bluuebunny/crossref_metadata_2025_split huggingface dataset:
THUR 171 Natalizumab effectiveness and safety in top uk patients
Authors: Richard Nicholas , Karen Rosales , Stephanie Licata , Feisal Syed Farooq Syed , Caroline Smethurst 
Published: October 2018

IntroductionThe TYSABRI® Observational Program (TOP) is an ongoing, global open-label study enrolling natalizumab-treated relapsing-remitting multiple sclerosis patients in real-world settings. Country-specific data can provide information on natalizumab’s benefit-risk in local clinical practice.MethodsClinical outcomes in UK and rest of world (ROW) TOP patients were compared.ResultsAs of May 2016, 134 UK and 5793 ROW patients were enrolled in TOP. Mean baseline Expanded Disability Status Scale (EDSS) score was 4.27 in the UK and 3.45 in ROW. Mean years on natalizumab was 3.52 in the UK and 3.04 in ROW. Annualized relapse rate (ARR) decreased by 89.7% (from 2.21 pre-natalizumab to 0.23 post natalizumab initiation; p<0.0001) in the UK and by 89.0% (from 1.99 to 0.22; p<0.0001) in ROW. In both cohorts, ARR decrease by baseline EDSS score was 91.0%–93.2% for <3.0 and 87.3%–88.9% for ≥3.0; mean EDSS score change from baseline over 6 years was <1.0. Overall, 9 of 134 UK patients (6.7%) experienced ≥1 serious adverse event.ConclusionsNatalizumab demonstrated similar effectiveness in the UK and ROW cohorts. Safety in the UK cohort was consistent with natalizumab’s established safety profile.SupportBiogenDisclosuresRN: grant/travel support from Biogen; KR, SL, SFSF, CS: Biogen employees.
WED 183 Cladribine tablets effects on t cell subsets in patients with early ms
Authors: Stuve Olaf , Soelberg-Sorensen Per , Leist Thomas , Hyvert Yann , Damian Doris , Boschert Ursula 
Published: October 2018

BackgroundBecause of the durable clinical effects of cladribine tablets 3.5 mg/kg (CT3.5) in patients with multiple sclerosis, the influence of treatment on cells with regulatory immune function is of interest.ObjectiveExamine effects on central memory; effector memory; and naturally occurring regulatory (nTregs) CD4 +T cells after first administration of CT3.5 in ORACLE-MS.MethodsPeripheral blood T-lymphocytes were immunophenotyped at baseline, and Weeks 5, 13, 24, 48 in CT3.5 treated patients (n=41). Absolute numbers and proportions of central memory (CD4+RO+CCR7+), effector memory (CD4+RO+CCR7-), Th1-type (CD4+CXCR3+), nTregs (CD4+CD25+CD127-), including naïve-like and memory-like nTregs were measured.ResultsGreatest median reductions in absolute numbers occurred at Week-13 for effector memory cells (−54%); Week-24 for central memory (−63%) and Th1-type cells (−51%); with similar/slightly increased levels at Week-48. There was ~5% reduction in proportion of central memory cells, but no change in proportions of effector memory and Th1-type cells. Absolute numbers of nTregs (−48%), naïve-like (−67%) and memory-like nTregs (−42%) decreased by Week-48. nTregs and naïve-like nTregs proportions were unchanged. Proportions of memory-like nTregs slightly increased up to 48 Weeks.ConclusionCT3.5 administration has a comparable effect on CD4+ T cell subpopulations, with no dramatic shifts in proportions.Disclaimerhttp://medpub-poster.merckgroup.com/ABN2018DISC_ORACLE.pdf
WED 190 Teriflunomide pregnancy registry: design and enrolment
Authors: David Rog , Christine Lebrun-Frenay , Nicola Seferta , Myriam Benamor , Susan Colilla , Philippe Truffinet , Angelo Ghezzi 
Published: October 2018

