UK Centres Research Articles

Efficacy of oral corticosteroids for acute preschool wheeze: a systematic review and individual participant data meta-analysis of randomised clinical trials

Oral corticosteroids are commonly used for acute preschool wheeze, although there is conflicting evidence of their benefit. We assessed the clinical efficacy of oral corticosteroids by means of a systematic review and individual participant data (IPD) meta-analysis. In this systematic review with IPD meta-analysis, we systematically searched eight databases (PubMed, Ovid Embase, CINAHLplus, CENTRAL, ClinicalTrials.gov, EudraCT, EU Clinical Trials Register, WHO Clinical Trials Registry) for randomised clinical trials published from Jan 1, 1994, to June 30, 2020, comparing oral corticosteroids with placebo in children aged 12 to 71 months with acute preschool wheeze in any setting based on the Population, Intervention, Comparison, Outcomes framework. We contacted principal investigators of eligible studies to obtain deidentified individual patient data. The primary outcome was change in wheezing severity score (WSS). A key secondary outcome length of hospital stay. We also calculated a pooled estimate of six commonly reported adverse events in the follow-up period of IPD datasets. One-stage and two-stage meta-analyses employing a random-effects model were used. This study is registered with PROSPERO, CRD42020193958. We identified 16 102 studies published between Jan 1, 1994, and June 30, 2020, from which there were 12 eligible trials after deduplication and screening. We obtained individual data from seven trials comprising 2172 children, with 1728 children in the eligible IPD age range; 853 (49·4%) received oral corticosteroids (544 [63·8%] male and 309 [36·2%] female) and 875 (50·6%) received placebo (583 [66·6%] male and 292 [33·4%] female). Compared with placebo, a greater change in WSS at 4 h was seen in the oral corticosteroids group (mean difference -0·31 [95% CI -0·38 to -0·24]; p=0·011) but not 12 h (-0·02 [-0·17 to 0·14]; p=0·68), with low heterogeneity between studies (I2=0%; τ2<0·001). Length of hospital stay was significantly reduced in the oral corticosteroids group (-3·18 h [-4·43 to -1·93]; p=0·0021; I2=0%; τ2<0·001). Subgroup analyses showed that this reduction was greatest in those with a history of wheezing or asthma (-4·54 h [-5·57 to -3·52]; pinteraction=0·0007). Adverse events were infrequently reported (four of seven datasets), but oral corticosteroids were associated with an increased risk of vomiting (odds ratio 2·27 [95% CI 0·87 to 5·88]; τ2<0·001). Most datasets (six of seven) had a low risk of bias. Oral corticosteroids reduce WSS at 4 h and length of hospital stay in children with acute preschool wheeze. In those with a history of previous wheeze or asthma, oral corticosteroids provide a potentially clinically relevant effect on length of hospital stay. Asthma UK Centre for Applied Research.

O166: Safety and Efficacy of Autologous Fat Grafting in the Treatment of Radiation-Induced Fibrosis and Contour Defects in Head and Neck Reconstruction

Abstract Background Multimodal treatment for head and neck cancer results in significant functional and cosmetic morbidity, often through contour deformity and radiation-induced skin fibrosis (RIF), affecting head and neck function and cosmesis. Autologous fat grafting is an emerging treatment for RIF. We conducted a retrospective cohort review of patient outcomes following autologous fat transfer for reconstruction of head and neck contour deformity and RIF. Methods A retrospective analysis was performed of patients treated at 2 UK centres between 2009-2022. Patient data collated included demographics, oncological treatment, reconstruction, operative details, and pre- and post-operative patient reported outcome measures (PROMs) including University of Washington Quality of Life Questionnaire (UW-QOL), Derriford Appearance Scale (DAS24) and Patient Outcomes of Surgery (POS). Patients were stratified by indication for AFG. Results A total of 45 patients were identified. 89% of patients (85% RIF, 92% contour deformity) reported cosmetic or functional improvement. Two patients (4%) reported no improvement, and three (7%) were lost to follow-up. Psychological health scores improved in patients following AFG for both RIF and contour deformity patients (DAS24, P&amp;lt; 0.0001). The UW-QOL scores revealed statistically significant improvements in multiple functional domains including appearance, activity, recreation, mood, and anxiety in both patients with RIF and contour deformities. Conclusion This study demonstrates that AFG is an effective technique for the correction of contour deformity and RIF in patients following treatment for head and neck cancer. Patients suffering from RIF demonstrated significant improvements in both functional and psychological domains.

O64: Aortic Trauma in the UK (UK): Vascular Interventions and Surgery in Trauma Audit (VISTA)

Abstract Background In the UK, the incidence, treatment strategies and clinical outcomes for aortic injury are unknown. Stent graft sizing can be challenging in the acute trauma setting which may increase the risk of stent graft complications. VISTA aimed to describe the UK burden and treatment of aortic trauma. Methods Subgroup analysis of a six-month multicentre, prospective audit of vascular injuries at 27 UK Major Trauma Centres by the National Trauma Research &amp; Innovation Collaborative and Vascular &amp; Endovascular Research Network. Results In total, 58 aortic injuries (43 thoracic, 15 abdominal) with 24 interventions (n=23 TEVAR) were analysed. The median age of TEVAR patients was 46 (IQR: 27 - 59) years and 92% were male. The median time to intervention was 288 (IQR: 208 - 722) minutes and 75% of cases were performed for grade 3 and 4 aortic injuries with one simultaneous carotid-subclavian bypass. A consultant vascular surgeon was documented as present in 75% of cases and the post-procedure mortality rate was 8%. Conclusion TEVARs performed for vascular trauma setting are currently excluded from the National Vascular Registry. UK centre performance, device surveillance and long-term outcomes for this patient cohort requires national monitoring to assure patient safety and drive care quality improvements.

