Kristianstad, Sweden

Supported Rescue Packs Post-discharge in Chronic Obstructive Pulmonary Disease

What is the problem being addressed? Chronic obstructive pulmonary disease (COPD) is a common lung condition in the United Kingdom, with a prevalence of 4.5% in population ≥40 years and rising4. In addition to daily symptoms such as cough and breathlessness that limit physical activity, people living with COPD are prone to unpredictable deteriorations in their health called 'exacerbations'. Exacerbations are sometimes severe enough to lead to hospital admission and are often driven by infections. A systematic review of patient outcomes in COPD identified exacerbations, especially severe hospitalised exacerbations, as the aspect of COPD that patients found most difficult to live with. Prior to the pandemic there were around 115,000 admissions to hospital with COPD exacerbations per annum6 and admissions are now returning to that level. Exacerbations are more common in the winter with greater circulation of respiratory viruses, and thus the burden of hospitalised exacerbations contributes to winter National Health Service (NHS) bed pressures and cost to the NHS. The annual healthcare cost for people with moderate and severe exacerbation of COPD in England was estimated to be nearly £1 billion in 20227. A particular problem after a hospitalised COPD exacerbation is re-admission to hospital. The National Asthma and COPD Audit Programme (NACAP) has shown that the re-admission rate is 23% at 30 days and 43% at 90 days2. A systematic review conducted by the authors identified comorbidities, previous exacerbations and increased length of stay as risk factors for 30- and 90-day all-cause readmission5. There are many interventions that can reduce the risk of COPD exacerbations but these are incompletely effective8. There is also evidence to suggest that earlier intervention with standard exacerbation treatment of antibiotics and/or corticosteroids (called a 'rescue pack') can hasten recovery, with a lessened chance of hospital admission9. As part of standard NHS care2, patients with COPD should have a 'discharge bundle' implemented, although this is often poorly delivered and has not been definitively shown to impact outcomes (likely because the wrong outcomes were chosen, and the bundle was poorly implemented)10. The provision of rescue packs is not a standard component of discharge bundles but these are sometimes provided according to local service preference3. Additionally, in usual clinical practice, some patients will have been prescribed rescue packs from primary care (GP) or a community respiratory team (CRT) prior to being hospitalised with COPD. Furthermore, patients may or may not have access to rescue packs from the GP or the CRT after hospital discharge. Although rescue packs are part of NICE guidance2, the available evidence suggests they are not effective unless provided in the context of a more comprehensive management/education plan that supports patients in their appropriate use11. In practice this usually does not happen3, with evidence that a patient with COPD will receive variable or often no support; with some patients receiving rescue packs on demand without considering antimicrobial resistance, predictable side-effects from steroid overuse, or reviewing appropriateness. The investigators have pilot data that show receiving a rescue pack on hospital discharge is controversial as the hospital team is not, in general, the team that provides ongoing support to use these. There is thus recognised over- and under-use of rescue packs, associated harm from these medicines and variable provision. Providing a rescue pack, with education on how to use and support for when to use, has not been specifically tested in the high-risk 90-day period for readmission following a hospitalised exacerbation. It is the investigators' hypothesis that rescue packs on discharge in addition to a comprehensive self-supported management plan, consisting of the Asthma+Lung UK written management plan and twice weekly automated phone and or text messaging during this 90 day high risk period, will reduce readmissions by 20% compared to standard care. Why is this research important in terms of improving the health of patients and health and care services? Reducing re-admission through provision of supported rescue pack use would benefit people living with COPD and the NHS. A reduction in readmissions of 20% could save the NHS £86 million per quarter (£344 million per annum). Conversely, demonstrating that rescue packs are not effective when used in this way will address controversy about use, and reduce pressure on antimicrobial resistance and harm from over-use of oral corticosteroids. Integrated care systems are rapidly developing out-of-hospital support for people with exacerbations of COPD including digitally supported virtual wards. The proposed trial will define the role of supported rescue pack provision in the design and implementation of these programmes, enhancing their ability to reduce demands on urgent and acute care. Whether positive or negative, this trial will help to reduce the current variation in service provision by providing a definitive answer to the study question. Furthermore, preventing exacerbations of COPD have been identified as a priority by the James Lind Alliance (JLA) Priority Setting Partnership (PSP)12.

ABTECT - Maintenance

All eligible subjects who have completed either one of the induction studies above mentioned, will be given the opportunity to take part in the present ABX464-107 study which consists of 2 treatment phases. This study consists of a 44-week maintenance treatment phase (Part 1 and Part 2), followed by a 4-year Long Term Extension (LTE) treatment phase and a 28-days follow-up period consisting in the End of Study (EOS) visit. The maintenance phase is a 44-week double blind, placebo-controlled, phase. Subjects who are clinical responders after 8 weeks induction will be randomized to Part 1, and those who are non-clinical responders will be randomized to Part 2. At the end of the 44-week maintenance phase, subjects will continue their allocated treatment until the maintenance phase is unblinded. Once the study is unblinded, all subjects receiving obefazimod will continue their allocated treatment. Subjects receiving placebo will be allocated to obefazimod 25 mg or can terminate the study.

