Dreieich-sprendlingen, Germany

APACE - Feasibility of Using Accelerometers to Measure Physical Activity in Cancer Patients on Early Phase Clinical Trials

Decision Support Tool for Revascularisation Options in Coronary Artery Disease

Closed-loop in Adults With Type 2 Diabetes

Purpose of clinical trial: To determine the efficacy, safety and utility of fully closed-loop insulin delivery over 26 weeks in the home setting in adults with type 2 diabetes. Study objectives: To determine the efficacy, safety and utility of fully closed-loop insulin delivery over 26 weeks in the home setting in adults with type 2 diabetes. 1. EFFICACY: The objective is to assess the ability of fully closed-loop insulin delivery to improve glucose control as measured by HbA1c (primary endpoint) and sensor glucose metrics. 2. SAFETY: The objective is to evaluate the safety of fully closed-loop insulin delivery in terms of episodes and severity of hypoglycaemia, and nature and severity of other adverse events. 3. UTILITY: The objective is to determine the acceptability and duration of use of the CGM and closed-loop system. 4. HUMAN FACTORS: The objective is to assess cognitive, emotional, and behavioural characteristics of participants and their response to the closed-loop system using validated questionnaires and semi-structured interviews. Participating clinical centres: UK - Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust. - Imperial College Healthcare NHS Trust, London - Manchester Royal Infirmary, Manchester University NHS Foundation Trust - King's College Hospital, King's College Hospital NHS Foundation Trust, London - Guy's and St Thomas' NHS Foundation Trust - Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust - University Hospitals of Leicester NHS Trust Switzerland - Inselspital, Bern University Hospital, Bern France - Centre Hospitalier Universitaire (CHU) de Toulouse Germany - Medical Center - University of Freiburg Austria - Medical University of Graz, Graz Czech Republic - Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague Sample Size: 224 participants (112 per group) will be randomised. Recruitment will target a minimum quota of 25% of participants using basal insulin and a minimum quota of 60% of participants using multiple daily insulin injections. Maximum duration of study for a subject: 30 weeks Recruitment: Participants will be recruited through outpatient diabetes clinics, primary care centres, social media advertising or other established methods at participating centres Consent: Participants will be asked to provide written informed consent. Baseline Assessment: Eligible participants will undergo baseline evaluation involving talking a medical history including demographics, height/weight, waist hip ratio and blood pressure measurement and blood samples for HbA1c, fasted lipid profile, renal and liver function. A urine albumin-creatinine ratio (ACR) will be performed, along with a urine pregnancy test in females of child-bearing age. Human factors questionnaires will be completed and a masked glucose sensor will be applied. Run-in Period: During a 2-3 week run-in period, participants will use their usual insulin therapy and wear a masked CGM system. At the end of the run-in period, for compliance, at least 10 days of CGM data needs to be recorded. CGM data during the run-in period will be used to assess baseline glucose control before the start of the intervention phase. Randomisation: Eligible participants will be randomised in a 1:1 ratio using central randomisation software to fully closed-loop or standard insulin therapy with CGM for 26 weeks. Randomisation will be stratified by site and baseline HbA1c. Fully closed loop insulin delivery (intervention arm): Following randomisation, participants in the closed-loop group will receive training on the study CGM, study insulin pump and closed-loop App during a 1-2 hour outpatient session. Competency on the use of the closed-loop system will be evaluated. Further training may be delivered as required. Participants will be advised to use the closed-loop system for the next 26 weeks. Standard insulin therapy with CGM (control arm): Following randomisation, participants in the control group will use their usual insulin therapy and the study CGM. Training on the use of the CGM will be provided. Participants will use standard insulin therapy and CGM for the next 26 weeks. 3 month study visit: Weight, waist hip ratio and blood pressure will be measured and a blood sample will be taken for measurement of HbA1c, fasted lipid profile, renal and liver function. Data from the closed-loop system and CGM system will be reviewed. Human factors questionnaires will be completed. End of study assessments: Weight, waist hip ratio and blood pressure will be measured and a blood sample will be taken for measurement of HbA1c, fasted lipid profile, renal and liver function. Urinary ACR will be measured. Human factors questionnaires will be completed and a subset of participants will participate in interviews. Study devices will be returned and participants will resume their usual insulin therapy and standard glucose monitoring. Procedures for safety monitoring during trial: Standard operating procedures for monitoring and reporting of all adverse events and adverse device events will be in place, including serious adverse events (SAE), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia. A data safety and monitoring board (DSMB) will be informed of all serious adverse events and any unanticipated serious adverse device effects that occur during the study and will review compiled adverse event data at periodic intervals. Criteria for withdrawal of subjects on safety grounds: A participant may terminate participation in the study at any time without necessarily giving a reason and without any personal disadvantage. An investigator can stop the participation of a subject after consideration of the benefit/risk ratio. Possible reasons are: - Participant is unable to demonstrate safe use of study devices as judged by the investigator - Serious adverse events - Significant protocol violation or non-compliance - Decision by the investigator, or the Sponsor, that termination is in the participant's best medical interest - Pregnancy, planned pregnancy, or breast feeding - Allergic reaction to insulin or severe allergic reaction to adhesive surface of infusion set or glucose sensor - Technical grounds (e.g. participant relocates)

