Snaith, United Kingdom

Adult SMA Research and Clinical Hub

Spinal muscular atrophy (SMA) is a genetic motor neuron disease with a broad spectrum of severity, affecting both infants and adults. Advances in treatment, including Nusinersen (Spinraza), onasemnogene abeparvovec (Zolgensma), and Risdiplam (Evrysdi), have significantly improved patient outcomes, highlighting the need for stronger clinical networks to monitor the long-term effects of these therapies. The Adult SMA REACH Study builds upon the success of SMA REACH UK, which has been instrumental in collecting natural history and treatment data for paediatric SMA patients. The study benefits from collaboration with TREAT-NMD, the UK SMA Patient Registry, and iSMAC, aligning with international efforts to harmonise SMA data collection. By leveraging Newcastle University's experience in global SMA initiatives, Adult SMA REACH aims to enhance patient care, inform clinical decision-making, and contribute to future SMA research.

Pediatric Expansion Study of the Sentio System

This study is performed to collect safety and performance data supporting the use of the Sentio system in children below 12 years of age. The system is currently available on the market for patients 12 years and above. It is a prospective, multicentre study sponsored by Oticon Medical AB, which will be conducted at eight hospitals across Europe (UK, Spain and the Netherlands). A total of 50 patients with a hearing loss than would benefit from treatment with a bone-anchored hearing system (BAHS) will be included. Participation is voluntary and the decision to participate must be well-founded and well informed. The Sentio system is a transcutaneous bone conduction hearing system (an implant and an external sound processor) for individuals with certain types of hearing losses. The implant is implanted into the bone behind the ear (mastoid and temporal bone area). After a period of skin healing, a sound processor which transmits sound waves to the implant can be magnetically attached. The implant transforms the sound waves to vibrations, which are then transmitted to the inner ear via the bone. The primary objective of the study is to demonstrate that the Sentio system improves the hearing on the implanted ear, compared with the unaided situation. The study includes eight study visits; one before surgery, the surgery visit, and six follow-up visits, with the last visit taking place 12 months after surgery.

A Real-world Wearables Study in Fabry Disease.

Trial assessments: Baseline questionnaires Baseline questionnaires will include the Hospital Anxiety and Depression Scale (HADS) and the EuroQol 5-dimension questionnaire (EQ-5D-5L). This will be administered via Qualtrics. Thigh-worn device (activPAL) Participants will attach the activPAL device to their anterior thigh for 8 days and continue their usual daily behaviour throughout the week. This will measure sitting, standing, stepping and sleep time. This device is accompanied by a hard copy daily diary, where participants will be asked to input the time they wake up, they get out of bed, they get into bed, and when they go to sleep. Clinical data Data from medical records will include disease phenotype and clinical severity including mutation type, lyso-Gb3, left ventricular mass index and diastolic dysfunction. Such data will be sourced from electronic patient records. Mainz Severity Score Index, and its age-adjusted score will be calculated from data on electronic patient records. These will be collected retrospectively from the previous 12 months upon enrolment.

Wearable Devices for Patient Monitoring in Long QT Syndrome

A Health App Using Recipes and Education Components to Facilitate Sustainable and Healthier Diets.

Overall aim: This pilot trial aims to understand the feasibility and acceptability of the syd app. The main focus is around the plant-based recipes and information pages delivered through the chat functionality. Specific objectives: The primary objective is to understand the feasibility and acceptability of setting up and running a trial with the syd app, focusing on the reach, adoption, implementation, and maintenance. The secondary objectives are to explore the indicative efficacy of the app in facilitating more sustainable and healthier diets, measured by a change in meat and legume intake, to what extent the recipes and information pages contribute to this effect, and whether there is a relationship between the self-perceived capabilities, opportunities and motivations to consume a sustainable and healthier diet. Intervention: The overall aim of syd is to enhance general wellbeing across nine domains, through completing activities and forming micro habits. The app has five main pages (Home, Daily Plan, Journal, Profile, and Chat). Users can input a goal, browse the 'activity pages', enter them into their daily plan, and complete them. When interacting with the app by completing activities, conversing in the chat, journaling or through other methods, the app calculates their 'life quality index' across all domains and presents this to users in the profile page. As the app focuses on multiple health behaviours rather than dietary change specifically, only some of the features are relevant to diet, mainly the 'activity pages' that contain food-related information and recipes. The information pages contain general information on certain aspects of diets for health and sustainability, quick tips in achieving dietary goals, and more detailed information on "What", "Why" and "How" one can adopt healthy dietary principles. The recipes are available for breakfast, lunch and dinner, and vary in their composition of healthy and sustainable foods. The chat function uses a large language model to converse and recommend content to users based on their engagement in the app overall, as well as the prompts users input into the chat. Sample size: The target sample size will be 99 (33 per arm), which will account for the possibility of 40% dropout in the first two weeks, which is typical for smartphone apps, and would still suffice the rule of thumb for 25 per group to be included in a pilot study to yield a small standardised effect size. Outcomes: Outcomes (and data) that will be collected and include 1) programme reach (population characteristics), 2) adoption of the app (participation and retention rates), 3) acceptability of the intervention (engagement with and usefulness of the app features), 4) implementation of delivering the intervention (compliance), 5) maintenance of the intervention (participant and organizational sustainability), and 6) efficacy of the intervention (indications of change in behavioural determinants and behaviours).

