ebook download Current Medical Diagnosis & Treatment 2019 58th Edition - eBook PDF all chapter

Current Medical Diagnosis & Treatment
2019 58th Edition - eBook PDF

Go to download the full and correct content document:
https://ebooksecure.com/download/current-medical-diagnosis-treatment-2019-ebook-
pdf/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...
CURRENT Medical Diagnosis and Treatment 2023 (Current

Medical Diagnosis & Treatment) (Fragment) 62nd Edition
Maxine Papadakis - eBook PDF
https://ebooksecure.com/download/current-medical-diagnosis-and-
treatment-2023-current-medical-diagnosis-treatment-fragment-
ebook-pdf/
CURRENT Medical Diagnosis & Treatment 2020 59th

edition- eBook PDF
https://ebooksecure.com/download/current-medical-diagnosis-
treatment-2020-ebook-pdf/
CURRENT Medical Diagnosis and Treatment 2021 60th

Edition- eBook PDF
(eBook PDF) CURRENT Medical Diagnosis and Treatment

Study Guide 2nd
http://ebooksecure.com/product/ebook-pdf-current-medical-
diagnosis-and-treatment-study-guide-2nd/
CURRENT Medical Diagnosis and Treatment 2023 62nd
Edition Maxine Papadakis - eBook PDF
Current medical diagnosis & treatment - 2021 60th

Edition Maxine A. Papadakis - eBook PDF
Current Medical Diagnosis & Treatment 2020 59th Edition

Maxine A. Papadakis - eBook PDF
treatment-2020-ebook-pdf-2/
CURRENT Diagnosis & Treatment Pediatrics 24th Edition

Edition William Hay - eBook PDF
https://ebooksecure.com/download/current-diagnosis-treatment-
pediatrics-ebook-pdf/
Current Diagnosis & Treatment Obstetrics & Gynecology,

12th Edition Lauren Nathan - eBook PDF
https://ebooksecure.com/download/current-diagnosis-treatment-
obstetrics-gynecology-12th-edition-ebook-pdf/
PLACEHOLDER FOR MARKETING PAGE
CMDT2019_FM_pi-xx.indd 1 05/07/18 2:02 PM

This page intentionally left blank

a LANGE medical book
2019
CURRENT
Medical Diagnosis
& Treatment
FIFT Y-EIGHTH EDITION
Edited by
Maxine A. Papadakis, MD
Professor of Medicine, Emeritus
Department of Medicine
University of California, San Francisco
Stephen J. McPhee, MD
Professor of Medicine, Emeritus
Division of General Internal Medicine
Associate Editor
Michael W. Rabow, MD
Professor of Medicine and Urology
Division of Palliative Medicine
With Associate Authors
New York Chicago San Francisco Athens London Madrid Mexico City
Milan New Delhi Singapore Sydney Toronto

Copyright © 2019 by McGraw-Hill Education. All rights reserved. Except as permitted under the United States Copyright
Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database
or retrieval system, without the prior written permission of the publisher.
ISBN: 978-1-26-011744-8
MHID: 1-26-011744-8
The material in this eBook also appears in the print version of this title: ISBN: 978-1-26-011743-1,
MHID: 1-26-011743-X.
eBook conversion by codeMantra

Version 1.0
All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a
trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of
infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps.
McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for
use in corporate training programs. To contact a representative, please visit the Contact Us page at www.mhprofessional.com.
Notice
Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment
and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in
their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publica-
tion. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher
nor any other party who has been involved in the preparation or publication of this work warrants that the information con-
tained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for
the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information
contained herein with other sources. For example and in particular, readers are advised to check the product information sheet
included in the package of each medication they plan to administer to be certain that the information contained in this work is
accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This
recommendation is of particular importance in connection with new or infrequently used medications.
TERMS OF USE
This is a copyrighted work and McGraw-Hill Education and its licensors reserve all rights in and to the work. Use of this
work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one
copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based
upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill Education’s
prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly
prohibited. Your right to use the work may be terminated if you fail to comply with these terms.
THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARAN-
TEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE
OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH
THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR
IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS
FOR A PARTICULAR PURPOSE. McGraw-Hill Education and its licensors do not warrant or guarantee that the functions
contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-
Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause,
in the work or for any damages resulting therefrom. McGraw-Hill Education has no responsibility for the content of any
information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable
for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use
the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to
any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.
Contents
Authors v 13. Blood Disorders 510
Preface xiii
Lloyd E. Damon, MD, &
1. Disease Prevention & Health Promotion 1 Charalambos Babis Andreadis, MD, MSCE
Michael Pignone MD, MPH, & René Salazar, MD 14. Disorders of Hemostasis, Thrombosis, &