Cascade screening in HBOC and Lynch syndrome: guidelines and procedures in a UK centre

In the 33 years since the first diagnostic cancer predisposition gene (CPG) tests in the Manchester Centre for Genomic Medicine, there has been substantial changes in the identification of index cases and cascade testing for at-risk family members. National guidelines in England and Wales are usually determined from the National Institute of healthcare Evidence and these have impacted on the thresholds for testing BRCA1/2 in Hereditary Breast Ovarian Cancer (HBOC) and in determining that all cases of colorectal and endometrial cancer should undergo screening for Lynch syndrome. Gaps for testing other CPGs relevant to HBOC have been filled by the UK Cancer Genetics Group and CanGene-CanVar project (web ref. https://www.cangene-canvaruk.org/). We present time trends (1990–2020) of identification of index cases with germline CPG variants and numbers of subsequent cascade tests, for BRCA1, BRCA2, and the Lynch genes (MLH1, MSH2, MSH6 and PMS2). For BRCA1/2 there was a definite increase in the proportion of index cases with ovarian cancer only and pre-symptomatic index tests both doubling from 16 to 32% and 3.2 to > 8% respectively. A mean of 1.73–1.74 additional family tests were generated for each BRCA1/2 index case within 2 years. Overall close to one positive cascade test was generated per index case resulting in > 1000 risk reducing surgery operations. In Lynch syndrome slightly more cascade tests were performed in the first two years potentially reflecting the increased actionability in males with 42.2% of pre-symptomatic tests in males compared to 25.8% in BRCA1/2 (p < 0.0001).

Laparoscopic or open abdominal surgery with thoracotomy for patients with oesophageal cancer: ROMIO randomized clinical trial.

This study investigated if hybrid oesophagectomy with minimally invasive gastric mobilization and thoracotomy enabled faster recovery than open surgery. In eight UK centres, this pragmatic RCT recruited patients for oesophagectomy to treat localized cancer. Participants were randomly allocated to hybrid or open surgery, stratified by centre and receipt of neoadjuvant treatment. Large dressings aimed to mask patients to their allocation for six days post-surgery. The authors present the intention-to-treat analysis of outcome measures from the first 3 months post-randomization, including the primary outcome, the patient-reported physical function scale of the EORTC QLQ-C30, and cost-effectiveness. Current Controlled Trials registration: ISRCTN 59036820 (feasibility study), 10386621 (definitive study). There was no evidence of a difference between hybrid (n = 267) and open (n = 266) surgery in average physical function over 3 months post-randomization: difference in means 2.1, 95% c.i. -2.0 to 6.2, P = 0.3. Complication rates were similar; for example, 88 (34%) participants in the open and 82 (32%) participants in the hybrid surgery groups experienced a pulmonary infection within 30 days. There was no evidence that hybrid surgery was more cost-effective than open surgery at 3 months. Patient-reported physical function in the 3 months post-randomization provided no evidence of a difference in recovery time between hybrid and open surgery, or a difference in cost-effectiveness. Both approaches to surgery were completed safely, with a similar risk of key complications, suggesting that surgeons who have a preference for one of the two approaches need not change their practice.

Digital technologies in bronchiectasis physiotherapy services: a survey of patients and physiotherapists in a UK centre.

We aimed to explore how digital technology is currently used, could be used and how services could be improved in order to optimise bronchiectasis physiotherapy care. Online surveys were designed and distributed amongst people with bronchiectasis and physiotherapists in Northern Ireland. Responses to closed and open question formats were collected and analysed. The survey was completed by 48 out of 100 physiotherapists (48%) between January 2020 and January 2021 and by 205 out of 398 people with bronchiectasis (52%) between October 2020 and October 2021. 56% of physiotherapists (27 out of 48) reporting using some type of digital technology to facilitate services, whereas 44% (21 out of 48) reported that they had never used a digital technology in this patient group. When physiotherapists were asked whether they would be likely to use certain remote and/or digital options to deliver follow-up care for airway clearance techniques, most (31-38 out of 48; 65-79%) indicated that they would. Regarding patient responses, most reported that they would use telephone consultation (145 out of 199, 73%) and a smaller proportion were likely to use video consultation (64 out of 199, 32%). The most commonly mentioned theme for improvement amongst patients was follow-ups, while improved access, quality of services and treatments were the most commonly mentioned amongst physiotherapists. Despite a large proportion of physiotherapists in this survey reporting no current use of digital technology in bronchiectasis physiotherapy care, there was significant interest and willingness to do so, amongst both physiotherapists and patients. This survey highlighted a range of care areas, specifically follow-up visits, where digital methods could be further explored.

