DOCSLIB.ORG

Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2018-027770 on 9 June 2019. Downloaded from Effectiveness assessment of riluzole in the prevention of oxaliplatin-induced peripheral neuropathy: RILUZOX-01: protocol of a randomised, parallel, controlled, double-blind and multicentre study by the UNICANCER- AFSOS Supportive Care intergroup Nicolas Kerckhove,1,2,3 Jérome Busserolles,3 Trevor Stanbury,4 Bruno Pereira,5 Valérie Plence,4 Franck Bonnetain,6 Ivan Krakowski,7 Alain Eschalier,2,3 Denis Pezet,3,8 David Balayssac3,5 To cite: Kerckhove N, ABSTRACT Strengths and limitations of this study Busserolles J, Stanbury T, et al. Introduction Most patients (>70%) experience acute Effectiveness assessment of neuropathic symptoms shortly after oxaliplatin infusions. riluzole in the prevention of ► First clinical study to assess riluzole to prevent oxal- These symptoms are not always resolved between oxaliplatin-induced peripheral iplatin-induced peripheral neuropathy. infusions. Overall, 30%–50% of patients suffer from neuropathy: RILUZOX-01: ► Randomised, double-blind, controlled study. chronic oxaliplatin-induced peripheral neuropathy (OIPN). protocol of a randomised, ► Intention-to-treat analysis. parallel, controlled, double-blind This cumulative and dose-dependent sensory neuropathy ► Metastatic cancer population not considered. and multicentre study by the limits compliance or results in oxaliplatin-based ► Post-chemotherapy follow-up limited to 12 months. UNICANCER-AFSOS Supportive chemotherapies to be substituted with less neurotoxic Care intergroup. BMJ Open agents. These treatment changes impair clinical outcomes, http://bmjopen.bmj.com/ 2019;9:e027770. doi:10.1136/ and may be associated with comorbidities, such as bmjopen-2018-027770 Ethics and dessimination The study was approved distress, depression and anxiety. Currently, no drug used by a French ethics committee (ref:39/18_1, ‘Comité de ► Prepublication history and to prevent or treat OIPN is sufficiently effective to be used Protection des Personnes’ Ouest-IV, France) and plans additional material for this routinely in clinical practice. There is, thus, an unmet to start enroling patients in September 2019. The trial is paper are available online. To therapeutic need to reduce the intensity of and/or prevent registered in EudraCT and clinicaltrials. gov. view these files, please visit OIPN. We hypothesised that riluzole would be an excellent the journal online (http:// dx. doi. Trial registration number N°2017-002320-25; org/ 10. 1136/ bmjopen- 2018- candidate to address this public health issue. Riluzole NCT03722680 027770). is approved for treating amyotrophic lateral sclerosis. In on September 27, 2021 by guest. Protected copyright. animals, there is a beneficial effect on sensorimotor and Received 6 November 2018 pain disorders, as well as related comorbidities, after INTRODUCTION Revised 26 February 2019 repeated administration of oxaliplatin. In humans, riluzole In recent years, the therapeutic manage- Accepted 20 May 2019 has shown neuroprotective, anxiolytic and antidepressive ment of cancer has evolved with improved effects. patients’ survival. However, most anticancer Methods and analysis RILUZOX-01 trial was designed agents induce adverse effects which signifi- as a randomised, controlled, double-blind study to cantly impact the quality of life of patients evaluate the efficacy of riluzole to prevent OIPN. Patients © Author(s) (or their and in some cases, cause early discontinua- with colorectal cancer and initiating adjuvant oxaliplatin- employer(s)) 2019. Re-use tion of treatments that can compromise the based chemotherapy are eligible. Patients (n=210) permitted under CC BY-NC. No effective clinical outcome.1 2 Consequently, commercial re-use. See rights will be randomly assigned to either riluzole or placebo, and permissions. Published by concomitantly with chemotherapy. The primary endpoint cancer therapy is a delicate balance between BMJ. is the change in OIPN intensity, assessed by the sensory minimising adverse effects without compro- For numbered affiliations see scale of the QLQ-CIPN20, after six 2-week cycles of mising the anticancer efficacy. This objec- end of article. chemotherapy. Secondary endpoints include incidence tive is even more difficult when anticancer and severity of neuropathy, grade of sensory