DOCSLIB.ORG

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): a Review

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): a Review Clinical Review & Education JAMA | Review Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review James M. Sanders, PhD, PharmD; Marguerite L. Monogue, PharmD; Tomasz Z. Jodlowski, PharmD; James B. Cutrell, MD Viewpoint pages 1769, and IMPORTANCE The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel 1767 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented Related article page 1839 challenge to identify effective drugs for prevention and treatment. Given the rapid pace of CME Quiz at scientific discovery and clinical data generated by the large number of people rapidly infected jamacmelookup.com by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. OBSERVATIONS No proven effective therapies for this virus currently exist. The rapidly Author Affiliations: Department of expanding knowledge regarding SARS-CoV-2 virology provides a significant number of Pharmacy, University of Texas potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in Southwestern Medical Center, Dallas vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved (Sanders, Monogue); Division of Infectious Diseases and Geographic and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to Medicine, Department of Medicine, have efficacy, and corticosteroids are currently not recommended. Current clinical evidence University of Texas Southwestern does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor Medical Center, Dallas (Sanders, Monogue, Cutrell); Pharmacy Service, blockers in patients with COVID-19. VA North Texas Health Care System, Dallas (Jodlowski). CONCLUSIONS AND RELEVANCE The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic Corresponding Author: James B. Cutrell, MD, Division of Infectious influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate Diseases and Geographic Medicine, potential therapies for COVID-19 highlight both the need and capability to produce Department of Medicine, University high-quality evidence even in the middle of a pandemic. No therapies have been shown of Texas Southwestern Medical effective to date. Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9113 (james.cutrell@ utsouthwestern.edu). JAMA. 2020;323(18):1824-1836. doi:10.1001/jama.2020.6019 Section Editors: Edward Livingston, Published online April 13, 2020. MD, Deputy Editor, and Mary McGrae McDermott, MD, Deputy Editor. he global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syn- Methods drome coronavirus 2 (SARS-CoV-2) began in Wuhan, T 1 China, in December 2019, and has since spread worldwide. As of A literature review was performed using PubMed to identify rel- April 5, 2020, there have been more than 1.2 million reported evant English-language articles published through March 25, 2020. cases and 69 000 deaths in more than 200 countries. This novel Search terms included coronavirus, severe acute respiratory syn- Betacoronavirus is similar to severe acute respiratory syndrome drome coronavirus 2, 2019-nCoV, SARS-CoV-2, SARS-CoV, MERS- coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV, and COVID-19 in combination with treatment and pharmacol- coronavirus (MERS-CoV); based on its genetic proximity, it likely ogy. The search resulted in 1315 total articles. Due to the lack of originated from bat-derived coronaviruses with spread via an RCTs, the authors also included case reports, case series, and unknown intermediate mammal host to humans.1 The viral review articles. The authors independently reviewed the titles and genome of SARS-CoV-2 was rapidly sequenced to enable diagnos- abstracts for inclusion. Additional relevant articles were identified tic testing, epidemiologic tracking, and development of preventive from the review of citations referenced. Active clinical trials were and therapeutic strategies. identified using the disease search term coronavirus infection on Currently, there is no evidence from randomized clinical trials ClinicalTrials.gov and the index of studies of novel coronavirus (RCTs)thatanypotentialtherapyimprovesoutcomesinpatientswith pneumonia in the Chinese Clinical Trial Registry.2 either suspected or confirmed COVID-19. There are no clinical trial