bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical nutrition treatment of women with gestational diabetes mellitus by a telemedicine system based on smartphones
Authors: Yang Ping , Lo Wenpin , He Zong‐lin , Xiao Xiao‐min
Published: May 2018

Aim

To explore whether WeChat platform‐based treatment of women with gestational diabetes mellitus (GDM) reduces the risk of perinatal complications and explore factors affecting gestational age at delivery.

Methods

Pregnant women with GDM (n = 107) and normal glucose tolerance (n =50, group C) according to oral glucose tolerance test (OGTT) results during gestational weeks 24–28 were included. Women with GDM were divided into groups A (n =57) and B (n =50) according to informed consent. According to GDM treatment norms, group B was given routine outpatient treatment and health education guidance. In addition to the interventions in group B, group A was given access to both a smartphone‐based telemedicine system and articles providing continuous health education. The PBG level in groups A and B was compared, as were differences in maternal and fetal outcomes. Data were analyzed by t‐test, analysis of variance (anova), chi‐square test and multiple linear regression, with P < 0.05 considered significant.

Results

Fasting blood glucose (FBG) and 2‐h postprandial blood glucose (PBG) were significantly lower and premature delivery was significantly less likely in group A than in group B (all P < 0.05). Compared with group B, caesarean section was more likely in group A (P < 0.05). Pregnancy‐induced hypertension had a higher incidence in group B than in group C (P < 0.05). Gestational age at delivery was associated with OGTT2h, premature fetal membrane rupture and self‐monitoring of blood glucose.

Conclusion

GDM treatment based on the WeChat platform effectively reduces FBG and 2‐h PBG and may improve pregnancy outcomes. However, 1‐h PBG was not affected by treatment. Obstetricians should consider the OGTT2h value to increase gestational age at delivery.
Concomitant Acute Toxic Leukoencephalopathy and Posterior Reversible Encephalopathy Syndrome
Authors: Özütemiz Can , Roshan Sarah Khanipour , Kroll Neil Joseph , Rykken Jeffrey B. , Ott Frederick , McKinney Alexander M.
Published: May 2018

BACKGROUND AND PURPOSE

Posterior reversible encephalopathy syndrome (PRES) and acute toxic leukoencephalopathy (ATL) are both potentially reversible clinicoradiologic entities. Although their magnetic resonance imaging (MRI) findings differ, rarely both may occur simultaneously in acutely encephalopathic patients. Our aim was to determine the incidence and causes of concomitant “ATL‐PRES.”

METHODS

Retrospective search of suspected acutely encephalopathic adults since 1998 throughout our picture archiving and communication system revealed 167 patients with PRES and 106 patients with ATL. Images of these patients were retrospectively evaluated by two neuroradiologists and a fellow to identify the cases which carry both features of PRES and ATL. Imaging findings were scored based on previously reported scoring system as mild, moderate, and severe. The clinical outcome of the patients was determined according to the modified Rankin scale.

RESULTS

Our search revealed a series of 6 patients (%2.2) in 273 patients who presented acutely with either encephalopathy or seizures, caused by various etiologies, including immunosuppression following transplantation (n = 2), hypertensive crisis (n = 2), chemotherapy (n = 1), and sepsis (n = 1). MRI demonstrated findings consistent with both PRES and ATL simultaneously on FLAIR and diffusion weighted imaging. Severity of imaging findings of concomitant “ATL‐PRES” was concordant with each other (rho ≈ 1.0, P < .00001), and each patient eventually returned to clinical baseline. This finding, along with their similar etiologies, raises the possibility of an underlying common pathophysiologic thread, perhaps being endothelial toxicity.

CONCLUSIONS

Concomitant “ATL‐PRES” was found in 2.2% of the patients in a large cohort of ATL and PRES. Etiologies varied. Clinical symptoms and MRI findings were potentially reversible.
Work Opportunities and Organizational Commitment in International Organizations
Authors: Giauque David , Varone Frédéric
Published: May 2018

This article applies social exchange theory to investigate the relationships between work opportunities and organizational commitment in four United Nations agencies. It demonstrates that international civil servants who are satisfied with their altruistic, social, and extrinsic work opportunities are more likely to declare high levels of organizational commitment. Furthermore, perceived organizational support mediates these relationships. The empirical findings highlight the importance of considering the specificity of organizational features in explaining international civil servants' attitudes and behaviors. Their preferences for altruistic, social, and extrinsic work opportunities are not similar to the motivational orientations and rewards valued by public or private sector employees, confirming the hybrid characteristics of international organizations. Drawing on these original results, the research identifies some practical implications for human resource management in international organizations.
Divine Variations
Authors: Keel Terence
Published: May 2018

The view that science and religion are necessarily in conflict has increasingly lost favor among scholars who have sought more nuanced theoretical frameworks for evaluating the configurations of these two bodies of knowledge in modern life. This book situates, for the first time, the modern study of race into scholarly debates concerning whether the conflict thesis is a viable analytic framework for assessing the relations between religion and science. Arguing that the conflict model is thoroughly inadequate, this book shows that the formation of the race concept in the minds of Western European and American scientists grew out of and remained indebted to Christian intellectual history. Religion was not subtracted from nor did it stand in conflict with constructions of race developed across the modern life and health sciences. The argument made in this book is based on a reexamination of paratheological texts and biblical commentaries from the seventeenth and eighteenth centuries, works in early Christian natural philosophy, seminal studies in German ethnology and early nineteenth-century American social science, debates among twentieth-century Progressive Era public health scientists, and contemporary genetic analysis of ancient human DNA. Divine Variations recovers the hidden history of how Euro-American scientists inherited from their Christian ancestors a series of ideas and reasoning strategies about race that profoundly shaped the modern biological construction of human difference.
The Ghost of Christian Creationism
Authors: Keel Terence
Published: May 2018

