Lengthy waits for follow-up testing are common for people with suspected epilepsy. This delays diagnosis, prolongs uncertainty and increases seizure risk. Initial EEGs are frequently inconclusive, yet follow-ups are often dictated by referral date, and there is no established method for risk-based prioritisation. Here, we tested whether an established digital EEG biomarker could help prioritise those most likely to have epilepsy for expedited follow-up EEG testing. We analysed 196 normal non-contributory (non-diagnostic) initial EEGs collected from six National Health Service (NHS) sites in England. From these recordings, we extracted eight previously validated computational features that quantify the likelihood that the EEG was recorded from someone with active epilepsy. We then used this information to reorder follow-up lists and compared outcomes against standard referral-based scheduling. We found that ordering for follow-up testing based upon the digital biomarker consistently prioritised people subsequently diagnosed with epilepsy; for a waitlist of 40 patients, the median number of follow-up EEGs needed to see 50% of true epilepsy patients was decreased by 6 (95% CI 4-7). The EEG diagnostic yield for epilepsy of follow-ups was increased relative to orderings based on time of referral (median increase in yield for epilepsy at 50% follow-up EEGs was 5%; 95 CI 4.9%-10%). Our study indicates that a routine EEG may furnish an objective risk metric that could accelerate second-line investigations and so reduce diagnostic delay whilst improving resource allocation in clinical practice.
Abstract Background and aims Tenecteplase (TNK) has been shown to be at least non inferior to Alteplase (rtPA) in the emergency treatment in acute ischaemic stroke but real world data is limited in the UK. This study aims to explore the safety and effectiveness of TNK in routine practice over one year. Methods Data from the National Stroke Registry for England, Wales, And Northern Ireland (The Sentinel Stroke National Audit Programme: SSNAP) were analysed for patients with ischaemic stroke treated with TNK and rtPA between October 2024 and September 2025. Results Of 12919 patients who underwent thrombolysis, 8284 (64.1%) received TNK and 4635 (35.9%) received rtPA. There were no differences in NIHSS on arrival (TNK 8, IQR: 5-15 vs rtPA 9, IQR 5-15, P>0.05). Higher rates of patients treated with TNK were thrombolysed within an hour of arrival (60.4% vs 52.8%, P<0.05) with faster door to needle times (53, IQR: 38-76 minutes vs 59, IQR: 42-86 minutes, P<0.05). There were higher rates of patients receiving rtPA who underwent thrombectomy (5.8% vs 6.9%, P<0.05). There were no differences in symptomatic intracranial haemorrhage (TNK: 3.3% vs rtPA: 3.4%, P>0.05). There were no differences in patients independent at discharge (modifed Rankin Score 0-2; TNK 49% vs rtPA 48%, P>0.05) nor inpatient mortality (TNK 10.8% vs rTPA 10.4%, P> 0.05). Conclusions Real world data revealed faster process times with TNK as well as similar effectiveness and safety outcomes supporting the transition of TNK over rtPA as the first line thrombolytic agent. Conflict of interest Kaili Stanley: nothing to disclose; Kevin Vasquez: nothing to disclose; Ajay Bhalla: nothing to disclose; Martin James: I have received speaker fees from Boehringer Ingelheim, the manufacturer of alteplase and tenecteplase.
Background The purpose of this scoping review was to systematically review the published literature of randomized controlled trials (RCT) in rectal cancer to generate a comprehensive list of study outcomes. The secondary objectives of this study were to describe trends in outcome reporting in rectal cancer RCTs with a particular focus on patient-reported outcome measures (PROM). Methods We systematically searched for rectal cancer RCTs suing several electronic databases. Eligible studies needed to be published after the year 2000 and had to evaluate a locoregional or systemic therapy for non-metastatic rectal cancer as its primary exposure. All reported outcomes were extracted verbatim from the article and subsequently re-categorized into “standardized outcome terms” and within OMERACT Core Areas of health. Data regarding the use of patient-reported outcome measures and the choice of primary outcome were also extracted. Results In total, 89 RCT’s were included: 56 (62.9%) were considered neoadjuvant trials, 24 (27.0) surgical trials, and 9 (10.1%) adjuvant trials. Fifty-three standardized outcome terms were identified and grouped into various domains and Core Areas. The primary outcomes utilized in each RCT were highly variable and differed by study type. In total, 37 (41.6%) trials used one or more patient-reported outcome measure as an outcome, mainly consisting of health-related quality of life. There were no significant trends in outcome reporting by year or author specialty. Conclusions A comprehensive list of study outcomes categorized into several domains and Core Areas was generated.
