bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital volume and outcomes for acute pulmonary embolism: multinational population based cohort study
Authors: Jiménez David , Bikdeli Behnood , Quezada Andrés , Muriel Alfonso , Lobo José Luis , de Miguel-Diez Javier , Jara-Palomares Luis , Ruiz-Artacho Pedro , Yusen Roger D , Monreal Manuel 
Published: July 2019

AbstractObjectivesTo evaluate the association between experience in the management of acute pulmonary embolism, reflected by hospital case volume, and mortality.DesignMultinational population based cohort study using data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry between 1 January 2001 and 31 August 2018.Setting353 hospitals in 16 countries.Participants39 257 consecutive patients with confirmed diagnosis of acute symptomatic pulmonary embolism.Main outcome measurePulmonary embolism related mortality within 30 days after diagnosis of the condition.ResultsPatients with acute symptomatic pulmonary embolism admitted to high volume hospitals (>40 pulmonary embolisms per year) had a higher burden of comorbidities. A significant inverse association was seen between annual hospital volume and pulmonary embolism related mortality. Admission to hospitals in the highest quarter (that is, >40 pulmonary embolisms per year) was associated with a 44% reduction in the adjusted odds of pulmonary embolism related mortality at 30 days compared with admission to hospitals in the lowest quarter (<15 pulmonary embolisms per year; adjusted risk 1.3% v 2.3%; adjusted odds ratio 0.56 (95% confidence interval 0.33 to 0.95); P=0.03). Results were consistent in all sensitivity analyses. All cause mortality at 30 days was not significantly reduced between the two quarters (adjusted odds ratio 0.78 (0.50 to 1.22); P=0.28). Survivors showed little change in the odds of recurrent venous thromboembolism (odds ratio 0.76 (0.49 to 1.19)) or major bleeding (1.07 (0.77 to 1.47)) between the low and high volume hospitals.ConclusionsIn patients with acute symptomatic pulmonary embolism, admission to high volume hospitals was associated with significant reductions in adjusted pulmonary embolism related mortality at 30 days. These findings could have implications for management strategies.
Validation of the five-tier Taiwan Triage and Acuity Scale for prehospital use by Emergency Medical Technicians
Authors: Ng Chip-Jin , Chien Cheng-Yu , Seak Julian Chen-June , Tsai Shang-Li , Weng Yi-Ming , Chaou Chung-Hsien , Kuo Chan-Wei , Chen Jih-Chang , Hsu Kuang-Hung 
Published: July 2019

ObjectivesThis study aimed to determine the inter-rater reliability of the five-level Taiwan Triage and Acuity Scale (TTAS) when used by emergency medical technicians (EMTs) and triage registered nurses (TRNs). Furthermore, it sought to validate the prehospital TTAS scores according to ED hospitalisation rates and medical resource consumption.MethodsThis was a prospective observational study. After training in five-level triage, EMTs triaged patients arriving to the ED and agreement with the nurse triage (TRN) was assessed. Subsequently, these trained research EMTs rode along on ambulance calls and assigned TTAS scores for each patient at the scene, while the on-duty EMTs applied their standard two-tier prehospital triage scale and followed standard practice, blinded to the TTAS scores. The accuracy of the TTAS scores in the field for prediction of hospitalisation and medical resource consumption were analysed using logistic regression and a linear model, respectively, and compared with the accuracy of the current two-tier prehospital triage scale.ResultsAfter EMT’s underwent initial training in five-level TTAS, inter-rater agreement between EMTs and TRNs for triage of ED patients was very good (κw=0.825, CI 0.750 to 0.900). For the outcome of hospitalisation, TTAS five-level system (Akaike’s Information Criteria (AIC)=486, area under the curve (AUC)=0.75) showed better discrimination compared with TPTS two-level system (AIC=508, AUC=0.66). Triage assignments by the EMTs using the the five-level TTAS was linearly associated with hospitalisation and medical resource consumption.ConclusionsA five-level prehospital triage scale shows good inter-rater reliability and superior discrimination compared with the two-level system for prediction of hospitalisation and medical resource requirements.
Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma
Authors: Cai Jiabin , Chen Lei , Zhang Zhou , Zhang Xinyu , Lu Xingyu , Liu Weiwei , Shi Guoming , Ge Yang , Gao Pingting , Yang Yuan , Ke Aiwu , Xiao Linlin , Dong Ruizhao , Zhu Yanjing , Yang Xuan , Wang Jiefei , Zhu Tongyu , Yang Deping , Huang Xiaowu , Sui Chengjun , Qiu Shuangjian , Shen Feng , Sun Huichuan , Zhou Weiping , Zhou Jian , Nie Ji , Zeng Chang , Stroup Emily Kunce , Zhang Xu , Chiu Brian C-H , Lau Wan Yee , He Chuan , Wang Hongyang , Zhang Wei , Fan Jia 
Published: July 2019

