Andrew Cook

Background: Currently, the most frequently used treatment for acute appendicitis in children in the United Kingdom (UK) is an appendicectomy. However, there is increasing scientific and patient interest and research into non-operative treatment of appendicitis. Despite a number of non-randomised studies in children and randomised studies in adults, comparative outcomes of non-operative treatment and appendicectomy in comparable groups of children remain unknown. Following the successful completion of a feasibility study, we now aim to perform a UK-based multi-centre open-label randomised controlled trial (RCT) to investigate the clinical and cost-effectiveness of non-operative treatment pathway of acute uncomplicated appendicitis in children compared with appendicectomy. Methods: Non-inferiority RCT with internal pilot, health economic evaluation and qualitative communication sub-study. The study is conducted in England, Northern Ireland, Scotland and Wales at both specialist children’s hospitals and district general hospitals. 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. Sample size is 376 participants, recruited by surgeons and supported by research staff and randomised with a 1:1 allocation ratio to either non-operative treatment pathway (intervention) or appendicectomy (control). Participants in the intervention arm are treated with antibiotics, analgesia and regular clinical assessment to ensure clinical improvement. Participants in the control arm receive appendicectomy. Randomisation is minimised by age, sex, duration of symptoms and centre. The primary end-point is a composite outcome of treatment success at 1 year following randomisation. Secondary outcomes include: duration of hospital stay, measures of recovery from acute appendicitis, complications, need for further treatment, persistent symptoms, health care resource use, quality of life and costs. Adverse events, serious adverse events and suspected unexpected serious adverse events are collected directly on the database and by paper form up to 12-month visit. Primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin to test the hypothesis that non-operative treatment pathway is non-inferior to appendicectomy. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative sub-study. This will include recording of recruitment consultations, which will inform future interventions to optimise recruitment. We have involved children, young people and parents in study design and delivery. Discussion: This RCT will allow determination of the comparative clinical and cost-effectiveness of non-operative treatment pathway compared to appendicectomy for children with uncomplicated acute appendicitis in the UK. Trial status: First planned enrolment—December 2022, first actual recruit—March 2022, current status of trial—open to recruitment. Trial registration: ISRCTN16720026 . Registered on July 28, 2021.

Background: Surgical outcomes are worse in people with diabetes, in part, because of the effects of hyperglycaemia, obesity and other comorbidities. Two important uncertainties in the management of people with diabetes undergoing major surgery exist: (1) how to improve diabetes management prior to an elective procedure and (2) whether that improved management leads to better post-operative outcomes. Objective: The Optimising Cardiac Surgery ouTcOmes in People with diabeteS project aimed to assess whether a pre-operative outpatient intervention delivered by a multidisciplinary specialist diabetes team could improve diabetes management and cardiac surgical outcomes for people with diabetes. Although the intervention could be applied to any surgical discipline, cardiothoracic surgery was chosen because 30–40% of those undergoing elective cardiac revascularisation have diabetes. Methods: The project had three phases: (1) designing the intervention, (2) a pilot study of the intervention and (3) a multicentre randomised controlled study in United Kingdom cardiothoracic centres to assess whether the intervention could improve surgical outcomes. The first two phases were completed, but the COVID-19 pandemic and its subsequent effects on cardiothoracic services and research capacity in the United Kingdom meant that the randomised controlled study could not be undertaken. Intervention development: Two rapid literature reviews were undertaken to understand what factors influence surgical outcomes in people with diabetes and what interventions have previously been tested. The Optimising Cardiac Surgery ouTcOmes in People with diabeteS intervention was based on an existing nurse-led outpatient intervention, delivered in the 3 months before elective orthopaedic surgery. This intervention reduced pre-operative glycated haemoglobin and reduced length of stay. We undertook a survey of United Kingdom cardiothoracic surgeons, which found limited and inconsistent pre-operative management of people with diabetes awaiting cardiothoracic surgery. A prototype intervention was developed following discussions with relevant stakeholders. Pilot study: The pilot feasibility study recruited 17 people with diabetes and was undertaken by the diabetes and cardiothoracic surgery departments at University Hospital Southampton NHS Foundation Trust. Biomedical data were collected at baseline and prior to surgery. We assessed how the intervention was used. In-depth qualitative interviews with participants and healthcare professionals explored perceptions and experiences of the intervention and how it might be improved. Thirteen people completed the study and underwent cardiothoracic surgery. All components of the Optimising Cardiac Surgery ouTcOmes in People with diabeteS intervention were used, but not all parts were used for all participants. Minor changes were made to the intervention following feedback from the participants and healthcare professionals. Median (interquartile range) glycated haemoglobin fell 10 mmol/mol (3–13) prior to surgery. The median duration of admission for surgery was 7 (interquartile range 6–9) days. Multicentre randomised controlled study of the United Kingdom cardiothoracic centres: We could not proceed to the multicentre randomised controlled study because of the impact of COVID-19 on the delivery of cardiothoracic surgical services and research capacity. Conclusion: There remains an urgent need to improve the surgical outcomes for people with diabetes. This project demonstrated that it is possible to develop a clinical pathway to improve diabetes management prior to admission. Limitations: We could not test the effectiveness of the intervention in a multicentre randomised controlled trial because of the COVID-19 pandemic. Future work: The intervention is available for future research or clinical implementation. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programmme as award number 16/25/12.