Preoperative N-terminal pro-B-type natriuretic peptide and myocardial injury after stopping or continuing renin–angiotensin system inhibitors in noncardiac surgery: a prespecified analysis of a phase 2 randomised controlled multicentre trial

BackgroundPatients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml−1) experience more complications after noncardiac surgery. Individuals prescribed renin–angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations. MethodsIn a preplanned analysis of a phase 2a trial in six UK centres, patients ≥60 yr old undergoing elective noncardiac surgery were randomly assigned either to stop or continue RAS inhibitors before surgery. The pharmacokinetic profile of individual RAS inhibitors determined for how long they were stopped before surgery. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury (plasma high-sensitivity troponin-T ≥15 ng L−1 or a ≥5 ng L−1 increase, when preoperative high-sensitivity troponin-T ≥15 ng L−1) within 48 h after surgery. The co-exposures of interest were preoperative plasma NT-proBNP (< or >100 pg ml −1) and stopping or continuing RAS inhibitors. ResultsOf 241 participants, 101 (41.9%; mean age 71 [7] yr; 48% females) had preoperative NT-proBNP >100 pg ml −1 (median 339 [160–833] pg ml−1), of whom 9/101 (8.9%) had a formal diagnosis of cardiac failure. Myocardial injury occurred in 63/101 (62.4%) subjects with NT-proBNP >100 pg ml−1, compared with 45/140 (32.1%) subjects with NT-proBNP <100 pg ml −1 {odds ratio (OR) 3.50 (95% confidence interval [CI] 2.05–5.99); P<0.0001}. For subjects with preoperative NT-proBNP <100 pg ml−1, 30/75 (40%) who stopped RAS inhibitors had myocardial injury, compared with 15/65 (23.1%) who continued RAS inhibitors (OR for stopping 2.22 [95% CI 1.06–4.65]; P=0.03). For preoperative NT-proBNP >100 pg ml−1, myocardial injury rates were similar regardless of stopping (62.2%) or continuing (62.5%) RAS inhibitors (OR for stopping 0.98 [95% CI 0.44–2.22]). ConclusionsStopping renin-angiotensin system inhibitors in lower-risk patients (preoperative NT-proBNP <100 pg ml −1) increased the likelihood of myocardial injury before noncardiac surgery.

One Tube Does Not Fit All: Parent Experiences and Decision-Making for Choosing a Nasogastric Tube or Gastrostomy for Their Child During Allogeneic Bone Marrow Transplant

Background: Children undergoing bone marrow transplant (BMT) are at risk of developing malnutrition. A feeding tube becomes a requirement for most children to meet their nutritional and medication requirements. Two tubes are typically used: nasogastric tube (NGT) or gastrostomy. At the UK center where this study took place, parents are offered a choice between these tubes. Objective: This qualitative data collection in a mixed methods study explored why parents choose either tube and their experiences of using it. Methods: Parents participated in 2 semistructured interviews. First, on admission to explore why they chose either tube. Second, 1–2 months postdischarge to explore their experience of using the tube. Interviews took place over 18 months. Transcripts were thematically analyzed. Results: Sixteen parents whose child had an NGT, 17 a gastrostomy, were interviewed. Choice was experienced across a continuum of difficulty and freedom. Many parents deferred to the expertise of professionals; others felt they were the experts in their child. Influential factors in decision-making included expected duration of need, the child’s age and activity, cosmetic differences, balancing gastrostomy surgery against NGT dislodgement, lay advice, healthcare professionals’ recommendations and prior tube feeding experiences. Conclusions: Parents valued choice appreciating 1 feeding tube might not suit every child. Implications for Practice: Choice of a gastrostomy or NGT should be offered to children prior to BMT. What is Foundational: Parents navigate a complex decision-making process when choosing a feeding tube for their child. Healthcare professionals can facilitate informed decision-making through collaborative discussions, inclusion of peer support, and provision of balanced information.

Making Sense of Here: revealing multiple narratives of place through artistic process and integrating art and artists into transdisciplinary research

The celebrated English Lake District, a national park and World Heritage Site, embraces complexity and tension. In landscape decision-making, farmers, landowners, policy makers, ecologists, residents, tourists and businesses have vested interests, as do the land and other-than-humans; yet the challenge remains in considering voices equitably and integrating complex environmental data. The art project Sense of Here (2018–2020), incorporating learning from local experts, scientists and land managers, and using walking, poetry, photography, film and installations, aimed to portray and connect multiple perspectives. Learning from Sense of Here was instrumental in the establishment of the multi-artist PLACE Collective within the UK Centre for National Parks and Protected Areas; and contributed to the Windermere Accord, formed through the Ensemble Fellowship to improve pathways to better understand, mitigate and adapt to environmental change. This paper shares insights from Sense of Here and considers the role of art in shifting patterns of dialogue across different silos.

Real world outcomes for maintenance avelumab treatment in locally advanced/metastatic urothelial cancer after platinum-based chemotherapy.

