Clinical trials

The macula is the centre of the retina; it gives central sight, colour and fine detail. People with diabetes may develop diabetic macular oedema (DMO). In DMO, fluid leaks from blood vessels and builds up at the macula, causing sight loss. DMO can be mild or severe; this is determined by measuring, in microns (µm), how thick the macula is. One µm is one-thousandth of a millimetre. People presenting with mild DMO (macula less than 400 µm thick; normally it is around 250 µm but varies with sex and ethnicity) are offered macular laser treatment. Laser works well for these patients. Subthreshold micropulse laser (SML), which does not damage the macula, works as well as standard laser, which produces a burn, and is cost-effective. However, many people present with severe DMO (macula 400 µm or thicker) where the laser does not work well. The standard treatment is eye injections of anti-VEGFs. VEGF stands for vascular endothelial growth factor. VEGF is high in eyes with DMO and causes blood vessel leakage. Anti-VEGFs block VEGF. They are given monthly to begin with, then every 2-3 months for months or years until DMO clears. In many patients DMO comes back after clearing and anti-VEGFs need to be re-started most often monthly initially again. To improve the care of people with severe DMO this study will compare the current standard care (anti-VEGFs alone) with a strategy in which patients begin with an anti-VEGF but switch to SML once the macula is less than 400 µm thick. Patients aged over 18 years with type 1 or type 2 diabetes and severe DMO can participate. They are randomly allocated either anti-VEGFs alone or anti-VEGFs then SML when the macula is less than 400 µm thick.

Regarding psychosocial factors and outcomes in total knee arthroplasty (TKA), most of the current literature and the investigators' previous work suggest that depression, anxiety and pre-operative pain strongly predict worse outcomes following TKA. Despite some conflicting evidence, on the whole, the current literature suggests that psychological intervention in TKA patients could help to improve outcomes. In recent years, Acceptance and Commitment Therapy (ACT) has been receiving more attention as it may be more effective than the more traditional cognitive behavioural therapy in treating older people with chronic pain. ACT includes a combination of acceptance and mindfulness methods along with activation and behaviour change methods. There have been several studies examining ACT in patients undergoing orthopaedic surgery. These studies have found that attending a pre-operative ACT workshop and receiving text messages reinforcing ACT can reduce use of pain medication, reduce post-operative pain and improve function following surgery. There are also two study protocols published which plan to investigate ACT in TKA patients but the findings of these studies are yet to be reported. In this feasibility study, the investigators propose to investigate the acceptability and feasibility of a pre-operative ACT workshop in TKA patients considered to be at risk of poorer outcome based on a depression score. If found to be acceptable and feasible to both patients and those who will deliver the ACT sessions, a larger study will be performed.

The number of patients requiring knee replacements is increasing every year due to the combination of an aging population, increased patient expectancy, and rising levels of obesity. Therefore, newer implants, or design features, are introduced on a regular basis to try to improve patient outcomes. In 2013, DePuy Synthes launched the Attune Knee System to provide improved range of motion and address the unstable feeling some patients experience whilst performing everyday activities, such as going down stairs. The Attune cementless rotating platform knee was first implanted in September 2016. In 2004, the first Triathlon total knee designed by Stryker was implanted. Registry figures for both the Attune and Triathlon knees are promising with good implant longevity and outcomes. There is only a small amount of literature available on the Attune knee as it is still a relatively new implant. Worldwide, the Triathlon is widely used and is also a well-established, successful implant used in the investigators' unit. This study will help to determine whether the Attune can improve patient outcomes in terms of gait analysis assessed by walking on a treadmill, patient reported outcome measures and X-ray outcomes when compared to the Triathlon knee. 90 patients who will undergo knee replacement and meet the inclusion criteria and agree to take part will be randomly placed in one of two groups to receive either the Attune or Triathlon knee implant.

Virtual reality (VR) uses computer technology to create a three-dimensional environment which the user can explore and interact with. VR can be used to distract the patient during an operation and has been used to avoid sedative premedication, increase patient satisfaction and decrease pain during nerve blocks. VR used alongside spinal anaesthetic for hip, knee and ankle operations has shown a trend of less sedation being required with no decrease in patient satisfaction. The most common type of anaesthesia given during total knee arthroplasty (TKA) is spinal. Spinal anaesthesia is given unless there are complications or other conditions present, and general anaesthesia is given instead. General anaesthesia puts the patient to sleep during the operation, whereas spinal anaesthesia allows the patient to stay awake, but numbs the lower half of the body so no pain is felt. Sedation is usually given with spinal anaesthesia to make the patient relaxed and sleepy. Light sedation will allow the patient to be awake but relaxed, whereas deeper sedation means the patient is more likely to be asleep and less likely to recall what happened during the operation. Sedation can cause a number of side effects including nausea, vomiting, headache, drowsiness, pain, confusion, memory loss and breathing difficulties. In this study, all patients will receive spinal anaesthesia. Group 1 will receive VR and a light level of sedation, whilst Group 2 will not receive VR but will receive a deeper level of sedation (standard of care). When using VR during TKA, a lighter level of sedation should be required. This could help to reduce side effects and aid quicker patient recovery. This pilot study aims to investigate this further.

Sepsis is a common and life-threatening condition caused by a dysregulated host immune response to infection. Given the prominent role of endothelial breakdown and dysfunction in sepsis, therefore, there is an urgent need to establish strategies to protect the endothelium and preserve microcirculatory function. This study is a randomised clinical study investigating intravenous fluid therapy and oral imatinib therapy in healthy human volunteers exposed to intravenous lipopolysaccharide (LPS). The objective of the study is to investigate the biological effects of fluid and imatinib therapy on LPS-induced microcirculatory dysfunction.

Feasibility study investigating CMR dobutamine stress testing before and after lung resection