Integrated Research Application System Research Articles

Preimplantation Genetic Testing for Aneuploidy (PGT-A) in In-Vitro Fertilisation (IVF) Treatment: Study Protocol for Pilot Phase of a Randomised Controlled Trial.

Introduction: Poor outcomes following IVF treatments are speculated to be due to the transfer of aneuploid embryos that cannot be identified based on morphological evaluation alone. This leads to patients requiring numerous embryo transfers and, consequently, a prolonged time interval before live birth. Embryo selection following preimplantation genetic testing for aneuploidy (PGT-A) with next-generation sequencing (NGS) has been suggested as an intervention to shorten time to pregnancy in women undergoing in vitro fertilisation (IVF). Past studies assessing the clinical efficacy of PGT-A in improving clinical outcomes have been conflicting and the associated clinical pregnancy rates and live birth rates following the transfer of a mosaic embryos have yet to be determined. None of the existing studies solely included women of advanced reproductive age (ARA). The pilot study and proposed RCT will determine if, compared to morphological evaluation alone, the use of PGT-A through NGS is a more clinically effective, safer, and more cost-effective way to provide IVF treatment in women of advanced reproductive age. Method and Analysis: The proposed pilot study will aim to randomise 100 patients within a single-centre study to evaluate recruitment, randomisation, and adherence to study protocol and allocated trail arms by participating patients. The results of the pilot study will enable us to determine the sample size for a larger study to establish the effectiveness of PGT-A in ARA women. Ethics and Dissemination: The study (Integrated Research Application System Number 236067) received approval from the Health Research Authority and Health and Care Research Wales (HCRW) and the East Midlands-Leicester South Research Ethics Committee (20/EM/0290). The results will be made available to patients, the funders, the Reproductive Medicine societies, and other researchers. Trial registration: ClinicalTrials.gov Identifier: NCT05009745, n.

Remote monitoring to improve low adherence in non-invasive ventilation: a protocol for a randomised controlled clinical trial (READ-NIV trial).

Obstructive sleep apnoea (OSA) is the most common sleep-related breathing disorder. Non-invasive ventilation (NIV) is essential for managing hypercapnic respiratory failure in patients with obesity hypoventilation syndrome (OHS) and those with co-existing OSA, where continuous positive airway pressure (CPAP) alone is insufficient. However, adherence to NIV can be challenging, with substantial non-compliance occurring due to factors such as discomfort and phobia. The objective of this protocol is to assess the improvement of adherence to NIV remotely monitored, as well as to record symptom control and long-term clinical outcomes, and to optimise healthcare resource usage. This is a prospective, randomised, and controlled (usual care) trial with a two-arm parallel group design, testing remote monitoring of home NIV (T4P device, SRETT, Paris, France) for 3 months in patients with OSA/OHS who have previously had low NIV adherence (<4 hours/night). This project has been approved by the research ethics committee/Health Research Authority (HRA) [Integrated Research Application System (IRAS) ID: 270108], as well as by Guy's & St Thomas' NHS Foundation Trust R&D Department. Outcomes will be compared between the intervention and the control group (NIV with vs. without remote monitoring). The trial will also assess suitability of the outcome parameters, and test whether the data collection, symptom questionnaires, and used healthcare resources are suitable to describe the impact on patient-related outcomes. This study is registered at ClinicalTrials.gov (NCT04884165).

Digital Remote Monitoring Using an mHealth Solution for Survivors of Cancer: Protocol for a Pilot Observational Study.

