DOCSLIB.ORG

The Effects of Anticonvulsants on Neurological Recovery After Spinal Cord Injury

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effects of Anticonvulsants on Neurological Recovery After Spinal Cord Injury THE EFFECTS OF ANTICONVULSANTS ON NEUROLOGICAL RECOVERY AFTER SPINAL CORD INJURY by Freda Warner B.Sc., University of Guelph, 2011 M.P.H., Simon Fraser University, 2015 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate and Postdoctoral Studies (Kinesiology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) September 2019 © Freda Warner, 2019 The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: The effects of anticonvulsants on neurological recovery after spinal cord injury Submitted by Freda Warner in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Kinesiology Examining Committee: John Kramer, Kinesiology Supervisor Tania Lam, Kinesiology Supervisory Committee Member Supervisory Committee Member Roanne Preston, Anesthesiology, Pharmacology and Therapeutics University Examiner Thomas Oxland, Mechanical Engineering University Examiner Additional Supervisory Committee Members: Supervisory Committee Member Supervisory Committee Member ii Abstract Spinal cord injury is a devastating neurological condition that results in varying degrees of sensory and motor loss, along with other health complications. Neurological recovery after spinal cord injury is generally thought to be limited to the 6-9 month period after injury, and there are currently no approved pharmacological interventions to improve this recovery. Overlapping with a proposed “window of opportunity” for interventions, neuropathic pain can occur early after injury and necessitate pharmacological management. Among the management options, anticonvulsants are routinely administered. Utilizing longitudinal observational human spinal cord injury data, this thesis explored the effects of anticonvulsants on neurological recovery after spinal cord injury using mixed effects regression, and conduct a meta-analysis on the acute progression of neuropathic pain. The research studies within this thesis are bookended by an introduction and methodology section (Chapters 1 and 2) and the discussion (Chapter 7). In Chapter 3, I examined the effect of anticonvulsants and found a beneficial association with motor recovery contingent on administration at 4 weeks. A review of patient records revealed that the majority of anticonvulsants being administered were gabapentinoids (i.e. pregabalin and gabapentin). To further examine whether this effect was specific to gabapentinoids or obtained by all anticonvulsants, Chapter 4 examined a unique spinal cord injured population administered non-gabapentinoid anticonvulsants and found no statistically significant associations with neurological recovery. Chapter 5 included a chart review to examine the effect of gabapentinoid-specific administration, and found a continued beneficial association with motor score, as well as the sensory outcome of light touch. Further, this chapter identified that very early administration (e.g. within 5 days) was necessary to achieve the largest benefit. Finally, Chapter 6 produced a longitudinal framework of neuropathic pain progression in clinical trials. In short, this thesis presents novel findings regarding the administration of anticonvulsants after spinal cord injury, and the beneficial association of gabapentinoid- specific anticonvulsants on motor recovery. Further, it provides an advance in our iii understanding of neuropathic pain progression after injury and a framework to guide future clinical trials. iv Lay summary Spinal cord injuries can result in a loss of sensation and movement. After injury there is usually an initial period of neurological recovery (i.e. recovery of movement and sensation), after which these impairments are permanent. There are currently no approved drugs that can help maximize this neurological recovery after injury. Anticonvulsants, including gabapentinoids, are drugs that are commonly administered after spinal cord injury for complications including neuropathic pain and seizures. Using human spinal cord injury cohort and registry data, I examined the effects of anticonvulsants on neurological recovery after spinal cord injury. Through secondary data analysis I identified that the early administration of gabapentinoid-specific anticonvulsants (and not anticonvulsants in general) was associated with an improvement in recovery. I also describe the progression of neuropathic pain after injury, with the goal of informing future clinical trials. v Preface A version of Chapter 1 is a published book chapter [Warner FM, Cragg J, Steeves JC, Kramer JLK. “Clinical trials and spinal cord injury: Challenges and therapeutic interventions.” In Neurological Aspects of Spinal Cord Injury. Springer, 2017]. I was the lead investigator, responsible for concept formation and all major manuscript composition. Cragg J, Steeves JC, and Kramer JLK were also responsible for concept formation and manuscript edits. Kramer JLK was the supervisory author on this project. A version of Chapter 3 has been published in Cell Reports [Warner FM, Cragg JJ, Jutzeler CR, Röhrich F, Weidner N, Saur M, Maier DD, Schuld C, EMSCI Study Group, Curt A, Kramer JK. Early administration of gabapentinoids improves motor recovery after human spinal cord injury. Cell Reports 2017; 18:1614-1618]. Cragg JJ, Jutzeler CR, Röhrich F, Weidner N, Saur M, Maier DD, Schuld C, and Curt A contributed to concept formation and manuscript edits. EMSCI Study Group was responsible for data collection. Kramer JK was the supervisory author on this