Axillary Management in Breast Cancer Patients with Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy

Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease. Aim: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years. Methods: Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio. Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node). Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years. Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years. Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness. Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years. Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated. Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination.

The Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis Study

This is a major pragmatic multi-centre prospective parallel group open RCT. It will be conducted in the UK, Australia and New Zealand, funding is being sought in several countries to expand recruitment internationally. The study is in 2 phases: the vanguard and main phase. Therefore the study will run an internal pilot to prove recruitment of the relevant number of participants during the initial 2 years. The over-arching aim is to determine whether early AVR results in better clinical outcomes and cost-effectiveness than a strategy of expectant management in asymptomatic patients with severe AS. The primary hypothesis is that early AVR or TAVI in asymptomatic patients with severe AS will result in a reduction in the composite primary outcome of cardiovascular (CV) death and hospitalisation for heart failure (HHF) when compared to the conventional approach of expectant management. Potential participants will be identified by a member of the clinical care team following diagnosis with severe AS. Participants will be screened for eligibility using pre-specified inclusion/exclusion criteria. Eligible participants will be provided with a written version of the participant information sheet detailing the exact nature of the study, what it will involve for the participant and any risks involved with taking part. Participants will be given at least 24 hours to consider the information and decide whether or not to take part. The study will randomise up to 2844 patients with severe asymptomatic AS to either allocated expectant management OR aortic valve replacement. Participants randomised to AVR will be placed on a waiting list with the aim that surgery will be performed within 3 months, dependent on local hospitals' waiting lists. Participants randomised to AVR will undergo routine tests/procedures which may include coronary angiography. If the outcome of the coronary angiography reveals coronary heart disease, the decision to perform CABG or PCI will be made by the responsible cardiac surgeon and cardiologist, in consultation with the patient. All analyses will be undertaken using the principles of intention-to-treat with participants analysed in the group they were randomised regardless of treatment received. EASY-AS is collaborating with the EVoLVeD study (Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis, Clinical Trials.gov NCT03094143). In centres where both EASY-AS and EVoLVeD are running, participants in EASY-AS will be offered the opportunity to take part in EVoLVeD. Funding has been granted by the British Heart Foundation (UK), Medical Research Future Fund (Aus) and Heart Foundation (NZ). The UK sponsor is the University of Leicester. Additional support and resources for the study will be provided by the participating Trusts and their corresponding Clinical Research Networks in the UK. The central co-ordination centre is the University of Leicester Clinical Trials Unit.

A Randomised Open-label Phase III Trial of REduced Frequency Pembrolizumab immuNothErapy for First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

Immunotherapy with pembrolizumab targeting the T cell inhibitory PD-1 receptor has significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). Approximately 3600 new patients are treated in the 1st line setting per year in England alone and up to 25% remain on 6 weekly pembrolizumab for 2 years. However, pharmacological and clinical trial data suggest current frequent dosing for 2 years result in overtreatment. Indeed, pembrolizumab remains bound to its target receptor for up to 100 days following a single dose and studies in multiple tumour types have found no relationship between dose and patient outcome. Moreover, anti-PD1 treated patients who respond but discontinue therapy either as planned after 2 years, or earlier because of toxicity, can either remain in remission and/or be sensitive to re-challenge with pembrolizumab. REFINE-lung will test whether reduced pembrolizumab dose frequency (9, 12, 15, 18 weeks) after 6 months of standard treatment is safe and effective. This UK study represents a unique opportunity to determine whether pembrolizumab dose frequency can be safely reduced in NSCLC, resulting in significant cost benefits to the NHS and globally, in addition to enhanced patient QoL associated with fewer hospital attendances and reduced toxicity.

