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Abstract Background Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT). Methods We undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019–2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events. Results At two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported. Conclusion Staff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned. Trial Registration ISRCTN13232859 (Registered 16/02/2018).

Background Opioids kill more people than any other drug. Naloxone is an opioid antagonist which can be distributed in take-home ‘kits’ for peer administration (take-home naloxone). Aim To determine the feasibility of carrying out a definitive randomised controlled trial of take-home naloxone in emergency settings. Design We used Welsh routine data (2015–21) to test the feasibility of developing a discriminant function to identify people at high risk of fatal opioid overdose. We carried out a cluster randomised controlled trial and qualitative study to examine experiences of service users and providers. We assessed feasibility of intervention and trial methods against predetermined progression criteria related to: site sign-up, staff trained, identification of eligible patients, proportion given kits, identification of people who died of opioid poisoning, data linkage and retrieval of outcomes. Setting This study was carried out in the emergency environment; sites comprised an emergency department and associated ambulance service catchment area. Participants At intervention sites, we invited emergency department clinicians and paramedics to participate. We recruited adult patients who arrived at the emergency department or were attended to by ambulance paramedics for a problem related to opioid use with capacity to consent to receiving the take-home naloxone and related training. Interventions Usual care comprised basic life support plus naloxone by paramedics or emergency department staff. The take-home naloxone intervention was offered in addition to usual care, with guidance for recipients on basic life support, the importance of calling the emergency services, duration of effect, safety and legality of naloxone administration. Results Discriminant function With low numbers of opioid-related deaths (1105/3,227,396) and a high proportion having no contact with health services in the year before death, the predictive link between death and opioid-related healthcare events was weak. Logistic regression models indicated we would need to monitor one-third of the population to capture 75% of the decedents from opioid overdose in 1-year follow-up. Randomised controlled trial Four sites participated in the trial and 299 of 687 (44%) eligible clinical staff were trained. Sixty take-home naloxone kits were supplied to patients during 1-year recruitment. Eligible patients were not offered take-home naloxone kits 164 times: ‘forgot’ (n = 136); ‘too busy’ (n = 15); suspected intentional overdose (n = 3). Qualitative interviews Service users had high levels of knowledge about take-home naloxone. They were supportive of the intervention but noted concerns about opioid withdrawal and resistance to attending hospital for an overdose. Service providers were positive about the intervention but reported barriers including difficulty with consenting and training high-risk opioid users. Health economics We were able to calculate costs to train staff at three sites (£40 per AS and £17 in Site 1 ED). No adverse events were reported. Progression criteria were not met – fewer than 50% of eligible staff were trained, fewer than 50% of eligible patients received the intervention and outcomes were not retrieved within reasonable timescales. Future work The take-home naloxone intervention needs to be developed and evaluated in emergency care settings, with appropriate methods. Limitations The Take-home naloxone Intervention Multicentre Emergency setting study was interrupted by coronavirus disease. Conclusions This study did not meet progression criteria for intervention or trial methods feasibility, so outcomes were not followed up and a fully powered trial is not planned. Trial registration This trial is registered as ISRCTN13232859. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/91/04) and is published in full in Health Technology Assessment; Vol. 28, No. 74. See the NIHR Funding and Awards website for further award information. Plain language summary Emergency ambulance staff and doctors in the emergency department regularly administer naloxone to people who have overdosed, reversing effects of the opioid – so-called ‘take-home naloxone’ – to administer to others in an emergency. We don’t know whether take-home naloxone saves lives. We carried out this feasibility study to see whether: we could identify a high-risk population to include in a trial to determine whether take-home naloxone reduces deaths from overdose ambulance paramedics and emergency department staff could be trained, and would then give out take-home naloxone kits to drug users they see. We included four areas in the study. We randomly selected two for distribution of take-home naloxone to patients at risk of or following an overdose by emergency department clinicians and local ambulance paramedics. We attempted to identify people at high risk of death from opioid overdose. We collected data about patients that were eligible and received take-home naloxone in the two intervention areas. We carried out interviews to find out about the views of patients and staff who gave out the kits. At the start, we agreed criteria that should be met for us to recommend that a full evaluation be carried out. We could not reliably identify people at high risk of death from opioid overdose, as deaths were rare in the population, and previous health service usage was variable. Less than half of eligible staff were trained to supply take-home naloxone (299/687, 44%), and less than half of eligible patients were given take-home naloxone (60/277, 21.7%) over 1 year. Patients were not offered take-home naloxone because staff forgot, were too busy or suspected an intentional overdose. Other patients left before receiving a kit. Service users liked the idea of take-home naloxone kits being provided in the emergency setting but reported resistance to attending hospital following an overdose. Service providers were supportive of providing take-home naloxone in the emergency setting but reported challenges in consent and training. Conclusion This study found that it was not feasible to deliver or evaluate this form of take-home naloxone, using this study design, in emergency care. Scientific summary Parts of this summary have been reproduced from Jones M, Bell F, Benger J, Black S, Buykx P, Dixon S, et al. Protocol for Take-home naloxone In Multicentre Emergency (TIME) settings: feasibility study. Pilot Feasib Stud 2020;6(1):1–10. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text. Background Opioids, such as heroin, kill more people worldwide by overdose than any other type of drug, and death rates associated with opioid poisoning in the United Kingdom (UK) are at record levels. Naloxone is an opioid antagonist which can be distributed in ‘kits’ for administration by witnesses in an overdose emergency. This intervention is known as take-home naloxone (THN). We know that THN can save lives on an individual level, but there is currently limited evidence about the effectiveness of THN distribution on an aggregate level, in specialist drug service settings or in emergency service (ES) settings. Notably, we do not know whether THN kits reduce deaths from opioid overdose in at-risk populations, if there are unforeseen harms associated with THN distribution or if THN is cost-effective. To address this research gap, we aimed to determine the feasibility of a fully powered cluster randomised controlled trial (RCT) of THN distribution in emergency settings. Aim To determine the feasibility of carrying out a definitive RCT of THN in emergency settings. Objectives To determine: the best form of THN kit, training and delivery whether a trial clustered by emergency department (ED) catchment area and the associated ambulance service (AS) is deliverable, as assessed against predefined progression criteria related to intervention, trial design and methods. Design We assessed feasibility of intervention and trial methods based upon the following predetermined progression criteria. Intervention feasibility Sign-up of four sites, including ≥ 50% eligible staff to complete training in delivering the intervention at each intervention site. Identification of ≥ 75% of people who have presented to ED or AS with opioid overdose or an opioid use-related problem over a 12-month period. THN kits issued to ≥ 50% eligible patients over a 12-month period at intervention sites. Serious adverse event rate [to be defined in agreement with Data Monitoring and Ethics Committee (DMEC)] of no more than 10% difference in intervention sites to control sites at the conclusion of recruitment. Trial methods feasibility Identification and inclusion for follow-up of ≥ 75% of people who died of opioid poisoning in the following year in the study areas according to Office of National Statistics (ONS) mortality data (previous ONS data suggest between 140 and 180 such deaths across the 4 participating sites during the study period). Matching and data linkage in ≥ 90% of cases not dissented at the conclusion of quantitative data collection. Retrieval of primary and secondary outcomes from National Health Service (NHS) Digital and National Welsh Informatics Service within 6 months of projected timeline. As the intervention tested is for administration to recipients of the THN kits and peers who may suffer an overdose, we needed to find a way to identify cohorts to include in outcome comparisons. We therefore analysed Welsh routine data to test the feasibility of developing a discriminant function to identify a high-risk population for fatal opioid overdose. We scoped anonymised routine retrospective data from 1 January 2015 to 30 November 2021, sourced from the Welsh Demographic Service Dataset (WDSD) to define the study population. To categorise death associated with an opioid overdose, the annual district death extract (ADDE) dataset was used in conjunction with the WDSD to calculate an individual-level study end date. Finally, we considered critical care, ED and hospital admissions as well as substance misuse treatment for the 36 months up to the end of the study period. We carried out a RCT clustered by site in the emergency environment with a qualitative study to examine processes of implementation, patient safety, costs of training NHS staff and experiences of service users and providers. Two intervention sites (paired ED and local AS catchment area) were randomly selected from the four participating sites. Usual practice was continued in the other two sites, acting as controls. Alongside the RCT, we collected qualitative data via semistructured interviews with service users from substance use treatment centres and third-sector organisations. The interview questions were guided by literature around opioid overdose experience and emergency naloxone use, with the aim to explore how opioid users interact with the knowledge, behaviour and attitudes towards the use of THN kits and training to use the kits. Focus groups and interviews with service providers (paramedics and ED clinical staff) were conducted to discuss barriers in the provision of THN in the emergency setting as well as facilitators to this implementation. We assessed the feasibility of collecting costs associated with THN provision in the emergency setting by measuring the health service contacts and incorporating healthcare resource groups (HRGs) into the analysis to produce an overall cost. Setting This feasibility study was carried out in the emergency care environment, across study sites each centred on a receiving ED and defined geographically as the local AS catchment area for that receiving ED. Participants At intervention sites, we invited ED clinicians and paramedics to participate in the trial and recruited adult patients who arrived at the ED or were attended by ambulance paramedics for a problem related to opioid use with capacity to consent to receiving the THN and related training. Participants were to be identified for outcome comparison by application of the discriminant function, if completed, to the study site general populations. Interventions Usual care comprised administration of basic life support plus naloxone by paramedics or ED staff. The THN intervention was offered in addition to usual care and included a multi dose THN kit (Prenoxad) containing 2 mg naloxone hydrochloride 1 mg/1 ml solution for intramuscular (IM) injection, and instructions on the correct administration of the naloxone dose. Recipients also received guidance on: BLS; the importance of calling the ES; duration of effect; the safety of naloxone in terms of adverse events and overdose; and the legality of bystander administration of naloxone. Results TABLE S1Assessment against preset progression criteria Criteria Achieved Criteria met Sign-up of four sites, including ≥ 50% eligible staff to complete training in delivering the intervention at each intervention site Site 1: ED trained 81.1%, AS trained 54% of eligible staffSite 2: ED trained 8.1%, AS trained 33.8% of eligible staff No Identification of ≥ 75% of people who have presented to ED or AS with opioid overdose or an opioid use-related problem over a 12-month period Unable to assess Not known THN kits issued to ≥ 50% eligible patients over a 12-month period at intervention sites 21.7% of eligible patients were given kits No Serious adverse event rate (to be defined in agreement with the DMEC) of no more than 10% difference in intervention sites to control sites at the conclusion of recruitment No serious adverse events were reported Yes Identification and inclusion for follow-up of ≥ 75% of people who died of opioid poisoning in the following year in the study areas according to ONS mortality data (previous ONS data suggest between 140 and 180 such deaths across the four participating sites during the study period) We were able to identify decedents from opioid poisoning in Wales but were unable to produce a discriminant function which included this group in a sufficiently small section of the general population, or to test these methods in a second population No Matching and data linkage in ≥ 90% of cases not dissented at the conclusion of quantitative data collection Due to significant delays in permissions processes for routine- linked data retrieval from NHS Digital, and low administration of THN kits, we did not attempt to match and link records for patients recruited to the trial No Retrieval of routinely recorded primary and secondary outcomes from national repositories within six-months of projected timeline Again, due to significant delays in permissions processes for routine- linked data retrieval, and low administration of THN kits, we did not attempt to retrieve routinely recorded primary and secondary outcomes No Discriminant function With low numbers of opioid-related deaths (1105/3,227,396) and a high proportion of them having no contact with health services in the year before death, the predictive link between death and opioid-related healthcare events was weak. Logistic regression models indicated we would need to monitor one-third of the population to capture 75% of the decedents from opioid overdose in 1-year follow-up. RCT In total, 299 of 687 (43.5%) eligible staff were trained to supply THN kits to eligible patients at the two sites (Site 1: ED n = 107, AS n = 121; Site 2: ED n = 25, AS n = 46). Sixty THN kits were supplied to eligible patients during the recruitment period (Site 1: ED n = 36, AS n = 4; Site 2: ED n = 16, AS n = 4). Eligible patients were recorded as not being offered THN kits 164 times, with reasons reported for not offering eligible patients kits: staff forgot (n = 136); staff too busy (n = 15); and suspected intentional overdose (n = 3). Staff recorded 626 people as being considered for inclusion but found not to be eligible, with reasons listed as: uncooperative including being abusive towards staff (n = 55); lack of capacity (n = 35); reduced consciousness level (n = 41); patient in custody (n = 21); and patient absconded (n = 161). Qualitative interviews Service users had high levels of knowledge about THN, with variable previous access to kits. They generally supported the provision of THN kits and training in the emergency setting and felt that it should be expanded further to chemists and needle exchanges. They also noted the importance of including loved ones in training and felt that this gave them a sense of empowerment and motivation to help others in an overdose situation. They noted concerns with regards to opioid withdrawal and resistance to attending hospital for an overdose. The service users reported that the provision of THN kits and training to friends and family of opioid users would possibly be more beneficial and believed that incorporating THN provision into normal practice would help mitigate some of these barriers. Interviews and focus groups with service providers found that they were supportive about the provision of THN kits and training in the emergency setting. However, they also reported barriers including difficulties consenting and training opioid users, a high turnover of staff impacting the cascade of the intervention as well as negative attitudes towards the patient group and the coronavirus disease 2019 (COVID-19) pandemic. No adverse events were reported. Conclusion This study did not meet progression criteria for intervention or trial methods feasibility, so outcomes were not followed up and a fully powered trial is not planned. There does appear to be appetite for THN kit provision and training in the emergency setting. We conclude that the THN intervention as defined and administered in the Take-home naloxone Intervention Multicentre Emergency setting (TIME) study was not feasible and should not therefore go forward to full trial. However, there may be space for further development of this complex intervention in emergency care – for example, for protocols to allow administration to family and friends of opioid users; as well as methods for definition and identification of study cohorts for outcome comparisons. Trial registration This trial is registered as ISRCTN13232859. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/91/04) and is published in full in Health Technology Assessment; Vol. 28, No. 74. See the NIHR Funding and Awards website for further award information.

Introduction Research has found differences in processes and outcomes of care between people in ethnic minorities and White British populations in some clinical conditions, although findings have been mixed. The Building an understanding of Ethnic minority people’s Service Use Relating to Emergency care for injuries study is investigating differences in presentation, experience and health outcomes between people from ethnic minorities and White British people who seek emergency health care for injury. Objective Our aim was to consult with stakeholders to define measurable outcomes available in routine ambulance and emergency department data; to assess the appropriateness of existing outcome measures for ethnic minorities and White British people; and to identify any gaps. Method Clinicians, public contributors, researchers, people from the third sector, public health, healthcare inclusion were invited to join an online workshop to discuss routine outcomes. Results Twenty participants attended the stakeholder consultation, with only one being a public contributor, a limitation. Eleven were from a minority ethnic background and seven were female. The integrated list of outcomes included 25 items, combining routine outcomes from the Building an understanding of Ethnic minority people's Service Use Relating to Emergency care for injuries protocol and literature (n = 17) with additional outcomes (n = 8). Notably, the initial list lacked provisions for safeguarding referrals and cases of treatment refusal, which were new additions. Safety concerns arose due to the lack of safeguarding referrals, treatment refusal and self-discharge. Factors such as pre-existing health conditions, injury location and experiences of discrimination were identified as possible influences on care quality and waiting times for ethnic minority patients. Conclusion Although the number of stakeholders taking part in our consultation was low, their participation identified outcomes not found in routine data, supporting the adoption of a mixed-methods approach to answer our research questions. A future consultation could look to include more public members and wider range of clinicians including those who work in safeguarding and rehabilitation services. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132744. Plain language summary Research has shown that people from ethnic minorities often have less favourable healthcare experiences and outcomes than white British people. Our BE SURE study aims to establish whether there are differences between these groups and whether this can be seen in routinely available health outcome data or through patients’ own words through questionnaires and interviews. Before starting data collection, we wanted to consult with people who may deliver or receive emergency health care for injuries, about what routinely available healthcare measures and outcomes we should include in the study. Twenty stakeholders joined the meeting: clinicians, paramedics, researchers and representatives from healthcare organisations, the third sector and a public contributor. We firstly explained what the study was about, and what we hoped to achieve during the online consultation meeting. We presented examples of measurable outcomes that we had included in our original research proposal for injuries. We broke into small groups to discuss these outcome measures and identify gaps. We also asked for comments and suggestions to check the appropriateness of these measures. Participants agreed that the proposed measures were mostly appropriate; these included tests, treatments, waiting times, referrals to other doctors, leaving the hospital against medical advice and time spent in the emergency department. They identified two new outcomes, which were safeguarding referrals and refusal of treatment. The final agreed list of outcomes was 25. Participants also discussed disparities in medication and treatments provided to ethnic minorities compared to white British people, such as pain relief. Additionally, they explored various factors that could affect care differently across these groups. For instance, ethnic minorities may experience discrimination, have distinct health issues or experience variations in the location, nature and severity of injuries. These factors could influence waiting times, pain management and overall quality of care.

