bluuebunny/crossref_metadata_2025_split huggingface dataset:
102  Translating logistical challenges into service improvement: MS infusional services during the covid-19 pandemic
Authors: Ramsay Stephen , Magill Fiona , Cartmill Glenn , Goldsmith Grainne , McKee Jon , Kennedy Fiona , Droogan Aidan , Hughes Stella , McDonnell Gavin 
Published: May 2022

BackgroundProviding care to Multiple Sclerosis (MS) patients has been a challenge during the Covid-19 pandemic. Locally, surge plans necessitated an abrupt change of facility for infusional services, now supervised by MS nurses, from an acute site (Royal Victoria Hospital, RVH) to a non-acute site at Musgrave Park Hospital (MPH).ObjectiveTo assess patient satisfaction with MS infusional therapies at a new, non-acute location and supervision of the service by MS Specialist nurses in comparison with previous arrangements.MethodsAnonymous patient surveys were developed and collected in order to assess patient demo- graphics and levels of satisfaction across various service domains.ResultsAll 120 offered surveys were returned. Overall, 97% recorded a satisfaction score of ≥8/10 (0–10, 10= extremely satisfied). Key areas of improvement: difficulty parking (0.8% vs 50% in RVH), difficulty of unit access (0.8% vs 38% previously), appointment punctuality (95% on time vs 35% previously), and comfort (83% vs 55% previously). Thematic analysis revealed several key improvement areas: access to MS nursing knowledge, cannulation, and punctuality.ConclusionThe urgently relocated service, with better access and specialist nursing input, was associ- ated with substantial improvements in patient experience. Despite current unprecedented pressures on healthcare delivery, unique opportunities remain for service improvement.sramsay03@qub.ac.uk|ABN Bursary76
005  Infusion associated reactions in ocrelizumab-treated multiple sclerosis patients
Authors: Das Esther , Bewick Claire , Collins Justine , Nash Cynthia , Fisniku Leonora 
Published: May 2022

Background and aimsInfusion-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.MethodsAll 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.Results28-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.ConclusionOur 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
119  Long-term effectiveness of natalizumab for RRMS: UK and global interim results from TYSABRI observational program
Authors: Nicholas Richard , Harrower Timothy , Liao Shirley , Vonsy Jean 
Published: May 2022

IntroductionThe TYSABRI Observational Program (TOP) is an ongoing observational study of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) patients. Country-specific data on relapse and disability outcomes, alongside global data, can provide information on natalizumab’s effectiveness in local practice.MethodsAnnualised relapse rate (ARR) was analysed in TOP UK (n=134) and global (N=6320) cohorts using data from July 2007 to November 2020. A subgroup analysis assessed ARR in patients with one prior disease modifying therapy (DMT) in the UK (n=64) and global (n=2795) cohorts. Cumulative probabilities of 24-week confirmed disability worsening and improvement will be presented.ResultsARR decreased in UK patients from 2.21 in the year before initiation to 0.16 on natalizumab (P<0.0001), consistent with a global decrease from 2.00 to 0.18 (P<0.0001). In patients with one prior DMT, ARR decreased in UK patients from 2.13 in the year before initiation to 0.15 on natalizumab (P<0.0001), similar to the global decrease from 2.03 to 0.16 (P<0.0001).ConclusionsThe reduction in ARR on natalizumab was similar in the TOP UK and global cohorts, including in the subset of patients with one prior DMT. These findings support the real-world effectiveness of natalizumab.Support.Biogen. Disclosures: Included on the poster. jean.vonsy@biogen.com
122  Neurological manifestations of haemophagocytic lymphohistiocytosis
Authors: Brown Rachel , Amarnani Raj , Flower Luke , Manson Jessica , Carr Aisling 
Published: May 2022

