bluuebunny/crossref_metadata_2025 huggingface dataset:
National survey of UK endoscopists showing variation in diathermy practice for colonic polypectomy
Authors: Verma Ajay M , Chilton Andrew P
Published: October 2018

Introduction

Diathermy practice in colonic polypectomy has a poor evidence base. We surveyed endoscopists across the UK to gain an insight in current diathermy practice.

Methods

An eight-question survey was designed to be compact, easy to complete, while still capturing the relevant data. This national survey was circulated by the endoscopy committees of the British Society of Gastroenterology and Association of Coloproctology of Great Britain and Ireland.

Results

The survey was open between February and October 2016. Analysis showed: (1) 250/348 (71.8%) completed the full survey, 159 gastroenterologists (63.6%), 36 surgeons (14.4%), 34 gastroenterology trainees (13.6%), 21 others (8.4%); (2) predominant use ofcoagulationcurrent for small pedunculated polypectomy, high rates of cold snare polypectomy for small sessile polyps (right 43.2% > left 34.4%); (3) acombination of coagulationandcuttingcurrent, orEndo Cut, was most popular for larger polypectomy; (4) low use ofEndo Cutmode irrespective of size/location of polyp (17.2%–32.0%); (5) 204/250 (81.6%) used reduced current settings for right colon polypectomy; and (6) 208/250 (83.2%) were confident on knowledge and use of diathermy.

Conclusion

This national survey exposes a wide variation in practice suggesting that colonoscopists employ diathermy modalities that they are comfortable with. As many complications are as direct result of thermal injury and polypectomy is the most frequent therapeutic intervention, appropriate training and formal guidance is lacking.
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming
Authors: Koutsioumpa Marina , Hatziapostolou Maria , Polytarchou Christos , Tolosa Ezequiel J , Almada Luciana L , Mahurkar-Joshi Swapna , Williams Jennifer , Tirado-Rodriguez Ana Belen , Huerta-Yepez Sara , Karavias Dimitrios , Kourea Helen , Poultsides George A , Struhl Kevin , Dawson David W , Donahue Timothy R , Fernández-Zapico Martín E , Iliopoulos Dimitrios
Published: October 2018

Objective

Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis.

Design

DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo.

Results

We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. KMT2D is transcriptionally repressed in human pancreatic tumours through DNA methylation. Clinically, lower levels of this methyltransferase associate with poor prognosis and significant weight alterations. RNAi-based genetic inactivation of KMT2D promotes tumour growth and results in loss of H3K4me3 mark. In addition, KMT2D inhibition increases aerobic glycolysis and alters the lipidomic profiles of pancreatic cancer cells. Further analysis of this phenomenon identified the glucose transporter SLC2A3 as a mediator of KMT2D-induced changes in cellular, metabolic and proliferative rates.

Conclusion

Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer.
Genetic risk factors for modulation of age at onset in Machado-Joseph disease/spinocerebellar ataxia type 3: a systematic review and meta-analysis
Authors: de Mattos Eduardo Preusser , Kolbe Musskopf Maiara , Bielefeldt Leotti Vanessa , Saraiva-Pereira Maria Luiza , Jardim Laura Bannach
Published: October 2018

Objectives

To perform a systematic review and meta-analysis of genetic risk factors for age at onset (AO) in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD).

Methods

Two authors independently reviewed reports on the mathematical relationship between CAG length at the expanded ATXN3 allele (CAGexp), and other genetic variants if available, and AO. Publications from January 1994 to September 2017 in English, Portuguese or Spanish and indexed in MEDLINE (PubMed), LILACS or EMBASE were considered. Inclusion criteria were reports with >20 SCA3/MJD carriers with molecular diagnosis performed by capillary electrophoresis. Non-overlapping cohorts were determined on contact with corresponding authors. A detailed analysis protocol was registered at the PROSPERO database prior to data extraction (CRD42017073071).

Results

Eleven studies were eligible for meta-analysis, comprising 10 individual-participant (n=2099 subjects) and two aggregated data cohorts. On average, CAGexp explained 55.2% (95% CI 50.8 to 59.0; p<0.001) of AO variability. Population-specific factors accounted for 8.3% of AO variance. Cohorts clustered into distinct geographic groups, evidencing significantly earlier AO in non-Portuguese Europeans than in Portuguese/South Brazilians with similar CAGexp lengths. Presence of intermediate ATXN2 alleles (27–33 CAG repeats) significantly correlated with earlier AO. Familial factors accounted for ~10% of AO variability. CAGexp, origin, family effects and CAG length at ATXN2 together explained 73.5% of AO variance.

Conclusions

Current evidence supports genetic modulation of AO in SCA3/MJD by CAGexp, ATXN2 and family-specific and population-specific factors. Future studies should take these into account in the search for new genetic modifiers of AO, which could be of therapeutic relevance.
WED 017 Call on me: expanding the consultant advice line for gps
Authors: Richard Ellis , Booth James , Julie Riley , Jen Duffy , Martin Wilson
Published: October 2018

Background

The Consultant Advice Line (CAL) is a service developed to provide telephone advice for GPs within our catchment. The hours of this service were extended in early 2017 to increase its capacity for GPs seeking guidance on neurological issues as part our Neuro Network Vanguard project.

Methodology

Data was routinely collected from calls received between 1 st March and 30th June 2017, and a sample of GPs completed an online survey after the call.