project and was involved in concept formation and manuscript edits. I was involved in concept formation and responsible for all analytical methods, data analysis, and manuscript composition. A version of Chapter 4 has been published in CNS Drugs [Warner FM, Jutzeler CR, Cragg JJ, Tong B, Grassner L, Bradke F, Geisler F, Kramer JK. The effect of non- gabapentinoid anitconvulsants on sensorimotor recovery after spinal cord injury. CNS Drugs 2019; 33(5):503-511]. Jutzeler CR and Cragg JJ contributed to concept formation and manuscript edits. Geisler F was responsible for the data collection and manuscript edits. Tong B, Grassner L, and Bradke F were responsible for content and manuscript edits. Kramer JK was the supervisory author on this project and was involved in concept formation and manuscript edits. I was involved in concept formation and responsible for all analytical methods, data analysis, and manuscript composition. In Chapter 5, Cragg JJ, Jutzeler CR, Maier D, and Curt A contributed to concept formation and chapter edits. Grassner L, Mach O, Curt A and the EMSCI Study Group were responsible for data collection and chapter edits. Kramer JK was the supervisory author on this project and was involved in concept formation and chapter edits. I was involved in concept formation and responsible for all analytical methods, data analysis, and chapter composition. A version of Chapter 6 has been published in the Journal of Neurotrauma [Warner FM, Cragg JJ, Jutzeler CR, Finnerup NB, Weargen L, Weidner N, Maier D, Kalke Y-B, Curt A, Kramer JK. Progression of neuropathic pain after acute spinal cord injury: a meta- analysis and framework for clinical trials. Journal of Neurotrauma 2019; 1-8]. Jutzeler CR, and Cragg JJ contributed to concept formation and manuscript edits. Finnerup NB, Weargen L, Weidner N, Maier D, Kalke Y-B, Curt A and the EMSCI sites were responsible for data collection and manuscript edits. Kramer JK was the supervisory author on this project and was involved in concept formation and manuscript edits. I was involved in concept formation and responsible for all analytical methods, data analysis, and manuscript composition. Ethics approvals for the studies contained in this thesis were obtained by the University of British Columbia’s Research Ethics board (certificates #H16-01119 and H16-03143). vi Table of contents Abstract ................................................................................................................ iii Lay summary ........................................................................................................ v Preface ................................................................................................................ vi Table of contents ................................................................................................ vii List of tables .......................................................................................................... x List of figures....................................................................................................... xii List of abbreviations ............................................................................................ xiii Acknowledgements ............................................................................................ xiv Chapter 1 Introduction .......................................................................................... 1 1.1 Overview: the search for acute interventions to improve neurological outcomes for individuals with spinal cord injuries .............................................. 1 1.2 Challenges of spinal cord injury trials .......................................................... 1 1.2.1 A “moving target”: effect of the natural progression of spinal cord injury ....................................................................................................................... 2 1.2.2 Low numbers
Load more

Recommended publications
  • Dissertationes Medicinae Universitatis Tartuensis 106 Dissertationes Medicinae Universitatis Tartuensis 106
    DISSERTATIONES MEDICINAE UNIVERSITATIS TARTUENSIS 106 DISSERTATIONES MEDICINAE UNIVERSITATIS TARTUENSIS 106 EPIDEMIOLOGY OF ADULT EPILEPSY IN TARTU, ESTONIA Incidence, prevalence and medical treatment ANDRE ÕUN TARTU UNIVERSITY PRESS Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia Dissertation is accepted for the commencement of the degree of Doctor of Medical Sciences on March 22, 2005 by the Council of the Faculty of Medicine, University of Tartu, Estonia Opponent: Dr. Tapani Keränen, University of Tampere, Finland Commencement: May 4, 2005 Publication of this dissertation is granted by the Faculty of Medicine, University of Tartu ISSN 1024–395X ISBN 9949–11–034–3 (trükis) ISBN 9949–11–035–1 (PDF)) Autoriõigus Andre Õun, 2005 Tartu Ülikooli Kirjastus www.tyk.ee Tellimus nr. 142 CONTENTS LIST OF ORIGINAL PUBLICATIONS......................................................... 8 ABBREVIATIONS......................................................................................... 9 I. INTRODUCTION ...................................................................................... 10 II. REVIEW OF THE LITERATURE ............................................................ 12 1. General aspects and methodology ......................................................... 12 1.1. Diagnostic accuracy ....................................................................... 12 1.2. Criteria, clinical characteristics and classifications........................ 13 1.2.1. Criteria for the activeness of epilepsy ................................
