Search

Abstract Anti-PD(L)-1 inhibition combined with platinum doublet chemotherapy (Chemo-IO) has become the most frequently used standard of care regimen in patients with non-small cell lung cancer (NSCLC). The negative impact of antibiotics on clinical outcomes prior to anti-PD(L)-1 inhibition monotherapy (IO) has been demonstrated in multiple studies, but the impact of antibiotic exposure prior to initiation of Chemo-IO is controversial. We assessed antibiotic exposures at two time windows: within 60 days prior to therapy (-60 d window) and within 60 days prior to therapy and 42 days after therapy (-60 + 42d window) in 2028 patients with advanced NSCLC treated with Chemo-IO and IO monotherapy focusing on objective response rate (ORR: rate of partial response and complete response), progression-free survival (PFS), and overall survival (OS). We also assessed impact of antibiotic exposure in an independent cohort of 53 patients. Univariable and multivariable analyses were conducted along with a meta-analysis from similar studies. For the -60 d window, in the Chemo-IO group (N = 769), 183 (24%) patients received antibiotics. Antibiotic exposure was associated with worse ORR (27% vs 40%, p = 0.001), shorter PFS (3.9 months vs. 5.9 months, hazard ratio [HR] 1.35, 95%CI 1.1,1.6, p = 0.0012), as well as shorter OS (10 months vs. 15 months, HR 1.50, 95%CI 1.2,1.8, p = 0.00014). After adjusting for known prognostic factors in NSCLC, antibiotic exposure was independently associated with worse PFS (HR 1.39, 95%CI 1.35,1.7, p = 0.002) and OS (HR 1.61, 95%CI 1.28,2.03, p

Background: There is a global shortage of nurses and new strategies are required to recruit, support and retain this staff group. Organisational culture can have a significant impact on staff wellbeing and commitment. Recent years have seen attempts to foster a compassionate culture across healthcare systems. However, little is known about how nurses initiate self-care and how they feel cared for by their organisation, particularly in times of acute stress and need. Aims: This paper aims to address the research question, ‘In what ways do nurses experience compassion (or not) during times of acute stress?’, identifying where and how compassionate acts were enacted by individuals, within teams or organisations. Methods: Semi-structured interviews were conducted with 50 UK National Health Service (NHS) nurses in a longitudinal qualitative study (between March 2020 and September 2022). Results: Three themes were derived from our narrative analysis including: (1) Learning and practising self-compassion; (2) The presence and absence of interpersonal compassion; and (3) Organisational (non) compassionate acts. Findings indicate that self-compassion requires permission and discipline, often being unfamiliar terrain for nurses. Interpersonal compassion can buoy nurses during challenging times but can often be absent across teams. Nurses’ experiences of organisational acts of compassion were limited, and they often felt de-valued, unsupported and replaceable. Conclusions: Compassionate acts are enacted across three levels (self, team and organisation). To retain staff, particularly in acutely stressful or challenging situations, organisations, and those responsible for nursing management and policy need to foster a systems-based approach to compassionate culture.

Abstract Background Sexual health is fundamental to the overall health and wellbeing of individuals and to the social and economic development of communities and countries. However, internationally young people endure a disproportionate burden of sexually transmitted infections and unintended pregnancies which can be associated with poor psycho-social outcomes. Digital sexual health interventions have been developed to increase young people’s access to sexual health services, but are currently underutilised. Aim This systematic review sought to identify the barriers and facilitators to young people’s engagement with bidirectional digital sexual health interventions, which are standalone two-way tailored interventions between a young person and healthcare professional. Methods The review was conducted in accordance with the JBI methodology for mixed methods systematic reviews, following a convergent integrated approach to synthesis and integration of qualitative and quantitative evidence. Searches of ten electronic databases were conducted, spanning database inception to January 2022. No restrictions were imposed on language, geographical location or community setting. All included studies were critically appraised with JBI Critical Appraisal tools. Data extraction was performed using standardised tools, followed by data transformation. Data synthesis followed the convergent integrated approach. Each stage was conducted by two independent reviewers. Results Eight thousand four hundred thirty-nine titles and abstracts and, subsequently, 255 full-texts underwent review. Nine studies were selected for inclusion with no studies added following forward and backward citation tracking. The included studies comprised three qualitative and six quantitative designs. Three meta synthesised findings were identified: (1) The design of a digital intervention for adolescent sexual health needs to reflect the end users’ specific needs (2) Young people need to feel comfortable when using a digital sexual health intervention (3) Potential barriers to engagement need to be addressed. The review identified that although barriers and facilitators to promoting young people’s engagement with bidirectional digital sexual health interventions are nuanced, young people’s privacy and security need to be prioritised for them to engage with digital interventions, regardless of the platform of choice. Conclusions Co-production of digital sexual health services, in partnership with young people, has shaped many of the insights reported in this systematic review. Further international research which places an emphasis on young people’s perspectives is vital to unleash the full potential of digital technology in this domain.

Using qualitative interview data (n = 142 interviews) generated with 50 nurses, over the course of the COVID-19 pandemic, this paper traces the trajectories of nurses in the UK and attempts to unpick the interplay between structure and agency in their narratives. Interviews were inductively analysed for themes and an additional narrative analysis was undertaken to preserve the form of each participant's narrative. We argue that nurses' pandemic trajectories occurred within the 'psychological vulnerability-stigma nexus' which operates within health and social care providers in the UK and whilst constraining nurses' agency at times it could also provide an impetus to act agentically. We found that the nurses' COVID-19 trajectories were characterised by: getting by, getting out (job-hopping) getting needs met and getting organised. We call for more considered systemic support to be generated and consistently provided to nurses to ensure retention of nurses and the security of society to avoid exacerbating existing workforce shortages.

Introduction Digital sexual health technologies for young people, such as websites, texting services and apps, could address some of the sexual health inequalities that many experience, since they have the potential to overcome concerns associated with traditional clinic based services such as embarrassment, privacy and accessibility. However, they are currently under-utilised internationally.Methods Using complexity theory and systems thinking as a theoretical framework, this qualitative descriptive study sought to explore the acceptability of digital sexual health technologies for 16–18 year olds. Data generation with 10 sexual health nurses with experience of digital service delivery took the form of minimally structured online one-to-one interviews lasting between 20 and 50 min. Focus groups of up to eight young people or individual interviews were used to explore 32 16–18 year olds’ perspectives. Interviews lasted between 18 and 48 min. Both datasets were analysed using Braun and Clarke’s reflexive thematic analysis.Results Three themes emerged from each dataset. Nurses’ themes were: (1) digital sexual health services can be more comfortable for young people, (2) digital sexual health services can be complimentary to clinic visits but do not replace them and (3) challenges exist in providing sexual health services to young people through digital technologies. The young people’s themes were: (1) sexual health is a ‘difficult issue’, (2) young people have specific expectations yet a desire for choice and (3) digital health interventions are not a panacea.Conclusions While digital sexual health interventions hold great potential, they need to be integral to the wider systems in which both young people and sexual health promotion services operate, otherwise there is a risk that their impact will be compromised. Collaborative approaches that connect causal factors and policy objectives and involve full engagement with all stakeholders are more likely to be efficacious.

Introduction: High-quality pre-registration student nurse training and development is integral to developing a sustainable and competent global nursing workforce. Internationally, student nurse recruitment rates have increased since the onset of the COVID-19 pandemic; however, attrition rates for student nurses are high. During the pandemic, many student nurses considered leaving the programme due to academic concerns, feeling overwhelmed, and doubting their clinical skills. Little was known about the extent to which nursing education prior to COVID-19 had prepared students for their role in managing the healthcare crisis or the impact on their resilience. Thus, this study aimed to explore how the COVID-19 pandemic impacted on the resilience levels of student nurses across the United Kingdom. Methods: Data were collected as part of a multi-site qualitative study named ‘COV-ED Nurse’ and involved pre-placement surveys, placement diaries, and post-placement interviews with nursing students. Student nurse participants were recruited from across the United Kingdom, from all years of study, and from all four nursing branches: children, adult, mental health, and learning disabilities. Participants were asked to complete a pre-placement survey that collected demographic details and information about their placement expectations. They were also asked to record a weekly audio-visual or written diary to describe their placement experiences, and, on completion of their placements, students were interviewed to explore their experiences of this time. Data were thematically analysed using the Framework Approach. Ethical approvals were obtained. Results: Two hundred and sixteen students took part in the wider study. The current study involved a subset of 59 students’ data. Four main themes were identified: ‘coping with increased levels of acuity’, ‘perceived risks of the pandemic’, ‘resilience when facing uncertainty and isolation’, and ‘the importance of coping mechanisms and support structures.’ Discussion: From this study, we have generated insights that can be applied to nursing research, education, policy, and practice and identified the wide-ranging impact that the COVID-19 pandemic had on student nurses and their abilities to remain resilient in an unstable environment. The value of communication and support networks from a wide range of sources was highlighted as key to navigating many uncertainties. In addition, the extent to which students were able to navigate their personal and professional roles and identities influenced their ability to cope with and continue along their training pathways.