Results

Volume of calls has more than doubled since expansion, with calls spread evenly through the week and from all CCG’s in our region. Feedback from GP’s was overwhelmingly positive with an average ‘call usefulness’ score of 9.2/10, and 100% saying they would use the service again. 40% reported the advice had avoided an outpatient referral.

Discussion

The provision of equitable neurology services is challenging in the current climate. New models of care such as this help to break down barriers between primary and specialist care, reducing undesirable variation in access to acute neurology input and reducing unnecessary referrals to secondary and tertiary care.
WED 225 Changing epidemiology of motor neurone disease in scotland
Authors: Danielle Leighton , Siddharthan Chandran ,   Consortium CARE-MND
Published: October 2018

Clinical Audit Research and Evaluation for Motor Neurone Disease (CARE-MND) (formerly the Scottish MND Register) is an electronic platform for prospective, population-based research in Scotland. We present the results of recent epidemiological analyses.

Capture-recapture methods were adopted to determine incidence of MND in 2015–2016: 1) notifications via CARE-MND, 2) Information Services Division (ISD) data i) hospital admissions, ii) death data, iii) riluzole prescriptions.

Crude prevalence of MND in Scotland is 7.61–7.64/100,000 of the population. Direct age standardised incidence in 2015 was 3.42/100,000 (95% CI: 2.99 to 3.91); in 2016, 2.89/100,000 (95% CI: 2.50 to 3.34). Using maximum likelihood estimates, coverage of the CARE-MND platform was 99.6% (2015) and 98.1% (2016). In view of high coverage, CARE-MND estimates alone will be presented for 2017.

Previous Scottish MND Register capture-recapture annual incidence estimates were 2.32/100,000 (95% CI: 2.26 to 2.37) in 1989–1998 (direct standardised). Our data suggest a changing landscape of MND in Scotland, with a rise in incidence by 36%. This could be attributed to improved neurological services in Scotland. Incidence is also 67% higher than Northern European estimates, which perhaps reflects our robust ascertainment methods. However, further work using population CARE-MND data aims to determine if genetic or environmental variables account for these findings.
WED 259 The challenge of mood and cognition screening in hasu
Authors: Kirsty Harkness , Ronan O’Malley , Gary Pratt
Published: October 2018

The National Clinical guideline for stroke, recommends that services for people with stroke should provide screening for mood and cognition within six weeks of stroke using validated tools. In HASU assessing mood and cognition in a timely fashion has been challenging. In 2013 a previous audit showed cognitive screening at 48% and mood screening at only 7%. We instituted a number of measures to improve compliance including education events for MDT staff, a bespoke stroke clerking proforma, to include data collection boxes. We also introduced the briefer ‘YALE questionnaire’ for mood, and the Montreal Cognitive Assessment Tool (MOCA). We also piloted occupational therapy staff using a ‘screening sticker’ in patient notes. A daily MDT was also introduced, primarily to improve patient flow, but also to prompt action planning. Mood screening improved to 92% and cognition screening to 95% on detailed notes audit. These high compliance figures were however not fully reflected on SSNAPP although compliance has improved. SSNAP data input is completed by a single coder, non clinical staff member. We plan to employ a second data clerk and further revise the stroke proforma.
THUR 262 Diagnosis of osas in neurology outpatients
Authors: Aayushi Shukla ,   Coebergh
Published: October 2018

Background

Obstructive sleep apnoea syndrome (OSAS) can present with neurological symptoms. Treatment of underlying OSAS can improve neurological comorbidities like Parkinson’s, epilepsy and Alzheimer’s. Early identification of OSAS may explain and improve symptoms. The aim of this study was to identify the association between the diagnosis of OSAS and presenting symptoms like headaches, memory problems, seizures and vertigo.

Methods

The medical records and polysomnography reports of 40 patients, newly diagnosed with OSAS by a consultant in a neurology outpatient clinic at a NHS district general hospital, were reviewed; the likelihood of OSAS explaining presenting symptoms was rated on a 1–4 scale.

Results

32 OSAS patients were included in the study (21 male and 11 female). 15 patients (46.8%) presented with headaches, 5 patients (15.6%) with memory problems, 5 patients (15.6%) suffered from (dissociative and epileptic) seizures and 1 patient (3.1%) suffered from vertigo. 10 patients (31%) newly diagnosed presented with none of these neurological symptoms. All 32 patients presented with at least one of the typical symptoms of OSAS for example daytime sleepiness, snoring, and witnessed apnoeas.

Conclusion

Undiagnosed OSAS is likely common in neurology outpatients and often can explain presenting symptoms and can be a treatable co-morbidity.
THUR 263 5 year review of our specialist obstetric-neurology clinic
Authors: Salwa Kamourieh , K Dhanjal Mandish , Pooja Dassan
Published: October 2018

Introduction

The confidential enquiry into maternal deaths has shown that neurological disorders are the second most frequent cause of indirect maternal death and lack of access to a specialist service was the main factor contributing to the number of preventable deaths.

Method

We looked at our local joint neuro-obstetric clinic over a 5 year period and studied the number of patients seen each year, the diagnosis, list of current medications and the referral route.

Results

The numbers of new patients seen in the clinic each year increased from 27 in 2013 up to 62 in 2017. Epilepsy was the commonest presentation, followed closely by migraines and then multiple sclerosis. With regards to medications, a third of epileptic patients were on dual anti-epileptic therapy and there were still patients taking sodium valproate at presentation. Initial referrals to the clinic were mainly from the local midwife-lead antenatal service. More recently, there has been a significant increase in referrals from the local neurology service and other allied specialties.

