bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing a patient blood management programme in Brazil: challenges and implications for developing countries
Authors: Benites B. D. , Addas‐Carvalho M.
Published: May 2018

Background

Patient blood management (PBM) programmes have the intention of promoting the rational use of blood, relying on up‐to‐date medical‐scientific evidence in a multidisciplinary approach, where the patient is the main focus of transfusion decisions. These programmes not only increase patient safety levels, but they also have the potential of lowering hospital costs. The aim of this study was to describe the implementation of a PBM programme at a University hospital in Brazil.

Study design and methods

The discussions regarding this PBM project were initially undertaken among the managers of the hospital's Transfusion Unit. Audits of transfusion practices were carried out, and these indices were presented in meetings with the Transfusion Committee and with other important stakeholders, in order for this information to support the delineation of the programme's work fronts.

Results

The project was promptly approved by the hospital's Board of Directors due to the relevance of the proposal, which required few financial resources as the project is mainly based on reorganization of workflows. The measures implemented included the following: didactic sessions aimed at the hospital staff, reformulation of the computerized system for the prescription of blood components, elaboration of a protocol for the use of antifibrinolytic drugs during the perioperative period and the institution of an outpatient clinic for evaluation of preoperative anaemia.

Conclusion

The benefits and challenges of a PBM project in a country with limited resources are analysed, discussing specificities in the scope of Brazilian Transfusion Medicine in a pioneering way.
Multimodality imaging of an azygous continuation of the caudal vena cava in a dog with pulmonary thromboembolic disease
Authors: Newman Robert J. , Egeler Kimberly M. , Conkling Amanda L. , Savage Mason Y.
Published: May 2018

A 5‐year‐old spayed female English Bulldog was evaluated for acute anorexia, lethargy, respiratory distress, and syncope. Contrast‐enhanced computed tomography revealed the vascular malformation of azygous continuation of the caudal vena cava with extensive thrombus formation and pulmonary arterial thromboembolic disease. The patient was hospitalized for supportive treatment and was prescribed long‐term clopidogrel therapy. The patient survived to discharge and at last follow‐up remained clinically stable. While this vascular malformation has been reported in canines, to the authors’ knowledge, this is the first reported case of pulmonary thromboembolic disease in a canine concurrent with this condition.
Transsphenoidal surgery: accuracy of an image‐guided neuronavigation system to approach the pituitary fossa (sella turcica)
Authors: Owen Tina J. , Chen Annie V. , Frey Stephen , Martin Linda G. , Kalebaugh Tobin
Published: May 2018

Objective

To determine the accuracy of locating the pituitary fossa with the Brainsight neuronavigation system by determining the mean target error of the rostral (tuberculum sellae) and caudal (dorsum sellae) margins of the pituitary fossa.

Study design

Experimental cadaveric study.

Animals

Ten canine cadavers.

Methods

Computed tomography (CT) and MRI were performed on each cadaver with fiducials in place. Images were saved to the neuronavigation computer and used to plan the drilling approach. The cadavers were placed in the surgical head clamp of the Brainsight system and positioned for a transsphenoidal approach. On the basis of the planning, 2 localization points were drilled, 1 each at the rostral and caudal margins of the pituitary fossa, and CT was repeated. Error was assessed from the difference in millimeters between the targets identified during Brainsight planning and the actual location of the 2 points drilled on each cadaver skull as identified by postdrilling CT.

Results

The rostral and caudal margins of the pituitary fossa provided 2 target points per cadaver. The median target error (interquartile range) for all target sites (n = 20) was 3.533 mm (range, 2.013‐4.745).

Conclusion

This stereotactic system allowed the surgeon to locate the rostral and caudal margins of the pituitary fossa with clinically acceptable accuracy and confidence.

Clinical significance

Using the Brainsight neuronavigation system for localization during transsphenoidal hypophysectomy may decrease morbidity and surgical time.
Alone at the Altar
Authors: Leavitt-Alcántara Brianna
Published: May 2018

This book reframes our understanding of single women and religious culture in colonial and nineteenth-century Latin America. Most works on women and early modern religion examine nuns, holy women, or religious “deviants,” and emphasize rising hostility towards female autonomy as officials moved to enclose unmarried women and intensive female religiosity (e.g. mysticism, asceticism). This study takes a different approach and examines ordinary laywomen, particularly the broad population of non-elite women living outside of both marriage and convent. Much like other Spanish American cities, Guatemala’s colonial capital was a city of women due to labor and migration patterns with many single and widowed women heading households. Alone at the Altar argues that laboring single women forged complex alliances with the Church, which shaped local religion and the spiritual economy, late colonial reform efforts, and post-Independence politics in Guatemala. Through an analysis of approximately 550 wills, as well as a variety of other sources such as hagiographies, religious chronicles, and ecclesiastical records, this study moves beyond anecdotal evidence and exemplary case studies, to consider broader patterns and the ways in which gender, social, and marital status shaped early modern devotional networks. By extending its analysis to 1870, the book also illuminates how the alliances between laboring women and the Catholic Church became politicized in the Independence era and influenced the successful rise of popular conservatism in Guatemala.
Epilogue
Authors: Leavitt-Alcántara Brianna
Published: May 2018