Objectives To compare the patterns of multimorbidity between people with and without rheumatic and musculoskeletal diseases (RMDs) and to describe how these patterns change by age and sex over time, between 2010 and 2019.Participants 103 426 people with RMDs and 2.9 million comparators registered in 395 Wales general practices (GPs). Each patient with an RMD aged 0–100 years between January 2010 and December 2019 registered in Clinical Practice Research Welsh practices was matched with up to five comparators without an RMD, based on age, gender and GP code.Primary outcome measures The prevalence of 29 Elixhauser-defined comorbidities in people with RMDs and comparators categorised by age, gender and GP practices. Conditional logistic regression models were fitted to calculate differences (OR, 95% CI) in associations with comorbidities between cohorts.Results The most prevalent comorbidities were cardiovascular risk factors, hypertension and diabetes. Having an RMD diagnosis was associated with a significantly higher odds for many conditions including deficiency anaemia (OR 1.39, 95% CI (1.32 to 1.46)), hypothyroidism (OR 1.34, 95% CI (1.19 to 1.50)), pulmonary circulation disorders (OR 1.39, 95% CI 1.12 to 1.73) diabetes (OR 1.17, 95% CI (1.11 to 1.23)) and fluid and electrolyte disorders (OR 1.27, 95% CI (1.17 to 1.38)). RMDs have a higher proportion of multimorbidity (two or more conditions in addition to the RMD) compared with non-RMD group (81% and 73%, respectively in 2019) and the mean number of comorbidities was higher in women from the age of 25 and 50 in men than in non-RMDs group.Conclusion People with RMDs are approximately 1.5 times as likely to have multimorbidity as the general population and provide a high-risk group for targeted intervention studies. The individuals with RMDs experience a greater load of coexisting health conditions, which tend to manifest at earlier ages. This phenomenon is particularly pronounced among women. Additionally, there is an under-reporting of comorbidities in individuals with RMDs.

Background Emergency healthcare services are under intense pressure to meet increasing patient demands. Many patients presenting to emergency departments could be managed by general practitioners in general practitioner–emergency department service models. Objectives To evaluate the effectiveness, safety, patient experience and system implications of the different general practitioner–emergency department models. Design Mixed-methods realist evaluation. Methods Phase 1 (2017–8), to understand current practice: rapid realist literature review, national survey and follow-up key informant interviews, national stakeholder event and safety data analysis. Phase 2 (2018–21), to collect and analyse qualitative (observations, interviews) and quantitative data (time series analysis); cost–consequences analysis of routine data; and case site data for ‘marker condition’ analysis from a purposive sample of 13 case sites in England and Wales. Phase 3 (2021–2), to conduct mixed-methods analysis for programme theory and toolkit development. Results General practitioners commonly work in emergency departments, but delivery models vary widely in terms of the scope of the general practitioner role and the scale of the general practitioner service. We developed a taxonomy to describe general practitioner–emergency department service models (Integrated with the emergency department service, Parallel within the emergency department, Outside the emergency department on the hospital site) and present a programme theory as principal output of the study to describe how these service models were observed to operate. Routine data were of variable quality, limiting our analysis. Time series analysis demonstrated trends across intervention sites for: increased time spent in the emergency department; increased emergency department attendances and reattendances; and mixed results for hospital admissions. Evidence on patient experience was limited but broadly supportive; we identified department-level processes to optimise the safety of general practitioner–emergency department models. Limitations The quality, heterogeneity and extent of routine emergency department data collection during the study period limited the conclusions. Recruitment was limited by criteria for case sites (time series requirements) and individual patients (with ‘marker conditions’). Pandemic and other pressures limited data collection for marker condition analysis. Data collected and analysed were pre pandemic; new approaches such as ‘telephone first’ and their relevance to our findings remains unexplored. Conclusion Findings suggest that general practitioner–emergency department service models do not meet the aim of reducing the overall emergency department waiting times and improving patient flow with limited evidence of cost savings. Qualitative data indicated that general practitioners were often valued as members of the wider emergency department team. We have developed a toolkit, based on our findings, to provide guidance for implementing and delivering general practitioner–emergency department services. Future work The emergency care data set has since been introduced across England to help standardise data collection to facilitate further research. We would advocate the systematic capture of patient experience measures and patient-reported outcome measures as part of routine care. More could be done to support the development of the general practitioner in emergency department role, including a core set of competencies and governance structure, to reflect the different general practitioner–emergency department models and to evaluate the effectiveness and cost effectiveness to guide future policy. Study registration This study is registered as PROSPERO CRD42017069741. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/145/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 10. See the NIHR Funding and Awards website for further award information. Plain language summary Hospital emergency departments are under huge pressure. Patients are waiting many hours to be seen, some with problems that general practitioners could deal with. To reduce waiting times and improve patient care, arrangements have been put in place for general practitioners to work in or alongside emergency departments (general practitioner–emergency department models). We studied the different ways of working to find out what works well, how and for whom. We brought together a lot of information. We reviewed existing evidence, sent out surveys to 184 emergency departments, spent time in the emergency departments observing how they operated and interviewing 106 staff in 13 hospitals and 24 patients who visited those emergency departments. We also looked at statistical information recorded by hospitals. Two public contributors were involved from the beginning, and we held two stakeholder events to ensure the relevance of our research to professionals and patients. Getting reliable figures to compare the various general practitioner–emergency department set-ups (inside, parallel to or outside the emergency department) was difficult. Our findings suggest that over time more people are coming to emergency departments and overall waiting times did not generally improve due to general practitioner–emergency department models. Evidence that general practitioners might admit fewer patients to hospital was mixed, with limited findings of cost savings. Patients were generally supportive of the care they received, although we could not speak to as many patients as we planned. The skills and experience of general practitioners were often valued as members of the wider emergency department team. We identified how the care provided was kept safe with: strong leaders, good communication between different types of staff, highly trained and experienced nurses responsible for streaming and specific training for general practitioners on how they were expected to work. We have produced a guide to help professionals develop and improve general practitioner–emergency department services and we have written easy-to-read summaries of all the articles we published. Scientific summary Background Emergency healthcare services are under intense pressure to meet the increasing patient demands. Many patients presenting to emergency departments (EDs) could be managed by general practitioners (GPs). We aimed to evaluate the effectiveness, safety, patient experience and system implications of the different models of GPs working in or alongside EDs (GP-ED). Objectives Identify which models are in place. Describe how the models work. Describe the outcomes of each model. Explain the relationships between contexts (C), mechanisms (M) and outcomes (O) to develop a programme theory to help inform service delivery in other settings. Design We conducted a mixed-methods realist evaluation to describe what works, for whom, in what circumstances and how over three phases. Phase 1: understanding current practice and which models are in place Rapid realist review Method We conducted a rapid realist review to develop initial theories about how different GP-ED models operate, supported by our co-applicants as an expert reference group. Results A total of 96 articles contributed to initial theories: how decisions on streaming patients to GP services are influenced; the role of GPs in EDs; patient satisfaction and safety concerns; the risk of provider-induced demand in highly visible services; and whether these services represent value for money. National survey and follow-up clinical director interviews Method We sent an online survey to 184 clinical directors (CDs) from Type 1 EDs in England and Wales to gather information on aims, implementation and delivering the GP-ED services. Thirty CDs who worked in services implemented since 2010 (a range of locations, models and sizes) were invited to take part in semistructured telephone interviews to explore: service operation, perceived successes and challenges. Results We received 77 responses out of 184 invitees (41.3%); 51 (66%) respondents used a GP-ED model. We interviewed 21 CDs. Findings were used to characterise and categorise GP-ED models to create a taxonomy, inform case study site selection and further theory development. National stakeholder event Method We held a National Stakeholder event in Bristol in 2018 (n = 48 attendees), to present findings from the review and survey, gather stakeholder feedback on a taxonomy of GP-ED models (in collaboration with researchers from the GP-ED team at the University of the West of England) and identify ‘marker conditions’ to guide data collection in Phase 2. Results The taxonomy included a description of the ‘form’ of the GP-ED models (inside the ED: Integrated with ED service delivery or a separate Parallel service; or Outside the ED: on or off the hospital site) and a description of how different constructs influence how the service may ‘function’ – as a traditional GP service or emergency medicine service. Five marker conditions were selected, including: child with a fever, cough/shortness of breath, abdominal pain, back pain and chest pain. (We added ‘headache’ as a further condition in Phase 2 of the study to enhance patient interview recruitment.) National patient safety data collection and analysis Method We searched Coroners’ Reports to Prevent Future Deaths (2013–8) and National Reporting and Learning System (NRLS) patient safety incident reports (2005–15) relating to diagnostic errors in GP-ED services. We coded these using the Patient Safety Classification System (PISA) framework and developed initial safety theories to inform data collection in Phase 2. Results We identified 9 relevant Coroners’ Reports and 217 NRLS reports. Initial theories were developed around: difficulty with triage and streaming processes; errors in clinical decision-making; and inadequate referral pathways and communication between services. Phase 2: case study mixed-methods data collection and analysis to describe how the general practitioner–emergency department models work and outcomes Qualitative data analysis Method We selected 13 case study sites reflecting different GP-ED models (3 Integrated, 4 Parallel, 3 Outside and 3 with no GP-ED model), different locations, sizes of ED and experience delivering the service. We visited all sites (2–4 days) and conducted observations and realist interviews with staff to refine initial theories. We requested local patient safety incident reports related to the GP-ED model and invited patients presenting with marker conditions for interviews to describe their experience. We analysed data from the multiple data sources and applied knowledge from conceptual frameworks and formal theories to refine our initial theories. We then mapped context–mechanism–outcome configurations against different GP-ED models to compare across different types of service. We presented findings at a second national event on 3 December 2019 (n = 70 attendees) for stakeholder feedback. Results Across all sites, we interviewed 106 staff members, collected 14 anonymised local patient safety incident reports, invited 748 patients to take part in telephone interviews and subsequently interviewed 24 patients. Theories were refined to describe: how streaming processes were influenced by nurse experience, guidance and overall operational and strategic management; how GPs found working in EDs influenced their clinical decision-making to maintain a usual GP approach or adopt an ED clinician approach, mitigating safety risks; factors that facilitate teamwork and communication between GP-ED services and the ED; how separate, visible GP-ED services are perceived to contribute to provider-induced demand; and patients’ expectations and experiences of using services. Routine data analysis Method We obtained patient-level data relating to ED attendances and subsequent hospital admissions from hospital episode statistics accident and emergency and admitted patient care (APC) data sets, via NHS Digital for study sites located in England; and from emergency department data set and patient episode database for Wales data sets (via secure anonymised information linkage) for one study site located in Wales. We summarised the attendance-level data as time series (per site, aggregating data for each study fortnight) for the following ED variables: Attendances; Reattendances; Hospital admissions (defined by patient record appearing in the APC data set); Investigations and Treatments; Time in ED; length of stay (LOS) of hospital admission. For all variables, we used standard time series analysis methods to assess the nature and extent of linear trends and seasonality in data before and after an intervention point at intervention sites. Results Data from 1 October 2010 to 30 September 2018 were eligible for inclusion and were of variable quality, tending to decrease as the level of integration between to GP-ED model and the ED decreased. We are more confident in the interpretations made about some outcomes (attendances, reattendances, admissions, LOS) than others (investigations, treatments, average time in ED) due to data quality. In general, at the GP-ED model sites, attendances increased over time. Reattendances within 28 days in the post-intervention period increased over that in the pre-intervention period in eight of the nine sites assessed. Overall, intervention sites also demonstrated a consistent trend of increasing average time in the ED across both the pre- and post-intervention phases. A mixed picture was seen in relation to hospital admissions in the Integrated and Parallel sites, with data quality issues at the Outside sites. Average length of hospital stay showed a mixed picture over all intervention sites. Cost–consequences analysis Method We conducted a cost–consequences analysis (CCA) using the routine data described above to consider the costs and resource consequences resulting from, or associated with, the use of the GP-ED model types compared to control sites. Results Negligible incremental ED attendance cost differences were observed between the model types and the control with an extremely small increased cost [£0.70, standard error (SE) £0.07] observed when looking at all models combined over control, though a saving of £72 (SE £3.18) when looking at inpatient admissions. When looking at ED visits by individual models, the Integrated model saw a small cost saving (£8.73, SE £0.07), but small cost increases were seen in the Parallel model (£9.51, SE £0.08) and the Outside model (£16.30, SE £0.16). With respect to inpatient admissions, all models saw small cost savings [£25 (SE £4.16) to £215 (SE £9.05)] with the Outside model showing the largest saving (£215, SE £9.05). Marker condition analysis Method We used a CCA as above to evaluate the management of six marker conditions at a Parallel GP-ED model as a case study site (the only site with data available during the pandemic period). Anonymised patient-level data were used to compare proportions of patients admitted to hospital (Pearson’s chi-squared test), and times (non-parametric Mann–Whitney U-test) for ED clinicians and GPs. A backward enter stepwise approach was taken with non-statistically significant variables (p > 0.05) removed. Results Emergency department clinicians saw most patients and those patients categorised as being more severely unwell. Across all marker conditions, GPs managed patients more quickly – the main driver being the time taken from treatment to discharge. Across all marker conditions, the trend was for GPs to admit fewer patients to inpatient care, compared with ED clinicians. This trend was more evident (and for some reaching statistical significance) among those requiring the lowest levels of intervention. Reattendance rates at 7 days were equal for both GPs and ED clinicians. Phase 3: mixed-method analysis, programme theory and toolkit development Mixed-methods analyses Method We conducted mixed-methods analyses to further refine our theories through two approaches: firstly, to identify questions raised through the qualitative data analysis to support, refute or refine through quantitative data analyses; then to identify noteworthy findings from the statistical analysis and cross-check with both the qualitative and marker conditions analyses. Results Streaming The marker condition and qualitative data analysis indicated the potential for GPs to improve the flow of the least unwell patients through the ED. However, at the whole ED level examined by the routine data, the analysis demonstrated increased time in the ED for patients at most sites. Therefore, our theories related to streaming and patient flow have limited support from quantitative data. General practitioner role Marker condition data from a single Parallel case study site showed that patients spent less time in the department and were less likely to be admitted, with no difference in reattendance rates at 7 days. Data on investigation use were of poor quality and not included in the analysis. Routine data for all intervention sites and three control sites also showed poor quality of investigation data. Any influence on time in the department and hospital admissions described in the marker condition data was not seen consistently in routine data analysis. While the marker conditions analysis supports the theory that a GP approach in an ED setting can be different to an ED clinician approach, it remains unclear whether this is due to individual clinicians’ management behaviours or service level differences in ways of working. The quantitative data did not identify particular GP-ED models associated with favourable outcomes potentially attributable to facilitating the ‘GP role’. Safety The routine data indicated increasing rates of reattendance at 28 days across most intervention and control sites. This may reflect changes in levels of morbidity among the population, public behaviours or service configurations (including availability of services elsewhere, notably in-hours primary care) rather than necessarily representing a change in the quality of the care provided at the ED. The marker condition data suggested that GP care in the ED appeared to be as safe as ED clinician care using reattendances within 7 days as a proxy. We have not identified data to develop our theory about strength of communication and teamworking within the ED. Patient experience While the marker conditions analysis indicated that patients attending ED who required the fewest investigations and treatments might be more satisfied by being seen by a GP due to a shorter ED stay, we could not identify any particular GP-ED model that appeared most likely to consistently decrease department stay. Demand Our theory about provider-induced demand in distinct and visible services is not supported by the data on ED attendances over the study period, but our qualitative findings suggest that there is a perceived additional demand for primary care at an ED in services where the primary care service is visible, easily accessible and more well known in the local area. Programme theory development We developed a programme theory, as the principal out of the research, presented as the patient journey through the three GP-ED models, to highlight similarities and differences. We recognise that each site had unique characteristics, so this represents a high-level summary of key features, rather than a description of every possible variation. At Integrated models, the streaming process is less influential. The ‘invisibility’ of the GP service means its impact on patient expectations is also more limited, but it allows for GPs to take on supervision of junior ED doctors, described positively at some sites. At Outside models, the process of ensuring that the right patient saw the GP was more complex, and open to potential problems. Their high visibility and accessibility were likely to have a greater impact on patients’ expectations and experiences. At these sites, GPs often took on a supervisory role for a wider primary care team. Parallel models showed the most variation in the way services were set up and the clarity of the GP role: some more like Integrated models others, Outside models. Toolkit We worked with study co-applicants and a stakeholder group of CDs to translate the research findings and programme theory into guidance for implementing and delivering GP-ED services. Some key points include: A culture including strong clinical leadership, encouraging mutual respect, interprofessional communication and teamworking is essential. To ensure that patients are efficiently and safely streamed, nurses should be highly trained and experienced; streaming pathways/protocols must be clear with senior oversight and include quality improvement systems. Training for GPs based on the type of GP-ED model in use and their intended role. Patients need to be informed about reasons for being streamed to different clinicians to help manage expectations. Conclusion General practitioners commonly work in EDs, but delivery models vary widely in terms of the scope of the GP role and the scale of the GP service. We developed a taxonomy to describe GP-ED models (Integrated, Parallel, Outside) and present a programme theory to describe how these models were observed to operate. Routine data were heterogeneous and of variable quality limiting analysis, including verification of the proposed theories, but trends were noted across intervention sites for: increased time spent in the ED, increased ED attendances and reattendances and mixed findings for hospital admissions. Findings suggest that GP-ED service models do not meet the aim of reducing ED waiting times and improving patient flow, with limited evidence of cost savings. Qualitative data indicated that GPs were often valued as members of the wider ED team, with significant appetite to utilise their specific skillset to provide care in the ED. We developed a toolkit, based on our findings, to provide guidance for implementing and delivering GP-ED services. Study registration This study is registered as PROSPERO CRD42017069741. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/145/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 10. See the NIHR Funding and Awards website for further award information.