    [Show full text]
  • Excipient: 0.4 Mg Lactose Monohydrate/Film-Coated Tablet
    1. NAME OF THE MEDICINAL PRODUCT [[Topiramate]25 mg film-coated tablets [Topiramate] 50 mg film-coated tablets [Topiramate] 100 mg film-coated tablets [Topiramate] 200 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 25 mg film-coated tablets Each film-coated tablet contains 25 mg of topiramate. Excipient: 0.4 mg lactose monohydrate/film-coated tablet. 50 mg film-coated tablets Each film-coated tablet contains 50 mg of topiramate. Excipient: 0.4 mg lactose monohydrate/film-coated tablet. 100 mg film-coated tablets Each film-coated tablet contains 100 mg of topiramate. Excipient: 0,05 mg sunset yellow (E110)/film-coated tablet. 200 mg film-coated tablets Each film-coated tablet contains 200 mg of topiramate. Excipient: 3.2 mg lactose monohydrate/film-coated tablet. For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. [Topiramate] 25 mg are available as white, round, biconvex film-coated tablets. [Topiramate] 50 mg are available as yellow, round, biconvex film-coated tablets. [Topiramate] 100 mg are available as orange, oblong, biconvex film-coated tablets. [Topiramate] 200 mg are available as pink, oblong, biconvex film-coated tablets. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Monotherapy in adults, adolescents and children over 6 years of age with partial seizures with or without secondary generalised seizures and primary generalised tonic-clonic seizures. Adjunctive therapy in children aged 2 years and above, adolescents and adults with partial onset seizures with or without secondary generalization or primary generaliszed tonic-clonic seizures and for the treatment of seizures associated with Lennox-Gastaut syndrome.
    [Show full text]
  • Classification and Analysis of a Large Collection of in Vivo Bioassay Descriptions
    RESEARCH ARTICLE Classification and analysis of a large collection of in vivo bioassay descriptions Magdalena Zwierzyna1,2, John P. Overington1,2¤* 1 BenevolentAI, London, United Kingdom, 2 Institute of Cardiovascular Science, University College London, London, United Kingdom ¤ Current address: Medicines Discovery Catapult, Mereside, Alderley Park, Alderley Edge, Cheshire, United Kingdom * [email protected] a1111111111 a1111111111 a1111111111 a1111111111 Abstract a1111111111 Testing potential drug treatments in animal disease models is a decisive step of all preclini- cal drug discovery programs. Yet, despite the importance of such experiments for transla- tional medicine, there have been relatively few efforts to comprehensively and consistently analyze the data produced by in vivo bioassays. This is partly due to their complexity and OPEN ACCESS lack of accepted reporting standardsÐpublicly available animal screening data are only Citation: Zwierzyna M, Overington JP (2017) accessible in unstructured free-text format, which hinders computational analysis. In this Classification and analysis of a large collection of in study, we use text mining to extract information from the descriptions of over 100,000 drug vivo bioassay descriptions. PLoS Comput Biol 13(7): e1005641. https://doi.org/10.1371/journal. screening-related assays in rats and mice. We retrieve our dataset from ChEMBLÐan pcbi.1005641 open-source literature-based database focused on preclinical drug discovery. We show that Editor: Nir London, Weizmann Institute of Science, in vivo assay descriptions can be effectively mined for relevant information, including experi- ISRAEL mental factors that might influence the outcome and reproducibility of animal research: Received: February 27, 2017 genetic strains, experimental treatments, and phenotypic readouts used in the experiments.