Healthy lifestyle interventions have a positive impact on multiple disease trajectories, including cancer-related outcomes. Specifically, appropriate habitual physical activity, adequate sleep, and a regular wholesome diet are of paramount importance for the wellness and supportive care of survivors of cancer. Mobile health (mHealth) apps have the potential to support novel tailored lifestyle interventions. This observational pilot study aims to assess the feasibility of mHealth multidimensional longitudinal monitoring in survivors of cancer. The primary objective is to test the compliance (user engagement) with the monitoring solution. Secondary objectives include recording clinically relevant subjective and objective measures collected through the digital solution. This is a monocentric pilot study taking place in Bangor, Wales, United Kingdom. We plan to enroll up to 100 adult survivors of cancer not receiving toxic anticancer treatment, who will provide self-reported behavioral data recorded via a dedicated app and validated questionnaires and objective data automatically collected by a paired smartwatch over 16 weeks. The participants will continue with their normal routine surveillance care for their cancer. The primary end point is feasibility (eg, mHealth monitoring acceptability). Composite secondary end points include clinically relevant patient-reported outcome measures (eg, the Edmonton Symptom Assessment System score) and objective physiological measures (eg, step counts). This trial received a favorable ethical review in May 2023 (Integrated Research Application System 301068). This study is part of an array of pilots within a European Union funded project, entitled "GATEKEEPER," conducted at different sites across Europe and covering various chronic diseases. Study accrual is anticipated to commence in January 2024 and continue until June 2024. It is hypothesized that mHealth monitoring will be feasible in survivors of cancer; specifically, at least 50% (50/100) of the participants will engage with the app at least once a week in 8 of the 16 study weeks. In a population with potentially complex clinical needs, this pilot study will test the feasibility of multidimensional remote monitoring of patient-reported outcomes and physiological parameters. Satisfactory compliance with the use of the app and smartwatch, whether confirmed or infirmed through this study, will be propaedeutic to the development of innovative mHealth interventions in survivors of cancer. PRR1-10.2196/52957.

Immune regulation and blood–brain barrier permeability in cerebral small vessel disease: study protocol of the INflammation and Small Vessel Disease (INSVD) study – a multicentre prospective cohort study

IntroductionThe INflammation and Small Vessel Disease (INSVD) study aims to investigate whether peripheral inflammation, immune (dys)regulation and blood–brain barrier (BBB) permeability relate to disease progression in cerebral small vessel disease...

Developing a core outcome set for the health outcomes for children and adults with congenital oesophageal atresia and/or tracheo-oesophageal fistula: OCELOT task group study protocol

IntroductionHeterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions...

Team Around the Patient: multi-professional opportunities to support care delivery in hospitals.

Background: Demands on healthcare are outstripping the resources available. Many organisations are struggling to recruit sufficient registered nursing staff to maintain service delivery and are re-evaluating how safe, high quality, sustainable care could be provided. The concept “Team Around the Patient” being piloted in Hywel Dda University Health Board seeks to understand who can provide what care outside of traditional workforce models. The objective of this study is to examine perceptions of key health board stakeholders of the Team Around the Patient model of care and establish research priorities, and to design and test a workforce analysis model to test the implementation of Team Around the Patient. The model will be designed for use in adult, acute inpatient hospital wards.&#x0D; Methods: Before implementing the Team Around the Patient on select adult surgical and medical wards semi structured interviews were undertaken with key health board stakeholders to gather their understandings and perspectives on the concept, and create a working definition. A purposive approach was taken to engage a range of professional opinions including corporate and operational nursing, patient experience, allied health professionals, workforce and operational development. Interview topics included opportunities, quality indicators, barriers and enablers and organisational impacts. Ethical approval was provided by Swansea University and through The Integrated Research Application System (IRAS). Interviews were recorded, transcribed and thematically analysed. &#x0D; Results: In total 15 participants were interviewed. High level findings show support for the concept, with many participants identifying the potential new roles to be included. Key quality indicators such as inpatient falls, medication errors, pressure damage, length of stay, complaints and staff experience were identified as being important measures for this concept. Challenges associated with introducing new roles were mainly associated with workforce culture, delegation and finance. &#x0D; Conclusion: The results indicate overall support for “Team around the Patient” as a model of care which will help to alleviate issues surrounding skill shortages, while introducing more collaborative, inter-professional working. Further research is underway to gain wider perspectives of the concept from national and international experts in the fields of health care, academia and policy makers. The next stage of the research will include observational studies of health care delivery in practice to test the model of workforce analysis. The aim will be to identify opportunities for non-nursing staff groups to support care delivery where a gap in practice, or inefficiencies in the timely delivery of care, has been identified.

Techniques to increase lumbar puncture success in newborn babies: the NeoCLEAR RCT.