Abstract Background The EVITE Immunity study investigated the effects of shielding Clinically Extremely Vulnerable (CEV) people during the COVID-19 pandemic on health outcomes and healthcare costs in Wales, United Kingdom, to help prepare for future pandemics. Shielding was intended to protect those at highest risk of serious harm from COVID-19. We report the cost of implementing shielding in Wales. Methods The number of people shielding was extracted from the Secure Anonymised Information Linkage Databank. Resources supporting shielding between March and June 2020 were mapped using published reports, web pages, freedom of information requests to Welsh Government and personal communications (e.g. with the office of the Chief Medical Officer for Wales). Results At the beginning of shielding, 117,415 people were on the shielding list. The total additional cost to support those advised to stay home during the initial 14 weeks of the pandemic was £13,307,654 (£113 per person shielded). This included the new resources required to compile the shielding list, inform CEV people of the shielding intervention and provide medicine and food deliveries. The list was adjusted weekly over the 3-month period (130,000 people identified by June 2020). Therefore the cost per person shielded lies between £102 and £113 per person. Conclusion This is the first evaluation of the cost of the measures put in place to support those identified to shield in Wales. However, no data on opportunity cost was available. The true costs of shielding including its budget impact and opportunity costs need to be investigated to decide whether shielding is a worthwhile policy for future health emergencies.

Abstract Natural environments can promote well-being through multiple mechanisms. Many studies have investigated relationships between residential green/blue space (GBS) and well-being, fewer explore relationships with actual use of GBS. We used a nationally representative survey, the National Survey for Wales, anonymously linked with spatial GBS data to investigate associations of well-being with both residential GBS and time in nature (N = 7631). Both residential GBS and time spent in nature were associated with subjective well-being. Higher green-ness was associated with lower well-being, counter to hypotheses (predicting the Warwick and Edinburgh Mental Well-Being Scale (WEMWBS): Enhanced vegetation index β = − 1.84, 95% confidence interval (CI) − 3.63, − 0.05) but time spent in nature was associated with higher well-being (four hours a week in nature vs. none β = 3.57, 95% CI 3.02, 4.13). There was no clear association between nearest GBS proximity and well-being. In support of the equigenesis theory, time spent in nature was associated with smaller socioeconomic inequalities in well-being. The difference in WEMWBS (possible range 14–70) between those who did and did not live in material deprivation was 7.7 points for those spending no time in nature, and less at 4.5 points for those spending time in nature up to 1 h per week. Facilitating access and making it easier for people to spend time in nature may be one way to reduce socioeconomic inequalities in well-being.

Abstract Introduction People who call emergency ambulances frequently are often vulnerable because of health and social circumstances, have unresolved problems or cannot access appropriate care. They have higher mortality rates. Case management by interdisciplinary teams can help reduce demand for emergency services and is available in some UK regions. We report results of interviews with people who use emergency ambulance services frequently to understand their experiences of calling and receiving treatment. Methods We used a two‐stage recruitment process. A UK ambulance service identified six people who were known to them as frequently calling emergency services. Through third‐sector organisations, we also recruited nine individuals with healthcare experiences reflecting the characteristics of people who call frequently. We gained informed consent to record and transcribe all telephone interviews. We used thematic analysis to explore the results. Results People said they make frequent calls to emergency ambulance services as a last resort when they perceive their care needs are urgent and other routes to help have failed. Those with the most complex health needs generally felt their immediate requirements were not resolved and underlying mental and physical problems led them to call again. A third of respondents were also attended to by police and were arrested for behaviour associated with their health needs. Those callers receiving case management did not know they were selected for this. Some respondents were concerned that case management could label frequent callers as troublemakers. Conclusion People who make frequent calls to emergency ambulance services feel their health and care needs are urgent and ongoing. They cannot see alternative ways to receive help and resolve problems. Communication between health professionals and service users appears inadequate. More research is needed to understand service users' motivations and requirements to inform design and delivery of accessible and effective services. Patient or Public Contribution People with relevant experience were involved in developing, undertaking and disseminating this research. Two public contributors helped design and deliver the study, including developing and analysing service user interviews and drafting this paper. Eight public members of a Lived Experience Advisory Panel contributed at key stages of study design, interpretation and dissemination. Two more public contributors were members of an independent Study Steering Committee.

BackgroundRoutine monitoring of Body Mass Index (BMI) in general practice, and via national surveillance programmes, is essential for the identification, prevention, and management of unhealthy childhood weight. We examined and compared the presence and representativeness of children and young people's (CYPs) BMI recorded in two routinely collected administrative datasets: general practice electronic health records (GP-BMI) and the Child Measurement Programme for Wales (CMP-BMI), which measures height and weight in 4-5-year-old school children. We also assessed the feasibility of combining GP-BMI and CMP-BMI data for longitudinal analyses.MethodsWe accessed de-identified population-level GP-BMI data for calendar years 2011 to 2019 for 246,817 CYP, and CMP-BMI measures for 222,772 CYP, held within the Secure Anonymised Information Linkage Databank. We examined the proportion of CYP in Wales with at least one GP-BMI record, its distribution by child socio-demographic characteristics, and trends over time. We compared GP-BMI and CMP-BMI distributions. We quantified the proportion of children with a CMP-BMI measure and a follow-up GP-BMI recorded at an older age and explored the representativeness of these measures.ResultsWe identified a GP-BMI record in 246,817 (41%) CYP, present in a higher proportion of females (54.2%), infants (20.7%) and adolescents. There was no difference in the deprivation profile of those with a GP-BMI measurement. 31,521 CYP with a CMP-BMI had at least one follow-up GP-BMI; those with a CMP-BMI considered underweight or very overweight were 87% and 70% more likely to have at least one follow-up GP-BMI record respectively compared to those with a healthy weight, as were males and CYP living in the most deprived areas of Wales.ConclusionsRecords of childhood weight status extracted from general practice are not representative of the population and are biased with respect to weight status. Linkage of information from the national programme to GP records has the potential to enhance discussions around healthy weight at the point of care but does not provide a representative estimate of population level weight trajectories, essential to provide insights into factors determining a healthy weight gain across the early life course. A second CMP measurement is required in Wales.

Abstract Background There is limited evidence in the literature on the long-term effectiveness and cost-effectiveness of treatments for Acute Severe Ulcerative Colitis (ASUC). The study aimed to perform decision analytic model-based long-term cost-utility analysis (CUA) of infliximab versus ciclosporin for steroid-resistant ASUC investigated in CONSTRUCT pragmatic trial. Methods A decision tree (DT) model was developed using two-year health effect, resource use and costs data from CONSTRUCT trial to estimate relative cost-effectiveness of two competing drugs from the United Kingdom (UK) National Health Services (NHS) perspective. Using short-term trial data, a Markov model (MM) was then developed and evaluated over further 18 years. Both DT and MM were combined to investigate cost-effectiveness of infliximab versus ciclosporin for ASUC patients over 20-year time horizon, with a rigorous multiple deterministic and probabilistic sensitivity analyses to address uncertainty in results. Results The decision tree mirrored trial-based results. Beyond 2-year trial follow-up, Markov model predicted a decrease in colectomy rate, but it remained slightly higher for ciclosporin. NHS costs and quality adjusted life years (QALYs) over base-case 20 year time horizon were £26,793 and 9.816 for ciclosporin and £34,185 and 9.106 for infliximab, suggesting ciclosporin dominates infliximab. Ciclosporin had 95% probability of being cost-effective at a willingness-to-pay (WTP) threshold value up to £20,000. Conclusion Using data from a pragmatic RCT, the cost-effectiveness models produced incremental net health benefit in favour of ciclosporin relative to infliximab. Results from long-term modelling indicated that ciclosporin remains dominant compared with infliximab for the treatment of NHS ASUC patients, however, these need to be interpreted cautiously. Trial registration CONSTRUCT Trial registration number ISRCTN22663589; EudraCT number: 2008- 001968-36 (Date 27/08/2008).

