bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of microsatellite instability to mismatch repair deficiency in malignant tumors of dogs
Authors: Inanaga Sakuya , Igase Masaya , Sakai Yusuke , Hagimori Kenji , Sunahara Hiroshi , Horikirizono Hiro , Itamoto Kazuhito , Baba Kenji , Ohsato Yoshiharu , Mizuno Takuya
Published: August 2022

Background

Microsatellite instability (MSI) is a type of genomic instability caused by mismatch repair deficiency (dMMR) in tumors. Studies on dMMR/MSI are limited, and the relationship between dMMR and MSI is unknown in tumors of dogs.

Objectives

We aimed to identify the frequency of dMMR/MSI by tumor type and evaluate the relationship between dMMR and MSI in tumors of dogs.

Animals

In total, 101 dogs with 11 types of malignant tumors were included.

Methods

We extracted DNA from fresh normal and tumor tissues. Twelve microsatellite loci from both normal and tumor DNA were amplified by PCR and detected by capillary electrophoresis. Each microsatellite (MS) was defined as MSI if a difference in product size between the tumor and normal DNA was detected. The dMMR was evaluated by immunohistochemistry with formalin‐fixed paraffin‐embedded tumor tissues. Next, we confirmed whether dMMR induces MSI by serial passaging of MMR gene knockout cell lines for 3 months.

Results

Microsatellite instability was detected frequently in oral malignant melanoma. The number of MSI‐positive markers was higher in cases with dMMR than in those with proficient MMR (P < .0001). Statistical analysis indicated that the occurrence of MSI in FH2305 might have relevance to dMMR. Furthermore, MSI occurred in dMMR cell lines 3 months after passaging.

Conclusions and Clinical Importance

Microsatellite instability and dMMR more frequently were found in oral malignant melanoma than in other tumors, and dMMR has relevance to MSI in both clinical cases and cell lines.
Medical students' rural practice intention: Academic performance matters
Authors: You You , Xie Ana , Cleland Jennifer
Published: August 2022

Introduction

Many countries are driving forward policies and practices to train medical students for later rural practice. Previous research has investigated individual (e.g., rural upbringing) and structural factors (e.g., curricular exposure) associated with rural practice intention. However, the relationship between academic performance in medical school and rural practice intention has been neglected, although optimisation theory suggests there may be a relationship. To address this gap, our aim was to identify the relationship between academic performance and rural practice intention.

Methods

Data were collected via a cross‐sectional (self‐report) survey in 2021. Participants were students from 60 of the 96 rural order directed (RODs) medical programmes across China. We asked students their rural practice intention. We conducted univariate analyses to test for associations between rural practice intention and independent variables, including socio‐demographics, ROD location, grade year and academic performance measures. We used multilevel logistic regression models to test whether students' academic performance in medical school could be used to predict rural practice intention, holding the other factors constant.

Results

There were 13 123 respondents, representing roughly 77.6% of the student population from the 60 schools. There was a statistically significant relationship between student (self)‐reported academic performance in medical school and rural practice intention. Higher performers had a lower likelihood (ORs: 0.65–0.78) of rural practice intention. This held across all performance measures (GPA rank, academic awards and student leadership) and for the sub‐group with rural upbringing (ORs: 0.68–0.78).

Discussion

This is the first study to identify a relationship between medical school performance and rural practice intention. The findings suggest that students maximise their utility when choosing career options, with higher performers having lower rural practice intention. These data provide insight into the complexity of medical career decision making and can be used by medical school and workforce planners to inform rural training, recruitment and retention strategies.
Sparse‐sensing and superpixel‐based segmentation model for concrete cracks
Authors: Xie Xiongyao , Cai Jielong , Wang Haozheng , Wang Qiang , Xu Jieying , Zhou Yingxin , Zhou Biao
Published: August 2022

Efficient image‐recognition algorithms to classify the pixels accurately are required for the computer‐vision‐based inspection of concrete defects. This study proposes a deep learning‐based model called sparse‐sensing and superpixel‐based segmentation (SSSeg) for accurate and efficient crack segmentation. The model employed a sparse‐sensing‐based encoder and a superpixel‐based decoder and was compared with six state‐of‐the‐art models. An input pipeline of 1231 diverse crack images was specially designed to train and evaluate the models. The results indicated that the SSSeg achieved a good balance between the recognition correctness and completeness and outperformed other models in both accuracy and efficiency. The SSSeg also exhibited good resistance to the interference of surface roughness, dirty stains, and moisture. The increased depth and receptive field of sparse‐sensing units guaranteed the representability; meanwhile, structured sparse characteristics protected the network from overfitting. The lightweight superpixel‐based decoder omitted skip connections, which greatly reduced the computation and memory footprint and enlarged the input size in the inference.
Optometry independent prescribing during COVID lockdown in Wales
Authors: Cottrell Paul , North Rachel , Sheen Nik , Ryan Barbara
Published: August 2022

Introduction

During the COVID‐19 lockdown, primary care optometry services in Wales moved to a hub model of provision. Three independent prescribing models were available in different areas: a commissioned Independent Prescribing Optometry Service (IPOS), independent prescribers that were not commissioned and no independent prescribers available. This allowed a unique opportunity for comparison.

Method

Optometry practices completed an online survey for each patient episode. Analysis of the data gave insight into patient presentation to urgent eye services and the drugs prescribed by optometrists. Medicines prescribed, sold or given and onward referral were compared between areas with an IPOS service (n = 2), those with prescribers but no commissioned service (n = 2) and those with no prescribers (n = 2).

