Mulhouse, 68100, France

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.

Airway Intervention Registry (AIR): Recurrent Respiratory Papillomatosis (RRP)

Primary aim: The overall goal is to improve the care of patients with Recurrent Respiratory Papillomatosis (RRP) - and the investigators aim to do this by determining the most effective and safe RRP treatments currently being used in patients in National Health Service (NHS) hospitals within the United Kingdom (UK) (information which is currently lacking). By determining the most effective treatments of RRP, the investigators will be able to increase the time interval between surgical interventions to maintain symptomatic control, reduce overall number of RRP interventions, severity and spread of papillomas in the airway, hospital visits, medications and ultimately improve quality of life in those suffering from RRP. By also capturing peri- and post-procedural details the investigators will be able to determine the relative safety of treatments and identify those which slow the progression of disease. From the data collected the investigators intend to identify patient subgroups (based on patient characteristics such as age, gender, human papillomavirus (HPV) type, location of papillomas, RRP severity and spread, comorbidities) who respond better to specific treatments, and also identify patient risk factors which contribute to the complication outcomes (such as tracheostomy). Secondary aims: - build an evidence base of the different RRP treatments used across the UK which will help to formulate hypotheses for future research in RRP and improve quality of life for RRP patients; - inform National Institute for Health and Care Excellence (NICE) interventional procedure guidance on radiofrequency cold ablation (IPG434,2012), which is currently under special arrangements due to lack of safety and efficacy evidence; - identify common symptoms or signs associated with RRP disease profile, to aid future diagnosis of RRP; - determine the geographical spread of RRP patients across the UK, to inform effective use of future NHS resources and inform the Department of Health strategy in its quadrivalent HPV vaccination programme (protecting against four types of HPV including types 6 and 11 commonly associated with RRP) currently offered to 12-13 year old girls within the NHS childhood vaccination programme; - inform future development of national clinical guidance on management of RRP to ensure that everyone receives the best care based on best available current knowledge; - determine impact of COVID on RRP patients including changes to RRP management, RRP symptoms. Objectives: The investigators will make use of an existing secure online database platform (the Airway Intervention Registry, AIR - developed and hosted by The Newcastle upon Tyne Hospitals NHS Foundation Trust, NUTH) and its associated infrastructure and develop it to capture additional observational outcomes from standard clinical practice and quality of life questionnaires from RRP patients. All RRP patients (any age) receiving treatment in any UK NHS hospital will be eligible for inclusion. Data collection will be open for 53 months with no minimum follow-up required for patients. Due to its recurrent nature (requiring regular hospital visits to maintain an open airway), following this patient population will allow the investigators to determine both the short- and long-term relative safety and efficacy of RRP treatments used in the UK. Consent will be required (from patients/parent/guardian) before data are entered into the online database.

Comparison Trial of Open-tip Pulsed Needle Biopsy and Conventional Core Biopsy in Axillary Lymph Nodes

It is the standard of care in the United Kingdom for women with suspected or confirmed breast cancer to undergo ultrasound of the ipsilateral axilla prior to surgery in order to detect nodal metastatic disease. Women with invasive breast cancer and normal axillary ultrasound will then undergo operative sentinel lymph node biopsy. This is usually at the same time as the surgical removal of the breast cancer by wide local excision or mastectomy but may be done as a separate procedure before (e.g. where neoadjuvant chemotherapy is planned) or after (e.g. if a non-operative diagnosis of invasive breast cancer was not made prior to surgery). Women who are found to have a positive sentinel lymph node biopsy (i.e. have axillary metastatic disease) normally undergo axillary node clearance (ANC) at a subsequent operation. This policy may change in the future, as evidence from the American Z0011 study suggests that women with low volume axillary metastatic disease do as well with no further axillary surgery plus standard adjuvant treatment as those that undergo ANC. Women who have abnormal lymph nodes on axillary ultrasound undergo tissue sampling with core needle biopsy (CNB), usually 14 Gauge (14G) under local anaesthetic or with fine needle aspiration cytology (FNAC). Women with proven axillary nodal metastases will then usually undergo axillary node clearance at the same operation as surgical removal of the primary tumour. The number of women who need to undergo more than one operation can therefore be minimised by maximising the number of women with axillary metastatic disease in whom this diagnosis is made preoperatively. Meta-analyses of published studies and more recent studies suggest that ultrasound has a sensitivity of ~60% and specificity of ~80% for the detection of metastatic lymph nodes. Although no randomised comparisons of 14G core needle biopsy (CNB) and FNAC have been performed, several studies have suggested that CNB is more accurate. Ultrasound-guided biopsy of nodes subsequently proven at surgery to contain metastases has a sensitivity of ~80% and a specificity of 100% and is more likely to be positive in those women with a higher nodal burden. Numerous studies suggest that increasing the volume of tissue removed may increase the diagnostic yield. Recently a new biopsy device indicated for the use in breast and axillary lymph nodes (NeoNavia biopsy system, NeoDynamics, Sweden) has become available. It incorporates a pneumatic needle insertion mechanism that is intended to provide better control of needle progression and enable stepwise insertion without noticeable deformation or displacement of surrounding tissue as visualized under ultrasound. Furthermore a new method of tissue acquisition is employed that has pre-clinically shown a significantly higher sampling yield compared to CNB. These characteristics indicate that the device could be well suited for axillary lymph node biopsies. Initial clinical results indicate that in axillary lesions deemed "technically difficult", i.e. where prior US-guided biopsies with CNB or FNA had yielded non-diagnostic histology results, the NeoNavia device performed successfully, thereby significantly altering clinical management.