Lumbar puncture is an essential tool for diagnosing meningitis. Neonatal lumbar puncture, although frequently performed, has low success rates (50-60%). Standard technique includes lying infants on their side and removing the stylet 'late', that is, after the needle is thought to have entered the cerebrospinal fluid. Modifications to this technique include holding infants in the sitting position and removing the stylet 'early', that is, following transection of the skin. To the best of our knowledge, modified techniques have not previously been tested in adequately powered trials. The aim of the Neonatal Champagne Lumbar punctures Every time - An RCT (NeoCLEAR) trial was to compare two modifications to standard lumbar puncture technique, that is, use of the lying position rather than the sitting position and of 'early' rather than 'late' stylet removal, in terms of success rates and short-term clinical, resource and safety outcomes. This was a multicentre 2 × 2 factorial pragmatic non-blinded randomised controlled trial. Infants requiring lumbar puncture (with a working weight ≥ 1000 g and corrected gestational age from 27+0 to 44+0 weeks), and whose parents provided written consent, were randomised by web-based allocation to lumbar puncture (1) in the sitting or lying position and (2) with early or late stylet removal. The trial was powered to detect a 10% absolute risk difference in the primary outcome, that is, the percentage of infants with a successful lumbar puncture (cerebrospinal fluid containing < 10,000 red cells/mm3). The primary outcome was analysed by modified intention to treat. Of 1082 infants randomised (sitting with early stylet removal, n = 275; sitting with late stylet removal, n = 271; lying with early stylet removal, n = 274; lying with late stylet removal, n = 262), 1076 were followed up until discharge. Most infants were term born (950/1076, 88.3%) and were aged < 3 days (936/1076, 87.0%) with a working weight > 2.5 kg (971/1076, 90.2%). Baseline characteristics were balanced across groups. In terms of the primary outcome, the sitting position was significantly more successful than lying [346/543 (63.7%) vs. 307/533 (57.6%), adjusted risk ratio 1.10 (95% confidence interval 1.01 to 1.21); p = 0.029; number needed to treat = 16 (95% confidence interval 9 to 134)]. There was no significant difference in the primary outcome between early stylet removal and late stylet removal [338/545 (62.0%) vs. 315/531 (59.3%), adjusted risk ratio 1.04 (95% confidence interval 0.94 to 1.15); p = 0.447]. Resource consumption was similar in all groups, and all techniques were well tolerated and safe. This trial predominantly recruited term-born infants who were < 3 days old, with working weights > 2.5 kg. The impact of practitioners' seniority and previous experience of different lumbar puncture techniques was not investigated. Limited data on resource use were captured, and parent/practitioner preferences were not assessed. Lumbar puncture success rate was higher with infants in the sitting position but was not affected by timing of stylet removal. Lumbar puncture is a safe, well-tolerated and simple technique without additional cost, and is easily learned and applied. The results support a paradigm shift towards sitting technique as the standard position for neonatal lumbar puncture, especially for term-born infants during the first 3 days of life. The superiority of the sitting lumbar puncture technique should be tested in larger populations of premature infants, in those aged > 3 days and outside neonatal care settings. The effect of operators' previous practice and the impact on family experience also require further investigation, alongside in-depth analyses of healthcare resource utilisation. Future studies should also investigate other factors affecting lumbar puncture success, including further modifications to standard technique. This trial is registered as ISRCTN14040914 and as Integrated Research Application System registration 223737. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/188/106) and is published in full in Health Technology Assessment; Vol. 27, No. 33. See the NIHR Funding and Awards website for further award information.

Investigating mortality and morbidity associated with UrINary incontinence during Older Womens Secondary Care Admissions and exploring nurses experiences of delivering related care (U-INconti): a mixed methods research protocol

IntroductionUrinary incontinence (UI) is associated with increasing age and is more frequently experienced by women. Despite 40% prevalence in the community, little is known about the prevalence/incidence of UI in...

Evaluation of a novel, multicomponent anxiety management programme for people with intellectual disability: protocol for a mixed-methods, quasi-experimental feasibility study

IntroductionStudies have shown some benefits to single approaches to psychological therapies for the treatment of anxiety in people with intellectual disability such as modified cognitive–behavioural therapy and mindfulness. To our...

Group cognitive stimulation therapy versus usual care for people with intellectual disabilities and dementia (CST-IDD) in the UK: protocol for a mixed-methods feasibility randomised controlled trial

IntroductionThe prevalence of dementia is almost five times higher in people with intellectual disabilities compared with the general population. However, evidence-based treatments for this population are lacking, as most randomised...

Can artificial intelligence accelerate the diagnosis of inherited retinal diseases? Protocol for a data-only retrospective cohort study (Eye2Gene)

IntroductionInherited retinal diseases (IRD) are a leading cause of visual impairment and blindness in the working age population. Mutations in over 300 genes have been found to be associated with...

FUTURE-GB: functional and ultrasound-guided resection of glioblastoma – a two-stage randomised control trial

IntroductionSurgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA)....