Conclusion

This data confirms that the number of patients seen in our service has more than doubled over the 5 year period, largely as a result of increased awareness of our easy-to-access multi-disciplinary clinic.
274 Exome analysis to investigate autosomal dominant vasovagal syncope
Authors: Jesuthasan Aaron , Keogh Michael , Chinnery Patrick
Published: October 2018

Introduction

Vasovagal syncope (VVS) is the most common cause of syncope in children and adults. Previous studies suggest a genetic component accounts for approximately 20% of cases, although the genes responsible are often unidentified. I studied the DNA of two distantly related individuals with VVS enrolled into the 100,000 Genomes Project to identify causal mutations.

Method

DNA was extracted from the patients, and analysed using an Ingenuity Variant Analysis program to detect the presence of mutations. The severity of each detected mutation was subsequently examined using two programs: Sorting Intolerant from Tolerant (SIFT) and Polymorphing Phenotyping v2 (PolyPhen-2).

Results

Using Ingenuity Variant Analysis, a mutation in the ACE (Angiotensin Converting Enzyme), EPAS1 (Endothelial PAS Domain Protein 1) and PLCG2 (Phospholipase C Gamma 2) genes of the VVS patients were identified. Further analysis using SIFT and PolyPhen-2 indicated the ACE mutation was likely to produce a defective protein whilst the EPAS1 and PLCG2 mutations were unlikely to have any effect on protein function.

Conclusion

My results support the involvement of the ACE mutation in the cause of VVS within the two studied patients. This may point towards a novel target for therapy within the individuals, should the findings be successfully validated.
WED 024 Acute model in gloucestershire
Authors: Harriet Ball , Rose Bosnell , Geraint Fuller
Published: October 2018

We operate a consultant led ‘post-acute’ model for Acute Neurology service delivery, with Advice and Guidance (an email service for GPs); attendance at twice daily ‘huddle’ meetings on MAU; and inpatient e-referrals. We have two sites, 683 inpatient beds in Gloucester Royal, and 379 in Cheltenham General. 10–15 of these inpatient beds (in Gloucester) are flexibly allocated under neurology.

We received 153 inpatient e-referrals over a 1 month audit (October 2017). 78% of these received an inpatient review (the remaining 22% were managed by email); 97% within 24 hours, 7 days per week; 100% by consultants. This averages 5 referrals per day (range 0–9). Patients can be transferred under neurology when beds are available (49 admissions/month).

The reasons for referral included focal neurological deficits (27%), headache (21%), epilepsy (14%), movement disorders (10%), unexplained loss of consciousness or possible seizure (9%), altered consciousness (8%), neurological infections (3%), and scan abnormalities (3%).

This rapid input is in line with the ABN’s Quality Standard for Unscheduled Care. The referral element of this service requires approximately 1.5–2 PAs on each weekday, and 1 PA on each weekend day. We are also about to start an acute neurology clinic (approx. 20 slots per week).
280 A screening questionnaire for transient loss of consciousness
Authors: Alistair Wardrope , Jenny Jamnadas-Khoda , Mark Broadhurst , A Grünewald Richard , J Howell Stephen , Matthias Koepp , Steve Parry , Sanjay Sisodiya , Matthew Walker , Markus Reuber
Published: October 2018

Background

Transient loss of consciousness (TLOC) is a common primary care presentation. 90% are due to syncope (S), epilepsy (E), or psychogenic non-epileptic seizures (PNES). Misdiagnosis and delayed diagnosis is common. We explore symptoms and witness observations that can classify patients with likely diagnoses of E, S, or PNES.

Methods

Patients with objectively-documented diagnoses of E, S, or PNES, and an attack witness, were invited to complete a questionnaire (capturing medical history, 86 peri-episodal experiences, and 31 witness observations). Iterative feature selection identified questions strongly predictive of diagnosis; a random forest trained on these classified patients into likely diagnoses of E, S, or PNES.

Results

249 patients (86 E, 79 s, 84 PNES) were randomly assigned to training or validation in a 2:1 ratio. Feature selection identified 36 highly-predictive questionnaire items. The classifier correctly diagnosed 86% of patients in validation. 100% of S were correctly diagnosed, 85.7% E and 75% PNES. A simpler 12-feature model correctly classified 76.7% of cases (E: 75%; S: 92.3%; PNES: 65.6%).

Conclusions

TLOC-associated symptoms and manifestations can contribute to a decision rule for primary/emergency care, assisting triage and referral. Determining a diagnostic pre-test probability from TLOC features can aid interpretation of investigation abnormalities of uncertain significance.
289 MRI abnormalities in mog antibody disease
Authors: S Huda , Al-Orainy Amal , Saldanha Anita , D Whittam , Denby Christine , Pandit Lekha , M Bhojak , A Jacob
Published: October 2018

Aims

To analyse the MRI abnormalities of myelin oligodendrocyte glycoprotein-antibody (MOG-Ab) associated demyelinating disease.

Methods

Clinical records and 165 MRIs from 56 patients with MOG-Abs were reviewed.

Results

The median age was 29(8–71) years and 52% percent were female. Common phenotypes included isolated optic neuritis (ON)=17, or transverse myelitis (TM)=16, ON+TM =12, and combinations of above groups with cerebral and/or brainstem involvement=11. Seventeen patients (30%) fulfilled NMOSD 2015 diagnostic criteria.

All patients had brain imaging and 89% (50/56) had spinal imaging. Common areas of MRI brain abnormality involved brainstem(32%), hemispheric white matter(29%), corticospinal tracts(21%), and U-fibres(20%). Dawson’s fingers were not detected in any patients.