Chapter 3 explores how polygenist carryovers emerged in early twentieth-century medical and public health studies on the links between race and disease. This persistence further embedded ideas about race derived from Christian intellectual history into the methods and reasoning of modern scientists and public health researchers. In the early twentieth century, the concept of biological determinism—the idea that the fixed biological makeup of a racial group determines its members’ health, behavior, and intelligence—reoccupies the epistemic space once filled explicitly by a theological view of nature. This chapter also introduces the work of the African American physician, ethicist, and social hygienist Charles V. Roman, who departed from the racial logic of his time. Roman stressed instead that the idea of common human ancestry should push public health researchers to think more critically about the social and environmental factors shaping health outcomes and black susceptibility to disease.
The Less Unsaid the Better
Authors: Osborne Evan
Published: May 2018

The question of how much free expression to tolerate hardly came up until the modern era. The creation in Europe of the printing press changed that and made expression a threat to long-standing social institutions. The nature of the new technology made it impossible to fully control the flow of books, pamphlets, and other printed material, but European governments tried. The argument in favor of a free press ultimately emerged, and the practice itself was institutionalized, mostly in Great Britain and northwestern Europe. The chapter emphasizes the self-regulating argument for free communication, that ideas beyond science would be improved if they must be subject to readers’ scrutiny. Particular attention is paid to Milton, Struensee and John Stuart Mill. The arguments made in favor of the broad protection of freedom of speech that prevail in much of the world are shown to have significant self-regulating components.
Building on Good Decisions with Authenticity and Sincerity
Authors: Alexandra Christina Countess of Frederiksborg , Fort Timothy L.
Published: May 2018

This chapter engages the reader with anecdote, showing that sincerity is both crucial for good, sustainable business conduct and that business conduct itself is most trustworthy--and most economically efficacious--if the conduct is driven by authentic values. Exploring beyond specific decisions and conduct, this chapter looks at examples of corporate culture, showing the ways in which culture is a crucial determinant for values-driven leadership. Extensive, empirical literature is discussed and synthesized according to the framework already articulated.
The Language of Religion
Authors: Bryce Benjamin
Published: May 2018

Immigrant adults participating in organized religion were fundamentally concerned with the place of their respective churches in Argentina. For German-speaking Catholics, that often meant using the German language to strengthen the place of their church in the face of a secularizing state. Some Lutherans were concerned that a shift from German to Spanish would prevent a new generation from remaining involved with their parents’ denomination. At the same time, other parents and children remain involved in religious communities while also demanding services in Spanish. In striking a balance between German and Spanish in order to create a united ethno-religious community, Lutheran and Catholic leaders also excluded many German speakers. The way that they chose to create community blocked out not only people of other denominations but also anyone who was not interested in organized religion.
Citizenship and Ethnicity
Authors: Bryce Benjamin
Published: May 2018

Between 1880 and 1930, German speakers in Buenos Aires, together with hundreds of thousands of other immigrants and their children, created a framework that defined the relationships among the state, the public sphere, religious institutions, ethnic organizations, and family that then evolved throughout the twentieth century. The definitions of German ethnicity slowly changed in Buenos Aires, as did the nature of the linguistic and cultural pluralism of Argentine society. Ideas about the future drove German-speaking immigrants to build and support a range of institutions. In so doing, however, these immigrants and second-generation bilinguals created overlapping German communities in Buenos Aires. They navigated among denominational, linguistic, German, and Argentine identities. Their ideas and actions about citizenship and belonging helped give shape to the meaning of ethnicity in Argentina.
Primitivism, Decolonization, and World Literature
Authors: Etherington Ben
Published: May 2018

The conclusion recapitulates the central claims of the study, especially with regard to the phenomenological notion that primitivism was a “project,” and points to areas for further research. It also discusses in greater depth the politics of primitivism, especially the notion that it had a “decolonial horizon.” This is undertaken through a brief comparative discussion of two accounts of the Haitian revolution written in the 1930s, Guy Endore’s Babouk and C. L. R. James’s The Black Jacobins. It finishes by considering in what respects literary primitivism might be considered an event of “world literature.”
The Kadi of Malta
Authors: White Joshua M.
Published: May 2018

This chapter turns to the Ottoman victims of Catholic corsairs and pirates who were carried off to Malta and Livorno to be sold as slaves and/or held for ransom. It focuses on the Ottoman magistrates (kadis) who, as judge-notaries, as captives, and as official mouthpieces of the Ottoman state, were involved in every stage of the ransom slavery industry in the eastern Mediterranean. From the late sixteenth century to the early eighteenth century, a number of Ottoman judges could always be found imprisoned in Maltese dungeons, where their legal expertise proved critical for preparing surety agreements and ransom contracts acceptable in courts throughout the Ottoman Mediterranean. The phenomenon of the kadis of Malta reflects the essential paradox of the seventeenth-century Ottoman Mediterranean: the inverse relationship between Ottoman maritime security and the importance of Ottoman law as an almost universally acceptable legal lingua franca from Istanbul to Malta.
The Legal Geography of Indigenous Bedouin Dispossession
Authors: Kedar Alexandre , Amara Ahmad , Yiftachel Oren
Published: May 2018