Antithrombotic Therapy 556
2. Common Symptoms 20 Andrew D. Leavitt, MD, & Tracy Minichiello, MD
Paul L. Nadler, MD, & Ralph Gonzales, MD, MSPH
15. Gastrointestinal Disorders 589
3. Preoperative Evaluation & Perioperative Kenneth R. McQuaid, MD

Management 46
Hugo Q. Cheng, MD 16. Liver, Biliary Tract, & Pancreas Disorders 688
Lawrence S. Friedman, MD
4. Geriatric Disorders 55
17. Breast Disorders 750
G. Michael Harper, MD, C. Bree Johnston, MD, MPH,
& C. Seth Landefeld, MD Armando E. Giuliano, MD, FACS, FRCSEd, &
Sara A. Hurvitz, MD
5. Palliative Care & Pain Management 72
18. Gynecologic Disorders 776
Michael W. Rabow, MD, Steven Z. Pantilat, MD,
Scott Steiger, MD, & Ramana K. Naidu, MD Jason Woo, MD, MPH, FACOG, &
Rachel K. Scott, MD, MPH, FACOG
6. Dermatologic Disorders 103
19. Obstetrics & Obstetric Disorders 811
Kanade Shinkai, MD, PhD, & Lindy P. Fox, MD
Vanessa L. Rogers, MD, & Scott W. Roberts, MD
7. Disorders of the Eyes & Lids 174 20. Rheumatologic, Immunologic, &

Paul Riordan-Eva, FRCOphth Allergic Disorders 840
David B. Hellmann, MD, MACP, &
8. Ear, Nose, & Throat Disorders 210 John B. Imboden Jr., MD
Lawrence R. Lustig, MD, & Joshua S. Schindler, MD
21. Electrolyte & Acid-Base Disorders 898
9. Pulmonary Disorders 252 Kerry C. Cho, MD
Asha N. Chesnutt, MD, Mark S. Chesnutt, MD, Niall 22. Kidney Disease 926
T. Prendergast, MD, & Thomas J. Prendergast, MD
Tonja C. Dirkx, MD, & Tyler Woodell, MD
10. Heart Disease 334
23. Urologic Disorders 966
Thomas M. Bashore, MD, Christopher B. Granger, MD,
Kevin P. Jackson, MD, & Manesh R. Patel, MD Maxwell V. Meng, MD, FACS,
Thomas J. Walsh, MD, MS, & Thomas D. Chi, MD
11. Systemic Hypertension 451 24. Nervous System Disorders 990
Michael Sutters, MD, MRCP (UK) Vanja C. Douglas, MD, &
Michael J. Aminoff, MD, DSc, FRCP
12. Blood Vessel & Lymphatic Disorders 483
Warren J. Gasper, MD, Joseph H. Rapp, MD, & 25. Psychiatric Disorders 1063
Meshell D. Johnson, MD Kristin S. Raj, MD, Nolan Williams, MD, &
Charles DeBattista, DMH, MD
iii

iv CMDT 2019 CONTENTS
26. Endocrine Disorders 1119 39. Cancer 1611

Paul A. Fitzgerald, MD Patricia A. Cornett, MD, Tiffany O. Dea, PharmD,
BCOP, Sunny Wang, MD, Lawrence S. Friedman,
27. Diabetes Mellitus & Hypoglycemia 1220 MD, Pelin Cinar, MD, MS, Kenneth R. McQuaid, MD,
Maxwell V. Meng, MD, FACS, & Charles J. Ryan, MD
Umesh Masharani, MB, BS, MRCP (UK)
40. Genetic & Genomic Disorders 1681
28. Lipid Disorders 1267 Reed E. Pyeritz, MD, PhD
Robert B. Baron, MD, MS
41. Sports Medicine & Outpatient