neuropathy, agents have neurotoxic effects responsible Correspondence to Dr Nicolas Kerckhove; intensity and features of neuropathic pain, health-related for disabling sensory and motor disorders. nkerckhove@ chu- quality of life, disease-free survival, overall survival and Chemotherapy-induced peripheral neurop- clermontferrand. fr safety. athy (CIPN), regarded as a potentially serious Kerckhove N, et al. BMJ Open 2019;9:e027770. doi:10.1136/bmjopen-2018-027770 1 Open access BMJ Open: first published as 10.1136/bmjopen-2018-027770 on 9 June 2019. Downloaded from adverse effects, is observed in >70% of patients treated excessive accumulation of glutamate, as previously with oxaliplatin.3 Most of the patients experience sensory observed in ischaemic animals.26–29 This effect preserves polyneuropathy including loss of sensitivity, paraesthesia, neuronal structures in the brain, spinal cord and retinal dysesthesia, burning sensations and acute pain induced or ischaemia.26 27 30 Other studies have demonstrated a neuro- exacerbated by the cold. These neuropathies are located protective role of riluzole in animal models of Parkinson's in the extremities and in the face and occur within hours disease,31 32 and post-traumatic neuropathic pain.33 We or days after oxaliplatin infusions (acute neuropathy). recently assessed and highlighted the benefit of riluzole These symptoms do not always resolve between treatment for sensorimotor and painful disorders, preventing oxal- cycles,4 and 30%–50% of patients suffer from chronic iplatin-induced peripheral nerve functional and morpho- oxaliplatin-induced peripheral neuropathy (OIPN).5 This logical alterations, as well as related oxaliplatin-induced 6 cumulative and dose-dependent sensory neuropathy comorbidities.34 leads to dose modifications, treatment delay and drug substitution with less neurotoxic agents. These treatment Riluzole and its interaction with the anticancer effect of 7 changes may reduce the effective clinical outcomes and oxaliplatin may be accompanied by comorbidities such as distress, 8 According to the recent recommendations of the Anal- depression and anxiety. In addition, the onset and gesic, Anaesthetic, and Addiction Clinical Trial Trans- chronic development of CIPN have important economic lations, Innovations, Opportunities, and Networks consequences. Health outcomes, healthcare (ie, medical (ACTTION),35 the study of new treatments related to and drug) and work loss costs incurred by patients with anticancer chemotherapy must consider their impact CIPN in four tumour types revealed that healthcare costs on disease progression and/or survival without relapse were $17 344 higher for patients with CIPN compared 9 (time after chemotherapy without cancer progression or with those without. Currently, none of the drugs used tumour recurrence). Several in vitro studies reported that for preventing or treating OIPN, except for duloxetine as 10 riluzole reduced the migration, invasion and prolifera- curative treatment, are sufficiently effective to be used tion of cells derived from melanoma,36 HT-29 (primary routinely in clinical practice.11” Therefore, when severe colon-derived) and T84 (lung metastasis-derived) human neuropathy occurs, dose reduction or discontinuation 34 cell lines. In vivo, we have shown in a spontaneous of chemotherapy are the main options to limit CIPN min/+ colorectal cancer (CRC) mouse model (APC mice) progression.12 13 that riluzole combined with oxaliplatin did not alter the At present, we have a better understanding of the mech- action of oxaliplatin: the rate of decrease in the number anism through which anticancer agents induce neuro- of tumours after treatment with oxaliplatin was identical toxicity.14–16 Oxaliplatin is known to damage the nuclei with or without riluzole.34 of DRG neurons, and induces channelopathy mainly on http://bmjopen.bmj.com/ voltage-gated sodium channels, but also on potassium channels of the K2P family (TREK, TRAAK).17 18 Notably, Rationale knock-out animals for TREK and TRAAK channels exhibit Based on robust preclinical data, the use of riluzole could an exaggerated cold sensitivity similar to that observed prevent and/or reduce the symptoms of OIPN, as well as in oxaliplatin-treated animals.19 In addition, oxaliplatin limit the incidence of related comorbidities. Moreover, 37 38 39 40 fails to induce cold