St%20cyr%20sur%20mer, France

Behind the Needle: Healthcare Professionals' Perspectives on HD Needling

Oto Smartphone App in Treating Tinnitus Amongst Adult Patients Compared with Standard Talking Therapies

Single-site randomised controlled study looking at tinnitus burden, insomnia severity and quality of life in adults with chronic primary subjective tinnitus when using Oto smartphone app compared with National Institute for Health and Care Excellence (NICE) approved tinnitus retraining therapy. This will be assessed objectively through questionnaires at the baseline meeting, one month, three months and six months.

Capsule Sponge Study in Eosinophilic Oesophagitis

Eosinophilic oesophagitis is a condition characterised by symptoms of dysphagia (swallowing difficulties) and/or food impaction in adults, with oesophageal biopsies (histology) showing a peak eosinophil count of >15 eosinophils/high power field (or >15 eosinophils/0.3mm2 or >60 eosinophils / mm2), and the absence of other causes of oesophageal. Evidence suggests that if inadequately treated there is increased risk of oesophageal fibrosis and stricture formation that can lead to progressive dysphagia, food bolus obstruction (food blockages) and increased morbidity. The degree of eosinophil infiltration in the mucosa is thought to reflect the disease activity better than patient symptoms. Current guidelines from Europe and newly published national guidelines from the British Society of Gastroenterology from the UK recommend reassessment of oesophageal eosinophilia after treatment to ensure remission This has traditionally involved repeating gastroscopies after each treatment (diet -after each food group, proton pump inhibitor (PPI), topical steroids) which is unpleasant for patients, expensive and labour intensive as well as producing a large carbon footprint. Since the start of the COVID-19 pandemic in January 2020 there has been restricted or delayed access to gastroscopy nationally and consequently many patients with EOE have had their repeat gastroscopies cancelled or postponed, increasing the risk of complications from undertreated disease. Capsule sponge (Cytosponge and Endosign being the current commercially produced example in the UK) is an oesophageal cell sampling device that is a 'pill on a string'. The patient swallows the pill with water and the sponge expands in the stomach. The nurse withdraws the string after 7 minutes and the sponge collects oesophageal cells on withdrawal. The sponge is sent for cytological analysis that identifies cells that can be stained for various biomarkers of Barrett's oesophagus (TFF3) and markers of dysplasia (p53 and atypia) as well as the opportunity to look at inflammation and in particular in this setting to assess the number of eosinophils and other histological and inflammatory markers supporting a diagnosis of EOE. The use of Capsule sponge in the diagnosis and monitoring of EOE has been described as an alternative to gastroscopy and a quantitative eosinophil count is possible on cytology to allow sequential assessment. The eosinophil count on cytology samples from Capsule sponge are similar to biopsies taken from the same patient at the same time, when assessed per high power field (area of 0.3mm2) in a single study. Over 10,000 Capsule sponge procedures have now been performed in the UK. The Capsule sponge service at East and North Herts trust has now performed over 1000 procedures making the trust the largest UK single site experience. The trial population will involve adult patients over 18 years who are known to have a histological diagnosis of EOE and are under follow up at East and North Herts NHS trust. Preclinical/Clinical Data The use of Capsule sponge in the monitoring of EOE has been described in a single prospective cross sectional 2-centre study in USA . There have been no studies to date assessing the clinical value of Capsule sponge in monitoring disease activity or response to treatment in adults in a real-world setting. Rationale - Does the use of Capsule sponge instead of endoscopy and biopsies in monitoring known non-stenotic EOE provide sufficient information to affect management decisions in a real-world setting? - Current