AbstractFunctional hypogonadism is a condition characterized by low testosterone concentrations, occurring more commonly in men as they age. The International Prostate Symptom Score (IPSS) is used to categorize the severity of lower urinary tract symptoms (LUTS) and related symptoms in hypogonadal men. Testosterone therapy (TTh) has previously shown potential in improving total IPSS in men with hypogonadism. However, concerns regarding the effects of urinary function following TTh often prevent treatment in hypogonadal men. To explore this further, two population-based single-center, prospective, cumulative registry studies were combined to contribute to a total population of 1176 men with symptoms of hypogonadism. The total population was separated into a TTh group receiving testosterone undecanoate (TU) for up to 12 years and a control group that did not receive treatment. IPSS was recorded at both baseline and at final recorded visit for each patient. Long-term TTh with TU in hypogonadal men resulted in significant improvements in IPSS categories, even in patients with severe symptoms at baseline. In the control group, untreated hypogonadal men experienced a worsening of IPSS categories. These data indicate that TTh improves LUTS in men with hypogonadism and suggest that previous concerns regarding urinary function may have been overstated.

Abstract The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs), with mutations linked to increased transmissibility, vaccine escape and virulence, has necessitated the widespread genomic surveillance of SARS-CoV-2. This has placed a strain on global sequencing capacity, especially in areas lacking the resources for large scale sequencing activities. Here we have developed three separate multiplex high-resolution melting assays to enable the identification of Alpha, Beta, Delta and Omicron VOCs. The assays were evaluated against whole genome sequencing on upper-respiratory swab samples collected during the Alpha, Delta and Omicron [BA.1] waves of the UK pandemic. The sensitivities of the eight individual primer sets were all 100%, and specificity ranged from 94.6 to 100%. The multiplex HRM assays have potential as a tool for high throughput surveillance of SARS-CoV-2 VOCs, particularly in areas with limited genomics facilities.

Testosterone therapy (TTh) is the primary treatment for aging men with functional hypogonadism. Whilst the benefits of testosterone (T) replacement are well-evidenced, the long-term data for TTh on metabolic and endocrine parameters is limited. Here we present the effect of TTh on endocrine parameters in hypogonadal men at a 12-year follow-up. In this single-centre, cumulative, prospective, registry study, 321 hypogonadal men (mean age: 58.9 years) received testosterone undecanoate injections in 12-week intervals for up to 12 years. Blood samples were taken at every other visit to measure levels of total T (TT), calculated free T, sex hormone-binding globulin (SHBG), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and prolactin. We observed an increase in TT of 15.5 nmol/L (p

Background and purpose: Deep learning contouring (DLC) has the potential to decrease contouring time and variability of organ contours. This work evaluates the effectiveness of DLC for prostate and head and neck across four radiotherapy centres using a commercial system. Materials and methods: Computed tomography scans of 123 prostate and 310 head and neck patients were evaluated. Besides one head and neck model, generic DLC models were used. Contouring time using centres’ existing clinical methods and contour editing time after DLC were compared. Timing was evaluated using paired and non-paired studies. Commercial software or in-house scripts assessed dice similarity coefficient (DSC) and distance to agreement (DTA). One centre assessed head and neck inter-observer variability. Results: The mean contouring time saved for prostate structures using DLC compared to the existing clinical method was 5.9 ± 3.5 min. The best agreement was shown for the femoral heads (median DSC 0.92 ± 0.03, median DTA 1.5 ± 0.3 mm) and the worst for the rectum (median DSC 0.68 ± 0.04, median DTA 4.6 ± 0.6 mm). The mean contouring time saved for head and neck structures using DLC was 16.2 ± 8.6 min. For one centre there was no DLC time-saving compared to an atlas-based method. DLC contours reduced inter-observer variability compared to manual contours for the brainstem, left parotid gland and left submandibular gland. Conclusions: Generic prostate and head and neck DLC models can provide time-savings which can be assessed with paired or non-paired studies to integrate with clinical workload. Reducing inter-observer variability potential has been shown.

Introduction Multiparametric MRI (mpMRI) has transformed the prostate cancer diagnostic pathway, allowing for improved risk stratification and more targeted subsequent management. However, concerns exist over the interobserver variability of images and the applicability of this model long term, especially considering the current shortage of radiologists and the growing ageing population. Artificial intelligence (AI) is being integrated into clinical practice to support diagnostic and therapeutic imaging analysis to overcome these concerns. The following report details a protocol for a systematic review and meta-analysis investigating the accuracy of AI in predicting primary prostate cancer on mpMRI.Methods and analysis A systematic search will be performed using PubMed, MEDLINE, Embase and Cochrane databases. All relevant articles published between January 2016 and February 2023 will be eligible for inclusion. To be included, articles must use AI to study MRI prostate images to detect prostate cancer. All included articles will be in full-text, reporting original data and written in English. The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. The QUADAS-2 score will assess the quality and risk of bias across selected studies.Ethics and dissemination Ethical approval will not be required for this systematic review. Findings will be disseminated through peer-reviewed publications and presentations at both national and international conferences.PROSPERO registration number CRD42021293745.

Abstract Understanding the psychological causes of variation in climate change belief and pro-environmental behaviour remains an urgent challenge for the social sciences. The “cooperative phenotype” is a stable psychological preference for cooperating in social dilemmas that involve a tension between individual and collective interest. Since climate change poses a social dilemma on a global scale, this issue may evoke similar psychological processes as smaller social dilemmas. Here, we investigate the relationships between the cooperative phenotype and climate change belief and behaviour with a representative sample of New Zealanders (N = 897). By linking behaviour in a suite of economic games to self-reported climate attitudes, we show robust positive associations between the cooperative phenotype and both climate change belief and pro-environmental behaviour. Furthermore, our structural equation models support a motivated reasoning account in which the relationship between the cooperative phenotype and pro-environmental behaviour is mediated by climate change belief. These findings suggest that common psychological mechanisms underlie cooperation in both micro-scale social dilemmas and larger-scale social dilemmas like climate change.