Cord imaging showed longitudinally extensive myelitis in 69% (20/29) and atrophy in 4% (2/47). Optic nerve imaging was abnormal in 69% (18/26) of patients, with bilateral lesions in 33% and long lesions (orbital and/or canalicular) in 83%.

On serial MRI, radiological improvement was observed in 76% (22/29; median interval- 14 months) and importantly asymptomatic new lesions were absent in 13 untreated patients after a median of 16.5 months.

Conclusions

Apart from optic nerve and spinal cord changes, brainstem and hemispheric white matter abnormalities are common in MOG-antibody disease. Irrespective of treatment, asymptomatic accrual of brain and/or spinal lesions is uncommon.
291 St george’s hyperacute neurology: right person, right time
Authors: Kuven Moodley , Valerie Jones , Mahinda Yogarajah , Kiran Samra , Umesh Vivekananda , Oliver Foster , Anthony Pereira , Gillian Cluckie , Niranjanan Nirmalananthan
Published: October 2018

The St George’s Hospital Hyperacute Neurology Service is a comprehensive consultant-delivered service in a regional neuroscience centre setting that builds on existing recommendations, incorporating hyperacute stroke assessments and the delirium multidisciplinary team. There is proactive daily inreach into acute medicine and the emergency department with Rapid Access Neurology ‘Hot’ clinics providing a means of avoiding admission referrals from primary care and supporting rapid discharge of ambulatory patients from ED. We present data from the first year of this service.

Results

1299 patients were reviewed (stroke:603; acute neurology:452; Hot clinics:244).

30% of all referrals were discharged directly from the ED and, with ‘hot’ clinics, contributed to 361 admissions avoided.

Stroke mimic utilisation of acute beds (11% reduction) and median thrombolysis times also improved (38 v30 mins). For admitted acute neurology patients, median(IQR) LoS=2.0 (0.0–7.0), representing a 50% improvement on previous performance (p<0.001). For hot clinics, the median wait for an appointment=4.0 days(IQR:2.0–6.0). No diagnostics were required in 25% of cases.

Conclusion

This new service complements existing hyperacute stroke pathways, improving outcomes for all neurology patients presenting to primary care, emergency and acute medical services. In particular, rapid access clinics appear to be an efficient means of providing unscheduled OP care.
295 Clinical outcome in mog-antibody disease: a large single site cohort
Authors: Silvia Messina , Maciej Jurynczyk , R Woodhall Mark , George Tackley , Saleel Chandratre , Cheryl Hemingway , Patrick Waters , Isabel Leite Maria , Jacqueline Palace
Published: October 2018

Background

MOG-antibody disease has been recently recognized as a demyelinating condition distinct from Multiple Sclerosis. Methods: A single-site study of 106 MOG-antibody positive patients (including a 63-patient incident cohort) describing the clinical phenotype and outcome.

Results

ON was the most common onset presentation (51%) and was bilateral in about half. From the survival curve analysis in the incident cohort we estimated that 38% of patients relapsed within 18 months. The risk was lower in patients immunosuppressed for >3 months (p=0.013). Permanent motor disability (EDSS ≥6; limited walking distance) and visual acuity ≤6/36 in at least one eye occurred in 3.7% and 13.2% respectively after a median disease duration of 68 months (range 2–484). Permanent bladder dysfunction was present in 23.6% patients and around 2/3 of these had bowel dysfunction. 20% of males had permanent erectile dysfunction (44% of males with TM at onset).

Conclusion

This is the largest single-centre cohort and the only incident cohort published, and shows that MOG-antibody disease is often relapsing but may be modified with 6–12 months of prednisolone. The prognosis is typically good, better than AQP4-antibody positive disease, but many patients are left with significant sphincter and erectile dysfunction and some with visual impairment.
WED 028 One person can make a difference: our experience in a busy london dgh
Authors: Lalloo Aadila , Raheem Bazo , Cocco Giovanni , Guzman Ana , Rose Michael , Niccolini Flavia , Silber Eli
Published: October 2018

Our Neurology unit is in a busy district general hospital; serving a deprived inner London community, providing a ward consultation service 5 days a week. The unit consists of 5 consultant Neurologists, a consultant Neuroradiologist and 2 specialist nurses. In 2016, a junior doctor was appointed. By analysing data from 10 months in 2015 and 2017; we assessed the impact on the delivery of Neurological care, before and after the appointment. The unit saw a 157% increase in number of patients seen, including a significant proportion now seen in ED and ambulatory care. This is equivalent to a minimum of 2 more patients each working day (n=872 vs. 1317). The percentage of patients seen on same day of referral (<12 hours) increased from 47% to 77%. The proportion of inpatients reviewed who were then followed up on the ward during their stay, increased from 13.9% to 35.5%, representing increased availability of continuing Neurology advice. The percentage of patients who waited more than 24 hours for Neurology input decreased from 14.9% to 5.83%. Our results support the appointment of a full time junior colleague to allow rapid, safe and ongoing Neurological input to patients and to support ED and admitting colleagues.
THUR 071 Towards an integrated tool for pnes assessment
Authors: Eleanor d’Ersu , Talal Al-Mayhani , Meneka Sidhu
Published: October 2018

Introduction

Psychogenic non-epileptic seizures (PNES) can present a real diagnostic challenge, with subsequent impact on the course of the disorder and its management. A number of studies have looked into predictive factors for PNES. However, no guidance is available for applying the findings of these studies in clinical practice.

