NIHRDataInsights/HRCSData huggingface dataset:
Title: BETTER-B: BETter TreatmEnts for Refractory Breathlessness - a feasibility study of the use of mirtazapine for refractory breathlessness
Funder: Marie Curie

Abstract: Breathlessness is a common and distressing symptom in many life-limiting conditions, including cancer, respiratory and heart disease. There are few treatments. Preliminary data suggest that serotonergic modulation is beneficial but rigorous evaluation has not been conducted. We wish to trial mirtazapine, a noradrenergic and specific serotonergic antidepressant that may be better tolerated than other antidepressants in this population. Before doing this though, it is vital to determine whether a sufficiently sized trial in this population of poor prognosis patients is feasible. AIMS To determine: • if a randomised, double-blind, placebo-controlled, phase III study of mirtazapine for refractory breathlessness is feasible in terms of recruitment. • the best approaches to recruitment in different settings, the acceptability of randomisation, placebo-control, and double-blinding to clinicians and patients. • the acceptability of potential phase III outcome measures and ways to minimise missing data. • the expected activity of mirtazapine, to further inform the phase III sample size. METHODS Design: Randomised placebo-controlled, double-blind, mixed-methods feasibility trial of 60 patients in outpatient, community and in-patient settings. Inclusion: Adults, diagnosis of cancer, chronic obstructive pulmonary disease(COPD), interstitial lung disease(ILD) or chronic heart failure on optimal treatment, unchanged for the previous week. Modified MRC dyspnoea scale grade 3 or 4, expected prognosis of 2 months. Exclusion: Existing antidepressant use, contra-indication to mirtazapine, Australiamodified Karnofsky Performance Scale 40 or less, cognitive impairment. Intervention: Oral mirtazapine, 15mg, for 28 days. If, after 14 days, average breathlessness intensity/24 hours has not improved by 1 point or more, on a 0–10 Numerical Rating Scale(NRS), the dose is doubled. Control: Placebo medication with titration as above. Outcomes: The number of patients recruited across 3 hospitals over a 12 month period (primary). Eligibility/recruitment rates in different settings, blinding, missing data at 28 days. Activity including: average breathlessness intensity in previous 24 hours (0–10 NRS), day 28, and at 7, 14, 21 days, QoL, breathlessness mastery/unpleasantness, anxiety, depression. Adverse events, medications and compliance. Qualitative interviews: On a purposively selected sample of 12-15 patients exploring views of trial and treatment. HOW THE RESULTS WILL BE USED The results will be used to determine the feasibility of proceeding with a large phase III trial in this setting and this population and the best methods/design for that study. They will inform future studies in patients with advanced diseases, especially recruitment and trial design, and advance our understanding of breathlessness and ways to research it.


Research activity codes: 7.2 END OF LIFE CARE;6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Development and practical application of landmarking in studies of time-varying exposures and survival
Funder: Medical Research Council

Abstract: It is vital to understand the effects of time-varying exposures on survival, for example to gain insight into biological mechanisms and to inform treatment decisions. Data such as electronic health records, which contain patient-level variables recorded longitudinally, enable us to study these effects. My proposed research focuses on (1) making dynamic predictions of survival to a future time horizon based on an individual's measurements up to a given time; (2) estimating the causal effects on survival of patterns in time-varying exposures, including continuous and binary exposures and intermediate events, taking into account time-varying confounding. These investigations can currently require quite different complex statistical methods, including joint modelling of exposure and survival data, multi-state modelling and causal inference methodology. A unified approach does not exist but is essential to enable applications from a wide range of researchers. I will develop statistical methods based on an approach called 'landmarking' to provide a unified and intuitive approach. A key advantage of landmarking is that it is based on the familiar method of Cox regression modelling. However, landmarking is currently limited to dynamic prediction and by lack of extensions to accommodate practical constraints. In Part 1 I will devise how to use multiple imputation to handle missing data and measurement errors in longitudinal measurements used in the setting of dynamic prediction. In Part 2 I will develop landmarking to enable estimation of the causal effects of time-varying exposures on survival, allowing for time-varying confounding. Despite the importance of nested case-control and case-cohort studies, especially in biobanks, there have been few attempts at extensions to this setting. In Part 3, I will address this by extending the methods of Parts 1 and 2. I will place an emphasis on practical application and provide software code where needed.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Setting up an Obstructive Sleep Apnoea Database; the first of its kind in the UK
Funder: The Royal College of Anaesthetists