584 Background: Maintenance Avelumab after platinum-based chemotherapy in metastatic-/locally advanced urothelial carcinoma has shown overall and progression free survival benefit in the JAVELIN Bladder 100 trial. We analysed real world outcomes from 6 UK centres. Methods: Retrospective electronic patient records review was carried out for patients treated between January 2021 and September 2023 at 6 UK centres. Patients whose disease had not progressed after platinum-based chemotherapy were started on maintenance avelumab 800mg given at 2 weekly intervals, starting within 12 weeks of last day of chemotherapy as per the National Cancer Drug Fund criteria. Survival outcomes were established using the Kaplan Meier method and compared by a log rank test using SPSS. Results: In total 80 patients (median age 73 years-range 21-86) were included of which 68% were male and 32% were female. 31(38.8%) had prior upper tract and 49(61.2%) had bladder cancers. Metastases were in the nodes only in 33(41.5%) patients whilst 16.9% and 42.3% had bone and visceral metastases respectively. The number of patients with ECOG PS 0,1 and 2 were 36 (45.0%), 33 (41.3%), and 10 (12.5%), respectively. After a median of six cycles of platinum-based chemotherapy, 11.3% had a complete response, and 54.9% had a partial response. Patients then proceeded to maintenance avelumab treatment. Before treatment, the median Neutrophil to Lymphocyte Ratio (NLR) was 2.89. The number of patients with NLR ≤2.89 was 37 (46.3%), and with &gt;2.89 were 38 (47.9%). Median number of cycles were 9 (range 1-66). At a median follow-up of 16.7 months, the median PFS was 8.3 months (95% CI 4.8-15.4). At the data cut-off, 37 patients had died, and 40 patients had progressed. Any grade of adverse event occurred in 34 (42.5%) patients. Grade 3 or higher toxicity rate was 7.5%. Two grade 3 allergic reactions were seen. One patient had Grade 3 immune mediated hepatitis and one patient had grade 3 immune mediated arthritis. Two grade 2 immune mediated colitis were reported. The ORR of avelumab maintenance therapy was 12.5%. 2 patients had a complete response, 8 had a partial response, and 43(53.7%) had stable disease. Within the limit of our small data set, univariate analysis for PFS revealed that there was no significant association between PFS and visceral metastases (p=0.2), bone metastases (p=0.2), node only metastases (p=0.6), primary site(p=0.9), and ECOG PS (p=0.6). However, NLR was a significant prognostic factor for PFS. The median PFS in patients with NLR ≤2.89 vs &gt;2.89 was 16.9 vs 4.2 months, respectively (p=0.001). Conclusions: Our multi centre UK real world data confirms that maintenance Avelumab treatment is well tolerated, and its efficacy data is consistent with previously reported clinical studies.

Does use of apalutamide enhance outcomes in combination with radiotherapy in metastatic hormone-sensitive prostate cancer? A real-world experience from the UK.

73 Background: Management of metastatic prostate cancer has undergone a significant change over the past decade, with the introduction of several novel agents and repurposing of others. Latest update from STAMPEDE trials shown prostate radiotherapy (RT) improves OS, without detriment in QoL in metastatic home sensitive prostate cancer mHSPC along with Docetaxel in those with low volume metastatic disease. There is no published data on impact of radiotherapy to prostate on Apalutamide treated mHSPC patients. Here we report our real-world experience of Apalutamide in mHSPC with radiotherapy. Methods: Patients with mHSPC (N = 266) from 5 UK centres, were treated with Apalutamide (240 mg) and ADT along with radiotherapy to prostate as per treating clinician’s discretion. The primary endpoint was objective rate (ORR) as determined by patients achieving a PSA decline of ≥90% (PSA90) and ≥50% (PSA50) and secondary endpoints included biochemical progression free survival (bPFS) and safety. Results: The median age for the whole cohort was 73.4 years (interquartile range 52 - 91), A total of 11.6% had received prior radical treatment (prostatectomy or radiotherapy for localised disease) and 88.4% had de novo metastatic disease. Median baseline PSA was 47 ng/ml (range 0.4-17100). The proportion of patients PSA90 and PSA50 at 3, 6 and 12 months is shown in the Table. Median PSA nadir was 0.1 ng/ml(rage 0.01- 48.2) and median time to reach nadir was 6 months (range 3-24 months). 13.5% (35) patients were treated with radiotherapy (RT) after at least 3 months (range 3 -6 months) of starting apalutamide. Patients received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) of radiotherapy (68 % vs 32%). Higher number of patients in RT group had achieved PSA90 compared to no radiotherapy cohort (97.14 % vs 87.3%, p =0.15). Patients treated with RT had median post treatment of PSA 0.01 ng/ml compared to 0.1 ng/ml in non RT group (p=0.0062). After median follow up of 8.4 months, proportion of patients shown biochemical progression in RT vs non RT group were 5.7 % vs 15 % respectively (p= 0.04). Patients with de novo metastatic disease have shown poor PSA response and higher chance of progression compared to patients who had initial radical treatment. Radiotherapy was well tolerated, with 17 % adverse events (Radiation Therapy Oncology Group grade 3–4) reported in radiotherapy group. Conclusions: Early experience of using apalutamide and radiotherapy in mHSPC showed improved PSA response and delayed progression. Treatment was well tolerated. Further follow up and clinical trials are needed to understand the impact on overall survival. [Table: see text]

A phase II trial of cemiplimab alone or in combination with standard of care chemotherapy in locally advanced or metastatic penile carcinoma (EPIC trial).