Aim

The aim is to combine the most recognised discriminative features into an integrated clinical tool, ultimately, to improve the predictive value of the medical assessment of patients with possible PNES in a clinic setting. This can be invaluable in centres with limited access to video telemetry (VT).

Methods

The following criteria were employed and compared with the results of VT as gold standard:

Patient comorbidities

Conversation analysis

Review of system questionnaire

Ictal semiology and autonomic activation

Postictal prolactin and lactate

Results and conclusion

This QIP will assess the reliability and validity of various criteria in recognising PNES clinically. Based on our findings, an integrated tool will then be designed as an adjunct to the standard medical assessment in settings where VT is not readily available.
WED 148 Imaging findings in autoimmune encephalitis: a retrospective review
Authors: Jawad Fazal , Nouman Sadiq , Michael Bowen , Wali Muhammad Wasim , Vijay Sawlani , Saiju Jacob
Published: October 2018

Background

Neuroimaging findings in autoimmune encephalitis may include normal MRI as well as limbic and extra-limbic involvement. Prompt recognition allows early immunosuppression and improved outcomes.

Methods

Retrospective review of patients with Autoimmune encephalitis over the last 5 years.

Results

We identified N-methyl-d-aspartate receptor (NMDAR) n=8, voltage gated potassium channel (VGKC) n=11, and leucine-rich glioma inactivated 1 (LGI1) n=11 encephalitis patients. 1/8 NMDAR encephalitis patients had abnormal MRI findings of T2 hyper intense signal in right anterior temporal and bilateral frontal and left insular lobe. DWI sequence showed restricted diffusion. 4/11 with VGKC encephalitis had positive MRI findings. Two patients had limbic involvement while one also had involvement of basal ganglia. Two patients had modest cerebral atrophy. Four patients had normal MRI findings. MRI scan was not available for three patients. 5/11 LGI1 encephalitis patients had bilateral mesial temporal lobe changes. In one patient, MRI could not be done due to permanent pacemaker. Five patients had normal MRI findings.

Conclusions

In our series, 33% patients had abnormal MRI findings consistent with a diagnosis of autoimmune encephalitis, which is lower than reported in literature. High clinical suspicion should lead to prompt diagnosis even in the absence of typical encephalitic changes on MRI.
WED 163 Monitoring for outcome assessment and trial recruitment of pwms
Authors: Kimberley Allen-Philbey , Ben Turner , Ozlem Yildiz , Joela Mathews , Gavin Giovannoni , Klaus Schmierer
Published: October 2018

Background

The time constraint of NHS care is difficult to reconcile with the comprehensive neurological assessment required to complete a mandatory EDSS for NHS England funded disease modifying treatment of people with multiple sclerosis (pwMS). We report our experience with parametric data collection in order to (i) inform DMT decisions and (ii) improve characterisation for recruitment of pwMS in clinical trials.

Methods

We implemented a battery consisting of the symbol digit modality test, 9-hole-peg-test, 25ft walking test and ABILHAND. pwMS were encouraged to sign up to the MS Register to record patient reported outcomes and ‘webEDSS’. Data from the MS Register and BartsMS Database were electronically linked.

Results

334 pwMS at different disease stages (EDSS 0–8.5) have been assessed at least annually. Of these, 64% had a relapsing and 36% a progressive disease course. Clinically meaningful data was obtained and displayed in an engaging portal for interpretation by the clinical team and pwMS.

Conclusion

It’s feasible to implement multidimensional monitoring of pwMS to benefit (i) management of pwMS and (ii) trial recruitment, particularly for pwMS with EDSS >6.5. Longitudinal follow-up and data analysis is underway. Standardisation of a simple, regularly collected, dataset may improve performance assessment between centres.
WED 164 EQ-5D in the assessment of relapse recovery in ms
Authors: Wynford-Thomas Ray , Harding Katharine , Hawton Annie , Hirst Claire , Tallantyre Emma , Green Colin , Robertson Neil
Published: October 2018

Rationale

50% of multiple sclerosis (MS) relapses result in permanent disability. Modelling recovery from relapse enables cost-effectiveness of interventions to be evaluated. The expanded disability status scale (EDSS) is cumbersome in clinical practice and may not reflect patient experience. The EQ-5D is a standardised measure of health status and a common currency used by agencies such as NICE.

Aim

To compare measurable recovery from relapse using EDSS and EQ-5D.

Method

EDSS and EQ-5D-3L were collected during clinician defined relapse and at 2 months follow-up, in 89 patients identified in a regional rapid access clinic.

Results

Median EDSS in relapse was 5.0 and 3.5 at follow-up; 67 (75%) patients experienced improvement in EDSS. The proportion of patients with EQ-5D scores of level 1 (fewest symptoms) increased in all 5 domains at 2 months, although anxiety/depression was the most resistant to improvement. Of those with EDSS improvement, only 49 (73%) reported improvement in their health state (EQ-5D).

Conclusion

EDSS improvement following relapse is not always accompanied by patient-reported improvement in health state (EQ-5D), which may be more effective in identifying ongoing health issues. Low-level discrepancies may also inform on the relative merit of EQ-5D versus EDSS in assessing recovery.
WED 165 The management of cognitive and behavioural symptoms in ms
Authors: Gloria Onwuneme , TA Hayat Tayyib , A Hosseini Akram
Published: October 2018

Background

Approximately half of MS patients (pwMS) experience cognitive impairments including domains such as memory, concentrations, executive functions, which can be exacerbated by mood disturbances and fatigue. NICE guidelines (CG168) recommend proactive identification of cognitive symptoms, assessment and referral to neuropsychology services or occupational therapy.