Background The Children and Young People’s Mental Health Trailblazer programme is funding the creation of new mental health support teams to work in schools and further education colleges. Mental health support teams directly support children and young people with ‘mild to moderate’ mental health problems and work with school and college staff to promote well-being for all. A new workforce of education mental health practitioners is being trained for the teams. Objective(s) The National Institute for Health and Care Research Birmingham, RAND and Cambridge Evaluation Rapid Evaluation Centre and Policy Innovation and Evaluation Research Unit undertook an early evaluation of the Trailblazer programme to examine the development, implementation and early progress of mental health support teams in the programme’s first 25 ‘Trailblazer’ sites. Design A mixed-methods evaluation, comprising three work packages: 1.Establishing the baseline and understanding the development and early impacts of the Trailblazer sites, including two rounds of surveys with key informants and participating education settings in all 25 sites. 2.More detailed research in five purposively selected Trailblazer sites, including interviews with a range of stakeholders and focus groups with children and young people. 3.Scoping and developing options for a longer-term assessment of the programme’s outcomes and impacts. Fieldwork was undertaken between November 2020 and February 2022. The University of Birmingham Institute for Mental Health Youth Advisory Group was involved throughout the study, including co-producing the focus groups with children and young people. Results Substantial progress had been made implementing the programme, in challenging circumstances, and there was optimism about what it had the potential to achieve. The education mental health practitioner role had proven popular, but sites reported challenges in retaining education mental health practitioners, and turnover left mental health support teams short-staffed and needing to re-recruit. Education settings welcomed additional mental health support and reported positive early outcomes, including staff feeling more confident and having faster access to advice about mental health issues. At the same time, there were concerns about children who had mental health problems that were more serious than ‘mild to moderate’ but not serious enough to be accepted for specialist help, and that the interventions offered were not working well for some young people. Mental health support teams were generally spending more time supporting children with mental health problems than working with education settings to develop ‘whole school’ approaches to mental health and well-being, and service models in some sites appeared to be more clinically oriented, with a strong focus on mental health support teams’ therapeutic functions. Limitations Despite efforts to maximise participation, survey response rates were relatively low and some groups were less well represented than others. We were not able to gather sufficiently detailed data to develop a typology of Trailblazer sites, as was planned. Conclusions Key lessons for future programme implementation include: –Whether mental health support teams should expand support to children and young people with more complex and serious mental health problems. –How to keep the twin aims of prevention and early intervention in balance. –How to retain education mental health practitioners once trained. Future work The findings have important implications for the design of a longer-term impact evaluation of the programme, which is due to commence in summer 2023. Study registration Ethical approval from the University of Birmingham (ERN_19-1400 – RG_19-190) and London School of Hygiene and Tropical Medicine (Ref: 18040) and Health Research Authority approval (IRAS 270760). Funding The Birmingham, RAND and Cambridge Evaluation Rapid Evaluation Centre is funded by the National Institute for Health and Care Research Health Services and Delivery Research programme (HSDR 16/138/31). The Policy Innovation and Evaluation Research Unit is funded by the NIHR Policy Research Programme (PR-PRU-1217-20602). A note on terminology This report uses the term ‘children and young people’s mental health services’ to describe all services that support children and young people who have difficulties with their mental health and emotional well-being. These services encompass prevention and universal provision, through to specialist and crisis support, including inpatient care. They are provided by NHS, local authority, voluntary, community and independent sector services, as well as schools and colleges. Some participants in the study refer to ‘child and adolescent mental health services’ (or CAMHS), which is an older term for specialist NHS mental health services for young people aged 0–18 (or, in some areas, 0–25) years. We also use the term ‘whole school approach’ to describe all the ways in which schools and colleges can address the emotional health of children and/or young people in their setting, which includes supporting those who are experiencing mental health problems to access appropriate help. In wider literature and debate, these activities are also referred to as holistic, universal, graduated or school-wide approaches to mental health and well-being. The national programme launched by the Department of Health and Department for Education to implement the proposals in the 2017 Green Paper Transforming Children and Young People’s Mental Health Provision was originally termed the Trailblazer programme. It was subsequently renamed the Children and Young People’s Mental Health Implementation programme, and only the first wave of sites was referred to as Trailblazers. As the study reported herein focuses exclusively on this first wave of Trailblazer sites, we have opted to use the programme’s original name. Plain language summary The Children and Young People’s Mental Health Trailblazer programme started in 2018 and is funding the creation of new mental health support teams to work in schools and further education colleges. Mental health support teams directly support children and young people with ‘mild to moderate’ mental health problems and help schools and colleges to promote well-being for all. The programme is also creating and training a new workforce of education mental health practitioners. Our study looked at the experiences of setting up and running mental health support teams in the first 25 areas involved in the programme (called Trailblazers). We wanted to understand what the teams were doing day-to-day, who was working in them, what was going well, whether there were any challenges, and what progress they were making. To do this, we looked at documents and information provided by the national programme team and collected our own data using surveys, interviews and focus groups. We found that the programme was making good progress, and that schools and colleges welcomed having additional mental health support. Children and young people told us how important it was to have somebody in their school or college who they could speak to about their mental health. Mental health support teams were generally spending more time supporting young people who had mental health difficulties than working with education settings to promote emotional well-being across the whole school or college community. There were also challenges. Some children had mental health problems that were more serious than ‘mild to moderate’ but not serious enough to be accepted for specialist support. The type of support that mental health support teams were providing was not suitable for all children and young people. Once education mental health practitioners had been trained, some moved on from their role quite quickly, leaving teams short-staffed. The findings have important implications for the design of a longer-term study to assess the impact of the programme, due to commence in summer 2023. Scientific summary Background The Children and Young People’s Mental Health Trailblazer programme was launched in 2018 to take forward the proposals set out in the Transforming Children and Young People’s Mental Health Provision Green Paper. The programme is being implemented in successive waves, with the first wave funding the creation of 58 mental health support teams (MHSTs) in 25 ‘Trailblazer’ sites. Across these sites, 1050 schools and further education colleges were recruited to participate in the programme, each of which received support from an MHST and was encouraged to appoint a senior lead for mental health for their setting (if they did not already have one in place). MHSTs have three core functions: (1) providing direct support to children and young people with mild to moderate mental health issues; (2) supporting education settings to introduce or develop their whole school/college approach to mental health and well-being; and (3) giving advice to staff in education settings and liaising with external specialist services to help children and young people to get the right support and stay in education. A new professional role has been created for the programme: education mental health practitioner (EMHP). The programme is being implemented in the context of a children’s mental health service under strain. Considerable and increasing levels of mental ill health in children and young people, historic underinvestment in children’s mental health services and the COVID-19 pandemic have contributed to services struggling to cope with increasing demand. Objectives The National Institute for Health and Care Research (NIHR) Birmingham, RAND and Cambridge Evaluation Rapid Evaluation Centre and Policy Innovation and Evaluation Research Unit undertook an early, process-oriented evaluation of the Trailblazer programme to examine the development, implementation and early progress of the MHSTs in the Trailblazer sites. The aims of the evaluation were to: 1.Understand the baseline position and contextual features of the Trailblazer sites, including the accessibility, quality and effectiveness of existing mental health services and support in education settings and perceived gaps in provision prior to the programme commencing. 2.Describe and understand the emerging delivery models, their leadership and governance, and explore how these vary across the Trailblazer sites and the potential implications of this variation for future effectiveness of the programme. 3.Describe the experience of MHSTs, education settings, clinical commissioning groups and local authority commissioners, children and young people’s mental health services and others of taking part in the delivery of the programme. 4.Capture views about the progress being made by Trailblazers towards the goals of the programme, early impacts and any unanticipated consequences in the initial phases of the programme. 5.Identify measures and data sources of relevance to assessing programme outcomes and costs as well as appropriate comparator areas and education settings to assess the feasibility and develop the design of a long-term outcome and economic evaluation. 6.Conduct formative and learning-oriented research, producing timely findings and highlighting their practical implications to inform ongoing implementation and support roll-out to sites in later waves of the programme. 