HAP-FAST: a feasibility study incorporating qualitative, mechanistic and costing sub-studies alongside a randomised pilot trial comparing chest x-ray to low-dose CT scan and empirical antibiotics to antibiotics guided by the BIOFIRE® FILM ARRAY® pneumonia plus panel in adults with suspected non-ventilator-associated hospital-cquired pneumonia.

INTRODUCTION: Non-ventilator-associated hospital-acquired pneumonia (nv-HAP) is the most common healthcare-associated infection (HCAI), is associated with high mortality and morbidity and places a major burden on healthcare systems. Diagnosis currently relies on chest x-rays to confirm pneumonia and sputum cultures to determine the microbiological cause. This approach leads to over-diagnosis of pneumonia, rarely identifies a causative pathogen and perpetuates unnecessary and imprecise antibiotic use. The HAP-FAST study aims to evaluate the feasibility of a randomised trial to evaluate the clinical impact of low-dose, non-contrast-enhanced thoracic CT scans and rapid molecular sputum analysis using the BIOFIRE® FILMARRAY® pneumonia plus panel (FAPP) for patients suspected with nv-HAP. METHODS AND ANALYSIS: The HAP-FAST feasibility study consists of a pilot randomised trial, a qualitative study, a costing analysis and exploratory analyses of clinical samples to investigate the immune-pathophysiology of HAP. Participants are identified and recruited from four acute hospitals in the Northwest of the UK. Using a Research Without Prior Consent model, the pilot trial will recruit 220 adult participants, with or without mental capacity, and with suspected HAP. HAP-FAST is a non-blinded, sequential, multiple assignment, randomised trial with two possible stages of randomisation: first, chest x-ray (CXR) or CT; second, if treated as nv-HAP, FAPP or standard microbiological processing alone (no FAPP). Pathogen-specific antibiotic guidance will be provided for FAPP results. Randomisation uses a web-based platform and followed up for 90 days. The feasibility of a future trial will be determined by assessing trial processes, outcome measures and patient and staff experiences. ETHICS AND DISSEMINATION: This study has undergone combined review by the UK NHS Research Ethics Committee and Health Research Authority. Results will be disseminated via peer-reviewed journals, via the funders' website and through a range of media to engage the public. TRIAL REGISTRATION NUMBER: NCT05483309.

Consultations about randomised controlled trials are shorter and less in-depth for socioeconomically disadvantaged patients compared to socioeconomically advantaged patients: qualitative analysis across three trials.

BACKGROUND: Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive. This study examined how trials are communicated verbally, comparing consultations involving patients from the most and least socioeconomically disadvantaged areas. METHODS: Secondary qualitative analysis of 55 trial consultation transcripts from 41 patients, sampled from 3 qualitative studies embedded in their respective UK multi-site, cancer-related randomised controlled trials. Patients living in the most and least socioeconomically disadvantaged areas, defined using English Indices of Multiple Deprivation decile scores, were purposively sampled. Analysis was largely thematic and drew on the constant comparison method. RESULTS: Recruiters communicated clinical uncertainty in a similar way for patients living in different socioeconomic areas. Consultations with disadvantaged patients were, on average, half the duration of those with advantaged patients, and tended to involve recruiters providing less in-depth explanations of trial concepts, used phrasing that softened trial arm risks, and described trial processes (e.g. randomisation) using informal or metaphorical phrasing. Disadvantaged and advantaged patients differed in the concerns they expressed; disadvantaged patients voiced fewer concerns and asked fewer questions but were also less likely to be invited to do so by recruiters. CONCLUSION: Interactions about trials unfolded in different ways between patients living in different socioeconomic areas, likely due to both patient- and recruiter-related factors. We present considerations for recruiters when discussing trials with patients from socioeconomically disadvantaged backgrounds, aimed at enhancing trial communication. Future research should examine disadvantaged patients' and recruiters' experiences of verbal trial communication to inform guidance that addresses the needs and preferences of underserved groups.

