Leonora Fisniku

Introduction Continuing medical education (CME) is essential for more than 100 million healthcare professionals worldwide, supporting enhancement of knowledge, skills, and patient outcomes. With a growing shift towards online and blended CME formats, expert-informed AI-based training (EIAT) is a novel e-training approach enabling rapid course creation and a timely content updates. However, its effectiveness remains underexplored. Methods A within-subject pre-post study was conducted with 17 medical students and professionals . Participants first completed a self-paced EIAT module, followed by live expert-led training (LET). Knowledge acquisition was measured via pre- and post-exams for each modality. Satisfaction, engagement, learning outcomes, and content quality were assessed using a 20-item CME-relevant feedback tool aligned with European Accreditation Council for CME standards. Paired t-test and McNemar’s tests were used to compare outcomes between the two training formats. Results EIAT completion was 76%, compared to 82% for LET. Pre-test scores were lower in LET (63 ± 11.4) than EIAT (73.8 ± 11.2), though not significantly different (p = 0.14). Mean knowledge gain was 17.3 ± 13.3 for EIAT (p = 0.0005) and 29.2 ± 13.2 for LET (p = 0.003), with no significant difference between modalities (mean difference 14.2 ± 21.5, p = 0.17) or in post-test scores (93.5 ± 5.5 vs. 93.3 ± 9.3, p = 0.79). Both formats achieved high satisfaction, with mean recommendation scores of 9.7 (SD = 0.67) for EIAT and 10 (SD = 0.0) for LET, respectively, and no significant differences across most evaluation domains (p > 0.05). Engagement was strong in both groups, though 71.4% of LET participants reported being ‘enthusiastically involved’ compared to 60% in EIAT, and 85.8% of LET participants gaining substantial practical knowledge versus 50% for EIAT (p = 0.08). Both formats were rated highly in terms of fairness, content quality, and absence of commercial bias. Conclusion: This pilot study provides preliminiary evidence that expert-informed AI is an effective alternative or complement to traditional live CME format. These findings offer further research into EIAT’s role in scalable, high-quality CME for healthcare professionals, laying the groundwork for future research and broader implementation.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS. Methods and analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0–6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years. Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate. The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression. Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur. Ethics and dissemination: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration numbers: NCT03387670 ; ISRCTN82598726 .

Background Adverse events are inevitable for many pharmacological interventions, including disease modifying treatment (DMT) in Multiple Sclerosis (MS). Amenorrhoea was reported in less than 2% in phase 3 trials of Natalizumab. Isolated cases have also been reported post marketing.We present a patient who developed secondary amenorrhoea linked to Natalizumab treatment for her relapsing-remitting MS (RRMS). Case A 36 year old female with highly-active RRMS was started on Natalizumab in June 2014. She developed secondary amenorrhoea by July 2014. Her blood results show low LH, normal FSH and low oestrogen and progesterone and normal thyroid function tests. She remained on Natalizumab for a year and her MS was stable. Due to continuing amenorrhoea Natalizumab was stopped and 3 months later she started menstruating regularly. Her hormonal changes were also normalised. Review of all her imaging from July 2014 – September 2016 revealed no evidence of a pituitary or hypothalamic abnormality or patho- logical enhancement. Patient was subsequently treated with Alemtuzumab and has remained stable. Conclusion Whereas a simple temporal association between a drug use and a particular event does not necessarily indicate a direct causal relationship, the occurrence of amenorrhoea in our patient linked to the start of Natalizumab and its resolution 3 months post treatment cessation, is too good of a coincidence to be fully dismissed. leonora.fisniku@nhs.net

Background andAim: Fingolimod, an oral immunomodulating drug is used in the management of relaps- ing-remitting MS (RRMS)-patients. Fingolimod-related macular oedema is reported in 0.4% of cases. Whereas pre-treatment optical coherence tomography (OCT) was used in the pivotal trials, the licensing of Fingolimod did not require this. We sought to assess the rate of abnormal pre-treatment OCTs in the patients treated with Fingolimod at Brighton and Sussex University Hospital (BSUH).Methods: We reviewed the OCTs of all RRMS-patients screened at BSUH prior to being started on Fingoli- mod from November 2013-September 2019. Patients screened elsewhere, were not included.Results: 135 patients were screened. 21(15%) were males; mean age 39 (range 25–74). Macular-OCT was normal in 133/135(98.5%) patients; in one patient a tiny cyst but no frank edema was noted; no post Fin- golimod macular oedema was noted; subretinal fluid was noted in another patient; this patient did not tolerate Fingolimod. No macular eodema was observed in any of the patients started on Fingolimod.Conclusions: Our data suggest the routine use of OCT as part of Fingolimod pre-screening is not justified. Rationalizating pre-screening investigations prior to starting disease-modifying-therapies, could avoid unnecessary delay in starting such treatments and provide better use of the resources. This data re- enforces the need for reviewing and auditing our protocols and guidelines.leonora.fisniku@nhs.net

Background and aims Infusion-associated-reactions (IARs) are a common side effect (SE) of Ocrelizumab, a disease modifying therapy (DMT) licensed for treatment of Multiple Sclerosis (MS). Tolerability is an important factor patients take into account when selecting a DMT. We sought to assess the frequency of IARs in the Ocrelizumab-treated MS-patients at Brighton & Sussex University Hospitals MS-Centre. Methods All Ocrelizumab-treated MS-patients data from February 2019 to January 2020 was reviewed. IARs classified as mild, moderate, severe and life-threatening as per Ocrelizumab proforma, during and 1-hour post infusion were recorded. Patients were advised to contact the infusion nurses if they experi- enced further symptoms in the next 24-hours post infusion. Results 28-patients received Ocrelizumab: 20(71%) females; mean age 41.7 years old (range 25–58); median EDSS 2 (range 0–6). 12(42.8%) patients had received no prior DMTs. 23(82.1) patients reported either nil or mild IARs; 7(25%) patients had mild IAR. 2(7.1%) patients had moderate IAR; 2(7.1%) patients had severe IAR, 1(3.6%) patient experiencing throat pain, swelling, rhinorrhoea and dyspnoea. 1(3.6%) patient experienced significant raised liver enzymes; 1(3.6%) patient had acute respiratory distress syndrome requiring treatment discontinuation. Conclusion Our data suggest that Ocrelizumab is generally well tolerated, however caution should be exercised and patient should be monitored closely especially in the initial infusion. Real world data provides useful information to share with patients when they are consented. leonora.fisniku@nhs.net