A Simple Breath Test to Detect Liver Cancer and Monitor Liver Conditions

A Trial of "APL-9796'' in Adults With Pulmonary Hypertension

Impact of Chronic Pulmonary Aspergillosis (CPA) on Health Status and Well-being

Prospective Ocular Imaging for Intracranial Pressure Evaluation

Raised ICP occurs in many serious neurological conditions including idiopathic intracranial hypertension (IIH), subarachnoid haemorrhage, haemorrhagic cerebrovascular accidents (CVA), meningitis, intracranial tumours and traumatic brain injury (TBI), and if undiagnosed or untreated can lead to blindness, brain injury and death. The need to accurately determine ICP is a frequent clinical dilemma in the fields of ophthalmology, neurology, neurosurgery, and emergency and critical care medicine, and traditionally has relied on a combination of clinical evaluation and measurement with lumbar punctures (LPs), or the surgical insertion of transcranial pressure transducers (ICP bolts), with or without additional computerised tomography (CT) and magnetic resonance imaging (MRI) scans which are often required in cases of suspected acutely elevated ICP. These invasive tests are the only direct methods of measuring the ICP, and carry risks of pain, post-procedural headaches and cerebrospinal fluid (CSF) leaking, intracranial haemorrhage, infection, neuronal and cortical injury, and rarely death. There are associated health service and patient costs, as these tests are cumulatively expensive and generally require inpatient admission and monitoring (with the exception of relatively few units well-versed with and resourced for day-case LPs). Given these risks, the evaluation of pragmatic, non-invasive methods of ICP measurement that are acceptable to patients have attracted increasing interest, which have included ultrasonic optic nerve sheath diameter measurement, transcranial doppler, pupillometry and tympanic membrane displacement, among others. The presence or absence of SVP on funduscopic examination has been a long used by clinicians to evaluate the likelihood of raised ICP. First described by Coccius, early mechanistic in-human studies found that SVPs disappear once the ICP rises above approximately 20 +/- 2.5 cmH2O. On the basis of clinician determination alone (by fundus examination), SVPs have been estimated to be present in 70-80% of all eyes and 80-90% of all individuals with presumably normal ICP, with a sensitivity of 0.89 and positive predictive value of 0.88 for excluding raised ICP. SVPs classically involve only short segments of retinal vein, usually on or in close proximity to the rim of the optic disc, and are theorised to arise due to differences in the rise and fall of intraocular pressure (IOP) and cerebrospinal fluid (CSF) pulse pressure (PP) with the cardiac cycle. Under normal physiological states, the mean retinal venous pressure (RVP) is consistently higher than mean IOP, which maintains continuous ocular venous outflow. As retinal veins are thin-walled and lack rigidity, fluctuations in surrounding pressure are directly transmitted to the vessels. The IOP rises and falls by approximately 1.5 mmHg in systole and diastole respectively, and this pressure variance is transmitted directly into the retinal veins. The retinal veins converge into the central retinal vein (CRV) which passes through the lamina cribrosa with the optic nerve, then exits the nerve sheath 10 mm behind the globe, entering the subarachnoid space where it becomes subject to changes in CSF PP. Unlike IOP, CSF PP only rises and falls by 0.5 mmHg during systole and diastole, thus in systole the transmitted rise in IOP causes the RVP to 1 mmHg higher than CSF PP relative to its normal pressure differential, and the opposite happens in diastole. This has the effect of causing the portion of the CRV which is most subject to this pressure differential (usually proximal to the optic disc) to collapse during systole as blood outflow increases, and to expand in diastole as blood outflow decreases, according to Poiseuille's law which states that flow rate is directly proportional to the pressure gradient. This effect diminishes the further the vein is away from the disc where it is dampened by surrounding structures, explaining why SVPs are generally most visible in short segments of veins, in close proximity to the disc. In situations of raised ICP, dampening and loss of SVPs are theorised to occur due to a rise in CSF PP that increases in a linear fashion with ICP. Eventually as ICP approaches or exceeds 20 cmH2O, the CSF PP matches that of the IOP pulse pressure, causing SVPs to disappear. The visibility of the SVP can also change independent of ICP, for example in situations of retinal vein occlusions and arterial occlusions which can abnormally alter RVP and directly injure retinal vessels leading to diminution of a visible SVP. SVPs have also