Background Cross-sectional evidence suggests that living near green and blue spaces benefits mental health; longitudinal evidence is limited. Objectives To quantify the impact of changes in green and blue spaces on common mental health disorders, well-being and health service use. Design A retrospective, dynamic longitudinal panel study. Setting Wales, UK. Participants An e-cohort comprising 99,682,902 observations of 2,801,483 adults (≥ 16 years) registered with a general practice in Wales (2008–2019). A 5312-strong ‘National Survey for Wales (NSW) subgroup’ was surveyed on well-being and visits to green and blue spaces. Main outcome measures Common mental health disorders, general practice records; subjective well-being, Warwick–Edinburgh Mental Well-being Scale. Data sources Common mental health disorder and use of general practice services were extracted quarterly from the Welsh Longitudinal General Practice Dataset. Annual ambient greenness exposure, enhanced vegetation index and access to green and blue spaces (2018) from planning and satellite data. Data were linked within the Secure Anonymised Information Linkage Databank. Methods Multilevel regression models examined associations between exposure to green and blue spaces and common mental health disorders and use of general practice. For the National Survey for Wales subgroup, generalised linear models examined associations between exposure to green and blue spaces and subjective well-being and common mental health disorders. Results and conclusions Our longitudinal analyses found no evidence that changes in green and blue spaces through time impacted on common mental health disorders. However, time-aggregated exposure to green and blue spaces contrasting differences between people were associated with subsequent common mental health disorders. Similarly, our cross-sectional findings add to growing evidence that residential green and blue spaces and visits are associated with well-being benefits: Greater ambient greenness (+ 1 enhanced vegetation index) was associated with lower likelihood of subsequently seeking care for a common mental health disorder [adjusted odds ratio (AOR) 0.80, 95% confidence interval, (CI) 0.80 to 0.81] and with well-being with a U-shaped relationship [Warwick–Edinburgh Mental Well-being Scale; enhanced vegetation index beta (adjusted) –10.15, 95% CI –17.13 to −3.17; EVI2 beta (quadratic term; adj.) 12.49, 95% CI 3.02 to 21.97]. Those who used green and blue spaces for leisure reported better well-being, with diminishing extra benefit with increasing time (Warwick–Edinburgh Mental Well-being Scale: time outdoors (hours) beta 0.88, 95% CI 0.53 to 1.24, time outdoors2 beta −0.06, 95% CI −0.11 to −0.01) and had 4% lower odds of seeking help for common mental health disorders (AOR 0.96, 95% CI 0.93 to 0.99). Those in urban areas benefited most from greater access to green and blue spaces (AOR 0.89, 95% CI 0.89 to 0.89). Those in material deprivation benefited most from leisure time outdoors (until approximately four hours per week; Warwick–Edinburgh Mental Well-being Scale: time outdoors × in material deprivation: 1.41, 95% CI 0.39 to 2.43; time outdoors2 × in material deprivation −0.18, 95% CI −0.33 to −0.04) although well-being remained generally lower. Limitations Longitudinal analyses were restricted by high baseline levels and limited temporal variation in ambient greenness in Wales. Changes in access to green and blue spaces could not be captured annually due to technical issues with national-level planning datasets. Future work Further analyses could investigate mental health impacts in population subgroups potentially most sensitive to local changes in access to specific types of green and blue spaces. Deriving green and blue spaces changes from planning data is needed to overcome temporal uncertainties. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (Project number 16/07/07) and will be published in full in Public Health Research; Vol. 11, No. 10. Sarah Rodgers is part-funded by the NIHR Applied Research Collaboration North West Coast. Plain language summary We investigated whether people who live near or visit green (parks, woodlands) and blue (riversides, beaches) spaces have fewer common mental health disorders (anxiety or depression), and better well-being. We considered whether changes in the amount of green and blue space around the home affected people’s mental health. We assessed the availability of local green and blue spaces. Annual exposure and access to local green and blue spaces were extracted from planning and satellite data. We linked these data to anonymised health records of 2,801,483 adults registered with a general practice from 2008 to 2019, and to survey answers about leisure visits to natural environments and well-being. We found: people who lived in greener and bluer areas were less likely to seek help for a common mental health disorder than those in less green or blue areas, with those living in the most deprived areas benefiting the most people who used green and blue spaces for leisure, especially those with the greatest levels of deprivation, had better well-being and were less likely to seek help for common mental health disorders no evidence that changing amounts of green and blue space affected how likely people were to seek help for common mental health disorders; this may be because we found mostly small changes in green and blue space, and we may not have allowed enough time between moving home and recording mental health. We found evidence for relationships between green and blue space and mental health. However, some analyses were restricted due to lack of data on changes in green and blue spaces. An important finding was that people in deprived communities appear to benefit the most. Provision of green and blue spaces could be a strategy to improve the mental health of people living in disadvantaged areas. Scientific summary Background Cross-sectional evidence suggests that living close to and spending time in and around green and blue spaces (GBS, e.g. parks, gardens, ponds, lakes, rivers) is associated with higher levels of well-being and fewer mental health problems. Some of these benefits could result from living near GBS; others (e.g. physical activity) are attributed to using GBS. There are few longitudinal studies examining whether changes in GBS affect subsequent mental health. Existing studies have largely had small cohorts, assessed change over a short time, did not investigate socioeconomic inequalities in effects and neglected to consider that some health benefits depend on using GBS rather than simple exposure. Objectives We examined the research questions: Is a greater residential exposure and access to GBS associated with the likelihood of seeking help for a common mental health disorder (CMD) in general practice? Is the association between exposure, or access to, GBS and seeking help for a CMD modified by socioeconomic disadvantage and moving home? Is a greater residential exposure associated with the likelihood of using general practice services? Is greater residential GBS exposure and access to GBS associated with higher subjective well-being or a lower likelihood of seeking help for CMD, and does intentional use of GBS for leisure mediate these associations? Are associations between residential GBS exposure and access to GBS and use and subjective well-being mediated by walking-specific physical activity and modified by socioeconomic disadvantage? Methods We used a dynamic longitudinal panel study design to retrospectively examine natural and non-random variation in GBS exposure during an 11-year period, with individual linkage to survey responses. Data sources We constructed an electronic cohort of the population of Wales using data from the Welsh Demographic Service Dataset. Household-level ambient greenness was determined from satellite imagery, access to GBS from planning records, CMD and service use from Welsh Longitudinal General Practice Dataset (WLGPD) and for a subgroup, well-being and behaviour responses to the National Survey for Wales (NSW, 2016/17 and 2018/19). Data are held in the Secure Anonymised Information Linkage (SAIL) databank. Inclusion criteria The cohort included everyone aged 16 years and over registered with a general practitioner (GP) providing patient records to the SAIL databank between January 2008 and October 2019 (‘the study period’). Those not registered with an appropriate GP, not having a Welsh residential address between January 2008 and October 2019, and not having sex/week of birth recorded were excluded from the study sample. Exposures Our primary environmental exposure was ambient greenness, measured yearly (2008–19) by mean enhanced vegetation index (EVI) averaged over a 300 m circular buffer centred on each residence. Our secondary environmental exposure was the potential for an individual to access GBS along paths/roads within 1600 m of each home, modelled for 2018. We captured changes only when individuals moved home. For research questions 1–3, GBS access was quantified by the number of potentially accessible GBS. For research questions 4–5, access was quantified as the proximity to the nearest GBS. Outcome measures For research questions 1–3, our primary outcome was seeking help for CMD in general practice, identified from practice records using a validated algorithm. Our secondary outcome was the quarterly count of general practice events. For research questions 4 and 5, our primary outcome was subjective well-being, measured by the Warwick–Edinburgh Mental Well-being Scale (WEMWBS) in the NSW. Secondary outcomes were life satisfaction (NSW) and seeking help for CMD in general practice. Self-reported time outdoors on recreational visits to GBS in Wales and walking-specific physical activity were identified (NSW). Statistical analysis Research questions 1–3 were addressed using complementary approaches: We first evaluated associations between cumulative EVI exposure and seeking help for CMD in general practice using multivariate logistic regression. Follow-up stopped when help was first sought for CMD or at the end of the study period. This time aggregated design allowed us to consider environmental exposure prior to seeking help for CMD in general practice and included differences between people. We conducted stratified analyses according to area-level deprivation (Welsh Index of Multiple Deprivation, WIMD) quintiles, home moves (none/one/more than one), history of seeking care for CMD in general practice (before January 2008) and urban-rural home location. Next, we assessed associations between longitudinal change in GBS exposures for the same individuals, and their subsequent likelihood of seeking help for CMD (primary outcome) using multivariate logistic regression. For the association with general practice services use (secondary outcome) we used Poisson regression. We used a panel design with a multilevel model structure (quarterly observations nested within individuals). We accounted for clustering of observations over time (using random effects), and unbalanced data (number of observations varying for individuals). Change in GBS exposure was modelled as a continuous variable relative to previous time periods. For people who did not move home, we modelled EVI change categories to examine in situ exposure changes. Stratified analyses were conducted for quintiles of WIMD and number of home moves. For research questions 4–5 we assessed whether GBS exposures were related to WEMWBS, life satisfaction and seeking help for CMD, and whether there was moderation by socioeconomic disadvantage. We examined whether the association between GBS exposures and WEMWBS, life satisfaction and seeking help for CMD, were mediated by time spent outdoors. Generalised additive models were used to identify any non-linear associations and inform subsequent generalised linear regression. When predicting WEMWBS, linear and quadratic terms for EVI were included and proximity to nearest GBS was categorised. For seeking help for CMD, EVI was categorised, and proximity was continuous. To assess moderation by socioeconomic disadvantage, we included interactions between material deprivation and the GBS exposures. Results The cohort included 2,801,483 individuals (99,682,902 observations). A total of 816,242 individuals (29.1%) sought help for CMD from their general practice at least once in the study period. Research question 1: Is a greater residential exposure and access to GBS associated with the likelihood of seeking health for CMDs in general practice? People who lived in homes surrounded by more ambient greenness (+ 0.1 EVI) were associated with 20% lower odds of seeking help for CMD in general practice [adjusted odds ratio (AOR) 0.80, 95% confidence interval (CI) 0.80 to 0.81]. More potentially accessible GBS (equivalent to 236 more GBS) were associated with 7% lower odds of seeking help for CMD (AOR 0.93, 95% CI 0.93 to 0.93). Every additional 360 m (0.1 unit) to the nearest GBS was associated with 5% higher odds of seeking help for CMD (AOR 1.05, 95% CI 1.04 to 1.05). People experiencing an increase of 0.1 mean EVI was not associated with seeking help for CMD in general practice (exposure change relative to: previous quarter/year/baseline AOR 1.00, 95% CI 1.00 to 1.00). Among the 1,611,581 people who did not move home (57.5% of the cohort), increases or decreases of ≥ 0.15 EVI relative to baseline were not associated with seeking help for CMD (AOR for ≥ +0.15 EVI 1.00, 95% CI 0.99 to 1.00; AOR for ≥ −0.15 EVI 1.00, 95% CI 1.00 to 1.01). Among those who moved home at least once, an increase in the number of potentially accessible GBS was not associated with seeking help for CMD in general practice (GBS increase relative to previous quarter/year/baseline: AOR 1.00, 95% CI 1.00 to 1.00). Research question 2: Is the association between exposure, or access to, GBS and seeking help for a CMD modified by socioeconomic disadvantage and moving home? Living in a home with greater EVI (+ 0.1) and more accessible GBS (+ 236) was associated with lower odds of seeking help for CMD in general practice in all deprivation quintiles and whether people moved. The odds of seeking help were lower for those who did not move (AOR non-movers 0.77, 95% CI 0.77 to 0.78; AOR moved > once 0.92, 95% CI 0.91 to 0.93). There was no evidence that EVI or GBS changes were associated with seeking help for a CMD for people living in either the most or least deprived urban areas. An increase of 0.1 mean EVI (relative to baseline) was associated with slightly lower odds of seeking help for CMD for people who moved home more than once (AOR 0.99, 95% CI 0.99 to 0.99) but not for those who moved once or had not moved. Association between different GBS exposures and seeking help for CMD in general practice were modified by urban–rural home location and a history of seeking help for CMD. Greater EVI was associated with lower odds of seeking help for a CMD for those living in rural areas (AOR 0.59, 95% CI 0.58 to 0.59) compared with urban areas (AOR 0.85, 95% CI 0.84 to 0.85). More potentially accessible GBS were only associated with lower odds of seeking help for CMD for those living in urban areas (AOR 0.89, 95% CI 0.89 to 0.89). In rural areas more GBS access was associated with higher odds of seeking help for CMD (AOR 1.10, 95% CI 1.08 to 1.12). More ambient greenness (+ 0.1 EVI) was associated with lower odds of seeking help for a CMD for those who had historically sought help for CMD (before January 2008) than people who had not (AOR 0.68 vs. 0.84). Research question 3: Is a greater residential exposure associated with the likelihood of using GP services? There was no evidence that an increase in mean EVI was associated with the number of general practice event days/quarter (adjusted incidence rate ratio relative to baseline: 1.00, 95% CI 1.00 to 1.00). Research question 4: Is greater residential GBS exposure and access to GBS associated with higher subjective well-being, or a lower likelihood of seeking help for CMD in general practice, and are these associations mediated by intentional use of GBS for leisure? Among NSW respondents with outcome measures (n = 5971) EVI was significantly related to well-being as measured by WEMWBS with a U-shaped relationship (linear regression; EVI −10.15, 95% CI −17.13 to −3.17; EVI2 12.49, 95% CI 3.02 to 21.97) and weekly time outdoors (linear relationship; EVI 43.41, 95% CI 6.85 to 79.97). Time outdoors was significantly positively related to WEMWBS [time outdoors (hours) 0.88, 95% CI 0.53 to 1.24, time outdoors (hours)2 −0.06, 95% CI −0.11 to −0.01] and life satisfaction [linear relationship; time outdoors (hours) 0.06, 95% CI 0.04 to 0.07]. There was no evidence that time outdoors mediated the relationship between EVI and WEMWBS/life satisfaction. EVI was not associated with CMD (EVI 0.4 to 0.8 vs.

Summary: Background: Living in greener areas, or close to green and blue spaces (GBS; eg, parks, lakes, or beaches), is associated with better mental health, but longitudinal evidence when GBS exposures precede outcomes is less available. We aimed to analyse the effect of living in or moving to areas with more green space or better access to GBS on subsequent adult mental health over time, while explicitly considering health inequalities. Methods: A cohort of the people in Wales, UK (≥16 years; n=2 341 591) was constructed from electronic health record data sources from Jan 1, 2008 to Oct 31, 2019, comprising 19 141 896 person-years of follow-up. Household ambient greenness (Enhanced Vegetation Index [EVI]), access to GBS (counts, distance to nearest), and common mental health disorders (CMD, based on a validated algorithm combining current diagnoses or symptoms of anxiety or depression [treated or untreated in the preceding 1-year period], or treatment of historical diagnoses from before the current cohort [up to 8 years previously, to 2000], where diagnosis preceded treatment) were record-linked. Cumulative exposure values were created for each adult, censoring for CMD, migration out of Wales, death, or end of cohort. Exposure and CMD associations were evaluated using multivariate logistic regression, stratified by area-level deprivation. Findings: After adjustment, exposure to greater ambient greenness over time (+0·1 increased EVI on a 0–1 scale) was associated with lower odds of subsequent CMD (adjusted odds ratio 0·80, 95% CI 0·80–0·81), where CMD was based on a combination of current diagnoses or symptoms (treated or untreated in the preceding 1-year period), or treatments. Ten percentile points more access to GBS was associated with lower odds of a later CMD (0·93, 0·93–0·93). Every additional 360 m to the nearest GBS was associated with higher odds of CMD (1·05, 1·04–1·05). We found that positive effects of GBS on mental health appeared to be greater in more deprived quintiles. Interpretation: Ambient exposure is associated with the greatest reduced risk of CMD, particularly for those who live in deprived communities. These findings support authorities responsible for GBS, who are attempting to engage planners and policy makers, to ensure GBS meets residents' needs. Funding: National Institute for Health and Care Research Public Health Research programme.

Abstract Background Approximately 75,000 people fracture a hip each year in the UK. This painful injury can be devastating—with a high associated mortality rate—and survivors likely to be more dependent and less mobile. Pain relief at the scene of injury is known to be inadequate. Intravenous morphine is usually given by paramedics, but opioids are less effective for dynamic pain and can cause serious side effects, including nausea, constipation, delirium and respiratory depression. These may delay surgery, require further treatment and worsen patient outcomes. We completed a feasibility study of paramedic-provided fascia iliaca compartment block (FICB), testing the intervention, trial methods and data collection. The study (RAPID) demonstrated that a full trial was feasible. In this subsequent study, we aim to test safety, clinical and cost-effectiveness of paramedic-provided FICB as pain relief to patients with suspected hip fracture in the prehospital environment. Methods We will conduct a pragmatic multi-centre individually randomised parallel-group trial, with a 1:1 allocation between usual care (control) and FICB (intervention). Hospital clinicians in five sites (paired ambulance services and receiving hospitals) in England and Wales will train 220 paramedics to administer FICB. The primary outcome is change in pain score from pre-randomisation to arrival at the emergency department. One thousand four hundred patients are required to find a clinically important difference between trial arms in the primary outcome (standardised statistical effect ~ 0.2; 90% power, 5% significance). We will use NHS Digital (England) and the SAIL (Secure Anonymised Information Linkage) databank (Wales) to follow up patient outcomes using routine anonymised linked data in an efficient study design, and questionnaires to capture patient-reported outcomes at 1 and 4 months. Secondary outcomes include mortality, length of hospital stay, job cycle time, prehospital medications including morphine, presence of hip fracture, satisfaction, mobility, and NHS costs. We will assess safety by monitoring serious adverse events (SAEs). Discussion The trial will help to determine whether paramedic administered FICB is a safe, clinically and cost-effective treatment for suspected hip fracture in the pre-hospital setting. Impact will be shown if and when clinical guidelines either recommend or reject the use of FICB in routine practice in this context. Trial registration ISRCTN15831813 . Registered on 22 September 2021.

Introduction Injuries are a major public health problem which can lead to disability or death. However, little is known about the incidence, presentation, management and outcomes of emergency care for patients with injuries among people from ethnic minorities in the UK. The aim of this study is to investigate what may differ for people from ethnic minorities compared with white British people when presenting with injury to ambulance and Emergency Departments (EDs).Methods and analysis This mixed methods study covers eight services, four ambulance services (three in England and one in Scotland) and four hospital EDs, located within each ambulance service. The study has five Work Packages (WP): (WP1) scoping review comparing mortality by ethnicity of people presenting with injury to emergency services; (WP2) retrospective analysis of linked NHS routine data from patients who present to ambulances or EDs with injury over 5 years (2016–2021); (WP3) postal questionnaire survey of 2000 patients (1000 patients from ethnic minorities and 1000 white British patients) who present with injury to ambulances or EDs including self-reported outcomes (measured by Quality of Care Monitor and Health Related Quality of Life measured by SF-12); (WP4) qualitative interviews with patients from ethnic minorities (n=40) and focus groups—four with asylum seekers and refugees and four with care providers and (WP5) a synthesis of quantitative and qualitative findings.Ethics and dissemination This study received a favourable opinion by the Wales Research Ethics Committee (305391). The Health Research Authority has approved the study and, on advice from the Confidentiality Advisory Group, has supported the use of confidential patient information without consent for anonymised data. Results will be shared with ambulance and ED services, government bodies and third-sector organisations through direct communications summarising scientific conference proceedings and publications.