Aim

To assess the local departmental MS service with regards to diagnosis and management of cognitive and behavioural symptoms.

Method

We conducted a retrospective audit of pwMS attending the specialist MS clinic since March 2017. Records were reviewed for documented evidence of: a discussion about cognitive and behavioural changes; use of assessment tools; management; referral. Data was also collected on demographics, presence of comorbidities, use of disease modifying therapy, and cognition-modulating medication.

Results

69% of pwMS demonstrated cognitive or behavioural symptoms including: fatigue (71%), poor memory (28%), depression, sleep disturbance, and concentration difficulties. Almost half expressed multiple symptoms. 47% of patients were referred for further management with OT, psychology services, or counselling.

Conclusion

This study highlights the ongoing need for greater focus on identification of cognitive and behavioural symptoms in the MS population. Furthermore, simple assessment tools such as questionnaires should be considered within the clinic for monitoring cognitive symptoms and response to intervention.
WED 168 Blood-brain barrier imaging with dynamic contrast-enhanced mri
Authors: Aravinthan Varatharaj , Maria Liljeroth , Angela Darekar , Henrik BW Larsson , Ian Galea , Stig P Cramer
Published: October 2018

Background

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can detect subtle blood-brain barrier (BBB) permeability. We developed a protocol and conducted experiments to validate the technique.

Methods

12 subjects with relapsing-remitting multiple sclerosis (RRMS) and 13 controls were recruited. Whole-brain 3D DCE-MRI at 3 Tesla was used to calculate the influx constant Ki (Patlak method). Values were derived for manual regions of interest (ROI) as well as segmented tissue masks. In controls, cerebral blood volume (CBV) was measured in grey and white matter.

Results

In RRMS, Ki in visibly-enhancing lesions was significantly higher than in normal-appearing white matter (NAWM) (p=0.002). Ki in NAWM was significantly higher in RRMS than controls, by both ROI (p=0.014) and segmentation (p=0.019) methods. In controls, Ki was significantly higher in grey than white matter (p=0.001). CBV (and therefore vascular surface area) was also significantly higher in grey matter (p=0.005), with a mean ratio of 1.9.

Conclusions

Our method produces results in line with the expected behaviour of a BBB permeability marker, and the grey/white matter CBV ratio is in agreement with the histologically-established value.
THUR 179 Ocrelizumab effect on neda in patient subgroups of opera I and opera II
Authors: Ben Turner , Caroline Papeix , Bruce Cree , Ludwig Kappos , Xavier Montalban , Jerry Wolinsky , Regine Buffels , Jian Han , Stephen Hauser
Published: October 2018

Background

In a pooled analysis of patients with relapsing multiple sclerosis in the Phase III OPERA I and OPERA II (NCT01247324/NCT014112333) studies, ocrelizumab increased the proportion of patients with no evidence of disease activity (NEDA) vs interferon β−1a (IFNβ1a); post hoc subgroup analyses are reported here.

Methods

NEDA (no 12 week confirmed disability progression, relapse, new/enlarging T2 lesions or T1 gadolinium enhancing lesions) rates were compared by Cochran–Mantel–Haenszel test on the pooled modified intent-to-treat (mITT) population (ocrelizumab, n=761 [600 mg intravenously every 24 weeks]; IFNβ1a, n=759 [44 μg subcutaneously three times weekly]; excludes patients with NEDA discontinuing for reasons unrelated to efficacy).

Results

Treatment benefit for NEDA in the mITT population with ocrelizumab vs IFNβ1a (47.7% vs 27.1%; p<0.001) was maintained across subgroups (ocrelizumab/IFNβ1a; p<0.001 unless stated): age (<40 years: 44.3%/22.6%; ≥40 years: 52.8%/33.7%), gender (male: 44.0%/22.2%; female: 49.7%/29.6%), prior [last 2 years] disease-modifying therapy (yes: 42.8%/23.9%; no: 49.5%/28.3%), prior relapses [last 12 months] (≤1: 49.2%/29.2%; ≥2: 44.2%/22.6%), baseline T1 Gd-enhancing lesions (none: 59.6%/38.8%; ≥1: 30.1%/10.2%) and baseline EDSS score (EDSS <2.5/<4.0: ocrelizumab 50.5%/50.3%, IFNβ1a 27.5%/26.4%; EDSS ≥2.5/≥4.0: ocrelizumab 46.0%/39.6%, IFNβ1a 26.9%/29.4% [NB: EDSS score ≥4: ocrelizumab/IFNβ1a p=0.043]).

Conclusions

Subgroup analyses were consistent with those of the overall pooled population on maintaining NEDA status.
WED 184 Cladribine tablets in clarity patients with high disease activity ms
Authors: Giovannoni Gavin , Rammohan Kottil , Cook Stuart , Comi Giancarlo , Rieckmann Peter , Soelberg-Sorensen Per , Vermersch Patrick , Dangond Fernando , Hicking Christine
Published: October 2018

Background

Patients with high disease activity (HDA) relapsing-remitting MS are less likely to attain no evidence of disease activity (NEDA; no relapses, MRI activity or progression).

Objective

Post-hoc analysis to compare the proportion of patients with NEDA with cladribine tablets 3.5 mg/kg (CT3.5) vs placebo.