Results

Data from 22,434 reported patient episodes from 81 optometry practices in six health boards between 14 April 2020 and 30 June 2020 were analysed. Urgent care accounted for 10,997 (49.02%) first appointments and 1777 (7.92%) follow‐ups. Most (18,006, 80.26%) patients self‐referred. The most common presenting symptom was ‘Eye pain/discomfort’ (4818, 43.81% of urgent attendances). Anterior segment pathology was the most reported finding at first (6078, 55.27%) and follow‐up (1316, 74.06%) urgent care appointments. Topical steroids (373, 25.99% of prescriptions) were the most prescribed medications. More medications were prescribed in areas with an IPOS service (1136, 79.16% of prescriptions) than areas with prescribers but no commissioned service. There were more follow‐up appointments in optometric practice and fewer urgent referrals to ophthalmology in IPOS areas.

Conclusion

Urgent care services were most utilised by patients with discomfort caused by anterior eye conditions. IPOS services enabled optometrists to manage conditions to resolution without referral and without reduction in medications sold or given. Commissioners should recognise the value in reducing burden in urgent ophthalmology and the need for follow‐up as part of a commissioned independent prescribing service.
Dental implantology and fibrous dysplasia: A 6‐year follow‐up case report and a literature review
Authors: Lizio Giuseppe , Pellegrino Gerardo , Corinaldesi Giuseppe , Ferraioli Lorenzo , Felice Pietro
Published: August 2022

Background and Aim

It is unclear if fibrous dysplasia (FD) represents a contraindication for implant borne rehabilitation, and only two successful cases are reported in the literature with a 4–2‐year follow‐up. The present paper discusses this issue reporting a full‐arch maxillary rehabilitation with a >5‐year follow‐up.

Materials and Methods

A 79‐year‐old woman complained of a progressive asymmetry of the medial facial third with inter‐arch occlusal alterations, reduced mandibular movements, upper right dental dislocation and mobility and toothache in the upper posterior jaw. The X‐ray supported monostotic FD diagnosis was followed by a remodelling intervention in general anaesthesia, with the extraction of the hopeless teeth. After that and the failed rehabilitation with a removable prosthetic device, the patient underwent implant placement procedure for a fixed ‘Toronto‐bridge’ prosthesis.

Results

After 6 years from implant loading, a posterior vestibular swelling of the affected maxilla was recorded, and one implant in 1.1 position had to be removed for peri‐implantitis, without compromising the rehabilitation.

Conclusions

The acceptable results obtained in this case should promote the dental implantology practice in FD affected jaws, evaluating the proper clinical situations and the more adequate technological solutions.
Neurological complications in pediatric liver transplant recipients
Authors: Menon Jagadeesh , Shanmugam Naresh , Rammohan Ashwin , Hakeem Abdul , Reddy Mettu Srinivas , Rela Mohamed
Published: August 2022

Introduction

There is paucity of data on neurological complications (NCs) and its predisposing factors, in pediatric liver transplant (PLT) recipients.

Methods

Records of seventy‐one children who underwent LT between October 2018 and November 2019 were reviewed. Patients were categorized into group A: with NC and group B: without NC in the post‐LT period. Various risk factors contributing to NC were studied.

Results

In total, 15 (21.1%) had NC (group A) and 56 (78.9%) had no NC in the post‐LT period. NC included cerebrovascular accident (n = 1), seizures (n = 5; 4 generalized, 1 focal), central pontine myelolysis (CPM) (n = 1), diaphragmatic palsy (n = 2), peripheral neuropathy (n = 1), extrapyramidal movements (n = 3), and encephalopathy beyond 96 h (n = 2). The median onset of NC was at 8.5 days post‐LT (1–58 days). Ten (66.7%) patients in group A had grades 2–4 hepatic encephalopathy (HE) prior to LT. Eight (14.3%) patients in group B also had pre‐LT neurological issues including HE in six, epilepsy and spastic diplegia in one each. On univariate analysis, pre‐existing HE, high PELD/MELD score, pre‐LT ventilation, pre‐LT infection, higher day 1 post‐operative bilirubin (all p < .05), and higher tacrolimus were found to predict post‐operative NC whereas on multivariate analysis, pre‐LT HE was the only predictive factor. Median follow‐up was 15.5 months. Four patients died in each group (survival log‐rank p = .369). All the surviving patients in group A (n = 11) fully recovered from the NC.

Conclusion

Pre‐transplant HE was the single most significant predisposing factor for post‐LT neurological complications.
Vulnerability to Fraud in Community Sport Organizations: A Multicountry Study on the Role of Organizational Capacity
Authors: Wicker Pamela , Misener Katie E. , Kihl Lisa A. , Cuskelly Graham
Published: August 2022

This study develops and tests a measure for perceived vulnerability to occupational fraud and examines the relationship between organizational capacity and perceived vulnerability to fraud in community sport organizations. Drawing on the opportunity dimension of fraud triangle theory and the concept of organizational capacity, the study identifies a number of risk and protection factors for vulnerability to fraud. Board members of community sport organizations in Australia, Germany, and North America were surveyed (n = 1,256). The results offer a reliable and valid scale assessing vulnerability to fraud in community sport organizations consisting of procedural and financial dimensions. The regression analyses indicate a set of risk factors for vulnerability to fraud, including the presence of paid staff, high annual and unbalanced budgets, and owning sport facilities. Protection factors include strategic planning, relationships with other institutions, and trust within the board. This knowledge can be used to design antifraud education and training resources.
Challenges to Culturally Responsive Teaching in Physical Education Teacher Education Alumni: A Mixed-Methods Analysis
Authors: Flory Sara B. , Nieman Craigory V. , Wylie Rebecca C.
Published: August 2022