Reconstruction in Extended MArgin Cancer Surgery

This is an observational multicentre retrospective and prospective cohort study, and a qualitative study. The project will have three working packages: - Work package 1 - maintenance of a colorectal surgery database - Work package 2 - prospective collaborative national UK study - Work package 3 - qualitative analysis with semi-structured interviews WORK PACKAGE 1 - COLORECTAL SURGERY DATABASE: Data collected includes: - Basic demographic information - Co-morbidities at time of surgery - Other cancer treatments - Final cancer staging and diagnosis - Type of procedure - Methods of reconstruction - Use of healthcare resource: (theatre time, surgical teams, use of consumables, index operation intensive care stay, total length of stay, planned or emergency readmissions, use of imaging for complications, re-interventions, and outpatient clinic use). - Morbidity - empty pelvis syndrome complications with collation of all complications that occurred summarised into: (the highest Clavien-Dindo (CD) score, and the comprehensive complication index by accumulating CD graded complications that a patient has as a result of their surgery. - Survival: overall and disease-free survival - Patient reported outcome measures Any other routinely collected clinical data will be included. Of particular mention we will include and analyse Cardiopulmonary exercise testing data, data derived from the perioperative medicine screening and assessment, data derived from prehabilitation, radiomic data e.g. muscle/fat structure and function derived from CT, MRI or PET-CT. WORK PACKAGE 2 - PROSPECTIVE COLLABORATIVE STUDY: Abdominoperineal excision and pelvic exenteration can be used in a wide range of cancer types, and in the case of pelvic exenteration can be used to manage both recurrent and primary cancers. The principal PROM used will be the EORTC QLQ-C30 with its modular questionnaires giving additional insight into disease-specific quality of life. All amendments have been made in line with NIHR RfPB funding received in November 2024. Patients will be recruited once a decision to undertake abdominoperineal excision or pelvic exenteration surgery has taken place. Participants will be sent a participant information sheet which will include the dates of when participants can expect follow up telephone calls, with information on how to contact the study team to change these should participants wish to. Once consented participants will undergo the following PROMs as part of their baseline questionnaire: - EORTC QLQ-C30 with specific cancer-type modules - EQ-5D-5L - LRRC QoL - Decision Regret - Comprehensive Score for Financial Toxicity (COST), financial status questionnaire (non-validated) and Patient employment status questionnaires. The investigators anticipate that participants will be able to self-assess the above PROMs on a paper printed form, however a member of the research team will be available to support the participant if required. Clinical information will also be collected pre-operatively, including: demographic information, co-morbidities, cancer staging, and previous cancer treatments. Patients will be given copies of the follow up questionnaires at this time so participants have them as a reference when completing follow up questionnaires. Patients can opt for either email or telephone follow up for quality of life, if opting for email REDCap study will automatically send out emails based on the date of surgery. The patient will then undergo their surgery with method of reconstruction at the discretion of the operating surgeon(s). Following the index admission researchers will enter details on the hospital stay: - Type of procedure - Methods of reconstruction - Theatre time - Theatre teams - Use of consumables - Length of intensive care and hospital stay - Use of imaging for complications - Re-interventions for complications - Discharge destination following index admission - Final cancer staging and other pathological outcomes. - Perineal and empty pelvis morbidity, and overall Clavien-Dindo and Comprehensive Complication Index - NHS healthcare utilisation costs - If applicable survival and cause of death At 3 months post-operatively questionnaires will be repeated over the telephone including: - EORTC QLQ-C30 with cancer-specific module - EQ-5D-5L - LRRC QoL - Decision Regret - Comprehensive Score for Financial Toxicity (COST), Patient reported heath resource utilisation and NHS healthcare utilisation costs. At this same time point researchers will review routinely collected clinical data and use of in-hospital health resources to include: - In-hospital health resource use: planned or emergency re-admissions, use of imaging to investigate complications, re-interventions (surgical and radiological), planned or unplanned outpatient visits. - Longitudinal CCI scores updated, and if applicable an increase in CD if a more severe complication develops. - If applicable cancer recurrence, survival and cause of death will be recorded. Patients will be emailed or telephoned on the date specified on their participant information sheet, however if this time is not convenient then a better time will be arranged with the patient. If participants do not respond to the email or first telephone call then the investigators will make a further three separate attempts to contact the patient. If there is still no response participants will be deemed lost to the study. This follow up process will be repeated again at 6 months and 12 months. At the 12 month time point the investigators will ask patients additional questions on their use of health care resources and their current financial status, to include: - Use of community health resource use due to complications including: GP appointments and nursing home care days required for recovery from surgery. - Use of healthcare resources at hospitals other than the treating hospital - clinic appointments and admissions At the end of this time the patient will have completed the study. WORK PACKAGE 3 - QUALITATIVE STUDY: The qualitative study will recruit patients from work packages 1 and 2. The investigators will invite 30 purposefully sampled patients that are 3 months following their surgery. Suitable patients will be contacted with a posted participant information sheet and a telephone follow up call to allow participants to ask questions about the study. Following informed consent semi-structured interviews will take place with semi-structured open questions to guide the discussions. Interviews will be recorded on an encrypted audiorecorder and then transcribed. The investigators will initially undertake three pilot interviews to review that the semi-structured interview schedule is adequate to fully explore our objectives and to obtain good quality interview transcripts for analysis. These pilot interviews once completed will be reviewed by the research team. The semi-structured interview schedule questions may be changed if the interviews are of poor quality, pilot interviews demonstrate new insights from participants that suggest fruitful lines of enquiry, or inconsistencies that require further exploration. If subsequent interviews are very different than the pilot interviews following these changes, then these early interviews will not be included in the qualitative analysis and additional patients will be recruited. Patients recruited at 3-months following surgery will be offered a repeat interview at 12-months following their surgery DATA ANALYSIS PLAN: Statistical analysis: The investigators will be collecting data on the timepoints as described above. Continuous data will be will be summarised using descriptive statistics (mean, median, standard deviation, lower and upper quartiles). Categorical data will be summarised using counts and percentages. As studies are non-randomised, the investigators will utilise regression models and principal component analysis to adjust for confounding in this observational study. In order to obtain our outcomes a brief summary of analyses is below. Work package 1 (Colorectal Database): Primary analysis: - Frequency of morbidity relating to the empty pelvis syndrome and perineal wound will be compared for different types of perineal reconstruction will be analysed using multiple linear regression. Secondary analysis: - Overall morbidity will be obtained using highest CD scores for different methods of perineal reconstruction analysed using multiple linear regression. - Disease free and overall survival will be analysed using Kaplan-Meier curves and log rank tests with a multivariate Cox regression hazard model to identify factors independently associated with survival, including method of reconstruction. Exploratory analysis: - Other factors including age, gender, BMI, final staging, co-morbidities, type of operation, neoadjuvant chemoradiotherapy and use of intra-operative electron radiotherapy will be included in the analysis - Other outcomes including primary operation time, lengths of stay, and readmissions will be explored Work package 2 (prospective study): Primary and secondary analysis: - Patient reported outcome measures will be analysed using regression models, including linear mixed-effects models for repeat measures and adjusted analyses. - The same clinical data fields will be collected as per work package 1, the analysis above repeated with exploratory analysis to find factors that are independently significantly associated with changes in the PROMs. Health economic analysis: Work package 1 (retrospective study): The investigators will collect data on use of hospital healthcare resources in each patient group. The investigators will collect resource use for each parameter required for each patient. The investigators will then undertake costing using a micro-costing approach and health resource group costing for each parameter. Applying costs to each parameter will use a combination of manufacturer prices for consumables, National Cost Collection for the NHS, National Schedule of NHS Costs, NHS National Tariff and the Unit Costs of Health and Social Care from the Personal Social Services Research Unit. The investigators will then report overall costs associated with different methods of perineal reconstruction and the cost of complications that were encountered. Work package 2 (prospective study): The investigators will collect hospital healthcare resource use data prospectively and apply micro-costing to these parameters in the same way as per work package 1 for each patient and their method of reconstruction. The investigators will also ask patients to provide us with use of community healthcare resources as a result of their surgery, data for which the investigators will not be able to obtain from their clinical notes. Participants will receive EQ-5D-5L and EORTC QLQ-C30 questionnaires at baseline, 3 months, 6 months and 12 months. From these responses the investigators will map onto EQ-5D-3L in order to reduce the overall number of questionnaires patients are undertaking in our study. This will allow us to plot EQ-5D-3L responses for different methods of reconstruction and plot the area under the curve. Within the trial time a health economic model would be built which would follow the NICE reference case and ISPOR Task Force guidelines on health economic analysis. This will enable us to present Quality Adjusted Life Years and incremental cost-effective ratios for the different methods of perineal reconstruction. Qualitative analysis: Audio transcription will be transcribed verbatim, checked against the recording and anonymised. Data will be uploaded to NVivo for data management. Preliminary summaries will be written after each interview to identify emerging themes to follow-up discussions. The follow-up interview will ask patients to reflect on the content of their previous interview and discuss any changes. Longitudinal interview analyses will use constant comparative methods from grounded theory and data coded using NVivo's framework matrix facility to examine themes longitudinally, enabling comparisons within each case and across cases, focusing on changes over time. The stages of data analysis, drawing on longitudinal comparisons, will include: 1. Initial reading: Review interview data. 2. Preliminary coding: Two researchers code the data. 3. Team meeting: Discuss and refine codes with wider research/PPI team. 4. Individual Case Coding: Code all interview data for each participant. 5. Categorising Codes: Group codes into categories for each case. 6. Longitudinal comparisons: Within case and category comparisons focussing on changes over time. 7. Focused coding: Examine categories in relation to emerging concepts and phases. 8. Discussion on Themes: PPI co-led focus group discussions of final themes. 9. Development and Dissemination: Report write up are dissemination. Based on an iterative process, emerging themes will be used to develop explanatory accounts. Analysis will draw on sociological perspectives of illness adaptation, recovery and self-management in addition to psychological theories of individual behaviour change. All qualitative and quantitative data will inform 3 patient focus groups, where PPI and charity collaborators along with 5 newly trained PPI members will discuss data analyses from a patient perspective, contributing to initial discussions around developing a patient decision aid.

