bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoid-X receptor agonism promotes remyelination in relapsing-remitting multiple sclerosis: a phase 2 clinical trial
Authors: L Brown J William , Cunniffe Nicholas G , Prados Ferran , Kanber Baris , Connick Peter , lin Robin Frank- , Chandran Siddharthan , Altmann Daniel , Chard Declan T , Coles Alasdair J 
Published: May 2022

BackgroundIn rodents, retinoid acid X receptor [RXR]-gamma agonists promote CNS remyelination.MethodsIn this double-blind phase 2a trial, participants with relapsing remitting multiple sclerosis (RRMS), stable on dimethyl fumarate, were randomised to bexarotene 300mg/m2 (a non-specific RXR agonist) or placebo for 6 months. The primary efficacy outcome was change in mean lesional magnetisation transfer ratio (MTR) for lesions below the within-patient median MTR. The secondary efficacy outcome was change in visual evoked potential (VEP) latency in eyes with electrophysiological evidence of optic neuropathy.Results52 patients were randomised to bexarotene or placebo. All bexarotene patients experienced adverse effects, notably central hypothyroidism (26 [100%]), hypertriglyceridaemia (24 [92%]), rash (13 [50%]) and neutropenia (10 [38%]). Two discontinued placebo and five discontinued bexarotene through adverse events.The primary efficacy outcome was negative (mean submedian lesion MTR change 0.25pu (bexarotene) vs 0.09pu (placebo), p=0.54), but significant effects were seen in grey matter lesions (p=0.008). Bexarotene reduced VEP latency in those with optic neuropathy (group difference 4·66 ms/eye, p=0·014).ConclusionsDespite a negative primary outcome, we found imaging and electrophysiological evidence of remyelination following RXR agonism in people with RRMS. Bexarotene’s safety profile precludes it’s use, but these data support selective RXR-gamma agonist development.william.brown@doctors.org.uk
Advanced blood and neuroimaging biomarkers of axonal injury after TBI in the prospective multi-centre BIO-AX-TBI study
Authors: Graham Neil , Zimmerman Karl , Moro Federico , Gradisek Primoz , Magnoni Sandra , Oddo Mauro , Zetterberg Henrik , Bertolini Guido , Sharp David ,   et al
Published: May 2022

BackgroundOutcomes after traumatic brain injury (TBI) are variable and frequently poor. Axonal injury is considered a significant determinant of outcome, which may be quantified using novel fluid biomark- ers and advanced MRI.MethodsBIO-AX-TBI is a multi-centre cohort study of acute moderate-severe TBI. Patients underwent clinical and blood biomarker/MRI assessment over one year. Blood levels of neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), total tau and S100B were quantified, with cerebral microdialysis facilitating measures in brain extracellular fluid.Results197 patients were assessed post-TBI. Compared with controls, TBI patients had significant acute elevations in GFAP, S100B, tau and UCH-L1, with NfL peaking subacutely and remaining elevated. NfL in plasma and brain interstitial fluid were highly correlated in the microdialysis subgroup. Diffusion tensor imaging (DTI) showed reduced fractional anisotropy, remaining chronically abnormal post-injury. Early cortical atrophy was predicted by acute plasma tau and chronic white matter atrophy was predicted by NfL. Clinical outcomes were accurately predicted by acute blood biomarker levels and DTI MRI.ConclusionsNeuronal/glial markers in blood provided a reliable readout of TBI severity and predicted clinical outcomes. NfL and DTI MRI were highly sensitive to white matter injury and predicted chronic atrophy.neil.graham@imperial.ac.uk
059  Switching CGRP monoclonal antibodies for chronic migraine: real-world outcomes of 37 episodes
Authors: Weatherall Mark , Matharu Manjit 
Published: May 2022

CGRP monoclonal antibodies (mAbs) have been shown in clinical trials to be effective therapies for episodic and chronic migraine. Three CGRP mAbs are licensed for use in the UK: erenumab, freman- ezumab, and galcanezumab. The overall efficacy of these three drugs is similar in published trials, but no head-to-head comparisons have been undertaken. Very little real world data on this question has been published. It is unknown, therefore, whether some patients may respond better to one member of this novel class of migraine therapeutics than others.The authors conducted a retrospective review of patients prescribed CGRP mAbs between 2018–2020, identifying 37 occasions on which a patient was switched from one CGRP mAb to another. In 24 cases, the switch was made because of lack of efficacy; in 13 cases, the switch was made because of side effects, cost, or other logistical factors.Where the switch was made because of lack of efficacy, 11/24 patients found the second CGRP mAb effective in significantly reducing the frequency of migraine days; in all but two of these cases patients moved from chronic migraine to episodic migraine. Where a switch was made for reasons other than efficacy, all patients found both CGRP mAbs were effective.In conclusion, patients with chronic migraine who fail to respond to, or do not tolerate, a first CGRP mAb should be offered treatment with another member of the class.mark.weatherall1@nhs.net
070  A pilot study assessing choroidal thickness in frontotemporal dementia and motor neuron disease
Authors: Chen Yingdi , Larraz Juan , Wong Michael , Pearson Tom , Kalam Sabrina , Glasmacher Stella , Davenport Richard , Newton Judy , Pal Suvankar ,   et al
Published: May 2022