Bracing Adolescent Idiopathic Scoliosis (BASIS) study - night-time versus full-time bracing in adolescent idiopathic scoliosis: study protocol for a multicentre, randomized controlled trial.

Aims: Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of 'full-time bracing' versus 'night-time bracing' in adolescent idiopathic scoliosis (AIS). Methods: UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination. Discussion: The primary outcome is 'treatment failure' (Cobb angle progression to 50° or more before skeletal maturity); skeletal maturity is at Risser stage 4 in females and 5 in males, or 'treatment success' (Cobb angle less than 50° at skeletal maturity). The comparison is on a non-inferiority basis (non-inferiority margin 11%). Participants are followed up every six months while in brace, and at one and two years after skeletal maturity. Secondary outcomes include the Scoliosis Research Society 22 questionnaire and measures of quality of life, psychological effects of bracing, adherence, anxiety and depression, sleep, satisfaction, and educational attainment. All data will be collected through the British Spine Registry.

Patient-centred outcomes following non-operative treatment or appendicectomy for uncomplicated acute appendicitis in children.

While non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient-centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared with appendicectomy, children allocated to non-operative treatment reported higher short-term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT. Trial registration number is ISRCTN15830435.

Patient and health practitioner views and experiences of a cancer trial before and during COVID-19: qualitative study.

BACKGROUND: Understanding patient and health practitioner perspectives on clinical trials can inform opportunities to enhance trial conduct and design, and therefore patient experience. Patients with haematological cancers have faced additional risk and uncertainty during the pandemic but it is unclear how they and practitioners have experienced cancer trials during this period. In the context of a haemato-oncology trial (PETReA), we compared patient and practitioner views and experiences of PETReA before and during COVID-19. METHODS: Qualitative study embedded within PETReA. Semi-structured interviews (N=41) with patients and practitioners from 16 NHS sites before (n=17) and during the first wave of COVID-19 (n=24). Analysis drew on the framework approach. RESULTS: Practitioners acknowledged the need for the trial to continue during the pandemic but their treatment preferences altered, becoming more pronounced for patients who had a favourable response to induction treatment, while staying unchanged for patients with a less favourable response. Practitioners commented that COVID-19 meant the evidence base for the trial arms was lacking or mixed, but that it likely increased the risks of maintenance treatment for patients with a favourable response to induction treatment. While only one participant interviewed withdrew from PETReA during the pandemic, others said they would consider withdrawing if information that they were at increased risk of severe illness from COVID-19 became available. During COVID-19, patients described less frequent contact with the trial team, which left some feeling less clear about their trial pathway. However, several described having in-depth, collaborative discussions with practitioners about the risks and benefits of randomisation in the context of COVID-19. Patients valued these discussions and were reassured by the emphasis practitioners placed on patients being free to withdraw if circumstances changed, and this helped patients feel comfortable about continuing in PETReA. CONCLUSIONS: The findings point to ways trial communication can support patients to feel comfortable about continuing in a trial during uncertain times, including adopting a more in-depth, collaborative exploration of the risks and benefits of trial arms with patients and emphasising voluntariness. The results are relevant to trialists recruiting patients who are clinically extremely vulnerable or are at increased risk of poor COVID-19 outcomes despite being vaccinated.

SAVER: sodium valproate for the epigenetic reprogramming of high-risk oral epithelial dysplasia-a phase II randomised control trial study protocol.

BACKGROUND: Sodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study. METHODS: One hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial. DISCUSSION: The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial. TRIAL REGISTRATION: The trial is registered with the European Clinical Trials Database ( Eudra-CT 2018-000197-30 ). ( http://www.isrctn.com/ISRCTN12448611 ). The trial was prospectively registered on 24/04/2018.

Ghrelin receptor signaling is not required for glucocorticoid-induced obesity in female mice.