Background: Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develop effective treatment strategies. The Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal Study is an observational study which addresses this need by investigating the heterogeneity of RVIs in hospitalised adults, aiming to identify clinical and biological predictors of adverse outcomes. This study aims to bridge critical knowledge gaps in the clinical course and the economic impact of RVIs by characterising the phenotypic diversity of these infections and their recovery patterns following hospital admission and thus assisting with the optimal design of future interventional studies. Methods and analysis: This prospective longitudinal observational study (V.6, 20 September 2023) will be conducted across multiple UK secondary care sites from August 2022 onwards, with an aim to enrol 1000 participants testing positive for RVI. Adults admitted with respiratory symptoms who test positive for RVIs via the BioFire® FilmArray® System or other validated diagnostic PCR tests will be enrolled. The data collected include patient demographics, clinical history, comorbidities and symptoms experienced prior to, during and after hospitalisation with follow-up after discharge at weeks 1, 2, 4, 8, 12 and 26. In addition, biological samples are collected at multiple time points during the hospital stay. The primary endpoints are to study the impact of different RVIs and identify predictors of disease progression and length of stay. Secondary endpoints include time to recovery and healthcare cost. Exploratory endpoints focus on biomarker profiles associated with virus type and clinical outcomes. Ethics and dissemination: The study protocol received ethical approval from the relevant committees (English Ethics Reference Number: 22/WM/0119; Scottish Ethics Reference Number: 22-SS-0101, 20/09/2023). For patients who lack the capacity to consent, the study complies with the Mental Capacity Act 2005, using a consultee process where a family member, carer or an independent clinician may provide assent on behalf of the patient. Data from all the study centres will be analysed together and disseminated through peer-reviewed journals, conference presentations and workshops. The study group will ensure that participants and their families are informed of the study findings promptly and in an accessible format. Trial registration number: ISRCTN49183956 .