The Epilogue considers how the Liberal Reform Era of the 1870s, dramatically undermined both laboring single women and the Catholic Church. Liberals directly undermined laboring women’s economic opportunities, enhanced male privileges, and promoted an exclusive nuclear family ideal, and at the same time targeted laywomen’s longtime devotional allies, expelling male religious orders, closing female convents, and abolishing lay brotherhoods, Third Orders, and most public displays of religiosity. But by the 1920s, a lay-led religious revival, supported by the Vatican, was underway and dozens of new Catholic associations emerged specifically for women. Today, laboring women are at the forefront of a new spiritual revival in Guatemala City, the rise of Pentecostalism, Evangelicalism, and charismatic Catholicism. This study’s long historical perspective suggests that the success of these movements derives from their ability to build upon Guatemala’s local religion, particularly forms of devotional expression and networking historically favored by laboring women.
High parasite diversity accelerates host adaptation and diversification
Authors: Betts A. , Gray C. , Zelek M. , MacLean R. C. , King K. C.
Published: May 2018

Between bacteria and phages, increasing phage diversity accelerates arms races with the host and leads to increased bacterial divergence.
Mapping the dark space of chemical reactions with extended nanomole synthesis and MALDI-TOF MS
Authors: Lin Shishi , Dikler Sergei , Blincoe William D. , Ferguson Ronald D. , Sheridan Robert P. , Peng Zhengwei , Conway Donald V. , Zawatzky Kerstin , Wang Heather , Cernak Tim , Davies Ian W. , DiRocco Daniel A. , Sheng Huaming , Welch Christopher J. , Dreher Spencer D.
Published: May 2018

A rapid screen for complex reactants

Chemists engaged in reaction discovery tend to report outcomes involving a few, relatively simple reactants. It remains a major challenge to fine-tune reported conditions when the reactants become more structurally complex, as often happens in pharmaceutical research. Lin
et al.
developed a protocol for rapidly screening different catalytic conditions for C–N coupling across a wide range of complex substrates. The product detection scheme relies on mass spectrometry of nanomole-scale reaction mixtures without any need for intervening chromatography.

Science
, this issue p.
eaar6236
Beyond fossil fuel–driven nitrogen transformations
Authors: Chen Jingguang G. , Crooks Richard M. , Seefeldt Lance C. , Bren Kara L. , Bullock R. Morris , Darensbourg Marcetta Y. , Holland Patrick L. , Hoffman Brian , Janik Michael J. , Jones Anne K. , Kanatzidis Mercouri G. , King Paul , Lancaster Kyle M. , Lymar Sergei V. , Pfromm Peter , Schneider William F. , Schrock Richard R.
Published: May 2018

Transforming nitrogen without carbon

How much carbon does it take to make nitric acid? The counterintuitive answer nowadays is quite a lot. Nitric acid is manufactured by ammonia oxidation, and all the hydrogen to make ammonia via the Haber-Bosch process comes from methane. That's without even accounting for the fossil fuels burned to power the process. Chen
et al.
review research prospects for more sustainable routes to nitrogen commodity chemicals, considering developments in enzymatic, homogeneous, and heterogeneous catalysis, as well as electrochemical, photochemical, and plasma-based approaches.

Science
, this issue p.
eaar6611
Appropriate and timely antibiotic administration for neonatal sepsis in Mesoamérica
Authors: Duber Herbert C , Hartford Emily A , Schaefer Alexandra M , Johanns Casey K , Colombara Danny V , Iriarte Emma , Palmisano Erin B , Rios-Zertuche Diego , Zuniga-Brenes Paola , Hernández-Prado Bernardo , Mokdad Ali H
Published: May 2018

Neonatal sepsis is a leading cause of mortality among children under-5 in Latin America. The Salud Mesoamérica Initiative (SMI), a multicountry results-based aid programme, was designed to improve maternal, newborn and child health in impoverished communities in Mesoamérica. This study examines the delivery of timely and appropriate antibiotics for neonatal sepsis among facilities participating in the SMI project. A multifaceted health facility survey was implemented at SMI inception and approximately 18 months later as a follow-up. A random sample of medical records from neonates diagnosed with sepsis was reviewed, and data regarding antibiotic administration were extracted. In this paper, we present the percentage of patients who received timely (within 2 hours) and appropriate antibiotics. Multilevel logistic regression was used to assess for potential facility-level determinants of timely and appropriate antibiotic treatment. Among 821 neonates diagnosed with sepsis in 63 facilities, 61.8% received an appropriate antibiotic regimen, most commonly ampicillin plus an aminoglycoside. Within 2 hours of presentation, 32.3% received any antibiotic and only 26.6% received an appropriate regimen within that time. Antibiotic availability improved over the course of the SMI project, increasing from 27.5% at baseline to 64.0% at follow-up, and it was highly correlated with timely and appropriate antibiotic administration (adjusted OR=5.36, 95% CI 2.85 to 10.08). However, we also found a decline in the percentage of neonates documented to have received appropriate antibiotics (74.4% vs 51.1%). Our study demonstrated early success of the SMI project through improvements in the availability of appropriate antibiotic regimens for neonatal sepsis. At the same time, overall rates of timely and appropriate antibiotic administration remain low, and the next phase of the initiative will need to address other barriers to the provision of life-saving antibiotic treatment for neonatal sepsis.
Health economic evaluation of a serum-based blood test for brain tumour diagnosis: exploration of two clinical scenarios
Authors: Gray Ewan , Butler Holly J , Board Ruth , Brennan Paul M , Chalmers Anthony J , Dawson Timothy , Goodden John , Hamilton Willie , Hegarty Mark G , James Allan , Jenkinson Michael D , Kernick David , Lekka Elvira , Livermore Laurent J , Mills Samantha J , O’Neill Kevin , Palmer David S , Vaqas Babar , Baker Matthew J
Published: May 2018

Objectives

To determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway.

Design

A model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion.

Setting

Explored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA.

Participants

Calculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum.

Main outcome measures

The primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost-effectiveness analysis.

Results

Results indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost-effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of £20 000–£30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately £40).

Conclusion

Use of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway.
Exploring emergency department 4-hour target performance and cancelled elective operations: a regression analysis of routinely collected and openly reported NHS trust data
Authors: Keogh Brad , Culliford David , Guerrero-Ludueña Richard , Monks Thomas
Published: May 2018

Objective

To quantify the effect of intrahospital patient flow on emergency department (ED) performance targets and indicate if the expectations set by the National Health Service (NHS) England 5-year forward review are realistic in returning emergency services to previous performance levels.

Design

Linear regression analysis of routinely reported trust activity and performance data using a series of cross-sectional studies.

Setting

NHS trusts in England submitting routine nationally reported measures to NHS England.

Participants

142 acute non-specialist trusts operating in England between 2012 and 2016.

Main outcome measures

The primary outcome measures were proportion of 4-hour waiting time breaches and cancelled elective operations.

Methods

Univariate and multivariate linear regression models were used to show relationships between the outcome measures and various measures of trust activity including empty day beds, empty night beds, day bed to night bed ratio, ED conversion ratio and delayed transfers of care.

Results

Univariate regression results using the outcome of 4-hour breaches showed clear relationships with empty night beds and ED conversion ratio between 2012 and 2016. The day bed to night bed ratio showed an increasing ability to explain variation in performance between 2015 and 2016. Delayed transfers of care showed little evidence of an association. Multivariate model results indicated that the ability of patient flow variables to explain 4-hour target performance had reduced between 2012 and 2016 (19% to 12%), and had increased in explaining cancelled elective operations (7% to 17%).

Conclusions

The flow of patients through trusts is shown to influence ED performance; however, performance has become less explainable by intratrust patient flow between 2012 and 2016. Some commonly stated explanatory factors such as delayed transfers of care showed limited evidence of being related. The results indicate some of the measures proposed by NHS England to reduce pressure on EDs may not have the desired impact on returning services to previous performance levels.
Mobilising identity through social media: psychosocial support for young people with life-limiting conditions
Authors: Peat George , Smith Joanna , Rodriguez Alison
Published: May 2018

EBN engages readers through a range of Online social media activities to debate issues important to nurses and nursing. EBN Opinion papers highlight and expand on these debates.
103 Exploring the influence of quantitative magnetic resonance imaging on decision-making in multiple sclerosis clinical practice
Authors: Beadnall Heidi N , Ly Linda , Wang Chenyu , Billiet Thibo , Ribbens Annemie , Hecke Wim Van , Zivadinov Robert , Barnett Michael H
Published: May 2018

Introduction

Quantitative magnetic resonance imaging (MRI) analysis is currently used in multiple sclerosis (MS) clinical trials. Quantitative MRI (QMRI) data derived using formal analysis techniques is not used in routine MS clinical practice and its effect on clinical decision-making is unknown. The study objective is to explore the influence that QMRI data has on clinical decision-making in real-world MS patients.

Methods

Clinical MS brain MRI scans (separated by one-year minimum, acquired on the same scanner from the same patient) were evaluated. All patients were on the same disease-modifying therapy (DMT) six months prior to and during the study. QMRI analyses were performed on scan pairs by; imaging analysts using specialised software [semi-automated], and MSmetrix [fully-automated]. Data was presented in two separate reports; local QMRI (semi-automated) and centralised QMRI (MSmetrix). Questionnaires were completed by the same neurologist for each subject using clinical data and standard MRI and QMRI reports.

Results

31 relapsing-MS patients (77.4% female), with baseline age 42.14 [10.70] years, disease duration 7.68 [4.89] years and EDSS score 1.40 (1.36), were evaluated. Injectable, oral and infusion DMTs were administered in 29.0%, 61.3% and 9.7% of patients respectively. According to questionnaire responses, 83.9% were predicted to have stable disease over the next year based on clinical reports alone and 67.7% with the addition of QMRI report data. DMT change would be considered in 16.1% based on clinical reports and 32.3% with QMRI report inclusion. Earlier clinical ±MRI follow up was considered in 51.6% (MRI only 41.9%;both 9.7%) when QMRI reports were reviewed.

