Guilford Surrey, United Kingdom

EUthyroid2: the Next Step Towards the Elimination of Iodine Deficiency and Preventable Iodine-related Disorders in Europe

BACKGROUND: Iodine deficiency (ID) is a leading risk factor for the development of thyroid disorders, of which in particular women are affected. During pregnancy, ID can increase the risk of developmental disorders in the offspring, however, it is considered as one of the most preventable causes of mental impairment in children. Therefore, the EUthyroid2 project aims to contribute to the prevention of ID and associated symptom and disease burden in adolescence and young women in Europe and beyond. AIM: An educational intervention is to be developed, implemented in ambulatory care settings and evaluated to effectively raise awareness for the risks of ID among young women (18-24 years) in three European countries (Norway, Poland, UK) as well as Bangladesh and Pakistan. METHODS: A cluster-randomised controlled trial is to be conducted in each of the five countries. 10 clusters per country (5 intervention group clusters and 5 control group clusters) are planned to achieve a final sample size of 200 study participants per implementing country with one baseline (before the intervention) and two follow-up measurements (2-4 weeks and 6-8 months after the intervention). In all, 1000 participants are to be recruited and data for all measurement points collected. Due to differences in the healthcare systems, the ambulatory care units, where the intervention will be implemented, may vary across the countries. Before recruiting the women, the healthcare professionals who carry out the intervention will receive a specially designed training program. To assure the intervention's functionality and effectiveness, recommendations for the development of complex interventions, appropriate theories and frameworks will be considered and a context analysis will be conducted. The primary outcome of the study is iodine awareness and knowledge measured by a newly developed questionnaire. Other outcomes includes measurement of iodine status (urinary iodine concentration), intake of dietary iodine sources (measured by a food frequency questionnaire), and iodine related behaviours. Sociodemographic characteristics and general dietary habits will also be measured. Descriptive analyses for all variables will be performed. Intervention groups will be compared to control groups over time to test effectiveness. Subgroup and country-specific analyses will also be computed. A process evaluation will be conducted to evaluate the implementation process with a convergent parallel mixed methods design. For this, healthcare professionals in the ambulatory care settings and the women who received the intervention will be invited to participate in an online survey. Further, ca. 20-30 semi-structured interviews will be conducted with women and healthcare professionals. CONCLUSION / OUTLOOK: The project results may support health authorities across countries to implement effective measures to reduce ID and associated risks. This may sustainably reduce the disease burden induced by ID for young women, pregnant women and their offspring.

The Next Step Towards the Elimination of Iodine Deficiency and Preventable Iodine-related Disorders in Europe

Detailed Description: BACKGROUND: Iodine deficiency (ID) is a leading risk factor for thyroid disorders and developmental impairments in offspring. It is recognized as one of the most preventable causes of mental impairment in children. The EUthyroid2 project aims to contribute to the prevention of ID and its associated symptoms and disease burden in adolescents across Europe and beyond. AIM: This project seeks to develop and implement an educational intervention in various educational settings, effectively raising awareness of the risks associated with iodine deficiency. METHODS: The intervention will be conducted in each participating country, with three clusters (secondary schools, high schools, and vocational schools) per country. The goal is to achieve a final sample of 4500 study participants in all countries combined, involving one baseline measurement and two follow-up assessments (2-4 weeks and 6-8 months post-intervention). Data will be collected at all measurement points, with variations in implementation accounted for due to differences between countries. To ensure the intervention's functionality and effectiveness, the project will consider recommendations for developing complex interventions, appropriate theoretical frameworks, and conduct a context analysis. Outcome measures will include a newly developed iodine awareness questionnaire (primary outcome) and an iodine-specific food frequency questionnaire. Additionally, socio-demographic characteristics will be measured. Descriptive analyses will be performed on all variables, with subgroup and country-specific analyses computed. A process evaluation will assess the implementation process using a convergent parallel mixed methods design, inviting teachers and students to participate in an online questionnaire. Semi-structured interviews will further enrich this evaluation. CONCLUSION/OUTLOOK: The results of the EUthyroid2 project may assist health authorities across participating countries in implementing effective strategies to reduce iodine deficiency and its associated risks. Ultimately, this could lead to a sustainable decrease in the disease burden induced by iodine deficiency.