hypersensitivity in knock-out mice riluzole has proven neuroprotective, anxiolytic 39 41 for TREK and TRAAK.17 We have also demonstrated that and antidepressive effects in several clinical studies. oxaliplatin modifies cold-specific fibres excitability by Thus, riluzole may be an excellent candidate to address on September 27, 2021 by guest. Protected copyright. decreasing their expression level, that is, inhibitor poten- this public health issue. tial of K2P channels,17 which in combination with TRPM8 No clinical studies have assessed the effect of riluzole defined the cold threshold.19 Cumulatively, these results on the symptoms of CIPN. However, patients with spinal suggested a key role of TREK and/or TRAAK channels cord injuries when treated with riluzole improved their in oxaliplatin-induced neuropathic
Load more

Recommended publications
  • The Role of Excitotoxicity in the Pathogenesis of Amyotrophic Lateral Sclerosis ⁎ L
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1762 (2006) 1068–1082 www.elsevier.com/locate/bbadis Review The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis ⁎ L. Van Den Bosch , P. Van Damme, E. Bogaert, W. Robberecht Neurobiology, Campus Gasthuisberg O&N2, PB1022, Herestraat 49, B-3000 Leuven, Belgium Received 21 February 2006; received in revised form 4 May 2006; accepted 10 May 2006 Available online 17 May 2006 Abstract Unfortunately and despite all efforts, amyotrophic lateral sclerosis (ALS) remains an incurable neurodegenerative disorder characterized by the progressive and selective death of motor neurons. The cause of this process is mostly unknown, but evidence is available that excitotoxicity plays an important role. In this review, we will give an overview of the arguments in favor of the involvement of excitotoxicity in ALS. The most important one is that the only drug proven to slow the disease process in humans, riluzole, has anti-excitotoxic properties. Moreover, consumption of excitotoxins can give rise to selective motor neuron death, indicating that motor neurons are extremely sensitive to excessive stimulation of glutamate receptors. We will summarize the intrinsic properties of motor neurons that could render these cells particularly sensitive to excitotoxicity. Most of these characteristics relate to the way motor neurons handle Ca2+, as they combine two exceptional characteristics: a low Ca2+-buffering capacity and a high number of Ca2+-permeable AMPA receptors. These properties most likely are essential to perform their normal function, but under pathological conditions they could become responsible for the selective death of motor neurons.
    [Show full text]
  • Repurposing Potential of Riluzole As an ITAF Inhibitor in Mtor Therapy Resistant Glioblastoma
    International Journal of Molecular Sciences Article Repurposing Potential of Riluzole as an ITAF Inhibitor in mTOR Therapy Resistant Glioblastoma Angelica Benavides-Serrato 1, Jacquelyn T. Saunders 1 , Brent Holmes 1, Robert N. Nishimura 1,2, Alan Lichtenstein 1,3,4 and Joseph Gera 1,3,4,5,* 1 Department of Research & Development, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA 91343, USA; [email protected] (A.B.-S.); [email protected] (J.T.S.); [email protected] (B.H.); [email protected] (R.N.N.); [email protected] (A.L.) 2 Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA 3 Jonnson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA 90095, USA 4 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA 5 Molecular Biology Institute, University of California-Los Angeles, Los Angeles, CA 90095, USA * Correspondence: [email protected]; Tel.: +00-1-818-895-9416 Received: 12 December 2019; Accepted: 31 December 2019; Published: 5 January 2020 Abstract: Internal ribosome entry site (IRES)-mediated protein synthesis has been demonstrated to play an important role in resistance to mechanistic target of rapamycin (mTOR) targeted therapies. Previously, we have demonstrated that the IRES trans-acting factor (ITAF), hnRNP A1 is required to promote IRES activity and small molecule inhibitors which bind specifically to this ITAF and curtail IRES activity, leading to mTOR inhibitor sensitivity. Here we report the identification of riluzole (Rilutek®), an FDA-approved drug for amyotrophic lateral sclerosis (ALS), via an in silico docking analysis of FDA-approved compounds, as an inhibitor of hnRNP A1.