This study examines the culturally responsive teaching self-efficacy of graduates from a Physical Education Teacher Education program focused on social justice issues. We examined barriers to culturally responsive teaching and areas where alumni felt least efficacious. Forty-three graduates of a Physical Education Teacher Education program completed the culturally responsive teaching self-efficacy scale and demographic questions via Qualtrics, and 13 completed a 45- to 60-min interview regarding urban teaching experience. Quantitative data were analyzed using descriptive statistics and comparative data analysis to determine areas of lower self-efficacy. Two major themes emerged from this data: (a) misalignment between expectations and reality and (b) lack of practical experiences with communication. Specific coursework, training, and supports need to be implemented to address the mismatch between participants’ lived experiences and their daily challenges upon induction. Physical Education Teacher Education programs need to critically examine the experiences preservice teachers have interacting and communicating with English language learners and their caregivers prior to induction.
C11orf94/Frey is a key regulator for male fertility by controlling Izumo1 complex assembly
Authors: Contreras Whendy , Wiesehöfer Caroline , Schreier Dora , Leinung Nadja , Peche Petra , Wennemuth Gunther , Gentzel Marc , Schröder Bernd , Mentrup Torben
Published: August 2022

Although gamete fusion represents the central event in sexual reproduction, the required protein machinery is poorly defined. In sperm cells, Izumo1 and several Izumo1-associated proteins play an essential role for this process. However, so far, the mechanisms underlying transport and maturation of Izumo1 and its incorporation into high molecular weight complexes are incompletely defined. Here, we provide a detailed characterization of the C11orf94 protein, which we rename Frey, which provides a platform for the assembly of Izumo1 complexes. By retaining Izumo1 in the endoplasmic reticulum, Frey facilitates its incorporation into high molecular weight complexes. To fulfill its function, the unstable Frey protein is stabilized within the catalytic center of an intramembrane protease. Loss of Frey results in reduced assembly of Izumo1 complexes and male infertility due to impaired gamete fusion. Collectively, these findings provide mechanistic insights into the early biogenesis and functional relevance of Izumo1 complexes.
A naturally arising broad and potent CD4-binding site antibody with low somatic mutation
Authors: Barnes Christopher O. , Schoofs Till , Gnanapragasam Priyanthi N.P. , Golijanin Jovana , Huey-Tubman Kathryn E. , Gruell Henning , Schommers Philipp , Suh-Toma Nina , Lee Yu Erica , Cetrulo Lorenzi Julio C. , Piechocka-Trocha Alicja , Scheid Johannes F. , West Anthony P. , Walker Bruce D. , Seaman Michael S. , Klein Florian , Nussenzweig Michel C. , Bjorkman Pamela J.
Published: August 2022

The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-Å x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach.
Ruptured chronic ectopic pregnancy presenting with a negative urine pregnancy test
Authors: Dunphy Louise , Rey Christina Arias , Arshad Ilyas , Hapangama Dharani K
Published: August 2022

An acute ectopic pregnancy is one of the most common gynaecological emergencies in clinical practice. The diagnosis is usually established by a combination of clinical examination findings, correlated with sonographic and laboratory results. However, a chronic ectopic pregnancy (CEP) may occur when the ectopically implanted gestation, mostly in the fallopian tubes, invades the underlying structures, causing protracted destruction at the site of implantation. Individuals may present with subacute or chronic abdominal pain, abnormal vaginal bleeding, amenorrhoea and a low bHCG. The correct diagnosis is often only established following laparoscopy or even histologically after the operation. The authors present the case of a woman in her 30 s presenting with severe right sided abdominal pain and a failing pregnancy at 10 weeks gestation. Her urine pregnancy test was negative, but her serum bHCG was 18 IU/L. A transvaginal ultrasound scan confirmed a ruptured right tubal ectopic pregnancy. A laparoscopic salpingectomy was performed. This case provides an important reminder that a CEP should always be considered in the differential diagnosis of women of reproductive age presenting with acute lower abdominal pain, despite a negative urine pregnancy test.
TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation
Authors: Chen Yuan-Siao , Cabrera Ernesto , Tucker Brady J , Shin Timothy J , Moawad Jasmine V , Totten Douglas J , Booth Kevin T , Nelson Rick F
Published: August 2022

Background

It is well established that biallelic mutations in transmembrane protease, serine 3 (TMPRSS3) cause hearing loss. Currently, there is controversy regarding the audiological outcomes after cochlear implantation (CI) forTMPRSS3-associated hearing loss. This controversy creates confusion among healthcare providers regarding the best treatment options for individuals withTMPRSS3-related hearing loss.

Methods

A literature review was performed to identify all published cases of patients withTMPRSS3-associated hearing loss who received a CI. CI outcomes of this cohort were compared with published adult CI cohorts using postoperative consonant-nucleus-consonant (CNC) word performance.TMPRSS3expression in mouse cochlea and human auditory nerves (HAN) was determined by using hybridisation chain reaction and single-cell RNA-sequencing analysis.