IntroductionTeriflunomide is contraindicated in pregnancy, based on developmental toxicity in rats and rabbits. During clinical development, despite requirements for contraceptive use, some pregnancies occurred. There were no signs of structural or functional deficits in newborns.MethodsThe multinational, prospective, observational International Teriflunomide Pregnancy Exposure Registry is enrolling teriflunomide-exposed pregnant women with MS. Signed informed consent is obtained prior to enrolment. In the UK, healthcare professionals submit information to the National Coordinating Centre (Manchester, UK). Infants are followed until 1 year old. Pregnancy outcomes, including birth defects and infant characteristics, are collected. Target recruitment: 196 women to achieve 104 live births, providing 80% power to detect 3.95-fold increase in risk of birth defects associated with teriflunomide exposure vs the European Surveillance of Congenital Anomalies (EUROCAT) network.ResultsAs of 26/04/2017, 14 patients have been recruited from 7 European countries (none in the UK). Six healthy babies have been born to date. One patient had an elective termination not motivated by abnormal prenatal test results or concerns regarding potential birth defects.ConclusionThis registry aims to provide data on pregnancy outcomes and infant development from teriflunomide-exposed women, which may help physicians provide better patient advice.Study supported by Sanofi.
THUR 192 Yearly lymphopenia rates in cladribine tablets-treated rms patients
Authors: Cook Stuart , Comi Giancarlo , Giovannoni Gavin , Rieckmann Peter , Soelberg-Sorensen Per , Vermersch Patrick , Dangond Fernando , Hicking Christine 
Published: October 2018

BackgroundCladribine tablets 3.5 mg/kg (CT3.5) demonstrated efficacy in RMS patients in CLARITY/CLARITY-Extension. Lymphopenia was common (CT3.5: mechanism of action).ObjectiveEvaluate whether lymphopenia persists following treatment/re-treatment with CT3.5 in CLARITY/CLARITY- Extension.MethodsLymphopenia by grade for patients randomised to CT3.5 throughout CLARITY/CLARITY-Extension (7 mg/kg cumulative 4 year dose; n=186) are reported. Patients with Grade 0 (G0) lymphopenia (≥1.0 × 109 cells/L) before the first course of CT and G0/1 (≥0.8 × 109 cells/L) before subsequent treatment in Years 2 (Y2), 3 and 4 were analysed.Results176 patients were G0 at the start of CLARITY (167 were G0/1; CLARITY-Extension). G3 lymphopenia was observed in 1% patients (Week-13, Y1), and in 7%, 11% and 12% patients at Week-12 in Y2, 3 and 4. In each year, G3 lymphopenia was observed in 1%, 4%, 4% and 4% patients (Week-24), in 1%, 2%, 2% and 2% patients (Week-36), and in 1% patients (Week-48) in Y2 only. G3 lymphopenia was reported in <18% patients at any time-point. No patients had G4 lymphopenia at the end of each treatment year.ConclusionsIn patients meeting treatment/re-treatment guidelines, no G4 lymphopenia occurred at the end of any treatment year; G3 lymphopenia was uncommon. Lymphocyte-based re-treatment criteria minimised the incidence of severe, sustained lymphopenia during 4 years’ treatment with CT.Disclaimerhttp://medpub-poster.merckgroup.com/ABN2018DISC_Year1-4.pdf
Assessing the risk of preterm birth for newborns with congenital heart defects conceived following infertility treatments: a population-based study
Authors: Tararbit Karim , Lelong Nathalie , Goffinet François , Khoshnood Babak 
Published: October 2018