    [Show full text]
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • An Advanced Drug Delivery System Targeting Brain Through BBB
    pharmaceutics Review Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB Mantosh Kumar Satapathy 1 , Ting-Lin Yen 1,2,† , Jing-Shiun Jan 1,†, Ruei-Dun Tang 1,3, Jia-Yi Wang 3,4,5 , Rajeev Taliyan 6 and Chih-Hao Yang 1,5,* 1 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan; [email protected] (M.K.S.); [email protected] (T.-L.Y.); [email protected] (J.-S.J.); [email protected] (R.-D.T.) 2 Department of Medical Research, Cathay General Hospital, Taipei 22174, Taiwan 3 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan; [email protected] 4 Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110, Taiwan 5 Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan 6 Department of Pharmacy, Neuropsychopharmacology Division, Birla Institute of Technology and Science, Pilani 333031, India; [email protected] * Correspondence: [email protected]; Tel.: +886-2-2736-1661 (ext. 3197) † These authors contributed equally to this work. Abstract: The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among Citation: Satapathy, M.K.; Yen, T.-L.; some of the limitations associated with current neurotherapeutics.
    [Show full text]
  • A Behavior-Based Drug Screening System Using A
    www.nature.com/scientificreports OPEN A behavior-based drug screening system using a Caenorhabditis elegans model of motor neuron Received: 22 August 2018 Accepted: 1 July 2019 disease Published: xx xx xxxx Kensuke Ikenaka1,6, Yuki Tsukada 2,3, Andrew C. Giles2,4, Tadamasa Arai5, Yasuhito Nakadera5, Shunji Nakano2,3, Kaori Kawai1, Hideki Mochizuki 6, Masahisa Katsuno 1, Gen Sobue 1,7 & Ikue Mori2,3 Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, for which there is no efective treatment. Previously, we generated a Caenorhabditis elegans model of ALS, in which the expression of dnc-1, the homologous gene of human dynactin-1, is knocked down (KD) specifcally in motor neurons. This dnc-1 KD model showed progressive motor defects together with axonal and neuronal degeneration, as observed in ALS patients. In the present study, we established a behavior-based, automated, and quantitative drug screening system using this dnc-1 KD model together with Multi-Worm Tracker (MWT), and tested whether 38 candidate neuroprotective compounds could improve the mobility of the dnc-1 KD animals. We found that 12 compounds, including riluzole, which is an approved medication for ALS patients, ameliorated the phenotype of the dnc-1 KD animals. Nifedipine, a calcium channel blocker, most robustly ameliorated the motor defcits as well as axonal degeneration of dnc-1 KD animals. Nifedipine also ameliorated the motor defects of other motor neuronal degeneration models of C. elegans, including dnc-1 mutants and human TAR DNA-binding protein of 43 kDa overexpressing worms. Our results indicate that dnc-1 KD in C.
    [Show full text]
  • Pharmacological Profile of Vascular Activity of Human Stem Villous Arteries
    Placenta 88 (2019) 12–19 Contents lists available at ScienceDirect Placenta journal homepage: www.elsevier.com/locate/placenta Pharmacological profile of vascular activity of human stem villous arteries T Katrin N. Sandera,c, Tayyba Y. Alia, Averil Y. Warrena, Daniel P. Haya, Fiona Broughton Pipkinb, ∗ David A. Barrettc, Raheela N. Khana, a Division of Medical Science and Graduate Entry Medicine, School of Medicine, University of Nottingham, The Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK b Division of Child Health, Obstetrics and Gynaecology, School of Medicine, City Hospital, Maternity Unit, Hucknall Road, Nottingham NG5 1PB, UK c Advanced Materials and Healthcare Technologies Division, Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK ARTICLE INFO ABSTRACT Keywords: Introduction: The function of the placental vasculature differs considerably from other systemic vascular beds of Pregnancy the human body. A detailed understanding of the normal placental vascular physiology is the foundation to Human understand perturbed conditions potentially leading to placental dysfunction. Placenta Methods: Behaviour of human stem villous arteries isolated from placentae at term pregnancy was assessed using Vascular function wire myography. Effects of a selection of known vasoconstrictors and vasodilators of the systemic vasculature Wire myography were assessed. The morphology of stem villous arteries was examined using IHC and TEM. Stem villous arteries ff Placental vessels Results: Contractile e ects in stem villous arteries were caused by U46619, 5-HT, angiotensin II and endothelin- 1(p≤ 0.05), whereas noradrenaline and AVP failed to result in a contraction. Dilating effects were seen for histamine, riluzole, nifedipine, papaverine, SNP and SQ29548 (p ≤ 0.05) but not for acetylcholine, bradykinin and substance P.