29. Nutritional Disorders 1276 Orthopedics 1690
Robert B. Baron, MD, MS Anthony Luke, MD, MPH, & C. Benjamin Ma, MD
42. Lesbian, Gay, Bisexual, & Transgender

30. Common Problems in Infectious

Health 1722

Diseases & Antimicrobial Therapy 1294
Juno Obedin-Maliver, MD, MPH, MAS, Patricia A.
Peter V. Chin-Hong, MD, &
Robertson, MD, Kevin L. Ard, MD, MPH, Kenneth H.
B. Joseph Guglielmo, PharmD
Mayer, MD, & Madeline B. Deutsch, MD, MPH
31. HIV Infection & AIDS 1338 e1. Anti-Infective Chemotherapeutic &

Mitchell H. Katz, MD Antibiotic Agents Online*
Katherine Gruenberg, PharmD, & B. Joseph
32. Viral & Rickettsial Infections 1377 Guglielmo, PharmD
Wayne X. Shandera, MD, &
Dima Dandachi, MD
e2. Diagnostic Testing & Medical Decision

Making Online*
33. Bacterial & Chlamydial Infections 1448 Chuanyi Mark Lu, MD
Bryn A. Boslett, MD, & e3. Information Technology in

Brian S. Schwartz, MD

Patient Care Online*
34. Spirochetal Infections 1493 Russ Cucina, MD, MS
Susan S. Philip, MD, MPH e4. Integrative Medicine Online*

Darshan Mehta, MD, MPH, &
35. Protozoal & Helminthic Infections 1510 Kevin Barrows, MD
Philip J. Rosenthal, MD
e5. Podiatric Disorders Online*
36. Mycotic Infections 1550 Monara Dini, DPM
Samuel A. Shelburne III, MD, PhD, &
Richard J. Hamill, MD e6. Women’s Health Issues Online*
Megan McNamara, MD, MSc, &
37. Disorders Related to Environmental Judith Walsh, MD, MPH

Emergencies 1564
e7. Appendix: Therapeutic Drug Monitoring &
Jacqueline A. Nemer, MD, FACEP, &

Laboratory Reference Intervals, &
Marianne A. Juarez, MD
Pharmacogenetic Testing Online*
38. Poisoning 1580 Chuanyi Mark Lu, MD
Kent R. Olson, MD Index 1743
*Free access to online chapters at www.accessmedicine.com/cmdt

Authors
N. Franklin Adkinson, Jr., MD Kevin Barrows, MD
Professor of Medicine, Johns Hopkins Asthma & Clinical Professor of Family and Community Medicine,
Allergy Center, Baltimore, Maryland Director of Mindfulness Programs, Osher Center for
fadkinso@jhmi.edu Integrative Medicine; Department of Family and
Allergic & Immunologic Disorders (in Chapter 20) Community Medicine, University of California, San
Francisco
Michael J. Aminoff, MD, DSc, FRCP Kevin.Barrows@ucsf.edu
Distinguished Professor and Executive Vice Chair, CMDT Online—Integrative Medicine
Department of Neurology, University of California,
San Francisco; Attending Physician, University of Thomas M. Bashore, MD
California Medical Center, San Francisco Professor of Medicine; Senior Vice Chief, Division of
michael.aminoff@ucsf.edu Cardiology, Duke University Medical Center, Durham,
Nervous System Disorders North Carolina
thomas.bashore@duke.edu
Charalambos Babis Andreadis, MD, MSCE Heart Disease
Associate Professor of Clinical Medicine, Division of
Hematology/Oncology, University of California, Sudhamayi Bhadriraju, MD, MPH
San Francisco Clinical Fellow, Department of Medicine, University of
Charalambos.Andreadis@ucsf.edu California, San Francisco
Blood Disorders References
Kevin L. Ard, MD, MPH Bryn A. Boslett, MD

