bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical decision-making at the end of life: a mixed-methods study
Authors: Taylor Paul , Johnson Miriam J , Dowding Dawn Wendy 
Published: October 2018

ObjectivesTo improve the ability of clinical staff to recognise end of life in hospital inpatients dying as a result of cancer and heart failure, and to generate new hypotheses for further research.MethodsThis mixed-methods study used decision theory as a theoretical basis. It involved a parallel databases-convergent design, incorporating findings from previously published research, with equal priority to study groups and synthesis by triangulation. The individual arms were (1) a retrospective cohort study of 102 patients with cancer and 81 patients with heart failure in an acute trust in the North of England, and(2) a semistructured interview study of 19 healthcare professionals caring for the same patient groups.ResultsThe synthesis of findings demonstrated areas of agreement, partial agreement, silence and dissonance when comparing the cohort findings with the interview findings. Trajectories of change are identified as associated with poor prognosis in both approaches, but based on different parameters. Management of patients has a significant impact on decision-making. The decision process requires repeated, iterative assessments and may benefit from a multidisciplinary approach. Uncertainty is a defining characteristic of the overall process, and objective parameters only have a limited role in predicting end of life.ConclusionsThe role of uncertainty is important as a trigger for discussions and a defined stage in a patient’s illness journey. This is consistent with current approaches to recognising irreversible deterioration in those with serious illness. This study contributes ongoing evidence that these concepts are vital for decision-making.
The impact of Northern Ireland’s abortion laws on women’s abortion decision-making and experiences
Authors: Aiken Abigail R A , Padron Elisa , Broussard Kathleen , Johnson Dana 
Published: October 2018

BackgroundIn Northern Ireland, abortion is illegal except in very limited circumstances to preserve a woman’s life or to prevent permanent or long-term injury to her physical or mental health. Abortions conducted outside the law are a criminal offence punishable by imprisonment. We assessed the impacts of Northern Ireland’s abortion laws on women’s decision-making and experiences in accessing abortion.MethodsBetween April 2017 and February 2018 we interviewed 30 women living in Northern Ireland who had sought abortion by travelling to a clinic in Great Britain or by using online telemedicine to self-manage a medication abortion at home. We interviewed women both before and after a policy change that allowed women from Northern Ireland access to free abortion services in Great Britain. We used a semi-structured in-depth approach and analysed the interviews using grounded theory methodology to identify key themes.ResultsFour key findings emerged from our analysis: (1) women experience multiple barriers to travelling for abortion services, even when abortion is provided without charge; (2) self-management is often preferred over travel, but its criminalisation engenders fear and isolation; (3) obstruction of import of abortion medications by Northern Ireland Customs contributes to stress, anxiety, a higher risk of complications, and trial of ineffective or unsafe methods; and (4) lack of clarity surrounding the obligations of healthcare professionals in Northern Ireland causes mistrust of the healthcare system.ConclusionsNorthern Ireland’s abortion laws negatively affect the quality and safety of women’s healthcare and can have serious implications for women’s physical and emotional health. Our findings offer new perspectives for the current policy debate over Northern Ireland’s abortion laws and suggest a public health rationale for decriminalising abortion.
National survey of UK endoscopists showing variation in diathermy practice for colonic polypectomy
Authors: Verma Ajay M , Chilton Andrew P 
Published: October 2018

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

ObjectiveDespite 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.DesignDNA 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.ResultsWe 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.ConclusionTogether 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

ObjectivesTo 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).MethodsTwo 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).ResultsEleven 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.ConclusionsCurrent 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

BackgroundThe 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.MethodologyData 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.ResultsVolume 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.DiscussionThe 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.
THUR 262 Diagnosis of osas in neurology outpatients
Authors: Aayushi Shukla ,   Coebergh
Published: October 2018

BackgroundObstructive 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.MethodsThe 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.Results32 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.ConclusionUndiagnosed 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

IntroductionThe 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.MethodWe 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.ResultsThe 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.ConclusionThis 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

IntroductionVasovagal 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. MethodDNA 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). ResultsUsing 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. ConclusionMy 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

BackgroundTransient 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.MethodsPatients 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.Results249 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%).ConclusionsTLOC-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

AimsTo analyse the MRI abnormalities of myelin oligodendrocyte glycoprotein-antibody (MOG-Ab) associated demyelinating disease.MethodsClinical records and 165 MRIs from 56 patients with MOG-Abs were reviewed.ResultsThe 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.ConclusionsApart 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.Results1299 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.ConclusionThis 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.