Background: Children in care are at elevated risk of mental health issues and poorer well-being, and social care and health services are under pressure to meet their needs. The Shared Training and Assessment for Well-Being programme is a recent approach to training and assessment designed to bring together foster carers and designated teachers to identify and meet the well-being needs of primary school-aged children in care, across the home and school contexts. Objectives: This feasibility randomised controlled trial addressed key questions concerning the acceptability of the Shared Training and Assessment for Well-Being intervention (including training, assessments, clinical review and feedback) and the feasibility of the research design for a larger randomised controlled trial (including recruitment, randomisation and outcome measures). Design: This was a two-arm randomised controlled trial (Shared Training and Assessment for Well-Being intervention vs. control group), with two points of data collection (baseline and 12-month follow-up) for our primary and secondary outcomes. Setting: The study focused on looked-after children from four local authorities in southern England. In the context of the COVID-19 pandemic, both the research and intervention activities were undertaken online with participants. Participants: Looked-after children aged 8–11 years were recruited from the participating local authorities, along with their foster/kinship carers and designated teachers. Carers for all children in the authorities meeting inclusion criteria were initially invited to participate. The original target sample size was 70 children, with 35 receiving the Shared Training and Assessment for Well-Being intervention and 35 in the control group. However, only 21 looked-after children were successfully recruited and randomised. Interventions: Shared Training and Assessment for Well-Being is an integrated approach that combines training on mental health, well-being and resilience for foster carers and designated teachers; a multi-informant assessment package; review of assessments by mental health experts; and feedback to enable key adults to respond to identified needs and strengths. COVID-19 adaptations enabled all key elements to be delivered remotely. Main outcome measures: Two multi-informant primary outcome measures were included as possible candidates for a larger randomised controlled trial: the Strengths and Difficulties Questionnaire and the Paediatric Quality of Life Scale. A further multi-informant secondary outcome measure was also included: the Behavioural and Emotional Rating Scale. Results: Feasibility was not demonstrated, as recruitment was heavily impacted by the COVID-19 pandemic and further attrition occurred over the extended project duration. For the small number who completed the Shared Training and Assessment for Well-Being package, key elements of the intervention were acceptable to participants. In addition, beyond issues with recruitment and retention, key aspects of the randomised controlled trial design, including randomisation, were acceptable. Limitations: It is impossible to distinguish precisely between impacts of COVID-19 and broader challenges with securing the capacity and stability needed to deliver and evaluate the Shared Training and Assessment for Well-Being intervention. Conclusions: Key elements of the Shared Training and Assessment for Well-Being intervention and randomised controlled trial process were acceptable, but the overall randomised controlled trial research design was not feasible in this study. The project was heavily compromised by the impact of the COVID-19 pandemic on foster carers, schools, local services and children. Future work: Potential strategies are suggested to address challenges with evaluating integrated training and assessment approaches aimed at key adults supporting looked-after children. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR127799.

Objectives: Over 9000 patients are diagnosed with oesophageal cancer annually in the United Kingdom (UK). Decision-making about treatment options is influenced by radiological staging, which may include computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS). The use of EUS varies considerably around the UK and, since the introduction of PET-CT, the added value of EUS has been questioned. The VALUE study aims to understand this variation and determine how often and why EUS changes treatment decisions. VALUE will also evaluate patient and clinician experiences and opinions of EUS. Methods: This is a prospective, observational study investigating EUS in oesophageal cancer staging. Patients will be recruited at up to eleven sites in the UK, where they will be consented (if eligible) and registered onto iMedidata RAVE. Clinical and demographic data, TNM staging, pre and post EUS treatment decisions, and complications will be collected. We will attempt to sample patients from ethnic minority backgrounds in the study population, as they are underrepresented in research. Up to 30 patients and 30 clinicians will be interviewed to evaluate the use of EUS and experiences of both patient and clinician. The primary endpoint is the proportion of cases that EUS changes treatment decisions. Secondary endpoints include identification of factors that clinicians’ and patients consider when deciding if EUS should be used, the time from diagnosis to treatment decision before and after EUS, and the reasons why EUS changed management. The study has been registered on Clinicaltrials.gov: NCT06440174. The trial is open to recruitment. Results: In total, 180 patients with potentially curable oesophageal cancer who are suitable for EUS will participate. Recruitment is currently planned until September 2025 and study results will be reported after June 2026. Conclusion: The VALUE study will enable a better understanding of how and why EUS is used in oesophageal cancer. This research will identify important factors that clinicians and patients consider when deciding EUS use and determine the frequency that EUS changes treatment decisions in the modern staging pathway. Advances in knowledge: The VALUE study is a prospective, multi-centre observational study investigating the use of EUS in the modern era of oesophageal cancer staging. The study aims to determine how often and why EUS changes treatment decisions. A qualitative component will explore both clinician and patient attitudes towards EUS.