Faculty, Division of Infectious Diseases, Massachusetts Assistant Professor, Division of Infectious Diseases,
General Hospital; Medical Director, National LGBT Department of Medicine, University of California,
Health Education Center, Fenway Institute; Instructor San Francisco
in Medicine, Harvard Medical School, Boston, Bryn.Boslett@ucsf.edu
Massachusetts Bacterial & Chlamydial Infections
kard@mgh.harvard.edu
Gay & Bisexual Men’s Health (in Chapter 42) Rachel Bystritsky, MD
Infectious Diseases Fellow, University of California,
Patrick Avila, MD San Francisco
Clinical Fellow, Division of Gastroenterology, Department References
of Medicine, University of California, San Francisco
References Hugo Q. Cheng, MD
Clinical Professor of Medicine, University of California,
Antoine Azar, MD San Francisco
Assistant Professor of Medicine, Division of Allergy & quinny.cheng@ucsf.edu
Clinical Immunology, Johns Hopkins Asthma & Preoperative Evaluation & Perioperative Management
Allergy Center, Baltimore, Maryland
aazar4@jhmi.edu Asha N. Chesnutt, MD
Allergic & Immunologic Disorders (in Chapter 20) Clinical Assistant Professor, Division of Pulmonary &
Critical Care Medicine, Department of Medicine,
David M. Barbour, PharmD, BCPS Oregon Health & Science University, Portland, Oregon
Pharmacist, Denver, Colorado Asha.Chesnutt2@providence.org
dbarbour99@gmail.com Pulmonary Disorders
Drug References
Mark S. Chesnutt, MD
Robert B. Baron, MD, MS Professor, Pulmonary & Critical Care Medicine, Dotter
Professor of Medicine; Associate Dean for Graduate and Interventional Institute, Oregon Health & Science
Continuing Medical Education; University of University, Portland, Oregon; Director, Critical Care,
California, San Francisco Portland Veterans Affairs Health Care System
baron@medicine.ucsf.edu chesnutm@ohsu.edu
Lipid Disorders; Nutritional Disorders Pulmonary Disorders

vi CMDT 2019 AUTHORS
Thomas D. Chi, MD Charles DeBattista, DMH, MD

Assistant Professor, Department of Urology, University of Professor of Psychiatry and Behavioral Sciences; Director,
California, San Francisco Depression Clinic and Research Program; Director of
tom.chi@ucsf.edu Medical Student Education in Psychiatry, Stanford
Urologic Disorders University School of Medicine, Stanford, California
debattista@stanford.edu
Peter V. Chin-Hong, MD Psychiatric Disorders
Professor, Division of Infectious Diseases, Department of
Medicine, University of California, San Francisco Madeline B. Deutsch, MD, MPH
peter.chin-hong@ucsf.edu Associate Professor of Clinical Family & Community
Common Problems in Infectious Diseases & Antimicrobial Medicine; Director, UCSF Transgender Care; Center of
Therapy Excellence for Transgender Health, University of
California, San Francisco
Kerry C. Cho, MD Madeline.Deutsch@ucsf.edu
Clinical Professor of Medicine, Division of Nephrology, Transgender Health & Disease Prevention (in Chapter 42)
kerry.cho@ucsf.edu Monara Dini, DPM
Electrolyte & Acid-Base Disorders Assistant Clinical Professor, Chief of Podiatric Surgery
Division, Department of Orthopedic Surgery,
Pelin Cinar, MD, MS University of California, San Francisco
Clinical Assistant Professor of Medicine in Oncology, monara.dini@ucsf.edu
University of California San Francisco; Director of CMDT Online—Podiatric Disorders
Quality Improvement, UCSF Helen Diller Family
Comprehensive Cancer Center Tonja C. Dirkx, MD
pelin.cinar@ucsf.edu Associate Professor of Medicine, Division of Nephrology,
Alimentary Tract Cancers (in Chapter 39) Department of Medicine, Oregon Health & Science
University, Portland, Oregon; Acting Nephrology
Patricia A. Cornett, MD Division Chief, Portland Veterans Affairs Health Care
Professor of Medicine, Division of Hematology/Oncology,
System
dirkxt@ohsu.edu
patricia.cornett@ucsf.edu
Kidney Disease
Cancer
Russ Cucina, MD, MS Vanja C. Douglas, MD