    [Show full text]
  • Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level
    International Journal of Molecular Sciences Review Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level Sweilem B. Al Rihani 1 , Lucy I. Darakjian 1, Malavika Deodhar 1 , Pamela Dow 1 , Jacques Turgeon 1,2 and Veronique Michaud 1,2,* 1 Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; [email protected] (S.B.A.R.); [email protected] (L.I.D.); [email protected] (M.D.); [email protected] (P.D.); [email protected] (J.T.) 2 Faculty of Pharmacy, Université de Montréal, Montreal, QC H3C 3J7, Canada * Correspondence: [email protected]; Tel.: +1-856-938-8697 Abstract: The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies.
    [Show full text]
  • NCT03679975 a Single Center Study to Evaluate the Effect of Riluzole
    NCT03679975 A Single Center Study to Evaluate the Effect of Riluzole Oral Soluble Film on Swallowing Safety in Individuals With Amyotrophic Lateral Sclerosis Protocol 18-Oct-2017 Protocol Number: 17MO1R-0012 Swallowing Safety in ALS Version No 2.0, October 18, 2017 Riluzole Oral Soluble Film A Single Center Study to Evaluate the Effect of Riluzole Oral Soluble Film on Swallowing Safety in Individuals With Amyotrophic Lateral Sclerosis Amendment 1 Summary of Changes from Version 1.0 (July 27, 2017) to Version 2.0 (October 18, 2017) Note: Major changes described in the following table have been made in this document to address the following issues: • Additional exclusion added to clarify the exclusion for the PAS score applies to any previous swallowing studies • Additional exclusion added for subjects with a history of two or more episodes of aspiration pneumonia requiring hospitalization • Modified hepatic function exclusion requirement for subjects currently on Riluzole • Modified hepatic function exclusion requirement for subjects receiving Riluzole for the first time • Added description of comprehensive and brief physical examinations and comprehensive neurological and brief neurological examinations Few minor changes involving wordsmithing for clarity and consistency, punctuation, and correction of typos have also been made but are not included in this table because they are not substantive changes. However, they are visible in the tracked-changes version of the protocol CONFIDENTIAL INFORMATION The information in this study protocol is confidential. Any disclosure, copying or distribution of the information contained within is strictly prohibited without written consent from MonoSol Rx LLC. Page 1 of 55 Protocol Number: 17MO1R-0012 Swallowing Safety in ALS Version No 2.0, October 18, 2017 Riluzole Oral Soluble Film Version No 1.0 July Amendment 1 (Version 2.0) Section 27, 2017 October 18, 2017 Rationale 3.