practice to monitor EOE disease activity with endoscopy and biopsies has been severely affected by the COVID19 pandemic resulting in delays to treatment and the risk of progressive stenotic disease and morbidity. - Gastroscopy is invasive, expensive, unpleasant and aerosol generating whilst Capsule sponge is cheaper, much less invasive does not require sedation and is preferred by patients and carries a lower carbon footprint. STUDY OBJECTIVES AND DESIGN Objectives Primary objectives: Does Capsule sponge instead of endoscopy and biopsies in monitoring known non stenotic EOE provide sufficient information to affect management decisions in a real-world setting? Do patients show a preference for Capsule sponge over endoscopy and biopsies? Secondary objectives: - Subgroup analysis by current treatment - Do Symptom scores reflect eosinophil count and other markers of inflammation on cytology and histology? - Complications - Failure to swallow rate - Inadequate cytology rate - Gastroscopy rate by 1year if not done simultaneously - Potential Cost savings compared with gastroscopy Endpoints/outcomes Primary Endpoints/outcomes: Descriptive analysis of management decision made as a result of the Capsule sponge findings Patient preference for Capsule sponge or gastroscopy Secondary Endpoints/outcomes: - Subgroup analysis by current treatment (diet/PPI/topical steroid/combination/no treatment) - Correlation between Symptom scores and eosinophil count and other markers of inflammation on cytology and histology - Additional cytological findings of EOE activity and inflammation - Other cytological findings: Barrett's oesophagus/dysplasia/other diagnoses - Number of Complications - Failure to swallow rate - Inadequate cytology rate - Gastroscopy rate if not done simultaneously - Cost savings - Patient satisfaction and pain scores Study Design - Purpose of research To identify a suitable alternative to endoscopic biopsies for monitoring patients with non-stenotic EOE. - Real-world prospective pragmatic interventional study in a single district general hospital secondary care setting with quantitative and qualitative outcome measures. Design chosen as pragmatic and comparative control study with endoscopy would be impractical due to COVID backlog, cost and such a study has already been performed - Data collection methods: - An excel database of patients with EOE will be established and used as a screening log. With demographic data, date of diagnosis, date of previous endoscopies, endoscopic findings (EREFS criteria if documented) eosinophil count on previous histology and any other histological supportive features, current and previous treatments documented. Reasons for ineligibility will also be documented. The study will be discussed with eligible patients at their normal clinic appointment and for eligible patients who agree to enrol in the study: The following will be sent to patient by email/post as preferred and the Capsule sponge service contact email and phone details: - Eligible patients will be sent copies of the trust standard Capsule sponge procedure information leaflet. - Copies of patient Information leaflet regarding the COSiE trial - Study specific Consent form - 2 week symptoms diary Dysphagia Symptom Questionnaire (DSQ) The following will be administered with the patient on the day of the Capsule sponge procedure: - Capsule sponge eligibility and safety questionnaire - Documentation of Current treatment and duration and compliance - Patient satisfaction survey after procedure Patient participation opinion group has been completed Number of subjects A total of 100 -140 evaluable patients will be enrolled in the study. This is thought to be an achievable sufficiently large sample target given the prevalence of EOE in the catchment population. The PI runs a dedicated EOE teleclinic every month that sees approximately 12 patients. It is estimated that 2/3 of these would be eligible for Capsule sponge. In addition, other patients with EOE are also followed up in 5 other consultant gastroenterology clinics that would be eligible for the study. Study Duration The length of time the study is expected to run over 2 years in order to recruit sufficiently large sample.