Conclusion

This preliminary retrospective study indicates that QMRI report data has the potential to influence clinical decision-making in relapsing-MS patients on DMT regarding disease stability assessment, therapy change contemplation, and consideration of earlier follow-up. This work supports a role for formal QMRI analysis and reporting as a clinical-decision support system in MS.
105 Snake eyes in the thoracic spine
Authors: Corbett Joel , Walsh Stephen , Bhuta Sandeep , Sabet Arman
Published: May 2018

Introduction

Bilateral anterior horn cell hyperintensity on spinal imaging (‘snake eyes’ sign) is seen in pathologies including cervical spondylosis, spinal cord infarction and Hirayama’s disease. Below is the first report of lower limb monomelic amyotrophy (MMA) with thoracic spine snake eyes sign. We present a case report of lower limb MMA with bilateral anterior horn hyperintensity, and literature review of cases with this clinico-radiologic presentation.

Case

A 47 year old man presented with an 11 year history of asymmetric, progressive, proximal right lower limb weakness and wasting following traumatic back injury. Eight years into the disease course left leg changes developed. There was no upper limb, bulbar nor respiratory involvement. Examination revealed widespread lower limb wasting, normal tone, marked proximal weakness, brisk reflexes and non-sustained clonus bilaterally. Upper limb and cranial nerve examinations were normal. MRI demonstrated T11–12 bilateral anterior horn cell hyper-intensity. Electromyography demonstrated denervation/re-innervation changes in the right vastus lateralis and to a lesser extent tibialis anterior. Muscle biopsy showed chronic denervation atrophy. Anti-ganglioside GM1 IgM was elevated. Further autoimmune testing, infectious screen, cerebrospinal fluid and neuromuscular disease gene analysis were negative. Steroid and intravenous immunoglobulin therapy were ineffective.

Case series describing lower motor neuron diseases (LMND) including MMA have not previously reported snake eyes sign in association with lower limb disease.1 Two recent publications describing thirty-two cases of LMND with cervical spine snake eyes sign report that all cases were associated with a relatively benign course and many were misdiagnosed as motor neuron disease (MND).2 3 The authors propose this as a previously unidentified mimic of motor neuron disease.

Conclusion

This is the first reported case of thoracic snake eyes sign with corresponding lower limb MMA. Lower motor neuron diseases with bilateral anterior horn cell hyper-intensity may represent a unique clinical form of MND with relatively slower progression.

References

. Nalini A, Gourie-Devi, Thennarasu K, et al. Monomelic Amyotrophy: Clinical profile and natural history of 279 cases seen over 35 years (1976–2010). Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration2014;15:457–465.

. Saski S. Sporadic lower motor neuron disease with a snake eyes appearance on the cervical anterior horns by MRI. Clinical Neurology and Neurosurgery2015;136:122–131.

. Lebouteux M, Franques J, Guillevin R, et al. Revisiting the Spectrum of Lower Motor Neuron Diseases with Snake Eyes Appearance on Magnetic Resonance Imaging. European Journal of Neurology2014;21:1233–1241.
110 Atrophy of the mediodorsal thalamus is associated with visual hallucinations in lewy body diseases
Authors: Matar Elie , Brooks Daniel , Harding Antony , Halliday Glenda
Published: May 2018

Introduction

Although limbic system dysfunction has been thought to underlie visual hallucinations in patients with Lewy body disorders, neuropathology within thalamic structures subserving limbic functions have not been examined. In this study, we assessed the degree of neuronal degeneration in thalamic regions involved in perceptual integration in patients with Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB).

Methods

Post-mortem samples were acquired from twenty-four individuals with Lewy body disease (5 PD, 9 PDD, 10 DLB) and 10 age-matched controls. The anterior principal (AP) and mediodorsal (MD) thalamic nuclei were delineated and analysed using stereological and quantitative neuropathological techniques.

Results

Volume loss within the MD nucleus was observed in patients with DLB (31%) and PDD (18%) but not PD compared to controls (ANOVA, p<0.05). The atrophy was significantly greater in those patients with hallucinations than those without (p<0.05). Somal atrophy was seen in all patient groups and did not correlate with volume loss or visual hallucinations. Interestingly, there was no neuronal loss in this region compared to controls in the Lewy body disease groups. Analysis of the AP nucleus revealed similar patterns of volume loss but with somal atrophy only in patients with PDD and DLB. Both these measures did not correlate significantly with visual hallucinations, but was significantly different in patients with dementia compared to PD only and controls (p<0.05).

Conclusion

These results suggest that afferent denervation of the mediodorsal thalamus may contribute to visual hallucinations. This appears to support models that implicate upstream components of the limbic circuitry in the generation of this phenomenon.
111 Epileptic seizures in multiple sclerosis
Authors: Walsh Stephen , Corbett Joel , Meng Tan K , Broadley Simon
Published: May 2018

Introduction

Epileptic seizures have been described in association with multiple sclerosis (MS) in both anecdotal case reports and case series. The recent identification of specific antibodies to myelin oligodendrocyte glycoprotein (MOG) protein in a small number of patients with demyelinating disease which may resemble neuromyelitis optica or acute disseminated encephalopathy, which may involve seizures, raises the possibility that anti-MOG antibody related demyelination may account for the association of epilepsy with MS.

Methods

We have undertaken a retrospective review of cases of MS diagnosed at the Gold Coast MS clinic over a 10 year period. All cases were systematically asked if they had ever had an epileptic seizure either via a patient completed questionnaire or at a clinic visit. Demographic and clinical information were also recorded. These data have been analysed using descriptive statistics and appropriate tests for significant differences between those with epilepsy and those without.