EPA-FFA to Treat Hospitalised Patients With COVID-19 (SARS-CoV-2)

Recruitment SSubjects hospitalised or attended the hospital ED with a confirmed diagnosis of SARS-CoV-2, will be contacted. Potential subjects will have the opportunity to ask any questions to the researchers. A member of the research team will provide a copy of the information sheet to the subject, who will have the opportunity to ask any questions to the researchers. Subjects expressing an interest in participating will be interviewed to explain the study in detail, and discuss the risks, benefits, goals and limitations of the study. Screening Procedures. Potentially eligible subjects will provide informed consent prior to any study specific procedures being conducted. Following the provision of informed consent, the subject's demographics and medical history especially that relating to SARS-CoV-2 will be documented. A physical examination and checks on vital signs (BP, pulse, temperature, respiration) will be conducted. Female subjects of child-bearing potential will undergo a urine pregnancy test. A blood sample will be drawn for routine haematology and biochemistry. Subjects will undergo tests for oxygen saturation, PaO2/FiO2 and interleukin-6 (IL-6). Subjects will be asked to provide details of any concomitant medications. Subjects with confirmed diagnosis of SARS-CoV-2, compliance with the inclusion and exclusion criteria and providing informed consent will be registered on the e-CRF to obtain a randomisation number. Baseline/Randomisation A physical examination and checks on vital signs (BP, pulse, temperature, respiration) will be conducted. Subjects will undergo tests for oxygen saturation, PaO2/FiO2 and interleukin-6. Haematology and biochemistry test (from screening) results will be confirmed as being acceptable. The study centre will dispense the IMP under blinded conditions according to a permuted block randomisation sequence (1:1 ratio for the two subject groups). The subjects will be trained on the dosing and asked to administer two capsules twice daily for 4 weeks. Subjects will then be provided with IMP on a daily basis by a suitably qualified and delegated member of the Investigator's team, for the duration of the treatment phase. Treatment Phase (Week 1-3) All subjects will receive standard of care treatment throughout the treatment phase on a day to day basis. This will include assessment of additional or alternative medication required for the treatment of SARS-CoV-2, requirement for intubation and invasive ventilation, requirement to transfer to intensive care unit or death. On a weekly basis, a physical examination and checks on vital signs (BP, pulse, temperature, respiration) will be conducted. Subjects will undergo tests for oxygen saturation, PaO2/FiO2 and IL-6. Subjects will be asked to provide details of any concomitant medications and changes in condition via adverse event (AE) query. Week 4 A physical examination and checks on vital signs (BP, pulse, temperature, respiration) will be conducted. Subjects will undergo tests for oxygen saturation, PaO2/FiO2 and IL-6. Female subjects of child-bearing potential will undergo a urine pregnancy test. A blood sample will be drawn for routine haematology and biochemistry. Subjects will be asked to provide details of any concomitant medications and changes in condition via AE query. Week 6 (Follow -up) 6 weeks after randomisation (or two weeks after early withdrawal), the subject will be contacted to check the occurrence of any other adverse events and review of medications. Haematology and biochemistry test (from week 4) results will be confirmed as being acceptable. Adverse events will be assessed by spontaneous reports by subjects.

Surgical and Oncological Outcomes in Patients With Ulcerative Colitis-associated Rectal Cancer

Inflammatory Bowel Disease (IBD) is a risk factor for the development of colorectal cancer (CRC). Despite improved targeted screening and timely prophylactic resection, up to 15% of all IBD-related mortality can be attributed to CRC. Previous reports suggest that IBD patients present with CRC at an earlier age and with more advanced disease than those with sporadic CRC. The literature is limited, however, with respect to colitis-associated rectal cancer (CARC), which has unique considerations such as surgical approach and the use of neoadjuvant therapy. Although total proctocolectomy is generally the procedure of choice for those with CARC, recent reports reported acceptable oncological outcomes after ileal pouch-anal anastomosis (IPAA) and ileorectal anastomosis (IRA). The impact of the type of surgical procedure on the oncologic outcome in patients with CARC is not well defined. The aim of this study is to investigate short-term surgical outcomes (postoperative complications at 30 days after surgery) and long-term oncological outcomes (disease-free survival) of CARC patients undergoing different surgical approaches.