Abstract Background Looked after children (LAC) that are placed in either a foster, kinship, residential care setting or transition to adoption continue to develop debilitating disorders that significantly impact their overall health and social well-being. The prevalence of these disorders is often depicted under broad categories such as mental, behavioural or neurodevelopmental disorders (NDDs). Limited in research is the prevalence of what specific disorders fall under these broad categories. NDDs such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) which fall under an umbrella group in the expert field of genetics and neuropsychiatry will be explored. Unsupported, these disorders can lead to suboptimal health and social outcomes for both the child and family. In the general population, the prevalence of these NDDs and impacts on health and social well-being are relatively well documented, but for minority groups such as LAC, research is extremely limited. This review aims to estimate the prevalence of NDDs among LAC and explore how they might impact the health and social well-being of these vulnerable children. If feasible, the review will compare the prevalence rates to those children who are not looked after, to illuminate any differences or similarities between populations. Methods PubMed, ASSIA, IBSS, Web of Science, PsychINFO, Scopus, Psych articles, Social Care Online, secondary, grey literature and government publications will be searched to identify any eligible studies. No restrictions will be placed on country, design or year of publication. Studies must provide primary data on the prevalence or incidence of NDDs for individuals < 25 years of age, supported by either a diagnostic code, standardised diagnostic assessment tool or survey response. The Joanna Briggs Institute (JBI) critical appraisal tools will be utilised to assess the quality and bias and the random-effects model used to estimate a pooled prevalence of NDDs. Discussion Attaining an estimated prevalence of these NDDs and identifying any impacts on health and social well-being might inform key stakeholders in health, educational and social sectors with important information that might aid in the early identification and intervention to safeguard and meet the unique needs of these children. Systematic review registration PROSPERO CRD4201913103 .

Rates of Multimorbidity (also called Multiple Long Term Conditions, MLTC) are increasing in many developed nations. People with multimorbidity experience poorer outcomes and require more healthcare intervention. Grouping of conditions by health service utilisation is poorly researched. The study population consisted of a cohort of people living in Wales, UK aged 20 years or older in 2000 who were followed up until the end of 2017. Multimorbidity clusters by prevalence and healthcare resource use (HRU) were modelled using hypergraphs, mathematical objects relating diseases via links which can connect any number of diseases, thus capturing information about sets of diseases of any size. The cohort included 2,178,938 people. The most prevalent diseases were hypertension (13.3%), diabetes (6.9%), depression (6.7%) and chronic obstructive pulmonary disease (5.9%). The most important sets of diseases when considering prevalence generally contained a small number of diseases, while the most important sets of diseases when considering HRU were sets containing many diseases. The most important set of diseases taking prevalence and HRU into account was diabetes & hypertension and this combined measure of importance featured hypertension most often in the most important sets of diseases. We have used a single approach to find the most important sets of diseases based on co-occurrence and HRU measures, demonstrating the flexibility of the hypergraph approach. Hypertension, the most important single disease, is silent, underdiagnosed and increases the risk of life threatening co-morbidities. Co-occurrence of endocrine and cardiovascular diseases was common in the most important sets. Combining measures of prevalence with HRU provides insights which would be helpful for those planning and delivering services.

Abstract This study used linked, routinely-collected datasets to explore incidence, clinical characteristics and outcomes of prostate cancer (PC) patients who experience a rise in prostate-specific antigen (PSA) levels despite androgen deprivation therapy (ADT), without evidence of metastases in their patient record, termed non-metastatic castration-resistant PC (nmCRPC). Routinely collected administrative data in Wales were used to identify patients diagnosed with PC and nmCRPC from 2000–2015. Logrank tests and Cox proportional hazard models were used to compare time-to-events across subgroups defined by PSA doubling time and age. Of 38,021 patients identified with PC, 1,465 met nmCRPC criteria. PC incidence increased over the study period, while nmCRPC categorizations reduced. Median time from PC diagnosis to nmCRPC categorization was 3.07 years (95% confidence interval [CI] 2.91–3.26) and from nmCRPC categorization to metastases/death was 2.86 years (95% CI 2.67–3.09). Shorter PSA doubling time (≤ 10 months, versus > 10 months) was associated with reduced time to metastases or death (2.11 years [95% CI 1.92–2.30] versus 5.22 years [95% CI 4.87–5.51]). Age was not significantly associated with time to metastases/death. Our findings highlight key clinical characteristics and outcomes for patients with nmCRPC prior to the introduction of recently approved treatments.

Introduction Childhood obesity and physical inactivity are two of the most significant modifiable risk factors for the prevention of non-communicable diseases (NCDs). Yet, a third of children in Wales and Australia are overweight or obese, and only 20% of UK and Australian children are sufficiently active. The purpose of the Built Environments And Child Health in WalEs and AuStralia (BEACHES) study is to identify and understand how complex and interacting factors in the built environment influence modifiable risk factors for NCDs across childhood.Methods and analysis This is an observational study using data from five established cohorts from Wales and Australia: (1) Wales Electronic Cohort for Children; (2) Millennium Cohort Study; (3) PLAY Spaces and Environments for Children’s Physical Activity study; (4) The ORIGINS Project; and (5) Growing Up in Australia: the Longitudinal Study of Australian Children. The study will incorporate a comprehensive suite of longitudinal quantitative data (surveys, anthropometry, accelerometry, and Geographic Information Systems data) to understand how the built environment influences children’s modifiable risk factors for NCDs (body mass index, physical activity, sedentary behaviour and diet).Ethics and dissemination This study has received the following approvals: University of Western Australia Human Research Ethics Committee (2020/ET000353), Ramsay Human Research Ethics Committee (under review) and Swansea University Information Governance Review Panel (Project ID: 1001). Findings will be reported to the following: (1) funding bodies, research institutes and hospitals supporting the BEACHES project; (2) parents and children; (3) school management teams; (4) existing and new industry partner networks; (5) federal, state and local governments to inform policy; as well as (6) presented at local, national and international conferences; and (7) disseminated by peer-reviewed publications.

Introduction Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the COVID-19 pandemic. Clinically extremely vulnerable people identified through algorithms and screening of routine National Health Service (NHS) data were individually and strongly advised to stay at home and strictly self-isolate even from others in their household. This study will generate a logic model of the intervention and evaluate the effects and costs of shielding to inform policy development and delivery during future pandemics.Methods and analysis This is a quasiexperimental study undertaken in Wales where records for people who were identified for shielding were already anonymously linked into integrated data systems for public health decision-making. We will: interview policy-makers to understand rationale for shielding advice to inform analysis and interpretation of results; use anonymised individual-level data to select people identified for shielding advice in March 2020 and a matched cohort, from routine electronic health data sources, to compare outcomes; survey a stratified random sample of each group about activities and quality of life at 12 months; use routine and newly collected blood data to assess immunity; interview people who were identified for shielding and their carers and NHS staff who delivered healthcare during shielding, to explore compliance and experiences; collect healthcare resource use data to calculate implementation costs and cost–consequences. Our team includes people who were shielding, who used their experience to help design and deliver this study.Ethics and dissemination The study has received approval from the Newcastle North Tyneside 2 Research Ethics Committee (IRAS 295050). We will disseminate results directly to UK government policy-makers, publish in peer-reviewed journals, present at scientific and policy conferences and share accessible summaries of results online and through public and patient networks.

Background: Incisional hernias can cause chronic pain and complications and affect quality of life. Surgical repair requires health-care resources and has a significant associated failure rate. A prospective, multicentre, single-blinded randomised controlled trial was conducted to investigate the clinical effectiveness and cost-effectiveness of the Hughes abdominal closure method compared with standard mass closure following surgery for colorectal cancer. The study randomised, in a 1 : 1 ratio, 802 adult patients (aged ≥ 18 years) undergoing surgical resection for colorectal cancer from 28 surgical departments in UK centres. Intervention: Hughes abdominal closure or standard mass closure. Main outcome measures: The primary outcome was the incidence of incisional hernias at 1 year, as assessed by clinical examination. Within-trial cost-effectiveness and cost–utility analyses over 1 year were conducted from an NHS and a social care perspective. A key secondary outcome was quality of life, and other outcomes included the incidence of incisional hernias as detected by computed tomography scanning. Results: The incidence of incisional hernia at 1-year clinical examination was 50 (14.8%) in the Hughes abdominal closure arm compared with 57 (17.1%) in the standard mass closure arm (odds ratio 0.84, 95% confidence interval 0.55 to 1.27; p = 0.4). In year 2, the incidence of incisional hernia was 78 (28.7%) in the Hughes abdominal closure arm compared with 84 (31.8%) in the standard mass closure arm (odds ratio 0.86, 95% confidence interval 0.59 to 1.25; p = 0.43). Computed tomography scanning identified a total of 301 incisional hernias across both arms, compared with 100 identified by clinical examination at the 1-year follow-up. Computed tomography scanning missed 16 incisional hernias that were picked up by clinical examination. Hughes abdominal closure was found to be less cost-effective than standard mass closure. The mean incremental cost for patients undergoing Hughes abdominal closure was £616.45 (95% confidence interval –£699.56 to £1932.47; p = 0.3580). Quality of life did not differ significantly between the study arms at any time point. Limitations: As this was a pragmatic trial, the control arm allowed surgeon discretion in the approach to standard mass closure, introducing variability in the techniques and equipment used. Intraoperative randomisation may result in a loss of equipoise for some surgeons. Follow-up was limited to 2 years, which may not have been enough time to see a difference in the primary outcome. Conclusions: Hughes abdominal closure did not significantly reduce the incidence of incisional hernias detected by clinical examination and was less cost-effective at 1 year than standard mass closure in colorectal cancer patients. Computed tomography scanning may be more effective at identifying incisional hernias than clinical examination, but the clinical benefit of this needs further research. Future work: An extended follow-up using routinely collected NHS data sets aims to report on incisional hernia rates at 2–5 years post surgery to investigate any potential mortality benefit of the closure methods. Furthermore, the proportion of incisional hernias identified by a computed tomography scan (at 1 and 2 years post surgery), but not during clinical examination (occult hernias), proceeding to surgical repair within 3–5 years after the initial operation will be explored. Trial registration: This trial is registered as ISRCTN25616490. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 34. See the NIHR Journals Library website for further project information.

Objectives Having multiple long term health conditions (MLTCs), also known as multimorbidity, is becoming increasingly common as populations age. Understanding how clusters of diseases are likely to lead to other diseases and the effect of multimorbidity on healthcare resource use (HRU) will be of great importance as this trend continues. Approach Graph-based approaches, also called network analysis in the literature, have been used previously to study multimorbidity. The use of hypergraphs, which are generalisations of graphs where edges can connect to any number of nodes, and their application to the problem of understanding multimorbidity will be discussed. Analysis using hypergraphs was carried out using a population-scale cohort of people in the Secure Anonymised Information Linkage (SAIL) Databank to find the diseases and disease sets which are most important based on a measure of prevalence and measures of healthcare resource utilisation in secondary care. Results The most important sets of diseases based on the centrality of a hypergraph weighted by a measure of prevalence featured hypertension, and the most important was hypertension and diabetes. The most important sets of diseases based on the centrality of a hypergraph weighted by a measure of unplanned inpatient HRU were arrhythmia, heart failure and hypertension while for a measure of outpatient HRU the most important set of diseases was diabetes and hypertension. Conclusion Hypergraphs are very flexible and general mathematical objects and there is still a great deal of development that can be done to make them more useful in epidemiological settings and beyond.

Background: Intravenous thrombolysis and intra-arterial thrombectomy are proven emergency treatments for acute ischaemic stroke, but they require rapid delivery to selected patients within specialist services. National audit data have shown that treatment provision is suboptimal. Objectives: The aims were to (1) determine the content, clinical effectiveness and day 90 cost-effectiveness of an enhanced paramedic assessment designed to facilitate thrombolysis delivery in hospital and (2) model thrombectomy service configuration options with optimal activity and cost-effectiveness informed by expert and public views. Design: A mixed-methods approach was employed between 2014 and 2019. Systematic reviews examined enhanced paramedic roles and thrombectomy effectiveness. Professional and service user groups developed a thrombolysis-focused Paramedic Acute Stroke Treatment Assessment, which was evaluated in a pragmatic multicentre cluster randomised controlled trial and parallel process evaluation. Clinicians, patients, carers and the public were surveyed regarding thrombectomy service configuration. A decision tree was constructed from published data to estimate thrombectomy eligibility of the UK stroke population. A matching discrete-event simulation predicted patient benefits and financial consequences from increasing the number of centres. Setting: The paramedic assessment trial was hosted by three regional ambulance services (in north-east England, north-west England and Wales) serving 15 hospitals. Participants: A total of 103 health-care representatives and 20 public representatives assisted in the development of the paramedic assessment. The trial enrolled 1214 stroke patients within 4 hours of symptom onset. Thrombectomy service provision was informed by a Delphi exercise with 64 stroke specialists and neuroradiologists, and surveys of 147 patients and 105 public respondents. Interventions: The paramedic assessment comprised additional pre-hospital information collection, structured hospital handover, practical assistance up to 15 minutes post handover, a pre-departure care checklist and clinician feedback. Main outcome measures: The primary outcome was the proportion of patients receiving thrombolysis. Secondary outcomes included day 90 health (poor status was a modified Rankin Scale score of > 2). Economic outputs reported the number of cases treated and cost-effectiveness using quality-adjusted life-years and Great British pounds. Data sources: National registry data from the Sentinel Stroke National Audit Programme and the Scottish Stroke Care Audit were used. Review methods: Systematic searches of electronic bibliographies were used to identify relevant literature. Study inclusion and data extraction processes were described using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: The paramedic assessment trial found a clinically important but statistically non-significant reduction in thrombolysis among intervention patients, compared with standard care patients [197/500 (39.4%) vs. 319/714 (44.7%), respectively] (adjusted odds ratio 0.81, 95% confidence interval 0.61 to 1.08; p = 0.15). The rate of poor health outcomes was not significantly different, but was lower in the intervention group than in the standard care group [313/489 (64.0%) vs. 461/690 (66.8%), respectively] (adjusted odds ratio 0.86, 95% confidence interval 0.60 to 1.2; p = 0.39). There was no difference in the quality-adjusted life-years gained between the groups (0.005, 95% confidence interval –0.004 to 0.015), but total costs were significantly lower for patients in the intervention group than for those in the standard care group (–£1086, 95% confidence interval –£2236 to –£13). It has been estimated that, in the UK, 10,140–11,530 patients per year (i.e. 12% of stroke admissions) are eligible for thrombectomy. Meta-analysis of published data confirmed that thrombectomy-treated patients were significantly more likely to be functionally independent than patients receiving standard care (odds ratio 2.39, 95% confidence interval 1.88 to 3.04; n = 1841). Expert consensus and most public survey respondents favoured selective secondary transfer for accessing thrombectomy at regional neuroscience centres. The discrete-event simulation model suggested that six new English centres might generate 190 quality-adjusted life-years (95% confidence interval –6 to 399 quality-adjusted life-years) and a saving of £1,864,000 per year (95% confidence interval –£1,204,000 to £5,017,000 saving per year). The total mean thrombectomy cost up to 72 hours was £12,440, mostly attributable to the consumables. There was no significant cost difference between direct admission and secondary transfer (mean difference –£368, 95% confidence interval –£1016 to £279; p = 0.26). Limitations: Evidence for paramedic assessment fidelity was limited and group allocation could not be masked. Thrombectomy surveys represented respondent views only. Simulation models assumed that populations were consistent with published meta-analyses, included limited parameters reflecting underlying data sets and did not consider the capital costs of setting up new services. Conclusions: Paramedic assessment did not increase the proportion of patients receiving thrombolysis, but outcomes were consistent with improved cost-effectiveness at day 90, possibly reflecting better informed treatment decisions and/or adherence to clinical guidelines. However, the health difference was non-significant, small and short term. Approximately 12% of stroke patients are suitable for thrombectomy and widespread provision is likely to generate health and resource gains. Clinician and public views support secondary transfer to access treatment. Future work: Further evaluation of emergency care pathways will determine whether or not enhanced paramedic assessment improves hospital guideline compliance. Validation of the simulation model post reconfiguration will improve precision and describe wider resource implications. Trial registration: This trial is registered as ISRCTN12418919 and the systematic review protocols are registered as PROSPERO CRD42014010785 and PROSPERO CRD42015016649. Funding: The project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 4. See the NIHR Journals Library website for further project information.

