidance for responsible research with women, children and families, we propose an interdisciplinary collaborative study with investigators in maternal-child health, infectious disease, and social science research across three international sites in the Wellcome Trust Major Overseas Programmes: Kenya, South Africa and Thailand.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Intermittent Preventive Treatment with DHA-piperaquine for malaria in pregnancy in areas with high sulphadoxine-pyrimethamine resistance in Africa
Funder: Medical Research Council

Abstract: Malaria in pregnancy (MiP) has devastating consequences for the mother and unborn child. The intermittent preventive therapy with sulphadoxine-pyrimethamine (IPTp-SP) strategy recommended by WHO is threatened by high levels of parasite resistance. The search for safe, effective and well-tolerated alternatives drugs or strategies for IPTp-SP has proven elusive. However, two recent exploratory trials showed IPTp with dihydroartemisinin-piperaquine (DP) to be well tolerated and associated with marked reductions in malaria infection, but they were not powered to evaluate the impact on adverse pregnancy outcome. WHO reviewed the evidence in July 2015 and concluded that DP is a promising alternative to SP but that a larger confirmatory trial is needed before implementation of IPTp-DP could be recommended. We will determine the efficacy, safety and cost-effectiveness of IPTp-DP in a definitive trial to inform WHO policy decision makers whether or not this is a suitable alternative strategy in endemic areas with high SP resistance. We will conduct a 24-month, multi-centre, 2-arm, double blind, placebo-controlled, individually randomised trial involving 2,942 women in 6 sites to determine if IPTp-DP (Eurartesim) is superior to the existing IPTp-SP strategy in areas in western Kenya (KEMRI) and Malawi (College of Medicine) with high SP resistance. The study has 80% power to detect a 20% reduction (RR=0.8) from 23% to 18.4% (a=0.05) in the primary outcome: 'adverse pregnancy outcome', a composite of foetal loss, live births born either small-for-gestational age, with low birthweight, or preterm, or neonatal death. It also provides 85% power to a prospective meta-analysis combining the evidence from this and previous trials to detect a 17% reduction in this outcome (a=0.05). It also includes sub-studies on the antimicrobial activity of SP, including on the gut and vaginal microbiota, cardiac safety studies of monthly DP, and an operational feasibility component.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Co-Infections Programme
Funder: Medical Research Council

Abstract: The HIV epidemic in Uganda disproportionately affects urban dwellers, and overall, 60% of HIV infected individuals are female. Core groups with high rates of sexual partner change, such as female sex workers, play an important role in both the initial establishment of sexually transmitted HIV epidemics and in the later contracting phases, as prevalence declines and HIV transmission again becomes more concentrated in groups at higher risk. Uganda is currently undergoing this later stage epidemic, and risk reduction interventions for high risk groups are needed to prevent a resurgence of HIV in both core groups and the general population. Uganda Virus Research Institute (UVRI) is mandated by Ministry of Health (MoH) to provide a platform and services for HIV treatment, prevention and care. Building on the experience with the first phase of the Good Health for Women Project, the UVRI team, in collaboration with MRC/UVRI is carrying out an enhanced prevention project in partnership with MoH community advisory board representatives. This consortium will provide structured guidance to implement this package of interventions through biomedical & behavioural interventions at the individual and dyadic levels to sex workers and their paying & non-paying partners; and structural interventions delivered at the community and policy levels. The goal is to improve the effectiveness of HIV prevention in Uganda by enhancing comprehensive HIV prevention services amongst FSW and their male partners. The Objectives are: a) To increase reported risk reduction practices by high risk women and their partners in Kampala, b) To increase awareness and understanding of condom use and alcohol abuse c) To increase awareness of HIV risk and vulnerability of high risk women and their male partners, policy makers and stakeholders in Kampala; d) To develop an EPP to include a detailed M&E framework These objectives are responsive to the GHI principle on women, girls and gender equality among others. We propose to scale up this package of services throughout Kampala. Targets are 1000 FSW, 300 men & 10 bar owners. This project is funded by the Government of the United States of America through the President’s Emergency Plan For Aids Relief (PEPFAR).


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: MICA: The role of placental infection in adverse pregnancy outcome.
Funder: Medical Research Council

Abstract: Adverse pregnancy outcome is often ascribed to "placental dysfunction". However, there is limited mechanistic understanding of the underlying cause. Multiple lines of evidence indicate that clinically unrecognized infection of the placenta is a plausible cause of placental inflammation and dysfunction, but definitive evidence is currently lacking. Since January 2008, we have been conducting a prospective cohort study of unselected nulliparous women attending the Rosie Hospital for antenatal care (funded by the Women's Health theme of the NIHR Cambridge Biomedical Research Centre). Women are recruited at the time of their first ultrasound examination. Participation involves obtaining maternal blood (for serum and plasma) at the first scan (typically ~12 weeks) and at 20, 28, and 36 weeks, plus ultrasound examinations at the same intervals. Following delivery, the placenta and membranes are sampled by a trained technician. We have recruited 4,544 women and all sample and data collection will be complete by May 2013. We will have complete blood and scan data from ~4,250 women and placental samples from ~4,000. We will use these samples to test our hypothesis that placental infection is involved in the aetiology of pre-eclampsia and/or fetal growth restriction (cases). We have the following specific aims: 1. To compare the frequency of detection of nucleic acids encoding for infectious agents in the placenta in cases and controls matched for key maternal and obstetric characteristics. 2. To compare (i) the type, appearance and level of immunoglobulins to infectious agents, and (ii) the level of cytokines associated with placental inflammation; in maternal blood at ~12, 20, 28 and 36 weeks gestational age in cases, in comparison with a common control group of randomly selected women from the same prospectively defined cohort. 3. To quantify placental inflammation (by histopathological and stereological assessment) in the same cases and matched controls, above.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Menstrual cups and unconditional cash transfer to reduce sexual and reproductive harm and school drop-out in adolescent schoolgirls in western Kenya
Funder: Medical Research Council