Professor of Hospital Medicine; Chief Health Information Sara & Evan Williams Foundation Endowed
Officer, UCSF Health System; University of California, Neurohospitalist Chair, Associate Professor of Clinical
San Francisco Neurology, Department of Neurology, University of
russ.cucina@ucsf.edu California, San Francisco
CMDT Online—Information Technology in Patient Care Vanja.Douglas@ucsf.edu
Nervous System Disorders
Lloyd E. Damon, MD
Professor of Clinical Medicine, Department of Medicine, Paul A. Fitzgerald, MD
Division of Hematology/Oncology; Director of Adult Clinical Professor of Medicine, Department of Medicine,
Hematologic Malignancies and Blood and Marrow Division of Endocrinology, University of California,
Transplantation, Deputy Chief of the Division of San Francisco
Hematology and Medical Oncology, University of paul.fitzgerald@ucsf.edu
California, San Francisco Endocrine Disorders
lloyd.damon@ucsf.edu
Blood Disorders Lindy P. Fox, MD
Associate Professor, Department of Dermatology,
Dima Dandachi, MD University of California, San Francisco
Infectious Diseases Fellow, Baylor College of Medicine, Lindy.Fox@ucsf.edu
Houston, Texas Dermatologic Disorders
Viral & Rickettsial Infections
Tiffany O. Dea, PharmD, BCOP

Oncology Pharmacist, Veterans Affairs Health Care System,
San Francisco, California; Adjunct Professor, Thomas J.
Long School of Pharmacy and Health Sciences, Stockton,
California
tiffany.dea@va.gov
Cancer

AUTHORS CMDT 2019 vii
Lawrence S. Friedman, MD Richard J. Hamill, MD

Professor of Medicine, Harvard Medical School; Professor Professor, Division of Infectious Diseases, Departments of
of Medicine, Tufts University School of Medicine, Medicine and Molecular Virology & Microbiology,
Boston, Massachusetts; The Anton R. Fried, MD, Chair, Baylor College of Medicine, Houston, Texas
Department of Medicine, Newton-Wellesley Hospital, rhamill@bcm.edu
Newton, Massachusetts; Assistant Chief of Medicine, Mycotic Infections
Massachusetts General Hospital, Boston
lfriedman@partners.org G. Michael Harper, MD
Liver, Biliary Tract, & Pancreas Disorders; Hepatobiliary Professor, Division of Geriatrics, Department of Medicine,
Cancers (in Chapter 39) University of California San Francisco School of
Medicine; San Francisco Veterans Affairs Health Care
Warren J. Gasper, MD System, San Francisco, California
Assistant Professor of Clinical Surgery, Division of Michael.Harper@ucsf.edu
Vascular and Endovascular Surgery, Department of Geriatric Disorders
Surgery, University of California, San Francisco
warren.gasper@ucsf.edu David B. Hellmann, MD, MACP
Blood Vessel & Lymphatic Disorders Aliki Perroti Professor of Medicine; Vice Dean for Johns
Hopkins Bayview; Chairman, Department of Medicine,
Armando E. Giuliano, MD, FACS, FRCSEd Johns Hopkins Bayview Medical Center, Johns Hopkins
Executive Vice Chair of Surgery, Associate Director of University School of Medicine, Baltimore, Maryland
Surgical Oncology, Cedars-Sinai Medical Center, hellmann@jhmi.edu
Los Angeles, California Rheumatologic, Immunologic, & Allergic Disorders
armando.giuliano@cshs.org
Breast Disorders Sara A. Hurvitz, MD
Associate Professor; Director, Breast Oncology Program,
Ilya Golovaty, MD Division of Hematology/Oncology, Department of
Research Fellow, Department of Medicine, University of Internal Medicine, University of California,
California, San Francisco Los Angeles
References shurvitz@mednet.ucla.edu
Breast Disorders
Ralph Gonzales, MD, MSPH
Associate Dean, Clinical Innovation and Chief Innovation John B. Imboden, Jr., MD
Officer, UCSF Health; Professor of Medicine, Division Alice Betts Endowed Chair for Arthritis Research;
of General Internal Medicine, Department of Medicine, Professor of Medicine, University of California,
University of California, San Francisco San Francisco; Chief, Division of Rheumatology,
ralph.gonzales@ucsf.edu Zuckerberg San Francisco General Hospital
Common Symptoms John.Imboden@ucsf.edu
Rheumatologic, Immunologic, & Allergic Disorders
Christopher B. Granger, MD
Professor of Medicine; Director, Cardiac Care Unit, Duke Kevin P. Jackson, MD
University Medical Center, Duke Clinical Research Assistant Professor of Medicine, Director of
Institute, Durham, North Carolina Electrophysiology, Duke Raleigh Hospital, Duke
christopher.granger@dm.duke.edu University Medical Center, Durham, North Carolina
Heart Disease k.j@duke.edu
Heart Disease
Katherine Gruenberg, PharmD
Assistant Professor, School of Pharmacy, University of Jane Jih, MD, MPH, MAS
California, San Francisco Assistant Professor of Medicine, Division of General
Katherine.Gruenberg@ucsf.edu Internal Medicine, Department of Medicine, University
CMDT Online—Anti-Infective Chemotherapeutic & of California, San Francisco
Antibiotic Agents References
B. Joseph Guglielmo, PharmD Meshell D. Johnson, MD