Results

428 cases with complete data were identified. Those with a history of epilepsy were slightly younger (median (range); 44.5 (27–64) years vs 4715–88 years), but this difference was not statistically significantly different. The gender ratio was the same for both groups (9/12 (75%) for those with epilepsy and 326/416 (78%)). There was no significant difference in age of onset, disease course, relapse frequency or level of disability. Although numbers are small, seizure appear to occur most frequently earlier in the disease course and are rarely an ongoing issue.

Conclusion

These data support earlier work indicating that epilepsy occurs in people with MS who are younger. This fits with the notion that seizures arise in the context of the inflammatory stage of multiple sclerosis rather than the degenerative phase. Further work needs to be undertaken to assess any association with anti-MOG antibodies and epileptic seizures in demyelinating disease.
020 Postural sway as a measure of disease severity in parkinson’s disease
Authors: Lueck Christian J , Ilschner Susanne , Smith Alex , Vlieger Robin , Das Chandi P , Looi Jeff CL , Apthorp Deborah
Published: May 2018

Introduction

The severity of Parkinson’s disease (PD) is difficult to assess accurately owing to the lack of a robust biological marker of disease progression, with consequent implications for prognosis and treatment. The current standard measure is the Unified Parkinson’s Disease Rating Scale (UPDRS) but this is hampered by considerable variability between observers and within subjects. Postural sway correlates well with complex brain functioning in other conditions. This study aimed to investigate the correlation of postural sway with the UPDRS and other non-motor measures of disease severity in patients with PD.

Methods

28 patients with PD (mean age 68 years, range 54–91; 18 male) underwent tests of cognition and quality of life [Montreal Cognitive Assessment (MoCA), Neuropsychiatry Unit Cognitive Assessment (NUCOG) and Parkinson’s Diseases Questionnaire (PDQ-39–1)], assessment of postural sway using a force plate, and assessment of clinical status using the motor component of the UPDRS.

Results

Sway path length showed strong correlations with PDQ-39–1, MoCA and the verbal fluency component of the NUCOG (r=0.63,–0.75 and −0.57, respectively; p=0.002,<0.001 and 0.002, respectively) and, to a lesser degree, with the UPDRS III (r=0.45, p=0.018).

Conclusion

Postural sway shows potential as a sensitive measure of disease severity and brain function in PD, either alone or in combination with other measures. It appears to correlate better with measures of cognition, both general and executive (verbal fluency), and the PDQ measure of disease severity than with the motor component of the UPDRS.
022 Piloting home infusions of natalizumab: a randomised crossover trial
Authors: Schultz Tim , Thomas Anne , Georgiou Paul , Juaton Mahasen , Simon Lorraine , Cusack Lynette , Naidoo Kerisha , Webb Kevin , Karnon Jon , Ravindran Janakan
Published: May 2018

Introduction

For people with multiple sclerosis, monthly infusions at specialist clinics are time consuming, potentially costly and restrictive. Conversely, increased demand for hospital services is driving innovation, including delivery of care in the home. We developed a rigorous model of care for home infusions of natalizumab, which was evaluated in a randomised crossover trial. This pilot study (i) tested feasibility and safety of home infusions, and (ii) compared acceptability and clinical effectiveness with usual clinic-based care in a hospital outpatients clinic.

Methods

We recruited 37 stable adult patients (at least 6 prior natalizumab infusions and assessed as safe by their neurologist) who were randomised to an AB or BA trial arm. After 3 infusions, patients crossed over to the alternate treatment for another 3 infusions. The following outcomes were assessed treatment adherence, patient safety outcomes, quality of life (Multiple Sclerosis Quality of Life Inventory, MSQLI), and patient satisfaction (Treatment Satisfaction Questionnaire for Medication, TSQM).

Results

Two patients moved out of Adelaide and withdrew. No adverse events resulting from the infusion in either the home or clinic setting were reported. There was no difference between home and clinic in the adherence rate (86/104, 82.7% at home) and (84/103, 81.6% at clinic) (X2=0.0, p=1.0) and number of infections during home care8 compared to clinic10 (X2=0.04, p=0.84). There was no difference in any of the nine sub-scales of the MSQLI (p>0.05). Of the four sub-scales of the TSQM (‘Effectiveness’, ‘Side effects’, ‘Convenience’, ‘Global satisfaction’), patients most recently receiving home care were significantly more satisfied with the Convenience of their treatment (p=0.0008).

Conclusion

Data from the pilot study suggest that delivery of infusions of natalizumab at home is feasible, safe and as effective as the hospital setting. Patients reported that home infusions were more convenient than the clinic.
025 The neural correlates of doorway freezing in parkinson’s disease
Authors: Matar Elie , Shine James M , Gilat Moran , Ehgoetz-Martens Kaylena , Ward Phillip B , Frank Michael J , Moustafa Ahmed , Naismith Sharon L , Lewis Simon JG
Published: May 2018

Introduction

Freezing of gait (FOG) in Parkinson’s disease (PD) is a disabling symptom of advanced PD and is frequently triggered upon passing through narrow spaces such as doorways.1 Despite being common, the mechanisms underlying this phenomenon are poorly understood. We have previously shown that increased footstep latency in a virtual reality (VR) environment is a surrogate measure of FOG.2 In this study we aimed to model doorway freezing utilising the VR paradigm in conjunction with functional magnetic resonance imaging (fMRI) to determine the neural correlates of this phenomenon.