Chronic exposure to high circulating glucocorticoid or ghrelin concentrations increases food intake, weight gain and adiposity, suggesting that ghrelin could contribute to the metabolic effects of chronic glucocorticoids. In male mice, however, blocking ghrelin receptor (GHSR) signaling increased the weight gain and adiposity induced by chronic corticosterone (CORT), rather than attenuating them. In the current study, we investigated the role of GHSR signaling in the metabolic effects of chronic exposure to high circulating CORT in female mice. To do this, female WT and GHSR KO mice were treated with either CORT in a 1% ethanol (EtOH) solution or 1% EtOH alone in their drinking water for 32 days (n = 5-8/group). Body weight, food, and water intake as well as vaginal cyclicity were assessed daily. As expected, CORT treatment-induced significant increases in body weight, food intake, adiposity and also impaired glucose tolerance. In contrast to results observed in male mice, WT and GHSR KO female mice did not differ on any of these parameters. Neither plasma levels of ghrelin, LEAP-2, the endogenous GHSR antagonist produced by the liver, nor their ratio were altered by chronic glucocorticoid exposure. In addition, CORT treatment disrupted vaginal cyclicity, produced a reduction in sucrose consumption and increased locomotor activity regardless of genotype. Chronic CORT also decreased exploration in WT but not GHSR KO mice. Collectively, these data suggest that most metabolic, endocrine, reproductive and behavioral effects of chronic CORT exposure are independent of GHSR signaling in female mice.

Coping With the COVID-19 Pandemic: Examining Gender Differences in Stress and Mental Health Among University Students.

The COVID-19 pandemic has imposed a wide variety of unprecedented challenges, many of which appear to be disproportionately affecting the mental health and well-being of young adults. While there is evidence to suggest university students experience high rates of mental health disorders, less is known about the specific impacts of the COVID-19 pandemic on student mental health and how they are coping with this stress. To address this gap, we conducted an online study among undergraduate students (n = 366) to examine the impact of the COVID-19 pandemic on academics, social isolation, and mental health, as well as the extent to which they have been implementing a variety of coping strategies. The pandemic had a more pronounced negative effect on female students' academics, social isolation, stress and mental health compared to male counterparts. Moreover, for females, frequent use of social media as a coping mechanism was associated with greater perceived negative impacts on their academic performance and stress levels, compared to males. However, frequent social media use related to similar negative mental health effects for both males and females. While male and female students both reported using substances to cope, for males the use of cannabis was associated with greater negative impacts on academic outcomes, stress and mental health compared to females. These findings highlight the need for adequate student support services across the post-secondary sector, and point to the importance of gender informed interventions to address the impacts of the COVID-19 pandemic.

Conservative treatment for uncomplicated appendicitis in children: the CONTRACT feasibility study, including feasibility RCT.

BACKGROUND: Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking. OBJECTIVES: The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children. DESIGN: This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set. SETTING: This study was set in three specialist NHS paediatric surgical units in England. PARTICIPANTS: Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set. INTERVENTIONS: Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial. DATA SOURCES: Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews. RESULTS: Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol. LIMITATIONS: Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time. CONCLUSIONS: A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres. FUTURE WORK: Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.

Appendicitis is usually treated with an operation to remove the appendix. But we have learned, from other research, that some children with appendicitis may not need an operation, and could be treated with antibiotics instead. To find out how these two different treatments compare with one another, we need to do a big study. First, though, we need to see if doing that kind of study would even be possible (or 'feasible'). We carried out a feasibility study that had several parts. First, we did a small study with children who had appendicitis, whereby children were randomly allocated to have either antibiotics or an operation, with an equal chance of having either treatment. Second, we asked parents and health-care staff about why they wanted, or did not want, to take part in that small study. This helped us to understand how to make a bigger future study as acceptable as possible to children, families and surgeons. Third, we asked parents, patients and surgeons what they think are the most important things ­ or 'outcomes' ­ we should look at in future research on children who have appendicitis. From that, we developed a list of outcomes that should be included in our future big study, so we can be certain that the research we do is likely to help parents and surgeons. Overall, we established that a future big study is feasible and we have plenty of information to help us with how to plan it best, so that it has the greatest possible chance of success. We were also guided in all of these steps of the research by a group of parents, children and young people, some of whom had appendicitis and some of whom did not.