Abstract: Abstract Background: There is an increasing number of patients with OSA requiring anaesthesia for surgery. Cautiousness with intra-operative opioids has been noted in the literature as has difficult bag mask ventilate and difficult laryngoscopy (DL). The RNTNE is the biggest sleep apnoea centre in England; giving rise to a high volume, high turnover patient cohort for evaluation. Aims: - Demonstrate opioid use in OSA patients does not cause adverse effects or delayed discharge. - To assess ease of bag mask ventilation and intubation grade in patients with OSA. - To devise a post-operative take home medication protocol and leaflet. Methods: Adult patients (>18 years old), ASA I-III, undergoing elective OSA and snoring surgery were included in this prospective audit. The survey consisted of two airway related questions: ease of bag mask ventilation, Cormack and Lehane grade of laryngoscopy. Analgesic related questions required: fentanyl usage and dose; morphine usage and dose; ketamine usage and dose. The data collection form also looked at whether the surgery was a day case procedure or not. The survey consisted of 7 day follow up pain scores and analgesic requirements. Results/Discussion: All patients received a short acting opiate and the majority received a long acting opiate intra-operatively. There were no reported adverse respiratory or sedative effects in the post-operative period. Three quarters of the cohort group were day case procedures. Our data set suggests that OSA alone does not significantly contribute to difficult bag mask ventilation or difficult laryngoscopy. Results showed almost all patients had ongoing pain at day 7 post-surgery. We offered phone advice to optimise symptoms and incorporated this information into our take home medication protocol and medication leaflet.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Air Pollution, housing and respiratory tract Infections in Children: NatIonal birth Cohort study (PICNIC)
Funder: Medical Research Council

Abstract: Respiratory tract infections (RTIs) are the most common reason for hospital admissions in children under five in the UK. We aim to quantify the extent to which in-utero, infant and childhood exposure to air pollution (AP), and adverse housing conditions (including overcrowding and damp/mould) are associated with the risk of RTI admissions in children less than 5 years old. We will use national administrative data birth cohorts including all children born in England in 2005-2014, and in Scotland 1997-2019, created via linkage between vital statistics, maternity and hospital admission datasets. We will further enhance these cohorts via linkage to Census 2011 data from mothers and their partners on housing conditions and socio-economic position, and small-area level data on AP and building characteristics. Our specific objectives are to: 1) Estimate the association between long-term exposure to ambient AP during pregnancy and infancy and the rate of RTI admissions in infants 2) Derive variables indicating adverse housing conditions (eg overcrowding, indoor air pollution, damp/mould) and estimate the association between housing exposures and infant RTI admissions 3) Based on the outcomes of analyses for objectives 1) and 2), estimate the relative contribution of AP and adverse housing conditions on infant RTI admissions 4) Estimate the relative contribution of AP exposure during pregnancy, infancy and early childhood and adverse housing conditions on RTI admissions in children aged less than five years 5) Establish the linked administrative data birth cohorts as resources for maternal and child health research Our results will inform policy makers, charities and parents about the relative contribution of AP exposure during pregnancy, infancy and early childhood and housing conditions to RTI admissions in children. Our legacy will include the two national birth cohorts, which will be made available to other researchers.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Microvesicles as crucial mediators of cytokine-dependent perioperative lung injury induced by mechanical ventilation
Funder: Medical Research Council

Abstract: Postoperative pulmonary complications (PPCs) are a common yet potentially fatal consequence of major surgery. Perioperative mechanical ventilation often produces unphysiological lung stretch instigating inflammation, which predisposes the lungs to PPCs and may evolve into ventilator-induced lung injury (VILI). Intra-alveolar cytokines such as TNF have been implicated in the pathophysiology of VILI, but its precise mechanism is still unclear. Microvesicles (MV) may serve as a hidden compartment of such cytokines within the alveolus, inducing cytokine-mediated lung inflammation during VILI. In this proposal, we aim to investigate the role of intra-alveolar MV-mediated inflammation in VILI, specifically focusing on MV-associated cytokine signalling, using a combined in vitro and in vivo approach. For in vitro, we will use a cell culture model of VILI, in which human alveolar epithelial cells (AECs) are mechanically stretched in mono-culture or co-culture with monocyte-derived macrophages. We will identify the mechanisms of stretch-induced MV production, cytokine packaging within MVs/MV subtypes, and MV-mediated AEC activation through their cargo cytokines. For in vivo, we will use a human model of VILI, in which serial bronchoalveolar lavage samples will be obtained from patients undergoing oesophagectomy and one lung ventilation (OLV). We will investigate MV profiles/cargo cytokines in lavage samples, define if pathological lung stretch during OLV diverts cytokine signalling from a soluble to MV-mediated pathway, and assess the bioactivity of patient-derived MVs using the in vitro culture model. The results will provide fundamental yet clinically-translatable knowledge to understand the in vivo roles/mechanisms of MV-mediated cytokine signalling during VILI. Our findings will offer important insights towards the development of novel MV-targeting strategies for ventilator-associated lung inflammation/injury in both perioperative and critical care patients.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Participatory Approaches in Mpemba for Developing Clean Air interventions (PAMODZI)
Funder: Wellcome Trust