Association of Middle Molecules Clearance With HDF Volume

People with severe kidney failure need treatment by dialysis or transplantation to stay alive. In the UK there are 25,000 people receiving treatment with haemodialysis (HD). Conventional haemodialysis works on the principle of diffusion for removal of toxins. Haemodiafiltration (HDF) is a technique of dialysis which implies the principle of convection in addition to diffusion. Large clinical trials comparing haemodiafiltration with conventional haemodialysis have reported better survival in patients having haemodiafiltration with large convection volume. The mechanism of survival benefit with high convection volume remains unclear. The investigators hypothesize that the benefit of high convection volume haemodiafiltration is due to enhanced removal of large sized toxins called 'middle molecules'. Additionally, it may also be due to better blood pressure control and less inflammation when dialysing using this technique. The literature so far has been inconsistent to confirm this. Understanding the relationship of haemodiafiltration convection volume with middle molecules removal and clinical parameters is crucial for adoption of this mode of treatment. Additionally, it can potentially transform the presently imperfect dialysis prescription based on small molecule removal to clinically relevant middle molecules removal. In this single centre cross sectional study, the investigators aim to recruit 400 adult participants who have been on haemodiafiltration for at least 3 months. Once consented, the participants will be observed in a single routine dialysis sessions (study visit) to record all the standard care clinical parameters and dialysis related information including dialysis convection volume from haemodiafiltration. Participants will also have routine blood tests at the start and end of the observed dialysis session and additional blood tests to measure the removal of middle molecules at the same time. The relationship of these observed clinical and measured toxins removal parameters with convection volume will be determined from the collected data.

Safety of AI-Powered Virtual Assistant in Outpatient Management of Heart Failure

HONEY for the Treatment of POst-Tonsillectomy Pain

Tonsillectomy is one of the most common surgical procedures performed in the UK. It can be a painful operation to recover from, particularly in adults. Amongst the recognised complications, poor oral intake secondary to uncontrolled pain can result in re-admission to hospital, development of localized infection and subsequent bleeding. Post-operative analgesia regimes can vary depending on the individual surgeon preference or departmental policies, however generally it involves regular simple analgesics including paracetamol, ibuprofen and topical analgesic throat sprays or rinses. Commonly, opioid based analgesics such as codeine, tramadol and oramorph are needed in the post-operative period. Whilst these are generally effective, they can be associated with significant side effects such as constipation, drowsiness and nausea and prolonged use is not recommended. Beehive products such as honey and propolis have been mentioned as wound dressings in ancient writings across the world, thousands of years before the advent of modern medicine. Honey is a by-product of flower nectar produced in the aero-digestive tract of bees and propolis is produced from plant resins, enriched with salivary enzymatic secretions. Honey has been shown to possess anti-bacterial and anti-inflammatory properties. Manuka honey is a mono-floral honey with potential wound repair and antibacterial activities. It is produced by bees fed on the flowers of the New Zealand Manuka bush (Leptospermum scoparium) and contains a significantly higher concentration of the 1,2-dicarbonyl compound methylglyoxal, which may account for its antibacterial activity. Manuka honey has been reported to stimulate the formation of new blood capillaries and the growth of fibroblasts and epithelial cells when applied topically to wounds. It is now part of the routine armamentarium of products used in the treatment of burns and external skin wounds in NHS Plastic surgery departments in the United Kingdom (UK). The clinical efficacy of Manuka honey in the oral and oropharyngeal cavities is controversial and quality, placebo controlled, randomized clinical trials are lacking. There are a number of systematic reviews that have described some benefit of Manuka honey in the treatment of radiation induced oro-mucositis, particularly in reducing treatment interruptions, preventing weight loss and pain control. The most recent PROSPECT (Procedure-specific postoperative pain management) guideline for tonsillectomy published in 2021 in the Anaesthesia journal, represented an international, multidisciplinary collaborative effort providing recommendations on the most effective pain management following tonsillectomy. The fourth of five summative recommendations, based on systematic review of the current literature, is that analgesic adjuncts such as postoperative honey is recommended. Honey could provide significant improvements in post-operative pain scores as well as provide opioid-sparing benefits. This is a powerful mandate for further research into the routine clinical usage of honey as an adjunct to post-tonsillectomy pain management. To date there have not been any placebo controlled, randomised clinical trials comparing the effectiveness of oral honey in post-tonsillectomy pain control in the UK. The aim of this double-blind, randomised, placebo controlled clinical trial is to compare the effect of Manuka honey with standard of care compared to placebo with standard of care on post-tonsillectomy pain and postoperative outcomes. The hypothesis is that the addition of Manuka honey to standard of care will result in a significant reduction in post-tonsillectomy pain scores compared to the placebo control. The null hypothesis is that there is no significant difference between Manuka honey compared to placebo in post-tonsillectomy pain scores. The primary endpoint/outcome are daily pain scores measured via Visual Analogue Scale (VAS). This is a continuous variable, which will be measured and recorded three times a day, every day for the first 14 days post-tonsillectomy. The secondary endpoint/outcomes include the number and frequency of concurrent analgesia usage, the rate of readmission to hospital, the rate of secondary haemorrhage, the rate of infection requiring antibiotics treatment, the speed of return to work. These are a mixture of continuous and ordinal variables and will be collected retrospectively.