CONservative TReatment of Appendicitis in Children: a randomised controlled feasibility Trial (CONTRACT).

OBJECTIVE: To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis. DESIGN: Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial. SETTING: Three specialist paediatric surgery centres in the UK. PATIENTS: Children (aged 4-15 years) with a clinical diagnosis of uncomplicated acute appendicitis. INTERVENTIONS: Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation). MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course. RESULTS: Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable. CONCLUSION: Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible. TRIAL REGISTRATION NUMBER: ISRCTN15830435.

Different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis: the SIRJIA mixed-methods feasibility study.

BACKGROUND: In the UK, juvenile idiopathic arthritis is the most common inflammatory disorder in childhood, affecting 10 : 100,000 children and young people aged < 16 years each year, with a population prevalence of around 1 : 1000. Corticosteroids are commonly used to treat juvenile idiopathic arthritis; however, there is currently a lack of consensus as to which corticosteroid induction regimen should be used with various disease subtypes and severities of juvenile idiopathic arthritis. OBJECTIVE: The main study objective was to determine the feasibility of conducting a randomised controlled trial to compare the different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis. DESIGN: This was a mixed-methods study. Work packages included a literature review; qualitative interviews with children and young people with juvenile idiopathic arthritis and their families; a questionnaire survey and screening log to establish current UK practice; a consensus meeting with health-care professionals, children and young people with juvenile idiopathic arthritis, and their families to establish the primary outcome; a feasibility study to pilot data capture and to collect data for future sample size calculations; and a final consensus meeting to establish the final protocol. SETTING: The setting was rheumatology clinics across the UK. PARTICIPANTS: Children, young people and their families who attended clinics and health-care professionals took part in this mixed-methods study. INTERVENTIONS: This study observed methods of prescribing corticosteroids across the UK. MAIN OUTCOME MEASURES: The main study outcomes were the acceptability of a future trial for children, young people, their families and health-care professionals, and the feasibility of delivering such a trial. RESULTS: Qualitative interviews identified differences in the views of children, young people and their families on a randomised controlled trial and potential barriers to recruitment. A total of 297 participants were screened from 13 centres in just less than 6 months. In practice, all routes of corticosteroid administration were used, and in all subtypes of juvenile idiopathic arthritis. Intra-articular corticosteroid injection was the most common treatment. The questionnaire surveys showed the varying clinical practice across the UK, but established intra-articular corticosteroids as the treatment control for a future trial. The primary outcome of choice for children, young people, their families and health-care professionals was the Juvenile Arthritis Disease Activity Score, 71-joint count. However, results from the feasibility study showed that, owing to missing blood test data, the clinical Juvenile Arthritis Disease Activity Score should be used. The Juvenile Arthritis Disease Activity Score, 71-joint count, and the clinical Juvenile Arthritis Disease Activity Score are composite disease activity scoring systems for juvenile arthritis. Two final trial protocols were established for a future randomised controlled trial. LIMITATIONS: Fewer clinics were included in this feasibility study than originally planned, limiting the ability to draw strong conclusions about these units to take part in future research. CONCLUSIONS: A definitive randomised controlled trial is likely to be feasible based on the findings from this study; however, important recommendations should be taken into account when planning such a trial. FUTURE WORK: This mixed-methods study has laid down the foundations to develop the evidence base in this area and conducting a randomised control trial to compare different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis is likely to be feasible. STUDY REGISTRATION: Current Controlled Trials ISRCTN16649996. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 36. See the NIHR Journals Library website for further project information.