Results

In aggregate, 27 patients (30 total CI ears) withTMPRSS3-associated hearing loss treated with CI, and 85% of patients reported favourable outcomes. Postoperative CNC word scores in patients withTMPRSS3-associated hearing loss were not significantly different than those seen in adult CI cohorts (8 studies). RobustTmprss3expression occurs throughout the mouse organ of Corti, the spindle and root cells of the lateral wall and faint staining within <5% of the HAN, representing type II spiral ganglion neurons. Adult HAN express negligible levels ofTMPRSS3.

Conclusion

The clinical features after CI and physiological expression ofTMPRSS3suggest against a major role of TMPRSS3 in auditory neurons.
Real-world experience of gene therapy with onasemnogene-abeparvovec (Zolgensma®) for patients with SMA-type1 in UK
Authors: Gowda Vasantha , Wraige Elizabeth , Ong Min , Atherton Mark , Majumdar Anirban , Marco Silvia Sanchez , Hughes Imelda , Mccullagh Gary , Muntoni Francesco , Jungbluth Heinz ,   et al
Published: August 2022

Retrospective review of referrals to the National-Multidisciplinary-Team (NMDT) in England (& Wales), and of the clinical records of SMAtype1 patients included for Zolgensma® therapy in the UK.

Data was available for 42 patients: 13, 12, 10, 6, 1 from Evelina-London, Sheffield, Bristol, Manchester and Belfast centres respectively.

Patients’ age ranged from 2-months to 46-months and weights from 4.44kg to 13.5kg. Post-Zolgensma-infusion monitoring:

Most patients had asymptomatic thrombocytopaenia in week-1, resolving by week-2. No thrombotic microangiopathy was reported. Majority developed transient transaminitis with mild/moderate elevation of AST/ALT. Some had more severe/prolonged transaminitis – Liver ultrasound, coagulation-studies and clinical examination remained normal: 11 (weight>7.5kg) had ALT-peaks of >100 IU/L; 22 (15/22 weighed >7.5kg) had AST-peaks of >100 IU/L – good response seen to doubling Prednisolone, where indicated. Echocardiograms remained normal in patients with elevated Troponin-I levels; 4 had levels >100ng/l, prednisolone doubled in one, with good response.

13/42 needed doubling of Prednisolone; 12/13 had weight >7.5kg.

CHOP-INTEND scores post gene-therapy were available for 22/42. Scores improved in all patients except one (difficult assessment). Improvement ranged from 2-24 points.

Conclusion

All patients tolerated the Zolgensma®-therapy well and have recovered well from any transient issues. No persistent complications from gene-therapy or steroid-cover were reported.
Using 31-phosphorus magnetic resonance spectroscopy (31P-MRS) to identify Parkinson’s Disease subgroups with bioenergetic dysfunction
Authors: Payne Thomas , Burgess Toby , Sassani Matilde , Bradley Stephen , Roscoe Sarah , Reed Emily , Wilkinson Iain D , Mortiboys Heather , Jenkins Thomas M , Bandmann Oliver
Published: August 2022

Background

Sporadic Parkinson’s disease (sPD) is an aetiologically heterogeneous disorder. Identification of distinct pathogenic mechanisms causing sPD will be crucial to develop future “Precision Medicine” approaches. 31P-MRS is a non-invasive tool that can quantify key bionenergetic metabolites in individual patients.

Objective

To determine whether 31P-MRS can identify mitochondrial dysfunction in the midbrain/sub- stantia nigra of individual PD patients and correlates with trial-relevant clinical aspects of PD.

Methods

31P-MRS spectra were obtained from 35 sPD patients and 25 healthy, age-matched controls. Spectra were analysed using the jMRUI software package and AMARES spectral fitting algorithm. Clinical assessment included widely utilised clinical rating scales, genetic analysis and the calculation of predicted risk of rapid disease progression.

Results

There was a significantly broader variance in 31P-MRS midbrain ATP with 1/3 of all PD patients having ATP levels > 2 standard deviations outside the mean control values (p=0.0030). Higher midbrain phosphocreatine was associated with greater risk of rapid disease progression (p= 0.0384).

Conclusions

31P-MRS may help to identify a subgroup of sPD with significant mitochondrial dysfunction or at higher risk of more rapid progression and facilitate stratification for future precision medicine neu- roprotective trials. Longitudinal studies are required to characterise if changes 31P-MRS measures mirror clinical progression.
057 Dementia and sociodemographic factors a review
Authors: Wu Kit , Vidot Micha , Mitchell James W , Nitkunan Arani , Carr Georgina
Published: August 2022

Background

Unwarranted variation in treatment, care and support for people with dementia is well documented. To improve equity of service, in line with the NHS Long Term Plan, it is imperative that we understand how sociodemographic factors affect management and care of dementia.

Aim

To review published literature between sociodemographic factors and clinical factors, diagnosis, treatment and outcomes for people with dementia.

Method

We conducted a focused review of published literature between 2000-2021 to outline the evidence describing the relationship between the ten protected characteristics of the Equality Act 2010 and clinical factors, treatment and outcomes in dementia. Other factors such as deprivation, settlement status, education and employment were also explored.

Results

There is an abundance of published literature on age, race, geographical variation, sex and gender. Evidence is lacking for relationship between disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, religion and belief, sexual orientation, immigration and settlement.