Intensive support teams for adults with intellectual disabilities displaying challenging behaviour: the IST-ID mixed-methods study

Background National policy recommends intensive support teams for all areas of England for adults with intellectual disabilities who display challenging behaviour. However, to the best of our knowledge, there has not been a systematic evaluation of intensive support teams to date. Objectives Our objectives were to identify and describe the geographical distribution and characteristics of intensive support teams in England; to create a typology of intensive support teams; to investigate clinical and cost outcomes of intensive support team models and factors associated with those outcomes; and to explore professionals’, service users’ and carers’ experiences and describe the wider system context in which they operate. Design This was a two-phase mixed-methods study. In phase 1, a national survey examined the intensive support team models in operation in England. In phase 2, an observational study of adults with intellectual disabilities investigated the clinical effectiveness and cost-effectiveness of the two intensive support team models. Semistructured interviews with intensive support team managers and professionals, carers, and adults with intellectual disabilities explored their experiences of intensive support team care. In parallel, we examined service-level outcomes related to the function of intensive support teams. Setting Phase 1 included 80 intensive support teams serving 242 community intellectual disability services in England. Phase 2 included 21 intensive support teams, half of which were in the enhanced intensive support teams model and half of which were in the independent model. Participants In phase 1, a total of 73 intensive support team managers provided data. In phase 2, a total of 226 participants with intellectual disabilities from 21 intensive support teams (enhanced: teams, n = 11; participants, n = 115; independent: teams, n = 10; participants, n = 111) were enrolled in the study. A total of 42 stakeholders were interviewed. Main outcome measure The main outcome measure was the Aberrant Behaviour Checklist-Community, version 2, total score. Additional data sources were the carer and self-reported questionnaires, qualitative interviews and focus groups. Results Two intensive support team models were identified in England – enhanced and independent. Challenging behaviour at 9 months was reduced in both intensive support team models (β 3.08, 95% confidence interval –7.32 to 13.48; p = 0.561), but the observed Aberrant Behaviour Checklist-Community, version 2, score reduction appeared larger in the independent model than in the enhanced model (21% vs. 13%, respectively). No statistically significant differences were found in the secondary outcomes [Psychiatric Assessment Schedule for Adults with Developmental Disabilities Clinical Interview organic condition (odds ratio 1.09, 95% confidence interval 0.39 to 3.02), affective or neurotic disorder (odds ratio 0.91, 95% confidence interval 0.32 to 2.59), or psychotic disorder score (odds ratio 1.08, 95% confidence interval 0.21 to 5.50); risk score (β 1.12, 95% confidence interval –0.44 to 2.68); or quality of life questionnaire score (β –2.63, 95% confidence interval –5.65 to 0.40)]. Similarly, no differences were observed between models in relation to cost-effectiveness (health and social care costs mean difference £3409.95, 95% confidence interval –£9957.92 to £4039.89; societal costs mean difference –£4712.30, 95% confidence interval –£11,124.85 to £2106.36). The experiences of stakeholders did not differ between the intensive support team models, with carers and adults with intellectual disabilities valuing service accessibility, person-centred care and engagement. All stakeholders reported a range of barriers to intensive support team care. Service-level data and the operational policies from intensive support teams showed variation in organisational function and the roles of intensive support teams. The most commonly delivered intervention was positive behaviour support. Conclusions The study describes the operation of intensive support teams in England and identified two distinct models. We did not find advantages or disadvantages associated with clinical outcomes between models, nor did we find cost differences. On this basis, we recommend that local services decide which model best suits their circumstances. Limitations This was not a randomised controlled trial. It is possible that confounding factors have not been controlled for as there was no matching between intensive support teams. Last, there was no comparison with usual care. Future work There is need to develop model fidelity and investigate clinical effectiveness and cost-effectiveness in a randomised controlled evaluation of intensive support teams against treatment as usual. Study registration This study is registered as ClinicalTrials.gov NCT03586375, Integrated Research Application System (IRAS) 239820 and National Institute for Health and Care Research (NIHR) Central Portfolio Management System (CPMS) 38554. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 33. See the NIHR Journals Library website for further project information.