This chapter is an overview of the “state of the art” in scholarship dealing with Negev (Naqab) Bedouins. It sets the book within relevant scholarly frameworks as a foundation for the empirical investigations of the chapters that follow. This chapter defines key concepts such as “Ethnocracy,” “settling society”, “gray space” and “hegemony;” and discusses the emergence and nature of critical legal geography. The chapter then reviews literature dealing with the dispossession of indigenous peoples, focusing on the evolution and nature of the terra nullius concept and its Israeli version —the “Dead Negev Doctrine” (DND).
Directed Improvisation in Administrative Financing
Authors: Ang Yuen Yuen
Published: May 2018

This chapter examines one of the oldest and most basic problems of governance: how to pay the bureaucracy. Following the 1994 tax reform, China’s local governments, even the relatively prosperous county of Zouping, face heightened budgetary pressures. Agencies and public service providers are therefore compelled to “self-finance”—that is, generate a portion of their own income and staff benefits. Contrary to popular opinion, practices of administrative self-financing are not arbitrary and lawless; rather, they are bound by rules, specifically, rules made by an intersecting matrix of vertical and horizontal authorities within the state. More broadly, this account illustrates a key condition of adaptation—which this chapter calls “directed improvisation.”
Fast and accurate analytical modeling of broadband noise for a low-speed fan
Authors: Sanjosé Marlène , Moreau Stéphane
Published: May 2018

The broadband noise sources are investigated on an isolated low-speed fan typical of engine cooling systems. Reynolds-averaged Navier-Stokes (RANS) simulations have been performed on a single blade passage for several flow rates at the same rotational speed. The flow structures responsible for the different noise contributions are identified by a systematic analysis of the simulation results. The aeroacoustic noise predictions are based on Amiet's model for rotating sources in free-field. The contribution of the turbulence-interaction noise and the trailing-edge noise are considered by the appropriate isolated blade response and statistical model of the turbulent sources. The flow parameters of the aeroacoustic response and the turbulent models are extracted from the RANS simulations. The radial evolution of the flow parameters for the different flow rates is analyzed and related to the three-dimensional flows in the machine. The acoustic predictions are validated with experimental spectra measured upstream of the fan in a reverberant room. The two considered mechanisms evolve differently with the flow rate. The leading-edge sources are dominant at low flow rate up to the design point and the self-noise becomes dominant at high flow rate for which the secondary flow structures are limited.
Effects of noise and talker intelligibility on judgments of accentedness
Authors: Gittleman Sarah , Van Engen Kristin J.
Published: May 2018

The goal of this study was to determine how noise affects listeners' subjective judgments of foreign-accented speech and how those judgments relate to the intelligibility of foreign-accented talkers. Fifty native English listeners heard native Mandarin speakers and native English speakers producing English sentences in quiet and in three levels of noise. Participants judged the accent of each speaker on a scale from 1 (native-like) to 9 (foreign). The results show that foreign-accented talkers were rated as less accented in the presence of noise, and that, while lower talker intelligibility was generally associated with higher (more foreign) accent ratings, the presence of noise significantly attenuated this relationship. In contrast, noise increased accent ratings and strengthened the relationship between intelligibility and accent ratings for native talkers. These findings indicate that, by obscuring the acoustic-phonetic cues that listeners use to judge accents, noise makes listeners less confident about the foreign (or native) status of a given talker.
German law allows use of DNA to predict suspects' looks
Authors: Vogel Gretchen
Published: May 2018

Bavaria opens the door to DNA phenotyping, provoking debate about the technique's ethics and accuracy.
AAAS extends science in theological education program
Authors: Hoy Anne Q.
Published: May 2018

Science in the Seminaries enhances science education across the religious community
The RNA face of phase separation
Authors: Polymenidou Magdalini
Published: May 2018

RNA regulates the formation, identity, and localization of phase-separated granules
Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates
Authors: Stone Mars , Bainbridge John , Sanchez Ana M. , Keating Sheila M. , Pappas Andrea , Rountree Wes , Todd Chris , Bakkour Sonia , Manak Mark , Peel Sheila A. , Coombs Robert W. , Ramos Eric M. , Shriver M. Kathleen , Contestable Paul , Nair Sangeetha Vijaysri , Wilson David H. , Stengelin Martin , Murphy Gary , Hewlett Indira , Denny Thomas N. , Busch Michael P.
Published: May 2018

Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes.
Prevalence of peritonitis and mortality in patients treated with continuous ambulatory peritoneal dialysis (CAPD) in Africa: a protocol for a systematic review and meta-analysis
Authors: Moloi Mothusi Walter , Kajawo Shepherd , Noubiap Jean Jacques , Mbah Ikechukwu O , Ekrikpo Udeme , Kengne Andre Pascal , Bello Aminu K , Okpechi Ikechi G
Published: May 2018

Introduction

Continuous ambulatory peritoneal dialysis (CAPD) is the ideal modality for renal replacement therapy in most African settings given that it is relatively cheaper than haemodialysis (HD) and does not require in-centre care. CAPD is, however, not readily utilised as it is often complicated by peritonitis leading to high rates of technique failure. The objective of this study is to assess the prevalence of CAPD-related peritonitis and all-cause mortality in patients treated with CAPD in Africa.