ABOUT JUVENILE IDIOPATHIC ARTHRITIS: Juvenile idiopathic arthritis refers to a group of conditions that cause inflammation and damage of the joints, starting in children and young people aged < 16 years. Treatments include anti-inflammatory medicines, disease-modifying/biologic medicines and corticosteroids. Young people often require corticosteroids at the start of their treatment, or in a flare with worsening inflammation, to get their juvenile idiopathic arthritis under control. A short course of corticosteroids can help and can be given by injection into the joint, through a drip into a vein, by injection into the muscle or in the form of tablets or liquid to be taken orally. Although they have been used for decades, there is no research to show the best way(s) of giving corticosteroids. STUDY AIMS: The study aimed to (1) agree on what corticosteroid treatments to compare in a treatment trial and the best way to measure changes in juvenile idiopathic arthritis to evaluate a quick-acting treatment and (2) find out if there are enough young people with active juvenile idiopathic arthritis in the UK to be included in such a study. METHODS: Published research on corticosteroids in juvenile idiopathic arthritis was reviewed. Health-care professionals were asked how they choose which corticosteroids to use and which method of administration to use. Interviews were carried out with children and young people and their families to (1) consider the design of a study comparing corticosteroid routes, (2) identify outcomes important to them and (3) determine whether or not they would be willing to take part in a future study. A 3-month feasibility study was carried out to collect details of children and young people with active juvenile idiopathic arthritis before and after corticosteroid treatment to measure improvements in juvenile idiopathic arthritis activity, and to see whether or not a larger study would be possible. FINDINGS: This study showed that corticosteroids are used in different ways across the UK. The views of children, young people and their families must be taken into account when designing a future study. This study calculated the number of young people who would be needed to take part in the future, showing that it would be possible to do a larger study that compared different corticosteroid treatments, which would help everyone to understand the best way to use corticosteroids.

Ensuring young voices are heard in core outcome set development: international workshops with 70 children and young people.

PLAIN ENGLISH SUMMARY: Researchers test treatments to ensure these work and are safe. They do this by studying the effects that treatments have on patients by measuring outcomes, such as pain and quality of life. Often research teams measure different outcomes even though each team is studying the same condition. This makes it hard to compare the findings from different studies and it can reduce the accuracy of the treatment advice available to patients. Increasingly, researchers are tackling this problem by developing 'core outcome sets'. These are lists of outcomes that all researchers working on a given condition should measure in their studies. It is important that patients have a voice in the development of core outcome sets and children and young people are no exception. But their voices have rarely been heard when core outcome sets are developed. Researchers are trying to address this problem and make sure that core outcome sets are developed in ways that are suitable for children and young people. As a first step, we held two international workshops with children and young people to listen to their views. They emphasised the importance of motivating young people to participate in developing core outcome sets, making them feel valued, and making the development process more interactive, enjoyable and convenient. We hope this commentary will encourage researchers to include children and young people when developing core outcome sets and to adapt their methods so these are suitable for young participants. Future research is important to examine whether these adaptations are effective. ABSTRACT: Background Different research teams looking at treatments for the same condition often select and measure inconsistent treatment outcomes. This makes it difficult to synthesise the results of different studies, leads to selective outcome reporting and impairs the quality of evidence about treatments. 'Core outcome sets' (COS) can help to address these problems. A COS is an agreed, minimum list of outcomes that researchers are encouraged to consistently measure and report in their studies. Including children and young people (CYP) as participants in the development of COS for paediatric conditions ensures that clinically meaningful outcomes are measured and reported. However, few published COS have included CYP as participants. COS developers have described difficulties in recruiting and retaining CYP and there is a lack of guidance on optimising COS methods for them. We aimed to explore CYP's views on the methods used to develop COS and identify ways to optimise these methods.Main body This commentary summarises discussions during two workshops with approximately 70 CYP (aged 10-18 years old) at the International Children's Advisory Network Research and Advocacy Summit, 2018. Delegates described what might motivate them to participate in a COS study, including feeling valued, understanding the need for COS and the importance of input from CYP in their development, and financial and other incentives (e.g. certificates of participation). For Delphi surveys, delegates suggested that lists of outcomes should be as brief as possible, and that scoring and feedback methods should be simplified. For consensus meetings, delegates advised preparing CYP in advance, supporting them during meetings (e.g. via mentors) and favoured arrangements whereby CYP could meet separately from parents and other stakeholders. Overall, they wanted COS methods that were convenient, enjoyable and engaging.Conclusion This commentary points to the limitations of the methods currently used to develop COS with CYP. It also points to ways to motivate CYP to participate in COS studies and to enhancements of methods to make participation more engaging for CYP. Pending much needed research on COS methods for CYP, the perspectives offered in the workshops should help teams developing COS in paediatrics and child health.