Evaluation of water fluoridation scheme in Cumbria: the CATFISH prospective longitudinal cohort study

Background Water fluoridation was introduced in the UK against a background of high dental decay within the population. Levels of decay have dramatically reduced over the last 40 years following widespread use of fluoride toothpaste. Objective The aim of the CATFISH (Cumbrian Assessment of Teeth a Fluoride Intervention Study for Health) study was to address the question of whether or not the addition of fluoride to community drinking water, in a contemporary population, lead to a reduction in the number of children with caries and, if so, is this reduction cost-effective? Design A longitudinal prospective cohort design was used in two distinct recruited populations: (1) a birth cohort to assess systemic and topical effects of water fluoridation and (2) an older school cohort to assess the topical effects of drinking fluoridated water. Setting The study was conducted in Cumbria, UK. Broadly, the intervention group (i.e. individuals receiving fluoridated drinking water) were from the west of Cumbria and the control group were from the east of Cumbria. Participants Children who were lifetime residents of Cumbria were recruited. For the birth cohort, children were recruited at birth (2014–15), and followed until age 5 years. For the older school cohort, children were recruited at age 5 years (2013–14) and followed until the age of 11 years. Intervention The provision of a ‘reintroduced fluoridated water scheme’. Main outcome measures The primary outcome measure was the presence or absence of decay into dentine in the primary teeth (birth cohort) and permanent teeth (older school cohort). The cost per quality-adjusted life-year was also assessed. Results In the birth cohort (n = 1444), 17.4% of children in the intervention group had decay into dentine, compared with 21.4% of children in the control group. The evidence, after adjusting for deprivation, age and sex, with an adjusted odds ratio of 0.74 (95% confidence interval 0.56 to 0.98), suggested that water fluoridation was likely to have a modest beneficial effect. There was insufficient evidence of difference in the presence of decay in children in the older school cohort (n = 1192), with 19.1% of children in the intervention group having decay into dentine, compared with 21.9% of children in the control group (adjusted odds ratio 0.80, 95% confidence interval 0.58 to 1.09). The intervention was found to be likely to be cost-effective for both the birth cohort and the older school cohort at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. There was no significant difference in the performance of water fluoridation on caries experience across deprivation quintiles. Conclusions The prevalence of caries and the impact of water fluoridation was much smaller than previous studies have reported. The intervention was effective in the birth cohort group; however, the importance of the modest absolute reduction in caries (into dentine) needs to be considered against the use of other dental caries preventative measures. Longer-term follow-up will be required to fully understand the balance of benefits and potential risks (e.g. fluorosis) of water fluoridation in contemporary low-caries populations. Limitations The low response rates to the questionnaires reduced their value for generalisations. The observed numbers of children with decay and the postulated differences between the groups were far smaller than anticipated and, consequently, the power of the study was affected (i.e. increasing the uncertainty indicated in the confidence intervals). Study registration This study is registered as Integrated Research Application System 131824 and 149278. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 11. See the NIHR Journals Library website for further project information.

Health and Lifestyle of Patients with Mesothelioma: Protocol for the Help-Meso Study

Patients with mesothelioma (PwM) have a poor prognosis and are at risk of adverse health outcomes and poor health-related quality of life. Sarcopenia and malnutrition are important prognostic factors for cancer patients and can be partially reversed with adequate nutrition and physical activity/exercise. There is a limited evidence base about the nutritional status of PwM, the understanding of which might potentially influence interventions in PwM. The primary aim of the Help-Meso (Health and Lifestyle of PwM) study is to describe the nutrition, appetite, physical activity and attitude towards lifestyle interventions of PwM. Patients, informal carers and health professionals will be invited to participate in semi-structured interviews and thematic analysis will be performed. The secondary aim of Help-Meso is to assess the feasibility of nutritional screening of PwM via a validated quantitative tool (Malnutrition Universal Screening Tool). The findings from this study will provide an understanding of the health and lifestyle of PwM and the corresponding attitudes of their informal carers and healthcare providers. This information will inform the design of future targeted interventions to improve the nutrition, quality of life of PwM and outcomes. The study has Research Ethics Committee (REC) and Health Research Authority approvals obtained from Wales REC7 (Integrated Research Application System (IRAS) project ID 287193).

Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study

IntroductionDigital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field,...