BackgroundFrontotemporal dementia and motor neurone disease are neurodegenerative disorders known to occur on a clinical continuum and to share underlying genetic and neuropathological char- acteristics. Retinal choroidal thickness (RCT) has been reported as a marker for inflammatory diseases. By comparing RCT between these disorders, this study aims to investigate the value of RCT in subclinical inflammation.MethodsSpectral domain optic coherence tomography (SD-OCT) images were analysed to evaluate RCT in 38 people with FTD(pwFTD) (median age 65(9)), 29 with MND (pwMND) (median age 66(15)) and 31 healthy controls (median age 54(20)). The regression of RCT with age was compared amongst the three groups.Results1) Accelerated choroidal thinning was found in pwMND in all choroidal locations, but only identified in the sub-fovea area of the pwFTD group. 2) Compared to age matched pwMND and healthy controls, choroidal thickness was significantly lower in the temporal region of pwFTD patient aged under 65 year.ConclusionThis study demonstrates an increase in rate of choroidal thinning in MND and FTD. Measurement of RCT using OCT may be a useful non-invasive surrogate biomarker to monitor subclinical inflammation and has potential for use as a secondary outcome measure in clinical trials of disease modifying treatments.ychen112@ed.ac.uk60
085  Ten year follow-up surveillance of paediatric acquired demyelinating syndromes (ADS) in the UK
Authors: Abdel-Mannan Omar , Absoud Michael , Benetou Christina , Hickson Helga , Chong WK , Hemingway Cheryl , Lim Ming , Wright Sukhvir , Hacohen Yael ,   et al
Published: May 2022

ObjectiveTo describe 10-year follow-up of children <16 years with acquired demyelinating syndromes (ADS) from a UK-wide prospective surveillance study.MethodsDiagnoses were retrieved from the patients’ records via the patients’ paediatric or adult neurolo- gist using a questionnaire. Demyelinating phenotypes, at follow-up, were classified by expert review panel.Results24/125 (19.2%) children, identified in the original study, were diagnosed with multiple sclerosis (MS, incidence of 2.04/million children/year); 23/24 fulfilled 2017 McDonald criteria at onset. AQP4-Ab neuromy- elitis optica spectrum disorders were diagnosed in 2/125 (1.6%, 0.26/million children/year), and relapsing MOG-Ab associated disease in 5/125 (4%, 0.43/million children/year). 4/125 seronegative non-MS patients relapsed and 85/125 (68%) remained monophasic over 10 years. 5/125 (4%) originally diagnosed with ADS were reclassified during follow-up: three children diagnosed initially with acute disseminated encepha- lomyelitis were subsequently diagnosed with acute necrotising encephalopathy (RANBP2 mutation), primary hemophagocytic lymphohistiocytosis (Munc 13–4 gene inversion) and anti-NMDA-R encephalitis. One child initially diagnosed with optic neuritis was later diagnosed with vitamin B12 deficiency, and one presenting with transverse myelitis was subsequently diagnosed with Sjögren’s syndrome.ConclusionsThe majority of ADS presentations in children are monophasic even at 10-year follow. Given the implications for treatment strategies, MS and CNS autoantibody mimics warrant extensive investigations.o.abdel-mannan@ucl.ac.uk|NIHR Bursary
089  COVID-19 vaccinations in multiple sclerosis: UK MS register participant survey
Authors: Huang Yun , Baheerathan Aravindhan , Middleton Rodden , Rodgers William , Dalton Katherine Tuite , Nicholas Richard ,   MS Register Research Group
Published: May 2022