ABTECT-1 - ABX464 Treatment Evaluation for Ulcerative Colitis Therapy -1

GEKO Venous Thromboembolism Prevention Study

Venous thromboembolism (VTE) is a disabling and potentially fatal outcome that may be acquired after having a stroke. The standard treatment to prevent the development of VTE is to give anticoagulation medication. However, this is not recommended in the UK after stroke. Instead the recommended treatment is Intermittent Pneumatic Compression (IPC), where cuffs placed around the lower legs are filled with air to help squeeze the legs and induce blood flow. However, not all patients are able to receive or tolerate IPC treatment. Another treatment which has shown promising results to prevent VTE in immobile patients after stroke, is with a medical device called the geko™ device. The geko™ device is a CE marked medical device which means the manufacturer has checked that the device complies with the essential safety and performance requirements for its' intended use which is to increase blood circulation to help prevent VTE. The aim of this study is to determine if the geko™ device is more effective at preventing VTE in immobile acute stroke patients, than the current IPC standard of care treatment. Following the consent process, stroke patients will be randomised to receive either IPC or geko device. Both devices will be applied until the patient can walk again without help, or for a maximum of 30 days. A compression Doppler exam of the legs will be conducted after 7 days or at discharge if the patient recovers earlier (optional) and after 14 days (mandatory). At 14 days post-randomisation, a patient questionnaire about the comfort of the device, as well as additional health information will be collected. At 30 days after randomisation, additional information about symptomatic DVTs or PEs etc., will be collected from the participant's medical notes. A final follow-up will then be conducted over the phone after 90 days to find out about the patient's recovery, health, mobility and quality of life.