Abstract: Air pollution is a major health risk worldwide, particularly in countries such as Malawi where smoke is widespread, both indoors and outside, and populations remain reliant on polluting fuels for cooking and heating. Research so far, largely using ‘improved cookstoves’, has failed to demonstrate the hoped-for health improvements in lung health. This study brings together the priorities of the research team with those of the communities which the research aims to benefit, from the start. I will use participant observation to explore the role of smoke in the context of a Malawian village, also measuring individuals’ smoke exposures as they go about their daily lives. Working with community members we will then use this information to develop a set of acceptable, context-appropriate clean air interventions. Finally, I will assess the effectiveness of these interventions in reducing smoke exposure through a small village-based trial. The study will build on the knowledge of members of the village, raising awareness of the issues and including participants in developing solutions from the start. This will assist in developing an effective, sustainable clean air intervention, as well as demonstrating a more engaged approach to Global Health research.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Platform technology for the removal of critically underserved air pollutants in homes
Funder: Innovate UK

Abstract: Nitrogen dioxide (NO2) is one of the most concerning and challenging pollutants the UK faces. Removing it from our air, particularly in domestic settings such as the home, is one of the UK's top priorities in its Clean Air Strategy. Immaterial is a spin-out company from the University of Cambridge that has developed a novel porous material that captures more NO2 on polluted days than possible with incumbent filtration media, and keeps it captured on clean days. This project will integrate these ground-breaking materials into prototypes equivalent in design and use to the air cleaning devices available commercially today, but with additional functionality. Immaterial is working closely with leading academics and device manufacturers in this project. The University of York will be testing the prototypes during typical domestic activities such as cooking and cleaning to independently verify the effectiveness and inform iterative prototype development at Immaterial. In parallel, Immaterial will be working with device manufacturers to rapidly deploy our technology into commercial products. Immaterial is an early-stage company, expert in porous materials. The company was founded in 2015 following the breakthrough discovery of a densified form of a class of materials known as monolithic metal-organic frameworks (MOFs) at the University of Cambridge. Immaterial is growing quickly and providing high-tech jobs, leveraging skills such as design, automation, data analytics, and materials and process technologies. Prior to this phase of the project, Immaterial used proprietary simulations to identify the most effective MOF structures for NO2 in the domestic environment and then produced and tested these structures in tuneable, densified forms. This is an approach that can be reproduced to develop enhanced cleaning materials for other critical gaseous pollutants. These may be pollutants well recognised today, such as ozone, or those that are identified as we come to better understand the causes and effects of indoor air pollution through studies such as the "Impeccable" and "Born in Bradford" projects undertaken by the University of York.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Do tree microbiomes clean up urban air pollution?
Funder: Natural Environment Research Council

Abstract: Overview Carbon monoxide (CO) is a ubiquitous trace gas in the atmosphere that is produced by natural processes. It is also a significant anthropogenic air pollutant produced by combustion processes. As a toxic gas, it contributes to the high burden of premature mortality and morbidity caused by air pollution. Microorganisms play a crucial role in the removal of CO from the atmosphere and have previously been identified as abundant members of soil microbial communities (Cordero et al., 2019, King and Weber, 2007). Surprisingly, we recently found that CO-degrading bacteria are also found in the phyllosphere of trees (Palmer et al., 2021), which is defined as the above ground parts of trees and constitutes a huge microbial habitat. We showed that leaf washings from two common UK tree species, hawthorn and holly, had the potential to degrade CO, indicating the presence of CO-degrading microorganisms. We identified a wide diversity of candidate CO-oxidising bacteria in the phyllosphere community using cultivation independent approaches of microbial community analysis using 16S rRNA as a taxonomic marker and the gene encoding the large subunit of the carbon monoxide dehydrogenase (CODH, encoded by coxL) as a functional marker. Data mining of environmental phyllosphere metagenomes suggests that the bacteria containing genes for CO oxidation could constitute up to 25% of the phyllosphere microbial community. These findings suggest that phyllosphere microbiota with the potential to degrade CO could drive a significant and previously unrealised sink in the global CO cycle (Palmer et al., 2021). This project will build on those findings and aim to characterise CO degrading microorganisms more widely in above ground habitats including trees and mosses. You will assess the abundance and activity of CO-degrading bacteria associated in these habitats, test the potential for CO degradation and assess whether CO-degrading bacteria are active in situ. This will provide fundamental new insights into the distribution of CO-degrading bacteria in above ground habitats and advance our understanding of the CO biogeochemical cycle. It may also lay the foundation for a mechanistic understanding of how phyllosphere microbiota may affect air quality, how air quality affects microbial activity, and it will potentially provide a basis for informed selection of tree species that could maximise microbial ecosystem services for mitigation of air pollution in urban areas.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Measurement of emissions from brake and tyre wear
Funder: Department for Transport