    [Show full text]
  • Original Article No Signal of Interactions Between Influenza Vaccines and Drugs Used for Chronic Diseases
    Original Article No signal of interactions between influenza vaccines and drugs used for chronic diseases: a case-by-case analysis of the vaccine adverse event reporting system and vigibase Carla Carnovale1*, Emanuel Raschi2*, Luca Leonardi2, Ugo Moretti3, Fabrizio De Ponti2, Marta Gentili1, Marco Pozzi4, Emilio Clementi4,5, Elisabetta Poluzzi2§ and Sonia Radice1§ 1 Unit of Clinical Pharmacology Department of Biomedical and Clinical Sciences L. Sacco, “Luigi Sacco” University Hospital, Università di Milano, 20157 Milan, Italy. 2 Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, BO, Italy. 3 Dept. of Diagnostics and Public Health, Section of Pharmacology, University of Verona, Verona, Italy. 4 Scientific Institute, IRCCS E. Medea, Bosisio Parini LC, Italy. 5 Clinical Pharmacology Unit, Department Biomedical and Clinical Sciences, CNR Institute of Neuroscience, L. Sacco University Hospital, Università di Milano, Milan, Italy. *Carla Carnovale and Emanuel Raschi contributed equally to this work §Sonia Radice and Elisabetta Poluzzi jointly directed this work. *Corresponding author: Emilio Clementi, Department of Biomedical and Clinical Sciences, Università di Milano Via GB Grassi, 74 - 20157 Milan, Tel: +39.02.50319643. Fax: +39.02.50319682 e-mail: [email protected] 1 ABSTRACT Background: An increasing number of reports indicates that vaccines against influenza may interact with specific drugs via drug metabolism. To date, actual impact of vaccine-drug interactions observed in the real world clinical practice has not been investigated. Research design and methods: From VAERS and VigiBase, we collected Adverse Event Following Immunization (AEFI) reports for individuals receiving vaccines against influenza recorded as suspect and selected cases where predictable toxicity was recorded with oral anticoagulants, antiepileptics and statins (i.e., hemorrhages, overdosage and rhabdomyolysis, respectively).
    [Show full text]
  • SUMMARY of PRODUCT CHARACTERISTICS This
    SUMMARY OF PRODUCT CHARACTERISTICS ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Valproato Semisódico Tecnifar 250 mg gastro-resistant tablets Valproato Semisódico Tecnifar 500 mg gastro-resistant tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Active substance: valproate semisodium Each gastro-resistant tablet of Valproato Semisódico Tecnifar 250 mg contains 269,.1 mg of valproate semisodium, equivalent to 250 mg of valproic acid. Excipient(s) with known effect: Sunset yellow (E110) – 0,.2 mg Each gastro-resistant tablet of Valproato Semisódico Tecnifar 500 mg contains 538,.2 mg of valproate semisodium, equivalent to 500 mg of valproic acid. Excipient(s) with known effect: Carmoisine (E122) – 0.104 mg Ponceau 4R (E124) - 0.091 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Gastro-resistant tablets. Valproato Semisódico Tecnifar 250 mg gastro-resistant tablets: Peach oblong tablet without inscriptions (approximated dimensions: length 14.5 mm, width 8 mm and thickness 5.5 mm). Valproato Semisódico Tecnifar 500 mg gastro-resistant tablets: Pink oblong tablets without inscriptions (approximated dimensions: length 19 mm, width 10 mm and thickness 6.3 mm). 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Treatment of manic episode in bipolar disorder when lithium is contraindicated or not tolerated. The continuation of treatment after manic episode could be considered in patients who have responded to valproate semisodium for acute mania., particularly in: Prophylactic treatment of the following types of headaches: M igraine, Chronic Daily Headache (Transformed Migraine and Persistent Migraine and Resistant Migraine) and Cluster Headache.