Introduction Chronic pain and disability are now well-recognised long-term complications of blunt chest wall trauma. Limited research exists regarding therapeutic interventions that can be used to address these complications. A recent feasibility study was completed testing the methods of a definitive trial. This protocol describes the proposed definitive trial, the aim of which is to investigate the impact of an early exercise programme on chronic pain and disability in patients with blunt chest wall trauma.Methods/analysis This mixed-methods, multicentre, parallel randomised controlled trial will run in four hospitals in Wales and one in England over 12-month recruitment period. Patients will be randomised to either the control group (routine physiotherapy input) or the intervention group (routine physiotherapy input plus a simple exercise programme completed individually by the patient). Baseline measurements including completion of two surveys (Brief Pain Inventory and EuroQol 5-dimensions, 5-Levels) will be obtained on initial assessment. These measures and a client services receipt inventory will be repeated at 3-month postinjury. Analysis of outcomes will focus on rate and severity of chronic pain and disability, cost-effectiveness and acceptability of the programme by patients and clinicians. Qualitative feedback regarding acceptability will be obtained through patient and clinician focus groups.Ethics/dissemination London Riverside Research Ethics Committee (Reference number: 21/LO/0782) and the Health Research Authority granted approval for the trial in December 2021. Patient recruitment will commence in February 2022. Planned dissemination is through publication in a peer-reviewed Emergency Medicine Journal, presentation at appropriate conferences and to stakeholders at professional meetings.Trial registration number ISRCTN65829737; Pre-results.

Abstract Background Opioids, such as heroin, kill more people worldwide by overdose than any other type of drug, and death rates associated with opioid poisoning in the UK are at record levels (World Drug Report 2018 [Internet]. [cited 2019 Nov 19]. Available from: http://www.unodc.org/wdr2018/ ; Deaths related to drug poisoning in England and Wales - Office for National Statistics [Internet]. [cited 2019 Nov 19]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2018registrations ). Naloxone is an opioid antagonist which can be distributed in ‘kits’ for administration by witnesses in an overdose emergency. This intervention is known as take-home naloxone (THN). We know that THN can save lives on an individual level, but there is currently limited evidence about the effectiveness of THN distribution on an aggregate level, in specialist drug service settings or in emergency service settings. Notably, we do not know whether THN kits reduce deaths from opioid overdose in at-risk populations, if there are unforeseen harms associated with THN distribution or if THN is cost-effective. In order to address this research gap, we aim to determine the feasibility of a fully powered cluster randomised controlled trial (RCT) of THN distribution in emergency settings. Methods We will carry out a feasibility study for a RCT of THN distributed in emergency settings at four sites, clustered by Emergency Department (ED) and catchment area within its associated ambulance service. THN is a peer-administered intervention. At two intervention sites, emergency ambulance paramedics and ED clinical staff will distribute THN to adult patients who are at risk of opioid overdose. At two control sites, practice will carry on as usual. We will develop a method of identifying a population to include in an evaluation, comprising people at risk of fatal opioid overdose, who may potentially receive naloxone included in a THN kit. We will gather anonymised outcomes up to 1 year following a 12-month ‘live’ trial period for patients at risk of death from opioid poisoning. We expect approximately 100 patients at risk of opioid overdose to be in contact with each service during the 1-year recruitment period. Our outcomes will include deaths, emergency admissions, intensive care admissions, and ED attendances. We will collect numbers of eligible patients attended by participating in emergency ambulance paramedics and attending ED, THN kits issued, and NHS resource usage. We will determine whether to progress to a fully powered trial based on pre-specified progression criteria: sign-up of sites (n = 4), staff trained (≥ 50%), eligible participants identified (≥ 50%), THN provided to eligible participants (≥ 50%), people at risk of death from opioid overdose identified for inclusion in follow-up (≥ 75% of overdose deaths), outcomes retrieved for high-risk individuals (≥ 75%), and adverse event rate (< 10% difference between study arms). Discussion This feasibility study is the first randomised, methodologically robust investigation of THN distribution in emergency settings. The study addresses an evidence gap related to the effectiveness of THN distribution in emergency settings. As this study is being carried out in emergency settings, obtaining informed consent on behalf of participants is not feasible. We therefore employ novel methods for identifying participants and capturing follow-up data, with effectiveness dependent on the quality of the available routine data. Trial registration ISRCTN13232859 (Registered 16/02/2018)

Background Skin cancer, including melanoma and non-melanoma (keratinocyte), is increasing in incidence in the UK. Accounting for half of all cancers in England and Wales, the disease significantly impacts overstretched dermatology services. Research suggests that 86% of melanoma is preventable with modified sun exposure. Educating children about sun safety in schools can help prevent skin cancer and is recommended by major health organisations. In England, teaching sun safety in primary schools is compulsory, while in Wales this is left to school discretion. Aims Understand how primary schools in Wales are responding to growing skin cancer rates and explore the effectiveness of sun safety policies in schools on knowledge and behaviour. Methods Sunproofed is a mixed-methods scoping study comprising 5 work packages (WP) using survey and routine electronic health record (EHR) data supplemented by qualitative case studies. Objective(s) are to: WP1: Discover if primary schools in Wales have sun safety policies; policy characteristics; determine factors that may influence their presence and identify areas where schools need support. WP2: Determine what EHR data is available regarding the incidence of sunburn in primary school children and the feasibility of using this data to evaluate the impact of sun safety policies. WP3: Understand the impact of sun safety policies on sun-safe knowledge and behaviour amongst children, parents, teachers, and school management; identify barriers and facilitators to schools implementing sun safety policies. WP4: Co-produce guidance regarding sun safety policies and best methods for implementation in schools. WP5: Disseminate guidance and findings widely to ensure impact and uptake. Discussion Skin cancer rates are increasing in the UK, straining limited resources. Sunproofed has the potential to inform the development of future prevention activities, both in Wales and beyond. This could reduce the number of skin cancer cases in the future and keep people healthier for longer.

Background: Protocols are an essential document for conducting randomised controlled trials (RCTs). However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Initiative in 2013. Presently, there is increasing use of cohorts and routinely collected data (RCD) for RCTs because these data have the potential to improve efficiencies by facilitating recruitment, simplifying, and reducing the cost of data collection. Reporting guidelines have been shown to improve the quality of reporting, but there is currently no specific SPIRIT guidance on protocols for trials conducted using cohorts and RCD. This protocol outlines steps for developing SPIRIT-ROUTINE, which aims to address this gap by extending the SPIRIT guidance to protocols for trials conducted using cohorts and RCD. Methods: The development of the SPIRIT-ROUTINE extension comprises five stages. Stage 1 consists of a project launch and a meeting to finalise the membership of the steering group and scope of the extension. In Stage 2, a rapid review will be performed to identify possible modifications to the original SPIRIT 2013 checklist. Other key reporting guidelines will be reviewed to identify areas where additional items may be needed, such as the Consolidated Standards of Reporting Trials (CONSORT) extension for trials conducted using cohorts and RCD (CONSORT-ROUTINE). Stage 3 will involve an online Delphi exercise, consisting of two rounds and involving key international stakeholders to gather feedback on the preliminary checklist items. In Stage 4, a consensus meeting of the SPIRIT-ROUTINE steering group will finalise the items to include in the extension. Stage 5 will involve the publication preparation and dissemination of the final checklist. Conclusion: The SPIRIT-ROUTINE extension will contribute to improving design of trials using cohorts and RCD and transparency of reporting.

Rationale Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.Approach The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.Reflection Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.Discussion EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Abstract Background In managing hip fracture, effective pain relief before admission to hospital is difficult without risking side effects. Although emergency departments routinely use fascia iliaca compartment block (FICB), there has been little evaluation of its use by paramedics before hospital admission. We aimed to assess whether a multi-centre randomised trial to evaluate FICB was feasible. Methods Volunteer paramedics used scratchcards to allocate patients with hip fracture at random between FICB and pain relief as usual. Primary outcomes were mortality and quality of life. We also measured adverse events, costs, final diagnosis, length of stay in hospital, pain scores and quality of care and collected qualitative data about acceptability to patients in interviews, and paramedics in focus groups. We pre-specified criteria for deciding whether to progress to a fully powered trial based on the recruitment of paramedics and patients, delivery of FICB, retrieval of outcome data, safety, acceptability, and diagnostic accuracy of hip fracture. Results We effectively met all progression criteria: we recruited 19 paramedics who randomly allocated 71 patients between trial arms between 28 June 2016 and 31 July 2017; 57 (31 experimental arm, 26 usual care arm, 80% overall) retrospectively consented to follow-up. Just over half (17/31) of experimental participants received FICB; all others had contraindications, including nine taking anticoagulants. Four of the 31 participants assigned FICB and six of the 26 assigned usual care died within 6 months of hospital admission. Serious adverse events were also similar: 3/35 experimental versus 4/36 in usual care. Paramedics’ recognition of hip fracture had sensitivity of 49/64 (77%) with a positive predictive value of 46/57 (81%). We received quality of life questionnaires for 30 of 49 patients (61%) at 1 month and 12 of 17 (71%) at 6 months. Patient satisfaction was similar: experimental mean 3.4 (n = 20) versus 3.5 (n = 13) for usual care. Conclusions RAPID met all progression criteria within reasonable limits. As equipoise remains, we plan to undertake a fully powered multi-centre trial to test clinical and cost effectiveness of paramedic-administered FICB at the scene of hip fracture. Trial registration ISRCTN 60065373 sought 5 November 2015.

Abstract Background Despite evidence from clinical trials that intravenous (IV) thrombolysis is a cost-effective treatment for selected acute ischaemic stroke patients, there remain large variations in the rate of IV thrombolysis delivery between stroke services. This study is evaluating whether an enhanced care pathway delivered by paramedics (the Paramedic Acute Stroke Treatment Assessment (PASTA)) could increase the number of patients who receive IV thrombolysis treatment. Methods Study design: Cluster randomised trial with economic analysis and parallel process evaluation. Setting: National Health Service ambulance services, emergency departments and hyper-acute stroke units within three geographical regions of England and Wales. Randomisation: Ambulance stations within each region are the units of randomisation. According to station allocation, paramedics based at a station deliver the PASTA pathway (intervention) or continue with standard stroke care (control). Study intervention: The PASTA pathway includes structured pre-hospital information collection, prompted pre-notification, structured handover of information in hospital and assistance with simple tasks during the initial hospital assessment. Study-trained intervention group paramedics deliver this pathway to adults within 4 h of suspected stroke onset. Study control: Standard stroke care according to national and local guidelines for the pre-hospital and hospital assessment of suspected stroke. Participants: Participants enrolled in the study are adults with confirmed stroke who were assessed by a study paramedic within 4 h of symptom onset. Primary outcome: Proportion of participants receiving IV thrombolysis. Sample size: 1297 participants provide 90% power to detect a 10% difference in the proportion of patients receiving IV thrombolysis. Discussion The results from this trial will determine whether an enhanced care pathway delivered by paramedics can increase thrombolysis delivery rates. Trial registration ISRCTN registry, ISRCTN12418919. Registered on 5 November 2015.

Introduction Multimorbidity is widely recognised as the presence of two or more concurrent long-term conditions, yet remains a poorly understood global issue despite increasing in prevalence.We have created the Wales Multimorbidity e-Cohort (WMC) to provide an accessible research ready data asset to further the understanding of multimorbidity. Our objectives are to create a platform to support research which would help to understand prevalence, trajectories and determinants in multimorbidity, characterise clusters that lead to highest burden on individuals and healthcare services, and evaluate and provide new multimorbidity phenotypes and algorithms to the National Health Service and research communities to support prevention, healthcare planning and the management of individuals with multimorbidity.Methods and analysis The WMC has been created and derived from multisourced demographic, administrative and electronic health record data relating to the Welsh population in the Secure Anonymised Information Linkage (SAIL) Databank. The WMC consists of 2.9 million people alive and living in Wales on the 1 January 2000 with follow-up until 31 December 2019, Welsh residency break or death. Published comorbidity indices and phenotype code lists will be used to measure and conceptualise multimorbidity.Study outcomes will include: (1) a description of multimorbidity using published data phenotype algorithms/ontologies, (2) investigation of the associations between baseline demographic factors and multimorbidity, (3) identification of temporal trajectories of clusters of conditions and multimorbidity and (4) investigation of multimorbidity clusters with poor outcomes such as mortality and high healthcare service utilisation.Ethics and dissemination The SAIL Databank independent Information Governance Review Panel has approved this study (SAIL Project: 0911). Study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.

Pesticides use in Southeast Asia has increased steadily, driven by the growth of large-scale commercial farming, as well as a desire to maximise food production in rural subsistence economies. Given that use of chemical pesticides, such as organophosphates and carbamates, has known potential health impacts, there are concerns about the safety of agricultural workers, and a need for a better evidence base to underpin regulation and worker education. This study, undertaken in 9 districts in Lao PDR, Thailand and Vietnam, will interview agricultural workers to investigate how they use pesticides, their knowledge of risks and self-protective practices, and their self-reported illness symptoms. In each district researchers will recruit and interview 120 participants engaged in vegetable farming, who have recently used pesticides, making a total of 1080 subjects divided equally between the three study countries. Workers' degree of pesticides exposure will be determined from acetyl cholinesterase concentrations in capillary blood samples collected using field test kits, and these data will be analysed together with the interview findings. Country findings will be compared and contrasted, and general patterns noted. Knowledge gained about risky behaviours, self-protective practices and degree of association with serious pesticides exposure will assist policy makers and inform health improvement programmes.

Introduction Green and blue spaces (GBS), such as parks, woodlands, rivers, and beaches, are thought to be important for mental health and wellbeing. Our longitudinal cohort contains objective household-level environment data linked at the invidual level to routinely recorded mental health data, augmented with cross sectional self-reported health behaviours, including leisure visits to the outdoors. Objectives and Approach Our overall approach will evaluate if residential proximity to GBS is associated with mental health and wellbeing, and if any associations are modified by visits to outdoors spaces following individual-level data linkage. Here, we examined cross-sectional survey data on time spent visiting nature outdoors. Wellbeing outcomes were assessed using self-reported scores. Data were analysed using generalised additive models in the SAIL Databank. Results Using a sample of National Survey for Wales respondents (2016/17, n=3,481), over 40% of adults in Wales reported spending less than 30 minutes outdoors each week. Weekly time outdoors was positively associated with wellbeing (p=0.007) and life satisfaction (p=0.03) having adjusted for potential confounders including, age, rurality, loneliness, employment status. Confidence intervals varied along the fitted GAM model. Models using a second wave of survey data (n≈7,000), anonymously record-linked to residential environment and health data will explore these associations further. Conclusion A previous study based in England (White et al. 2019) found an upper wellbeing benefit threshold of 2 hours per week for time spent in nature. This was not apparent in our preliminary models, but may be revealed in further analyses. We will next incorporate longitudinal mental health and environmental data for 2 million adults living in Wales, UK. Linking to ambient and accessible residential GBS, while taking into account changes due to migration and actual visits, will allow us to provide valuable guidance to local government, who are often responsible for provisioning and maintaining outdoor facilities.