Pre-therapeutic MRI Assessment of Early-Stage Rectal Cancer and Significant Rectal Polyps to Avoid Major Resectional Surgery

Many patients diagnosed with Early Rectal Cancer (ERC) are currently over-treated. Most patients with confirmed ERC will undergo an MRI, but some are not correctly identified in endoscopy and immediately removed. Of those who undergo MRI, 69% are over-staged and undergo major surgery or unnecessary radiotherapy when local excision surgery to preserve the patients rectum, and quality of life, would have been possible. <10% of patients with ERC are staged accurately and offered local excision, with the majority who are staged as ERC on MRI still undergoing major surgery, likely due to uncertainty in the staging report. Prof Gina Brown developed a more accurate radiological staging system (PRESERVE) or ERC, whereby T2 tumours are identified and classified according to the degree of preservation of the individual layers of the rectal wall. It has been shown that PRESERVE enabled better identification of ERC suitable for local excision from the expected 30% to 89% accuracy. This improved accuracy was replicated in a further study by training a cohort of 12 radiologists. It is predicted that wider adoption of PRESERVE will result in increased organ-preserving surgery from the current rates of 10% to >50%.

Add-Aspirin: A Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours

A phase III, multi-centre, double-blind, placebo-controlled randomised trial which aims to assess whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with non-metastatic common solid tumours. The trial has four parallel tumour site-specific cohorts (breast, colorectal, gastro-oesophageal and prostate cancer). An overarching protocol ensures each cohort is as comparable as possible to allow a combined analysis of overall survival as a co-primary outcome measure in addition to individual tumour site-specific analyses of disease recurrence and survival. Participants who have undergone potentially curative treatment (surgery or other radical treatment), including any standard neo-adjuvant or adjuvant therapy for breast, colorectal, gastro-oesophageal or prostate cancer or have participated in any pre-approved trials and satisfy the eligibility criteria. Participants will be randomly assigned to 100mg aspirin, 300mg aspirin or matched placebo. All tablets will be enteric-coated to be taken daily for at least five years. Prior to randomisation, all potential participants will take open-label 100mg aspirin daily for a run-in period of approximately 8 weeks to assess tolerability and adherence. The trial incorporates a feasibility phase during which recruitment feasibility, treatment adherence, safety and use of the run-in period will be assessed.

Product Surveillance Registry

Study to Evaluate the Pharmacokinetics and Pharmacodynamics of AZD4604 Given Via the Turbuhaler® Device in Adults With Mild Asthma.

This is a multicentre, randomised, placebo-controlled, single-blind study to characterise PK and PD of AZD4604, administered twice daily (BID) using a Turbuhaler or a Genuair device. Participants who have mild asthma with a raised FeNO will be randomised into the study to evaluate AZD4604 versus placebo, at 2 dose levels delivered via: a) the Turbuhaler device and b) the Genuair device. The study will be comprised of: - A screening period (Day -42 to Day-3) - Participants will be randomised to one of 5 treatment arms where participants will either receive BID doses of AZD4604 or placebo from Day 1 to Day 9 and a single dose on Day 10. - A follow-up Visit on Day 16 The total duration of the study will be for 58 days.

A Study to Investigate the Pharmacokinetics of Midazolam After Repeated Doses of Camizestrant (AZD9833) and to Investigate the Pharmacokinetics of Camizestrant When Administered Alone and in Combination With Carbamazepine in Healthy Post-Menopausal Female Participants

This is an open-label, fixed sequence, 2-part (Part A and Part B), drug-drug interaction study in healthy post-menopausal female participants. Participants enrolled in Part A may subsequently also participate in Part B. Part A of the study will assess the effect of repeated oral doses of camizestrant on the PK of a single oral dose of midazolam. It will comprise: - A Screening Period of maximum 28 days. - Three Treatment Periods during which participants will be resident at the Clinical Unit from the day before study intervention administration (Day -1) until after the last camizestrant PK sample on Day 8. 1. Period 1: participants will receive a single oral dose of midazolam (Day 1). 2. Period 2: participants will receive an oral once daily (OD) dose of camizestrant (Day 2 to Day 6). 3. Period 3: participants will receive a single oral dose of midazolam and camizestrant (Day 7). - A Follow-up Visit, for which the participant will return to the Clinical Unit 7 (± 2) days after the last camizestrant PK sample in Period 3. Part B of the study will assess the effect of multiple oral doses of carbamazepine on the PK of a single oral dose of camizestrant. It will comprise: - A Screening Period of maximum 28 days. - Two Treatment Periods during which participants will be resident at the Clinical Unit from the day before study intervention administration (Day -1) until after the last camizestrant PK sample on Day 25. 1. Period 1: participants will receive a single oral dose of camizestrant (Day 1) with PK sampling on Day 1 to Day 4. 2. Period 2: participants will receive low oral doses (Dose 1) of carbamazepine twice a day (BID) on Day 4 to Day 6, mid oral doses (Dose 2) of carbamazepine BID on Day 7 to Day 9, and high oral doses (Dose 3) of carbamazepine BID on Day 10 to Day 24. On Day 22, participants will receive a single oral dose of camizestrant. - A Follow-up Visit, for which the participant will return to the Clinical Unit 7 (± 2) days after the last camizestrant PK sample in Period 2.