datasupportinganyprophylactictherapy.Morethan300activeclini- cal treatment trials are underway. This narrative review summa- SARS-CoV-2: Virology and Drug Targets rizes current evidence regarding major proposed treatments, re- purposed or experimental, for COVID-19 and provides a summary SARS-CoV-2, a single-stranded RNA-enveloped virus, targets cells of current clinical experience and treatment guidance for this novel through the viral structural spike (S) protein that binds to the epidemic coronavirus. angiotensin-converting enzyme 2 (ACE2) receptor. Following 1824 JAMA May 12, 2020 Volume 323, Number 18 (Reprinted) jama.com © 2020 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) Review Clinical Review & Education Figure. Simplified Representation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Lifecycle and Potential Drug Targets MACM ROPO P HAGH AGE Tocilizumab SARS-CoV-2 Sarilumab Binds IL-6 receptor Prevents IL-6 receptor activation S protein IL-6 Inhibits IL-6 signaling ACE2 receptor Exocytosis TMPRSS2 A LVEOLOLL UUSS Soluble IL-6 receptor Camostat mesylate HOSS T CELLEL Inhibits TMPRSS2 Arbidol Prevents viral cell entry Targets S protein/ACE2 Membrane fusion interaction Chloroquine and endocytosis Inhibits membrane fusion Hydroxychloroquine of the viral envelope Inhibits viral entry and endocytosis by multiple mechanisms as well as host immunomodulatory effects Assembly Structural proteins Lopinavir Uncoating Ribavirin Darunavir Translation Remdesivir RNA Inhibits 3– Favipiravir RNA chymotrypsin- like protease Inhibits viral RdRp Translation RNA synthesis Polypeptides Nonstructural RNA-dependent Proteolysis proteins RNA polymerase (RdRp) Schematic represents virus-induced host immune system response and viral processing within target cells. Proposed targets of select repurposed and investigational products are noted. ACE2, angiotensin-converting enzyme 2; S protein, spike protein; and TMPRSS2, type 2 transmembrane serine protease. receptor binding, the virus particle uses host cell receptors and trials (including those not yet recruiting, recruiting, active, or com- endosomes to enter cells. A host type 2 transmembrane serine pleted) included pharmacological therapy for the treatment of protease, TMPRSS2, facilitates cell entry via the S protein.3 Once COVID-19 in adult patients. Of these 109 trials, 82 are interven- inside the cell, viral polyproteins are synthesized that encode for tional studies, with 29 placebo-controlled trials. Per description of the replicase-transcriptase complex. The virus then synthesizes the studies, there are 11 phase 4, 36 phase 3, 36 phase 2, and 4 RNA via its RNA-dependent RNA polymerase. Structural proteins phase 1 trials. Twenty-two trials were not categorized by phase or are synthesized leading to completion of assembly and release of not applicable. viral particles.4-6 These viral lifecycle steps provide potential tar- gets for drug therapy (Figure). Promising drug targets include nonstructural proteins (eg, 3-chymotrypsin-like protease, papain- Review of Selected Repurposed Drugs like protease, RNA-dependent RNA polymerase), which share homology with other novel coronaviruses (nCoVs). Additional Agents previously used to treat SARS and MERS are potential can- drug targets include viral entry and immune regulation didates to treat COVID-19. Various agents with apparent in vitro ac- pathways.7,8 Table 1 summarizes the mechanism of action and tivity against SARS-CoV and MERS-CoV were used during the SARS major pharmacologic parameters of select proposed treatments and MERS outbreaks, with inconsistent efficacy. Meta-analyses of or adjunctive therapies for COVID-19. SARS and MERS treatment studies found no clear benefit of any spe- cific regimen.37,38 Below, the in vitro activity and published clinical experiences of some of the most promising repurposed drugs for Ongoing Clinical Trials COVID-19 are reviewed. The search terms COVID OR coronavirus OR SARS-COV-2 on Clinical- Chloroquine and Hydroxychloroquine Trials.gov resulted in 351 active trials, with 291 trials specific to Chloroquine and hydroxychloroquine have a long-standing history COVID-19 as of April 2, 2020. Of these 291 trials, approximately 109 in the prevention and treatment of malaria and the treatment of jama.com (Reprinted) JAMA May 12, 2020 Volume 323, Number 18 1825 © 2020 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 1826 JAMA Clinical Review & Education Table 1. Summary of Pharmacology for Select Proposed COVID-19 Treatments May 12, 2020 Volume 323, Number 18 Major drug-drug Agent Target Adult dose/administration Contraindications Toxicities interactions Special populations Repurposed agents Chloroquine phosphate Blockade of viral entry by 500 mg by mouth every 12-24 h × 5-10 d. Available as: Hypersensitivity to Common: Abdominal cramps, CYP2D6 and CYP3A4 May be