Secondary (acquired) haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which can occur in the context of infection, malignancy or rheumatological disease and is associated with high mortality. Early recognition facilitates access to effective biological therapies and engage- ment with specialist MDTs which focus on managing the underlying trigger. Neurological manifestations are associated with poor prognosis but are not well described.We retrospectively reviewed 40 cases of secondary HLH in UCLH/NHNN; 25 had neurological compli- cations. Median age at onset: 36 years (range 11–79); 8 females. Causes of HLH were haematological malignancy (14), rheumatological disease (3), infection (2) and other/unknown (6). Neurological involve- ment portended higher morbidity and mortality: 21/40 ICU support; 19/40 in hospital death (15/25 and 16/25 with neurology). Neurological presentations included confusion (10) and reduced consciousness (5), headache (7), neuropathy (3) and myopathy (1). Based on symptomatology, radiological, CSF and metabolic and histological information we propose mechanistic causality of neurological manifesta- tions into: disease infiltration (13/25), metabolic (12/25), iatrogenic (2/25). The role of the cytokine storm in metabolic neurological derangement requires further investigation.We designed a minimal neurology dataset to improve prospective data collection instituted via the UK HiHASC (Hyperinflammatory and HLH Across Speciality Collaboration). A management algorithm is in development.rachelbrown@ucl.ac.uk|ABN Bursary86
126  A case report of the emergence of neurosarcoidosis after COVID-19 infection
Authors: Robinson Rebecca , Nelson Adam , Hughes Stella , Kinney Michael 
Published: May 2022

IntroductionSarcoidosis is a granulomatous disease with protean manifestations. The aetiology is not fully understood. Infectious agents are considered to potentially contribute to its pathogenesis. This case report highlights the emergence of neurosarcoidosis after COVID-19 infection.Case: A 48 year old female developed cough, myalgia and fatigue and was diagnosed with COVID-19 based on serological testing in April 2020. Post-infection, she developed a reactive arthritis, then presented in June with left facial lower motor neuron weakness, initially treated as a Bell’s palsy with a significant neuralgic component. This pain resolved with steroid treatment. One month later she developed multiple cranial neuropathies and bilateral leg weakness. MRI brain showed bilateral enhancement of the trigeminal and facial nerves. CSF was abnormal (CSF protein 0.95g/L, WCC 9/uL). Leg power rapidly improved with intravenous immunoglobulins, and FDG-PET identified mediastinal and axillary hilar lymphadenopathy. A neck node showed non-necrotising granulomatous inflammation. CSF angiotensin converting enzyme was elevated (2.07umol/min/L). She has since commenced high dose steroids for probable neurosarcoidosis.DiscussionThis case suggests a possible association between COVID-19 and the emergence of sarcoidosis. At present the strength of any association is uncertain and putative mechanisms remain to be determined.rrobinson17@qub.ac.uk88
139  Presentation of a rare dysautonomic variant of Guillain-Barré syndrome
Authors: Huang Yun , Baheerathan Aravindhan , Pritchard Jane 
Published: May 2022

Guillain-Barré Syndrome (GBS) is an inflammatory disease of the peripheral nervous system. We describe the case of a gentleman who presented with a predominant dysautonomic variant of GBS.A 55-year-old gentleman presented with a sub-acute onset, progressive syndrome characterised by a combination of ascending distal upper and lower limb paraesthesia, postural dizziness, early satiety and constipation. This was preceded by an upper respiratory tract infection and vaccinations for pneumo- coccus and influenza. On examination, he had length-dependent reduction to pinprick and tempera- ture sensation, normal power, preserved reflexes, with significant orthostatic hypotension. MRI brain and whole spine was unremarkable. Cerebrospinal fluid analysis showed albumino-cytological dissociation and nerve conduction studies was consistent with subacute onset demyelinating polyradiculoneuropa- thy. A diagnosis of pandysautonomic variant of GBS was formulated. He was treated with 5 days of intravenous immunoglobulin (IVIg) (0.4kg/kg/day) with improvements in orthostatic hypotension from day 3 of treatment.While autonomic instability is common in GBS, a predominant autonomic presentation without motor weakness can represent a rare pandysautonomic variant of GBS. This case illustrates the importance of early detection of autonomic dysregulation in GBS, the requirement for close monitoring and use of IVIg as an effective therapeutic management of autonomic dysfunction.yun.huang@nhs.net
141  Guillain-Barre as a post-operative syndrome following resection of anaplastic astrocytoma
Authors: Leahy Christopher , Lavin Tim , Gosal David , Herwadkar Amit , D’Urso Pietro , Cahill Varduhi 
Published: May 2022