Enhancing communication, informed consent and recruitment in a paediatric urgent care surgical trial: a qualitative study.

BACKGROUND: Recruiting patients to paediatric trials can be challenging, especially in trials that compare markedly different management pathways and are conducted in acute settings. We aimed to enhance informed consent and recruitment in the CONTRACT trial (CONservative TReatment of Appendicitis in Children a randomised controlled Trial; ISRCTN15830435) - a feasibility trial that compared non-operative treatment (antibiotics) versus appendicectomy for uncomplicated acute appendicitis. METHODS: Qualitative study embedded within CONTRACT and conducted across three UK children's hospitals. Data were transcribed audio-recordings of 85 CONTRACT recruitment consultations with 58 families; and semi-structured interviews with 35 health professionals and 28 families (34 parents, 14 children) invited to participate in CONTRACT. Data analysis drew on thematic approaches. Throughout CONTRACT, we used findings from the ongoing qualitative analysis to inform bespoke communication training for health professionals recruiting to CONTRACT. Before and after training we also examined qualitative changes in communication during consultations and quantitative changes in recruitment rates. RESULTS: Bespoke communication training focussed on presenting the trial arms in a balanced way, emphasising clinical equipoise, exploring family treatment preferences and managing families' expectations about the trial's treatment pathways. Analysis of recruitment consultations indicated that health professionals' presentation of treatment arms became increasingly balanced following training, (e.g. avoiding imbalanced terminology) and recruitment rose from 38 to 62%. However, they remained reluctant to explore families' treatment preferences and respond with further information to balance these preferences. Analyses of interviews identified the time constraints of the urgent care setting, concerns about coercion, and reservations about exposing children to conversations about treatment risks as reasons for this reluctance. Interviews with families indicated the importance of clear explanations of trial treatment timings and sensitive communication of treatment allocation for both recruitment and retention. CONCLUSIONS: Following bespoke training based on the qualitative analyses, health professionals presented CONTRACT to families in clearer and more balanced ways and this was associated with an increase in the recruitment rate. Despite training, health professionals remained reluctant to explore families' treatment preferences. We provide several recommendations to enhance communication, informed consent, recruitment and retention in future trials in urgent care settings.

Challenges Conveying Clinical Equipoise and Exploring Patient Treatment Preferences in an Oncology Trial Comparing Active Monitoring with Radiotherapy (ROAM/EORTC 1308).