The next generation of surgical robotics is poised to disrupt healthcare systems worldwide, requiring new frameworks for evaluation. However, evaluation during a surgical robot’s development is challenging due to their complex evolving nature, potential for wider system disruption and integration with complementary technologies like artificial intelligence. Comparative clinical studies require attention to intervention context, learning curves and standardized outcomes. Long-term monitoring needs to transition toward collaborative, transparent and inclusive consortiums for real-world data collection. Here, the Idea, Development, Exploration, Assessment and Long-term monitoring (IDEAL) Robotics Colloquium proposes recommendations for evaluation during development, comparative study and clinical monitoring of surgical robots—providing practical recommendations for developers, clinicians, patients and healthcare systems. Multiple perspectives are considered, including economics, surgical training, human factors, ethics, patient perspectives and sustainability. Further work is needed on standardized metrics, health economic assessment models and global applicability of recommendations.

Background: Randomised controlled trials are designed to assess the superiority, equivalence or non-inferiority of a new health technology, but which trial design should be used is not always obvious in practice. In particular, when using equivalence or non-inferiority designs, multiple outcomes of interest may be important for the success of a trial, despite the fact that usually only a single primary outcome is used to design the trial. Benefit–risk methods are used in the regulatory clinical trial setting to assess multiple outcomes and consider the trade-off of the benefits against the risks, but are not regularly implemented in publicly funded trials. Objectives: The aim of the project is to aid the design of clinical trials with multiple outcomes of interest by defining when each trial design is appropriate to use and identifying when to use benefit–risk methods to assess outcome trade-offs (qualitatively or quantitatively) in a publicly funded trial setting. Methods: A range of methods was used to elicit expert opinion to answer the project objectives, including a web-based survey of relevant researchers, a rapid review of current literature and a 2-day consensus workshop of experts (in 2019). Results: We created a list of 19 factors to aid researchers in selecting the most appropriate trial design, containing the following overarching sections: population, intervention, comparator, outcomes, feasibility and perspectives. Six key reasons that indicate a benefit–risk method should be considered within a trial were identified: (1) when the success of the trial depends on more than one outcome; (2) when important outcomes within the trial are in competing directions (i.e. a health technology is better for one outcome, but worse for another); (3) to allow patient preferences to be included and directly influence trial results; (4) to provide transparency on subjective recommendations from a trial; (5) to provide consistency in the approach to presenting results from a trial; and (6) to synthesise multiple outcomes into a single metric. Further information was provided to support the use of benefit–risk methods in appropriate circumstances, including the following: methods identified from the review were collated into different groupings and described to aid the selection of a method; potential implementation of methods throughout the trial process were provided and discussed (with examples); and general considerations were described for those using benefit–risk methods. Finally, a checklist of five pieces of information that should be present when reporting benefit–risk methods was defined, with two additional items specifically for reporting the results. Conclusions: These recommendations will assist research teams in selecting which trial design to use and deciding whether or not a benefit–risk method could be included to ensure research questions are answered appropriately. Additional information is provided to support consistent use and clear reporting of benefit–risk methods in the future. The recommendations can also be used by funding committees to confirm that appropriate considerations of the trial design have been made. Limitations: This research was limited in scope and should be considered in conjunction with other trial design methodologies to assess appropriateness. In addition, further research is needed to provide concrete information about which benefit–risk methods are best to use in publicly funded trials, along with recommendations that are specific to each method. Study registration: The rapid review is registered as PROSPERO CRD42019144882. Funding: Funded by the Medical Research Council UK and the National Institute for Health and Care Research as part of the Medical Research Council–National Institute for Health and Care Research Methodology Research programme.