been reported as appearing less frequently in patients with open-angle glaucoma (OAG) and normal-tension glaucoma (NTG) with decreasing SVP visibility associated with increasing functional field loss, though the exact mechanism is unclear. Orbit-related pathology such as thyroid eye disease (TED) has also been reported to cause absence of SVPs, presumably due to the external compressive effect on the optic nerve causing raised retrolaminar venous pressure. Furthermore, as noted above, 10% (or more) of individuals in adult populations with no known issues related to intracranial pressure may have an absent SVP determined through clinician examination alone, although it is well reported that high inter-observer variability and the general inclusion of glaucomatous patients in earlier cohorts may have confounded this finding. A final consideration is the effect of patient posture on SVP visibility. Studies that describe SVPs typically have patients sat erect and upright, postured on a slit-lamp or fundus image capture device, however it has been demonstrated that changing posture from an upright to lateral decubitus position (which raises the ICP by ~8-10 cmH2O) can reduce SVP amplitude by much as ~18% in healthy participants with visible SVPs. Studies utilising video capture of optic disc pulsations, for example using OCT devices, have shown that high fidelity optic disc recordings can increase the detection rate of SVPs up to 99% in healthy adult patients with otherwise normal optic discs, increasing the viable utility of SVPs as a biomarker to estimate ICP. Additional advantages of using video capture devices include the capacity to record captured video allowing for detection, verification, and quantification of SVPs, the option to use different light wavelengths to improve vessel contrast and visibility (such as infra-red and red-free imaging), and improved resolution thanks to sophisticated optics and post-processing software. Studies have shown that OCT videos compared to standard fundus slit-lamp examination improve the visibility of SVPs from 48.6% to 86.7% of patients, particularly for patients with more subtle SVPs, with a high inter-rater reliability of 0.82 (Cohen a). The same studies have also reported significantly higher mean 24-hour ICP and 24-hour pulse amplitude in patients with no SVP compared to patients with SVP present, and a significant association between higher ICP and reduced SVP grade. The main drawbacks of wider use of OCT devices to non-invasively assess ICP include the limited portability of the devices, the training required to acquire and interpret high-quality images, and difficulties capturing images in patients who cannot sit upright. To overcome the limitations of video capture on fixed-position OCT devices, hand-held fundus video capture devices are being increasingly developed and evaluated, either as purpose-built standalone video capture platforms (such as the EpiCam or Zeiss Visuscout) or in the form of smartphone/device attachments to ophthalmoscopes (such as the PanOptic Plus Ophthalmoscope, PPO). The above study, which reported reduction in SVP amplitude of 18% comparing upright to lateral decubitus posturing, measured SVP amplitude as a function of difference in venous pixel density between maximal and minimal vessel diameter on videos recorded by a tablet-mounted ophthalmoscope capturing at 30 frames per second (fps). This allows for SVP detection in individuals who would not otherwise be able to posture at a slit-lamp for clinician assessment. The main drawback to this and other studies of hand-held devices has been the lack of data and quantification of SVP metrics in individuals with raised ICP, absence of comparison to more established optic disc video capture devices such as OCT, and the need for expert clinician analysis or post-processing. Additionally, advances in video capture technology have led to recent significant improvements in video quality with current generation smartphones able to capture 4K resolution videos, which provide high-fidelity videos of the fundus. The capabilities of modern imaging hardware have allowed better visualisation of retina and optic disc than ever before, even using hand-held devices. Therefore, there exists scope for an automated tool that can be used to detect, localise and quantify SVPs. This may, in turn, feed into the development of automated tools to estimate contemporaneous ICP using these imaging data, which would have applications in the diagnosis and monitoring of disorders associated with raised ICP. This may potentially spare patients from currently required invasive tests of ICP measurement including LPs or intracranial bolts, in hospital and community settings.

Evaluation of Outcomes Following Rotator Cuff Repair Using the REGENETEN Bioinductive Implant: a Prospective, Multi-Center Global Registry