We present a case of Guillain Barre Syndrome (GBS) following resection of a brain neoplasm. A 43 y.o. man presented with diplopia and lower back pain 2 weeks after resection of left mesiotemporal and fusiform gyrus grade III IDH 1 mutant anaplastic astrocytoma. Within a week he was unable to ambulate due to marked leg weakness. Examination showed bilateral weakness of lateral rectus muscles and lower motor bilateral facial weakness. Hip flexion was 1/5 bilaterally, otherwise 0/5. Tone was flaccid. Lower limb reflexes were absent and plantar responses were mute. Imaging showed no evidence of tumour recurrence or drop metastasis. CSF analysis demonstrated raised WCC (43/ul WBCs, <1/ul RBCs), protein was markedly elevated at 4.33 g/l and glucose normal. Cytology was negative for malignancy consist- ently. He was treated 5-days of intravenous immunoglobulin (2g/kg). He walked without assistance on discharge and his recovery was sustained at 6 months follow up. Neurophysiology showed a generalised, non- length dependent, motor> sensory, demyelinating neuropathy. This case highlights the importance of considering GBS as a potential cause of progressive neurological deficit in the postoperative period where “atypical” CSF findings are confounded by the preceding neurosurgical intervention.christopherleahy@doctors.org.uk
010  Safety and efficacy of long-term dimethyl fumarate treatment
Authors: Gold Ralf , Giovannoni Gavin , Theodore Phillips J , Bar-Or Amit , Fox Robert J , Chen Chongshu , Parks Becky , Kapadia Shivani 
Published: May 2022

IntroductionENDORSE (NCT00835770) evaluated the safety and efficacy of dimethyl fumarate (DMF) treatment for ≥10 years (Y) in relapsing-remitting MS (RRMS) patients.MethodsPatients treated continuously with DMF 240 mg BID in DEFINE/CONFIRM and ENDORSE were assessed for relapse, confirmed disability progression (CDP), serious adverse events (SAEs), and patient- reported outcomes (PROs): (36-item short form health survey [SF-36]; 5-dimension QoL [EQ-5D]).ResultsOf 618 patients treated for ≥10Y, 38%(192/501) were continuously-treated BID. Mean (SD) age 41.6 (8.7) Y; 68% female. Most (51%[98/192]) patients remained relapse-free or had ≤1 relapse, 73%(141/192); median time-to-first-relapse was 58 weeks. Mean baseline (SD) EDSS score was 2.24 (1.18); patients with EDSS ≤3.5: Y2 89%(164/184), Y8 80%(148/184), Y10 79%(146/184). From Y0–10, 64%(122/191) patients had no CDP. Seventy-seven (40%) patients experienced SAEs; primarily MS relapse 18%(34/192) or infections 6%(12/192). From Y0–10, serious infection incidence did not increase and SF-36 and EQ-5D remained stable.ConclusionsPatients continuously treated with DMF BID for ≥10Y had low incidence of relapses; the pro- portion of patients with EDSS ≤3.5, patients with CDP, PROs, and incidence of serious infections remained stable over 10Y reinforcing the safety and efficacy of long-term DMF treatment for RRMS patients.SupportBiogen; disclosures detailed on poster.g.giovannoni@qmul.ac.uk
020  Long-term efficacy of ocrelizumab in relapsing multiple sclerosis: 6 study years
Authors: Giovannoni Gavin , Kappos Ludwig , Seze Jerome de , Hauser Stephen L , Overell James , Koendgen Harold , Prajapati Kalpesh , Manfrini Marianna , Wang Qing , Wolinsky Jerry S 
Published: May 2022