Professor and Dean, School of Pharmacy, University of Associate Professor of Medicine, Division of Pulmonary
California, San Francisco and Critical Care Medicine; Director of Faculty
BJoseph.Guglielmo@ucsf.edu Diversity, Department of Medicine, University of
Common Problems in Infectious Diseases & Antimicrobial California, San Francisco
Therapy; CMDT Online—Anti-Infective meshell.johnson@ucsf.edu
Chemotherapeutic & Antibiotic Agents Blood Vessel & Lymphatic Disorders; Alcohol Use Disorder
(Alcoholism) (in Chapter 25)

viii CMDT 2019 AUTHORS
C. Bree Johnston, MD, MPH Chuanyi Mark Lu, MD

Medical Director of Palliative and Supportive Care, Professor, Department of Laboratory Medicine, University
PeaceHealth St. Joseph Medical Center, Bellingham, of California, San Francisco; Chief, Hematology,
Washington; Clinical Professor of Medicine, University Hematopathology & Molecular Diagnostics,
of Washington Laboratory Medicine Service, Veterans Affairs Health
bjohnston@peacehealth.org Care System, San Francisco, California
Geriatric Disorders mark.lu@va.gov
CMDT Online—Appendix: Therapeutic Drug Monitoring
Marianne A. Juarez, MD & Laboratory Reference Intervals, & Pharmacogenetic
Assistant Clinical Professor, Department of Emergency Testing; CMDT Online—Diagnostic Testing & Medical
Medicine, University of California, San Francisco Decision Making
Marianne.Juarez@ucsf.edu
Disorders Related to Environmental Emergencies Anthony Luke, MD, MPH
Professor of Clinical Orthopaedics, Department of
Mitchell H. Katz, MD Orthopaedics; Director, UCSF Primary Care Sports
Clinical Professor of Medicine, Epidemiology & Medicine; Director, Human Performance Center at the
Biostatistics, University of California, San Francisco; Orthopaedic Institute, University of California,
Director of Health Services, Los Angeles County San Francisco
mkatz@dhs.lacounty.gov anthony.luke@ucsf.edu
HIV Infection & AIDS Sports Medicine & Outpatient Orthopedics
Bhavika Kaul, MD Lawrence R. Lustig, MD

Clinical Fellow, Department of Pulmonary & Critical Care Howard W. Smith Professor and Chair, Department of
Medicine, University of California, San Francisco Otolaryngology—Head & Neck Surgery, Columbia
References University Medical Center & New York Presbyterian
Hospital, New York, New York
Elaine Khoong, MD, MS lrl2125@cumc.columbia.edu
Primary Care Research Fellow, Department of Medicine, Ear, Nose, & Throat Disorders
References C. Benjamin Ma, MD
Professor, Department of Orthopaedic Surgery; Chief,
Lucinda Kohn, MD Sports Medicine and Shoulder Service, University of
Dermatology Resident, Department of Dermatology, California, San Francisco
University of California, San Francisco MaBen@orthosurg.ucsf.edu
References Sports Medicine & Outpatient Orthopedics
C. Seth Landefeld, MD Anne Mardy, MD