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

MIRRORS-FROZEN - Comparing Open Vs Robotic Surgery in the Management of Women with Complex Pelvic Adnexal Masses ≤ 8cm.

Open surgical staging is the current standard practice in managing women with complex adnexal masses suspicious of cancer. The diagnostic dilemma of early-stage ovarian cancer often leads to overtreatment by laparotomy in a number of patients with benign or borderline pathology. MIRRORS-FROZEN (pilot) is a feasibility study that aims to establish whether the MIRRORS-FROZEN protocol can operate successfully and whether patients are willing to be recruited and randomized to either of the trial arms. The pilot trial also examines the feasibility and appropriateness of collecting a number of surgical, oncological, and patient-reported outcomes. The aim is to provide proof of concept that a larger, adequately powered multi-centre RCT is feasible. Patients referred to the MDT with complex adnexal pelvic mass(es) or cyst(s) will be identified through the MDT meeting and screened against the eligibility criteria. Complex adnexal pelvic masses are defined as O-RADS-3 and deemed high risk of cancer as per subjective expert opinion, or O-RADS-4, O-RADS-5, and masses with an IOTA ADNEX score of ≥ 10%. As per standard practice, all patients referred with suspicious pelvic mass(es) will undergo a staging CT scan, serving as the primary screening tool to determine suitability for MIRRORS-FROZEN (pilot). In situations where MRI has been performed as staging imaging, the diameter of the cyst(s) or mass(es) will be used. The largest diameter of the cyst(s) or mass(es) should be ≤ 8 cm. In cases of bilateral masses or cysts, the larger cyst will be used to determine suitability for inclusion in the trial. Potential participants will then be contacted by the trial coordinator or an appropriately trained member of the trial team to introduce the trial and provide the participant information leaflet and study consent form, along with the contact details of the trial team, at least 24 hours before the standard preoperative clinic appointment. Those who express interest in participating will undergo a comprehensive consent process conducted by an adequately trained member of the trial team. Following the consent process, baseline data collection will take place along with the baseline trial questionnaires. All eligible participants who have consented to participate in the trial will be randomized using an online randomization service, Sealed Envelope™. Randomization will be at a ratio of 2:1 (MIRRORS-Frozen vs. standard treatment), using a simple randomization algorithm carried out by the trial coordinator/PI or a designated member of the trial team. After randomization and theatre allocation, participants will be contacted by a member of the trial team to inform participants of their allocation. No blinding or masking of allocation will occur, as both the participant and surgeon need to be aware of the allocation. The trial coordinator/PI and statistician will not be blinded to the groups. Participants randomized to the MIRRORS-FROZEN protocol will undergo an initial laparoscopic phase. A thorough inspection of the abdomino-pelvic cavity will be performed to determine the feasibility of proceeding robotically. In patients randomized to the robotic arm and deemed suitable to proceed, peritoneal fluid or washings will be retrieved, followed by robotic excision of the mass(es) and its retrieval in a bag. The choice of specimen retrieval method, whether through a wound protector ring or vaginally, is left to the discretion of the individual surgeon. Following retrieval of the mass(es), it will be sent for frozen section analysis as per standard pathology department practice to determine the extent of the surgery. The surgery continues robotically; however, conversion to laparotomy can be considered at any point at the discretion of the individual surgeon, in the event of surgical difficulty where it is felt to be in the patient's best interest. For example, in situations of complex adhesions or to achieve intact removal of the cyst. Participants randomized to the open arm will start with a midline abdominal incision from the outset, with intraoperative frozen section assessment. Frozen section results will determine the extent of surgery in both the trial arms and the following surgical steps to be performed in both trial arms: For participants with benign pathology, the surgery may either end or proceed to completion hysterectomy and removal of the remaining tube(s) and ovary(ies), based on the patient's preference and agreed consent. For participants with borderline pathology, surgical staging will be performed and includes: peritoneal biopsies of normal surfaces, including from the undersurface of the right hemidiaphragm, bladder reflection, Pouch of Douglas, right and left paracolic gutters, and both pelvic sidewalls; infracolic omentectomy; hysterectomy and contralateral salpingo-oophorectomy unless preservation of fertility is desired; and appendicectomy for mucinous tumours. If the mass is malignant, surgical staging should include: peritoneal biopsies of normal surfaces, including from the undersurface of the right hemidiaphragm, bladder reflection, Pouch of Douglas, right and left paracolic gutters, and both pelvic sidewalls (4-6 biopsies); supracolic omentectomy; retroperitoneal lymph node assessment of pelvic and para-aortic nodes, with removal of enlarged lymph nodes as a minimum (may be omitted in mucinous tumours); hysterectomy and contralateral salpingo-oophorectomy apart from cases of apparent Stage 1A disease where fertility preservation is desired; and appendicectomy if abnormal. The trial participants will be followed up for six weeks, and patient-reported outcome questionnaires will be collected at trial-specified points. The trial questionnaires include The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the ovarian cancer module (EORTC QLQ-OV28) complementing the EORTC QLQ-C30. The Hospital Anxiety and Depression Scale (HADS), consisting of 14 items, scored on a Likert scale and 11-point pain scale (0-10), will be used. The EQ5D-5L questionnaire will also be used to collect health economic data. All the required trial data will be recorded directly on an e-Case Record Form (eCRF) using The Research Electronic Data Capture (REDCap). The collection of Patient Reported Outcomes (PROMs) will be carried out via emails, containing a link sent to the trial participants at specific trial points. All trial appointments will be tailored around the patient's routine hospital visits, negating the need for extra visits. Anticipating a small standardized difference and aiming to achieve 80% power for the main trial, the investigators aim to recruit 40 women within a 24-month recruitment window. This sample size is pragmatically set to provide precision in estimating predefined feasibility criteria, such as the consent rate, ensuring timely recruitment. The key feasibility parameters will be assessed, offering foundational insights for the main trial.