7.Understand how MHSTs adapted their services and ways of working in response to the COVID-19 pandemic, and explore experiences of and learning from these changes, as well as their legacy. Methods We completed a mixed-methods evaluation combining quantitative and qualitative data collection across all 25 sites with in-depth qualitative insights from five purposively selected Trailblazers. The study comprised three work packages: •Work package 1: establishing the baseline and understanding the development and early impact of the Trailblazers. Participating education settings and key individuals who had a central role in the design and implementation of the MHSTs in their area were surveyed twice: December 2020 to May 2021 and October–November 2021. We received responses from 299 (30%, first survey) and 159 (17%, second survey) education settings; and from 76 (30%, first survey) and 65 (27%, second survey) key informants. We also interviewed the programme’s national leads (n establishing the baseline and understanding the development and en establishing the bn establishing the baseline and understanding the development and early impact of the Trailblazers. d documentation, and the development of demographic and mental health service profiles for the 25 sites, using publicly available data. •Work package 2: more detailed research with a range of stakeholders in five purposively selected Trailblazer sites, including focus groups with children and young people. A total of 71 interviews were completed with local stakeholders including MHST lead organisations and staff, school and college staff, individuals in Trailblazer governance and management roles, and wider partners including specialist NHS mental health services, voluntary organisations and local authorities. Five online focus groups were held with a total of 32 children and young people who attended schools where MHSTs were operating. •Work package 3: scoping and developing options for a longer-term assessment of the programme’s outcomes and impacts. This work was highly responsive and included reviewing the design and methods of recent evaluations of initiatives and pilots similar to the Trailblazers; ongoing advice and discussions with, and commentary on preparatory work undertaken by, the national programme team; a draft theory of change; and a full proposal for an initial impact evaluation. The Institute for Mental Health Youth Advisory Group at the University of Birmingham acted as an expert reference group for this research, and were involved throughout: from design through to preparation of this report. A key part of their role was co-producing the focus group research with children and young people, including co-designing the recruitment materials and topic guides, co-facilitating the focus groups and contributing to the analysis and presentation of the findings (see Chapter 9). Results Implementation and governance The Trailblazers had achieved a great deal in a relatively short space of time. While the local set-up process had been extensive, complex and rushed, some 12 months after the first cohort of EMHPs started their training all 58 MHSTs were operational in some form. The involvement of young people, parents and carers in the design and delivery of MHSTs was variable and often low, despite it being an aspiration that they be involved throughout the programme. There was a view that local governance and leadership was not yet truly shared across health, education and other key stakeholder groups and that the way in which the programme had been set up was dominated by the NHS as funder and by local mental health services. The pandemic created significant challenges for implementation, including delays to whole school activities; however, MHSTs adapted their offer and ways of working to ensure the continuation of support for young people and to education settings. These adaptations included the use of remote support. Stakeholders suggested that a hybrid model of in-person and remote delivery will be used going forward. The pandemic also had a considerable impact on the mental health and well-being of children and young people, and staff in education settings, as well as on access to specialist services. Children and young people described how home schooling had left them feeling disconnected, demotivated and sometimes without adequate support, as well as the difficulties transitioning back into school or college. Service models, delivery and gaps in support MHSTs were delivering a range of activities within the three core functions, with teams spending proportionally more time providing direct support than on their other two functions. Some teams were clinically oriented, while others took a more holistic/education-focused approach. The approach taken appeared to be most strongly influenced by the type of organisation(s) leading the programme (e.g. NHS vs. voluntary sector), and existing local infrastructure, relationships and skill sets. Teams also varied in the number of education settings they were working with, their staffing composition, and how whole school activities were being delivered (with this being led, in some areas, by specialist local partners or specialist roles within MHSTs). MHSTs had implemented strategies to reach and engage diverse groups and different mental health needs. However, stakeholders noted that some groups were underserved by MHSTs including children and young people with special educational needs or neurodiversity, those from ethnic minority backgrounds and some religious backgrounds, and children with challenging family or social circumstances (e.g. financial hardship, domestic abuse, or living in care). These issues concerning MHSTs’ reach and effectiveness were attributed to several factors, including gaps in the initial training programme and the limitations of the type of interventions that EMHPs had been trained to deliver (mainly time-limited, low-intensity cognitive behaviour therapy), which were felt to be poorly suited to some groups of children and young people and some mental health problems. Education settings were generally satisfied with the MHST service, and MHST staff spoke positively about working with education settings. However, a mismatch between education settings’ expectations or perceived support needs and what MHSTs could offer was sometimes reported, which hampered relationship building. Defining what was within the scope of ‘mild to moderate’ mental health was challenging, and practising within this scope was harder still. Some sites held a firm boundary around ‘mild to moderate’ mental health, whereas others provided support to children and young people with more serious and complex needs. There was a lack of clarity from programme regional and national leads about whether MHSTs should remain within their intended scope or offer flexibility to support children beyond this. Although MHSTs could refer young people with more complex needs to specialist services, there were long waiting times and restricted capacity in existing mental health services. Concern was expressed about children and young people falling through the gap between MHSTs’ ‘mild to moderate’ remit and the criteria for specialist support. Workforce and retention The EMHP role and training programme had been popular, but retaining EMHPs once in post was one of the biggest challenges reported by Trailblazers. Interviewees identified various reasons for poor retention including the role being seen as a stepping stone to other careers, lack of opportunities for career development and progression, frustration at the parameters of the role or limitations of the CBT approach and high workloads. Challenges recruiting senior team members were also common. There had been initial concerns about senior staff being recruited from other local mental health services, given the potential for this to create staffing shortages elsewhere in the local system, but many had come to the view that the movement of staff between services was positive inasmuch as it had helped build understanding and relationships. The degree of integration between MHSTs and specialist NHS services varied between areas, with some teams reporting a tension between working closely with other services and establishing a clear and distinctive identity within the diverse landscape of mental health providers in their area. Engagement and experiences of education settings, and children and young people Engagement of schools and colleges was felt to be critical to the success of the programme, as was the senior mental health lead role. Some education settings needed more help to prepare for the programme and make the most of the support on offer from their MHST, and there was disappointment about the delayed roll-out of the senior mental health leads training. Many education settings reported that constraints of time and competing commitments meant that mental health leads could not always engage with their MHST as much as they would have liked and this was a barrier to implementation and success. Children and young people were not always aware that there was an MHST in their education setting or what it did. Those who had had direct contact with the team (either receiving one-to-one support or through involvement in group or whole school activities) had a better understanding of MHSTs; their experiences of this contact had been universally positive and they were able to articulate more clearly how the school cared for their emotional well-being. Children and young people gave several examples of ways in which their education setting was promoting and supporting well-being for all pupils, and these were acknowledged and valued. Programme progress and outcomes Education settings reported positive early effects from participating in the programme, including staff feeling more confident talking to children and young people about mental health issues, being able to access advice about mental health issues more easily, and having quicker access to support for children and young people with some mental health problems. Improvements in children and young people’s understanding of mental health and well-being were also widely reported, as were strengthened relationships between education settings, mental health services and other local partners. Many education settings had invested in mental health support since joining the programme, although it was unclear whether this was a direct impact of the programme or due to other factors (e.g. a response to the COVID-19 pandemic). Various enabling factors critical to programme implementation and success were identified, including a supportive local context, multi-agency working to ensure that key organisations and sectors could influence the design and delivery of the programme, clear governance structures, sharing learning and co-production with children, young people and their families. Implications of the study findings for longer-term evaluation Key implications include: •There is considerable value in the longer-term evaluation focusing on understanding for which groups of children and young people, and which mental health problems, the standard MHST intervention is less suitable or beneficial. •Consideration must be given to which outcomes to measure, in consultation with children, young people, parents and carers. Some of the outcomes expected at the start of the programme may no longer be realistic, especially those relating to service use, given the impact of COVID-19. •Careful work will be required to define the programme’s ‘ecological’ impacts, and when these might be expected to occur since whole school effects are likely to be more diffuse and take longer to become visible. Limitations The study focused only on the first 25 Trailblazer sites in the programme. These sites were chosen for characteristics thought likely to drive rapid progress and learning and therefore the findings from this evaluation may not be reflective of experiences across the programme as a whole. Survey response rates were generally low, and some groups were less well represented in interview samples, including staff from educational settings and specialist NHS mental health services. The study did not include research to explore children and young people’s experiences of receiving mental health support from an MHST. Conclusions There have been substantial and unprecedented changes in the wider context since the programme started. The COVID-19 pandemic has further increased inequalities in mental health and access to support, and gaps between services appear to be widening. Critical decisions will need to be taken about what, if any, role MHSTs should have in providing support to children and young people beyond the ‘mild to moderate’ remit that the programme was designed to address. There is also the question of how the programme can continue to retain a dual focus on mental health promotion (e.g. through the development of whole school approaches) and early intervention, and what additional support or resources might help educational partners and settings maximise the opportunities offered by the programme. Alongside strategies for workforce creation and training, more work is needed to ensure that trained staff are retained and can develop in their roles. Funding The Birmingham, RAND and Cambridge Evaluation Rapid Evaluation Centre is funded by the NIHR Health Services and Delivery Research programme (HSDR 16/138/31). The Rapid Evaluation Centre and Policy Innovation and Evaluation Research Unit is funded by the NIHR Policy Research Programme (PR-PRU-1217-20602).