    [Show full text]
  • The Management of Motor Neurone Disease
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.74.suppl_4.iv32 on 1 December 2003. Downloaded from THE MANAGEMENT OF MOTOR NEURONE DISEASE P N Leigh, S Abrahams, A Al-Chalabi, M-A Ampong, iv32 L H Goldstein, J Johnson, R Lyall, J Moxham, N Mustfa, A Rio, C Shaw, E Willey, and the King’s MND Care and Research Team J Neurol Neurosurg Psychiatry 2003;74(Suppl IV):iv32–iv47 he management of motor neurone disease (MND) has evolved rapidly over the last two decades. Although still incurable, MND is not untreatable. From an attitude of nihilism, Ttreatments and interventions that prolong survival have been developed. These treatments do not, however, arrest progression or reverse weakness. They raise difficult practical and ethical questions about quality of life, choice, and end of life decisions. Coordinated multidisciplinary care is the cornerstone of management and evidence supporting this approach, and for symptomatic treatment, is growing.1–3 Hospital based, community rehabilitation teams and palliative care teams can work effectively together, shifting emphasis and changing roles as the needs of the individuals affected by MND evolve. In the UK, MND care centres and regional networks of multidisciplinary teams are being established. Similar networks of MND centres exist in many other European countries and in North America. Here, we review current practice in relation to diagnosis, genetic counselling, the relief of common symptoms, multidisciplinary care, the place of gastrostomy and assisted ventilation, the use of riluzole, and end of life issues. c TERMINOLOGY c Motor neurone disease (MND) is a synonym for amyotrophic lateral sclerosis (ALS).
    [Show full text]
  • Aspirin Use Associated with Amyotrophic Lateral Sclerosis: a Total Population-Based Case-Control Study
    J Epidemiol 2015;25(2):172-177 doi:10.2188/jea.JE20140070 Original Article Aspirin Use Associated With Amyotrophic Lateral Sclerosis: a Total Population-Based Case-Control Study Ching-Piao Tsai1, Feng-Cheng Lin2,3, Johnny Kuang-Wu Lee4, and Charles Tzu-Chi Lee5 1Neurology, Neurological Institute, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan 2Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 3Department of Neurology, Pingtung Hospital, Ministry of Health and Welfare, Taiwan 4General Education Center, University of Taipei, Taipei, Taiwan 5Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan Received April 3, 2014; accepted September 30, 2014; released online December 27, 2014 Copyright © 2014 Ching-Piao Tsai et al. This is an open access article distributed under the terms of Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: The association of aspirin use and nonsteroid anti-inflammatory drug (NSAID) use with amyotrophic lateral sclerosis (ALS) risk is unclear. This study determined whether use of any individual compound is associated with ALS risk by conducting a total population-based case-control study in Taiwan. Methods: A total of 729 patients with newly diagnosed ALS who had a severely disabling disease certificate between January 1, 2002, and December 1, 2008, comprised the case group. These cases were compared with 7290 sex-, age-, residence-, and insurance premium-matched controls. Drug use by each Anatomical Therapeutic Chemical code was analyzed using conditional logistic regression models. False discovery rate (FDR)-adjusted P values were reported in order to avoid inflating false positives.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Scientific Discussion
    SCIENTIFIC DISCUSSION This module reflects the initial scientific discussion for the approval of RILUTEK. This scientific discussion has been updated until 1 January 2004. For information on changes after this date please refer to module 8B. 1. Introduction Rilutek tablets contain riluzole, a new chemical entity of the benzothiazole class. Riluzole is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). The indication is based on data derived from two pivotal clinical trials in which it has been demonstrated that riluzole induces a modest extension of the life of patients with ALS regardless of the onset type. The claimed indication for this medicinal product is :“To extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis (ALS)". ALS is a progressive degenerative disorder of motor neurons and motor cortex. The symptoms of ALS are characterised by a progressive and irreversible decrease of muscle strength. The following definition of the pathology of ALS is found in the Oxford Textbook of Medicine: “a disease in which degeneration affects motor neurons in the anterior horns of the grey matter of the spinal cord, in certain somatic motor nuclei of the cranial nerves and in the cerebral cortex. There is no inflammatory reaction and microscopy provides no clue to the cause of the initially asymmetrical but progressive neuronal loss. As both upper and lower neurons are affected to varying degrees in different patients, the symptomatology is diverse.” The disease has an unremitting course of wasting and weakness and is usually fatal within three years. Although the pathogenesis of ALS is not completely elucidated and no validated models exist in which riluzole may be tested, it is suggested that glutamate (the primary excitatory neurotransmitter in the central nervous system) plays a role for cell death in the disease.
    [Show full text]