Evaluating the feasibility of a real world pharmacovigilance study (OPTIMISE:MS).

BACKGROUND: Clinical trial populations do not fully reflect routine practice. The power of routinely collected data to inform clinical practice is increasingly recognised. METHODS: The OPTIMISE:MS pharmacovigilance study is a prospective, pragmatic observational study, conducted across 13 UK MS centres. Data were collected at the time of routine clinical visits. The first participant was recruited on 24th May 2019; data were extracted on 11th November 2021. RESULTS: 2112 participants were included (median age 44.0 years; 1570 (72%) female; 1981 (94%) relapsing-remitting MS). 639 (30%) were untreated at study entry, 205 (10%) taking interferon beta/copaxone, 1004 (47%) second/third generation DMT first line and 264 (13%) had escalated from a platform DMT. 342 clinical events were reported, of which 108 infections. There was an increased risk of adverse events in people taking second/third generation DMT (RR 3.45, 95%CI 1.57-7.60, p<0.01 vs no DMT). Unadjusted Poisson regression demonstrated increased incident adverse events in people taking natalizumab (IRR 5.28, 95%CI 1.41-19.74, p<0.05), ocrelizumab (IRR 3.24, 95%CI 1.22-8.62, p<0.05), and GA biosimilar (Brabio) (IRR 4.89, 95%CI 1.31-18.21, p<0.05) vs no DMT. CONCLUSIONS: Routinely collected healthcare data can be used to evaluate DMT safety in people with MS. These data highlight the potential of pragmatic studies to guide understanding of risks and benefits associated with DMT.

Assessment of Potential Risk Factors for the Development of Persistent Postural-Perceptual Dizziness: A Case-Control Pilot Study.

Objectives: (1) To assess whether neuroticism, state anxiety, and body vigilance are higher in patients with persistent postural-perceptual dizziness (PPPD) compared to a recovered vestibular patient group and a non-dizzy patient group; (2) To gather pilot data on illness perceptions of patients with PPPD. Materials and Methods: 15 cases with PPPD and two control groups: (1) recovered vestibular patients (n = 12) and (2) non-dizzy patients (no previous vestibular insult, n = 12). Main outcome measures: Scores from the Big Five Inventory (BFI) of personality traits, Generalized Anxiety Disorder - 7 (GAD-7) scale, Body Vigilance Scale (BVS), Dizziness Handicap Inventory (DHI), modified Vertigo Symptom Scale (VSS) and Brief Illness Perception Questionnaire (BIPQ). Results: Compared to non-dizzy patients, PPPD cases had higher neuroticism (p = 0.02), higher introversion (p = 0.008), lower conscientiousness (p = 0.03) and higher anxiety (p = 0.02). There were no differences between PPPD cases and recovered vestibular patients in BFI and GAD-7. PPPD cases had higher body vigilance to dizziness than both control groups and their illness perceptions indicated higher levels of threat than recovered vestibular patients. Conclusion: PPPD patients showed statistically significant differences to non-dizzy patients, but not recovered vestibular controls in areas such as neuroticism and anxiety. Body vigilance was increased in PPPD patients when compared with both recovered vestibular and non-dizzy patient groups. PPPD patients also exhibited elements of negative illness perception suggesting that this may be the key element driving the development of PPPD. Large scale studies focusing on this area in the early stages following vestibular insult are needed.

Technical note: can resting state functional MRI assist in routine clinical diagnosis?

Despite some differences in clinical presentation, it is often difficult to differentiate between dementia with Lewy bodies (DLB), clinical Alzheimer's dementia (AD) and Parkinson's disease dementia. However, differentiation can be crucial, especially as patients with DLB characteristically have a hypersensitivity to most antiemetic and neuroleptic drugs as they affect the cholinergic and dopaminergic system, potentially leading to life-threatening catatonia, loss of cognitive function and muscle rigidity. The aim of this study is to evaluate if resting state (RS) functional MRI (fMRI) can be used in routine practice on a 1.5 T scanner to differentiate between AD and DLB on an individual basis. We age- and gender-matched a known DLB patient with an AD patient and a human control (HC). Individual independent component analysis was carried out. Region of interest seeds were chosen from the midcingulate and insula regions. Functional connectivity from insula to midcingulate and within the midcingulate network (part of the Salience network) was lower in DLB than AD or HC. RS-fMRI on a 1.5 T scanner, in a routine clinical setting, detected abnormal functional connectivity patterns and allowed differentiation of DLB and AD in a routine clinical setting. This is the first evaluation of RS-fMRI in a routine clinical setting. It shows that incorporating RS-fMRI into the clinical scanning protocol can assist in early diagnosis and likely assist in monitoring the natural history of the disease or disease modifying treatments.