TPS14 Background: Penile cancer is rare, &lt;1% of male malignancies diagnosed each year, but its incidence is increasing with an 18% increase over the last decade projected to rise a further 9% in the next 10 years. Patients with locally advanced/metastatic penile cancer (la/mPC) have very few treatment options and there is a lack of clinical trial data to guide management. Cisplatin containing combination chemotherapy regimens are regarded as the standard of care (SOC) in this setting. However, with response rates of 50% or less there is a need to further improve treatment outcomes. PDL1 is upregulated in 40–60% of PC cases and is correlated with poor prognosis making a case for immunotherapy as a treatment for la/mPC. The PD-1 inhibitor cemiplimab is approved for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (SCC) suggesting efficacy against penile SCC. The EPIC trial was set up to evaluate the benefit and safety of cemiplimab alone, or, in combination with SOC chemotherapy in patients with la/mPC. Methods: This is a non-randomised, 2 arm, phase II multi-centre trial. Arm 1 cemiplimab + SOC chemotherapy (local site choice of cisplatin/5FU, TPF or TIP regimes); Arm 2 single agent cemiplimab. The choice of arm decided by the investigator site based on chemotherapy eligibility. 47 patients will be recruited from 10 UK centres: 29 patients into ARM 1 who will receive 4 cycles of cemiplimab 350mg IV q3 weekly + SOC chemotherapy, followed by single agent cemiplimab x 30 cycles (24 months total). 18 patients into ARM 2 who will receive single agent cemiplimab 350mg IV q3 weekly x 34 cycles (24 months total). The primary endpoint is clinical benefit rate (CBR) of cemiplimab: objective response rate (ORR) plus stable disease as assessed radiologically (RECIST 1.1) at 12 weeks from first dose in patients with la/mPC. Secondary end-points include safety, tolerability, CBR at 1, 2 and 3 years, ORR, progression-free survival, overall survival and assessment of patient health status and quality of life using the patient reported outcome measures EQ-5D-5L and EORTC QLQ-C30. Each arm will be analysed separately as a Fleming A’Hern study α=0.05 + power (1-β)=0.8. Arm 1 assumes 25% meeting the clinical end point is a poor treatment (p0=0.25) and 50% is a good treatment (p1=0.5). Arm 2 assumes 5% meeting the clinical end point is a poor treatment (p0=0.05) and 25% is a good treatment (p1=0.25). Progress: By February 2023 10 UK sites had been opened to recruitment. The first patient entered the trial in November 2021 and to date 25 patients have been recruited into Arm 1 and 10 into Arm 2. Opening sites was slower than anticipated following emergence from the COVID pandemic. However, a recruitment rate of 1-2 patients per month has shown the feasibility of running a trial for this rare patient population. Clinical trial information: ISRCTN95561634 .

Rituximab compared to intravenous cyclophosphamide in adults with connective tissue disease-associated interstitial lung disease: the RECITAL RCT

Background Interstitial lung disease frequently complicates systemic autoimmune disorders including scleroderma, idiopathic inflammatory myositis and mixed connective tissue disease, resulting in considerable morbidity and mortality. Based on the results of trials undertaken in scleroderma, cyclophosphamide is the standard of care for individuals with severe or progressive connective tissue disease-associated interstitial lung disease. Observational studies suggest that the anti-CD20 monoclonal antibody, rituximab is an effective rescue therapy in treatment of refractory connective tissue disease-associated interstitial lung disease, but it has not been studied as first-line therapy in clinical trials. Objectives To compare the safety and efficacy of rituximab against that of cyclophosphamide as treatment for individuals with severe, progressive interstitial lung disease associated with scleroderma, idiopathic inflammatory myositis or mixed connective tissue disease. Methods This was a Phase IIb, multicentre, randomised, double-blind, double-dummy study assessing the superiority of rituximab compared with cyclophosphamide, conducted in rheumatology or interstitial lung disease units at 11 UK centres. The study recruited individuals with extensive and/or progressive connective tissue disease-associated interstitial lung disease, excluding those with significant comorbidities, including airflow obstruction. Participants were randomised 1 : 1 to receive either rituximab 1 g given intravenously, twice at an interval of 2 weeks, or intravenous cyclophosphamide given monthly for 6 months at a dose of 600 mg/m2 body surface area. The primary end point for the study was the change in forced vital capacity at 24 weeks. Secondary end points included safety and tolerability, corticosteroid exposure, forced vital capacity change at 48 weeks and patient-reported quality of life. A cost-effectiveness analysis was undertaken to assess the impact of rituximab use in the United Kingdom National Health Service. Results One hundred and one subjects (70 females) with a mean age of 56.3 years were randomised; 51 to rituximab and 50 to cyclophosphamide. Ninety-seven were included in the modified intention-to-treat population for the primary and secondary efficacy analyses (49 in the rituximab group and 48 in the cyclophosphamide group). 38.6% had scleroderma, 44.6% idiopathic inflammatory myositis and 16.8% mixed connective tissue disease. Four subjects withdrew prior to the first dose of therapy (two in each arm). At 24 weeks, both rituximab and cyclophosphamide improved forced vital capacity from baseline [(mean ± standard deviation) 97 ± 234 and 99 ± 329 ml, respectively]. Using an adjusted mixed-effects model corrected for diagnosis and baseline forced vital capacity the difference in forced vital capacity at 24 weeks between rituximab and cyclophosphamide was −40 ml (95% CI −153 to 74 ml), p = 0.49. Other physiological and quality-of-life parameters improved in both arms following treatment but were not statistically significantly different between groups. Numerically fewer adverse events were reported by subjects receiving rituximab. Corticosteroid exposure over the 48 weeks of the trial was numerically less in the rituximab arm [13,291 (±14,657) mg of hydrocortisone equivalent per subject in the cyclophosphamide arm versus 11,469 (±10,041) mg per subject in the rituximab group; these differences did not reach statistical significance]. Limitations of the study include a disproportionate number of subjects being recruited from a single centre and insufficient subjects in each subgroup to determine whether there were treatment differences between individual connective tissue diseases. Based on the results of the trial, from a UK healthcare payer perspective, rituximab is more cost-effective than cyclophosphamide as a treatment for severe or progressive connective tissue disease-interstitial lung disease. Conclusions Rituximab improved forced vital capacity and patient-reported quality of life at 24 weeks but was not superior to cyclophosphamide. Rituximab should be considered as a therapeutic alternative to cyclophosphamide in individuals with connective tissue disease-associated interstitial lung disease requiring systemic therapy. Future work should explore the role of repeated dosing of rituximab and the use of rituximab earlier in the course of connective tissue disease-associated interstitial lung disease. Trial registration This trial is registered as ISRCTN16474148. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 11/116/03) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 4. See the NIHR Funding and Awards website for further award information.