Methods and analysis

We will search PubMed, EMBASE, SCOPUS, Africa Journal Online and Google Scholar for studies conducted in Africa from 1 January 1980 to 30 June 2017 with no language restrictions. Eligible studies will include cross-sectional, prospective observational and cohort studies of patients treated with CAPD. Two authors will independently screen, select studies, extract data and conduct risk of bias assessment. Data consistently reported across studies will be pooled using random-effects meta-analysis. Heterogeneity will be evaluated using Cochrane’s Q statistic and quantified using I2statistics. Graphical and formal statistical tests will be used to assess for publication bias.

Ethics and dissemination

Ethical approval will not be needed for this study as data used will be extracted from already published studies. Results of this review will be published in a peer-reviewed journal and presented at conferences. The Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015) framework guided the development of this protocol.

PROSPERO registration number

CRD42017072966.
Alcohol-related presentations to emergency departments in Ireland: a descriptive prevalence study
Authors: McNicholl Brian , Goggin Deirdre , O’Donovan Diarmuid
Published: May 2018

Objectives

To determine the prevalence of alcohol-related presentations in all 29 emergency departments (EDs) in Ireland and compare with non-alcohol-related presentations in order to identify opportunities for improvements in the quality of patient care and related data collection.

Design and setting

Descriptive prevalence study reviewing all records in the same four 6-hour periods in every 24-hour ED in the country.

Participants

3194 persons who attended EDs over four specified 6-hour periods.

Primary outcome measures

The prevalence of alcohol-related presentations, comparison with non-alcohol-related presentations and the categorisation of these presentations according to WHO International Statistical Classification of Diseases and Related Health Problems 10th Revision codes.

Results

The total number of presentations was 3194 in the four 6-hour periods, of whom 189 (5.9%) were alcohol related, varying from 29.0% in the early hours of Sunday morning to 1.2% on Monday morning (p>0.0001). The alcohol-related presentations were more likely to be men, attend on early hours of Sunday morning, arrive by ambulance, leave before being seen by a doctor or leave against medical advice; and they were less likely to be admitted to hospital.

Conclusions

Alcohol-related presentations are a significant burden on EDs and ambulance services, especially in the early hours of Sunday mornings. Addressing the alcohol-related burden on EDs requires improvements in data collection and information systems, the development of appropriate interventions and related referral services and better preventive actions for alcohol-related harm.
107 First come, first served: a comparison of first-ever seizure patients and those presenting after recurrent-untreated seizures
Authors: Holper Sarah , Foster Emma , Kwan Patrick
Published: May 2018

Introduction

First seizure diagnosis may be delayed due to financial, geographical or social barriers to healthcare, or misdiagnosis with differentials including syncope or stroke. Seizures may recur until correct diagnosis and appropriate treatment is instituted; meanwhile, patients may experience increased seizure-related morbidity and mortality. We compare patient and seizure characteristics between a first-ever ‘new-onset’ seizure (NOS) cohort, and a recurrent-untreated seizure (RUS) cohort.

Method

Medical charts were reviewed to extract information on patient demographics and clinical characteristics using a standardised proforma. Inclusion criteria were patients aged 18 or over who attended a tertiary-level Melbourne hospital between 1 January 2008 and 30 November 2016 with discharge codes ICD-10 G40-Epilepsy, G41-Status epilepticus, or R56.9-Unspecified convulsions.

Results

367 episodes were identified. 151 episodes met inclusion criteria: new-onset seizures (115) and recurrent-untreated seizures.36 216 excluded cases included pre-existing epilepsy (186), and non-seizure events.30 RUS-cohort experienced a median of two seizures prior to coming to medical attention, most commonly focal impaired awareness seizures (50.00%). Considering the index seizure, focal seizures were more common in RUS-cohort (36.11 vs 24.35%) while primary generalised seizures predominated in NOS-cohort (62.61% vs 50.00%). Compared to NOS-cohort, RUS-cohort was more likely to have unprovoked seizures (72.22% vs 55.65%), identifiable remote risk factors (41.67% vs 26.09%), younger age (69 vs 76), normal MRI and EEG, and be discharged on antiepileptic drugs (86.11% vs 73.91%). RUS-cohort was more likely to receive Neurology outpatient follow-up (72.22% vs 39.99%), and in a more timely manner compared to NOS-cohort (30.56% vs 11.31% saw a Neurologist within a month of discharge).

Conclusion

Recurrent-untreated seizures often have subtler semiology and are more likely to have normal MRI and EEG results than patients presenting immediately following new-onset seizures. RUS-cohort tend to receive more inpatient investigations and AED prescriptions, and are offered more timely neurology follow-up than NOS-cohort.
112 Blood spot testing for late onset pompe disease
Authors: Dobbins Julia , Pyragius Tim , Brion Kristian , Chin Sharon , Gurner Melissa , Pacyna Janina , Stark Samantha , Fletcher Janice M
Published: May 2018

Introduction

Pompe disease is classified by age of onset and presentation. Late-onset Pompe disease (LOPD) generally presents with progressive limb-girdle and respiratory muscle weakness. Diagnosis is confirmed following dried blood spot (DBS) enzyme assay by a second method, either mutation or glucose tetra-saccharide analysis.

Methods

From 2000 to 2016, acid α –glucosidase (GAA) activity in DBS was measured using the immuno-capture assay of . Umapathysivam et al. (2001) From 2016 testing used the multiplex tandem mass spectrometry method (6-PLEX LC-MSMS, Perkin Elmer), measuring six lysosomal storage disease enzymes from one DBS. Glucose tetra-saccharides were measured by mass spectrometry and mutation analysis of the GAA gene was performed using either Sanger or Next Generation Sequencing, the latter confirmed by sequencing.