Professor of Medicine; Chair, Department of Medicine Clinical Fellow, Maternal Fetal Medicine and Medical
and Spencer Chair in Medical Science Leadership, Genetics, University of California, San Francisco
University of Alabama at Birmingham References
sethlandefeld@uab.edu
Geriatric Disorders Umesh Masharani, MB, BS, MRCP (UK)
Professor of Medicine, Division of Endocrinology and
Andrew D. Leavitt, MD Metabolism, Department of Medicine, University of
Professor, Departments of Medicine (Hematology) and California, San Francisco
Laboratory Medicine; Medical Director, UCSF Adult umesh.masharani@ucsf.edu
Hemophilia Treatment Center, University of California, Diabetes Mellitus & Hypoglycemia
San Francisco
andrew.leavitt@ucsf.edu Kenneth H. Mayer, MD
Disorders of Hemostasis, Thrombosis, & Antithrombotic Co-Chair and Medical Research Director, The Fenway
Therapy Institute; Director of HIV Prevention Research, Beth
Israel Deaconess Medical Center; Professor of
Medicine, Harvard Medical School, Boston,
Massachusetts
kmayer@fenwayhealth.org
Gay & Bisexual Men’s Health (in Chapter 42)

AUTHORS CMDT 2019 ix
Megan McNamara, MD, MSc Jacqueline A. Nemer, MD, FACEP

Associate Professor of Medicine, Case Western Reserve Professor of Emergency Medicine, Director of Quality &
University School of Medicine; Louis Stokes Cleveland Safety, Director of Advanced Clinical Skills,
Veterans Affairs Medical Center, Cleveland, Ohio Department of Emergency Medicine, University of
Megan.Mcnamara@va.gov California, San Francisco
CMDT Online—Women’s Health Issues jacqueline.nemer@ucsf.edu
Disorders Related to Environmental Emergencies
Kenneth R. McQuaid, MD
Chief, Gastroenterology and Medical Service, Juno Obedin-Maliver, MD, MPH, MAS
San Francisco Veterans Affairs Medical Center; Assistant Professor, Department of Obstetrics,
Professor of Clinical Medicine, Marvin H. Sleisenger Gynecology, and Reproductive Sciences, University of
Endowed Chair and Vice-Chairman, Department of California, San Francisco and San Francisco Veterans
Medicine, University of California, San Francisco Affairs Medical Center; Founder and Investigator,
Kenneth.Mcquaid@va.gov Lesbian, Gay, Bisexual, and Transgender Medical
Gastrointestinal Disorders; Alimentary Tract Cancers Education Research Group, Stanford University School
(in Chapter 39) of Medicine, Stanford, California
Juno.Obedin-Maliver@ucsf.edu
Darshan Mehta, MD, MPH Lesbian & Bisexual Women’s Health (in Chapter 42)
Medical Director, Benson-Henry Institute for Mind Body
Medicine, Massachusetts General Hospital; Associate Kent R. Olson, MD
Director of Education, Osher Center for Integrative Clinical Professor of Medicine, Pediatrics, and Pharmacy,
Medicine, Harvard Medical School and Brigham and University of California, San Francisco; Medical
Women’s Hospital, Boston Director, San Francisco Division, California Poison
dmehta@mgh.harvard.edu Control System
CMDT Online—Integrative Medicine kent.olson@ucsf.edu
Poisoning
Maxwell V. Meng, MD, FACS
Professor, Chief of Urologic Oncology, Department of Steven Z. Pantilat, MD
Urology, University of California, San Francisco Professor of Medicine, Department of Medicine;
max.meng@ucsf.edu Kates-Burnard and Hellman Distinguished Professor of
Urologic Disorders; Cancers of the Genitourinary Tract Palliative Care; Director, Palliative Care Program,
(in Chapter 39) University of California, San Francisco
steve.pantilat@ucsf.edu
Tracy Minichiello, MD Palliative Care & Pain Management
Clinical Professor of Medicine, University of California,
San Francisco; Chief, Anticoagulation and Thrombosis Charles Brian Parks, DPM
Services, San Francisco Veterans Affairs Medical Assistant Clinical Professor, Chief of Podiatric Surgery
Center Division, Department of Orthopedic Surgery,
Tracy.Minichiello@ucsf.edu University of California, San Francisco
Disorders of Hemostasis, Thrombosis, & Antithrombotic Charles.Parks@ucsf.edu
Therapy CMDT Online— Flatfoot (Pes Planus) (in Chapter e5)
Paul L. Nadler, MD Manesh R. Patel, MD

Clinical Professor of Medicine; Director, Screening and Associate Professor of Medicine, Division of Cardiology,
Acute Care Clinic, Division of General Internal Department of Medicine; Director of Interventional
Medicine, Department of Medicine, University of Cardiology, Duke University Medical Center, Durham,
California, San Francisco North Carolina
Paul.Nadler@ucsf.edu manesh.patel@duke.edu
Common Symptoms Heart Disease
Ramana K. Naidu, MD Susan S. Philip, MD, MPH