Quantifying the Impact of Avian Influenza on the Northern Gannet Colony of Bass Rock Using Ultra-High-Resolution Drone Imagery and Deep Learning

Drones are an increasingly popular choice for wildlife surveys due to their versatility, quick response capabilities, and ability to access remote areas while covering large regions. A novel application presented here is to combine drone imagery with neural networks to assess mortality within a bird colony. Since 2021, Highly Pathogenic Avian Influenza (HPAI) has caused significant bird mortality in the UK, mainly affecting aquatic bird species. The world’s largest northern gannet colony on Scotland’s Bass Rock experienced substantial losses in 2022 due to the outbreak. To assess the impact, RGB imagery of Bass Rock was acquired in both 2022 and 2023 by deploying a drone over the island for the first time. A deep learning neural network was subsequently applied to the data to automatically detect and count live and dead gannets, providing population estimates for both years. The model was trained on the 2022 dataset and achieved a mean average precision (mAP) of 37%. Application of the model predicted 18,220 live and 3761 dead gannets for 2022, consistent with NatureScot’s manual count of 21,277 live and 5035 dead gannets. For 2023, the model predicted 48,455 live and 43 dead gannets, and the manual count carried out by the Scottish Seabird Centre and UK Centre for Ecology and Hydrology (UKCEH) of the same area gave 51,428 live and 23 dead gannets. This marks a promising start to the colony’s recovery with a population increase of 166% determined by the model. The results presented here are the first known application of deep learning to detect dead birds from drone imagery, showcasing the methodology’s swift and adaptable nature to not only provide ongoing monitoring of seabird colonies and other wildlife species but also to conduct mortality assessments. As such, it could prove to be a valuable tool for conservation purposes.

Glioblastoma and radiotherapy: A multicenter AI study for Survival Predictions from MRI (GRASP study).

The aim was to predict survival of glioblastoma at 8 months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. Retrospective and prospective data were collected from 206 consecutive glioblastoma, isocitrate dehydrogenase -wildtype patients diagnosed between March 2014 and February 2022 across 11 UK centers. Models were trained on 158 retrospective patients from 3 centers. Holdout test sets were retrospective (n = 19; internal validation), and prospective (n = 29; external validation from 8 distinct centers). Neural network branches for T2-weighted and contrast-enhanced T1-weighted inputs were concatenated to predict survival. A nonimaging branch (demographics/MGMT/treatment data) was also combined with the imaging model. We investigated the influence of individual MR sequences; nonimaging features; and weighted dense blocks pretrained for abnormality detection. The imaging model outperformed the nonimaging model in all test sets (area under the receiver-operating characteristic curve, AUC P = .038) and performed similarly to a combined imaging/nonimaging model (P > .05). Imaging, nonimaging, and combined models applied to amalgamated test sets gave AUCs of 0.93, 0.79, and 0.91. Initializing the imaging model with pretrained weights from 10 000s of brain MRIs improved performance considerably (amalgamated test sets without pretraining 0.64; P = .003). A deep learning model using MRI images after radiotherapy reliably and accurately determined survival of glioblastoma. The model serves as a prognostic biomarker identifying patients who will not survive beyond a typical course of adjuvant temozolomide, thereby stratifying patients into those who might require early second-line or clinical trial treatment.