Results

Between 2000 and 2016, approximately 1500 samples were screened for Pompe disease with 77 positives, a diagnosis rate of 5.1%. Of these, 33 were infantile Pompe disease, with 44 LOPD. Since May 2016, a further 850 patients have been screened for Pompe disease using the MSMS method and of these, 28 patients have screened as positive, with 19 confirmed as having Pompe disease, either by molecular testing or urine tetra-saccharide measurement, a diagnosis rate of 2.2%. Of these 19 patients, 17 are LOPD, with only two infants being diagnosed in this time. Seven adults are still to be confirmed by a second test.

Conclusion

The number of patients presenting for testing follows the recent Australian government funding for enzyme replacement therapy for adults with LOPD. The ease of submitting a dried blood spot sample for testing has contributed to an increase in test requests, although this may also reflect an increased recognition of this condition. These patients may have already been diagnosed clinically, but in the absence of a treatment, there was little benefit in a formal diagnosis.
030 A rapidly progressive dermatomyositis with fatality – lessons to learn
Authors: Islam Fariha , Malhotra Abhishek , Sachdev Anish
Published: May 2018

Introduction

We report a case of dermatomyositis in a 43 year old male who presented with transient mild proximal muscle weakness but died from rapidly progressive pulmonary disease within 3 months of diagnosis.

Case

The patient presented with proximal muscle weakness, arthralgia and classic dermatomyositis rashes. He had a history of Huntington’s disease mutation with a positive family history. He had raised creatine kinase (CK) and electromyography showed myopathic changes. The diagnosis was confirmed by skin and muscle biopsy and positive anti-myositis antibodies; PM-Scl(75), MDA5 and SRP. Screening for underlying malignancy was negative but a CT chest scan showed bilateral areas of reverse halo-opacity suggestive of interstitial lung disease (ILD) although he had no respiratory symptoms at the time. He had input from dermatology, rheumatology and respiratory teams and commenced on prednisone 1 mg/kg with pneumocystis prophylaxis. He underwent bronchoscopy and broncho-alveolar lavage that did not isolate any organisms and cell differential was normal. His muscle weakness had resolved even prior to starting steroids and his CK normalised on high dose prednisolone but he developed progressive shortness of breath that led to a second admission within two months. Repeat CT chest showed extensive bilateral infiltrative disease and pneumo-mediastinum. No infective cause was found. He deteriorated rapidly despite intubation, broad-spectrum antibiotics, steroids and extracorporeal membrane oxygenation. He died whilst being considered for lung transplantation.

Conclusion

This case provides valuable lessons. Even in cases of mild muscle disease, the extra-muscular involvement can be severe and life threatening in dermatomyositis. Anti-myositis antibodies can be helpful in predicting the course of disease including extra-muscular involvement. The anti-MDA5 antibodies are associated with amyopathic dermatomyositis associated with a rapidly progressive ILD and often with pneumo-mediastinum and has a poor prognosis as in our case. One should consider more aggressive therapy for these patients from the outset.
033 Effect of ocrelizumab on upper limb function in patients with primary progressive multiple sclerosis (PPMS) in the oratorio study (ENCORE)
Authors: Fox Edward , Markowitz Clyde , Applebee Angela , Montalban Xavier , Wolinsky Jerry S , Belachew Shebeshih , Fiore Damian , Han Jian , Musch Bruno , Giovannoni Gavin
Published: May 2018

Introduction

Upper limb (UL) functional impairment is prevalent among PPMS patients and alters quality of life. The nine-hole peg test (9HPT) is a validated quantitative assessment of UL function in MS.

Methods

9HPT was administered at baseline and every 12 weeks until study end. The average 9HPT-times from two trials of dominant- and non-dominant-hands were compared; the hand with the lower baseline time was termed ‘better-hand’, and the hand with the higher baseline time was termed ‘worse-hand’. Average dominant- and non-dominant-hand times were combined and termed ‘both-hands’. Analyses included time-to-confirmed progression (CP) in hand function, defined as ≥15%, ≥20% or ≥25% increase in 9HPT-time from baseline, confirmed at 12- and 24 weeks, and change in 9HPT-time from baseline to Week-120.

Results

Compared with placebo, ocrelizumab reduced the time-to 12- and 24-week-CP of ≥15% increase on 9HPT by 37% (hazard ratio [HR]=0.627; p=0.001) and 39% (HR=0.607; p=0.002) for both-hands, 30% (HR=0.699; p=0.011) and 40% (HR=0.599; p<0.001) for better-hand and 29% (HR=0.705; p=0.016) and 28% (HR=0.717; p=0.040) for worse-hand. The time-to 12- and 24-week-CP of ≥20% increase on 9HPT was reduced by 44% (HR=0.561; p<0.001) and 45% (HR=0.545; p<0.001) for both-hands, 28% (HR=0.723; p=0.046) and 35% (HR=0.646; p=0.014) for better-hand and 37% (HR=0.632; p=0.005) and 40% (HR=0.599; p=0.004) for worse-hand. Ocrelizumab also reduced the time-to 12- and 24-week-CP of ≥25% increase on 9HPT by 48% (HR=0.520; p<0.001) and 49% (HR=0.507; p<0.001) for both-hands, 30% (HR=0.698; p=0.048) and 39% (HR=0.613; p=0.015) for better-hand, and 48% (HR=0.521; p<0.001) and 42% (HR=0.578; p=0.004) for worse-hand. At week-120, the increase from baseline 9HPT-time for both-hands and worse-hand was significantly smaller with ocrelizumab vs placebo (p<0.001 and p=0.041, respectively); for better hand, the increase was smaller with ocrelizumab; difference was not significant (p=0.056).