BackgroundEfficacy/safety of ocrelizumab in relapsing multiple sclerosis were demonstrated in the OPERA I/II (NCT01247324/NCT01412333) double-blind period (DBP). We assessed the efficacy of switching to or maintaining ocrelizumab after 4 years of the open-label extension (OLE).MethodsAt OLE commencement, patients continued ocrelizumab (OCR-OCR) or switched from interferon-β-1a to OCR (IFN-OCR). Adjusted annualised relapse rate (ARR), time-to-onset of 24-week confirmed disability progression (CDP24) and risk of requiring a walking aid (Expanded Disability Status Scale score ≥6.0) from DBP baseline were analysed.ResultsAmong IFN-OCR switchers, ARR decreased year-on-year from 0.2 in the pre-switch year to 0.04 in OLE Year 4; OCR-OCR continuers maintained low ARRs (pre-switch, 0.13; OLE Year 4, 0.05). CDP24 was lower year-on-year in OCR-OCR continuers versus IFN-OCR switchers in the pre-switch year (7.7% vs 12.0%) and at OLE Year 4 (19.2% vs 23.7%); p<0.05 all comparisons. Over the DBP and OLE, risk of requiring a walking aid was 44% lower (p=0.004) in OCR-OCR continuers versus IFN-OCR switchers.ConclusionsAfter 6 years of follow-up, rates of patients with CDP24 and risk of requiring a walking aid remained lower in earlier initiators of ocrelizumab (OCR-OCR) versus those initially receiving IFN (IFN-OCR), demonstrating maintained benefits of earlier treatment with ocrelizumab.g.giovannoni@qmul.ac.uk
028  Cladribine to halt deterioration in people with advanced multiple sclerosis (ChariotMS)
Authors: Lieberman David R , Mangat Harpreet K , Schmierer Klaus 
Published: May 2022

BackgroundDisease modifying treatments (DMTs) have transformed the management of people with MS (pwMS). However, patients with an EDSS>6.5 (pwAMS) are considered beyond DMT due to (i) focus on ambulation as outcome measure, (ii) assumption that in pwAMS inflammation plays no role, and(iii) disregard for potentially length-dependent neuro-axonal damage. Cladribine is a CNS penetrant, effective, convenient and relatively safe DMT. Cladribine effectively depletes B cell subsets, particularly memory B cells, a potential key mechanism of disease control in pwMS.AimsTo test the efficacy, safety and cost-effectiveness of cladribine tablets in pwAMS (EDSS 6.5–8.5), expand the mechanistic understanding of cladribine in pwAMS and provide evidence for NHS adoption.MethodsRandomised, double-blind, placebo-controlled phase IIb trial. The primary outcome measure is 9-hole peg test speed at 104 weeks vs baseline. To detect a 15% treatment effect in 9-HPT peg speed with 90% power at 5% significance and 20% drop-out we calculated a sample size of n=200 across 20 UK sites.ConclusionsChariotMS will be the first DMT-trial focussing on pwAMS. If successful, ChariotMS would expand the DMT landscape to include pwAMS and provide a platform for potential add-on therapies. ChariotMS is due to start recruitment nationwide from 1 Sep 2020.david.lieberman@nhs.net
Neuroinflammation and protein aggregation co-localize across the spectrum of frontotemporal dementia
Authors: Bevan-Jones Richard , Cope Thomas , Jones Simon , Kaalund Sanne , Allinson Kieren , Hong Young , Arnold Robert , Patterson Karalyn , O’Brien John , Rowe James 
Published: May 2022

Frontotemporal dementia is clinically and neuropathologically heterogeneous, but each major phenotype has been associated with both aggregation of misfolded protein and neuroinflammation. We used positron emission tomography, with [11C]PK-11195 to measure activated microglia, and [18F]AV-1451 to quantify the burden of Tau or TDP-43, in 31 patients with frontotemporal dementia (10 behavioural variant, 11 semantic variant and 10 non-fluent variant) and 15 matched controls, to test the hypothesis that neuroinflamma- tion co-localises with pathological protein aggregation.Analyses included: (1) region-of-interest binding potentials; (2) pairwise correlation across regions between ligands; (3) principal component analysis of each ligand distribution and (4) multivariate classification of binding distributions.The analyses converged in showing (a) significant differences in [11C]PK-11195 binding between each patient group and controls in frontotemporal regions; (b) a strong positive correlation between [11C] PK-11195 and [18F]AV-1451 binding in all disease groups, across widespread cortical regions. Thesein vivoresults were confirmed bypost mortemimmunohistochemistry in 12 brains. In addition, we found (c) distinct distributional patterns of [11C]PK-11195 binding associated with different frontotemporal dementia syndromes, that supported more accurate classification of participants than [18F]AV-1451.Neuroinflammation may be important in shaping the clinical and neuropathological patterns of fronto- temporal dementia, and be a target for disease-modification.richard.bevanjones@doctors.org.uk
038  Pregnancy outcomes in patients treated with ocrelizumab
Authors: Brex Peter , Oreja-Guevara Celia , Wray Sibyl , Buffels Regine , Zecevic Dusanka , Vukusic Sandra 
Published: May 2022