One of the problems facing an ageing population is functional decline associated with reduced levels of physical activity (PA). Traditionally researcher or clinician input is necessary to capture parameters of gait or PA. Enabling older adults to monitor their activity independently could raise their awareness of their activitiy levels, promote self-care and potentially mitigate the risks associated with ageing. The ankle is accepted as the optimum position for sensor placement to capture parameters of gait however, the waist is proposed as a more accessible body-location for older adults. This study aimed to compare step-count measurements obtained from a single inertial sensor positioned at the ankle and at the waist to that of a criterion measure of step-count, and to compare gait parameters obtained from the sensors positioned at the two different body-locations. Step-count from the waist-mounted inertial sensor was compared with that from the ankle-mounted sensor, and with a criterion measure of direct observation in healthy young and healthy older adults during a three-minute treadmill walk test. Parameters of gait obtained from the sensors at both body-locations were also compared. Results indicated there was a strong positive correlation between step-count measured by both the ankle and waist sensors and the criterion measure, and between ankle and waist sensor step-count, mean step time and mean stride time (r = .802-1.0). There was a moderate correlation between the step time variability measures at the waist and ankle (r = .405). This study demonstrates that a single sensor positioned at the waist is an appropriate method for the capture of important measures of gait and physical activity among older adults.

BackgroundThe increased use of wearable sensor technology has highlighted the potential for remote telehealth services such as rehabilitation. Telehealth services incorporating wearable sensors are most likely to appeal to the older adult population in remote and rural areas, who may struggle with long commutes to clinics. However, the usability of such systems often discourages patients from adopting these services. ObjectiveThis study aimed to understand the usability factors that most influence whether an older adult will decide to continue using a wearable device. MethodsOlder adults across 4 different regions (Northern Ireland, Ireland, Sweden, and Finland) wore an activity tracker for 7 days under a free-living environment protocol. In total, 4 surveys were administered, and biometrics were measured by the researchers before the trial began. At the end of the trial period, the researchers administered 2 further surveys to gain insights into the perceived usability of the wearable device. These were the standardized System Usability Scale (SUS) and a custom usability questionnaire designed by the research team. Statistical analyses were performed to identify the key factors that affect participants’ intention to continue using the wearable device in the future. Machine learning classifiers were used to provide an early prediction of the intention to continue using the wearable device. ResultsThe study was conducted with older adult volunteers (N=65; mean age 70.52, SD 5.65 years) wearing a Xiaomi Mi Band 3 activity tracker for 7 days in a free-living environment. The results from the SUS survey showed no notable difference in perceived system usability regardless of region, sex, or age, eliminating the notion that usability perception differs based on geographical location, sex, or deviation in participants’ age. There was also no statistically significant difference in SUS score between participants who had previously owned a wearable device and those who wore 1 or 2 devices during the trial. The bespoke usability questionnaire determined that the 2 most important factors that influenced an intention to continue device use in an older adult cohort were device comfort (τ=0.34) and whether the device was fit for purpose (τ=0.34). A computational model providing an early identifier of intention to continue device use was developed using these 2 features. Random forest classifiers were shown to provide the highest predictive performance (80% accuracy). After including the top 8 ranked questions from the bespoke questionnaire as features of our model, the accuracy increased to 88%. ConclusionsThis study concludes that comfort and accuracy are the 2 main influencing factors in sustaining wearable device use. This study suggests that the reported factors influencing usability are transferable to other wearable sensor systems. Future work will aim to test this hypothesis using the same methodology on a cohort using other wearable technologies.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

ABSTRACT Understanding the complex interactions between virus and host that drive new strain evolution is key to predicting the emergence potential of variants and informing vaccine development. Under our hypothesis, future dominant human norovirus GII.4 variants with critical antigenic properties that allow them to spread are currently circulating undetected, having diverged years earlier. Through large-scale sequencing of GII.4 surveillance samples, we identified two variants with extensive divergence within domains that mediate neutralizing antibody binding. Subsequent serological characterization of these strains using temporally resolved adult and child sera suggests that neither candidate could spread globally in adults with multiple GII.4 exposures, yet young children with minimal GII.4 exposure appear susceptible. Antigenic cartography of surveillance and outbreak sera indicates that continued population exposure to GII.4 Sydney 2012 and antigenically related variants over a 6-year period resulted in a broadening of immunity to heterogeneous GII.4 variants, including those identified here. We show that the strongest antibody responses in adults exposed to GII.4 Sydney 2012 are directed to previously circulating GII.4 viruses. Our data suggest that the broadening of antibody responses compromises establishment of strong GII.4 Sydney 2012 immunity, thereby allowing the continued persistence of GII.4 Sydney 2012 and modulating the cycle of norovirus GII.4 variant replacement. Our results indicate a cycle of norovirus GII.4 variant replacement dependent upon population immunity. Young children are susceptible to divergent variants; therefore, emergence of these strains worldwide is driven proximally by changes in adult serological immunity and distally by viral evolution that confers fitness in the context of immunity. IMPORTANCE In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree. Neither evades current adult immunity, yet young children are likely susceptible. By comparing serological responses, we demonstrate that population immunity varies by age/exposure, impacting predicted susceptibility to variants. Repeat exposure to antigenically similar variants broadens antibody responses, providing immunological coverage of diverse variants but compromising response to the infecting variant, allowing continued circulation. These data indicate norovirus GII.4 variant replacement is driven distally by virus evolution and proximally by immunity in adults.

Abstract Background After internal carotid artery (ICA) injury during endoscopic skull base surgery, the majority of patients undergo ICA embolization or stenting to treat active extravasation or pseudoaneurysm development. However, management practices when embolization or stenting is not required have not been well described. The objective of this study was to determine how patients with ICA injury but no embolization, stenting, or ligation do long‐term and ascertain the reconstruction methods utilized. Methods Twenty‐nine cases of ICA injury were identified in an international multi‐institutional retrospective review. Of these, we identified six cases that were not treated with embolization, stenting, or ICA sacrifice. Information was available for five cases. Results A muscle patch was used in the immediate repair of each case. A nasoseptal flap was used in one case. Prefabricated nasal tampons were used in all cases. Nasal packing was initially left in for a median of 7 days prior to removal. The initial muscle patch was reinforced with a second muscle graft in one case. One case demonstrated ICA bleeding at the time of packing removal and was repacked an additional week. Follow‐up for each of these cases was at least 2 years. No cases of subsequent carotid rupture were found and none of these cases ultimately underwent endovascular stenting. Radiation or proton therapy has not been subsequently used in any of these patients. Conclusions This study details the reconstruction, lessons learned, and long‐term follow‐up for five cases of ICA injury not treated with embolization, stenting, or ligation.

Abstract Background Globally the population of older adults is increasing. It is estimated that by 2050 the number of adults over the age of 60 will represent over 21% of the world’s population. Frailty is a clinical condition associated with ageing resulting in an increase in adverse outcomes. It is considered the greatest challenge facing an ageing population affecting an estimated 16% of community-dwelling populations worldwide. Aim The aim of this systematic review is to explore how wearable sensors have been used to assess frailty in older adults. Method Electronic databases Medline, Science Direct, Scopus, and CINAHL were systematically searched March 2020 and November 2020. A search constraint of articles published in English, between January 2010 and November 2020 was applied. Papers included were primary observational studies involving; older adults aged > 60 years, used a wearable sensor to provide quantitative measurements of physical activity (PA) or mobility and a measure of frailty. Studies were excluded if they used non-wearable sensors for outcome measurement or outlined an algorithm or application development exclusively. The methodological quality of the selected studies was assessed using the Appraisal Tool for Cross-sectional Studies (AXIS). Results Twenty-nine studies examining the use of wearable sensors to assess and discriminate between stages of frailty in older adults were included. Thirteen different body-worn sensors were used in eight different body-locations. Participants were community-dwelling older adults. Studies were performed in home, laboratory or hospital settings. Postural transitions, number of steps, percentage of time in PA and intensity of PA together were the most frequently measured parameters followed closely by gait speed. All but one study demonstrated an association between PA and level of frailty. All reports of gait speed indicate correlation with frailty. Conclusions Wearable sensors have been successfully used to evaluate frailty in older adults. Further research is needed to identify a feasible, user-friendly device and body-location that can be used to identify signs of pre-frailty in community-dwelling older adults. This would facilitate early identification and targeted intervention to reduce the burden of frailty in an ageing population.

Background: Evidence for effectiveness of nurse-led interventions for cancer-related symptoms is of variable quality. This study aimed to identify, appraise and evaluate the nature and effectiveness of nurse-led interventions on symptoms for people with cancer. Methods: A systematic review and meta-analysis. Ten major databases were searched (2000 to 2018, no language restrictions). Two reviewers applied a priori selection criteria; data extraction included design, population, cancer type, and cancer-related symptoms. Interventions and providers were profiled using TIDieR reporting guidelines, and content analysis of components. Methodological quality was assessed using Cochrane risk of bias. A meta-analysis was performed using mean and standardised mean differences with 95% confidence intervals. Overall certainty was assessed using GRADE. Results: From 29193 records, 149 studies (n = 107286 participants) from 22 countries were eligible. Interventions included multiple components; education and psychological approaches dominated. Pooled meta-analyses found evidence of benefit for nurse-led interventions on measures of constipation (MD −4.54, 95% CI −8.08 to −0.99; 645 participants; 6 trials; I2 = 0%; P = 0.01); nausea and vomiting (MD −1.97, 95% CI −3.61 to −0.33; 957 participants; 8 trials; I 2 = 12%; P = 0.02) and fatigue (MD −4.63, 95% CI −7.97 to −1.30; 1208 participants; 11 trials; I2 = 34%; P = 0.007). Psychological morbidity (anxiety, depression, mood) also improved. However, few trials used consistent outcome measures, interventions were poorly defined, and certainty of evidence was low or very low. Conclusion: Nurse-led interventions improve specific cancer-related symptoms, including psychological morbidity. Enhanced reporting and collaboration to develop a minimum core dataset would strengthen the quality of evidence.