Video Analysis of Errors and Technical Performance Within Minimally Invasive Surgery Short Title: Video Analysis in Minimally Invasive Surgery (VAMIS)

There are 2.5 million people who have cancer in the UK, projected to increase to 4M by 2030. Over the past three decades, there has been a rapid uptake of minimally invasive (keyhole) surgery i.e. laparoscopic and robotic techniques, to treat cancer across different specialties. Robotic surgery is a well-established modality; the most commonly used robot for surgery (da Vinci) has been used in more than 8.5 million procedures, 1.25 million of which were in 2020. Previous research from our group developed valid methods to accurately assess surgical skill and errors in laparoscopic procedures using video analysis of rectal cancer surgery. The methods and tools developed were able to link surgeons' technical skill, including errors made, to patient outcome i.e. those who scored better had better outcomes. Investigators hypothesise that understanding and optimising surgical processes and errors will reduce unwarranted variations and improve the performance of the entire surgical team that is ultimately hoped to enhance patient safety and outcomes. With an increasing use of robotic systems across different specialties, there is an need to standardize training, assessment, testing and sign-off as a competent robotic surgeon in order to improve patient safety. A study from the 1990s estimated that more than 250,000 people die in the USA every year from medical error. Another study from the USA reported between 2000-2013 10,624 adverse events relating to robotic procedures. Experts raised concerns over surgical curricula being random and insufficient to ensure patient safety, leading to the development of EAU Robotic Urology Section Curriculum (ERUS). In addition, an independent review by the Emergency Care Research Institute (ECRI) on health technology hazards identified a lack of robotic surgical training as one of the top 10 risks to patients. Comparisons are frequently made between the aviation industry and surgery in terms of adverse event analysis and non-technical skills. The aviation industry, however, has mandatory, recurrent, reassessment and requalification throughout the career pathway and an internationally agreed standard for training, which robotic surgery does not. Our research group has a track record in developing objecting assessment tools to aid training and accredit laparoscopic surgery and will utilise this expertise to enrichen assessment tools in robotic surgery. Given the link between surgical skill and error counts to patient outcome, this research team aims to analyse surgical video within robotic surgery in different procedures to further understand the surgical process and errors made. Further understanding of these processes could enhance our knowledge and ability to provide meaningful feedback and accurately assess surgeons. This in turn, it is hoped, will enhance performance and improve patient outcomes. Aim This research project aims to assess robotic techniques for surgical phases and error detection that would permit the objective assessment of surgical performance, allowing the assessment of surgeon and procedure specific proficiency gain curves (learning curves) and identifying training needs. 4.1 Objectives 1. Develop a standardised and agreed segmentation of the operations (Delphi system) 2. Video error analysis: Application of OCHRA into Robotic assisted radical prostatectomy 3. Video error analysis: Application of OCHRA into robotic rectal cancer surgery (anterior resection TME) 4. Validation of assessment tool scoring, video analysis to patient outcomes i.e., morbidity, histopathological data 5. Development of formative assessment tools for generic and specific-procedures 6. Video error analysis: Development, evaluation and application of automation and video error analysis (artificial intelligence and machine learning) in minimally-invasive surgery. 7. Qualitative data review of surgeons' perception of TSE after using the platform. 8. Qualitative data review of surgeons' perception of effect on learning curve. 9. Analyse kinematic data to further understand its role in errors and skill in minimally-invasive surgery 10. Development of summative assessment tools to aid certification and accreditation. . Study design: Observational study collecting anonymised video data and uploaded to Touch Surgery platform. Recruiting sites and Principal investigators: University College London Hospitals (Mr Ashwin Sridhar), Yeovil District Hospital NHS Foundation Trust (Professor Nader Francis), Queen Alexandra Hospital, Portsmouth (Professor Jim Khan), The Christie (Mr Chelliah Selvasekar) and Northwick Park & St Marks Hospitals (Mr Danilo Miskovic). Prospective data upload: Patient identification: The local team will identify patients in clinic/multi disciplinary team meetings based on adherence to inclusion criteria. The patient will be approached by a GCP trained member of the research team ideally at least 24 hours after they have been informed about the study and have had time to read the patient information sheet provided in clinic or posted to them. If the team is only able to provide information on the day of surgery, considering video recording is standard and it doesn't affect their care, this would be deemed acceptable. Consent and information sheets will be kept short in order to minimise disruption to patient care. Any surgeon willing to contribute their video data for analysis will be given access to the Touch Surgery Platform to review their own videos and annotate, these videos will also be added to a shared group with the clinical research team for analysis. The surgeon will be consented to allow their data to be analysed and results disseminated, which will be anonymised. If they wish, they can ask for analysis feedback. Surgeons will be recruited by their local Principal Investigator at each site, who will be working closely with the research team at The Griffin Institute. Data capture and analysis Surgical videos will be recorded via an encrypted hard drive or The Touch Surgery™ Enterprise DS1 Computer. The Touch Surgery™ Enterprise DS1 Computer is connected to the operating room's video imaging system with a HDMI cable (or other compatible wired connectivity). A member of the operating room staff uses the Touch Surgery™ Enterprise DS1 Wireless Controller to select the procedure and surgeon name. A custom file name and notes can also be added, and users are prompted with a reminder not to input any patient personal information. Throughout the case, and whilst the recording is in process, the video passes through our AI-powered safeguard, RedactOR™, before it is saved to the Touch Surgery™ Enterprise DS1 Computer. RedactOR™ works on the video in real-time to determine when the scope has exited the patient. The algorithm then pixelates the video frames, and will continue to do so, until the scope re-enters the patient. All videos will be uploaded to TSE and therefore be processed through RedactOR™. This redaction is irreversible, thereby giving additional confidence that visual information that could identify a patient is transmitted, processed or stored. Upon direction by the authorised user, the video is uploaded from the Touch Surgery™ Enterprise DS1 Computer to our secure cloud provided by Amazon Web Services (AWS). AWS complies with ISO 9001, ISO 27001, ISO 27017, and ISO 27018, and audited against HDS (France). Touch SurgeryTM Enterprise DS1 Computer will record, process and provide analytics on video recordings of minimal-access surgical procedures. These are recorded through the standard operating stack and require no additional steps or changes to