Characterisation of Endothelial Cells in Different Inflammatory Pathologies

The immune system is a complex network of cells and molecules that protects the body from infection and injury. When the immune system is activated, it produces inflammation, which is a natural response to help heal the body. However, too much inflammation can be harmful and lead to serious complications, such as sepsis, low blood pressure, organ failure and death. The interaction of cells that line the blood vessels (endothelial cells, EC) with the immune system, is believed to be the root cause of these symptoms. When exposed to inflammation, the instructional molecules (RNA) inside the EC change. This leads to a change of operation promoting the severe symptoms previously mentioned. Researchers have developed new safe techniques to collect these cells from the blood vessels of patients to study disorders like diabetes, heart disease and stroke. This technique involves gently inserting a metal guidewire into an arm vein to collect ECs. This study plans to collect ECs from patients undergoing surgery or admitted to intensive care. We also plan to collect control samples from healthy volunteers. Samples will be collected over the duration of the patients to RSFT. The RNA will be removed from the cells and counted to highlight changes in instructions in the cells. Data from this study will potentially highlight new pathways involved in inflammation and help classify how some patients will react to current treatments. To obtain this data, this study will be split into 2 parts. Part 1 focuses on collecting one sample from a patient when they are at their most unwell states and comparing that to a sample from a healthy person. Part 2 will focus on key mRNA molecules identified during Part 1 and identifying how their expression changes over time.

Comparative Effectiveness and Safety of ELIOS in Patients With Open-Angle Glaucoma Undergoing Cataract Surgery

Investigating the Role of Energy Balance Modification on Health Responses in Chronic Lymphocytic Leukaemia

This study aims to perform a randomised control trial of exercise or exercise plus nutritional guidance on the physiological and immunological health of adults diagnosed with chronic lymphocytic leukaemia (CLL). Recruited participants will be randomised to either 12 weeks of an exercise-only program, an exercise-plus nutritional guidance program or a no-exercise control group. Fasting blood samples collected at Baseline and 12 weeks will measure absolute CLL cell counts, immune function, and inflammatory and metabolic biomarkers. A series of physical fitness assessments will be assessed at baseline and 12 weeks to determine physiologic reserve and resilience against external stressors. Additionally, participants will be asked to return 12 weeks after completing the intervention to assess the legacy effects of the intervention on the same physiological and blood-based biomarkers of health.