Methods

In our study, nineteen patients who routinely experience FOG performed a previously validated VR gait paradigm3 where they used foot-pedals to navigate a series of doorways. Patients underwent testing randomised between both their ‘ON’ and ‘OFF’ medication states. Task performance in conjunction with blood oxygenation level dependent signal changes were compared within each patient.

Results

We were able to reproduce the finding that patients in the OFF state demonstrated significantly longer ‘footstep’ latencies as they passed through a doorway in the VR environment compared to the ON state. As seen clinically with FOG this locomotive delay was primarily triggered by narrow doorways rather than wide doorways. fMRI analysis revealed that doorway-provoked footstep delay was associated with selective hypoactivation in the pre-supplementary motor area (pSMA) bilaterally. Task-based functional connectivity analyses showed that this delay was inversely correlated with the degree of functional connectivity between the pSMA and the subthalamic nucleus (STN) across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associated with increased connectivity between the bilateral STN.

Conclusion

These findings suggest that the effect of environmental cues on triggering FOG reflects a degree of impaired processing within the pSMA and disrupted signalling between the pSMA and STN, thus implicating the ‘hyperdirect’ pathway in the generation of this phenomenon.

References

. Giladi N, Treves TA, Simon ES, Shabtai H, Orlov Y, Kandinov B, Paleacu D, Korczyn AD. Freezing of gait in patients with advanced Parkinson’s disease. J Neural Transm (Vienna)2001;108:53–61.

. Matar E, Shine JM, Naismith SL, Lewis SJ.Virtual realitywalking and dopamine: opening new doorways to understanding freezing of gait in Parkinson’s disease. J Neurol Sci 2014;344:182–5.

. Shine JM, Matar E, Bolitho SJ, Dilda V, Morris TR, Naismith SL, Moore ST, Lewis SJ. Modelling freezing of gait in Parkinson’s disease with a virtual reality paradigm. Gait Posture2013;38:104–8.
026 Characteristics of advanced parkinson’s disease patients seen in movement disorder clinics – australian results from the cross-sectional observe study
Authors: Evans Andrew , Fung Victor SC , O’Sullivan John , Stell Rick , White Richard , Williams David , Onuk Koray
Published: May 2018

Introduction

To evaluate the proportion of Parkinson’s disease (PD) patients identified as having advanced Parkinson’s disease (APD) according to physician’s judgement: Australian results.

Methods

This cross-sectional, non-interventional observational study was performed in movement disorder clinics from 18 countries. Results from the Australian cohort are presented here. Participants included consecutive adults with PD attending a routine clinical visit, or inpatients at participating clinical sites, and who could speak English. The primary outcome was the proportion of patients diagnosed with APD via physician judgement. Secondary objectives included to evaluate clinical characteristics of APD versus non-APD; to assess the percentage of APD considered for device-aided therapies (DAT); to explore referral practices for APD; and to compare the percentage of APD identified in routine clinical practice by physician’s judgment to APD identified based on APD criteria derived using the Delphi method.

Results

100 patients were recruited in Australia: 61.0% (95%CI 51.4%–70.6%) diagnosed with APD by physician judgement. Patients were 66.6±8.5 years, 65% were male, were living at home (97%), and diagnosed for median 10.7 years (0–30.5 years). Motor fluctuations were present in 68%. For those with APD, referral was predominantly to enable access to DAT (49%), while for non-APD, referral was largely for diagnostic purposes (41%). Referral to a movement disorder clinic occurred 4.8 years (median) following diagnosis for APD, or 3.6 years for non-APD. While 62% were eligible for DAT, only two-thirds of these received them. The most commonly used DAT was deep brain stimulation (64.3%). There was fair agreement between physician’s judgement and the APD criteria by Delphi method (Cohen’s kappa) 0.325 (95%CI 0.150–0.500).

Conclusion

The definition of APD requires refinement in order to facilitate greater agreement among movement disorder specialists. A third of PD patients eligible for DAT remain untreated. Current Australian practice is weighted towards deep brain stimulation.
028 Treating progressive multiple sclerosis
Authors: Hughes Jordana , Jokubaitis Vilija , Slee Mark , Lechner-Scott Jeannette , Walt Anneke Van der , Butzkueven Helmut , Kalincik Tomas
Published: May 2018

Introduction

We showed that the available immunotherapies do not modify disability outcomes when used in secondary progressive multiple sclerosis. However, these therapies are effective in advanced active multiple sclerosis. Primary progressive multiple sclerosis may present with or without superimposed relapses. Significance of these relapses for disability accumulation and treatment remains contested. We aimed to examine the effect of the available immunotherapies in primary progressive multiple sclerosis.

Methods

1427 eligible patients with primary progressive multiple sclerosis from MSBase were studied. Confirmed disability progression of disability was compared between treated and untreated propensity score-matched cohorts. Multivariable regression models were used to compare disability accrual between primary progressive multiple sclerosis with and without superimposed relapses. Finally, the effect of therapy on disability accrual in cohorts with and without superimposed relapses was analysed.