INTRODUCTION: Providing balanced information that emphasizes clinical equipoise (i.e., uncertainty regarding the relative merits of trial interventions) and exploring patient treatment preferences can improve informed consent and trial recruitment. Within a trial comparing adjuvant radiotherapy versus active monitoring following surgical resection for an atypical meningioma (ROAM/EORTC-1308), we explored patterns in communication and reasons why health practitioners may find it challenging to convey equipoise and explore treatment preferences. MATERIALS AND METHODS: Qualitative study embedded within ROAM/EORTC-1308. Data were collected on 40 patients and 18 practitioners from 13 U.K. sites, including audio recordings of 39 patients' trial consultations, 23 patient interviews, and 18 practitioner interviews. Qualitative analysis drew on argumentation theory. RESULTS: Practitioners acknowledged the importance of the research question that the trial aimed to answer. However, they often demonstrated a lack of equipoise in consultations, particularly with eligible patients who practitioners believed to be susceptible to side effects (e.g., cognitive impairment) or inconvenienced by radiotherapy. Practitioners elicited but rarely explored patient treatment preferences, especially if a patient expressed an initial preference for active monitoring. Concerns about coercing patients, loss of practitioner agency, and time constraints influenced communication in ways that were loaded against trial participation. CONCLUSIONS: We identified several challenges that practitioners face in conveying equipoise and exploring patient treatment preferences in oncology, and particularly neuro-oncology, trials with distinct management pathways. The findings informed communication about ROAM/EORTC-1308 and will be relevant to enhancing trial communication in future oncology trials. Qualitative studies embedded within trials can address difficulties with communication, thus improving informed consent and recruitment. ROAM/EORTC-1308 RCT: ISRCTN71502099. IMPLICATIONS FOR PRACTICE: Oncology trials can be challenging to recruit to, especially those that compare treatment versus monitoring. Conveying clinical equipoise and exploring patient treatment preferences can enhance recruitment and patient understanding. This study focused on the challenges that practitioners encounter in trying to use such communication strategies and how practitioners may inadvertently impede patient recruitment and informed decision making. This article provides recommendations to support practitioners in balancing the content and presentation of trial management pathways. The results can inform training to optimize communication, especially for neuro-oncology trials and trials comparing markedly different management pathways.

Protective parents and permissive children: what qualitative interviews with parents and children can tell us about the feasibility of juvenile idiopathic arthritis trials.

BACKGROUND: Patient recruitment can be very challenging in paediatric studies, especially in relatively uncommon conditions, such as juvenile idiopathic arthritis (JIA). However, involving children and young people (CYP) in the design of such trials could promise a more rapid trajectory towards making evidence-based treatments available. Studies involving CYP are advocated in the literature but we are not aware of any early stage feasibility studies that have qualitatively accessed the perspectives of parents and CYP with a long term condition to inform design and conduct of a trial. In the context of a feasibility study to inform the design of a proposed randomised controlled trial of corticosteroid induction regimen in JIA, we explored families' perspectives on the proposed trial and on JIA trials generally. METHODS: We analysed interviews with 27 participants (8 CYP aged 8-16 years and 19 parents) from four UK paediatric rheumatology centres. CYP had recently received corticosteroids to treat JIA. Audio-recorded interviews were transcribed and analysed thematically, drawing on the Framework Method. RESULTS: Both parents and CYP were capable of engaging with the logic of the proposed trial but pointed to challenges with its design. Treatment preferences influenced willingness to participate in the proposed trial. The preferences of older children and their parents often differed, with CYP being more willing to participate in the proposed trial than parents. Families' current treatment preferences were largely informed by past positive and negative treatment experiences. Some participants also indicated that their treatment preferences were influenced by those of their clinicians. CONCLUSION: Previous research has typically focused on deficits in patients' understandings of trials. We found that both parents and CYP understood trial concepts and were able to identify potential flaws in the proposed trial. We propose recommendations to optimise the design of a planned corticosteroid induction regimen trial in JIA. Accessing both parents' and CYP's perspectives helps to identify and address recruitment challenges, which will ultimately optimise informed consent and future recruitment.

Children's views on research without prior consent in emergency situations: a UK qualitative study.

