A multicentre,allocation concealed,randomised,open-label Bayesian adaptive multi-arm platform trial with pre-defined triggers for efficacy and futility stopping (as compared to usual care). The trial will stratify participants by biological markers into different subphenotypes. Initial stratification will be into hyperinflammatory and hypoinflammatory subphenotypes in ARDS based on plasma biomarker profiles. Regular adaptive analyses will enable efficient identification of treatment effects within each subphenotype,stopping interventions where there is evidence of efficacy or futility,and bringing in new interventions and new ...

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In the United Kingdom each year about 7000 babies are born very preterm and need specialist neonatal care. Necrotising enterocolitis (NEC) is a serious gut condition affecting 1 out of 10 extremely preterm babies (those who are born before 28 completed weeks of pregnancy). Babies with NEC commonly require surgery and, of these, one out of three unfortunately will not survive. About half of NEC survivors have long-term neurodevelopmental problems like cerebral palsy or learning difficulties. Risk factors for NEC ...

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Sometimes, after a first-time shoulder dislocation, surgery is offered to help stop the shoulder from slipping out of place again. This is a common injury in young people, especially those who play sport. During surgery, doctors repair the damaged tissues around the shoulder using keyhole (arthroscopic) techniques, followed by rehabilitation to help regain movement and strength. Others are treated with rehabilitation alone to strengthen the shoulder without surgery. At the moment, there is no clear evidence to show which option ...

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Certain anti-seizure medications (ASMs) are known to carry a teratogenic risk and are associated with higher rates of impaired physical and neurodevelopmental outcomes in the children of women with epilepsy. However, there remains a considerable gap in our current knowledge regarding the risk/safety profile of the majority of ASMs when used during pregnancy, including commonly prescribed ASMs such as lamotrigine and levetiracetam. We will investigate the health and development of children who were exposed in utero to ASMs and whose ...

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Previous research has highlighted that children,young people and families have unmet information needs at the end of treatment. We do not currently know whether children,young people and families in the UK are receiving the information they need at the end of treatment and how far children and young people are included in the conversations. Provision of information at the end of treatment sets the foundations for children and young people being able to successfully engage with future long-term follow up services ...

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While blood transfusions save lives in the neonatal critical care setting, there is increasing awareness that transfusion of blood products is an independent predictor of adverse outcome. Infants in a neonatal intensive care unit (NICU) are among the most frequently transfused patients with the incidence and severity of major neonatal morbidities known to correlate with the number and volume of red blood cell (RBC) transfusions they receive. The spectrum of post-transfusion effects on organs and tissues which manifest ...

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This is a double-blind, randomised, multicentre, placebo-controlled, comparative phase II efficacy trial. The trial will be conducted with two treatment groups in the form of a parallel group comparison and will serve to compare oral treatment with daily doses of 75 mg [25 mg three times a day (TID)] and potentially 30 mg (10 mg TID) of ZED1227 vs placebo for treatment of celiac disease. The screening period will be up to 4 weeks, followed by a 3-week single-blind placebo run-in ...

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Study Aim To investigate how often diagnostic delays or errors of carbon monoxide (CO) poisoning happen in Emergency Departments (EDs) in UK. Background Carbon monoxide (CO) poisoning is a common but often overlooked medical emergency. CO poisoning occurs when people are exposed to this odourless and invisible gas, often produced by faulty heaters, car engines, or other fuel-burning appliances. Symptoms like headaches, dizziness, or nausea can be confused with other illnesses, making diagnosis difficult. If not recognised quickly, CO poisoning can ...

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Multiple sclerosis (MS) affects more than 130,000 people in the UK and over 2.5 million people worldwide. MS often begins with a relapsing-remitting phase (RRMS). However,over time,many people with RRMS start to find that they no longer recover after a flare-up (also known as a relapse) and get steadily worse,resulting in increased disability. This is known as secondary progressive MS (SPMS). A smaller number of people experience a gradual decline from the beginning,known as primary progressive MS (PPMS). SPMS and ...

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Research question: Does post-operative radiotherapy following surgery for pathological fractures improve pain and quality of life? Background: Approximately 70% of people with advanced breast and prostate cancer develop bone metastases, causing ‘pathological’ fractures requiring surgery to stabilise or replace the affected bone. Following surgery, patients usually receive radiotherapy (RT). Despite widespread use, no high-quality evidence exists that post-operative RT improves pain, quality of life nor reduces the risk of re-operation. RT has side-effects, requires additional hospital visits and scans, can delay other effective ...

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