Discussion

Better understanding of sociodemographic factors of our patient group is key to improving equity of care. This review has identified gaps in knowledge on factors that may affect how patients access care to dementia services.
077 Opiate and headache prescribing patterns in idiopathic intracranial hyperten- sion: a matched controlled retrospective cohort study
Authors: Sassani Matilde , Adderley Nicola , Subramanian Anuradhaa , Perrins Mary , Niranthara-kumar Krishnarajah , Mollan Susan , Sinclair Alexandra
Published: August 2022

We aimed to evaluate adjusted hazard ratio (aHR) for new-onset headache as well as headache medi- cation prescribing, opiate use and headache burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls.

Data from IQVIA Medical Research Data, an anonymised, nationally representative UK database, from January-1995 to September-2019, was used. Women with IIH were matched by age and body mass index with women without IIH with migraine (migraine controls), and women without IIH or migraine (popula- tion controls).

3411 IIH patients, 30,879 migraine and 33,495 population controls were included. aHR for new onset headache in IIH compared to population controls was 3.09 (95%-confidence interval=2.78-3.43). In the first year post-diagnosis, 58% of IIH patients were prescribed acetazolamide and 20% topiramate. 20% of IIH patients were prescribed opiates within the first year of diagnosis, reducing to 17% after six years. In migraine, 8% and 11% were prescribed opiates within one year and six years post-diagnosis, respec- tively. More headache preventative medications were prescribed in IIH compared to migraine controls.

Opiate and simple analgesics are more likely to be prescribed in IIH, with patients trialling more preven- tative medications compared to controls, suggesting headaches may be more refractory to treatment.
083 Intravenous magnesium for acute presentations of migraine to A&E
Authors: Laurente Raphael , See Isaiah , Lane Charlie , Alim-Marvasti Ali , Balaratnam Michelle , Chandratheva Arvind , Matharu Manjit , Simister Robert , Kamourieh Salwa , Haider Salman
Published: August 2022

Background and aim

Studies have demonstrated the role of magnesium on acute migraine attacks and prophylaxis via voltage-dependent blockade of N-methyl-D-aspartate (NMDA)-coupled channels. Our aim was to study the tolerability of intravenous (IV) magnesium in the treatment of migraine in the Emergency Department (ED) and the Same Day Emergency Care (SDEC) unit of University College Hospital, London.

Methods

We performed a non-randomised open-label trial to establish the safety of IV magnesium sulfate. Patients were recruited from the ED or the SDEC unit of the hospital after being reviewed by consultant Neurologists from Aug 2021 – Jan 2022. Magnesium levels were measured prior to administration of the drug and complications were closely monitored.

Results

35 patients with status migrainosus were recruited; 30 were females and their mean age was 39 years (SD: 13.5 in years). All had normal serum magnesium levels prior to drug administration. No ECG changes were identified. None developed serious adverse symptoms during or immediately after infusion. A beneficial effect was noted in 15 patients, no effect in 10, and missing data in 10.

Conclusion

Administration of IV Magnesium is an effective and tolerated adjunct for the management of migraine. Efficacy studies are currently underway.
105 A rare presentation of Bickerstaff’s brainstem encephalitis
Authors: Terry Robyn , Wislocka-Kryjak Magdalena
Published: August 2022

Bickerstaff’s Brainstem Encephalitis (BBE) is a condition causing impairment of sensorium in association with ophthalmoplegia and ataxia. Here we present a case of BBE presenting with bilateral vocal cord paralysis.

A 35-year-old female presented with a sore throat and shortness of breath in the context of a fall and ankle injury the previous day. She became confused and agitated in hospital. Several hours after pres- entation she was found cyanosed with stridulous breathing (with normal saturations). Fibre-optic nasola- ryngoscopy revealed bilateral vocal cord palsy. She was intubated and transferred to ICU. Investigations including a full infection screen, CSF analysis and MRI were normal and non-diagnostic. Examination during a sedation hold revealed a unilateral third, fourth, and bilateral sixth and seventh cranial nerve palsies. She had flaccid quadriparesis and was globally areflexic. Nerve conduction studies showed a motor predominant polyneuropathy. A diagnosis of BBE was made based on the clinical findings with acute confusion. She was treated with plasma exchange and immunoglobulins and was discharged with almost complete recovery.

There are no previous case reports of vocal cord paralysis being the presenting feature of BBE. Neurologi- cal disease accounts for only 12% of cases of bilateral cord palsy. These causes may be systemic such as myasthenia gravis or diphtheria, or focal affecting the nucleus ambiguus in the medulla. However, clini- cians must recognise these cases promptly to ensure adequate investigation and treatment.
112 Parkinson’s disease and sociodemographic factors: a review
Authors: Wu Kit , Vidot Micha , Mitchell James W , Nitkunan Arani , Carr Georgina
Published: August 2022

Background

Unwarranted variation in treatment, care and support for people with Parkinson’s Disease (PD) is well documented. To improve equity of service, in line with the NHS Long Term Plan, it is imperative that we understand how sociodemographic factors affect management and care of PD.

Aim

To review published literature between sociodemographic factors and clinical factors, diagnosis, treatment and outcomes for people with PD.

Method

We conducted a focused review of published literature between 2000-2021 to outline the evidence describing the relationship between the ten protected characteristics of the Equality Act 2010 and clinical factors, treatment and outcomes in PD. Other factors such as deprivation, settlement status, education and employment were also explored.

Results

There is an abundance of published literature on age, disability, sex and gender over the twenty- year period. Studies on race and education and employment yielded mixed results. Evidence is lacking for gender reassignment, marriage and civil partnership, pregnancy and maternity, religion and belief, sexual orientation, deprivation, geographical variation (within UK), immigration and settlement.