Background: The introduction of ‘Freedom to Speak Up Guardians’ into every NHS trust in England was intended to support workers and trusts to better raise, respond to and learn from speaking-up concerns. However, only broad guidance was provided on how to implement the role. As a result, there is the potential for important local differences to emerge as the role is implemented across England. Objectives: The overall aim of this study was to better understand the implementation of Guardians in acute trusts and mental health trusts. Design: The Freedom to Speak Up Guardian role was conceptualised as a complex intervention consisting of several interacting and interlocking components spanning the macro level (national organisations), the meso level (individual trusts) and the micro level (employees, teams and wards/units). A mixed-methods study was designed, which consisted of three work packages: (1) a systematic narrative review of the international literature regarding interventions promoting ‘speaking up’ by health-care employees; (2) semistructured telephone interviews with Guardians working in acute hospital trusts and mental health trusts; and (3) qualitative case studies of Freedom to Speak Up Guardian implementation, consisting of observations and interviews undertaken in four acute trusts and two mental health trusts. Interviews were also undertaken with national stakeholders. Setting: Acute trusts and mental health NHS trusts in England. Participants: Work package 2: Freedom to Speak Up Guardians (n = 87) were interviewed. Work package 3: 116 interviews with key stakeholders involved in pre-implementation and early implementation decision-making, workers who had spoken up to the Guardian, and national stakeholders. Results: Wide variability was identified in how the Guardian role had been implemented, resourced and deployed by NHS trusts. ‘Freedom to Speak Up Guardian’ is best considered an umbrella term, and multiple versions of the role exist simultaneously across England. Any comparisons of Guardians’ effectiveness are likely to be possible or meaningful only when this variability is properly accounted for. Many Freedom to Speak Up Guardians identified how a lack of available resources, especially time scarcity, negatively and significantly affected their ability to effectively respond to concerns; their opportunities to collect, analyse and learn from speaking-up data; and, more generally, the extent to which they developed their role and speak-up culture. Limitations: It is possible that those whom we interviewed were more receptive of Freedom to Speak Up Guardians or may have been biased by ‘socially desirability’, and their answers may not always have represented respondents’ true perceptions. Conclusions: Optimal implementation of the Guardian role has five components: (1) establishing an early, collaborative and coherent strategy congruent with the values of Freedom to Speak Up fosters the implementation of (2) policies and robust, yet supportive, practices (3) informed by frequent and reflexive monitoring of Freedom to Speak Up implementation that is (4) underpinned by sufficient time and resource allocation that leads to (5) a positive implementation climate that is congruent with Freedom to Speak Up values and is well placed to engender positive and sustainable Freedom to Speak Up culture and the well-being of a Guardian. Future work: The following recommendations for future research are considered to be of equal priority. Studies of the speaking-up experiences of minority communities and ‘seldom-heard’ workforce groups are a priority requirement. There is also value in undertaking a similar study in non-hospital settings and where peripatetic working is commonplace, such as in ambulance services and in primary care settings. The role of human resources and ‘middle managers’ in the management of concerns is an area requiring further research, especially regarding concerns relating to unprofessional and transgressive behaviours. Devolved administrations in Scotland and Wales have adopted different approaches to speaking up; research undertaken in these contexts would offer valuable comparative insights. Researching the Guardian role ≥ 5 years post implementation is recommended to understand the medium-term impact and the longer-term sustainability of the role and well-being of Guardians. Study registration: This study is registered as ISRCTN38163690 and has the study registration CRD42018106311. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 23. See the NIHR Journals Library website for further project information.

Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression.

Background: The acute hospital setting has become a key site of care for people living with dementia. People living with dementia are one of the largest populations in our hospitals, with the Department of Health and Social Care recognising that 25–50% of all acute hospital admissions are people who are also living with dementia. However, people living with dementia are a highly vulnerable group in the hospital setting and, following an acute admission, their functional abilities can deteriorate quickly and significantly. Detailed research is required to explore what constitutes ‘good care’. Objectives: This study’s focus was a common, but poorly understood, aspect of everyday care for people living with dementia during an acute admission, that is continence care. We asked the following questions: what caring practices are observable when interacting with this patient group? How do ward teams respond to and manage continence needs? What informs these approaches? What are staff doing and why? Design: This ethnography was informed by the symbolic interactionist research tradition, focusing on understanding how action and meaning are constructed within a setting. In-depth evidence-based analysis of everyday care enabled us to examine how ward staff responded to the continence care needs of people living with dementia and to follow the consequences of their actions. We carried out a mixed-methods systematic narrative review to refine our approach to fieldwork and analysis. Setting: This ethnography was carried out for 180 days, across 12 months, in six wards in three hospitals across England and Wales that were purposefully selected to represent a range of hospital types, geographies and socioeconomic catchments. Participants: In addition to general observations, 108 individuals participated directly in this study, contributing to 562 ethnographic interviews. Ten detailed case studies were also undertaken with people living with dementia. Results: This study identified ‘pad cultures’ as an embedded practice on these acute wards. The routine use of continence pads among people living with dementia (regardless of continence and independence) was widespread. The use of continence pads was viewed as a precautionary strategy, the rationale being to provide safeguards, ensure containment and prevent ‘accidents’ or incontinence episodes, with an expectation that patients living with dementia not only will wear pads, but will use them. Conclusions: These ‘pad cultures’ enabled the number of unscheduled interruptions to the institutionally mandated timetabled work of these wards to be reduced, but had significant impacts on people living with dementia and, in turn, wider consequences for these individuals and their identities. Ward staff described feeling abandoned with the responsibility of caring for large numbers of people living with dementia, believing that it was impossible to work in other ways to support their patient’s continence. Limitations: The limitations identified included the potential for the Hawthorne effect to influence data collection. Future work: In collaboration with a specialist dementia care and continence teams, the findings are informing the development of education and training at the interactional and organisational level. Study registration: This study is registered as PROSPERO CRD42018119495. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 14. See the NIHR Journals Library website for further project information.

It has long been known that nursing work is challenging and has the potential for negative impacts. During the COVID-19 pandemic most nurses’ working landscapes altered dramatically and many faced unprecedented challenges. Resilience is a contested term that has been used with increasing prevalence in healthcare with health professionals encouraging a “tool-box” of stress management techniques and resilience-building skills. Drawing on narrative interview data ( n = 27) from the Impact of Covid on Nurses (ICON) qualitative study we examine how nurses conceptualized resilience during COVID-19 and the impacts this had on their mental wellbeing. We argue here that it is paramount that nurses are not blamed for experiencing workplace stress when perceived not to be resilient “enough,” particularly when expressing what may be deemed to be normal and appropriate reactions given the extreme circumstances and context of the COVID-19 pandemic.

Context: Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective: To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition: We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis: We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions: Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary: Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility.

Introduction The introduction of multiparametric MRI (mpMRI) has improved almost every aspect of the prostate cancer diagnostic pathway. However, the novel imaging technique, prostate-specific membrane antigen positron emission tomography (PSMA PET) may have demonstrable accuracy in detecting and staging prostate cancer. Here, we describe a protocol for a systematic review and meta-analysis comparing mpMRI to PSMA PET for the diagnosis of suspected prostate cancer.Methods and analysis A systematic search of MEDLINE, EMBASE, PubMed and Cochrane databases will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed for screening, data extraction, statistical analysis and reporting. Included papers will be full-text articles providing original data, written in English articles and comparing the use of PSMA PET with mpMRI in the diagnosis of prostate cancer. All studies published between July 1977 and March 2021 will be eligible for inclusion. Study bias and quality will be assessed using Quadas-2 score. To ensure the quality of the reporting of studies, this protocol is written following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist.Ethics and dissemination Ethical approval will not be required for this systematic review. Findings will be disseminated through peer-reviewed publications and presentations at both national and international conferences.PROSPERO registration number CRD42021239296.

The local delivery of growth factors such as BMP-2 is a well-established strategy for the repair of bone defects. The limitations of such approaches clinically are well documented and can be linked to the need for supraphysiological doses and poor spatio-temporal control of growth factor release in vivo. Using bioprinting techniques, it is possible to generate implants that can deliver cytokines or growth factors with distinct spatiotemporal release profiles and patterns to enhance bone regeneration. Specifically, for bone healing, several growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic proteins (BMPs), have been shown to be expressed at different phases of the process. This protocol aims to outline how to use bioprinting strategies to deliver growth factors, both alone or in combination, to the site of injury at physiologically relevant dosages such that repair is induced without adverse effects. Here we describe: the printing parameters to generate the polymer mechanical backbone; instructions to generate the different bioinks and allow for the temporal control of both growth factors; and the printing process to develop implants with spatially defined patterns of growth factors for bone regeneration. The novelty of this protocol is the use of multiple-tool fabrication techniques to develop an implant with spatio-temporal control of growth factor delivery for bone regeneration. While the overall aim of this protocol was to develop an implant for bone regeneration, the technique can be modified and used for a variety of regenerative purposes.Graphic abstract: 3D Bioprinting Spatio-Temporally Defined Patterns of Growth Factors to Tightly Control Bone Tissue Regeneration.

Biomechanical analysis of gait is commonly used in physiotherapy. Ground reaction forces during phases of gait is one element of kinetic analysis. In this article, we analyze if the MoveSole® smart insole is valid and accurate equipment for measuring ground reaction forces in clinical physiotherapy. MoveSole® StepLab is a mobile measurement system for instant underfoot force measurements during gait. Unique electromagnetic film (EMFI) based sensor technology and printed electronics production technology is integrated in the MoveSole® StepLab measurement system. The MoveSole® StepLab measures plantar ground reaction force distribution over the sensors and provides an estimation of the maximum total ground reaction force. We developed a two phase validation process to extract relevant parameters and compared the results to a Kistler force plate using the BioWare® analyzing program as a reference method. Our results show that MoveSole® smart insoles reach the strong level of accuracy needed in clinical work concerning highest ground reaction forces during step (Pearson correlation .822 - .875). The correlation of the time when the maximum ground reaction force occurred was moderate, e.g. during heel strike or toe-off (Pearson correlation natural gait speed .351 - .462, maximum gait speed .430). Our conclusion is that MoveSole® smart insoles are a potential tool for analyzing and monitoring gait ground reaction forces during physiotherapy processes.