Assessment of Lipoprotein(a) and Endogenous Fibrinolysis in Atherosclerotic Cardiovascular Disease/Aortic Valve Disease

The risk of a clot forming in a blood vessel, which can cause a heart attack or stroke, is determined partly by how "sticky" the blood is and partly by the effectiveness of the natural defences in the blood in dissolving any clots that start forming (clot lysis, or "fibrinolysis"). In the last few years, using new blood testing techniques, we and other groups, have shown that individuals who have less effective natural clot lysis, have a much higher risk of heart attack, stroke and death, even despite current best medications. Therefore, we would like to find medications that can make clot lysis more effective, in such individuals, to reduce their risk of stroke and heart attack. Unfortunately, most blood thinning tablets for long term use do not improve clot lysis. Earlier, our group has shown that the anticoagulant apixaban, mildly improved clot lysis Elevated concentration of Lp(a) in the blood is a risk factor for the development of cardiovascular disease including coronary artery disease and narrowing of the aortic valve. Lp(a) may exert its adverse effects by impairing fibrinolysis. Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, including fibrin clots. Lp(a) has a high degree of homology to plasminogen (a pro-enzyme that is cleaved to form plasmin) and may cause thrombosis by competitively inhibiting t-PA-mediated plasminogen activation and tPA-mediated clot lysis. Furthermore, Lp(a) stimulates the activity of PAI-1, which is the major inhibitor of the fibrinolytic system. Until recently, Lp(a) has been considered a non-modifiable cardiovascular risk factor as few therapies are available to sufficiently reduce Lp(a) levels. New data, however, have shown that novel cholesterol lowering treatments, namely PCSK9 inhibitors and inclisiran (a long-acting silencing RNA) can reduce Lp(a) levels by approximately 20-25%. Given Lp(a) is a causal risk factor for cardiovascular outcomes, it is important to know if a reduction in Lp(a) can favourably modify endogenous fibrinolysis. If Lp(a) level is directly related to the effectiveness of endogenous fibrinolysis, then medications that reduce Lp(a) (currently PCSK9i and/or inclisiran, and others in development) could be used as targeted treatment for patients who despite optimal antithrombotic therapy, demonstrate impaired endogenous fibrinolysis.