standard care. Currently, procedures are routinely recorded in the operating room for training purposes to allow review and debrief after a procedure or to evaluate where improvements could be made. The dVLogger box additional records endoscope video in stereo and robotic movement data. No audio will be recorded. This data is collected by an encrypted hard drive and used by WEISS who will anonymise the data sent to Intuitive Surgical Inc. WEISS will have access to the study ID to link analysis to patient data, Intuitive will not. This research team does not anticipate that there will be any new material ethical issues associated with the recording system and surgical video feed. Operative steps will be closely analysed using this software, applying machine learning and OCHRA methodology techniques to identify phases and errors of minimally-invasive surgical operations. Researchers trained in these methodologies will be observing and analysing the data. Data upload to TSE will be anonymised with no patient identifiable data, but the clinical research team will pseudonymise patient data and outcomes including demography, identifiers to follow up outcome, surgeons' grade/level of expertise. Video editing software will be used to annotate and highlight surgical video data to categorise phases and errors. STUDY SETTING Data will be collected at multiple centres that have the capability to capture minimally-invasive surgery videos in the following procedures initially: patients undergoing a robotic-assisted cancer procedures including prostatectomy, cystectomy and anterior resection (rectal cancer operation). Patients will be approached during the consent process at participating research sites: University College London Hospitals, Queen Alexandra Hospital (Portsmouth), The Christie (Manchester) Northwick Park & St Mark's Hospitals and Yeovil District Hospital NHS Foundation Trust. However, it will expand to any NHS site performing minimally-invasive surgery and willing to participate. It is appropriate to have multiple sites, as this will provide the most data and ensure a richer data set to address the research objectives Site requirements; to perform minimally-invasive surgery and have video capturing devices installed. Data will be collected at each site and analysed by the clinical research team. Sampling including size of sample Sampling will be from a clinical setting during the consent process. Participant number: This project requires uploading a large number of video recorded cases in order to conduct the research and achieve all the primary and secondary end points. The type of cases will vary from generic laparoscopic procedures that will aid development initial phases of the project such as segmentation, to more advanced procedure segmentation e.g. Robotic prostatectomy and robotic rectal cancer surgery. Since OCHRA was applied extensively in laparoscopic rectal cancer surgery, a comparison will also be made with robotic, hence, video recording of laparoscopic colorectal cases will be required. In order to achieve this number investigators will partner with a number of hospitals including Yeovil District Hospital NHS Foundation Trusts, University College London Hospitals, Queen Alexandra Hospital (Portsmouth), The Christie (Manchester) and Northwick Park & St Marks Hospital. There is no formal power calculation in this study but investigators aim to record as many procedures as possible within the time frame of the project and with a maximum 250 from each centre. The researchers aim to conduct full OCHRA analysis including error annotation up to 50 videos per specialty. 7.3 Recruitment Patients at sites contributing to video analysis will be identified before surgery and consented using a standardised form and information leaflet. Patients will be identified and clinic or multidisciplinary team meetings and approached by the local research team by a GCP trained healthcare professional. They will explain the study and provide a patient information sheet which they can read at home. Over 24 hours after the first approach they will then be asked if they would consent to the study, this would be easily done on the day of the operation, using a separate consent form to the procedure consent form. There is minimal risk of coercion as it is a low risk, observational study, with no intervention or change to standard care. 7.3.1 Sample identification Healthcare professionals such as doctors, clinical nurse specialists or research nurses can identify patients who may be eligible for the study. Similarly, if trained appropriately, any of the above could take consent as it is low risk. If any healthcare professional not involved in the study is asked questions about it, they could let the research team know to contact the patient. Patients will be identified before surgery and will be provided with a patient information sheet and consented using a standardised form stating that the data will be anonymised and used for video analysis only. Clinical data and patient participants will be pseudonymized with a unique study identification number. Study ID numbers will be assigned with a local trust code e.g. UCL-001 and in order of upload to Touch Surgery, there is no need to randomise the numbers. There will be no advertisements or external recruitment, patients will only be approached if they are undergoing a minimally-invasive surgical procedure and have capacity and time to consent. A Participant Information Sheet will be provided to the identified patient to describe the study and what their involvement means explaining they can withdraw at any time, that it is anonymous and investigators believe ultimately through their involvement they will improve patient care through improving knowledge of surgical skill. 7.3.2 Consent Patient consent will be informed and at the same time of procedure consent, as all ethical concerns that could be associated with the study have been addressed, and due to the standard of routine recording surgeries in the participating sites. Participants will be allowed to ask questions, withdraw without reason at any time and it will not affect their care. Research entry and consent would take place at the same time as procedure consent. The use of translators (friends/relatives or professional services) would be at the discretion of the PI or co-investigator taking consent. Research entry is not possible without informed written consent. Where possible, translation for the PIS and consent form will be provided through the Trust translational services. If it is not available or there is not enough time pre-operatively, non-English speakers will be excluded from the study if they do not have the fluency to read & comprehend PIS and ICF. ETHICAL AND REGULATORY CONSIDERATIONS Patient confidentiality Patient confidentiality will be maintained. Surgical videos will be stored securely on Touch SurgeryTM Enterprise (TSE; https://www.touchsurgery.com/). No patient identifying information will be attached to the videos that are uploaded to the Touch SurgeryTM Enterprise platform, which will be monitored at the point of capture, using a real-time safeguarding algorithm, to ensure confidentiality. No audio is collected to maintain confidentiality. Clinical data will be collected and accessed by only the clinical research team, who all have employment or honorary contracts at the clinical sites. All clinical data will be kept on NHS password-protected computers, on a password-protected Microsoft Excel spreadsheet on Trust premises, accessible only by the clinical research team. Digital Surgery Ltd team cannot access clinical data and patient participants will be assigned with a unique study identification number, so the identity of the patient