P1145 Assessing disease control in inflammatory bowel disease (IBD) – a real world cross-sectional study in the UK

Abstract Background There is a paucity of data on disease control in patients with inflammatory bowel disease (IBD) in clinical practice. The Proportion Of suboptimal Disease Control And Strategy of Treatment in IBD (PODCAST-IBD) multicentre, non-interventional study aimed to quantify real-world rates of disease control using the STRIDE-II recommendations, explore contributors to, and the economic burden of, suboptimal disease control. Methods Cross sectional assessment of patients with IBD attending routine clinic appointments was carried out in four UK centres between Oct 2022 and Jan 2023. Clinician-reported outcomes, patient-reported outcomes and retrospective data from medical chart review were used to assess IBD control against red flags aligned to the STRIDE-II recommendations (Table). Health care resource utilisation (HCRU) was calculated using NHS reference costs. Results Data was available from 198 patients (Crohn's disease [CD]: 103, ulcerative colitis [UC]: 95) and most were currently receiving long-term IBD-specific treatment (CD: 85%, UC: 78%). IBD was suboptimally controlled in 52.4% (54/103) of patients with CD and 45.3% (49/95) with UC. Impaired quality of life (QOL), defined as Short inflammatory bowel disease questionnaire (SIBDQ) score &amp;lt;50, was the most frequent contributor to suboptimal disease control for both UC and CD. Other frequent contributors were systemic steroid overuse, extraintestinal manifestations (EIM), failure to achieve clinical improvement and perianal disease (Figure). Suboptimal disease control has a detrimental impact on fatigue and disability, demonstrated by lower (indicating more fatigue) mean total FACIT-F score in suboptimally controlled disease (CD: 81.5 vs 125, UC: 87.4 vs 122.8) and IBD Disk, a 10-item self-questionnaire used to assess IBD-related disability. HCRU more than doubled in patients with suboptimal vs optimal control (CD: £4,746 vs £1,924; UC: £2,428 vs £1,121), driven by more hospital admissions and emergency room visits in patients with suboptimal disease control. Patients with suboptimal disease control had higher rates of work productivity loss than those with optimal control (CD: 41.7% vs 11.9%, UC: 38.0% vs 22.6%). Conclusion This UK cross-sectional study found that IBD was suboptimally controlled in around one-half of patients based on STRIDE-II recommendations. Of those with suboptimally controlled disease one-third had impaired QOL making it the most common contributor. Suboptimal control of IBD had a considerable economic impact; HCRU more than doubled and productivity fell. Physicians could consider regular QOL assessments to prompt timely disease monitoring to enable identification of early active disease and ensure appropriate treatment.

1877 Recruitment to a phase 3, RCT in Parkinson’s: strategies and association between participant characteristics and PI specialty

Abstract Introduction Falls are a common complication of Parkinson’s disease, driven in part by an underlying cholinergic deficit that contributes to gait and cognitive impairment. Phase 2 studies have established that amelioration of this deficit using cholinesterase inhibitors may reduce falls. Methods CHIEF-PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson's Disease) is a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease that recruited from NHS sites. Relationships between the Principal Investigators’ specialty and the participants baseline characteristics were evaluated using linear, logistic and ordinal logistic regression. Cognitive impairment was defined as MoCA ≤26, while falls in the prior 12 months were separated into ordinal quartiles (1-2, 3-5, 6-12, 13+). Results Recruitment to CHIEF-PD commenced in January 2020 and completed in April 2023. Recruitment increased up until the start of the pandemic and thereafter there were 2 peaks. Potential participants were identified through clinic lists, databases, via national and local media and charities. 600 participants were enrolled across 38 sites. Sites enrolled between 1 and 74 participants, each. The median recruitment rate was 19 participants per month (IQR 6-27). 14 (37%) sites had Principal Investigators that were neurologists and 24 (63%) sites had PIs that were geriatricians. Most participants (76%) were over the age of 65 years. Compared with neurologists, geriatricians recruited older patients (difference in means 2.08 (95% CI 0.68, 3.48); p=0.004), with similar levels of cognitive impairment (OR 1.20 (95% CI 0.85, 1.69); p=0.293) and a lower fall rate (OR 0.46 (95% CI 0.34, 0.62); p&amp;lt;0.001) at baseline. Conclusion Recruitment of older participants to a Clinical Trial of an Investigational Medicinal Product (CTIMP) trial throughout the Covid-19 pandemic across 38 UK centres was feasible using multiple strategies. Characteristics of participants varied according to the sub-speciality of the Principal Investigator at the site.

Role of routine investigations post cardiac devices implants in detecting peri-procedural complications: A retrospective analysis from a tertiary UK center.