ObjectiveThe lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC.DesignApplying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 patients with HCC, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularisation for feature selection.ResultsThe 5hmC-Seal data from patients with HCC showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer staging system from non-HCC (validation set: area under curve (AUC)=88.4%; (95% CI 85.8% to 91.1%)), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumours (eg, ≤2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC=84.6%; (95% CI 80.6% to 88.7%)), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (eg, smoking/alcohol intake history).ConclusionWe have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.
Are observed associations between a high maternal prepregnancy body mass index and offspring IQ likely to be causal?
Authors: Coo Helen , Fabrigar Leandre , Davies Gregory , Fitzpatrick Renee , Flavin Michael 
Published: July 2019

BackgroundA high maternal prepregnancy body mass index has been associated with lower offspring IQ, but it is unclear if the relationship is causal. To explore this, our objectives were to compare maternal and paternal estimates and to assess whether certain factors mediate the association.MethodsWe analysed data from the Avon Longitudinal Study of Parents and Children, which initially recruited 14 541 women residing in Avon, UK, with an expected date of delivery in 1991–1992. Data were collected during and after pregnancy by questionnaire, medical record abstraction and clinical assessment. At approximately 8 years of age, psychologists administered an abbreviated form of the Wechsler Intelligence Scale for Children-III. We fit multivariable logistic regression models to estimate parental prepregnancy obesity and overweight–offspring IQ associations. Counterfactually defined indirect (mediated) effects of maternal prepregnancy obesity on offspring IQ were estimated through path analysis.ResultsAmong 4324 mother–father–child triads and using normal weight as the referent, we observed consistently stronger associations for maternal prepregnancy obesity and offspring performance IQ (eg, adjusted β (95% CI)=−3.4 (−5.7 to −1.2) vs −0.97 (−2.9 to 0.96) for paternal obesity). The indirect effects of maternal obesity on offspring IQ through pathways involving gestational weight gain and duration of breastfeeding were small but significant.ConclusionOur findings are consistent with a weak biologic effect of maternal adiposity in pregnancy on offspring performance IQ. Given the growing prevalence of obesity worldwide, more evidence is needed to resolve the correlation versus causation debate in this area.
118 Case series: subacute combined degeneration of the spinal cord in vitamin B12-replete recreational nitrous oxide abusers
Authors: Blair Chris , Tremonti Chris , Edwards Leon , Haber Paul , Halmagyi Michael 
Published: July 2019

IntroductionWithin a few years of its discovery in late 18th century, nitrous oxide was being used recreationally for its pleasurable effects. It remains in widespread use as an inhaled stimulant today, and can be legally acquired in bulk quantities with relative ease. In the body prolonged exposure to nitrous oxide leads to the oxidization of vitamin B12, rendering it unusable in key enzymatic reactions necessary for myelin synthesis. Over time this qualitative deficiency leads to a central demyelination syndrome that characteristically develops despite normal serum vitamin B12 levels and, with continued exposure to nitrous oxide, resists treatment with vitamin B12 supplementation.MethodNitrous oxide abusers presenting with a central demyelination syndrome were enrolled in this case series. Serum levels of vitamin B12, active B12, folate and homocysteine were measured. Nitrous oxide exposure was discontinued, and all patients were treated in accordance with evidence-based guidelines.ResultsEight patients presented with predominantly moderate-to-severe clinical deficits. The majority were vitamin B12 replete. In most cases individuals had actively engaged in prolonged vitamin B12 supplementation in an attempt to circumvent the harmful pathophysiology, of which they were loosely aware. Following treatment and rehabilitation several patients were discharged into full-time care, and most had significant residual disability at follow-up.ConclusionsThis case series not only illustrates the tragic consequences of abuse of this widely available and legally procured stimulant, but also highlights the futility of pursuing a nominally ‘protective’ strategy of vitamin B12 supplementation in the context of continued nitrous oxide exposure.
133 B cell depletion therapy resulting in sustained remission of severe autoimmune complications following alemtuzumab treatment of multiple sclerosis
Authors: Massey Jennifer , Sutton Ian 
Published: July 2019