Introduction There is an increasing body of evidence to suggest that visibility of prostate cancer on magnetic resonance (MRI) may be related to likelihood of adverse pathological outcomes. Biochemical recurrence (BCR) after radical prostatectomy remains a significant clinical challenge and a means of predicting likelihood of this prior to surgery could inform treatment choice. It appears that MRI could be a potential candidate strategy for BCR prediction, and as such, there is a need to review extant literature on the prognostic capability of MRI. Here, we describe a protocol for a systematic review and meta-analysis of the utility of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) in predicting BCR following radical prostatectomy for prostate cancer treatment.Methods and analysis PubMed, MEDLINE, Embase and Cochrane databases will be searched and screening will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In order to meet the inclusion criteria, papers must be English-language articles involving patients who have had bpMRI or mpMRI for suspected prostate cancer and have undergone radical prostatectomy as definitive therapy. Patients must have had prostate-specific antigen monitoring before and after surgery. All relevant papers published from July 1977 to October 2020 will be eligible for inclusion. The Newcastle-Ottawa score will be used to determine the quality and bias of the studies. This protocol is written in-line with the PRISMA protocol 2015 checklist.Ethics and dissemination There are no relevant ethical concerns. Dissemination of this protocol will be via peer-reviewed journals as well as national and international conferences.PROSPERO registration number CRD42020206074.

Abstract Introduction There is an urgent need to develop effective interventional treatments for people with Alzheimer's disease (AD). AD results from a complex multi‐decade interplay of multiple interacting dysfunctional biological systems that have not yet been fully elucidated. Epidemiological studies have linked several modifiable lifestyle factors with increased incidence for AD. Because monotherapies have failed to prevent or ameliorate AD, interventional studies should deploy multiple, targeted interventions that address the dysfunctional systems that give rise to AD. Methods This randomized controlled trial (RCT) will examine the efficacy of a 12‐month personalized, multimodal, lifestyle intervention in 60 mild cognitive impairment (MCI) and early stage AD patients (aged 50+, amyloid positivity). Both groups receive data‐driven, lifestyle recommendations designed to target multiple systemic pathways implicated in AD. One group receives these personalized recommendations without coaching. The other group receives personalized recommendations with health coaching, dietary counseling, exercise training, cognitive stimulation, and nutritional supplements. We collect clinical, proteomic, metabolomic, neuroimaging, and genetic data to fuel systems‐biology analyses. We will examine effects on cognition and hippocampal volume. The overarching goal of the study is to longitudinally track biological systems implicated in AD to reveal the dynamics between these systems during the intervention to understand differences in treatment response. Results We have developed and implemented a protocol for a personalized, multimodal intervention program for early AD patients. We began enrollment in September 2019; we have enrolled a third of our target (20 of 60) with a 95% retention and 86% compliance rate. Discussion This study presents a paradigm shift in designing multimodal, lifestyle interventions to reduce cognitive decline, and how to elucidate the biological systems being targeted. Analytical efforts to explain mechanistic or causal underpinnings of individual trajectories and the interplay between multi‐omic variables will inform the design of future hypotheses and development of effective precision medicine trials.

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes.

Introduction Focal therapy has emerged as a promising treatment option for men with localised prostate cancer. However, most of the evaluation of postoperative function has taken place at a relatively high, non-granular level. Most of the data we use to provide informed consent for our patients is obtained from retrospective series, or derived from prospective studies whose primary outcome was oncological. Finally, most studies have focused on erectile function and overlooked other, presumably important, elements of male sexual function. The present study aims at studying in-depth the sexual consequences of focal therapy with various energy sources.Methods and analysis This will be a mixed-methods research study based on a retrospective and prospective cohort, recruited in parallel. The retrospective cohort will consist of patients treated with focal irreversible electroporation, and the prospective cohort of patients treated with three focal therapy energies. Participants will be recruited from two UK urology centres, one National Health Service and one private. On consent, patients will fill in self-administered validated questionnaires (International Index of Erectile Function-15 (IIEF-15), Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF)) and semistructured interviews will be organised to collect patients’ expectations and postoperative changes in domains such as erection, ejaculation, orgasm, libido/sexual desire, masculinity/virility, penile morphology, pain or discomfort, regret, shame, cancer-related stress, overall impact and partner satisfaction. An exploratory thematic analysis will be performed to detail recurring themes that will be grouped into clusters of experiences. We will then be able to find clusters of agreement and disagreement that will be illustrated using exemplar patient quotations.Ethics and dissemination Ethical approval was obtained (Regional Ethics Committee reference 20/NW/0335), as well as Health Research Authority approval. Results will be published in open-access peer-reviewed journals. Findings will also be translated into patient information resources (leaflets, online information sheets).Trial registration number ISRCTN11634296; Pre-results.

Introduction Multiparametric MRI (mpMRI) has improved risk stratification for men with suspected prostate cancer. Indeed, mpMRI-visible tumours tend to be larger and of higher pathological grade than mpMRI-invisible tumours; however, concern remains around significant cancer that is undetected by mpMRI. There has been considerable recent interest to investigate whether tumour conspicuity on mpMRI is associated with additional histopathological features (including cellular density, microvessel density and unusual prostate cancer subtypes), which may have important clinical implications in both diagnosis and prognosis. Furthermore, analysis of these features may help reveal the radiobiology that underpins the actual mechanisms of mpMRI visibility (and invisibility) of prostate tumours. Here, we describe a protocol for a systematic review of the histopathological basis of prostate cancer conspicuity on mpMRI.Methods and analysis A systematic search of the MEDLINE, PubMed, Embase and Cochrane databases will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be used to guide screening, thematic reporting and conclusions drawn from all eligible studies. Included papers will be full-text, English-language articles, comparing the histopathological characteristics of mpMRI-visible lesions and mpMRI-invisible tumours. All studies published between January 1950 and January 2020 will be eligible for inclusion. Studies using confirmatory immunohistochemistry for the identification of immune subsets or structural components will be included. Study bias and quality will be assessed using a modified Newcastle-Ottawa scale. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist. If appropriate, a meta-analysis will be conducted comparing histopathological feature frequency between mpMRI-visible and mpMRI-invisible disease.Ethics and dissemination No ethical approval will be required as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals and presentations at national and international conferences.PROSPERO registration number CRD42020176049

Introduction The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%–20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic review and novel bioinformatic analysis of the genomic basis of prostate cancer conspicuity on mpMRI.Methods and analysis A systematic search of MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included papers will be full text articles, written between January 1980 and December 2019, comparing molecular characteristics of mpMRI-visible lesions and mpMRI-invisible lesions at the DNA, DNA-methylation, RNA or protein level. Study bias and quality will be assessed using a modified Newcastle-Ottawa score. Additionally, we will conduct a novel bioinformatic analysis of supplementary material and publicly available data, to combine transcriptomic data and reveal common pathways highlighted across studies. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist.Ethics and dissemination Ethical approval will not be required, as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.PROSPERO registration number CRD42019147423.

Articular cartilage (AC) possesses a limited healing potential, meaning that untreated focal joint defects typically progress, leading to the development of degenerative diseases such as osteoarthritis. Several clinical strategies exist that aim to regenerate AC; however, recapitulation of a fully functional, load-bearing tissue remains a significant challenge. This can be attributed, at least in part, to a paucity of biomaterials that truly mimic the native tissue and provide appropriate cues to direct its regeneration. The main structural component of articular cartilage, type II collagen, does not readily gelate at body temperature, challenging the development of cartilage extracellular matrix (cECM)-derived injectable hydrogels and bioinks for AC tissue engineering and bioprinting applications. Here, we describe the development and rheological characterisation of a methacrylated cartilage ECM-based hydrogel/bioink (cECM-MA), which could be photocrosslinked when exposed to ultraviolet (UV) light. Functionalisation of the collagen backbone with methacryloyl groups had a negligible effect on triple helix stability, as demonstrated by circular dichroism spectroscopy. These cECM-MA bioinks demonstrated shear-thinning properties and could be loaded with bone marrow mesenchymal stem cells (BM-MSCs), micro-extruded to generate self-supporting 3D constructs of predefined size and shape, and then photocrosslinked using UV light. Analysis of the cell-laden constructs showed that the BM-MSCs were viable post-printing and underwent chondrogenesis in vitro, generating a tissue rich in sulphated glycosaminoglycans and collagens. These results support the use of methacrylated, tissue-specific ECM-derived hydrogels as bioinks for 3D bioprinting and/or as injectables for cartilage tissue engineering applications.