Methods

Patients from CLARITY were retrospectively stratified using 2 definitions of HDA based on relapse history, prior treatment, and MRI characteristics: HRA (n=261) and HRA plus disease activity on treatment (HRA+DAT) [n=289]). Data for patients treated with CT3.5 or placebo who fulfilled these criteria and achieved NEDA status were compared over the 2 years using odds ratios (OR) and 95% CI.

Results

HRA subgroup: 76% of CT3.5-treated patients were relapse-free and 84% were T1 Gd+ lesion free vs 49% and 31%, respectively, for placebo. HRA+DAT subgroup: 77% of CT3.5-treated were relapse-free and 85% were T1 Gd+ lesion free vs 50% and 32%, respectively, for placebo. In the HRA and HRA+DAT subgroups, 43.2% and 43.7%, respectively, of CT3.5-treated patients were disease activity free compared with 8.7%, (OR: 8.02; 95% CI: 3.93 to 16.35; p<0.0001) and 9.0% (OR: 7.82; 95% CI: 4.03 to 15.19; p<0.0001) respectively, for placebo. In the overall population, composite NEDA score favored CT over placebo (OR: 4.46; 95% CI: 3.18 to 6.26; p<0.0001).

Conclusions

Treatment with CT3.5 significantly increased the proportion of HDA patients with NEDA vs placebo.

Disclaimer

http://medpub-poster.merckgroup.com/ABN2018DISC_NEDA.pdf
Analysis of urinary macrophage migration inhibitory factor in systemic lupus erythematosus
Authors: Vincent Fabien B , Slavin Laura , Hoi Alberta Y , Kitching Arthur Richard , Mackay Fabienne , Harris James , Kandane-Rathnayake Rangi , Morand Eric F
Published: October 2018

Objective

To characterise the clinical relevance of urinary macrophage migration inhibitory factor (uMIF) concentrations in patients with systemic lupus erythematosus (SLE).

Methods

MIF, adjusted for urine creatinine, was quantified by ELISA in urine samples from 64 prospectively recruited patients with SLE. Serum MIF and urinary monocyte chemoattractant protein 1 (uMCP-1) were quantified by ELISA in a subset of patients (n = 39). Disease activity was assessed using the SLE Disease Activity Index-2000 (SLEDAI-2K) score.

Results

uMIF was detectable in all patients with SLE. uMIF was positively correlated with overall SLEDAI-2K, was significantly higher in patients with SLE with high disease activity (SLEDAI-2K≥10) compared with those with inactive disease (SLEDAI-2K<4), and this association remained significant after adjusting for ethnicity, flare and use of immunosuppressants. uMIF was also significantly higher in SLE patients with flare of disease, although not confirmed in multivariable analysis. No significant differences in uMIF levels were observed according to the presence of renal disease activity, as assessed by renal SLEDAI-2K or biopsy-confirmed lupus nephritis. In contrast, uMCP-1 was significantly higher in SLE patients with active renal disease. uMIF expression was not associated with irreversible organ damage accrual or glucocorticoid use.

Conclusions

These data suggest uMIF as a potential overall but not renal-specific SLE biomarker, whereas uMCP-1 is a renal-specific SLE biomarker.
Contributory injustice in psychiatry
Authors: Miller Tate Alex James
Published: October 2018

I explain the notion of contributory injustice, a kind of epistemic injustice, and argue that it occurs within psychiatric services, affecting (at least) those who hear voices. I argue that individual effort on the part of clinicians to avoid perpetrating this injustice is an insufficient response to the problem; mitigating the injustice will require open and meaningful dialogue between clinicians and service user organisations, as well as individuals. I suggest that clinicians must become familiar with and take seriously concepts and frameworks for understanding mental distress developed in service user communities, such as Hearing Voices Network, and by individual service users. This is especially necessary when these concepts and frameworks explicitly conflict with medical or technical understandings of users’ experiences. I defend this proposal against three objections.
Arterial occlusions increase the risk of in-stent restenosis after vertebral artery ostium stenting
Authors: Li Jingzhi , Hua Yang , Needleman Laurence , Forsberg Flemming , Eisenbray John R , Li Zhaojun , Liu Ran , Tian Xiaojie , Jiao Liqun , Liu Ji-Bin
Published: October 2018

Objective

The study was designed to investigate if vascular occlusion in the internal carotid artery (ICA) or the contralateral vertebral artery (VA) contribute to developing in-stent restenosis (ISR) in patients with vertebral artery ostium stenosis (VAOS).

Methods

420 consecutive patients treated with VAOS stents (from a population of 8145 patients with VAOS) from January 2013 to December 2014 were analyzed in this retrospective study; 216 with drug eluted stents and 204 with bare metal stents. Based on pre-stent DSA findings, patients were divided into four groups: both carotid and vertebral arteries patent (PAT), ICA occlusion (ICA-OCC), contralateral VA occlusion (CVA-OCC), and combined occlusions (C-OCC). The incidence of ISR (stenosis >50%) was compared between groups using Cox regression analysis.

Results

Of the 420 patients, the mean incidence of ISR was 36.4%, with a median 12 months of follow-up (IQR 3–12). Logistic regression analysis showed that drug eluting stent had less ISR than bare metal stent (OR=0.38, 95% CI 0.19 to 0.75, P=0.01). Cox regression analysis showed that CVA-OCC (HR=1.63, P=0.02) and C-OCC (HR=3.30, P=0.001) were risk factors for ISR but not ICA-OCC (P=0.31). In the CVA-OCC and C-OCC groups, in-stent peak systolic velocity (PSV) ≥140 cm/s, 1 day after successful stenting, was associated with subsequent development of ISR (OR=2.81, 95% CI 1.06 to 7.43, P=0.04).