Clinical Experience of Maintaining Patient Safety in Hospital

The National Institute for Health and Care Excellence clinical guidance CG161 recommends that all patients admitted to hospital over the age of 65 and those with specific underlying conditions between the age of 50 and 64 are considered at high risk of falls and a documented falls risk assessment is undertaken on admission. However, whilst advising the use of an appropriate multifactorial risk assessment (MFA) NICE also acknowledges that there is no evidence of the efficacy of most falls prevention methods in hospital and that high quality randomised controlled trials (RCT) conducted in the UK are required to improve the existing evidence base. Falls are referred to as accidents but statistically they have been shown not to demonstrate a pattern of chance which suggests a causal process. Contributing factors leading to falls have been recognised as; postural stability, gait, sensory deficit, neuromuscular impairment, psychological conditions, impact of medications, environmental risks and medical risks such as stroke and cardiac issues. Significant research has been undertaken in relation to falls in the community and as such there are useful clinical guidelines published by both NICE and World Falls Guidelines for preventing and managing patients falls in their home. Whilst patients may be at less risk in their own environment, when admitted to hospital usually single or multiple risk factors apply, even if only for a limited period due to the nature of their presenting condition. It is therefore necessary to assess all patients who are admitted to hospital to establish the level of risk they face and to prescribe interventions with the goal of preventing an accidental fall. In the UK, 30 - 50% of accidental falls in hospital lead to some injury and 1-3% of those sustain a fracture. In-patient falls are a significant cause of morbidity and mortality, with an estimated 247,000 occurring annually at a cost of £2.3billion to the NHS. In-patient falls have consistently been the biggest single category of reported incidents since the 1940's. Little has changed in the 39 years since the that paper and with falls accounting for 85% of all hospital acquired conditions in the USA it is safe to say this is a global issue. A recent Australian study estimated that the annual cost of attempts to prevent in-hospital falls across six health services consumed AU$590 million per year in resources. The areas of greatest investment were 18% physiotherapy, 14% 24 hour observation, 12% falls assessments and 11% falls prevention alarms and there is a lack of quality research to support their efficacy as falls prevention strategies. The generalisable level of success of these strategies is still not known. It seems that health services across the world are investing time and effort in strategies for which there is an absence of evidence. The recently published World Guidelines for Falls Prevention has confirmed there remains no research supporting the use of technology such as falls alarms or nonslip socks (NSS) in hospitals and as such recommends only standard falls prevention methods. As a result of increasing reimbursement costs for hospital treatments, in 2008 the Centres for Medicaid & Medicare Services, health insurance companies in the United States of America (US), removed reimbursement to hospitals for costs incurred by patient falls and any associated trauma resulting in increasing financial burden to hospitals. The impact on staff suffering 'second victim phenomena' as a result of adverse incidents and the cost to patients who suffer pain, disability, and death is incalculable.

Manganese-enhanced Magnetic Resonance Imaging (MEMRI) in Heart Failure With Preserved Ejection Fraction

Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML

EXercise Therapy in Axial SpA, Inflammation and Biologic Therapy (ExTASI-B)

Over 200,000 people in the UK have axial spondyloarthritis. In 80% of cases the condition begins in the second or third decade of life. Exercise is encouraged as an essential treatment of axial spondyloarthritis (axSpA), with the potential to both promote well-being, increase flexibility and range of movement, improve posture and reduce stiffness and pain. axSpA is an inflammatory arthritis and raised levels of indicators ('markers') of this inflammatory process (e.g. CRP) can be detected in the blood of patients. These markers are released as a consequence of the condition, but some, such as TNF-alpha and interleukin-17 (IL-17), also promote further disease development. In other inflamed patient groups we have shown that regular exercise (brisk walking) can lower the levels of these pro-inflammatory markers in the blood and increase levels of anti-inflammatory markers, independently of weight loss. Despite axSpA being an inflammatory condition with prescribed medication focused on reducing inflammation there are no studies that have assessed the potential of exercise to act as an anti-inflammatory adjuvant to biologic therapy in axSpA. This research will investigate the effect of 12 weeks of a home-based walking exercise intervention on measures of systemic inflammation and body composition, well-being and measures of disease activity using established and validated methods in 20 axSpA patients on regular biologic therapy and compare this group with 20 patients on regular biologic therapy who carry on with their standard care and normal levels of activity. Also, a baseline comparison will be conducted between a group of 20 healthy individuals and axSpA patients (40).This proof-of-concept study will determine the potential of exercise as an adjuvant anti-inflammatory treatment for patients with axSpA taking biologic medication.

SCAD : a Registry of Spontaneous Coronary Artery Dissection

Observational, multicentre, international retrospective and prospective cohort study. Since this is an observational study, a formal sample size is not necessary. At least 500 prospectively recruited patients and 500 historical cases will be enrolled. Patient data will be collected at the following time-points: - First SCAD event visit (retrospectively on chart review) - First follow-up: at time of enrolment - Yearly follow-up: up to 1, 2, 3, 4 and 5 years post enrolment or until study completion Approximately 30 countries and 120 sites will participate in this registry.

Volatile Organic Compounds as Breath Biomarkers in Squamous Oesophageal Neoplasms

In this prospective multicentre case-control study, the investigators will recruit a total of 518 patients. These will be divided into the following groups: 1. Cancer group (n=259): Patients with treatment naive, histopathology confirmed OSCC. 2. Control group (n=259): Patients who have undergone or are undergoing an upper gastrointestinal (GI) endoscopy as part of their investigation for upper GI symptoms and are found to have either - (i) A normal upper GI tract or (ii) Benign upper GI disease. Eligible and willing participants will be asked to provide two breath samples by exhaling into single-use breath collection bags. Using a custom designed gas sampling pump, the breath VOCs will be transferred onto thermal desorption (TD) tubes at a controlled flow rate. When the participants' breath sampling is complete, room air (Blank) samples will be taken onto additional TD tubes using the same process. Once collected, the TD tubes will be transported to Imperial College London (The Hanna lab), where they will be analysed.

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.