The increased use of sensor technology has been crucial in releasing the potential for remote rehabilitation. However, it is vital that human factors, that have potential to affect real-world use, are fully considered before sensors are adopted into remote rehabilitation practice. The smart sensor devices for rehabilitation and connected health (SENDoc) project assesses the human factors associated with sensors for remote rehabilitation of elders in the Northern Periphery of Europe. This article conducts a literature review of human factors and puts forward an objective scoring system to evaluate the feasibility of balance assessment technology for adaption into remote rehabilitation settings. The main factors that must be considered are: Deployment constraints, usability, comfort and accuracy. This article shows that improving accuracy, reliability and validity is the main goal of research focusing on developing novel balance assessment technology. However, other aspects of usability related to human factors such as practicality, comfort and ease of use need further consideration by researchers to help advance the technology to a state where it can be applied in remote rehabilitation settings.

Early detection of Rheumatoid Arthritis (RA) and other neurological conditions is vital for effective treatment. Existing methods of detecting RA rely on observation, questionnaires, and physical measurement, each with their own weaknesses. Pharmaceutical medications and procedures aim to reduce the debilitating effect, preventing the progression of the illness and bringing the condition into remission. There is still a great deal of ambiguity around patient diagnosis, as the difficulty of measurement has reduced the importance that joint stiffness plays as an RA identifier. The research areas of medical rehabilitation and clinical assessment indicate high impact applications for wearable sensing devices. As a result, the overall aim of this research is to review current sensor technologies that could be used to measure an individual’s RA severity. Other research teams within RA have previously developed objective measuring devices to assess the physical symptoms of hand steadiness through to joint stiffness. Unfamiliar physical effects of these sensory devices restricted their introduction into clinical practice. This paper provides an updated review among the sensor and glove types proposed in the literature to assist with the diagnosis and rehabilitation activities of RA. Consequently, the main goal of this paper is to review contact systems and to outline their potentialities and limitations. Considerable attention has been paid to gloved based devices as they have been extensively researched for medical practice in recent years. Such technologies are reviewed to determine whether they are suitable measuring tools.

Capturing hand motions for hand function evaluations is essential in the medical field. For many allied health professionals, measuring joint range of motion (ROM) is an important skill. While the universal goniometer (UG) is the most used clinical tool for measuring joint ROM, developments in current sensor technology are providing clinicians with more measurement possibilities than ever. For rehabilitation and manual dexterity evaluations, different data gloves have been developed. However, the reliability and validity of sensor technologies when used within a smart device remain somewhat unclear. This study proposes a novel electronically controlled sensor monitoring system (ECSMS) to obtain the static and dynamic parameters of various sensor technologies for both data gloves and individual sensor evaluation. Similarly, the ECSMS was designed to closely mimic a human finger joint, to have total control over the joint, and to have an exceptionally high precision. In addition, the ECSMS device can closely mimic the movements of the finger from hyperextension to a maximum ROM beyond any person’s finger joint. Due to the modular design, the ECSMS’s sensor monitoring board is independent and extensible to include various technologies for examination. Additionally, by putting these sensory devices through multiple tests, the system accurately measures the characteristics of any rotary/linear sensor in and out of a glove. Moreover, the ECSMS tracks the movement of all types of sensors with respect to the angle values of finger joints. In order to demonstrate the effectiveness of sensory devices, the ECSMS was first validated against a recognised secondary device with an accuracy and resolution of 0.1°. Once validated, the system simultaneously determines real angles alongside the hand monitoring device or sensor. Due to its unique design, the system is independent of the gloves/sensors that were tested and can be used as a gold standard to realise more medical equipment/applications in the future. Consequently, this design greatly enhances testing measures within research contact and even non-contact systems. In conclusion, the ECSMS will benefit in the design of data glove technologies in the future because it provides crucial evidence of sensor characteristics. Similarly, this design greatly enhances the stability and maintainability of sensor assessments by eliminating unwanted errors. These findings provide ample evidence for clinicians to support the use of sensory devices that can calculate joint motion in place of goniometers.

PURPOSE: Herpes zoster ophthalmicus (HZO) after COVID-19 vaccination has been reported in numerous case studies. However, no large-scale epidemiologic studies have been conducted to date. The purpose of this study was to determine whether COVID-19 vaccination is associated with an increased risk of HZO. DESIGN: Retrospective before-and-after risk interval analysis. METHODS: RESULTS: In total, 1,959,157 patients received a dose of a COVID-19 vaccine during the study period and met eligibility criteria. A total of 80 individuals without a prior history of HZO were included in the analysis because they developed HZO in the risk or control period. Patients had a mean age of 54.0 years (SD = 12.3 years). There were 45 cases of HZO in the risk interval after COVID-19 vaccination. There was not an increased risk of HZO after vaccination with BNT162b2 (IRR = 0.90, 95% CI: 0.49-1.69, P = .74), mRNA-1273 (IRR = 0.74, 95% CI: 0.36-1.54, P = .42), or Ad26.COV2.S (IRR = 0.50, 95% CI: 0.07-2.56, P = .42). CONCLUSIONS: This study found no evidence of increased risk of HZO after COVID-19 vaccination, providing reassurance for patients and providers who may be concerned about the safety profile of the COVID-19 vaccines.

BACKGROUND: The introduction of multiparametric magnetic resonance imaging (mpMRI) has improved the diagnosis of suspected prostate cancer, accurately risk-stratifying men before a biopsy. However, pre-biopsy mpMRI represents a significant deviation from the traditional approach of prostate specific antigen testing with subsequent systematic transrectal ultrasound-guided prostate biopsy and we have not yet explored the views of men who experience this new pathway. The purpose of the PACT study (PAtient views and aCceptance of mulTiparametric MRI) is to explore men’s perceptions of mpMRI. METHODS: PACT will be conducted at teaching hospitals in which mpMRI is central to the prostate cancer diagnostic pathway using a two-phase, mixed-methods, quantitative and qualitative approach. In phase I, men referred with suspected prostate cancer will complete detailed surveys to explore their views on the mpMRI-directed pathway compared to the traditional pathway and on what constitutes ‘significant’ prostate cancer. In phase II, these themes will be expanded upon with in-depth, semi-structured interviews. Qualitative data will be transcribed and thematically analysed, and quantitative questionnaire responses will be analysed statistically. DISCUSSION: PACT will provide the first detailed insight into patient perceptions on the use and acceptability of mpMRI. Furthermore, results from PACT will help contribute to the resolution of outstanding controversies that surround this technology.

We report a method for creating hybrid organic-inorganic “nanoflowers” using calcium or copper ions as the inorganic component and a recombinantly expressed elastin-like polypeptide (ELP) as the organic component. Polypeptides provide binding sites for the dynamic coordination with metal ions, and then such noncovalent complexes become nucleation sites for primary crystals of metal phosphates. We have shown that the interaction between the stimuli-responsive ELP and Ca2+ or Cu2+, in the presence of phosphate, leads to the growth of micrometer-sized particles featuring nanoscale patterns shaped like flower petals. The morphology of these flower-like composite structures is dependent upon the temperature of growth and has been characterized by scanning electron microscopy. The composition of nanoflowers has also been analyzed by energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The temperature-dependent morphologies of these hybrid nanostructures, which arise from the controllable phase transition of ELPs, hold potential for morphological control of biomaterials in emerging applications such as tissue engineering and biocatalysis.

Background: Between 2018 and 2025, a national implementation programme is funding more than 500 new mental health support teams (MHSTs) in England, to work in education settings to deliver evidence-based interventions to children with mild to moderate mental health problems and support emotional wellbeing for all pupils. A new role, education mental health practitioner (EMHP), has been created for the programme. Aims: A national evaluation explored the development, implementation and early progress of 58 MHSTs in the programme's first 25 'Trailblazer' sites. This paper reports the views and experiences of people involved in MHST design, implementation and service delivery at a local, regional and national level. Methods: Data are reported from in-depth interviews with staff in five Trailblazer sites (n = 71), and the programme's regional (n = 52) and national leads (n = 21). Results: Interviewees universally welcomed the creation of MHSTs, but there was a lack of clarity about their purpose, concerns that the standardised CBT interventions being offered were not working well for some children, and challenges retaining EMHPs. Conclusions: This study raises questions about MHSTs' service scope, what role they should play in addressing remaining gaps in mental health provision, and how EMHPs can develop the skills to work effectively with diverse groups. [ABSTRACT FROM AUTHOR]