FIT in Diverticulitis

What is the purpose of the study? The main aim of this study is to see if a faecal immunochemical test (FIT), could be used as an alternative to currently used follow-up investigations, of colonoscopy, flexible sigmoidoscopy or CT (computerised tomography) colonography, for patients who have an episode of acute diverticulitis to exclude a colorectal cancer (CRC). As stated in the ASCPGBI consensus guidelines 2021 the risk of CRC in those with CT diagnosed uncomplicated diverticulitis is 1.6-1.9% and in those with complicated diverticulitis 7.8-10.9%. Our primary aim is to determine whether single, or multiple faecal haemoglobin and faecal calprotectin results after an episode of acute diverticulitis can be used to risk stratify for further investigations to exclude colorectal cancer. Our secondary aims are: To determine whether single, or multiple faecal haemoglobin and faecal calprotectin results after an episode of acute diverticulitis could be used to risk stratify for further investigations to exclude other colonic findings such as high-risk adenoma? Would including demographic factors such as age or anaemia allow better risk stratification? Assess the faecal microbiome in patients with acute diverticulitis and how it changes as inflammation settles. Any antibiotic treatment will also be recorded and the effect on the faecal microbiome analysed. Inclusion criteria: Computerised tomography diagnosis of acute diverticulitis Participants capable of giving informed consent Aged ≥ 18 years Planned for colonoscopy, flexible sigmoidoscopy or CT colonoscopy after diverticulitis diagnosis Exclusion criteria: Paediatric patients (<18 years) Not provided at least 1 FIT sample Unable to/unwilling to provide informed consent Withdrawal of consent for inclusion in study Previous pan-proctocolectomy, subtotal colectomy surgery, or presence of stoma Diagnosed with colorectal cancer Mental health illness limiting compliance Treated in hospital with colonic resection Did not have colonoscopy, flexible sigmoidoscopy or CT colonoscopy Recruitment: Patients who attend hospital with a diagnosis of acute diverticulitis confirmed on a CT scan and who have had a clinical decision to follow-up with either a colonoscopy, flexible sigmoidoscopy or CT colonography will be approached for written consent to participate. Patients will then be posted a patient information leaflet and a pack with collection devices to take samples at home and post back. The results of their follow-up investigation (colonoscopy, flexible sigmoidoscopy or CT colonography + any histology) will be collected when completed Involvement for patients will involve collecting and posting back in pre-paid envelopes faecal samples on their first solid stool (or as soon as possible after diagnosis) and at 3 and 6 weeks post-diagnosis. Sample size: 275 - Estimated using available data on diverticulitis and stratified data from FIT use in 2WW patients.

Effects of a Supplement to Target Ageing Mechanisms on Vascular Function (STAMINA)

Estimation of the Dietary Requirement for Vitamin D in Ethnic Groups

The aim of this study is to perform a double-blind, randomised, dose-response trial of vitamin D3 supplementation in United Kingdom (UK)-dwelling adults of white European, South Asian, and black African/Caribbean ethnicity to investigate the distribution of dietary intakes needed to maintain adequate vitamin D status in winter, as indicated by serum 25(OH)D concentrations at ranges of >25 to 50 nmol/L. In addition, this study will investigate the effect of vitamin D3 supplementation on immune health, muscular strength, and overall health. Recruited participants will be randomised to take 400, 1000, or 2000 IU for 12 weeks. Fasting blood samples collected at baseline and 12 weeks will measure biochemical markers of vitamin D status (serum 25(OH)D, calcium, parathyroid hormone, albumin), lipid profile, ferritin, micronutrient status, and immune and inflammatory biomarkers. Muscular strength will be measured using sit-to-stand and grip strength tests. Questionnaires, food diaries, and dosimeters will be used to gather data on lifestyle, physical activity, dietary intake, and sun exposure.