BackgroundOcrelizumab is approved for the treatment of relapsing forms and primary progressive multiple sclerosis (MS).MethodsWe report analyses of pregnancies in women who received ocrelizumab in clinical trials/post- marketing sources up to 31/03/2019. Contraceptive requirements for women of childbearing potential were per label (during treatment and for 6/12 months after the last infusion) or adapted in clinical trials (two methods for 6 months or until 48 weeks after the last infusion/until B-cell repletion [whichever longer]). Foetal exposure was defined as the last infusion occurring within 3 months of conception or during pregnancy if the conception date was unknown.ResultsA total of 362 ocrelizumab-exposed pregnancies in women with either MS (N=267), rheumatoid arthritis/systemic lupus erythematosus (N=33) or an unknown indication (N=62) have been reported. Of the 267 pregnancies in women with MS, 118 were considered to have foetal exposure, 47 did not have foetal exposure and 102 had unknown foetal exposure. Preliminary pregnancy outcomes in MS patients include: 62 live births, 86 ongoing pregnancies, 25 elective abortions, 10 spontaneous abortions, 1 stillbirth, 3 ectopic pregnancies, 22 lost to follow-up and 58 unknown/unreported outcomes.ConclusionsCases to date do not suggest an increased risk of adverse pregnancy/foetal outcomes with ocrelizumab.p.brex@nhs.net
The mitogenome of Urnula craterium
Authors: Mukhopadhyay Jigeesha , Wai Alvan , Hutchison Leonard J. , Hausner Georg 
Published: May 2022

Urnula craterium (Schwein.) Fr. (1851) has been reported from North America, Europe, and Asia, and can be a pathogen on various hardwood species. In this study, we investigated the mitochondrial genome of U. craterium. The biology and taxonomy of this fungus is poorly studied and there are no mitogenomes currently available for any member of the Sarcosomataceae (Order Pezizales). The complete mitogenome of U. craterium comprises 43 967 bps and encodes 14 protein-coding genes, a complete set of tRNAs and rRNA genes. A novel feature of the mitogenome is the presence of a single subunit DNA polymerase-coding region that is typically associated with linear invertron-type plasmids. The mitogenome may offer insights into the evolution of mitogenomes among members of the Pezizales with regards to gene content and order, mobile elements, and genome sizes.
Skewness-based characterization of silicon photomultipliers
Authors: Vinogradov S. 
Published: May 2022

AbstractCharacterization of SiPMs is an objective of high importance in almost any research, development, and application of these unique photon detectors. Two decades of characterization method developments resulted in a comprehensive and elegant methodology based on a precisely resolved number of fired SiPM cells or the SiPM spectrum. Spectrum fitting procedures are very sensitive to a proper selection of many initial guess values including parameters of minor importance and happen to be unreliable. Moreover, conventional methods are useless for degraded or unresolved SiPM spectra. This challenge was anticipated for SiPM-based detectors of high-luminosity particle calorimeters where a severe radiation degradation of the SiPMs would co-exist with their acceptable performance. To address it, one can measure a mean and variance of SiPM charge responses relying on a priori known Excess Noise Factor of the SiPM but its stability during SiPM degradation is uncertain. This study proposes and evaluates a new approach for the SiPM characterization based on the first three statistical moments (mean, variance, and skewness) of its charge response including skewness. It assumes the Generalized Poisson distribution of the number of fired cells and provides simple closed-form analytical expressions for the parameter estimation. It allows determining a gain, a number of detected photons, and a probability of correlated events directly from raw data. The skewness-based characterization is anticipated to be especially useful for mass testing and continuous monitoring of SiPMs in large-scale experiments due to its simplicity and robustness. Initial evaluations of the method show promising results.