is not known to them, to preserve patient confidentiality. The data from dVLogger data sent to Intuitive is anonymised and sent on an encrypted hard drive. Data protection To capture the surgical videos, a video cable non-intrusively connects the standard video outputs of the surgical video monitor, surgical robotic device, or stack into the Touch SurgeryTM Enterprise encrypted computing equipment, the DS1. The DS1 is not a medical device. The DS1 runs Digital Surgery Limited's proprietary, in-situ AI safeguarding algorithm (RedactOR™), which redacts, via automatic pixelation, out-of-body surgical video footage, to remove identifiable personal data, in real-time. The encrypted computing equipment then transfers the anonymised videos to Touch SurgeryTM Enterprise platform; built upon a secure cloud server provided by Amazon Web Services in Europe, operated by Digital Surgery Limited. All anonymised data handling will be performed by designated, trained members of the clinical research team at TGI and technical research team at Digital Surgery Limited. All clinical data handling will be performed only by designated, trained members of the clinical team at The Griffin Institute. Digital Surgery Limited products and services (Touch Surgery ™ Enterprise) are compliant with the General Data Protection Regulation of 2018 (GDPR) and UK Data Protection Act of 2018 (UK GDPR). The data custodian will be the Chief Investigator Professor Nader Francis. Personal data will be stored in line with respective trust data retention standard procedures. This will remain for up to 5 years. Potential risks Investigators expect no difference between those patients in the trial or not. All patients require the operation as part of their routine care and this study does not alter the way the surgeon performs the case in any way, routinely surgeons will record operations, there is no change to standard care nor are additional patient visits required. Any potential risk to patient confidentiality has been addressed and sufficiently mitigated by the study protocol. There are no additional risks to the staff as part of this study. It will not impact surgical rotas; theatre lists or scheduled operations. The only possible potential risk with this study is identification of significant errors on the video analysis that are not detected by the operating team and therefore no corrective action taken. However, the nature of this project involves reviewing the videos a significant period of time after the operation. Any sequelae from this event would have been apparent in the post operative period well before video analysis is conducted. If there are any learning points, however, these will be communicated with the PI at each site. Potential benefits Researchers hypothesise that understanding and optimising surgical processes, and errors will reduce unwarranted variations and improve the performance of the entire surgical team that will ultimately enhance the patient's surgery and outcomes. It is noted that there is no direct benefit to the individual patient taking part other than potentially helping to improve the safety of standard routine surgical procedures in future operations. Researchers hope that this technology will be used to improve surgical training and preparation of the entire operating theatre team and optimise performance and standardisation. It is hypothesised that the implementation of this technology may benefit patients by reducing surgical variations and errors and may also enable monitoring and assessment of surgical competence based on reliable, actionable data. If patient loses capacity to consent during study If the patient loses capacity before consent then they will not be invited to participate (in accordance with inclusion criteria). If they are suspected of losing capacity afterwards then the participant will remain in the study at the clinician's discretion as this is an observational study will no unremediated risks. Physical security arrangements for storage of personal data Videos will be in electronic format and retained in encrypted storage. Procedural data will be directly uploaded from the device to a secure cloud server provided by AWS (Ireland, Europe), which is GDPR compliant. AWS will be used to store all media and data, which conforms to the ISO 27001 security management standard and is a member of the Cloud Security Alliance. Any transfer between the study sites would be in encrypted storage formats or through a secured internet connection. Data from the video recordings of surgery will be extracted, transferred and analysed using computerised software based at Digital Surgery Ltd. in London, UK. No patient data will be shared with Digital Surgery Limited in the duration of this study. Only Yeovil District Hospital NHS Foundation Trust/TGI (restricted to the clinical research team) will access and retain identifiable information such as study files. Yeovil District Hospital NHS Foundation Trust will only collect the minimum required information for the purposes of the study. Recruitment Arrangements and informed Consent Following informed consent to participate, the study patient participants will be assigned with a unique study identification number. This identifier is pseudo anonymised to the clinical research team. Patient consent forms will be securely stored in locked cupboards and password protected NHS equipment, NHS sites, with access restricted to the only authorised members of the clinical research team. How will researchers ensure the confidentiality of personal data? / Who will have access to participants' personal data during the study? The surgical video and associated metadata on Touch SurgeryTM Enterprise cannot identify the participant. Participant personal data (any data that may identify a participant) is not necessary for the service Touch SurgeryTM Enterprise provides to the study site. Only the clinical research team has access to identifiable information about the participant. Access restrictions are in place to mitigate any risk to confidentiality of participant personal data. Data will be used, stored and transferred in an encrypted format, and handled in accordance with the UK Data Protection Act of 2018 (UK GDPR). Where will the data generated by the study be analysed and by whom? Data generated will be analysed by the clinical research team. Only anonymised data will be transferred to Touch SurgeryTM Enterprise (UK) and analysed by authorised members of the Digital Surgery Limited team for the purpose of the study, to identify key markers such as surgical phases and associated variations. Intuitive Surgical Inc. will receive anonymised data from the dVLogger via an encrypted hard drive. Pseudonymised data will be analysed by the research team at TGI and WEISS. This will be stored on secure servers with access limited to the team. Based on previous similar uses of OCHRA errors in colonic surgery, error count results are expected to be normally distributed (however, this will be confirmed using detrended QQ statistical plots prior to analysis). Task and type specific error counts can be compared with Mann-Whitney U test. OCHRA as previously described is a validated methodology to manually, accurately and reliably assess errors in a minimally invasive procedure. Data from this can then be statistically analysed and linked to patient data including demography and outcome Digital Surgery data science team will be involved in video analysis through analytic reporting. Qualitative questionnaires will be used at the end of the study to evaluate surgeons' opinion and gain insights on the use of surgical video and novel analytics. This will be done using thematic analysis. SPSS will be used for all data analysis.