IntroductionAlemtuzumab is a pan-lymphocyte ablating anti CD-52 monoclonal antibody licensed for the treatment of relapsing remitting multiple sclerosis (RRMS). Despite being classified as a high efficacy therapy, clinical application of alemtuzumab has been hampered by the frequent occurrence of secondary autoimmune disease (AID), with clinical trials and single-centre follow up cohorts estimating an incidence of up to 50% at seven years post treatment. Despite the establishment of pharmacovigilance programs to monitor for common complications of alemtuzumab, management guidelines for these conditions are lacking.MethodsHere, we report a series of cases of female patients treated with alemtuzumab for RRMS who developed treatment refractory secondary AID complications; specifically acquired haemophilia A (AHA) and an autoimmune encephalitis (AIE).ResultsWe report the sustained remission of these severe autoimmune disorders following administration of anti-CD20 therapy. This supports the current understanding of alemtuzumab associated AIDs, which occur in a time frame in which B-cell hyperpopulation and peripheral expansion occurs following initial lymphoablation.ConclusionsThus, we suggest that B-cell depletion should be initiated early in patients with severe, refractory complications of alemtuzumab. Furthermore, we suggest vigilant monitoring of patients with a preceding history of autoimmune thyroid disease following alemtuzumab treatment, as our experience suggests these patients have already demonstrated the potential to develop secondary AID.
029 Time equals brain – retrospective analysis of thrombolysis in regional australia to determine factors which influence door to needle time
Authors: Nindra Udit , Wonson Toni M , Fuller Karen 
Published: July 2019

IntroductionMinimising delay in thrombolysis is a key outcome in acute stroke care.MethodsA 3 year retrospective cohort analysis of all acute stroke admissions in Wollongong Hospital, a major regional referral centre in New South Wales, was completed to determine the causes of in-hospital delays for thrombolysis. Data collected included age, baseline National Institute of Health Stroke Scale (NIHSS) score, onset time, arrival time, CT imaging & reporting time and outcomes of the event.ResultsFrom 656 admissions, 70 cases of thrombolysis were recorded 56 cases of endovascular thrombectomy. The mean time from onset to arrival was 85 minutes, from arrival to CT was 31 minutes and from door to needle time (DNT) was 108 minutes. Multiple regression analysis revealed a an inverse linear association between onset to arrival time and DNT. Age, stroke severity and gender were not shown to impact treatment times. The results showed that there was a paradoxical association between arrival time and DNT. The cause for this was not clearly identified but similar to previous studies is likely to be contributed by a lack of urgency when initiating management.1 2ConclusionFor every 30-minute delay in hospital arrival, there was a 13- minute reduction in DNT. In light of this, education trials to promote ‘time equals brain’ understanding amongst stroke first responders is being implemented to aim to reduce DNT to less than 80 minutes. The results of this are anticipated to be available in mid 2019.ReferencesAlbers GW, Bates VE, Clark WM. Intravenous tissue-type plasminogen activator for treatment of acute stroke: The Standard Treatment with Alteplase to Reverse Stroke (STARS) Study. Journal of the American Medical Association 2000; 283:1145–1150.Romano JG, Muller N, Merino JG, Forteza AM, Koch S, Rabinstein AA. In-hospital delays to stroke thrombolysis: paradoxical effct of early arrival. Neurological Research 2007;29:664–666.
030 Management and attitudes towards persons with epilepsy in general practice: how far have we come?
Authors: Sharobeam Angelos , Mamun Abul , Beran Roy G 
Published: July 2019