Introduction With the rapidly changing landscape of rectal cancer treatment, it is becoming increasingly challenging for clinicians to interpret and synthesise the vast amount of high-quality evidence being generated. A core outcome set (COS) for clinical trials in rectal cancer would help address issues surrounding outcome selection and reporting. The purpose of this research project is to develop a COS to be used in research comparing different treatment paradigms in the management of rectal cancer.Methods and analysis This will be a mixed-methods project, including a systematic review, semi-structured interviews and a Delphi consensus process. The project was designed in accordance with the COMET (Core Outcome Measures in Effectiveness Trials) Handbook, which provides a framework for COS development based on existing evidence. A multidisciplinary Study Advisory Group, composed of rectal cancer providers, methodologists and patients, will oversee the project. A systematic review will be performed to identify an inclusive list of outcomes reported by researchers in previous rectal cancer trials. Outcomes will be collapsed into various core areas and domains according to the OMERACT Filter V.2.0. Semi-structured interviews with rectal cancer survivors and their partners/caregivers will help identify additional patient-centric outcomes not captured in the systematic review. Finally, after a final list of outcomes is generated, patients and healthcare professionals will be invited to participate in a Delphi process to develop the final COS.Ethics and dissemination The study has received full approval with the Research Ethics Committee at the Integrated Health and Social Services Network for West-Central Montreal (health network responsible for the Jewish General Hospital) (REC: 2025-4377) and the Institutional Review Board of the Mount Sinai School of Medicine (IRB: STUDY-25-00515). The results of this study will be presented at national and international meetings and a manuscript will be submitted for publication in a high-impact surgery and/or oncology peer-reviewed journal.Trial registration number The study was registered in the COMET database in December 2023 (https://www.comet-initiative.org/Studies/Details/2941). The full systematic review protocol, along with the search strategy and inclusion/exclusion criteria, was registered online in September 2023 (researchregistry.com; reviewregistry1705).
Abstract Inflammatory bowel diseases (IBD), principally Crohn’s disease (CD) and ulcerative colitis (UC), are common chronic disorders involving inflammation and often progressive tissue damage. Genome-wide association studies have mapped many risk signals, but the causal variants, effector genes and relevant cellular contexts remain difficult to resolve, limiting mechanistic interpretation and therapeutic translation. Here we performed a multi-ancestry GWAS meta-analysis of 125,992 individuals with IBD and more than 1.2 million controls, identifying 619 independent association signals (374 novel) at 420 IBD regions that account for 77–80% of SNP-based heritability. Fine-mapping resolved 81 high-confidence variants, 41 not previously reported. Although most signals were shared between CD and UC, 39% showed IBD subtype specificity, with UC signals showing stronger enrichment in functional annotations from intestinal epithelial, secretory and enteroendocrine cells, and CD showing stronger genetic correlations with circulating inflammatory biomarkers, including C-reactive protein and glycoprotein acetylation. Latent causal modelling supported a causal effect of decreased high-density lipoprotein on CD risk. By integrating bulk and single-cell eQTL and pQTL resources using colocalisation and Mendelian randomisation, together with coding-variant evidence from exome sequencing, we prioritised 664 candidate effector genes across 341 signals, including 390 newly implicated IBD genes, revealing new biological mechanisms and candidate therapeutic targets supported by human genetics.