Abstract: As part of the Government’s commitment to decarbonise transport and improve air quality, this research aims to fill the knowledge gaps for brake and tyre wear emissions (non-exhaust emissions), and develop recommendations on how to better assess and control these emissions which will persist after a transition to zero tailpipe emission vehicles. • The project aims to: • - Develop a robust measuring system and methodology for measuring and characterising particles emitted from brake and tyre wear in real driving conditions • - Fill knowledge gaps in the measurement and characterisation of brake and tyre wear emissions from road vehicles • - Investigate the effect of the use of regenerative braking on brake and tyre wear emissions • The overarching aim of this project is to develop knowledge to inform policy and legislation aiming at reducing emissions from brake and tyre wear on a domestic and international level, in line with the Government’s commitment to cleaner air and transport. [NOTES: This five year study was conducted by Arup AECOM, with Ricardo Energy & Environment being the lead contractor]

Lay abstract: As part of the Government’s commitment to decarbonise transport and improve air quality, this research aims to fill the knowledge gaps for brake and tyre wear emissions (non-exhaust emissions), and develop recommendations on how to better assess and control these emissions which will persist after a transition to zero tailpipe emission vehicles. • The project aims to: • - Develop a robust measuring system and methodology for measuring and characterising particles emitted from brake and tyre wear in real driving conditions • - Fill knowledge gaps in the measurement and characterisation of brake and tyre wear emissions from road vehicles • - Investigate the effect of the use of regenerative braking on brake and tyre wear emissions • The overarching aim of this project is to develop knowledge to inform policy and legislation aiming at reducing emissions from brake and tyre wear on a domestic and international level, in line with the Government’s commitment to cleaner air and transport.

Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Respiratory Disease
Funder: Medical Research Council

Abstract: The CTU has been collaborating with the Respiratory Trials Unit (RTU) at the Churchill Hospital, Oxford over a number of years in the conduct of multi-centre trials. The main focus of the research programme is in pleural disease and sleep disorders. Although in the past the British Thoracic Society was active in multi-centre trials in respiratory disease in recent years there was been very limited funding and little activity in this area apart from trials in lung cancer. The current initiative began with a trial, MIST1, which assessed the role of streptokinase in pulmonary empyema; this was funded by the MRC and was a collaboration between the RTU in Oxford and the Clinical Trials Unit. The unexpected findings from that multi-centre trial has had considerable influence over the management of that condition and led to further trials and has provided important information on the nature of the pathogens involved in this disease and the corresponding differences in outcomes. A second trial assessing whether DNase or Alteplase, improve pleural fluid drainage in pleural infection, (MIST2) was recently completed A further series of trials in pleural disease is focussed on patients with malignant pleural effusions. These trials (TIME1 and TIME2) are addressing problems associated with pleurodesis (preventing re-accumulation of fluid), in particular the most optimum form of drainage and the analgesic most likely to minimise the associated pain. Smaller drains may be less painful but may not be as effective. TIME3 is addressing the role of fibrinolytics in reducing breathlessness.||Sleep disorders affect around 4% of the adult male population. Poor quality sleep associated with frequent waking through the night can lead to sever daytime symptoms which inhibit the ability to work effectively and may lead to accidents, particularly in drivers. For patients with severe obstructive sleep apnoea trials have shown the most effective treatment to be nasal CPAP which enables the patient to have a good nights sleep. The role of CPAP in those with moderate sleep apnoea is less clear, however there may be benefits in terms of reduction in risk factors for cardiovascular disease since CPAP reduces blood pressure while sleeping. The MOSAIC trial assesses whether there is benefit in sleepiness reduction in patients with moderate apnoea and whether their risk factor scores, as measured by the Framingham index, can be reduced. The PREDICT trial is assessing whether older patients could benefit from CPAP.|


Research activity codes: 6.3 MEDICAL DEVICES;6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY