St. Imier, Switzerland

Rapid Examination of Acute CT

A recent survey published in a local conference (Master 2023) asked 100 junior doctors across 16 Trusts in the UK (including ELHT and MFT) about their experience of CT. This showed that confidence in CT requesting and interpretation is very limited. From the same survey it seems that CT is very superficially taught in medical schools with no system given for interpretation. 90% of those surveyed said they would benefit from more educational resources in CT. The investigators hope to develop a CT interpretation resource to help the non-radiologist when looking at CT scans. This study aims to see how non-radiologists currently approach a CT scan to gain understanding of the needs of the new resources. There is no similar study in the literature investigating how the non-radiologist approaches CT scans. There has been investigation of foundation doctors experience in radiology, however the focus was on plain xrays, not CT interpretation. The investigators plan to use a thematic analysis in data interpretation. Rationale for using Thematic analysis. - Recognised method of identifying patterns/ themes in qualitative data for learning and teaching research. - Provides a flexible methodology approach which is not reliant on a particular educational theory. Hence it is able to deal with relatively uncharted area of how non-radiologists interpret radiological images. Process of thematic analysis . Using the 6-step approach. Step Aims Comments 1. Data familiarisation Studying the transcripts & video with notes on initial impressions. 2. Initial codes derived Grouping data in a meaningful and systematic way. 3. Search for themes Discerning any significant pattern in the data. 4. Review themes Review the support for each theme and if they cover the entire data set. 5. Define themes Clear description of each theme covering the points it is addressing, any sub-themes it contains and how they relate to one-another. 6. Write-up Report on the key points, from this study, which are influencing CT scan interpretation and how it could be taught. - The proposed study is using an inductive and latent level approach for the data analysis. This was selected as it allows the flexibility to look beyond what is being said. The semantic approach was considered too restrictive as it assumes a predefined understanding of the subjects' cognitive strategy in dealing with image interpretation. In contrast, by combining the oral presentation with the manipulation of the image and the answering of key questions there will be a better chance of appreciating the underlying cognitive approach being employed. - Open coding will be used for the transcripts analysed so far. This allows them to be modified under the influence of more data. - Currently,qualitative data analytic software (e.g. ATLAS, Nvivo etc.) are not using. The reason being the researcher's need for first-hand familiarisation with a novel dataset. Once this preliminary phase has been carried out consideration will be given to using UCLan's access to Nvivo. This decision will take into account personal preferences, experiences with the preliminary data and the anticipated size of the data base. • Once preliminary themes have been proposed a review will be made to see which codes they address. Unlinked codes will prompt further analysis of the themes, considered of new themes or development of sub-themes. This iterative process continues with new data until a steady state is achieved and no new themes are being generated.

Impact of Apalutamide in Metastatic Hormone Sensitive Prostate Cancer Patients

ULTRA LONG: BioFreedom Ultra

A Case-control Study Comparing Glycaemic Control in Pancreatic Cancer Patients vs Healthy Matched Individuals.

The pancreas has two key functions related to digestion and metabolism. The first function of the pancreas is to produce exocrine enzymes which are released into the small intestine to help with the digestion of food. The second function is to produce endocrine hormones, such as insulin and glucagon, which help regulate glycaemic control. Impaired glucose metabolism and pancreatic cancer is temporally and pathogenically linked, with pancreatic tumours altering the secretion of key glucose regulatory hormones. Improved glucose regulation and lower glucose concentrations 3 months post-diagnosis of pancreatic ductal adenocarcinoma, a type of pancreatic cancer, has shown to increase overall survival. The aim of this study is to continuously monitor blood glucose concentrations for a 7-day period in pancreatic cancer patients whilst undergoing their typical daily routines and to compare this to age matched healthy individuals. The comparison between healthy individuals and pancreatic cancer patients will investigate the severity of the difference between healthy glycaemic control and glycaemic control in those with pancreatic cancer. The comparison between pancreatic cancer patients undergoing chemotherapy and those not undergoing chemotherapy will help investigate the impact of chemotherapy on glycaemic control. This will help provide evidence as to what impact pancreatic cancer has on glycaemic control, whether continuous glucose monitors might be useful to regulate symptoms in patients, as a baseline to tailor an exercise intervention to regulate blood glucose concentrations and to investigate whether health inequalities impact glycaemic control. The investigators plan to carry out the study on a small subset of patients, 30 with pancreatic cancer (15 undergoing chemotherapy and 15 not undergoing chemotherapy) and 15 healthy individuals.

SCOOT: Sample Collection for DART

The results from this study will be linked with the data from the DART study (also collecting data through the Lung Health Check programme) to develop new ways of using computer technology (artificial intelligence) to improve lung health care. The studies use computer programs (called 'algorithms') which can be trained to analyse medical samples. Once developed, these algorithms can be used to support doctors by increasing their speed and accuracy of diagnosing issues.