    [Show full text]
  • Univerza V Ljubljani Fakulteta Za Farmacijo
    UNIVERZA V LJUBLJANI FAKULTETA ZA FARMACIJO MOJCA ULE MAGISTRSKA NALOGA ENOVITI MAGISTRSKI ŠTUDIJ FARMACIJA Ljubljana, 2017 UNIVERZA V LJUBLJANI FAKULTETA ZA FARMACIJO MOJCA ULE ANALIZA IZBIRE SOLI ZDRAVILNIH UČINKOVIN V ZDRAVILIH, REGISTRIRANIH V ZDA MED LETI 2007 IN 2015 ANALYSIS OF ACTIVE PHARMACEUTICAL INGREDIENT SALT SELECTION IN DRUG PRODUCTS REGISTERED IN USA BETWEEN THE YEARS 2007 AND 2015 ENOVITI MAGISTRSKI ŠTUDIJ FARMACIJA Ljubljana, 2017 Magistrsko nalogo sem opravljala pod mentorstvom izr. prof. dr. Zdenka Časarja. Podatke za izvedbo analize sem pridobila iz javno dostopnih spletnih virov. Zahvala Mentorju izr. prof. dr. Zdenku Časarju se iskreno zahvaljujem za strokovno pomoč in vzpodbudo med pisanjem magistrske naloge. Posebna zahvala gre mojim staršem, ki so mi omogočili pot do univerzitetne izobrazbe ter me podpirali. Izjava Izjavljam, da sem magistrsko nalogo samostojno izdelala pod mentorstvom izr. prof. dr. Zdenka Časarja. Mojca Ule Ljubljana, 2017 I VSEBINA Kazalo vsebin 1 UVOD ................................................................................................................................. 1 1.1 KLASIFIKACIJA FARMACEVTSKIH TRDNIH SNOVI ......................... 1 1.2 POLIMORFNE OBLIKE ................................................................................. 2 1.3 SOLVATI ........................................................................................................... 4 1.4 KOKRISTALI ..................................................................................................
    [Show full text]
  • Evaluation of Carcinogenicity Studies of Medicinal Products for Human Use Authorised Via the European Centralised Procedure
    Regulatory Toxicology and Pharmacology xxx (2011) xxx–xxx Contents lists available at ScienceDirect Regulatory Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/yrtph Evaluation of carcinogenicity studies of medicinal products for human use authorised via the European centralised procedure (1995–2009) ⇑ Anita Friedrich a, , Klaus Olejniczak b a Granzer Regulatory Consulting and Services, Zielstattstrasse 44, 81379 Munich, Germany b Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany article info abstract Article history: Carcinogenicity data of medicinal products for human use that have been authorised via the European Received 25 October 2010 centralised procedure (CP) between 1995 and 2009 were evaluated. Carcinogenicity data, either from Available online xxxx long-term rodent carcinogenicity studies, transgenic mouse studies or repeat-dose toxicity studies were available for 144 active substances contained in 159 medicinal products. Out of these compounds, 94 Keywords: (65%) were positive in at least one long-term carcinogenicity study or in repeat-dose toxicity studies. Medicinal products Fifty compounds (35%) showed no evidence of a carcinogenic potential. Out of the 94 compounds with Carcinogenicity positive findings in either carcinogenicity or repeat-dose toxicity studies, 33 were positive in both mice Rodents and rats, 40 were positive in rats only, and 21 were positive exclusively in mice. Long-term carcinogenic- ity studies in two rodent species were available for 116 compounds. Data from one long-term carcinoge- nicity study in rats and a transgenic mouse model were available for eight compounds. For 13 compounds, carcinogenicity data were generated in only one rodent species. One compound was exclu- sively tested in a transgenic mouse model.