Results

173 treated and 373 untreated patients were matched. No differences in the risk of disability progression (p=0.79) and improvement (p=0.98) were observed over the median 3 year follow-up.

The likelihood of disability progression was relatively lower in patients with superimposed relapses (hazard ratio=0.83, p<0.01). We observed an association between the proportion of time on immunotherapy and the hazard of disability progression in active (hazard ratio=0.96, p=0.01) but not in the inactive primary progressive disease (p=0.21).

Conclusion

Superimposed relapses in primary progressive multiple sclerosis represent a favourable prognostic marker, associated with slower disability accrual. This is most likely attributed to the effectiveness of immunotherapy in active primary progressive disease. Relapse activity, therefore, is a treatable modifier of disability accrual in primary progressive disease.
003 A markov/multi-state model of progression and dynamics of seizure freedom in in large cohort of patients with epilepsy
Authors: Simpson Hugh D , Chen Zhibin , Kwan Patrick , Brodie Martin
Published: May 2018

Introduction

Epilepsy is a common and often highly morbid disease, associated with a not insignificant mortality. Some aspects of epilepsy have been well studied, for example the genetic basis and phenomenology of certain epilepsy syndromes, while other aspects such as long-term outcomes in large cohorts of epilepsy patients are less well studied. Mathematical modelling can assist in the analysis and interpretation of patterns and trends in long-term cohort data, that might not otherwise be obvious intuitively or using standard statistical methods.

Methods

Markov chain and state based modelling have been successfully used in analysing the progression of stages of disease in other specialties, such as chronic kidney disease and diabetic retinopathy. We applied this methodology to disease progression in epilepsy, by applying it to long-term cohort data. We used data from a longitudinal observational cohort study of 1795 patients with newly diagnosed epilepsy, for up to 30 years. The patients were managed in typical, real world clinical practice.

Results

We created a framework for conceptualising the natural history of epilepsy as a step-wise progression of disease through various stages, determined by seizure freedom and antiepileptic drug schedule. We adapted mathematical frameworks based on Markov chain and multi-state models to this model. We generated transition probabilities representing the dynamics of moving between stages of disease. This allowed us to analyse the dynamics of progression, and hence prognosis, in one of the largest and longest followed epilepsy cohorts in the world.

Conclusion

Epilepsy can be conceptualised as multi-stage, stepwise disease process. Markov and multistate models can be used to model the natural history of epilepsy, and inform us of the likely outcomes of epilepsy at the various stages in its progression. This quantification of outcomes can help us better inform patients of their prognosis at various stages in their illness.
045 Delayed-release dimethyl fumarate demonstrated no difference in clinical outcomes versus fingolimod in patients with relapsing-remitting multiple sclerosis: results from the real-world effect study
Authors: Sloane Jacob , Theodore Phillips J , Calkwood Jonathan , Walt Anneke Van der , Min Jinny , Okwuokenye Macaulay , Taylor Catherine
Published: May 2018

Introduction

In real world comparative effectiveness studies of relapsing-remitting multiple sclerosis (RRMS) patients, treatment with delayed-release dimethyl fumarate (DMF) compared with fingolimod (FTY) for ≤2 years was associated with no statistically significant differences in relapse outcomes. We assessed the real-world effectiveness of DMF compared with FTY in RRMS patients at 12 months.

Methods

EFFECT (NCT02776072) was an observational, international, retrospective, single time point, medical record review study undertaken to evaluate the effectiveness of DMF and other disease-modifying therapies (DMTs). Patient eligibility criteria included age ≥18 years, diagnosis of RRMS, treatment naïve or 1 prior DMT (interferon or glatiramer acetate), DMT treatment initiation after ,December 2010and ≥12 months of medical record data following DMT initiation. Endpoints included Kaplan-Meier estimated proportion of patients relapsed at 12 months and annualised relapse rate (ARR). Substantive baseline covariates were used in estimating propensity score. The data were divided into 4 strata using propensity score. After assessing for balance in baseline covariates between treatment groups, Kaplan-Meier estimates and estimate of treatment effects were pooled across strata of propensity score.

Results

Of the 826 DMF and 785 FTY patients enrolled at sites in 17 countries, 816 and 781 patients respectively, were included in the full analysis set. Treatment groups were balanced after propensity score stratification. At 12 months, 86% of DMF-treated patients and 94% of FTY-treated patients remained on therapy. In the trimmed full analysis set, the estimated proportion of DMF patients that relapsed at 12 months was 12% compared with 13% for FTY patients; hazard ratio (95% CI) 1.07 (0.78, 1.46; p=0.6926). At 12 months after treatment initiation, the adjusted ARR ratio (95% CI) was 1.09 (0.80, 1.49; p=0.5754) for patients treated with DMF compared with FTY.

Conclusion

Over 12 months, treatment with DMF versus FTY was associated with no statistically significant difference on relapse outcomes.
050 Latitude continues to be associated with ms prevalence: an updated meta-analysis
Authors: Wang Wendy , Simpson Steve , Taylor Bruce
Published: May 2018

Introduction

Previous studies have demonstrated a strong latitudinal gradient in multiple sclerosis (MS) prevalence, likely related to interplay between genetic and environmental factors, particularly vitamin D and sun exposure. Herein, we update our 2010 meta-analysis of the latitudinal gradient of MS prevalence, seeking to assess the presence and magnitude of the gradient and whether it has changed since our 2010 analysis.