Discussion

PD impacts on many facets of life. This review has identified many gaps in knowledge of the effect of sociodemographic factors affecting PD. More research is needed to better provide a more equitable service to patients.
125 Real world data evaluating efficacy and safety of oral cladribine for multiple sclerosis
Authors: Nasir Moneeb , Rabvukwa Plaxedes , Fuller Sarah , Chaudhuri Abhijit , Mattoscio Miriam
Published: August 2022

Background

Oral cladribine has been effective in clinical trials but only a few studies report real world data. This study assessed efficacy and safety of oral cladribine in an east London hospital.

Methods

Data were retrospectively collected on clinical relapses, new MRI lesions, EDSS change, annu- alised relapse rates (ARR), lymphocyte counts, and infections.

Results

56 patients had cladribine in our study (33 had cladribine years 1+2; 23 had only year 1; mean follow-up 24.9 months). Of 56 patients: 3 (5.4%) had a clinical relapse, 7 (12.5%) developed new asymp- tomatic MRI lesions, and 12 (21.4%) had EDSS progression. Overall, ongoing disease activity (either clinical relapse, MRI activity or EDSS progression) was seen in 15/56 patients (26.8%). EDSS improvement was seen in 12 patients (21.4%). Multiple logistic regression showed that prior ARR (p=0.18), baseline EDSS (p=0.52) and gender (p=0.49) did not influence likelihood of ongoing disease activity. Lymphopenia was seen in 31/56 patients (grade 3 = 6; grade 4 = 0).

Conclusions

Fewer patients had relapses in our study as compared to other similar studies. This may be due to the lower median baseline EDSS (3.5) and shorter follow-up in our cohort. The proportion of patients with EDSS progression, however, was similar to other studies.
147 Siponimod preserves retinal thickness: findings from the EXPAND OCT substudy
Authors: Vermesch Patrick , Gold Ralf , Bar-Or Amit , Cree Bruce , Fox Robert , Giovannoni Gavin , Li Bingbing , Piani-Meier Daniela , Karlsson Goeril , Kappos Ludwig
Published: August 2022

Aim

To evaluate changes in retinal thickness (µm), including the retinal nerve fibre layer (RNFL) and combined ganglion cell and inner plexiform layers (GCIPL), in patients receiving siponimod or placebo.

Methods

Changes in optical coherence tomography (OCT) measurements from screening to M12 and M24 were compared between the two treatment groups using mixed models for repeated measures adjusted for treatment, age, sex and respective baseline OCT variables.

Results

The OCT sub-study included 159 patients (siponimod, n=104; placebo, n=55). RNFL thickness at M12 numerically favoured siponimod (0.39 vs −0.99; p=0.099) but not at M24 (−0.05 vs. 0.48; p=0.642). However, fewer assessments were available for RNFL at M24 than M12. The between-group difference in GCIPL thinning was 0.21 (−2.55 vs −2.76; p=0.875) at M12 and 3.82 (−0.47 vs −4.29; p=0.01) at M24. Siponimod reduced retinal thinning vs placebo at M12 (change from baseline: 0.66 vs −1.86; p=0.006) and M24 (−0.05 vs −2.3; p=0.033). Changes of retinal thickness and GCIPL at the subfield areas also favoured siponimod over placebo.

Conclusions

These results support the sensitivity of OCT as a measure of tissue damage in progressive MS and are in line with previously reported beneficial effects of siponimod on other neurodegeneration related outcomes. Funding: Novartis Pharma AG, Basel, Switzerland.
148 Treating newly diagnosed relapsing-remitting multiple sclerosis (RRMS): a 2021 clinician survey in the United Kingdom
Authors: Evangelou Nikos , Mattoscio Miriam , Coutts Mhairi , Andiappan Mano , Sawtell Teresa , Rhys Katherine
Published: August 2022

Background

As new treatment approaches become available for RRMS it is important to understand clinical treatment decision-making.

Methods

We used a structured questionnaire to interview UK healthcare professionals (HCPs) about their clinical treatment approaches for RRMS.

Results

Of 38 HCPs interviewed, 53% were multiple sclerosis (MS) Consultants, 34% MS specialist nurses, 11% neurologists with an MS interest (3% other). The most important treatment goals for newly diagnosed RRMS were modifying/reducing relapse, delaying progression to disability and maintaining quality of life, reported by 63% (24/38), 58% (22/38) and 50% (19/38) of respondents, respectively. 74% of respond- ents strongly agreed and 24% agreed early treatment is essential for better outcomes in most patients. The (mean [SD]; n=37) estimated percentage of patients treated with high efficacy early or escalation approaches were 42.1% (21.8) and 58.3% (20.8), respectively; 66% of respondents agreed these proportions reflected the treatment approach they would like to take. For those disagreeing (34%), the mean (SD) reported percentage of patients they would ideally treat with high efficacy and escalation approaches were 66.2% (18.0) and 33.8% (18.0), respectively.