    [Show full text]
  • Antiepileptika (ATC-Code: N03 *)
    Wirkstoffziele Stand: 19. August 2021 iStockphoto.com/Krasyuk Eine Information der Kassenärztlichen Vereinigung Bayerns ° [email protected] ° www.kvb.de/ verordnungen Wirkstoffgruppe: Antiepileptika (ATC-Code: N03 *) Ziel 4: Generika möglichst mit Rabattvertrag verordnen! Erläuterung / Maßnahmen zur Umsetzung Die möglichst rabattierten, generischen Wirkstoffe sollten unter Abwägung der patientenindi- viduellen Erfordernisse und Risiken bevorzugt eingesetzt werden, um das Wirtschaftlichkeits- ziel zu erreichen. Die Behandlung der Epilepsie ist zum Teil stark limitiert, da einige Wirkstoffe eine enge the- rapeutische Breite besitzen und daher nicht oder nur unter engen Voraussetzungen ausge- tauscht werden sollten. Die Ersteinstellung auf ein Generikum eines pharmazeutischen Un- ternehmers ist problemlos möglich, die spätere Umstellung auf einen anderen Hersteller un- ter Umständen nicht.1 Bei folgenden Wirkstoffen ist zu beachten, dass aufgrund der Substitutionsausschlussliste kein Austausch in Generika bzw. Rabattverträge durch den Apotheker mehr erfolgt, unab- hängig davon, ob ein aut-idem-Ausschluss gesetzt wurde: Carbamazepin (retardiert), Pheno- barbital, Phenytoin, Primidon, Valproinsäure (retardiert). Die Verordnung muss hier eindeu- tig, das heißt unter namentlicher Angabe eines Fertigarzneimittels, erfolgen. Die britische Commission on Human Medicines empfiehlt darüber hinaus, dass bei folgenden Wirkstoffen ein aut-idem Austausch erwogen werden könnte: Clonazepam, Lamotrigin, Oxcarbazepin, Topiramat und Zonisamid. Die
    [Show full text]
  • Tegretol Data Sheet
    NEW ZEALAND DATA SHEET 1. PRODUCT NAME TEGRETOL® 200 mg Tablets TEGRETOL® 400 mg Tablets TEGRETOL® 200 mg CR Tablets TEGRETOL® 400 mg CR Tablets TEGRETOL®100 mg / 5 mL Syrup 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Active substance Tablets • 200 mg: Each tablet contains 200 mg carbamazepine • 400 mg: Each tablet contains 400 mg carbamazepine CR tablets • 200 mg: Each modified-release film-coated, divisible tablet contains 200 mg carbamazepine • 400 mg: Each modified-release film-coated, divisible tablet contains 400 mg carbamazepine Syrup • 5 mL: Each 5 mL of syrup contains 100 mg carbamazepine For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM • Tablet containing 200mg carbamazepine. Round, white, flat tablet, 9mm in diameter, with bevelled edges. Imprinted CG on one side, and G/K on the scored side. • Tablet containing 400mg carbamazepine. White, flat, rod-shaped tablet with bevelled edges. 17mm in length and 5.5mm in width. Imprinted CG/CG on one side and LR/LR on the second side; both sides of the tablet are scored. • Controlled Release Tablet containing 200mg carbamazepine. Beige-orange, ovaloid- shaped, film-coated divisible tablet with slightly convex faces. Approximate length is 12.2mm, and approximate width is 5.6mm. Both sides are scored; one side is imprinted C/G, and the other side H/C. • Controlled Release Tablet containing 400mg carbamazepine. Brown-orange, ovaloid- shaped, film-coated divisible tablet, with slightly convex faces. Approximately 16.7mm in length, and approximately 6.6mm in width. Imprinted CG/CG on one side, and ENE/ENE on the other side; both sides are scored.