Conclusion

Ocrelizumab treatment lowered the risk of progression of upper extremity disability, measured by 9HPT, compared with placebo in PPMS patients.
036 Mobile intraluminal long segment carotid thrombus causing ischaemic stroke
Authors: Nham Benjamin , Hawke Simon
Published: May 2018

Introduction

Mobile or free-floating long segment intraluminal thrombus within the carotid artery is a rare entity that has a high likelihood of causing recurrent ischaemic strokes if left untreated. There is no consensus about whether medical or surgical management of the carotid intraluminal thrombus represents the best management option. We present a case of an 83 year old man who presented with an ischaemic stroke secondary to this condition.

Case

An 83 year old man presented to a regional hospital with acute right arm weakness and facial droop outside the timeframe for thrombolysis. CT carotid angiogram and carotid doppler showed non-occlusive mobile intraluminal thrombus involving a 3 cm segment of the vessel, just distal to the bifurcation. An MRI brain scan demonstrated an acute left MCA infarct. The patient declined carotid endarterectomy and was treated with intravenous heparin infusion. This was stopped one week later after he developed a thigh hematoma. Repeat CT angiogram revealed resolution of the thrombus and an underlying 30% non-calcific carotid plaque. He was treated with secondary prevention stroke agents.

Management options of the mobile carotid thrombus include anticoagulation, commonly with intravenous heparin in the acute phase, or surgical management. It is unclear from the evidence which is superior. The literature suggests initial anticoagulation for 7–10 days resulted in a low rate of recurrent ischaemic events and that carotid revascularisation, if indicated, could later be safely performed or delayed if necessary.

Conclusion

Mobile intraluminal carotid thrombus is a rare cause of ischaemic stroke. These mobile thrombi are often secondary to underlying ulcerated carotid plaques. In our case, medical management with intravenous heparin was a safe and effective treatment option with excellent functional recovery and resolution of the thrombus.
037 Post-transplant lymphoproliferative disorder in skeletal muscle arising seven years after allogeneic stem cell transplant
Authors: Powell Alice , Sy Joanne , Barnett Yael , Mosalski Simon , Brew Bruce , Fay Keith , Tomlinson Susan
Published: May 2018

Introduction

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognised serious complication of transplantation. However, it rarely affects muscle.

Methods

A case report detailing presentation, evaluation, management and outcome of a patient with acute on chronic proximal myopathy on a background of allogeneic stem cell transplant is described. The patient was diagnosed with PTLD affecting skeletal muscle.

Results

A 54 year old man presented with painful proximal myopathy seven years after successful allogeneic stem cell transplant for acute myeloid leukaemia. He had been managed with immunosuppression for extensive cutaneous graft versus host disease (GVHD) from the time of transplant. Initial quadriceps muscle biopsy showed changes in keeping with GVHD and features suggestive of drug-related necrotising myositis. The painful myalgia evolved to include bulbar muscles with dysphagia despite pulse steroid and intravenous immunoglobulin therapy. A positron emission tomography (PET) scan demonstrated intense and extensive hyper-metabolism in multiple muscle groups in keeping with diffuse myositis with the most prominent activity involving neck muscles, the left shoulder girdle and left arm musculature. A second biopsy of the sternocleidomastoid demonstrated infiltration with haematolymphoid cells consistent with post-transplant lymphoproliferative disorder. Treatment with reduction in immunosuppression, rituximab and rehabilitation saw improvement in myalgia and weakness. Unfortunately, exacerbation of chronic GVHD ensued following reduction in immunosuppression and contributed to oesophageal stricturing eventually requiring a percutaneous endoscopic gastrostomy tube for feeding.

Conclusion

This case highlights the complex morbidity of allogeneic stem cell transplant and the need to consider PTLD in the differential for patients who present with neurological symptoms.
041 Predictors of clinical outcomes in patients with brain abscess
Authors: Amornpojnimman Thanyalak , Korathanakhun Pat
Published: May 2018

Introduction

Brain abscess is an intra-parenchymal suppurative infectious condition of the brain caused by various microorganisms and potentially resulting in a life-threatening condition. Despite Thailand being located in a tropical region, studies on brain abscess are quite limited and outdated. Most of the published data in the Thai population were collected during a period when advanced neuroimaging techniques were not widely available. This issue contributed to late diagnosis and treatment that impacted the clinical outcomes. Therefore, our study aims to identify predictors of mortality among patients with brain abscess in Thailand.

Methods

We retrospectively studied patients diagnosed with brain abscess admitted to Songklanagarind hospital in Songkhla, Thailand between 2002 and 2017. Demographic data, neurological status, clinical presentations, predisposing factors, microbiological profiles, neuroimaging findings, treatments, and outcomes were collected from electrical medical records. Predictors of death outcome were analysed by univariate and multivariate logistic regression analysis.