Conclusion

Contralateral VA occlusion at the time of stenting increased the risk of ISR, especially if stent PSV on day 1 was >140 cm/s. Bare metal stents had more ISR than drug eluting stents.
Risk factors for post-9/11 chronic rhinosinusitis in Fire Department of the City of New York workers
Authors: Putman Barbara , Zeig-Owens Rachel , Singh Ankura , Hall Charles B , Schwartz Theresa , Webber Mayris P , Cohen Hillel W , Prezant David J , Bachert Claus , Weiden Michael D
Published: October 2018

Objectives

Chronic rhinosinusitis (CRS) has high socioeconomic burden but underexplored risk factors. The collapse of the World Trade Center (WTC) towers on 11 September 2001 (9/11) caused dust and smoke exposure, leading to paranasal sinus inflammation and CRS. We aim to determine which job tasks are risk factors for CRS in WTC-exposed Fire Department of the City of New York (FDNY) firefighters and emergency medical services (EMS) workers.

Methods

This cohort study included a 16-year follow-up of 11 926 WTC-exposed FDNY rescue/recovery workers with data on demographics, WTC exposure, job tasks and first post-9/11 complete blood counts. Using multivariable Cox regression, we assessed the associations of WTC exposure, work assignment (firefighter/EMS), digging and rescue tasks at the WTC site and blood eosinophil counts with subsequent CRS, adjusting for potential confounders.

Results

The rate of CRS was higher in firefighters than EMS (1.80/100 person-years vs 0.70/100 person-years; p<0.001). The combination of digging and rescue work was a risk factor for CRS (HR 1.54, 95% CI 1.23 to 1.94, p<0.001) independent of work assignment and WTC exposure.

Conclusions

Compared with EMS, firefighters were more likely to engage in a combination of digging and rescue work, which was a risk factor for CRS. Chronic irritant exposures associated with digging and rescue work may account for higher post-9/11 CRS rates among firefighters.
Early coronary angiography and survival after out-of-hospital cardiac arrest: a systematic review and meta-analysis
Authors: Khera Rohan , CarlLee Sheena , Blevins Amy , Schweizer Marin , Girotra Saket
Published: October 2018

Background

Although acute myocardial infarction is a common cause of out-of-hospital cardiac arrest (OHCA), the role of early coronary angiography in OHCA remains uncertain. We conducted a meta-analysis of observational studies to determine the association of early coronary angiography with survival in OHCA.

Methods

We searched multiple electronic databases for published studies on early coronary angiography in OHCA between 1 January 1990 and 18 January 2017. Studies were included if (1) restricted to only OHCA, (2) included an exposure group that underwent early coronary angiography within 1  day of arrest onset and a concurrent control group that did not undergo early coronary angiography, and (3) reported survival outcomes. We used a random-effects model to obtain pooled OR. I2﻿ statistics and Cochran’s Q test were used to determine between-study heterogeneity.

Results

A total of 17 studies with 14 972 patients were included, of whom 6424 (44%) received early coronary angiography. Early coronary angiography was associated with higher odds of survival (pooled OR 2.54 (95% CI 1.94 to 3.33)) and survival with favourable neurological outcome (pooled OR 2.37 (95%  CI 1.71 to 3.28)). However, there was substantial heterogeneity in our pooled estimate (I2=88%  and p value for Cochran’s test <0.0001 for both outcomes). The large heterogeneity in pooled estimates was reduced after including adjusted estimates when available, and was explained by differences in methodological rigour and characteristics of included studies.

Conclusion

Among patients resuscitated from OHCA, early coronary angiography is associated with increased survival to discharge and favourable neurological outcome.
Survival in patients with univentricular hearts: the impact of right versus left ventricular morphology
Authors: Erikssen Gunnar , Aboulhosn Jamil , Lin Jeannette , Liestøl Knut , Estensen Mette E , Gjesdal Ola , Skulstad Helge , Døhlen Gaute , Lindberg Harald Lauritz
Published: October 2018

Objective

Patients with univentricular hearts (UVH) have high mortality despite modern treatment, and better methods to identify patients at highest risk are needed. We wanted to improve risk stratification in patients with UVH by focusing on the prognostic significance of single right versus single left ventricular morphology (SRV vs SLV).

Methods

All 395 patients with UVH operated at our centre were prospectively included from 1972 to 2016 (195 SRV, 166 SLV, 34 mixed or indeterminate ventricular morphology). Diagnoses, UVH morphology, types of all operations and time and causes of death or heart transplantation (HTX) were recorded. The primary endpoint was death or HTX.

Results

Among the 111 non-Fontan patients, 88 died (SRV 62 vs SLV 20; p<0.0001), 32 due to heart failure (SRV 23 vs SLV 5; p=0.0012). Twenty-five  years of cumulative SRV versus SLV survival among the 284 Fontan patients (41 deaths/HTX) was 66.9% vs 87.9% (p=0.0027), partly explained by more deaths/HTX due to heart failure among patients with SRV (p=0.0006). Survival in patients with SRV with and without hypoplastic left heart syndrome (HLHS) was similar. SRV versus SLV was a strong predictor of death/HTX in multivariable proportional hazards analyses (RR 3.3, 95% CI 1.6 to 6.6).

Conclusion

SRV versus SLV is a strong short-term and long-term predictor of survival among patients with UVH, mainly explained by higher rates of death/HTX due to heart failure in the SRV group. Our findings apply to patients with SRV both with and without HLHS.