Conclusions

Whilst the majority of HCPs agreed that early treatment of RRMS is essential, there was vari- ability in reported and ideal treatment approaches.
149 Down but not out repurposing depression treatments for multiple sclerosis with the UK MS register
Authors: Rodgers Jeff , Middleton Rod , Witts James , Craig Elaine , Tuite-Dalton Katie , Nicholas Richard ,   MS Register Research Group
Published: August 2022

Introduction

Repurposing treatments in multiple sclerosis (MS) has resulted in several candidates that are currently in phase 2 and 3 trials but to test candidate therapies requires a prolonged and costly study. Real world data offers the opportunity to assess in non-randomised data the potential of a range of commonly used therapies. The UK MS register is a UK-wide real-world dataset of 20,000 subjects where regular MS outcomes are collected. Using this dataset, we have recently shown the benefits of disease modifying therapies, and smoking cessation in MS. We aimed to determine if such a resource could be used to determine to utility of potential repurposed drug candidates

Methods

Of 20,000 subjects in the UK MS register we identified those on any antidepressants treatment who had at least 2 follow up visits from baseline after starting treatment. We then identified those who had completed the Hospital Anxiety and Depression Scale (HADS) and the Multiple Sclerosis Impact Scale (MSIS-29) scales in addition at each visit.

Results

3559 subjects on 4294 unique antidepressant treatments were identified (SSRIs: 1852, Tricyclics: 1893, SNRIs: 365. NaSSa: 164, and SARIs: 20). 533 had a baseline visit and 2 follow-up visits with HADS and MSIS-29 questionnaires, where baseline was the beginning of treatment.

Conclusions

The UK MS Register cohort of pwMS can be utilised to support real-world initiatives to inves- tigate potential repurposed candidates.
151 Updated analysis of pregnancy outcomes for patients with MS in a dimethyl fumarate exposure registry
Authors: Rog David , Hellwig Kerstin , McGuigan Christopher , Mokliatchouk Oksana , Branco Filipe , Lyons Jennifer , Everage Nicholas
Published: August 2022

Introduction

Dimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies potential foetal risk. Given limited pregnancy data, the UK and Ireland have enrolled DMF-exposed pregnant women in an ongoing international registry assessing pregnancy outcomes. In the general population, 62% of pregnancies end in live birth, 22% in abortion, and 16% in foetal loss, with similar rates in multiple sclerosis (MS) patients.

Methods

Women with MS exposed to DMF since the first day of their last menstrual period before con- ception/during pregnancy were included. UK/Ireland Coordinating Centres liaised directly with patients and healthcare providers.

Results

As of March 2021, 403 patients (19 UK/Ireland) were enrolled. Of 350 reported pregnancy outcomes (19 UK/Ireland), 329 (94%) represented live births (100% UK/Ireland). Of 326 infants with known gestational age,

298 births (91%) were full-term (100% UK/Ireland) and 28 (9%) premature (<37 weeks). Of the 21 (6%) cases of foetal loss, 19 were spontaneous abortions (1 each ectopic and molar pregnancy) and 2 foetal deaths (>28 weeks). There was one neonatal death. Nine infants (2 UK/Ireland) had EUROCAT-confirmed birth defects.

Conclusions

The observations are consistent with MS and general populations.

Support

Biogen. Disclosures on poster.
153 ChariotMS – cladribine to halt deterioration in people with advanced multiple sclerosis (pwAMS)
Authors: Schmierer Klaus , Baker David , Nawaz Tanjil , Allen-Philbey Kimberley , Barkhof Frederik , Chataway Jeremy , Hooper Richard , Mihaylova Borislava , Hobart Jeremy , Pavitt Sue
Published: August 2022

Background

Disease-modifying treatments (DMT) have transformed the management of people with MS. However, those with an EDSS>6.5 (pwAMS) are considered not suitable for DMT due to (i) a focus on ambulation as outcome measure, (ii) the assumption that in pwAMS, inflammation plays no role, and (iii) a disregard for potentially length-dependent neuro-axonal damage. Cladribine tablets (Mavenclad®) is an effective, convenient, relatively safe DMT licensed for people with highly-active relapsing MS. Cladrib- ine depletes B (less so T) cell subsets, particularly memory B cells, putatively key for disease control in MS.

Aims

To test efficacy, safety and cost-effectiveness of cladribine tablets in pwAMS (EDSS 6.5-8.5), expand mechanistic understanding of cladribine and provide evidence for NHS adoption.

Methods

Randomised, double-blind, placebo-controlled phase IIb trial. Primary outcome measure, 9-hole peg test speed at 104 weeks vs baseline. Sample size calculations indicated n=200 required to detect 15% treatment effect in 9HPT peg-speed with 90% power at 5% significance and 20% drop-out.

Results

Nine/20 trial sites currently open for recruitment. Five participants already enrolled. Full recruit- ment predicted in Q1/2023.

Conclusions

ChariotMS is the first DMT-trial focussing on pwAMS. If successful, ChariotMS could expand the DMT landscape to include pwAMS, and provide a platform for add-on therapies.
154 Incidence of persistent lymphopenia in people with multiple sclerosis on dimethyl fumarate
Authors: Wood Callum , Pickersgill Trevor , Willis Mark , Robertson Neil , Tallantyre Emma
Published: August 2022

Background

Dimethyl fumarate (DMF) is a disease modifying therapy (DMT) used to manage Multiple Sclerosis (MS). The recently revised Summary of Product Characteristics (SPC) recommends increased monitoring or cessation of this medication for persistent (> 6 months) lymphopenia, because of an increased risk of Progressive Multifocal Leukoencephalopathy. Awareness of the frequency of persistent lymphopenia will guide clinical decisions regarding drug choice and safety monitoring.

Methods

Medical records of 146 patients with MS, started on DMF between 2014-2020 who received > 6 months of treatment were reviewed to identify the incidence, duration, and risk factors of persistent lymphopenia.