Results

81 patients were enrolled in the study. Forty-seven patients (58%) were male and 34 patients (42%) were female. The overall mean age was 47.68±16.92 years. The common risk factors of brain abscess were immunocompromised state (38.3%) and the extension of a peri-cranial infection (24.7%). The common clinical presentations were headache (61.7%), fever (50.6%), and hemiplegia (34.6%). Eleven patients (13.6%) were dead at hospital discharge. The independent factor associated with death outcome identified by multivariate analysis was confusion (odds ratio 7.67, 95% CI 1.95–30.14; p=0.003).

Conclusion

The current study shows that increased immunocompromised state is a predisposing factor of brain abscess. The independent factor associated with death was confusion, which correlated with septic encephalopathy.
046 Efficacy and safety of intravenous immunoglobulin (IVIG) IGPRO10 in chronic inflammatory demyelinating polyneuropathy (CIDP)
Authors: Sabet Arman , Mielke Orell , Schaik Ivo N van , Leger Jean-Marc , Bril Vera , Gloven Nan van , Hartung Hans Peter , Lewis Richard A , Sobue Gen , Lawo John-Philip , Durn Billie L , Cornblath David R , Bleecker Jan LDe , Sommer Claudia , Robberecht Wim , Saarela Mika , Kamienowski Jerzy , Stelmasiak Zbigniew , Tackenberg Bjorn , Merkies Ingemar SJ
Published: May 2018

Introduction

We analysed the efficacy and safety of IVIG IgPro10 (CSL Behring) in two CIDP studies: PRIMA and PATH.

Methods

PRIMA was a prospective, open-label, single-arm study in 28 CIDP patients (n=13 IVIG-pretreated; n=15 untreated) investigating efficacy and safety of IgPro10 for induction (2 g/kg) and maintenance therapy (1 g/kg every 3 weeks for 21 weeks). This regimen was also used for 207 IVIG-pretreated patients during the 10–13 week pre-randomization phase of the PATH study (before randomization to subcutaneous immunoglobulin maintenance therapy or placebo). Both studies investigated a 1-point decrease in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score as a response parameter, and evaluated changes in mean grip strength and Medical Research Council (MRC) score. Treatment-emergent adverse events (AEs) were assessed.

Results

Response rate was 76.9% (95% confidence interval [CI] 49.7–91.8) in PRIMA (IVIG-pretreated patients) at week 21% and 72.9% (95%CI 66.5–78.5) in PATH at week 13; median time to first INCAT response was 3.0 and 3.7 weeks, respectively. Median (Q1;Q3) improvements in outcome measures (baseline to last observation) for PRIMA pre-treated patients and PATH, respectively, were: INCAT, −2.0 (-3.0;−1.0) and −1.0 (-2.0;0.0) points; grip strength, 5.0 (-9.0;22.0) and 9.4 (1.3;18.8) kPa; and MRC score, 5.0 (3.0;10.0) and 3.0 (0.0;6.0) points. In the PRIMA safety population (n=28), 108 AEs occurred in 22 (78.6%) patients (0.417/infusion); 284 AEs in 100 (48.3%) patients (0.175/infusion) were reported in the PATH safety population (n=207). Headache was the most frequent AE. Causally related serious AEs in PRIMA and PATH occurred in 2 and 7 patients, respectively.

Conclusion

Similar efficacy results of IgPro10 in CIDP were observed in PRIMA and the PATH pre-randomization period. IgPro10 is well tolerated, with clinically meaningful improvement in disability in CIDP patients.

Study Support

CSL Behring
056 Perampanel and secondarily generalised seizures in a pooled analysis of phase III studies and their open-label extension: effect of enzyme-inducing antiepileptic drugs
Authors: Ko David , Williams Betsy , Patten Anna , Laurenza Antonio
Published: May 2018

Introduction

Perampanel is approved for adjunctive treatment of partial seizures, with or without secondarily generalised seizures (SGS), and primary generalised tonic-clonic seizures in epilepsy patients aged ≥12 years. Approval of perampanel for partial seizures was based on three randomised, double-blind, placebo-controlled, Phase III Studies 304 (NCT00699972), 305 (NCT00699582) and 306 (NCT00700310); patients completing these could enter open-label extension (OLEx) Study 307 (NCT00735397). Here, we report efficacy of perampanel as adjunctive treatment of SGS by co-administration of enzyme-inducing antiepileptic drugs (EIAEDs) versus non-EIAEDs in both the Phase III and OLEx studies.

Methods

In the double-blind studies, patients (≥12 years) with partial seizures, with or without SGS, receiving 1–3 AEDs at Baseline were randomised to placebo or 2–12 mg/day perampanel for 19 weeks. In the OLEx, patients received ≤12 mg/day perampanel for ≤272 weeks. Efficacy assessments included median percent change in SGS frequency/28 days, SGS 50% and 75% responder and seizure-freedom rates.

Results

For patients with SGS at pre-perampanel Baseline, 564 were in the double-blind studies and 388 received perampanel for ≥1 year in the OLEx. In the double-blind studies, perampanel co-administered with an EIAED (carbamazepine, eslicarbazepine, oxcarbazepine, phenytoin) had reduced efficacy compared with non-EIAEDs due to increased clearance; this was particularly evident at higher doses, although these differences were still greater than placebo. In the OLEx, concomitant administration of both non-EIAEDs and EIAEDs was associated with sustained efficacy, with slightly better efficacy during the first, second and third years of perampanel exposure for non-EIAEDs compared with EIAEDs.

Conclusion

Perampanel demonstrated good and sustained long-term efficacy against SGS. With the recent FDA approval of perampanel for monotherapy use for partial seizures, non-EIAED data may be more relevant for consideration if perampanel is used as a single agent (no other AED) while real-world data and experience are accumulated.