Peri-procedural complications associated with cardiac implantable electronic devices are not uncommon. European Society of Cardiology guidelines recommend device checks of all devices within 72h of implant. European Heart Rhythm Association expert practical guide on Cardiac implantable electronic devices (CIEDs) recommend that a chest x-ray (CXR) should be performed within 24h to rule out pneumothorax and document lead positions. First, the rate of peri-procedural complications associated with CIED implants at our center, as well as patient and/or procedural-related factors that are associated with higher rates of complications, is analyzed. Second, the yield of the guideline-recommended measures in the early detection of peri-procedural complications is examined. Consecutive de novo transvenous device implants at our center in 2019 were retrospectively analyzed. Patients' demographics, types and indications for device therapy, procedural reports, device checks, and CXRs were obtained from the hospital electronic records. A total of 578 patients (Age 74±16 years, 68% male) were included. All patients had routine post-procedure CXRs and device checks. There were 16 (2.8%) complications; 7 (1.2%) pneumothoraxes, 6 (1%) pericardial effusions, and 3 (0.5%) lead displacements. Procedure time correlated significantly with complications; in uncomplicated cases it was 99±43 min versus 127±50 min in procedures associated with complications (p=.02). Routine post CIED implantation CXRs can detect early peri-procedural complications, while repeat post mobilization device checks has low yield of detection of complications. The only statistically significant predictor of peri-procedural complications is the duration of the procedure; longer procedures were associated with higher rates of complications.

Comparative effectiveness of standard vs. AI-assisted PET/CT reading workflow for pre-treatment lymphoma staging: a multi-institutional reader study evaluation.

Fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) is widely used for staging high-grade lymphoma, with the time to evaluate such studies varying depending on the complexity of the case. Integrating artificial intelligence (AI) within the reporting workflow has the potential to improve quality and efficiency. The aims of the present study were to evaluate the influence of an integrated research prototype segmentation tool implemented within diagnostic PET/CT reading software on the speed and quality of reporting with variable levels of experience, and to assess the effect of the AI-assisted workflow on reader confidence and whether this tool influenced reporting behaviour. Nine blinded reporters (three trainees, three junior consultants and three senior consultants) from three UK centres participated in a two-part reader study. A total of 15 lymphoma staging PET/CT scans were evaluated twice: first, using a standard PET/CT reporting workflow; then, after a 6-week gap, with AI assistance incorporating pre-segmentation of disease sites within the reading software. An even split of PET/CT segmentations with gold standard (GS), false-positive (FP) over-contour or false-negative (FN) under-contour were provided. The read duration was calculated using file logs, while the report quality was independently assessed by two radiologists with >15 years of experience. Confidence in AI assistance and identification of disease was assessed via online questionnaires for each case. There was a significant decrease in time between non-AI and AI-assisted reads (median 15.0 vs. 13.3 min, p < 0.001). Sub-analysis confirmed this was true for both junior (14.5 vs. 12.7 min, p = 0.03) and senior consultants (15.1 vs. 12.2 min, p = 0.03) but not for trainees (18.1 vs. 18.0 min, p = 0.2). There was no significant difference between report quality between reads. AI assistance provided a significant increase in confidence of disease identification (p < 0.001). This held true when splitting the data into FN, GS and FP. In 19/88 cases, participants did not identify either FP (31.8%) or FN (11.4%) segmentations. This was significantly greater for trainees (13/30, 43.3%) than for junior (3/28, 10.7%, p = 0.05) and senior consultants (3/30, 10.0%, p = 0.05). The study findings indicate that an AI-assisted workflow achieves comparable performance to humans, demonstrating a marginal enhancement in reporting speed. Less experienced readers were more influenced by segmentation errors. An AI-assisted PET/CT reading workflow has the potential to increase reporting efficiency without adversely affecting quality, which could reduce costs and report turnaround times. These preliminary findings need to be confirmed in larger studies.

Cost-Utility Analysis of Total Ankle Replacement Compared with Ankle Arthrodesis for Patients Aged 50-85 Years with End-Stage Ankle Osteoarthritis: The TARVA Study.

Patients with end-stage ankle osteoarthritis suffer from reduced mobility and quality of life and the main surgical treatments are total ankle replacement (TAR) and ankle fusion (AF). Our aim was to calculate the mean incremental cost per quality-adjusted life-year (QALY) of TAR compared with AF in patients with end-stage ankle osteoarthritis, over 52 weeks and over the patients' lifetime. We conducted a cost-utility analysis of 282 participants from 17 UK centres recruited to a randomised controlled trial (TARVA). QALYs were calculated using index values from EQ-5D-5L. Resource use information was collected from case report forms and self-completed questionnaires. Primary analysis was within-trial analysis from the National Health Service (NHS) and Personal Social Services (PSS) perspective, while secondary analyses were within-trial analysis from wider perspective and long-term economic modelling. Adjustments were made for baseline resource use and index values. Total cost at 52 weeks was higher in the TAR group compared with the AF group, from the NHS and PSS perspective (mean adjusted difference £2539, 95% confidence interval [CI] £1142, £3897). The difference became very small from the wider perspective (£155, 95% CI - £1947, £2331). There was no significant difference between TAR and AF in terms of QALYs (mean adjusted difference 0.02, 95% CI - 0.015, 0.05) at 52 weeks post-operation. The incremental cost-effectiveness ratio (ICER) was £131,999 per QALY gained 52 weeks post-operation. Long-term economic modelling resulted in an ICER of £4200 per QALY gained, and there is a 69% probability of TAR being cost effective at a cost-effectiveness threshold of £20,000 per QALY gained. TAR does not appear to be cost effective over AF 52 weeks post-operation. A decision model suggests that TAR can be cost effective over the patients' lifetime but there is a need for longer-term prospectively collected data. Clinical trial registration ISRCTN60672307 and ClinicalTrials.gov NCT02128555.