Load more

Recommended publications
  • COVID-19) Pandemic on National Antimicrobial Consumption in Jordan
    antibiotics Article An Assessment of the Impact of Coronavirus Disease (COVID-19) Pandemic on National Antimicrobial Consumption in Jordan Sayer Al-Azzam 1, Nizar Mahmoud Mhaidat 1, Hayaa A. Banat 2, Mohammad Alfaour 2, Dana Samih Ahmad 2, Arno Muller 3, Adi Al-Nuseirat 4 , Elizabeth A. Lattyak 5, Barbara R. Conway 6,7 and Mamoon A. Aldeyab 6,* 1 Clinical Pharmacy Department, Jordan University of Science and Technology, Irbid 22110, Jordan; [email protected] (S.A.-A.); [email protected] (N.M.M.) 2 Jordan Food and Drug Administration (JFDA), Amman 11181, Jordan; [email protected] (H.A.B.); [email protected] (M.A.); [email protected] (D.S.A.) 3 Antimicrobial Resistance Division, World Health Organization, Avenue Appia 20, 1211 Geneva, Switzerland; [email protected] 4 World Health Organization Regional Office for the Eastern Mediterranean, Cairo 11371, Egypt; [email protected] 5 Scientific Computing Associates Corp., River Forest, IL 60305, USA; [email protected] 6 Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK; [email protected] 7 Institute of Skin Integrity and Infection Prevention, University of Huddersfield, Huddersfield HD1 3DH, UK * Correspondence: [email protected] Citation: Al-Azzam, S.; Mhaidat, N.M.; Banat, H.A.; Alfaour, M.; Abstract: Coronavirus disease 2019 (COVID-19) has overlapping clinical characteristics with bacterial Ahmad, D.S.; Muller, A.; Al-Nuseirat, respiratory tract infection, leading to the prescription of potentially unnecessary antibiotics. This A.; Lattyak, E.A.; Conway, B.R.; study aimed at measuring changes and patterns of national antimicrobial use for one year preceding Aldeyab, M.A.
    [Show full text]
  • 2021 Offerings Include
    JAMA 2021 Offerings Include: Print Edition Rate Card Effective January 1, 2021 • Patient Page Publication • Selections A supplement of curated articles on a therapeutic topic • Microsites Contact Account Manager for Information Contacts Editor Howard C. Bauchner, MD Boston University School of Medicine Insertion Order or Billing Questions Reprints Denise Steinhauser JAMA, JAMA Cardiology, JAMA Internal Medicine, (312) 464-2455 JAMA Ophthalmology, JAMA Neurology, JAMA Oncology, [email protected] JAMA Psychiatry and JAMA Network Open Marsha Fogler, Account Manager Production Questions JAMA Network Reprint Sales Michael Deegan [email protected] (312) 464-2401 USA: 1-800-482-1450 [email protected] Rest of World: 1-856-489-4446 Please include in the email the specific issue of JAMA in which your ad is running. (Note: JAMA is a weekly.) JAMA Dermatology, JAMA Otolaryngology-Head & Neck Surgery, JAMA Pediatrics, JAMA Surgery, and JAMA Network Open Display + Online Advertising Rachel Sisholtz Pharmaceutical | Device JAMA Network Reprint Sales (862) 261-9600 [email protected] Maureen Reichert USA: 1-800-482-1450 [email protected] Rest of World: 1-856-489-4446 (862) 261-9616 General Inquiries and Non-Profit Organization requests: Nancy Souza JAMA Network Reprints Communications [email protected] [email protected] (862) 261-9615 Requests from non-profit organizations, AMA members, medical Jeff Bonistalli societies, and academic institutions. Director of Advertising Pharmaceutical & Devices [email protected] Health Systems Branding | Products and Service | CME Recruitment Advertising (800) 262-2260 | (312) 464-5909 Fax [email protected] Thalia Moss [email protected] Anna Frazier Director of Advertising Health Systems & Recruitment [email protected] Domestic Subscription Rates (800) 262-2350 Online Site Licensing (312) 464-4371 Page 2 JAMA 2021 Print Edition Rate Card Rates 1.