Study support

Eisai Inc.
058 ANTI-CASPR2-ANTIBODY associated encephalitis in a 63-year old male with chronic lymphocytic leukaemia
Authors: Lilley Kate , Swayne Andrew , Watson Emily , Kee Rachel , Wong David , Lehn Alexander , Brown Helen , O’Gorman Cullen , Sheikh Nabeel , Bird Robert , Prain Kerri , Gillis David , Wong Richard C , Blum Stefan
Published: May 2018

Introduction

This case from a tertiary neurology centre reports a novel association between the emerging clinical entity of anti-contactin associated protein-2 (CASPR-2) antibody encephalitis and chronic lymphocytic leukaemia (CLL).

Case

We describe a 63 year old Maori male truck-driver who presented with progressive altered personality, speech, cognition and perception over 9 months. The patient also developed choreiform movements, broad-based gait, incontinence, sleep apnoea with type 2 respiratory failure and episodic loss of consciousness. 12 months prior, he had been diagnosed with low-risk CLL, for which he remained untreated. MRI of the brain revealed mid-sagittal bilateral mid-temporal T2/FLAIR hyperintensities. Cerebrospinal fluid examination showed a mononuclear pleocytosis (WCC 270×10^6/L) with 15% of these CD5/CD19/CD23 positive and 92% CD3/CD5 positive CD 19 negative on flow cytometry, protein was also elevated at 2600 mg/L. The interplay between CLL and inflammation is uncertain. Anti-Caspr2-antibody was identified in CSF and serum. The patient was treated with a combination of fludarabine, cyclophosphamide, rituximab, dexamethasone and intravenous immunoglobulin (IVIG). Clinical status improved and antibody titre decreased from 580 to 241 pM in three weeks and to 55pM (negative <85 pM) at five months. Symptoms worsened when IVIG doses were missed. He returned home after inpatient rehabilitation, showed striking clinical improvement at 12 month follow-up and continues on maintenance IVIG therapy.

Conclusion

Whilst paraneoplastic VGKC encephalitis has been described associated with a number of malignancies, this is the first reported case of CASPR-2 antibody present in association with CLL.

References

. Van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ. The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nature Reviews Neurology2017;13(5):290–301.

. Nogai H, Israel-Willner H, Zschenderlein R, Pezzutto A. Improvement in Paraneoplastic Limbic Encephalitis after Systemic Treatment with Rituximab in a Patient with B-Cell Chronic Lymphocytic Leukaemia. Case Reports in Haematology2013;2013:Article ID958704.

. Van Sonderen A, Ariño H, Petit-Pedrol M, et al. The Clinical Spectrum of Caspr2 antibody-associated disease. Neurology2016;87:521–528.

. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, et al. Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain2000;123:1481–1494.
060 Association of brain volume loss and neda outcomes in patients with relapsing multiple sclerosis in the opera i and opera ii studies (ENCORE)
Authors: Traboulsee Anthony , Arnold Douglas , Klawiter Eric C , Havrdova Eva , Fiore Damian , Zheng Ray , Julian Laura , Giovannoni Gavin
Published: May 2018

Introduction

Brain volume loss (BVL) occurs in multiple sclerosis (MS) patients, reflecting irreversible tissue damage. No evidence of disease activity (NEDA), a composite measure assessing absence of clinical and magnetic resonance imaging (MRI) disease activity has emerged as important treatment goal in MS and may be associated with preservation of brain tissue and BVL prevention.

Methods

Patients in OPERA-I/II (NCT01247324/NCT01412333) received 600 mg ocrelizumab (intravenous) very 24 weeks or 44 µg subcutaneous interferon beta-1a (IFNβ-1a) 3x-weekly for 96 weeks. Brain MRI assessments were completed at baseline and 24/48/96 Weeks. Brain volume normalised for head size was measured using SIENAX software. Percent change in whole brain volume (WBV) was determined using SIENA software, changes in cortical grey (GMV) and white (WMV) matter volumes were measured using validated, locally developed Jacobian integrator atrophy software. NEDA was defined as absence of relapses, 12-week confirmed disability progression, T1 Gd–enhancing lesions and new and/or enlarging T2-lesions. Changes from baseline in brain volume were examined in NEDA patients and those with evidence of disease activity (EDA), using the mixed-effects model for repeated measures method.

Results

The analysis included 1520 patients (ocrelizumab-761; IFNβ-1a-759). Over 96 weeks, 569 (37%) patients [ocrelizumab-363 (48%); IFNβ-1a-206(27%); p<0.001] had NEDA. Compared with EDA patients, NEDA patients had significantly less WBV loss from baseline (30%-reduction; p<0.001). In the NEDA group, ocrelizumab patients had significantly less WBV loss (32%-reduction; p<0.001), WMV loss (34%-reduction; p=0.044) and GMV loss (30%-reduction; p<0.001) from baseline than IFNβ-1a patients. In the EDA group, ocrelizumab patients had significantly less WBV loss (11%-reduction; p=0.047) and GMV loss (21%-reduction; p<0.001) but not WMV loss (1.03%-increase; p=0.90) from baseline than IFNβ-1a patients.

Conclusion

These findings highlight the importance of NEDA as treatment goal with respect to brain tissue preservation regardless of treatment choice. Ocrelizumab may confer additional benefits in NEDA patients NEDA beyond what is observed with IFNβ-1a.