IntroductionPrevious surveys of general practitioners (GP) attitudes regarding epilepsy and people with epilepsy (PWE), conducted 20–30 years ago1 2, identified the need for further education in epilepsy care for GPs. This follow up study of GPs in Sydney, Australia, was conducted to determine the degree of changes in knowledge, attitudes and management of PWE, to evaluate if there had been significant improvement during this period.MethodsA piloted questionnaire addressing epilepsy investigations, preferred care provider and attitudes towards epilepsy was developed and completed by a representative sample of Sydney GPs.ResultsA total of 52 completed responses were received. 36 out of 47 GPs (77%) chose neurologists as the most important care giver, followed by the GP (9/47; 18.7%), 25/51 respondents (49%) mentioned they never personally initiated anti-epileptic medication (AEM) and another 27% (14/51 GPs) rarely commenced AEM therapy. 6/50 GPs did not mention EEG as a routine investigation and 21/50 did not mention MRI as routine for PWE. The five most commonly prescribed AEMs, according to frequency were sodium valproate (42), carbamazepine (37), levetiracetam (31), lamotrigine (16) and phenytoin (15). Newer AEMs, available for over a decade in Australia were not mentioned. Emotional, behavioral psychosocial issues were perceived to be more common amongst PWE.ConclusionThe study indicates little perceptual shift regarding GP’s attitudes to epilepsy, and significant deficiencies in knowledge, particularly with regards to investigations and management. The findings reinforce a need for more formal training of GPs caring for PWE.ReferencesBeran RG, Read T. A survey of doctors in Sydney, Australia: perspectives and practices regarding epilepsy and those affected by it. Epilepsia. 1983;24(1):79–104.Frith JF, Harris MF, Beran RG. Management and attitudes of epilepsy by a group of Sydney general practitioners. Epilepsia. 1994;35(6):1244–7.
033 Cluster of creuzfeldt-jakob disease in the south western sydney local health district population in the past 5 years
Authors: Dhanapalaratnam Roshan , Cappelen-Smith Cecilia , Thomas Peter , Beran Roy G 
Published: July 2019

IntroductionNoting a perceived increased case-load of Creuzfeldt-Jakob disease (CJD) patients at Liverpool Hospital, in the South-Western Sydney Local Health District (SWSLHD), the authors questioned the accepted death from CJD incidence of 1 per million.MethodsWe reviewed the District Health-Information-Exchange (HIE) database for all admissions with CJD diagnoses in SWSLHD hospitals, over a 5-year period 2014–2018. The SWSLHD services a population of 1,001,437. The HIE identified cases were reviewed according to World Health Organization (WHO) diagnostic criteria as used by the Australian national CJD registry. Definite and probable CJD cases were included in the study. Incidence per year was calculated from the final case number across the 5-year SWSLHD population.Results26 patients coded with a diagnosis of CJD were identified from HIE database over the period. These cases were critically reviewed and 20 confirmed as definite (n=4) or probable CJD (n=16) cases. The diagnoses of excluded patients (n=6) were herpes simplex encephalitis, paraneoplastic encephalitis, delirium, and 2 with progressive multifocal leukoencephalopathy. Calculated incidence based on 5-year SWSLHD population was 4.16 cases per 1 million population/year.ConclusionsIn the 5-year period, we note an incidence of definite and probable CJD cases in the SWSLHD population, four times the national and worldwide reported rates. Cases from the last 2-months of 2018 are pending at the time of submission, which may alter these observations. These findings most likely represent a cluster of cases in the SWSLHD area but may alternatively reflect either better recognition or increased incidence of CJD.
047 Acute lumbosacral plexopathy after blood loss in a patient with bilateral common iliac artery occlusion
Authors: Katz Matthew , McCombe Pamela 
Published: July 2019