    [Show full text]
  • Routinedatenbasierte Untersuchungen Zum Off-Label-Use in Der Ambulanten Versorgung
    Routinedatenbasierte Untersuchungen zum Off-Label-Use in der ambulanten Versorgung Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften - Dr. rer. nat.- Universität Bremen Fachbereich Human- und Gesundheitswissenschaften vorgelegt von Michael Dörks Bremen, im Juni 2013 Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS GmbH Danksagung Diese Dissertation sowie die hiermit in Verbindung stehenden Publikationen wären ohne die Anregungen und Unterstützung meiner Familie, meiner Freunde und vieler Kolleginnen und Kollegen nicht möglich gewesen. Ihnen möchte ich an dieser Stelle danken. Mein besonderer Dank gilt Frau Prof. Dr. Edeltraut Garbe, die diese Arbeit in vielerlei Hinsicht erst ermöglichte. Großer Dank gilt weiterhin Herrn Prof. Dr. Hajo Zeeb und Herrn PD Dr. Falk Hoffmann für die Bereitschaft zur Erstellung der Gutachten. Erstgutachter: Prof. Dr. med. Hajo Zeeb, M.Sc. Zweitgutachter: PD Dr. P.H. Falk Hoffmann, MPH Datum der Disputation: 01.11.2013 Inhaltsverzeichnis 1 Einleitung 2 2 Off-Label-Use 5 2.1 Definition von Off-Label-Use .................. 5 2.2 Bedeutung des Off-Label-Use im Spannungsfeld von Leistungs- erbringung, Gesetzeslage und medizinischem Fortschritt ................. 7 2.3 Off-Label-Use in der Pädiatrie ................. 9 2.4 Off-Label-Use in der Onkologie ................ 11 3 Die German Pharmacoepidemiological Research Database (Ge- PaRD) und ihre Nutzung zur Untersuchung des Off-Label-Use 13 3.1 Beschreibung von GePaRD ................... 14 3.2 Nutzung von Sozialdaten für die Forschung .......... 18 3.3 Untersuchung des Off-Label-Use ................ 19 4 Beispiele eigener Studien zur routinedatenbasierten Untersuchung des Off-Label-Use in der ambulanten Versorgung 21 4.1 Treatment of paediatric epilepsy in Germany: antiepileptic drug utilisation in children and adolescents with a focus on new antiepileptic drugs ....................
    [Show full text]
  • Incidence of Malformations After Early Pregnancy Exposure to Modafinil In
    Letters multivariable analyses. In a fully adjusted model, a previous Conflict of Interest Disclosures: None reported. positive PCR test result (relative risk, 1.52 [95% CI, 1.44-1.60]; Funding/Support: This work was supported by grants R24AG064191 from the P < .001) and reported high suspicion of virus exposure (rela- National Institute on Aging and R01LM012836 from the National Library of Medicine. tive risk, 1.23 [95% CI, 1.18-1.28]; P < .001) were associated with Role of the Funder/Sponsor: The funders had no role in the design and seroprevalence (Table 2). conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to Discussion | A 13.7% prevalence of SARS-CoV-2 antibodies in this submit the manuscript for publication. large cohort study of HCP in the greater NYC area was similar Disclaimer: The views expressed in this article are those of the authors and do to that among adults randomly tested in New York State not represent the views of the National Institutes of Health, the US Department of Health and Human Services, or any other government entity. Dr Davidson is (14.0%)4 but higher than among adults in Los Angeles (4.1%).5 a member of the US Preventive Services Task Force (USPSTF). This article does HCP in a single hospital in Belgium had lower seroprevalence not represent the views and policies of the USPSTF. (6.4%), which was significantly associated only with house- Additional Contributions: We thank the members of the Northwell Health hold contact.6 In this study, high levels of HCP-reported sus- COVID-19 Research Consortium who contributed to this study: Lance B.
    [Show full text]
  • Complete Thesis
    University of Groningen Deprescribing in older people van der Meer, Helene Grietje IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2019 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): van der Meer, H. G. (2019). Deprescribing in older people: development and evaluation of complex healthcare interventions. Rijksuniversiteit Groningen. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 30-09-2021 UITNODIGING DEPRESCRIBING PEOPLE IN OLDER Voor het bijwonen van de openbare verdediging van het proefschrift: DEPRESCRIBING IN OLDER PEOPLE DEPRESCRIBING Development and evaluation of complex IN OLDER PEOPLE healthcare interventions Helene Grietje (Heleen) van der Meer was born on Development and evaluation of complex door healthcare interventions 5 August 1990 in Papenburg, Germany, to Wytze Jan HELEEN VAN DER MEER van der Meer, dentist, and Klaaske van der Meer- Jansen, cardiac care nurse.
    [Show full text]