Abstract: Cluster randomised controlled 4-arm superiority trial examining the impact and cost-effectiveness of menstrual cups, compared or combined with unconditional cash transfer, to improve rural girls' retention in secondary school and protect their sexual and reproductive health (SRH) in western Kenya. The objective is to reduce girls' exposure to drivers which increase SRH harms and compromise girls' successful school completion. A sample of 4032 girls, in 56 school clusters block randomised into 4 arms, will be followed for 2 years (6 terms). Allowing 8%/year migration loss this gives a power of 90% to detect 30% reduction in a composite primary endpoint (HIV, HSV-2, and school drop-out incidence); and 89% to detect a 52% reduction in HSV-2, 80% to detect a 36.3% reduction in drop-out, and 20% to detect a 50% reduction in HIV alone. Demographic surveillance facilitates home consent and follow-up to differentiate migration loss from school drop-out. Secondary outcomes measured through costings, surveys and qualitative studies are the cost-effectiveness of harms averted, intervention use and safety, girls' sexual behaviour, and quality of life measures. The trial follows completion of a pilot study showing safe cup use by rural Kenyan primary schoolgirls, and potential impact on STI's and school drop-out. Cash transfer reduced HIV, HSV-2 and sexual risks in Malawian schoolgirls but requires replication and comparison with alternative interventions. Hazards were not detected in prior studies but adverse events will be monitored. Girls clubs, beneficiary trial advocacy groups and government ministry partners will guide development, assess process evaluation, and develop materials for implementation packages that have direct application for programme scale-up. Trial outcomes will be disseminated widely to inform policy, guide research, and advocate for the health and equity of adolescent schoolgirls in impoverished communities.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: HCVAVERT: designing a trial to cure hepatitis C virus (HCV) in HCV-infected pregnant women And prevent VERTical HCV transmission
Funder: Medical Research Council

Abstract: O1 HCV MTCT O1a: Assemble published/ unpublished data to inform a staged model of MTCT. Contact authors and networks for aggregated and individual patient data (IPD). Analyse IPD on a study-by-study basis in the first instance. O1b: Construct a model of the timing of MTCT, using data from (O1a) to estimate parameters using multi-parameter evidence synthesis. O2 DAA safety O2a: Review published/ unpublished pre-clinical safety and availability of DAAs in high-burden LMIC. O2b: Establish a prospective registry of women becoming pregnant on DAAs in Egypt, and their infants, and contact existing known cases, through liver units, antenatal and other clinics responsible for DAA treatment. Collect follow-up data current/ historical pregnancy outcomes. Review pharmacovigilance pregnancy registries for DAAs. O3 Cost-effectiveness O3a: Adapt an existing Markov model on HCV for pregnant women O3b: Build on transmission probabilities estimated in O1b and review data (including SE Asia) to inform key model parameters O3c: Estimate incremental cost effectiveness ratio (ICER) of screening and treatment strategies vs. SOC, across different settings, prevalence, HIV co-infection, and cost scenarios. Conduct sensitivity analyses to assess key model parameters to capture in the trial. O4 Implementation O4a: Conduct assessments of current practice regarding screening and care pathways. Semi-structured interviews with clinic staff will take place in 2 antenatal clinics in Egypt (Ain Shams + one other) and 2 in Ukraine (Odessa, Kiev and/or Dnipropetrovsk) to identify practice and key gaps which need strengthening for a trial. O4b: Design and implement a DAA acceptability survey to elicit views from pregnant and post-partum women (cured and not cured) engaged in care. n=300 pregnant/post-partum women, and 20 clinicians will complete a quantitative survey. Focus groups/ roundtable discussions with patients, clinicians and key stakeholders will be held.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Feasibility study of the Home-based Exercises for Responsible Sex (HERS) intervention to promote correct and consistent condom use among young women
Funder: Medical Research Council

Abstract: The DoH has identified the need to reduce rates of sexually transmitted infections (STIs) as a priority for improving sexual health. Although condoms can be highly protective against the transmission of most STIs, there is evidence that they are often not used consistently or correctly. There is a need to develop effective brief interventions designed to promote correct and consistent condom use. In line with MRC guidance for developing and evaluating complex interventions, the aims of this early phase study are to define, develop, specify, and assess the feasibility of a behaviour change intervention to increase condom use (The Home-based Exercise for Responsible Sex (HERS) Intervention) among young women aged 16-25. HERS-UK is modelled on the HERS-US programme for women and the Kinsey Institute Homework Intervention Strategy (KIHIS/HIS-UK), designed to improve condom skills, enjoyment, and self-efficacy among young men, and which have demonstrated evidence of efficacy. The HERS intervention is novel in that it a) targets the drivers for non-condom use relevant to young women, b) aims to increase condom use by targeting outcome expectancies related to pleasure and enjoyment of sex, which have been identified as important determinants of non-use behaviour; c) will have been adapted with extensive user participation to ensure future successful implementation, and d) will have an accompanying intervention manual specifying targeted outcomes, behaviour, behavioural determinants, behaviour change techniques, methods of delivery, and proposed mechanisms of action, thus ensuring that the future main study can draw conclusions about what has worked and why. Women at risk of STIs through the non-use of condoms with new and casual partners will be recruited from GUM and outreach services in Hampshire. The study will involve a literature review, development consultation, intervention delivery and feasibility, follow-up, and recommendations for a definitive trial.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH