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Kathleen Mary Noon, Stephen Maxwell Montgomery, Nicholas Adlard, Michel Anton Kroes
OBJECTIVES: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modelling on cost-effectiveness of disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly-active [HA] RRMS), alemtuzumab (in HA RRMS), and natalizumab (in rapidly-evolving severe RRMS)...
June 20, 2018: Journal of Medical Economics
Jing Chen, Bruce V Taylor, Leigh Blizzard, Steve Simpson, Andrew J Palmer, Ingrid A F van der Mei
BACKGROUND: The direct comparative evidence on treatment effects of available multiple sclerosis (MS) disease-modifying therapies (DMTs) is limited, and few studies have examined the benefits of DMTs on employment outcomes. We compared the effects of DMTs used in the previous 5 years on improving the work attendance, amount of work and work productivity of people with MS. METHODS: The Australian MS Longitudinal Study collected data from participants on DMTs usage from 2010 to 2015 and whether DMTs contributed to changes in employment outcomes...
June 19, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
M A Piena, M Heisen, L W Wormhoudt, J van Wingerden, S T F M Frequin, B M J Uitdehaag
AIM: In active relapsing remitting multiple sclerosis (RRMS) patients requiring second-line treatment, the Dutch National Health Care Institute (ZiN) has not stated a preference for either alemtuzumab, fingolimod or natalizumab. Our aim was to give healthcare decision-makers insight into the differences in cost accumulation over time between alemtuzumab - with a unique, non-continuous treatment schedule - and fingolimod and natalizumab for second-line treatment of active RRMS patients in the Netherlands...
June 18, 2018: Journal of Medical Economics
K Pape, F Zipp, S Bittner
The spectrum of therapeutic options for immunotherapy of multiple sclerosis is continuously broadening. After the approval of cladribine and ocrelizumab in Europe, two new drugs are now available with ocrelizumab being the first approved option for treatment of primary progressive multiple sclerosis; however, the increased use of highly effective therapies is accompanied by a rise in severe side effects. During recent months, special attention was paid to the new progressive multifocal leukoencephalopathy (PML) risk assessment in natalizumab-treated patients, cardiac side effects of fingolimod, cases of idiopathic thrombocytopenic purpura and listeria meningitis associated with alemtuzumab and cases of daclizumab-treated patients with liver failure or encephalitis...
June 7, 2018: Der Nervenarzt
Luca Prosperini, Matteo Lucchini, Shalom Haggiag, Paolo Bellantonio, Assunta Bianco, Maria Chiara Buscarinu, Fabio Buttari, Diego Centonze, Antonio Cortese, Laura De Giglio, Roberta Fantozzi, Elisabetta Ferraro, Arianna Fornasiero, Ada Francia, Simonetta Galgani, Claudio Gasperini, Girolama Alessandra Marfia, Enrico Millefiorini, Viviana Nociti, Simona Pontecorvo, Carlo Pozzilli, Serena Ruggieri, Marco Salvetti, Eleonora Sgarlata, Massimiliano Mirabella
OBJECTIVE: To directly compare fingolimod (FNG) and dimethyl fumarate (DMF) on no evident disease activity (NEDA) status in patients with relapsing-remitting multiple sclerosis (RRMS) from 7 multiple sclerosis outpatient clinics in Central Italy. METHODS: We analyzed data of patients with RRMS who started an oral agent, namely DMF or FNG, either as first treatment (naives) or after switching from self-injectable drugs (switchers). We performed a propensity score (PS)-based nearest-neighbor matching within a caliper of 0...
June 6, 2018: Neurology
Claude Mékiès, Olivier Heinzlef, Béatrice Jenny, Anne-Laure Ramelli, Pierre Clavelou
Background: The development of oral treatments for relapsing-remitting multiple sclerosis (RRMS) may alter patient satisfaction and quality of life (QoL). The aim of this survey was to evaluate treatment satisfaction and QoL in patients treated with fingolimod in everyday clinical practice in France. Methods: Neurologists treating MS in France were invited to participate in the survey by telephone. Each physician was expected to recruit up to six patients with RRMS currently being treated with fingolimod...
2018: Patient Preference and Adherence
J Frau, M P Sormani, A Signori, S Realmuto, D Baroncini, P Annovazzi, E Signoriello, G Maniscalco, S La Gioia, C Cordioli, B Frigeni, S Rasia, G Fenu, R Grasso, A Sartori, R Lanzillo, M L Stromillo, S Rossi, B Forci, E Cocco
OBJECTIVE: There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself, or if it is due to the natural course of highly active multiple sclerosis (MS). We aimed to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. METHODS: Patients with relapsing-remitting MS (RRMS) who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis...
May 31, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Bruce A C Cree, Douglas L Arnold, Mark Cascione, Edward J Fox, Ian M Williams, Xiangyi Meng, Lesley Schofield, Nadia Tenenbaum
Objective: In relapsing-remitting multiple sclerosis (RRMS), suboptimal adherence to injectable disease-modifying therapies (iDMTs; interferon β-1a/b, glatiramer acetate) is common, reducing their effectiveness. Patient retention on oral fingolimod and iDMTs was evaluated in PREFER MS , a randomized, parallel-group, active-controlled, open-label, 48-week study. Methods: Patients were included if they had RRMS, were aged 18-65 years and had Expanded Disability Status Scale score up to 6, enrolled at 117 US study sites, were treatment naïve or had received only one iDMT class...
2018: Therapeutic Advances in Neurological Disorders
Nuria Suelves, Andrés Miguez, Saray López-Benito, Gerardo García-Díaz Barriga, Albert Giralt, Elena Alvarez-Periel, Juan Carlos Arévalo, Jordi Alberch, Silvia Ginés, Verónica Brito
Deficits in striatal brain-derived neurotrophic factor (BDNF) delivery and/or BDNF/tropomyosin receptor kinase B (TrkB) signaling may contribute to neurotrophic support reduction and selective early degeneration of striatal medium spiny neurons in Huntington's disease (HD). Furthermore, we and others have demonstrated that TrkB/p75NTR imbalance in vitro increases the vulnerability of striatal neurons to excitotoxic insults and induces corticostriatal synaptic alterations. We have now expanded these studies by analyzing the consequences of BDNF/TrkB/p75NTR imbalance in the onset of motor behavior and striatal neuropathology in HD mice...
May 27, 2018: Molecular Neurobiology
Brandi Vollmer, Justin M Honce, Stefan Sillau, John R Corboy, Timothy Vollmer, Kavita Nair, Enrique Alvarez
BACKGROUND: Due to the recurrence of disease activity in multiple sclerosis (MS) patients, a washout period of <3 months has been suggested for the transition from natalizumab (NTZ) to fingolimod (FTY). However, very short transition periods of <1 month may be more beneficial. METHODS: Retrospective analysis of patients from the Rocky Mountain MS Center at the University of Colorado who were: a) on NTZ for ≥6 months prior to switching to FTY; b) had a transition period ≤ 6 months; and c) initiated FTY treatment prior to November 2013...
July 15, 2018: Journal of the Neurological Sciences
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
Sebastian Luger, Annette Schwebler, Rajkumar Vutukuri, Nerea Ferreiros Bouzas, Sandra Labocha, Yannick Schreiber, Robert Brunkhorst, Helmuth Steinmetz, Josef Pfeilschifter, Waltraud Pfeilschifter
Background: Sphingolipids are versatile signaling molecules derived from membrane lipids of eukaryotic cells. Ceramides regulate cellular processes such as proliferation, differentiation and apoptosis and are involved in cellular stress responses. Experimental evidence suggests a pivotal role of sphingolipids in the pathogenesis of cardiovascular diseases, including ischemic stroke. A neuroprotective effect has been shown for beta-adrenergic antagonists in rodent stroke models and supported by observational clinical data...
2018: Therapeutic Advances in Neurological Disorders
Laura Weinstock, Amanda M Furness, Shawn Herron, Sierra S Smith, Sitara Sankar, Samantha G DeRosa, Dadi Gao, Molly E Mepyans, Anna Scotto Rosato, Diego L Medina, Ayelet Vardi, Natalia S Ferreira, Soo Min Cho, Anthony H Futerman, Susan A Slaugenhaupt, Levi B Wood, Yulia Grishchuk
Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision. Currently there is no therapy for MLIV. It is caused by loss of function of the lysosomal channel mucolipin-1, also known as TRPML1. Knockout of the Mcoln1 gene in a mouse model mirrors clinical and neuropathological signs in humans. Using this model, we previously observed robust activation of microglia and astrocytes in early symptomatic stages of disease. Here we investigate the consequence of mucolipin-1 loss on astrocyte inflammatory activation in vivo and in vitro and apply a pharmacological approach to restore Mcoln1-/- astrocyte homeostasis using a clinically approved immunomodulator, fingolimod...
May 16, 2018: Human Molecular Genetics
S Viswanathan
No abstract text is available yet for this article.
May 12, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Dirk Deleu, Boulenouar Mesraoua, Beatriz Canibaño, Gayane Melikyan, Hassan Al Hail, Lubna El-Sheikh, Musab Ali, Hassan Al Hussein, Faiza Ibrahim, Yolande Hanssens
The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) have considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs, promote patient satisfaction and increase therapeutic adherence. This article reviews the salient features about the mode of action, efficacy, safety and tolerability profile of approved oral DMTs in RRMS and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region...
May 15, 2018: Current Medical Research and Opinion
Sajad Karampoor, Hamid Zahednasab, Masoud Etemadifar, Hossein Keyvani
Multiple Sclerosis (MS) is a neuroinflammatory disease of the central nervous system (CNS) in which immune system plays a crucial role in progression of the disease. An enormous amount of research has been shown that immune mediators such as cytokines and chemokines are the culprits of MS propagation suggesting that modulation of such molecules may pave the path to hinder the disease development. It has been shown that both CD21 and CD83 contribute to the resolution of inflammation occurred in MS. CD21 and CD83 have also been ascribed to Epstein Barr virus (EBV) infection (the prime suspect of MS causality) and the levels of vitamin D, respectively...
July 15, 2018: Journal of Neuroimmunology
L Ferre', F Clarelli, G Sferruzza, M A Rocca, E Mascia, M Radaelli, F Sangalli, G Dalla Costa, L Moiola, M Aboulwafa, F Martinelli Boneschi, G Comi, M Filippi, V Martinelli, F Esposito
BACKGROUND: Several studies have shown an association between 25-hydroxyvitamin D (25[OH]D) levels and multiple sclerosis (MS) susceptibility and/or level of disease activity in patients treated with first line drugs. AIMS: To investigate whether baseline 25[OH]D values could influence disease activity also during treatment with the second-line drug fingolimod (FTY). PATIENTS AND METHODS: We enrolled 176 MS patients who started FTY at the San Raffaele Hospital (OSR) MS center with available 25[OH]D measurement at the time of treatment start...
May 13, 2018: Neurological Sciences
Robert Zivadinov, Jennie Medin, Nasreen Khan, Jonathan R Korn, Niels Bergsland, Michael G Dwyer, Tanuja Chitnis, Robert T Naismith, Enrique Alvarez, Peter Kinkel, Stanley Cohan, Samuel F Hunter, Diego Silva, Bianca Weinstock-Guttman
BACKGROUND AND PURPOSE: Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of active disease (NEAD). METHODS: MS and clinical outcome and MRI in the United States (MS-MRIUS) is a multicenter, retrospective study that included 590 relapsing-remitting MS patients, who initiated fingolimod, and were followed for a median of 16 months...
May 11, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
M Kraft, U K Zettl, T Noack, R Patejdl
BACKGROUND: Sphingosine and its metabolite sphingosine phosphate (S1P) regulate a multitude of biological functions, including the contractile state of smooth. Gastrointestinal side effects have been reported in patients treated with FTY720, a sphingosine analog that is approved for the treatment of multiple sclerosis. The aim of this study was to characterize the effects of FTY720 on rat gastric fundus smooth muscle under basal conditions and during activation induced by high-K+ solution...
May 8, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Maria Donata Benedetti, Antonio Marangi, Silvia Bozzetti, Francesca Gobbin, Marco Turatti, Maurizio Pea, Alberto Gajofatto, Stelio Mocella
Fingolimod is a commonly used treatment for highly active relapsing-remitting multiple sclerosis (MS). We describe the case of a 50-year old man on fingolimod since 2011 who presented, in April 2017, with a voluminous swelling of the left tonsil. A left tonsillectomy was performed, and histological exam disclosed a papillary squamous cell carcinoma of the palatine tonsil, with an in situ hybridization positive for human papillomavirus (HPV)-16 DNA. Neither lymph nodes involvement nor other metastases were detected...
May 2, 2018: Multiple Sclerosis and related Disorders
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