IntroductionWe present a case of a 56 year old male with bilateral, asymmetric leg weakness from ischemic lumbosacral plexopathy. This followed acute blood loss from an episode of self-harm, which occurred in the setting of chronic thrombotic occlusion of bilateral common iliac artery (CIA) stents.MethodsA detailed history, examination and neurophysiology study were performed in addition to reviewing case notes and results of other investigations. A brief literature review was also completed.ResultsThe patient presented with acute blood loss following self-inflicted lacerations to his anterior neck and both wrists. He had asymmetric flaccid, areflexic weakness of his legs with decreased sensation over the right foot and absent distal leg pulses. Magnetic resonance imaging (MRI) of brain and whole spine was normal. Computed tomography angiogram (CTA) revealed significant distal aortic atherosclerotic disease with complete occlusion of bilateral CIA stents. The patient underwent endovascular re-stenting of both common iliac arteries with a good angiographic result. An electromyogram per-formed one month later was supportive of a lumbosacral plex-opathy, mainly on the right.Only three cases of acute ischemic lumbosacral plexopathy have been reported in the setting of aorto-iliac occlusive disease.1–3ConclusionIschemic injury to the lumbosacral plexus is rare, especially outside the surgical setting as seen in this case. It is important to consider this cause in any patient presenting with rapid onset asymmetric, bilateral leg weakness as early recognition and reperfusion may prevent further damage and reduce long-term disability.ReferencesSchreuder AH, Fennis TF, Teijink JA, Koehler PJ. Lumbosacral plexopathy associated with aortoiliac occlusive disease. J Neurol. 2007;254(6):803–5.Chhetri SK, Lekwuwa G, Seriki D, Majeed T. Acute flaccid paraparesis secondary to bilateral ischaemic lumbosacral plexopathy. QJM. 2013;106(5):463–5.Yun S. Ischaemic lumbosacral plexopathy following an acute thrombosed abdominal aortic aneurysm mimicking stroke: A case report. Hong Kong Journal of Emergency Medicine. 2016;23(2):52–6.
063 Headache with periorbital ecchymosis; a rare clinical entity
Authors: Vijayan Srimathy , Orr Carolyn , Franconi Catherine 
Published: July 2019

ObjectivesPrimary headache disorders are common with migraine and tension headache accounting for the vast majority of cases. A smaller proportion suffer from trigeminal autonomic cephalgia (TAC). We present a 23-year-old Caucasian female who described characteristic, episodic headaches starting with a dull retro-orbital/bi-frontal pressure evolving, over the course of 1 minute, to experience florid periorbital ecchymosis. While this phenomenon has been described in the literature, the characteristics of our case are unique and noteworthy of reporting.MethodsWe reviewed the literature surrounding this rare entity by using PubMed/OVID databases and the search terms ‘Headache AND ecchymosis’.ResultsCase reports exist in older patients1–3, where the headache is side locked and associated with other autonomic characteristics such as periorbital oedema, conjunctival injection and tearing. Our case is a young female with only ecchymosis in a unilateral and/or bilateral manner and no other autonomic or indeed migraine features. The patient underwent vascular/cranial imaging and blood tests to exclude haematological, autoimmune, vasculitic causes for this presentation which were unrewarding.ConclusionVariations on this clinical entity are described;1–4 we hope this report may bring attention to this fascinating phenomenon. The pathophysiological process is likely to be similar to those implicated in TACs, namely activation of the trigemino-neurovascular system and facial autonomic pathways. The release of neuromediators such as CGRP, VIP and Substance P cause blood vessel fragility resulting in diapedesis. Optimal treatment regimens are unknown but various agents have been trialled. Our patient declined treatment and continues to be followed.ReferencesDeBroff B, et al. Migraine Associated with Periorbital Ecchymosis. Headache 1990;30:260–263.Dafer R, et al. Atypical Chronic Headache and Recurrent Facial Ecchymosis: A Case Report. Neuro-Ophthalmology 2011;35:76–77.Nozzolillo D, et al. Migraine associated with facial ecchymoses ipsilateral to the symptomatic side. J Headache Pain ( 2004) 5:256–259.Sethi PK, et al. Teaching neuroimages: Red forehead dot syndrome and migraine revisited. Neurology 2015;85;e28.