Introduction Common mental health disorders (CMD) are significant contributors to impaired health and well-being, and drive greater health resource utilisation. Electronic health records (EHR) are increasingly used for case identification of CMD when ascertaining social determinants of mental health. We seek to compare self-reported well-being indicators in groups identified using EHR-based CMD methods. Objectives and Approach The National Survey for Wales (NSW) contains self-reported well-being indicators (Warwick Edinburgh Mental Well-being Scale, WEMWBS) recorded annually on ~7,000 individuals. We combined data from two NSWs and linked well-being indicators with Welsh Longitudinal General Practice (WLGP) data within the Secure Anonymised Information Linkage (SAIL) Databank, using individual response dates. We then used WGLP data to algorithmically derive identifiers of CMD cases within survey respondents. This individual-level linkage enables a comparison of NSW responses in CMD and non-CMD cases, and to assess sensitivity and specificity of the current CMD algorithm. Results Survey participants comprised 18,450 adults aged 16+ and living in Wales during 16/17 or 18/19. WEMWBS responses indicate 2,338 (12.6%) participants could be considered possibly depressed, and 2,268 (12.3%) probably depressed with low mental well-being (LMW). For participants with LMW, a 42/58 percentage split is observed between male/female respondents, compared to a 45/55 respective split of those not identified with LMW. Participants with LMW recorded low measures for overall satisfaction with life, 998 (44%) reported a value of 5 or less (/10) compared to 1123 (7%) participants not identified with LMW. Similarly, 828 (37%) participants identified with LMW reported 5 or less (/10) on the life worthwhile index, compared to 800 (5%) of non-LMW participants. Conclusion / Implications Linkage to the NSW provides a rich data source to compare objective well-being to algorithmically derived CMD cases from routinely collected primary care data. The individual-level linkage involved will allow for the wider determinants of mental health disorders to be examined.

Introduction A growing evidence base indicates health benefits are associated with access to green-blue spaces (GBS), such as beaches and parks. However, few studies have examined associations with changes in access to GBS over time. Objectives and Approach We have linked cross-sector data collected within Wales, United Kingdom, quarterly from 2008 to 2019, to examine the impact of GBS access on individual-level well-being and common mental health disorders (CMD). We created a longitudinal dataset of GBS access metrics, derived from satellite and administrative data sources, for 1.4 million homes in Wales. These household-level metrics were linked to individuals using the Welsh Demographic Service Dataset within the Secure Anonymised Information Linkage (SAIL) Databank. Linkage to Welsh Longitudinal General Practice data within SAIL enabled us to identify individual-level CMD over time. We also linked individual-level self-reported GBS use and well-being data from the National Survey for Wales (NSW) to routine data for cross-sectional survey participants. Results We created a longitudinal cohort panel capturing all 2.84 million adults aged 16+ living in Wales between 2008 and 2019 and with a general practitioner (GP) registration. Individual-level health data and household-level environmental metrics were linked for each quarter an individual is in the study. Household addresses were linked to 97% of the cohort, creating 110+ million rows of anonymously linked cross-sector data. The cohort provides an average follow-up period of 8 years, during which 565,168 (20%) adults received at least one CMD diagnosis or symptom. Conclusion / Implications This example of multi-sectoral data linkage across multiple environmental and administrative data sources has created a rich data source, which we will use to quantify the impact of changes in GBS access on individual–level CMD and well-being. This evidence will inform policy in the areas of health, planning and the environment.

Introduction The electronic Frailty Index (eFI) and the Hospital Frailty Risk Score (HFRS) have been developed in primary and secondary care respectively. Objectives and Approach Our objective was to investigate how frailty progresses over time, and to include the progression of frailty in a survival analysis. To do this, we performed a retrospective cohort study using linked data from the Secure Anonymised Information Linkage Databank, comprising 445,771 people aged 65-95 living in Wales (United Kingdom) on 1st January 2010. We calculated frailty, using both the eFI and HFRS, for individuals at quarterly intervals for 8 years with a total of 11,702,242 observations. Results We created a transition matrix for frailty states determined by the eFI (states: fit, mild, moderate, severe) and HFRS (states: no score, low, intermediate, high), with death as an absorbing state. The matrix revealed that frailty progressed over time, but that on a quarterly basis it was most likely that an individual remained in the same state. We calculated Hazard Ratios (HRs) using time dependent Cox models for mortality, with adjustments for age, gender and deprivation. Independent eFI and HFRS models showed increased risk of mortality as frailty severity increased. A combined eFI and HFRS revealed the highest risk was primarily determined by the HFRS and revealed further subgroups of individuals at increased risk of an adverse outcome. For example, the HRs (95% Confidence Interval) for individuals with an eFI as fit, mild, moderate and severe with a high HFRS were 18.11 [17.25,19.02], 20.58 [19.93,21.24], 21.45 [20.85,22.07] and 23.04 [22.34,23.76] respectively with eFI fit and no HFRS score as the reference category. Conclusion Frailty was found to vary over time, with progression likely in the 8-year time-frame analysed. We refined HR estimates of the eFI and HFRS for mortality by including time dependent covariates.

Introduction Research involving care homes is often difficult due to a lack of data and ethical issues. Wales (United Kingdom) contains approximately 1.3million residences, of these 717 are officially recorded as care homes for older people. Objectives and Approach Our objective was to develop a predictive methodology for identifying care homes in administrative data. We used two data sources within the Secure Anonymised Information Linkage Databank to conduct our study. The Welsh Demographic Service Dataset (WDSD) contains all residences in Wales and demographic details of their occupants. An anonymised dataset of deterministically matched care home addresses was used to determine which of the residences in the WDSD were care homes. We used details in the WDSD to determine the average age of the occupants, the number of people who moved into the residence in a year, and the number of people who died in a year. We were interested in care homes for older people and restricted all the residences in the WDSD to only those with an average age of 50+ years. We applied logistic regression to determine a probabilistic match for care homes based on the above characteristics. We determined an optimal cut-point for the probability of a residence being a care home based on the sensitivity and specificity. Results Restricting the WDSD to have an average age of occupants of 50+ created a dataset of 3,939 residences, containing 562 care homes. After applying the logistic model to predict the care homes, we found an optimal probability cut-point which resulted in 548 true positives, 105 false positives, 14 false negatives, and 3,272 true negatives. Implications Identification of care homes in an anonymised databank using only demographic data allows research into healthcare pathways for this hard to reach and under-researched population.

Introduction Around a third of people aged 65+, and around half of people aged 80+ fall at least once a year in the United Kingdom. Homes may be adapted to try to prevent falls, but evidence on the effectiveness of home adaptations is limited. Objectives and Approach Our objective was to determine if proactive (Care&Repair service) and reactive (rapid response) home adaptations provided by Care&Repair Cymru resulted in a reduced risk of a fall for older people aged 60+ in Wales. We constructed a longitudinal dataset from the Secure Anonymised Information Linkage Databank. We created quarterly intervals for 5-years pre and post the date a home adaptation was received, or a randomly assigned date for the comparator. Per quarter, we created a binary indicator of whether someone had a fall at home that was recorded in either the emergency department or hospital admission data sources for Wales. We included key demographic variables as covariates. We analysed the data using logistic regression and a difference-in-difference approach. Results We analysed 634,046 individuals, of whom 60,794 received the proactive Care&Repair service, and 47,244 received the reactive rapid response service. People receiving proactive or reactive home adaptations from Care & Repair were at around a two-fold increased risk of falling, compared to those who did not receive home adaptation with Odds Ratios (ORs) of 2.13 [95%CI: 2.07, 2.20] and 2.73 [2.64,2.81] respectively. Falls risk increased per quarter for all individuals, but after intervention delivery, the rate of increase fell in the intervention groups. Conclusion People receiving home adaptations from Care&Repair had a higher chance of a fall, indicating the service was successfully identifying those in need. Falls risk increased for everyone over time, but this was counteracted for people receiving an intervention.

Introduction Multi-morbidity is a widely recognised but poorly understood global issue that appears to be increasing in prevalence, according to the UK’s Academy of Medical Sciences (AMS) report in 2018. Disease clustering, their determinants and consequences are poorly researched. Better understanding would help drive prevention and improved clinical care, services and patient outcomes. Objectives and Approach Development of two comprehensive population-wide e-cohorts, derived utilising data linkage techniques and including multi-sourced anonymised routine health and demographic data held within the SAIL Databank. The objective is to characterise multi-morbidity and its clustering, determinants and outcomes and compare methods using a) prospective cohort design using multiple data sources in Wales and b) retrospective cohort design to examine household level and environment clustering using GP data in demographically diverse populations (Wales and North East London). The prospective e-cohort focuses on adults living in Wales on 1 st January 2000 and followed up to 2020, including data from the NHS population register, deaths, inpatients, outpatients, Emergency Department, GP, disease registries, laboratory data, and population surveys with QoL measures. This e-cohort will be harmonised with other sites across the UK. The retrospective e-cohort is designed to harmonise with a North East London e-cohort, including all individuals living in Wales on 24 th April 2018 and registered with a GP. Results 2.8 and 2.2 million individuals have been included in the prospective and retrospective cohorts respectively, with 43.6 million person years of follow up. Established comorbidity indices and published phenotypes from libraries are being applied to the data to create initial prevalence and incidence estimates for further analysis. Important clusters will be determined by associations with mortality and excess healthcare utilisation. Conclusion/Implications Building the e-cohorts has involved multiple disciplines across organisations. Multi-morbidity prevalence estimates and study designs will be compared prior to statistical analyses and machine learning methods to evaluate clustering and determinants.

Objectives: We sought to explore the sociodemographics and primary care service utilization among people who died from opioid overdose and to assess the possibility of using this information to identify those at high risk of opioid overdose using routine linked data. Methods: Data related to decedents of opioid overdose between January 1, 2012 and December 31, 2015 were linked with general practitioner (GP) records over a period of 36 months prior to death. Results: Of n = 312 decedents of opioid overdose, 73% were male (n = 228). Average age at death was 40.72 (SD 11.92) years. A total of 63.8% of the decedents were living in the 2 most deprived quintiles according to the Welsh Index of Multiple Deprivation. Over 80% (n = 258) of the decedents were recorded as having at least 1 GP episode during the 36-month observation period prior to death. The median number of episodes per decedent was 75 [38-118]. Overall, 31.8% (n = 82) of decedents with at least 1 GP episode received a prescription for a proton pump inhibitor and 31% (n = 80) were prescribed a broad-spectrum antibiotic. According to their GP records, less than 10% were referred to or receiving specialist drug treatment (n = 24, 9.3%); or were known to be drug dependent (n = 21, 8.14%), or a drug user (n = 5, 1.94%). In all, 81% were recorded as smokers (n = 209) and 10.5% as ex-smokers (n = 27). Conclusions: The majority of decedents of opioid overdose were in contact with GP services prior to death. GPs are either often unaware of high-risk opioid use, or rarely record details of opioid use in patient notes. It is possible that GP awareness of high-risk opioid use could be increased. For example, awareness of the risks associated with opioid use, and the relationship between the sociodemographic and clinical characteristics of opioid overdose decedents could be raised using educational materials prominently displayed in waiting areas. Clinicians in primary care may be in an excellent position to intervene in problematic opioid use.

Background The use of anonymised routine linked data in designing and conducting randomised controlled trials (RCTs) has great potential. Sample sizes can be large, inclusion rates high and follow up periods prolonged, while the disruption to participants’ usual routines may be minimised. However, challenges and limitations in using routine linked data in RCTs remain. Aims To describe, in primary and emergency settings, challenges and opportunities associated with designing and conducting RCTs using anonymised linked routine data to identify study participants and gather outcomes. Methods In each of these trials we have used routine linked data as a key part of the research study design: PRISMATIC (a stepped wedge trial of predictive risk stratification in primary care) utilised linked data outcomes related to emergency admissions to hospital, GP activity and outpatient appointments. Outcomes were included for 230,000 people registered to participating GP practices in the Swansea area SAFER 2: a cluster randomised trial of referral to falls services by ambulance paramedics included linked data outcomes related to subsequent emergency episodes for 4,655 patients across three UK regions TIME: feasibility trial of Take Home Naloxone randomised by city; routine linked data used to identify population for inclusion in follow up and outcomes Regulatory processes - ethics, research and information governance permissions - have caused delay in each trial; inclusion rates have been much higher than is usual in RCTs (outcomes for >80% of eligible patients); large trials have been achievable at reasonable cost (each trial

Background People who frequently call the 999 ambulance service present an operational challenge to providers and their needs are inadequately met by current service provision. Aim of research To understand patterns and health outcomes of frequent calling and to work with stakeholders to co-produce guidance for formal testing in a future evaluation. Methods In this mixed methods study I will carry out a scoping review of national and international literature, including grey literature. I will identify two cohorts of patients 12 months retrospectively who meet the frequent caller threshold. Twelve month health outcomes for both cohorts will be explored through anonymised linked data outcomes using general linear model. I will examine the views of patients using qualitative Bio-photographic interview method with a follow up interview at six months. This will be supported with provider focus groups. All interviews will be thematically analysed. I plan to use information collected from this study to work with two public members, patients and stakeholders to co-produce guidance for optimal care. Results Findings will include follow up of eligible patients (n=400); successful data matching and data linkage; retrieval of outcomes within 12 months. Outcomes will include: adverse events, deaths, emergency admissions; 999 attendances. Bio-photographic interviews with completed scrap books and interviews based on the books (n=34). Care provider focus groups (n= 22). Output Co-produced guidance developed with stakeholders. Conclusion Frequent callers with high needs represent a significant policy challenge to emergency ambulance services. This study will inform on the characteristics of frequent callers and how to address their care supported with a co-produced guidance for care providers.

BackgroundRefractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.AimsTo estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627).MethodWe undertook a cost-effectiveness analysis alongside a randomised trial evaluating RO DBT plus TAU versus TAU alone for refractory depression in three UK secondary care centres. Our economic evaluation, 12 months after randomisation, adopted the perspective of the UK National Health Service (NHS) and personal social services. It evaluated cost-effectiveness by comparing the net cost of RO DBT with the net gain in quality-adjusted life-years (QALYs), estimated using the EQ-5D-3L measure of health-related quality of life.ResultsThe additional cost of RO DBT plus TAU compared with TAU alone was £7048 and was associated with a difference of 0.032 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of £220 250 per QALY. This ICER was well above the National Institute for Health and Care Excellence (NICE) upper threshold of £30 000 per QALY. A cost-effectiveness acceptability curve indicated that RO DBT had a zero probability of being cost-effective compared with TAU at the NICE £30 000 threshold.ConclusionsIn its current resource-intensive form, RO DBT is not a cost-effective use of resources in the UK NHS.Declaration of interestR.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from the National Institute for Health Research (NIHR). T.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd, and a grant outside the submitted work from the Medical Research Council. He was co-director of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two directors of Radically Open Ltd. H.O'M. reports personal fees outside the submitted work from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.R. provides RO DBT supervision through her company S C Rushbrook Ltd. I.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M. Stanton reports personal fees outside the submitted work from British Isles DBT Training, Stanton Psychological Services Ltd and Taylor & Francis. M. Swales reports personal fees outside the submitted work from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis. B.W. was co-director of Radically Open Ltd between November 2014 and February 2015.