Prevention of gestational diabetes in pregnant women with obesity: protocol for a pilot randomised controlled trial

BackgroundObesity in pregnancy increases the risk of gestational diabetes mellitus (GDM) and associated adverse outcomes. Despite metabolic differences, all pregnant women with obesity are considered to have the same risk of developing GDM. Improved risk stratification is required to enable targeted intervention in women with obesity who would benefit the most. The aim of this study is to identify pregnant women with obesity at higher risk of developing GDM and, in a pilot randomised controlled trial (RCT), test feasibility and assess the efficacy of a lifestyle intervention and/or metformin to improve glycaemic control.MethodsWomen aged 18 years or older with a singleton pregnancy and body mass index (BMI) ≥ 30kg/m2 will be recruited from one maternity unit in London, UK. The risk of GDM will be assessed using a multivariable GDM prediction model combining maternal age, mid-arm circumference, systolic blood pressure, glucose, triglycerides and HbA1c. Women identified at a higher risk of developing GDM will be randomly allocated to one of two intervention groups (lifestyle advice with or without metformin) or standard antenatal care. The primary feasibility outcomes are study recruitment, retention rate and intervention adherence and to collect information needed for the sample size calculation for the definitive trial. A process evaluation will assess the acceptability of study processes and procedures to women. Secondary patient-centred outcomes include a reduction in mean glucose/24h of 0.5mmol/l as assessed by continuous glucose monitoring and changes in a targeted maternal metabolome, dietary intake and physical activity. A sample of 60 high-risk women is required.DiscussionEarly risk stratification of GDM in pregnant women with obesity and targeted intervention using lifestyle advice with or without metformin could improve glucose tolerance compared to standard antenatal care. The results from this feasibility study will inform a larger adequately powered RCT should the intervention show trends for potential effectiveness.Trial registrationThis study has been approved by the NHS Research Ethics Committee (UK IRAS integrated research application system; reference 18/LO/1500). EudraCT number 2018-000003-16.

Rationale and design of the brain magnetic resonance imaging protocol for FutureMS: a longitudinal multi-centre study of newly diagnosed patients with relapsing-remitting multiple sclerosis in Scotland.

Introduction: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically and is notably high in Scotland. Disease trajectory varies significantly between individuals and the causes for this are largely unclear. Biomarkers predictive of disease course are urgently needed to allow improved stratification for current disease modifying therapies and future targeted treatments aimed at neuroprotection and remyelination. Magnetic resonance imaging (MRI) can detect disease activity and underlying damage non-invasively in vivo at the micro and macrostructural level. FutureMS is a prospective Scottish longitudinal multi-centre cohort study, which focuses on deeply phenotyping patients with recently diagnosed relapsing-remitting MS (RRMS). Neuroimaging is a central component of the study and provides two main primary endpoints for disease activity and neurodegeneration. This paper provides an overview of MRI data acquisition, management and processing in FutureMS. FutureMS is registered with the Integrated Research Application System (IRAS, UK) under reference number 169955. Methods and analysis: MRI is performed at baseline (N=431) and 1-year follow-up, in Dundee, Glasgow and Edinburgh (3T Siemens) and in Aberdeen (3T Philips), and managed and processed in Edinburgh. The core structural MRI protocol comprises T1-weighted, T2-weighted, FLAIR and proton density images. Primary imaging outcome measures are new/enlarging white matter lesions (WML) and reduction in brain volume over one year. Secondary imaging outcome measures comprise WML volume as an additional quantitative structural MRI measure, rim lesions on susceptibility-weighted imaging, and microstructural MRI measures, including diffusion tensor imaging and neurite orientation dispersion and density imaging metrics, relaxometry, magnetisation transfer (MT) ratio, MT saturation and derived g-ratio measures. Conclusions: FutureMS aims to reduce uncertainty around disease course and allow for targeted treatment in RRMS by exploring the role of conventional and advanced MRI measures as biomarkers of disease severity and progression in a large population of RRMS patients in Scotland.

Co-ordinated care for people affected by rare diseases: the CONCORD mixed-methods study