IntroductionGlobal efforts in vaccine development against SARS-CoV-2 saw the Pfizer-BioNTech vaccine approved for use in the United Kingdom (UK) on 2nd December 2020. There have long been discussions around vaccination in patients with multiple sclerosis (pwMS). We conducted a patient survey as part of the UK MS Register (UKMSR), to understand pwMS views on COVID vaccination.MethodPwMS were invited by email to complete a COVID-19 vaccine online questionnaire as part of the UKMSR on 7th December 2020.ResultsA total of 3092 pwMS completed the survey by 7th January 2021. 69.1% of patients indicated they are definitely going to get a COVID-19 vaccine, 16.1% probably, 9.1% possibly, 3.4% probably not and 2.3% definitely not. Factors examined includes gender, age, highest educational attainment and type of MS. Additionally, we explored whether previous experiences of vaccinations affected attitudes towards COVID vaccination. The top reasons for not taking a COVID vaccine included safety concerns and insufficient information.ConclusionThis UKMSR patient survey showed 85.2% of pwMS intend to get vaccinated against SARS- CoV-2, which is higher than the UK general public of 67% (1). More information on vaccine safety in pwMS would be helpful in making informed decisions.ReferencesYouGov Research: How many Britons are willing to take a coronavirus vaccine? 11–12 November 2020yun.huang@nhs.net
110  UK multiple sclerosis service audit of 70 centres: MS-MDTs
Authors: Rog David , Hobart Jeremy , Mathews Joela ,   Raising the Bar 4 MS UK MS Study Group
Published: May 2022

IntroductionThe UK MS service audit builds upon GIRFT’s recommendation for disease-specific data. Here, we address MS-specific Multidisciplinary Team (MS-MDT) meetings, an NHSE requirement for services prescribing disease modifying treatments (DMTs), although the wider MS-MDT parameters are less clear.AimTo document the characteristics and variability in UK MS-MDTs.MethodsWe asked all MS services to complete service questionnaires, supplemented with individual clinician interviews. Specifically, we asked about occurrence, frequency, who attends, and numbers and types of patients discussed at, MS-MDTs.ResultsForty-six of the 70 centres (68%) had an MS-MDT, 63% were weekly. Neuroradiologists attended only 49%, MS Coordinators 79% and Neuropharmacists 50%, of meetings. Neurology SpRs (73%) and Research Registrars (62%), attended the majority of MS-MDTs. A mean of 9 patients (range 1–40, SD 7) were discussed, predominantly complex patients and/or those considered for high efficacy DMTs.ConclusionsThere was considerable variation in the occurrence, frequency, composition and types of patients discussed at UK MS MDTs. Neuroradiologists absence is concerning, given the central role of MRI in MS clinical decision-making. Neuropharmacists and MS coordinators absence, limits the wider benefits from MS Team members. The MS-MDT is a regular touch point and a significant educational opportunity for the whole team, including trainees. We recommend that the UK MS community defines the param- eters of an MS-MDT so that these can be consistently implemented, through job-planning, across services.davidrog@srft.nhs.uk80
115  Impact of siponimod on myelination across SPMS subgroups: post-hoc analysis from EXPAND MRI substudy
Authors: Arnold DL , Bar-Or A , Cree BAC , Giovannoni G , Gold R , Vermersch P , Piani-Meier D , Arnould S , Kappos L ,   et al
Published: May 2022

BackgroundChanges in magnetization transfer ratio (MTR) are a marker of changes in myelin density and brain tissue integrity. Siponimod improved lesional MTR recovery in the overall EXPAND secondary progressive multiple sclerosis (SPMS) population.ObjectivesInvestigate the effect of siponimod on MTR changes in SPMS subgroups.MethodsThis prospective sub-study assessed the effect of siponimod versus placebo on median nor- malized MTR (nMTR) in normal appearing brain tissue (NABT), cortical Grey Matter (cGM) and normal appearing white matter (NAWM). Subgroups were defined by: disease history, severity and duration, EDSS score, Symbol Digit Modalities Test score, and inflammatory disease activity.ResultsThere was an attenuation in median nMTR decrease versus placebo across all subgroups (all p<0.05 except EDSS≥6 subgroup, p=0.064). In the active SPMS subgroup, siponimod attenuated median nMTR decrease across NABT, cGM and NAWM by 91–109% (p<0.01 all); and in the non-active SPMS subgroup by 170– 198% (p=0.0151 for NAWM, p>0.05 for NABT, cGM).ConclusionsOver 24 months, siponimod attenuated the decrease in median nMTR in brain tissues across patient subgroups characterized by disease activity and severity, with most pronounced effects in NAWM. This supports preclinical studies, showing beneficial CNS effects on myelination.teresa.sawtell@novartis.com
118  Sustained reduction of disability and cognitive decline with long-term siponimod in EXPAND active SPMS patients
Authors: Giovannoni G , Kappos L , Fox RJ , Vermersch P , Cree BAC , Benedict RHB , Bar-Or A , Piani-Meier D , Ritter S ,   et al
Published: May 2022