ObjectivesTo quantify the risk of preterm birth (PTB) for newborns with congenital heart defects (CHDs) conceived following infertility treatments, and to examine the role of multiple pregnancies in the association between infertility treatments and PTB for newborns with CHD.MethodsWe used data from a population-based, prospective cohort study (EPICARD EPIdémiologie des CARDiopathies congénitales) including 2190 newborns with CHD and excluding cases with atrial septal defects born to women living in the Greater Paris area between May 2005 and April 2008. Statistical analysis included logistic regression to take into account potential confounders (maternal characteristics, invasive prenatal testing, CHD prenatal diagnosis, medically induced labour/caesarean section before labour, birth year). The role of multiple pregnancies was assessed using a path-analysis approach, allowing decomposition of the total effect of infertility treatments on the risk of PTB into its indirect (mediated by the association between infertility treatments and multiple pregnancies) and direct (mediated by mechanisms other than multiple pregnancies) effects.ResultsPTB occurred for 40.6% (95% CI 28.7 to 52.5) of newborns with CHD conceived following infertility treatments vs 12.7% (95% CI 11.3 to 14.2) for spontaneously conceived newborns (p<0.001). After taking into account potentially confounding factors, infertility treatments were associated with a 5.0-fold higher odds of PTB (adjusted OR=5.0, 95% CI 2.9 to 8.6). Approximately two-thirds of this higher risk of PTB associated with infertility treatments was an indirect effect (ie, due to multiple pregnancies) and one-third was a direct effect (ie, not mediated by multiple pregnancies).ConclusionNewborns with CHD conceived following infertility treatments are at a particularly high risk of PTB, exposing over 40% of them to the ‘double jeopardy’ of CHD and PTB.
Characterisation of circulating biomarkers before and after cardiac resynchronisation therapy and their role in predicting CRT response: the COVERT-HF study
Authors: McAloon Christopher J , Barwari Temo , Hu Jimiao , Hamborg Thomas , Nevill Alan , Hyndman Samantha , Ansell Valerie , Musa Anntoniette , Jones Julie , Goodby Julie , Banerjee Prithwish , O’Hare Paul , Mayr Manuel , Randeva Harpal , Osman Faizel 
Published: October 2018

AimsCardiac resynchronisation therapy (CRT) is effective treatment for selected patients with heart failure (HF) but has ~30% non-response rate. We evaluated whether specific biomarkers can predict outcome.MethodsA prospective single-centre pilot study of consecutive unselected patients undergoing CRT for HF between November 2013 and December 2015 evaluating cardiac extracellular matrix biomarkers and micro-ribonucleic acid (miRNA) expression before and after CRT assessing ability to predict functional response and survival. Each underwent three assessments (pre-implant, 6  weeks and 6  months postimplant) including: New York Heart Association (NYHA) class, echocardiography, electrocardiography, 6  min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Plasma markers of cardiac fibrosis assessed were: N-terminal pro-peptides of collagen I and III, collagen I C-terminal telopeptides (CTx) and matrix metalloproteinases (MMP-2 and MMP-9) as well as a panel of miRNAs (miRNA-21, miRNA-30d, miRNA-122, miRNA-133a, miRNA-210 and miRNA-486).ResultsA total of 52 patients were recruited; mean age (±SD) was 72.4±9.4 years; male=43 (82.7%), ischaemic aetiology=30 (57.7%), mean QRS duration=166.4±23.5  ms, left bundle branch block (LBBB) morphology = 39 (75.0%), mean NYHA=2.7±0.6, 6MWT=238.8±130.6  m, MLHFQ=46.4±21.3  and left ventricular ejection fraction (LVEF)=24.3%±8.0%. Mean follow-up=1.7±0.3  and 5.8±0.7 months. There were 27 (55.1%) functional responders (3 no definable 6-month response; 2 missed assessments and 1 long-term lead displacement). No marker predicted response, however, CTx and LBBB trended most towards predicting functional response.ConclusionNo specific biomarkers reached significance for predicting functional response to CRT. CTx showed a trend towards predicting response and warrants further study.Trial registration numberNCT02541773.
Cannabis and epilepsy
Authors: Thomas Rhys H , Cunningham Mark O 
Published: October 2018

Click here to listen to the PodcastThe one-third of people who do not gain seizure control through current treatment options need a revolution in epilepsy therapeutics. The general population appears to be showing a fundamental and rapid shift in its opinion regarding cannabis and cannabis-related drugs. It is quite possible that cannabidiol, licensed in the USA for treating rare genetic epilepsies, may open the door for the widespread legalisation of recreational cannabis. It is important that neurologists understand the difference between artisanal cannabidiol products available legally on the high street and the cannabidiol medications that have strong trial evidence. In the UK in 2018 there are multiple high-profile reports of the response of children taking cannabis-derived medication, meaning that neurologists are commonly asked questions about these treatments in clinic. We address what an adult neurologist needs to know now, ahead of the likely licensing of Epidiolex in the UK in 2019.
Ehlers-Danlos syndromes: state of the art on clinical practice guidelines
Authors: Sulli Alberto , Talarico Rosaria , Scirè Carlo Alberto , Avcin Tadej , Castori Marco , Ferraris Alessandro , Frank Charissa , Grunert Jürgen , Paolino Sabrina , Bombardieri Stefano , Schneider Matthias , Smith Vanessa , Cutolo Maurizio , Mosca Marta , Malfait Fransiska 
Published: October 2018

ObjectiveTo report the effort of the European Reference Network for Rare and Complex CONnective tissue and musculoskeletal diseases NETwork working group on Ehlers-Danlos syndromes (EDS) and related disorders to assess current available clinical practice guidelines (CPGs) specifically addressed to EDS, in order to identify potential clinician and patient unmet needs.MethodsSystematic literature search in PUBMED and EMBASE based on controlled terms (MeSH and Emtree) and keywords of the disease and publication type (CPGs). All the published articles were revised in order to identify existing CPGs on diagnosis, monitoring and treatment of EDS.ResultsLiterature revision detected the absence of papers reporting good quality CPGs to optimise EDS patient care. The current evidence-based literature regarding clinical guidelines for the EDS was limited in size and quality, and there is insufficient research exploring the clinical features and interventions, and clinical decision-making are currently based on theoretical and limited research evidences.ConclusionsMany clinician and patient unmet needs have been identified.
The contribution of viruses and bacteria to community-acquired pneumonia in vaccinated children: a case–control study
Authors: Bhuiyan Mejbah Uddin , Snelling Thomas L , West Rachel , Lang Jurissa , Rahman Tasmina , Granland Caitlyn , de Gier Camilla , Borland Meredith L , Thornton Ruth B , Kirkham Lea-Ann S , Sikazwe Chisha , Martin Andrew C , Richmond Peter C , Smith David W , Jaffe Adam , Blyth Christopher C 
Published: October 2018

IntroductionRespiratory pathogens associated with childhood pneumonia are often detected in the upper respiratory tract of healthy children, making their contribution to pneumonia difficult to determine. We aimed to determine the contribution of common pathogens to pneumonia adjusting for rates of asymptomatic detection to inform future diagnosis, treatment and preventive strategies.MethodsA case–control study was conducted among children <18 years in Perth, Western Australia. Cases were children hospitalised with radiologically confirmed pneumonia; controls were healthy children identified from outpatient and local immunisation clinics. Nasopharyngeal swabs were collected and tested for 14 respiratory viruses and 6 bacterial species by Polymerase chain reaction (PCR). For each pathogen, adjusted odds ratio (aOR; 95% CI) was calculated using multivariate logistic regression and population-attributable fraction (95% CI) for pneumonia was estimated.ResultsFrom May 2015 to October 2017, 230 cases and 230 controls were enrolled. At least one respiratory virus was identified in 57% of cases and 29% of controls (aOR: 4.7; 95% CI: 2.8 to 7.8). At least one bacterial species was detected in 72% of cases and 80% of controls (aOR: 0.7; 95% CI: 0.4 to 1.2). Respiratory syncytial virus (RSV) detection was most strongly associated with pneumonia (aOR: 58.4; 95% CI: 15.6 to 217.5). Mycoplasma pneumoniae was the only bacteria associated with pneumonia (aOR: 14.5; 95% CI: 2.2 to 94.8). We estimated that RSV, human metapneumovirus (HMPV), influenza, adenovirus and Mycoplasma pneumoniae were responsible for 20.2% (95% CI: 14.6 to 25.5), 9.8% (5.6% to 13.7%), 6.2% (2.5% to 9.7%), 4% (1.1% to 7.1%) and 7.2% (3.5% to 10.8%) of hospitalisations for childhood pneumonia, respectively.ConclusionsRespiratory viruses, particularly RSV and HMPV, are major contributors to pneumonia in Australian children.
Mixed-methods evaluation of a ban on tobacco advertising and promotion in Banyuwangi District, Indonesia
Authors: Sebayang Susy K , Dewi Desak Made Sintha Kurnia , Lailiyah Syifa’ul , Ahsan Abdillah 
Published: October 2018

IntroductionTobacco advertisement bans in Indonesia are rare and seldom evaluated. The recent introduction of an outdoor tobacco advertisement (OTA) ban in Banyuwangi District, East Java, Indonesia provided an opportunity to evaluate such policy.MethodsUsing a mixed-methods approach, we undertook an observational study of OTA in 15 locations where such advertising had been prohibited. We also interviewed a sample of 114 store-owners/storekeepers and 131 community members, and conducted indepth interviews with government officials and the Public Order Agency (POA), the designated enforcement agency.ResultsIn phase 1 we found only one location was free of advertisements. We identified 667 advertisement points and 1283 advertisement materials in the study location; of these, 7% and 7.8% were within 25 m of schools and religious sites, respectively. Phase 2 showed that 68% of the respondents were unaware of the regulation, but many supported an OTA ban. Indepth interviews revealed that not all members of the POA were familiar with the regulation. POA members believed they will enforce the regulation better if higher level regulation for ban on tobacco advertisements, promotions and sponsorships was made and digital application is available to support surveillance.ConclusionPolicy violations were evident 1 year after the launch of OTA ban in Banyuwangi. Tobacco advertisements are still visible, including near schools and religious sites, potentially stimulating adolescents to smoke. Regional regulation and setting specific violation reductions as a performance indicator for POA could improve compliance. App-based technology could assist violation surveillance and reporting, as could awareness-raising campaigns that encouraged community support to report violation through the apps.
Economic costs of diseases and deaths attributable to bidi smoking in India, 2017
Authors: John Rijo M 
Published: October 2018

ObjectiveTo estimate the economic burden of diseases and deaths attributable to bidi smoking in India for persons aged 30–69 years.MethodsThe National Sample Survey data on healthcare expenditures, data on bidi smoking prevalence from the Global Adult Tobacco Survey and relative risks of all-cause mortality from bidi smoking are used to estimate the economic burden of diseases and deaths attributable to bidi smoking in India using a prevalence-based attributable-risk approach. Costs are estimated under the following heads: (1) direct medical expenditure of treating diseases; (2) indirect morbidity costs and (3) indirect mortality costs of premature deaths.FindingsThe total economic costs attributable to bidi smoking from all diseases and deaths in India in the year 2017 for persons aged 30–69 years amount to INR805.5 billion (US$12.4 billion), of which 20.9% is direct and 79.1% is indirect cost. Men bear 93.7% of the total costs.ConclusionThe total annual economic costs of bidi smoking amount to approximately 0.5% of India’s gross domestic product, while the excise tax revenue from bidi is only half a per cent of its economic costs. The direct medical costs of bidi smoking amount to 2.24% of total health expenditure. Since the poor bear a disproportionately large share of the economic costs of bidi smoking, the unregulated use of bidi would potentially push more households in India, which incur heavy out-of-pocket expenditures on healthcare, into poverty.
Optimization for white organic light-emitting diode based on DCJTB as color conversion layer
Authors: Wang Pei , Wang Zhen , Chen Ai , Xie Jia-Feng , Zheng Xin 
Published: October 2018

In this paper, combining phosphorescence and fluorescence to form white light was realized based on DCJTB:PMMA/ITO/NPB/TCTA/FIrpic:TCTA/TPBi/Ir(ppy)3:TPBi/TPBi/Cs2CO3/Al. The effects of red fluorescence on this white light device was studied by adjusting the concentration of DCJTB. The study shows that the device with a DCJTB concentration of 0.7% in the color conversion layer (CCL) generates a peak current efficiency and power efficiency of 23.4 cd ⋅ A[Formula: see text] and 7.5 lm ⋅ W[Formula: see text], respectively. And it is closest to the equal-energy white point of (0.33, 0.33) which shows a CIE (Commission Internationale de L’Eclairage) coordinate of (0.35, 0.43) and a color rendering index (CRI) of 70 at current density of 10 mA ⋅ cm[Formula: see text]. In order to improve the efficiency, we design and fabricate both high efficient and pure white organic light-emitting diode (WOLED) by replacing the single blue emission layer (EML) with double EMLs of FIrpic:TCTA and FIrpic:TPBi. The further study shows that, when the layers of EML is three and the concentration of DCJTB at 0.7%, the device exhibits good performance specifically, at current density of 10 mA ⋅ cm[Formula: see text], the current efficiency of 28.2 cd ⋅ A[Formula: see text] (power efficiency of 10.3 lm ⋅ W[Formula: see text]), and the CIE coordinate of (0.33, 0.31) (CRI of 80.38).
Genetic deletion of the alamandine receptor MRGD leads to dilated cardiomyopathy in mice
Authors: Oliveira Aline Cristina , Melo Marcos Barrouin , Motta-Santos Daisy , Peluso A. Augusto , Souza-Neto Fernando , da Silva Rafaela F. , Almeida Jonathas F. Q. , Canta Giovanni , Reis Adelina M. , Goncalves Gleisy , Cerri Gabriela , Coutinho Danielle , Guedes de Jesus Itamar Couto , Guatimosim Silvia , Linhares Natalia D. , Alenina Natalia , Bader Michael , Campagnole-Santos Maria José , Santos Robson A. Souza 
Published: October 2018

We have recently described a new peptide of the renin-angiotensin system, alamandine, a derivative of angiotensin-(1–7). Mas-related G protein-coupled receptor member D (MrgD) was identified as its receptor. Although similar cardioprotective effects of alamandine to those of angiotensin-(1–7) have been described, the significance of this peptide in heart function is still elusive. We aimed to evaluate the functional role of the alamandine receptor MrgD in the heart using MrgD-deficient mice. MrgD was localized in cardiomyocytes by immunofluorescence using confocal microscopy. High-resolution echocardiography was performed in wild-type and MrgD-deficient mice (2 and 12 wk old) under isoflurane anesthesia. Standard B-mode images were obtained in the right and left parasternal long and short axes for morphological and functional assessment and evaluation of cardiac deformation. Additional heart function evaluation was performed using Langendorff isolated heart preparations and inotropic measurements of isolated cardiomyocytes. Immunofluorescence indicated that the MrgD receptor is expressed in cardiomyocytes, mainly in the membrane and perinuclear and nuclear regions. Echocardiography showed left ventricular remodeling and severe dysfunction in MrgD-deficient mice. Strikingly, MrgD-deficient mice presented a pronounced dilated cardiomyopathy with a marked decrease in systolic function. Echocardiographic changes were supported by the data obtained in isolated hearts and inotropic measurements in cardiomyocytes. Our data add new evidence for a major role for alamandine/MrgD in the heart. Furthermore, our results indicate that we have identified a new gene implicated in dilated cardiomyopathy, unveiling a new target for translational approaches aimed to treat heart diseases. NEW & NOTEWORTHY The renin-angiotensin system is a key target for cardiovascular therapy. We have recently identified a new vasodepressor/cardioprotective angiotensin, alamandine. Here, we unmasked a key role for its receptor, Mas-related G protein-coupled receptor member D (MrgD), in heart function. The severe dilated cardiomyopathy observed in MrgD-deficient mice warrants clinical and preclinical studies to unveil its potential use in cardiovascular therapy. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/mrgd-deficiency-leads-to-dilated-cardiomyopathy/ .