Background: About one-third of patients who are depressed do not respond to antidepressant medication (ADM) and traditional psychotherapy shows limited benefits. However, most randomised trials have excluded the most sick patients, especially with comorbid personality disorder. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting emotionally overcontrolled personality, which is common in refractory depression. Objective: To evaluate the efficacy, cost-effectiveness and therapeutic mechanisms of RO DBT for patients with refractory depression. Design: The Refractory depression: Mechanisms and Efficacy of RO DBT (RefraMED) trial was a multicentre, parallel-group, randomised trial in which participants were randomised to receive either RO DBT plus treatment as usual (TAU) or TAU alone. Participants were assessed at 7, 12 and 18 months after randomisation. Therapeutic mechanisms were explored in causal analyses. Setting: Participants were recruited from three secondary care NHS organisations in the UK: Dorset, Hampshire and North Wales. Participants: Patients were eligible if they were aged ≥ 18 years, had a Hamilton Rating Scale for Depression (HRSD) score of at least 15, had a current diagnosis of major depressive disorder in the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I, were suffering either refractory or chronic depression and, in their current episode, had taken an adequate dose of ADM for at least 6 weeks without relief. Patients who met criteria for dramatic-erratic personality disorder (Cluster B), bipolar disorder or psychosis or who had a primary diagnosis of substance dependence or abuse were excluded. Interventions: The intervention, RO DBT, comprised 29 weekly individual sessions lasting 1 hour and 27 weekly skills classes lasting 2.5 hours. Participants allocated to TAU could access any treatment offered by the NHS or privately. Main outcome measures: The reported HRSD score 12 months after randomisation and cost per quality-adjusted life-year (QALY). Results: A total of 250 participants were allocated at random: 162 (65%) participants were randomised to RO DBT plus TAU and 88 (35%) were randomised to TAU. The difference between RO DBT and TAU in the primary outcome at 12 months was not statistically significant. Nevertheless, after 7 months, participants randomised to RO DBT had substantially, and significantly, reduced depressive symptoms, relative to TAU, by 5.40 HRSD points [standardised mean difference 1.03 points, 95% confidence interval (CI) 0.94 to 9.85 points; p = 0.02]. Thereafter, RO DBT remained the better treatment with net, but non-significant, reductions of 2.15 HRSD points (standardised mean difference 0.41 points, 95% CI –2.28 to 6.59 points; p = 0.29) after 12 months and 1.69 points (standardised mean difference 0.32 points, 95% CI –2.84 to 6.22 points; p = 0.42) after 18 months. Participants allocated to TAU could access any treatment offered by the NHS or privately. Participants randomised to RO DBT reported significantly better psychological flexibility and emotional coping than TAU participants; these differences increased over time. From the perspective of the NHS and personal social services, RO DBT was not cost-effective; the incremental cost-effectiveness ratio was £220,000 per QALY, which is considerably above the willingness-to-pay threshold of £30,000 set by the National Institute for Health and Care Excellence (NICE). RO DBT participants reported eight possible serious adverse reactions compared with none by TAU participants; however, we believe that this imbalance was a result of major differences in reporting opportunities. The Data Monitoring and Ethics Committee agreed that there was no reason to suspect that RO DBT was harmful. Conclusions: Although RO DBT achieved the target effect size (Cohen’s d) with a d of 0.4 at the primary end point of 12 months, this was not significant. RO DBT was not cost-effective by NICE criteria. Nevertheless, RO DBT enhanced psychological flexibility and emotional coping, which are potential mechanisms of change. Limitations: Analysing only 190 participants, instead of the target of 245, reduced the statistical power of the trial. Future work: Future studies should aim to refine RO DBT, by maintaining clinical effectiveness while reducing costs, and to evaluate it for a wider range of overcontrolled disorders over a longer period. Trial registration: Current controlled trials ISRCTN85784627. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 5, No. 7. See the NIHR Journals Library website for further project information.

Background: Cold homes and fuel poverty contribute to health inequalities in ways that could be addressed through energy efficiency interventions. Objectives: To determine the health and psychosocial impacts of energy performance investments in low-income areas, particularly hospital admissions for cardiorespiratory conditions, prevalence of respiratory symptoms and mental health status, hydrothermal conditions and household energy use, psychosocial outcomes, cost consequences to the health system and the cost utility of these investments. Design: A mixed-methods study comprising data linkage (25,908 individuals living in 4968 intervention homes), a field study with a controlled pre-/post-test design (intervention, n = 418; control, n = 418), a controlled multilevel interrupted time series analysis of internal hydrothermal conditions (intervention, n = 48; control, n = 40) and a health economic assessment. Setting: Low-income areas across Wales. Participants: Residents who received energy efficiency measures through the intervention programme and matched control groups. Main outcome measures: Primary outcomes – emergency hospital admissions for cardiorespiratory conditions, self-reported respiratory symptoms, mental health status, indoor air temperature and indoor relative humidity. Secondary outcomes – emergency hospital admissions for chronic obstructive pulmonary disease-related cardiorespiratory conditions, excess winter admissions, health-related quality of life, subjective well-being, self-reported fuel poverty, financial stress and difficulties, food security, social interaction, thermal satisfaction and self-reported housing conditions. Methods: Anonymously linked individual health records for emergency hospital admissions were analysed using mixed multilevel linear models. A quasi-experimental controlled field study used a multilevel repeated measures approach. Controlled multilevel interrupted time series analyses were conducted to estimate changes in internal hydrothermal conditions following the intervention. The economic evaluation comprised cost–consequence and cost–utility analyses. Data sources: The Patient Episode Database for Wales 2005–14, intervention records from 28 local authorities and housing associations, and scheme managers who delivered the programme. Results: The study found no evidence of changes in physical health. However, there were improvements in subjective well-being and a number of psychosocial outcomes. The household monitoring study found that the intervention raised indoor temperature and helped reduce energy use. No evidence was found of substantial increases in indoor humidity levels. The health economic assessment found no explicit cost reductions to the health service as a result of non-significant changes in emergency admissions for cardiorespiratory conditions. Limitations: This was a non-randomised intervention study with household monitoring and field studies that relied on self-response. Data linkage focused on emergency admissions only. Conclusion: Although there was no evidence that energy performance investments provide physical health benefits or reduce health service usage, there was evidence that they improve social and economic conditions that are conducive to better health and improved subjective well-being. The intervention has been successful in reducing energy use and improving the living conditions of households in low-income areas. The lack of association of emergency hospital admissions with energy performance investments means that we were unable to evidence cost saving to health-service providers. Future work: Our research suggests the importance of incorporating evaluations with follow-up into intervention research from the start. Funding: The National Institute for Health Research Public Health Research programme.

Background: With a higher proportion of older people in the UK population, new approaches are needed to reduce emergency hospital admissions, thereby shifting care delivery out of hospital when possible and safe. Study aim: To evaluate the introduction of predictive risk stratification in primary care. Objectives: To (1) measure the effects on service usage, particularly emergency admissions to hospital; (2) assess the effects of the Predictive RIsk Stratification Model (PRISM) on quality of life and satisfaction; (3) assess the technical performance of PRISM; (4) estimate the costs of PRISM implementation and its effects; and (5) describe the processes of change associated with PRISM. Design: Randomised stepped-wedge trial with economic and qualitative components. Setting: Abertawe Bro Morgannwg University Health Board, south Wales. Participants: Patients registered with 32 participating general practices. Intervention: PRISM software, which stratifies patients into four (emergency admission) risk groups; practice-based training; and clinical support. Main outcome measures: Primary outcome – emergency hospital admissions. Secondary outcomes – emergency department (ED) and outpatient attendances, general practitioner (GP) activity, time in hospital, quality of life, satisfaction and costs. Data sources: Routine anonymised linked health service use data, self-completed questionnaires and staff focus groups and interviews. Results: Across 230,099 participants, PRISM implementation led to increased emergency admissions to hospital [ΔL = 0.011, 95% confidence interval (CI) 0.010 to 0.013], ED attendances (ΔL = 0.030, 95% CI 0.028 to 0.032), GP event-days (ΔL = 0.011, 95% CI 0.007 to 0.014), outpatient visits (ΔL = 0.055, 95% CI 0.051 to 0.058) and time spent in hospital (ΔL = 0.029, 95% CI 0.026 to 0.031). Quality-of-life scores related to mental health were similar between phases (Δ = –0.720, 95% CI –1.469 to 0.030); physical health scores improved in the intervention phase (Δ = 1.465, 95% CI 0.774 to 2.157); and satisfaction levels were lower (Δ = –0.074, 95% CI – 0.133 to –0.015). PRISM implementation cost £0.12 per patient per year and costs of health-care use per patient were higher in the intervention phase (Δ = £76, 95% CI £46 to £106). There was no evidence of any significant difference in deaths between phases (9.58 per 1000 patients per year in the control phase and 9.25 per 1000 patients per year in the intervention phase). PRISM showed good general technical performance, comparable with existing risk prediction tools (c-statistic of 0.749). Qualitative data showed low use by GPs and practice staff, although they all reported using PRISM to generate lists of patients to target for prioritised care to meet Quality and Outcomes Framework (QOF) targets. Limitations: In Wales during the study period, QOF targets were introduced into general practice to encourage targeting care to those at highest risk of emergency admission to hospital. Within this dynamic context, we therefore evaluated the combined effects of PRISM and this contemporaneous policy initiative. Conclusions: Introduction of PRISM increased emergency episodes, hospitalisation and costs across, and within, risk levels without clear evidence of benefits to patients. Future research: (1) Evaluation of targeting of different services to different levels of risk; (2) investigation of effects on vulnerable populations and health inequalities; (3) secondary analysis of the Predictive Risk Stratification: A Trial in Chronic Conditions Management data set by health condition type; and (4) acceptability of predictive risk stratification to patients and practitioners. Trial and study registration: Current Controlled Trials ISRCTN55538212 and PROSPERO CRD42015016874. Funding: The National Institute for Health Research Health Services Delivery and Research programme.

ABSTRACT Objectives Over £68M was invested in a housing regeneration programme (Arbed) in 2010-2011 to improve the energy performance of houses in a number of deprived areas across Wales. Houses within the areas were retrofitted with measures, such as external wall insulation, solar hot water systems, solar panels and air source heat pumps. The study aims to establish whether such interventions improve residents’ physical and mental health, and the economic impact of change in health outcomes. Approach Address and intervention data were collected from 28 administrative centres and anonymously linked within the SAIL (Secure Anonymised Information Linkage) databank. Two comparator groups were created, one consisting of social houses, another from properties situated in the most deprived areas of Wales. Individuals with continuous residence of at least 60 days over a 10 year period were selected to create a dynamic cohort. Data on emergency hospital admissions and primary care records were extracted from SAIL to assess the impact of investments on healthcare utilisation for cardiovascular and respiratory conditions. Healthcare utilisation data also contributed towards an economic evaluation and excess winter admissions analyses. Results The final dataset comprises data from over half a million people contributing more than 3 million person years of exposure time to build up trends of hospital admissions across the study period. The intervention cohort consists of over 35,000 people, with about 7,000 separate hospital admissions recorded for our primary outcome. The analysis is based on a pooled time series regression using a difference-in-difference approach to estimate the health impact of the programme. Conclusion Retrospective analysis of such a natural experiment using routinely collected health data is possible using data linkage techniques. Final results will show whether social programmes to improve energy efficiency to homes in fuel poor areas have a wider impact on the healthcare resource utilisation of residents. We discuss the requirement for more standardised, accurate and timely data capture at the time of such economic investments to ensure the future feasibility of such studies. This project was funded by the National Institute for Health Research, Public Health Research (PHR) program (project number 11/3020/05) (http://www.nets.nihr.ac.uk/projects/phr/11302005).

Background: Emergency calls are frequently made to ambulance services for older people who have fallen, but ambulance crews often leave patients at the scene without any ongoing care. We evaluated a new clinical protocol which allowed paramedics to assess older people who had fallen and, if appropriate, refer them to community-based falls services. Objectives: To compare outcomes, processes and costs of care between intervention and control groups; and to understand factors which facilitate or hinder use. Design: Cluster randomised controlled trial. Participants: Participating paramedics at three ambulance services in England and Wales were based at stations randomised to intervention or control arms. Participants were aged 65 years and over, attended by a study paramedic for a fall-related emergency service call, and resident in the trial catchment areas. Interventions: Intervention paramedics received a clinical protocol with referral pathway, training and support to change practice. Control paramedics continued practice as normal. Outcomes: The primary outcome comprised subsequent emergency health-care contacts (emergency admissions, emergency department attendances, emergency service calls) or death at 1 month and 6 months. Secondary outcomes included pathway of care, ambulance service operational indicators, self-reported outcomes and costs of care. Those assessing outcomes remained blinded to group allocation. Results: Across sites, 3073 eligible patients attended by 105 paramedics from 14 ambulance stations were randomly allocated to the intervention group, and 2841 eligible patients attended by 110 paramedics from 11 stations were randomly allocated to the control group. After excluding dissenting and unmatched patients, 2391 intervention group patients and 2264 control group patients were included in primary outcome analyses. We did not find an effect on our overall primary outcome at 1 month or 6 months. However, further emergency service calls were reduced at both 1 month and 6 months; a smaller proportion of patients had made further emergency service calls at 1 month (18.5% vs. 21.8%) and the rate per patient-day at risk at 6 months was lower in the intervention group (0.013 vs. 0.017). Rate of conveyance to emergency department at index incident was similar between groups. Eight per cent of trial eligible patients in the intervention arm were referred to falls services by attending paramedics, compared with 1% in the control arm. The proportion of patients left at scene without further care was lower in the intervention group than in the control group (22.6% vs. 30.3%). We found no differences in duration of episode of care or job cycle. No adverse events were reported. Mean cost of the intervention was £17.30 per patient. There were no significant differences in mean resource utilisation, utilities at 1 month or 6 months or quality-adjusted life-years. In total, 58 patients, 25 paramedics and 31 stakeholders participated in focus groups or interviews. Patients were very satisfied with assessments carried out by paramedics. Paramedics reported that the intervention had increased their confidence to leave patients at home, but barriers to referral included patients’ social situations and autonomy. Conclusions: Findings indicate that this new pathway may be introduced by ambulance services at modest cost, without risk of harm and with some reductions in further emergency calls. However, we did not find evidence of improved health outcomes or reductions in overall NHS emergency workload. Further research is necessary to understand issues in implementation, the costs and benefits of e-trials and the performance of the modified Falls Efficacy Scale. Trial registration: Current Controlled Trials ISRCTN60481756 and PROSPERO CRD42013006418. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 13. See the NIHR Journals Library website for further project information.

Background: The efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness. Objective: To compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC. Method: Between May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years. Results: The 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682; p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096; p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353; p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188; p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493; p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546; p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917; p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114; p = 0.998); deaths (all three who died received infliximab; p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773; p

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P

ObjectiveTo evaluate effectiveness, safety and cost-effectiveness of Computerised Clinical Decision Support (CCDS) for paramedics attending older people who fall.DesignCluster trial randomised by paramedic; modelling.Setting13 ambulance stations in two UK emergency ambulance services.Participants42 of 409 eligible paramedics, who attended 779 older patients for a reported fall.InterventionsIntervention paramedics received CCDS on Tablet computers to guide patient care. Control paramedics provided care as usual. One service had already installed electronic data capture.Main outcome measuresEffectiveness: patients referred to falls service, patient reported quality of life and satisfaction, processes of care.SafetyFurther emergency contacts or death within one month.Cost-effectivenessCosts and quality of life. We used findings from published Community Falls Prevention Trial to model cost-effectiveness.Results17 intervention paramedics used CCDS for 54 (12.4%) of 436 participants. They referred 42 (9.6%) to falls services, compared with 17 (5.0%) of 343 participants seen by 19 control paramedics [Odds ratio (OR) 2.04, 95% CI 1.12 to 3.72]. No adverse events were related to the intervention. Non-significant differences between groups included: subsequent emergency contacts (34.6% versus 29.1%; OR 1.27, 95% CI 0.93 to 1.72); quality of life (mean SF12 differences: MCS -0.74, 95% CI -2.83 to +1.28; PCS -0.13, 95% CI -1.65 to +1.39) and non-conveyance (42.0% versus 36.7%; OR 1.13, 95% CI 0.84 to 1.52). However ambulance job cycle time was 8.9 minutes longer for intervention patients (95% CI 2.3 to 15.3). Average net cost of implementing CCDS was £208 per patient with existing electronic data capture, and £308 without. Modelling estimated cost per quality-adjusted life-year at £15,000 with existing electronic data capture; and £22,200 without.ConclusionsIntervention paramedics referred twice as many participants to falls services with no difference in safety. CCDS is potentially cost-effective, especially with existing electronic data capture.Trial registrationISRCTN Register ISRCTN10538608.