Methods

Studies published between 2010 and 2017 were located via EMBASE, ISI and PubMed, using standardised search terms; data was extracted from peer-reviewed studies. These studies were added to the studies collected in our previous analysis. Prevalence estimates were adjusted for study prevalence year. Where age/sex-specific data were available, prevalence values were age/sex standardised to the 2009 European population. For the 2010–2017 interval, 85 prevalence studies were found, 53 of which met inclusion criteria, yielding 108 new prevalence points. The latitudinal association with MS prevalence was assessed by meta-regression.

Results

There was a significant positive gradient in MS prevalence with increasing latitude (6.89/100,000 per degree latitude), attenuating slightly to 5.60/100,000 on age-standardisation, these associations persisting on adjustment for diagnostic criteria used. Of note, the age-standardised gradient was significantly stronger (p=0.044) than that from our previous study.

Conclusion

This updated meta-analysis confirms that MS prevalence is still strongly positively associated with increasing latitude.
055 Effect of common concomitant antiepileptic drugs during adjunctive treatment with perampanel: post hoc analysis from the open-label extension of a phase III study in patients with idiopathic generalised epilepsy
Authors: O’Brien Terence J , Bibbiani Francesco , Patten Anna , Laurenza Antonio , Williams Betsy
Published: May 2018

Introduction

Perampanel is approved for adjunctive treatment of partial seizures, with or without secondarily generalised seizures, and primary generalised tonic-clonic (PGTC) seizures in epilepsy patients aged ≥12 years. Perampanel is also approved for monotherapy use for partial seizures in the US. This post hoc analysis assessed the effects of the most common concomitant Baseline antiepileptic drugs (AEDs) on discontinuation rates and treatment-emergent adverse event (TEAE) incidence during adjunctive treatment with perampanel in patients (aged ≥12 years) with idiopathic generalised epilepsy (IGE) and PGTC seizures in the open-label extension (OLEx) Phase of Study 332 (NCT02307578).

Methods

Patients completing the double-blind study could receive perampanel (≤12 mg/day) during the OLEx (6 week blinded Conversion Period;≤136 weeks’ Maintenance). Here, we report results for perampanel >4–8 mg/day and >8–12 mg/day.

Results

Most common concomitant Baseline AEDs were valproic acid (n=55), lamotrigine (n=53), levetiracetam (n=37), topiramate (n=21) and zonisamide (n=12); patients may have received >1 of these Baseline AEDs. The most common reasons for discontinuing were adverse event(s) (AE), ‘other’ and patient choice. Lamotrigine: patient choice, n=6/34 (>4–8 mg/day); AE/‘other’, both n=3/19 (>8–12 mg/day). Levetiracetam: patient choice, n=5/27 (>4–8 mg/day); AE, n=2/10 (>8–12 mg/day). Topiramate: ‘other’, n=3/15 (>4–8 mg/day); AE/‘other’, both n=1/6 (>8–12 mg/day). Valproic acid: patient choice, n=6/38 (>4–8 mg/day); ‘other’, n=4/17 (>8–12 mg/day). Zonisamide: patient choice/‘other’, both n=2/10 (>4–8 mg/day); no discontinuations (>8–12 mg/day). Patient-reported TEAEs ranged from: 88.2% (lamotrigine) to 93.3% (topiramate) for perampanel >4–8 mg/day, and 70.6% (valproic acid) to 100.0% (topiramate and zonisamide) for perampanel >8–12 mg/day. The most common TEAE was dizziness.

Conclusion

In this post hoc analysis, primary reasons for discontinuation and TEAE incidence differed between the most common Baseline AED subgroups and perampanel dose range, although TEAE types were similar. These data provide additional information on the safety of adjunctive perampanel in patients with IGE.

Study support

Eisai Inc.
063 Actinomyces cavernous sinus infection: a case and systematic literature review
Authors: Lubomski Michal , Dalgliesh James , Lee Kenneth , Damodaran Omprakash , McKew Genevieve , Reddel Stephen
Published: May 2018

Case

We report an unusual case of a 63 year old man who developed progressive right-sided exophthalmos, painful ophthalmoplegia, headaches and fevers with worsening depression over a two-month period, subsequently identified as an Actinomyces cavernous sinus (CS) infection. Preliminary diagnoses included giant cell arteritis then Tolosa-Hunt syndrome, with a transient response to steroids. Investigations showed a bland CSF and highly metabolically active brain FDG-PET suggesting lymphoma. Biopsy of the mass demonstrated gram-positive filamentous bacteria with Actinomyces-like colonies with sulphur granules. Actinomyces CS infections are rare. They often mimic non-infectious etiologies including other inflammatory and infiltrative conditions, vascular and neoplastic causes, particularly lymphoma.

Conclusion

Clinicians should consider infective CS syndromes in fluctuating painful ophthalmoplegias with poor response to steroids. In our view, “Tolosa-Hunt” should not be used as a diagnosis but merely used as a descriptor for syndromes that resolve with corticosteroids in the absence of a more precise diagnosis.