BackgroundIn the EXPAND study, patients with active SPMS (aSPMS) demonstrated a reduced risk of 3/6-month confirmed disability progression (3m/6m CDP) and risk of decline in cognitive processing speed (CPS, 6-month confirmed cognition worsening of ≥4-point on Symbol Digit Modalities Test [6mCCW]) versus placebo.ObjectivesAssess long-term efficacy and safety of siponimod in patients with aSPMS.MethodsIn aSPMS patients who entered the EXPAND Extension, time to 3m/6mCDP, 6mCCW, and annu- alized relapse rate (ARR) were assessed for the Continuous (siponimod in Core and Extension) and Switch (placebo in Core and open-label siponimod in Core/Extension) groups.ResultsRisk of 6mCDP was reduced by 29% (0.71 [0.57–0.90]; p=0.0044) for Continuous versus Switch group, corresponding to approximately 70% delay in time to 6mCDP. The risk of 6mCCW for Continuous versus Switch group was reduced by 33% (0.67 [0.53–0.86]); p=0.0018), corresponding to approximately 70% delay in time to 6mCCW. A significant reduction in ARR for the Continuous versus Switch groups was observed in patients with or without active disease.ConclusionsLong-term data analyses showed that siponimod effects on disability, cognitive processing speed, and relapse outcomes in patients with active SPMS are sustained up to 5 years, and highlight the value of early treatment initiation.teresa.sawtell@novartis.com
025  Baseline data from OPTIMISE: MS – a prospective, real word pharmacovigilance study in MS
Authors: Dobson Ruth , Craner Matthew , Waddingham Ed , Cavey Ana , Miller Aleisha , Matthews Paul M ,   on behalf of all OPTIMISE:MS investigators
Published: May 2022

BackgroundTherapeutic options in MS have increased rapidly, but real-world safety data is limited. Safety signals have emerged from clinical trials and early clinical experience with newer MS therapies, however the rates at which these occur in a real-world, UK MS population is unknown.MethodsOPTIMISE: MS is a longitudinal observational study that will recruit at least 4000 people with MS eligible for DMT from centres across the UK. It will follow them up for at least 5 years in the first instance using electronic case records. Serious adverse events (SAEs), DMT use and disease outcomes will be captured. The study design has been informed by rheumatological biologic registries and is anticipated to expand in scope, as participants consent to be re-contacted regarding sub-studies.ResultsSince its initiation in June 2019, 906 people with MS have enrolled. 72% are female (mean age44.5 (SD 11.1); mean disease duration 8.9 years (SD 7.3)) 95% study population have RRMS and 35% were receiving DMT prior to consent. Data from a larger cohort will be presented.ConclusionsThis study has the potential to deliver clinically meaningful data on the association of MS DMT with serious adverse events in a real-world population. The association of SAEs with lymphopaenia, and prior DMT/DMT switching will be studied. Rates of malignancies will be examined with particular reference to immunosuppressive therapies.ruth.dobson@qmul.ac.uk
051  The capture of a UK minimum data set for MS
Authors: Nicholas Richard , Craig Elaine , Middleton Rod , Ford David , Tuite-Dalton Katie ,   UK MS Register Group
Published: May 2022

BackgroundThe UK Multiple Sclerosis Register (UKMSR) was established in 2011 to capture ‘real world’ data from people with MS (pwMS) and the NHS. Capturing clinical data from the NHS for research is time consuming for clinical staff, can involve complicated governance, security and data quality issues. UKMSR has implemented quality controls, validation rules, new capture systems and site reporting to improve this.MethodCompare the Minimum Data Set (MDS) consisting of 7 items including demographics and EDSS for quality and quantity in the first 3 years (pilot phase) to the most recent 3 years of data captureResultsCompletion of MDS (100% valid and completed values) (2011–2014) 4 sites, n=884. MDS received= 159 (17.9%), Time to add site ~3 Months (2017–2020) 48 Sites, n= 8836. MDS received = 5791 (65.5%), Time to add site ~6 WeeksConclusionThe UKMSR has improved the clinical capture of MDS from a vastly increased number of patients and clinical sites. Improved validation standards and systems have increased data quality. Sites are added more quickly and rapidly notified of data quality issues for correction, making the data more useful to the site and ultimately of more utility to researchers.richard.nicholas@btinternet.com
Patterns of pollen dispersal and pollen capture in the hybridizing cattails,Typha latifoliaandTypha angustifolia
Authors: Pieper Sara J. , Freeland Joanna R. , Dorken Marcel E. 
Published: May 2022