    [Show full text]
  • Maximizing Diagnostic Value & Efficiency for Abnormal Lfts in The
    Maximizing Diagnostic Value & Efficiency for Abnormal LFTs in the Primary Care Setting Michael Kriss, MD Assistant Professor Associate Program Director, Transplant Hepatology Fellowship Division of Gastroenterology & Hepatology Section of Liver Disease & Transplantation University of Colorado School of Medicine Disclosures No conflicts of interest to disclose Learning Objectives At the completion of today’s talk, physicians will: 1. Recognize high value practices in evaluating and referring patients with abnormal liver enzymes 2. Identify essential components of the diagnostic evaluation of abnormal liver enzymes 3. Apply high value principles to complex patients requiring co-management by liver specialists https://www.ncbi.nlm.nih.gov/pubmed/27995906 https://www.ncbi.nlm.nih.gov/pubmed/27995906 Alcoholic liver disease Hepatitis B virus Primary biliary cholangitis NAFLD/NASH Hepatitis C virus Primary sclerosing cholangitis Autoimmune hepatitis Hemochromatosis Wilson’s disease https://www.aasld.org/publications/practice-guidelines What is normal…? ACG 2016 Guidelines “A true healthy normal ALT level in prospectively studied populations without identifiable risk factors for liver disease ranges from 29 to 33 IU/l for males and 19 to 25 IU/l for females, and levels above this should be assessed by physicians” “Clinicians may rely on local lab ULN ranges for alkaline phosphatase and bilirubin” Kwo PY et al. ACG Practice Guideline: Evaluation of Abnormal Liver Chemistries. AJG 2017 Critical to characterize pattern… Abnormal LFT 101 Hepatocellular Mixed Cholestatic AST/ALT Alk Phos Hyperbilirubinemia Bilirubin Kwo PY et al. ACG Practice Guideline: Evaluation of Abnormal Liver Chemistries. AJG 2017 Critical to characterize pattern… Abnormal LFT 101 ALT AP R = ALT ULN / AP ULN Hepatocellular Mixed Cholestatic AST/ALT R=2-5 Alk Phos R>5 R<2 Hyperbilirubinemia Bilirubin Kwo PY et al.
    [Show full text]
  • A New Tool for the Diagnosis of Choledocholithiasis. a Case Control Study
    DOI: https://doi.org/10.22516/25007440.446 Original article Elevated transaminases: a new tool for the diagnosis of choledocholithiasis. A case control study James Yurgaky-Sarmiento, MD,1 William Otero-Regino, MD,2* Martín Gómez-Zuleta, MD.3 Abstract OPEN ACCESS Introduction: Choledocolithiasis (CLD) affects 10% of patients with gallstones. Citation: Bile duct obstruction is associated with pancreatitis, cholangitis, and rupture of Yurgaky-Sarmiento J, Otero-Regino W, Gómez-Zuleta M. Elevated transaminases: a new tool the common bile duct. This condition usually presents with increased alkaline for the diagnosis of choledocholithiasis. A case control study. Un estudio de casos y controles. Rev Colomb Gastroenterol. 2020;35(3):319-328. https://doi.org/10.22516/25007440.446 phosphatase, GGTP and bilirubin levels. In the last decade, it has been found that up to 10% of patients with CLD have elevated aminotransferases levels. ............................................................................ In Latin America, this alteration has not been studied. The aim of the present 1 Internist, endocrinologist, gastroenterologist, Universidad Nacional de Colombia; Bogotá, work was to determine the prevalence of transaminase elevation and its evo- Colombia. lution. Methodology: Case-control study. ALT was measured on admission, 2 Professor of Medicine, Gastroenterology Coordinator, Universidad Nacional de Colombia, at 48 h and at 72 h. If ultrasound was normal, MRCP and/or echo-endoscopy Hospital Universitario Nacional de Colombia. Gastroenterologist, Clínica Fundadores; Bogotá, and ERCP were performed, as appropriate. Results: A total of 72 patients with Colombia. 3 Associate Professor of Medicine, Gastroenterology Unit, Universidad Nacional de Colombia, choledocholithiasis (CLD) (cases) and 128 with cholecystitis without choledo- Hospital Universitario Nacional de Colombia.
    [Show full text]
  • Determining Ribavirin's Mechanism of Action Against Lassa Virus Infection
    www.nature.com/scientificreports OPEN Determining Ribavirin’s mechanism of action against Lassa virus infection Received: 28 March 2017 Paola Carrillo-Bustamante1, Thi Huyen Tram Nguyen2,3, Lisa Oestereich4,5, Stephan Accepted: 4 August 2017 Günther4,5, Jeremie Guedj 2,3 & Frederik Graw1 Published: xx xx xxxx Ribavirin is a broad spectrum antiviral which inhibits Lassa virus (LASV) replication in vitro but exhibits a minor effect on viremiain vivo. However, ribavirin significantly improves the disease outcome when administered in combination with sub-optimal doses of favipiravir, a strong antiviral drug. The mechanisms explaining these conflicting findings have not been determined, so far. Here, we used an interdisciplinary approach combining mathematical models and experimental data in LASV-infected mice that were treated with ribavirin alone or in combination with the drug favipiravir to explore different putative mechanisms of action for ribavirin. We test four different hypotheses that have been previously suggested for ribavirin’s mode of action: (i) acting as a mutagen, thereby limiting the infectivity of new virions; (ii) reducing viremia by impairing viral production; (iii) modulating cell damage, i.e., by reducing inflammation, and (iv) enhancing antiviral immunity. Our analysis indicates that enhancement of antiviral immunity, as well as effects on viral production or transmission are unlikely to be ribavirin’s main mechanism mediating its antiviral effectiveness against LASV infection. Instead, the modeled viral kinetics suggest that the main mode of action of ribavirin is to protect infected cells from dying, possibly reducing the inflammatory response. Lassa fever (LF) is a severe and often fatal hemorrhagic disease caused by Lassa virus (LASV), a member of the Arenaviridae virus family.
    [Show full text]
  • The Journal Impact Factor Denominator Defining Citable (Counted) Items
    COMMENTARIES The Journal Impact Factor Denominator Defining Citable (Counted) Items Marie E. McVeigh, MS The items counted in the denominator of the impact fac- tor are identifiable in the Web of Science database by hav- Stephen J. Mann ing the index field document type set as “Article,” “Re- view,” or “Proceedings Paper” (a specialized subset of the VER ITS 30-YEAR HISTORY, THE JOURNAL IMPACT article document type). These document types identify the factor has been the subject of much discussion scholarly contribution of the journal to the literature and and debate.1 From its first release in 1975, bib- are counted as “citable items” in the denominator of the im- liometricians and library scientists discussed its pact factor. A journal accepted for coverage in the Thom- Ovalue and its vagaries. In the last decade, discussion has 6 son Reuters citation database is reviewed by experts who shifted to the way in which impact factor data are used. In consider the bibliographic and bibliometric characteristics an environment eager for objective measures of productiv- of all article types published by that journal (eg, items), which ity, relevance, and research value, the impact factor has been are covered by that journal in the context of other materi- applied broadly and indiscriminately.2,3 The impact factor als in the journal, the subject, and the database as a whole. has gone from being a measure of a journal’s citation influ- This journal-specific analysis identifies the journal sec- ence in the broader literature to a surrogate that assesses tions, subsections, or both that contain materials likely to the scholarly value of work published in that journal.