Evaluation of Four New Ready to Drink Oral Nutritional Supplements: Adult ONS Trial

Disease-related malnutrition (DRM) is a highly prevalent condition which leads to significant adverse health and economic burden. For the management of patients with DRM, oral nutritional supplements (ONS) are recommended and often prescribed (typically 1-3/day). ONS are energy- and nutrient-dense feeds that provide macro and micro-nutrients, designed to increase nutritional intake when diet alone is insufficient to meet daily nutritional requirements. The use of ONS has been shown to be effective for managing DRM by improving patient outcomes, including alleviating disease symptoms, aiding recovery from illness, regaining strength and improving quality of life, and reducing mortality. Additionally, the use of ONS has been reported to be cost effective in the healthcare setting due to reduced complications, fewer hospitalisations, and a reduced length of hospital stay. An important outcome to enable ONS to be clinically and physiologically effective is compliance (i.e., how much the patient consumes relative to what is prescribed). Whilst good compliance to ONS in both hospital and community patients has been reported (78%), compliance in some patient groups has been reported to be as low as 35%. Poor compliance has been reported due to inability to consume the required volume, poor palatability, and taste fatigue. Furthermore, with increasing trends in plant-based food consumption and veganism, the lack of plant-based ONS may reduce compliance in vegan patients or those wishing to reduce animal-derived consumption for cultural or religious reasons. Consequently, there is a clear need for the development of different types of ONS which better cater both for patients with reported low compliance, but also patients with potentially higher compliance when presented with increased variety and choice. The aim of this study is to evaluate compliance, acceptability, gastrointestinal tolerance, nutrient intake, appetite, nutritional status, and safety of four new ready to drink ONS. This is a prospective, longitudinal, 28-day intervention study with a 1-day baseline period. During the intervention period, patients will receive one of the four ONS for 28 days alongside their routine diet.