Background A condition is defined as rare if it affects fewer than 1 in 2000 people in the general population. Limited evidence suggests that care is poorly co-ordinated for people affected by rare conditions. Objectives To investigate if and how care of people with rare conditions is co-ordinated in the UK, and how people affected by rare conditions would like care to be co-ordinated. Design A mixed-methods study comprising (1) a scoping review to develop a definition of co-ordinated care and identify components of co-ordinated care (n = 154 studies); (2) an exploratory qualitative interview study to understand the impact of a lack of co-ordinated care (n = 15 participants); (3) a national survey among people affected by rare conditions of experiences of care co-ordination (n = 1457 participants); (4) a discrete choice experiment of preferences for co-ordination (n = 996 participants); (5) the development of a taxonomy of co-ordinated care for rare conditions (n = 79 participants); and (6) a review of costs of providing co-ordinated care. Setting Health services for people affected by rare conditions, including gatekeeping to social care provision and third-sector care. Participants Adult patients with rare conditions, parents/carers of children or adults with rare conditions and health-care professionals (e.g. doctors, nurses and allied health professionals) involved in the care of people with rare conditions. No limits were set on the rare conditions included or where people live in the UK. Participants were sampled from patient and provider networks and organisations. Results A definition of co-ordinated care for rare conditions was developed. Care for people affected by rare diseases was found to be not well co-ordinated. For example, only 12% of 760 adult patients affected by a rare disease reported that they had a formal care co-ordinator, 32% reported that they attended a specialist centre and 10% reported that they had a care plan. Patients, parents/carers and health-care professionals all would like care to be better co-ordinated, with some differences in preferences reported by patients and parents/carers and those reported by health-care professionals. Our taxonomy of care co-ordination for rare conditions outlined six domains: (1) ways of organising care, (2) ways of organising teams, (3) responsibilities, (4) how often care appointments and co-ordination take place, (5) access to records and (6) mode of communication. Limitations It was not possible to capture the experiences of people affected by every rare condition. Our sampling strategy in the study may have been biased if study participants were systematically different from the population affected by rare conditions. The cost analysis was limited. Conclusions There is evidence of a lack of co-ordinated care for people affected by rare diseases. This can have a negative impact on the physical and mental health of patients and families, and their financial well-being. Future work Further research would be beneficial to develop feasible, clinically effective and cost-effective models of care co-ordination, using the taxonomy developed in this study. Study registration This study is registered as NIHR Clinical Research Network Portfolio reference number 41132, Research Registry reference number research registry6351 and Integrated Research Application System reference number 254400. Funding This project was funded by the National Institute for Health Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 5. See the NIHR Journals Library website for further project information.

Precarious employment and self-reported health: a cross-sectional analysis

BackgroundAssociations between precarious employment and poorer health outcomes are well documented. However, which components of this multidimensional construct are associated with adverse health is unknown. The primary aim of this study was to examine associations between the different domains of precarious employment and self-reported health. MethodsWe used data from 1016 respondents (634 women and 382) to the COVID-19 Employment and Health in Wales Study, a nationally representative household survey of the so-called working-age population (18–64 years). The study was done on May 25 and June 22, 2020, using a push-to-web approach (letter invitation to an online survey; response rate: 6·9%). Respondents provided details of their main job in February, 2020, including information on their contract type and different domains of employment precariousness as assessed by the Employment Precariousness Scale. These domains were: temporariness (length of time working under temporary arrangements); disempowerment (control over work schedule); vulnerability (perceived treatment at work); wages (pay and ability to afford basic and unexpected expenses); and rights. Health measures were self-reported pre-existing health conditions, general health, and mental wellbeing (calculated with the Short Warwick Edinburgh Mental Wellbeing Score). To examine associations between domains of precarious employment and health, chi-squared analysis and multinomial logistic regression (adjusted for sex, age, deprivation, contract type, and self-reported health) were done. The Health Research Authority approved this study (Integrated Research Application System reference: 282223). FindingsThe domains of precarious employment that showed the strongest associations with poor health, independently of contract type, were high vulnerability precariousness (associated with pre-existing condition: adjusted odds ratio 2·44 [95% CI 1·32–4·49], p=0·004; poor general health: 2·35 [1·23–4·51], p=0·010; low mental wellbeing: 2·74 [1·30–5·75], p=0·008); high wage precariousness (associated with pre-existing condition: 1·66 [1·08–2·57], p=0·022; poor general health: 2·21 [1·33–3·69], p=0·002; low mental wellbeing: 3·16 [1·54–6·45], p=0·002); and moderate wage precariousness (associated with pre-existing condition: 1·68 [1·20–2·36], p=0·003; and low mental wellbeing: 2·25 [1·19–4·29], p=0·013). InterpretationBefore the COVID-19 pandemic, tackling poverty in those in work and perceived fair treatment in the workplace appear to have been important in improving the health of the working-age population of the UK. Longitudinal analyses are required to establish the effect of the pandemic on employment conditions and on whether these domains remain adversely associated with health. FundingNo funding to declare.