OBJECTIVES: We explored children's views on research without prior consent (RWPC) and sought to identify ways of involving children in research discussions. DESIGN: Qualitative interview study. SETTING: Participants were recruited through a UK children's hospital and online advertising. PARTICIPANTS: 16 children aged 7-15 years with a diagnosis of asthma (n=14) or anaphylaxis (n=2) with recent (<12 months) experience of emergency care. RESULTS: Children were keen to be included in medical research and viewed RWPC as acceptable in emergency situations if trial interventions were judged safe. Children trusted that doctors would know about their trial participation and act in their best interests. All felt that children should be informed about the research following their recovery and involved in discussions with a clinician or their parent(s) about the use of data already collected as well as continued participation in the trial (if applicable). Participants suggested methods to inform children about their trial participation including an animation. CONCLUSIONS: Children supported, and were keen to be involved in, clinical trials in emergency situations. We present guidance and an animation that practitioners and parents might use to involve children in trial discussions following their recovery.

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility): study protocol for a randomised controlled Trial.

BACKGROUND: Currently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial. METHODS/DESIGN: The study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery. DISCUSSION: In this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design. TRIAL REGISTRATION: ISRCTN15830435 . Registered on 8 February 2017.

Utilizing Lung Cancer Risk Prediction Models to Promote Smoking Cessation: Two Randomized Controlled Trials.

PURPOSE: The current project sought to examine whether delivery of lung cancer risk projections (calculated using the Liverpool Lung Project [LLP] risk model) predicted follow-up smoking status. DESIGN: Two single-blinded randomized controlled trials. SETTING: Stop Smoking Services in Liverpool (United Kingdom). PARTICIPANTS: Baseline current smokers (N = 297) and baseline recent former smokers (N = 216) were recruited. INTERVENTION: Participants allocated to intervention groups were provided with personalized lung cancer risk projections, calculated using the LLP risk model. MEASURES: Baseline and follow-up questionnaires explored sociodemographics, smoking behavior, and lung cancer risk perceptions. ANALYSIS: Bivariate analyses identified significant differences between randomization groups, and logistic regression models were developed to investigate the intervention effect on the outcome variables. RESULTS: Lung cancer risk projections were not found to predict follow-up smoking status in the trial of baseline current smokers; however, they did predict follow-up smoking status in the trial of baseline recent former smokers (odds ratio: 1.91; 95% confidence interval: 1.03-3.55). CONCLUSION: The current study suggests that lung cancer risk projections may help maintain abstinence among individuals who have quit smoking, but the results did not provide evidence to suggest that lung cancer risk projections motivate current smokers to quit.

Paramedics' views on their seizure management learning needs: a qualitative study in England.

INTRODUCTION: The UK ambulance service often attends to suspected seizures. Most persons attended to will not require the facilities of a hospital emergency department (ED) and so should be managed at scene or by using alternative care pathways. Most though are transported to ED. One factor that helps explain this is paramedics can have low confidence in managing seizures. OBJECTIVES: With a view to ultimately developing additional seizure management training for practicing paramedics, we explored their learning needs, delivery preferences and potential drivers and barriers to uptake and effectiveness. DESIGN AND SETTING: Semistructured interviews were conducted with a purposive sample of paramedics from the English ambulance service. Interviews were transcribed and thematically analysed. PARTICIPANTS: A diverse sample of 19 professionals was recruited from 5 different ambulance NHS trusts and the College of Paramedics. RESULTS: Participants said seizure management was neglected within basic and postregistration paramedic training. Most welcomed additional learning opportunities and identified gaps in knowledge. This included how to differentiate between seizure types and patients that do and do not need ED. Practical, interactive e-learning was deemed the most preferable delivery format. To allow paramedics to fully implement any increase in skill resulting from training, organisational and structural changes were said to be needed. This includes not penalising paramedics for likely spending longer on scene. CONCLUSIONS: This study provides the first evidence on the learning needs and preferences of paramedics regarding seizures. It can be used to inform the development of a bespoke training programme for paramedics. Future research should develop and then assess the benefit such training has on paramedic confidence and on the quality of care they offer to seizure patients.