Results

Overall, 16 (11%) people with MS taking DMF experienced persistent moderate lymphopenia (0.5-0.7x109/L for > 6m) and 5 (3%) experienced persistent severe lymphopenia (<0.5 x 109/L for > 6m). Mean times to persistent moderate and severe lymphopenia were 10.6 months and 25.5 months respec- tively. Increased age was a predictor for persistent lymphopenia (B=0.071, p=0.004); sex and previous DMT were not.

Conclusion

Persistent moderate – severe lymphopenia is relatively common in people on DMF. More robust guidelines for both risk/benefit of continuing DMF despite persistent lymphopenia, and DMT sequencing following DMF in people with lymphopenia are required.
155 Reasons for stopping MS disease modifying treatment in a UK cohort
Authors: John Freddie St , Froud Joseph , Willis Mark , Anderson Valerie , Uzochukwu Emeka , Wynford-Thomas Ray , Tallantyre Emma , Robertson Neil ,   et al,   on behalf of UK MS Registries Consortium
Published: August 2022

Background

Success of disease modifying therapy (DMT) for relapsing MS (RMS) is dependent on both effectiveness and adherence. We have explored reasons for stopping DMT in a large multicentre RMS cohort to inform disease management.

Methods

Data was collected from sequential RMS patients receiving a DMT in 8 UK MS centres. DMT discontinuation events were recorded according to a standardised classification comprising: adverse event, increased risk of adverse event, lack of efficacy, onset of progressive disease, patient choice, pregnancy/pre-conceptual care, other, unknown.

Results

Data from 6,816 prescriptions in 4,102 patients (female 72%, mean 1.7 prescriptions, range 1-6 per patient) were analysed. The most common reason for stopping was lack of efficacy (37%) followed by adverse event (31%), increased risk of adverse event (10%) and then pregnancy/preconceptual care (9%). Reasons for stopping varied by treatment duration, age, sex and DMT. DMT discontinuation due to adverse events fell from 51% in year 1, to 15% in years 5-10; discontinuation due to lack of efficacy rose from 22% to 45%. Increasing disability was rarely a reason to stop DMT.

Conclusions

These data provide valuable insights into the real-world utility of MS DMTs and could provide a rationale to refine existing treatment pathways.
Acute inflammatory CNS diseases following vaccination against SARS-CoV-2
Authors: Francis Anna , Camera Valentina , Elhadd Kariem , Craner Matthew , Attfield Katherine , Iversen Astrid , Huda Saif , Fugger Lars , Palace Jacqueline
Published: August 2022

Background

Vaccination is a recognised trigger of ADEM and approximately 50% paediatric cases have antibodies to MOG. The SARS-CoV-2 mass vaccination programme could therefore trigger cases of MOGAD. Neuromyelitis optica (NMO) is an autoimmune inflammatory condition of the CNS associ- ated with antibodies to AQP4.

Method

Ten patients (ages 22 – 65 years) with antibodies to MOG or AQP4 were referred to the NHS England NMO service having developed acute onset CNS inflammation within 8 weeks of vaccination.

Results

Eight patients had MOGAD, seven of whom received the AstraZeneca vaccine (AZV) and one the Pfizer vaccine (PV). Only the post-PV MOGAD patient presented with typical adult-onset phenotype of isolated ON. All post-AZV MOGAD patients presented atypically; 85.7% had LETM and 71.4% had intrac- erebral lesions, resembling ADEM more commonly seen in paediatric MOGAD. The atypical presentation supports a causative role of AZV, but the role of PV is less convincing.

Two patients had AQP4-NMOSD with typical demographic features. Both received AZV. Less typically, one young adult presented with LETM rather than characteristic young adult ON, the other had a silent short segment myelitis, which is rarely seen in AQP4-NMOSD. Both patients achieved good outcomes.

Conclusion

We discuss the potential causation and pathophysiological mechanisms.
167 mTBI Predict: a prospective biomarker study to predict outcomes in mild traumatic brain injury
Authors: Lyons Hannah , Belli Tony , Blanch Richard , Hampshire Adam , Jensen Ole , Mitchell James , Rogers Jack , Seemungal Barry , Withnall Rich , Sinclair Alexandra ,   et al
Published: August 2022

Background

Mild traumatic brain injury (mTBI) is common accounting for 1.4 million hospital visits annually in the UK. Although classified as mild it leads to disproportionate impact on future health. Many suffer long-term disability driven by post-traumatic headache, mood and visual disturbances, vestibular dys- function, post-traumatic stress disorder, cognitive impairment and inability to work. Biomarkers to predict these outcomes are an unmet need.

Methods

We will conduct a longitudinal, prospective cohort study over 8 years, recruiting 800 participants (military, civilian and sports injuries) with an acute diagnosis of mTBI. At onset, assessment of biomarkers will include brain imaging, cerebral physiology, blood and saliva, headache, mental health, vision, balance, and cognitive performance. We will evaluate the ability of biomarkers to predict long-term complications at 6, 12 and 24 months (and at 10 years plus though NHS digital data).

Discussion

This UK mTBI consortium aims to identify accurate, reproducible and clinically practical mul- timodal biomarkers in mTBI. Biomarkers would identify those with a good prognosis who could rapidly return to activity and those likely to suffer complications focussing prompt and targeted therapy. This programme of research aims to deliver a step change in patient care and bring much needed advances in mTBI management.