An Investigator-initiated Linked Study to OCEANIC-AF

The risk of a clot forming in a blood vessel, which can cause a heart attack or stroke, is determined partly by how "sticky" the blood is and partly by the effectiveness of the natural defences in the blood in dissolving any clots that start forming (clot lysis, or "fibrinolysis"). There are available tests that can assess how "sticky" the blood is, and we can overcome that with specific blood-thinning medications (such as anticoagulants [such as warfarin, apixaban, rivaroxaban] and antiplatelet agents [such as aspirin and clopidogrel]). However, we have not been able to assess the effectiveness of natural clot dissolving mechanisms, until recently. In the last few years, using new blood testing techniques, we and other groups, have shown that individuals who have less effective natural clot lysis, have a much higher risk of heart attack, stroke and death. Therefore, we would like to find medications that can make clot lysis more effective, in such individuals, to reduce their risk of stroke and heart attack. Unfortunately, most blood thinning tablets for long term use do not improve clot lysis. Earlier, our group has shown that the anticoagulant apixaban, mildly improved clot lysis. We would now like to assess clot lysis in patients taking apixaban and compare it to patients taking a very new type of anticoagulant called asundexian, to see if asundexian can improve clot lysis more than apixaban. The easiest way to do this, is to test additional blood samples from patients who are already taking part in a clinical trial comparing apixaban and asundexian (OCEANIC-AF). OCEANIC-AF is a phase 3, multicentre, randomised clinical trial, comparing asundexian, a new type of blood thinner (factor XI inhibitor) with a commonly used blood thinner (apixaban, a factor X inhibitor), to see if it carries a lower risk of bleeding. This is a prospective observational linked study to the main OCEANIC-AF study, to be undertaken in 2 centres in England. Patients enrolled in OCEANIC-AF at these 2 centres will have 4 additional blood samples taken, at baseline before starting the investigational drug or comparator, then at the 3, 6 and 12 month visits.

Study to evaLuate the effIcacy and Safety of abeLacimab in High-risk Patients With Atrial Fibrillation Who Have Been Deemed Unsuitable for Oral antiCoagulation (LILAC-TIMI 76)

A Study to Evaluate the Introduction of New Staffing Models in Intensive Care: a Realist Evaluation (SEISMIC-R)

Background: Optimising deployment of the scarce nursing workforce in the intensive care unit (ICU) is paramount for patient safety, and staff wellbeing. ICU staffing models are determined by National Health Service (NHS) service specification, with 1:1 patient to registered nurse (RN) ratios for the highest acuity patients. A rapid expansion of ICU capacity during COVID19 led to adoption of alternative models, using more support staff, non-ICU qualified nurses and other professionals, reaching up to 70% at surge. The strengths, weaknesses, costs and effects of these models, and benefits of retaining them, remain uncertain. Lower nurse-staffing levels, and high workload, have been associated with adverse outcomes for patients, staff and organisations although ICU-specific evidence is limited. Studies focus on levels of RNs, contributing little to understanding consequences of changes retained post-COVID, or to guiding adoption of alternative staffing models. It is unclear how changes in staffing or specific models affect various outcomes. Aim: To identify the key components of an optimal nurse staffing model for deployment in ICU. Objectives/Methods: Guided by a realist framework, the investigators propose to interlink workstreams (WS) over 2 years to allow cross-fertilisation of ideas/hypotheses and inform emerging programme theories. 1. To identify and describe organisation of models, exploring intended mechanisms and outcomes for how different models work, the investigators will conduct: - a UK survey (WS 1) of all 294 ICUs in England/Wales/Northern Ireland (NI)/Scotland that will identify staffing models emerging/retained since COVID19, compared with United Kingdom (UK) service specifications. - a realist evaluation (WS 2, cross-cutting workstream) and detailed case studies involving six sites, and 30-40 interviews with: nurses/senior nurses; organisational leads; critical care network managers/commissioners; families/patients, to test emerging programme theories. Rapid ethnographies (n=30), will elucidate how staffing decisions are made. 2. To provide estimates of variability in demand for nursing staff and estimate associations between staffing patterns and patient outcomes, the investigators will: - use administrative e-roster (nurse staffing roster) data and patient data (WS 3) from the Intensive Care National Audit and Research Centre Case Mix Programme (2019-2023) to assess whether and how patient/staff outcomes vary with differing staff models between units/case study sites. 3. To develop simulation models to show the impact of models on capacity, cost and patient flow, the investigators will use simulation modelling (WS 4) to explore scenarios for different staffing policies given case mixes of case study units, swiftly and with no patient impact. Analysis: Data integration occurs across all workstreams in WS 5. Theories developed from WS2 case studies will be further tested against WS 3 observational data and inform WS 4 mathematical simulation models of ICU capacity, patient outcomes and patient flow, to inform emerging propositions for the realist evaluation programme theories as context-mechanism-outcome configurations.