Early Vasopressors in Sepsis

Sepsis results from overwhelming reactions to microbial infections where the immune system initiates dysregulated responses that lead to remote organ dysfunction, shock and ultimately death. Sepsis remains a significant global issue - as well as direct mortality, survivors suffer long term reductions in patient centred outcomes, with reduced quality of life and functional status. Patients with hypotension and organ hypoperfusion as a result of sepsis have poorer outcomes by dysregulated inflammation, endothelial dysfunction, immune suppression, and organ dysfunction. Current guidelines highlight the importance of early fluid resuscitation, but the association of early fluid therapy with improved outcomes is unclear. In the resuscitation phase, current practice is to give intravenous (IV) fluid and intermittent vasopressor boluses if required, before, for some patients, continuous vasopressor infusion via a central venous line in Intensive Care (ICU). An alternative, early continuous peripheral vasopressor infusion (PVI) is not routine practice in the UK. Current practice in the UK is guided by NICE Sepsis guidance and the international Surviving Sepsis Campaign (SSC) consensus recommendations. Both specify intravenous fluid administration as a central tenet of early resuscitation of patients with septic shock, with intravenous vasopressor administration recommended after intravenous fluid resuscitation. NICE recommend boluses of 500ml of crystalloid and "refer to critical care for review of management including need for central venous access and initiation of vasopressors". SSC recommend 30ml/kg crystalloid in first hour, followed by vasopressors to maintain MAP>65. The current NICE fluid resuscitation guideline, November 2020, continues to emphasise 500ml boluses of crystalloid as usual care. A recent international survey of 100 critical care and EM physicians regarding intravenous fluid resuscitation practice, confirmed that an initial bolus of 1000ml of crystalloid, followed by 500ml boluses of crystalloid remained the most common management strategy for the initial treatment of septic shock. This persisted despite the lack of benefit demonstrated in three landmark trials of protocolised sepsis management. In recent years, there has been increasing acceptance of peripheral administration of norepinephrine, based on evidence of safety and efficacy. The Intensive Care Society published guidance on peripheral vasopressor infusion in November 2020. We have recently conducted a survey amongst ED and ICU clinicians in the UK regarding attitudes and current practice related to the use of intravenous peripheral vasopressors. Eighty two respondents provided the following answers 1. Experience of use of any intravenous vasopressor in ED was high (81%); 2. Exclusive PVI made up 23% of all vasopressor use in ED; 3. Norepinephrine (norepinephrine) was the most common vasopressor (54%); 4. Barriers to PVI were local protocols and an appropriate level of care in the destination ward for a patient on vasopressor infusion.

PreOperative Endocrine Therapy for Individualised Care With Abemaciclib

In women with hormone sensitive early breast cancer, taking a hormone therapy (also known as endocrine therapy) for at least five years after surgery is very effective at reducing the risk of the cancer returning. However, for some women their cancer may eventually become resistant to these drugs. POETIC-A Registration part will identify those who have a higher risk of developing resistance to standard endocrine therapy (ET). At least 8000 women diagnosed with early stage breast cancer will enter the Registration stage from 80 centres. Study doctors will use aromatase inhibitors (AIs), a type of ET, to treat the cancer for between 2 weeks and 6 months before surgery. A sample will be taken from the cancer during surgery and the study laboratory will measure a biological marker called Ki67. If the level of Ki67 does not drop after 2 weeks of AI treatment, the patient is likely to be less sensitive to endocrine therapy, and the study doctor will explore additional treatments after surgery in the POETIC-A Treatment part. Everyone who agrees to join the Treatment stage (2032 patients) will be randomly put into one of the 2 treatment groups; Group1: ET only; or Group2: ET plus a new drug called abemaciclib. The first aim of the Treatment stage is to confirm whether abemaciclib given in combination with ET is more effective than giving ET alone in preventing the cancer coming back. The study laboratory will perform a second test on the cancer sample, called an AIR-CIS test. This test aims to find out if particular groups of patients based on their tumour biology are more suitable for treatment with abemaciclib. Patients in Group 2 will receive ET plus abemaciclib for 2 years. Patients in both groups will have regular study visits during this period.

Tracking Mutations in Cell Free Tumour DNA to Predict Relapse in Early Colorectal Cancer

TRACC Part B: Despite potentially curative surgery +/- adjuvant chemotherapy, a proportional of patients with early stage CRC will experience disease relapse. Current tools for surveillance, e.g., blood sampling for tumour markers (CEA) are neither sensitive nor specific. We hypothesise that detection of mutations in circulating free DNA (cfDNA) in plasma can predict relapse in patients with early stage CRC. Circulating cell free tumour DNA (ctDNA) maintains the same mutations that are present in tumour. In colorectal cancer CRC, primary tumours and& metastases exhibit high genomic concordance. Therefore the TRACC study TRACC Part B is investigating whether serial blood samples taken from in patients with stage II and III fully resected early stage CRC colorectal cancer that have undergone potentially curative surgery, blood samples to can be used to detect and& quantify ctDNA may in order to identify minimal residual disease MRD and predict relapse earlier than existing methods. CtDNA may ultimately help identify a subset of patients that are or are unlikely to benefit from adjuvant chemotherapy and could therefore safely spare some patients from receiving unnecessary chemotherapy & its associated side-effects. TRACC Part C: We hypothesis that ctDNA guided adjuvant chemotherapy administration will enable biomarker driven selection of patients who would and would not benefit from adjuvant chemotherapy and thereby reduce the proportion of patient receiving unnecessary adjuvant chemotherapy, reducing the potential side effects associated with it, but without compromising disease free survival (DFS). : This part of the study will use tThe blood test ctDNA result from a post-operative blood sample willto guide adjuvant chemotherapy treatment decisions. The study aims to demonstrate that athe de -escalation strategy of ctDNA guided adjuvant chemotherapy is non-inferior to standard of care treatment as measured by 3 year DFS in patients with high risk stage II and stage III CRC, in those who have no evidence of MRD (ctDNA negative). after surgery for patients with colorectal cancer who are following the standard of care pathway. Patients are randomised at the post- operative time point to: Arm A (standard of care adjuvant chemotherapy), or Arm B (ctDNA guided adjuvant chemotherapy) arm. For the ct DNA guided arm, patients who are ctDNA negative at this time point will have their chemotherapy de-escalated.

Myeloma XIV: Frailty-adjusted Therapy in Transplant Non-Eligible Patients With Newly Diagnosed Multiple Myeloma

EASi-KIDNEY™ (The Studies of Heart & Kidney Protection With BI 690517 in Combination With Empagliflozin)