    [Show full text]
  • Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir
    RESEARCH ARTICLE Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir Ana I. de AÂ vila1, Isabel Gallego1,2, Maria Eugenia Soria3, Josep Gregori2,3,4, Josep Quer2,3,5, Juan Ignacio Esteban2,3,5, Charles M. Rice6, Esteban Domingo1,2*, Celia Perales1,2,3* 1 Centro de BiologõÂa Molecular ªSevero Ochoaº (CSIC-UAM), Consejo Superior de Investigaciones CientõÂficas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain, 2 Centro de InvestigacioÂn BiomeÂdica en Red de Enfermedades HepaÂticas y Digestivas (CIBERehd), Barcelona, Spain, 3 Liver Unit, Internal Medicine, Laboratory of Malalties Hepàtiques, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d a11111 ÂHebron, (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035, Barcelona, Spain, 4 Roche Diagnostics, S.L., Sant Cugat del ValleÂs, Spain, 5 Universitat AutoÂnoma de Barcelona, Barcelona, Spain, 6 Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, United States of America * [email protected] (ED); [email protected] (CP) OPEN ACCESS Abstract Citation: de AÂvila AI, Gallego I, Soria ME, Gregori J, Quer J, Esteban JI, et al. (2016) Lethal Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by an Mutagenesis of Hepatitis C Virus Induced by excess of mutations acquired during replication in the presence of a mutagen. Here we Favipiravir. PLoS ONE 11(10): e0164691. show that favipiravir (T-705) is a potent mutagenic agent for hepatitis C virus (HCV) during doi:10.1371/journal.pone.0164691 its replication in human hepatoma cells. T-705 leads to an excess of G ! A and C ! U tran- Editor: Ming-Lung Yu, Kaohsiung Medical sitions in the mutant spectrum of preextinction HCV populations.
    [Show full text]
  • Web of Science Benefits
    Thomson.com Web of Science® What it offers. Why it matters to you. What Web of Science delivers How your work will benefit Content is the cornerstone For decades, the Thomson Scientific (formerly ISI) The result of this ongoing collection development? Excellence Editorial Development group has carefully Quality by default. without evaluated journals for potential inclusion in the excess database. Your search results will include only accurate, reliable, —— relevant data. You'll get not just more hits, but more The objective is to include only the most quality hits. You'll get the influential, relevant, and credible journal right answers, information available. If you publish — You'll easily find high impact quicker articles upon which to base your articles — increasing The criteria are detailed, unbiased, and time- the quality and credibility of your published work, tested — examining basic publishing standards, resulting in more publication in more prestigious timeliness, editorial scope and objectives, and sources. citation analyses. If you research — You'll be able to quickly identify The process is "publisher-neutral" — commercial, potential collaborators with prolific, significant citation open access, society, and university publishers are records. And tracking your own citation record will treated equally. help you demonstrate your work's impact on your field. Every publication indexed within Web of Science has passed through this rigorous evaluation If you teach — Your students will be assured of using process. the highest quality resources — finding valuable information in journals they may not have the knowledge and experience to seek on their own. It's a fact ... As of March 2006, the total number of Web of Science records is approximately 37 million.