Pollen dispersal regulates the formation of the invasive, wind-pollinated hybrid cattail Typha × glauca Godron, the F1offspring of the broadleaf ( Typha latifolia L.) and narrowleaf ( Typha angustifolia L.) cattail. An earlier study suggested that pollen dispersal by T. latifolia might be spatially restricted, with most dispersal occurring over distances less than 2 m. Restricted pollen dispersal would imply that hybrid formation primarily occurs within mixed stands of cattails. Hybrid formation might also be affected by preferential receipt of conspecific pollen, but this has not been investigated for cattails. We compared patterns of pollen dispersal for T. latifolia and T. angustifolia using a wind tunnel. We then tested whether patterns of pollen receipt were biased toward the capture of conspecific versus heterospecific pollen using monospecific cattail stands with a single local pollen source. Results from the wind tunnel partially supported the previous finding of spatially restricted pollen dispersal for T. latifolia, the paternal parent of F1hybrids. Pollen receipt by T. angustifolia was biased toward the capture of conspecific pollen. Localized pollen dispersal by T. latifolia and preferential conspecific pollen capture by T. angustifolia should reduce rates of hybrid formation below that expected under random mating.
Taking to “heart” the proposed legislation for permanent daylight saving time
Authors: Carter Jason R. , Knutson Kristen L. , Mokhlesi Babak 
Published: May 2022

In March 2022, the US Senate passed the Sunshine Protection Act that would abolish the biannual change in clocks each fall and spring and permanently adopt daylight saving time that aligns with the “spring forward” time change each March. A number of scientific and medical societies have endorsed the abolishment of the biannual clock change, but oppose the permanent adoption of daylight saving time. Instead, leading organizations such as the American Academy of Sleep Medicine (AASM) and the Society for Research on Biological Rhythms (SRBR) position statements highlight peer-reviewed evidence in favor of a permanent shift to standard time. The present perspectives will summarize some of the key AASM and SRBR recommendations, with a particular focus on the potential cardiovascular implications of a legislative change that would result in a permanent switch to either standard time or daylight saving time. Collectively, although there is building scientific consensus that abolishing the biannual time change has several sleep and circadian health benefits, the preponderance of evidence is opposite to the current legislation and instead suggests a permanent switch to standard time may offer the maximum health and safety benefits. This scientific evidence should be considered as the United States House of Representatives considers the Sunshine Protection Act. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/daylight-saving-time-and-cardiovascular-risk/ .
Impact of Blood Pressure in the Early 40s on Left Atrial Volumes in the Mid‐60s: Data From the ACE 1950 Study
Authors: Rønningen Peter Selmer , Berge Trygve , Solberg Magnar Gangås , Enger Steve , Pervez Mohammad Osman , Orstad Eivind Bjørkan , Kvisvik Brede , Aagaard Erika Nerdrum , Lyngbakken Magnus Nakrem , Ariansen Inger , Røsjø Helge , Steine Kjetil , Tveit Arnljot 
Published: May 2022

Background
Echocardiographic measures of left atrial volumes are powerful predictors of cardiovascular events and important for assessing diastolic dysfunction. Despite this, there is limited knowledge of factors influencing left atrial remodeling. In particular, the impact of blood pressure in those in their early 40s on left atrial volumes later in life has not been sufficiently elucidated.

Methods and Results

We linked data from individuals born in 1950 who participated in the Age 40 Program, and the ACE (Akershus Cardiac Examination) 1950 Study. We divided the study population into quartiles of systolic blood pressure in their early 40s and assessed the proportion of individuals with an enlarged left atrium in their mid‐60s. The associations between blood pressure and left atrial volumes were assessed in linear regression analyses. Of the 2591 individuals included in this study, 1302 (50.3%) were women, and the mean age in the Age 40 Program was 40.1±0.3 years. Systolic blood pressure was 128.1±13.6 mm Hg and diastolic blood pressure was 78.3±9.5 mm Hg. Mean age in the ACE 1950 Study was 64.0±0.6 years. The proportion of individuals with an enlarged left atrium increased across the quartiles of systolic blood pressure (
P
=0.001). Systolic blood pressure was independently associated with left atrial volumes; the end‐systolic volume was 0.09 mL (95% CI, 0.04–0.14 mL) larger per 1‐mm Hg higher systolic blood pressure.

Conclusions
Our findings suggest that increased blood pressure in those in their early 40s is relevant for left atrial remodeling later in life.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01555411.