    [Show full text]
  • Babes and Boobs? Analysis of JAMA Cover Art Jocalyn P Clark
    Papers BMJ: first published as 10.1136/bmj.319.7225.1603 on 18 December 1999. Downloaded from Babes and boobs? Analysis of JAMA cover art Jocalyn P Clark Abstract Of the 15 covers depicting women, 12 included Department of babies and six showed nudity. In contrast, only one Public Health Objective To determine the representation of the Sciences, University male image included a child and none contained of Toronto, Toronto, sexes in JAMA cover art. nudity. In the cover depicting a man with a child, the Canada M5S 1A8 doctoral candidate Design Review of 50 consecutive issues. man is not the child’s father but its doctor. Babes and Setting JAMA, March 1997-March 1998. boobs were featured in 12 of the 50 covers. Correspondence to: Main outcome measures Numbers and nature of J P Clark, Centre for Research in covers portraying men and women. Women’s Health, Results Of the 50 covers, 34 depicted humans. 15 Conclusions Toronto, Canada depicted women, 13 men, and 6 were of mixed or M5G 1N8 Visual imagery associated with medical journals shapes [email protected] indeterminate sex. 11 pictures of women included a our understanding of health and the human body. child and five included nudity. One cover showed a Images of babes and boobs in cover art emphasise BMJ 1999;319:1603–5 man with a child (not as a father) and none depicted women’s sexual and domestic roles, representing nudity. Men were depicted exclusively in authoritative women in traditional and stereotypical ways that under- roles. mine contemporary beliefs in the equality, autonomy, Conclusions Much of the cover art gives strong and status of women.34 These representations do not messages about sexual stereotypes that are reflect women’s contributions to the domains of science, inappropriate in modern society.
    [Show full text]
  • To Ebola Reston
    WHO/HSE/EPR/2009.2 WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 EPIDEMIC AND PANDEMIC ALERT AND RESPONSE WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 © World Health Organization 2009 All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distin- guished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the policies of the World Health Organization.
    [Show full text]
  • Elevated Transaminases During Medical Treatment of Acromegaly: A
    European Journal of Endocrinology (2006) 154 213–220 ISSN 0804-4643 CASE REPORT Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis H Biering1, B Saller4,*, J Bauditz1, M Pirlich1, B Rudolph2, A Johne3, M Buchfelder5,*, K Mann6,*, M Droste7,*, I Schreiber4, H Lochs1 and C J Strasburger1,* 1Department of Gastroenterology, Hepatology and Endocrinology, 2Institute of Pathology and 3Institute for Clinical Pharmacology, Charite´-Universita¨tsmedizin Berlin, 10117 Berlin, Germany, 4Pfizer Pharma GmbH, Karlsruhe, Germany, 5Department of Neurosurgery, University Hosiptal, Erlangen, Germany, 6Division of Endocrinology, Department of Medicine, University of Duisberg-Essen, Germany and 7Oldenburg, Germany (Correspondence should be addressed to C J Strasburger, Division of Clinical Endocrinology, Department of Medicine, Charite´-Universita¨tsmedizin Berlin, Schumannstr. 20/21, 10117 Berlin, Germany; Email: [email protected]) *On behalf of the German pegvisomant investigators Abstract Objective: The new GH receptor antagonist pegvisomant is the most effective medical therapy to nor- malize IGF-I levels in patients with acromegaly. Based on currently available data pegvisomant is well tolerated; however, treatment-induced elevation of transaminases has been reported and led to the necessity for drug discontinuation in some patients in the pivotal studies. The aim of this study was to evaluate and characterize the prevalence of elevated transaminases and to describe in detail the findings in a single case who required drug discontinuation because of elevation of transaminases which emerged during treatment and who underwent liver biopsy. Design and methods: Retrospective safety analyses were carried out on 142 patients with acromegaly receiving pegvisomant treatment in Germany between March 2003 and the end of 2004.
    [Show full text]
  • How Severe and Prevalent Are Ebola and Marburg Viruses?
    Nyakarahuka et al. BMC Infectious Diseases (2016) 16:708 DOI 10.1186/s12879-016-2045-6 RESEARCHARTICLE Open Access How severe and prevalent are Ebola and Marburg viruses? A systematic review and meta-analysis of the case fatality rates and seroprevalence Luke Nyakarahuka1,2,5* , Clovice Kankya2, Randi Krontveit3, Benjamin Mayer4, Frank N. Mwiine2, Julius Lutwama5 and Eystein Skjerve1 Abstract Background: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24–100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases. Methods: Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA. Results: The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0–76.0%), I2 = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5–80.0%, I2 = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%–11.0%, I2 = 98.7%), whereas that for Marburg virus was 1.2% (0.5–2.0%, I2 = 94.8%).
    [Show full text]