Assistant Professor, Department of Anesthesia and Assistant Clinical Professor, Division of Infectious
Perioperative Care, Division of Pain Medicine, Diseases, Department of Medicine, University of
University of California, San Francisco; Pain Physician California, San Francisco; Disease Prevention and
& Anesthesiologist, California Orthopedics and Spine, Control Branch, Population Health Division,
Medical Director of Pain Management, Marin General San Francisco Department of Public Health,
Hospital, Greenbrae, California San Francisco, California
ramonaidu@me.com susan.philip@sfdph.org
Palliative Care & Pain Management Spirochetal Infections

x CMDT 2019 AUTHORS
Michael Pignone, MD, MPH Joseph H. Rapp, MD

Professor of Medicine; Chair, Department of Medicine, Professor of Surgery, Emeritus, Division of Vascular and
Dell Medical School, The University of Texas at Austin Endovascular Surgery, University of California,
pignone@austin.utexas.edu San Francisco
Disease Prevention & Health Promotion Joseph.Rapp@ucsf.edu
Blood Vessel & Lymphatic Disorders
Toya Pratt, MD
Clinical Fellow, Female Pelvic Medicine & Reconstructive Paul Riordan-Eva, FRCOphth
Surgery, Kaiser Permanente-University of California, Consultant Ophthalmologist, King’s College Hospital,
San Francisco London, United Kingdom
References paulreva@doctors.org.uk
Disorders of the Eyes & Lids
Niall T. Prendergast, MD
Instructor in Medicine, Barnes-Jewish Hospital, Scott W. Roberts, MD
Washington University School of Medicine, Saint Associate Professor, Obstetrics and Gynecology,
Louis, Missouri; Fellow, Division of Pulmonary, Allergy University of Texas Southwestern Medical Center,
and Critical Care Medicine, Department of Medicine, Dallas, Texas
University of Pittsburgh School of Medicine. scott.roberts@utsouthwestern.edu
Pittsburgh, Pennsylvania Obstetrics & Obstetric Disorders
prendergastn@wustl.edu
Pulmonary Disorders Patricia A. Robertson, MD
Professor, Department of Obstetrics, Gynecology, and
Thomas J. Prendergast, MD Reproductive Sciences, University of California,
Clinical Professor of Medicine, Oregon Health & Science San Francisco
University; Pulmonary Critical Care Section Chief, Patricia.Robertson@ucsf.edu
Portland Veterans Affairs Health Care System, Lesbian & Bisexual Women’s Health (in Chapter 42)
Portland, Oregon
thomas.prendergast@va.gov Vanessa L. Rogers, MD
Pulmonary Disorders Associate Professor, Obstetrics and Gynecology,
University of Texas Southwestern Medical Center,
Reed E. Pyeritz, MD, PhD Dallas, Texas
William Smilow Professor of Medicine and Genetics, vanessa.rogers@utsouthwestern.edu
Raymond and Ruth Perelman School of Medicine of Obstetrics & Obstetric Disorders
the University of Pennsylvania, Philadelphia
reed.pyeritz@uphs.upenn.edu Philip J. Rosenthal, MD
Genetic & Genomic Disorders Professor, Department of Medicine, University of
California, San Francisco; Associate Chief, Division of
Michael W. Rabow, MD, FAAHPM HIV, Infectious Diseases, and Global Health,
Helen Diller Family Chair in Palliative Care, Professor of Zuckerberg San Francisco General Hospital
Clinical Medicine and Urology, Division of Palliative philip.rosenthal@ucsf.edu
Medicine, Department of Medicine; Director, Symptom Protozoal & Helminthic Infections
Management Service, Helen Diller Family
Comprehensive Cancer Center, University of Charles J. Ryan, MD
California, San Francisco Professor of Clinical Medicine and Urology; Thomas
Mike.Rabow@ucsf.edu Perkins Distinguished Professor in Cancer Research;
Palliative Care & Pain Management Program Leader, Genitourinary Medical Oncology,
Helen Diller Family Comprehensive Cancer Center,
Leena T. Rahmat, MD University of California, San Francisco
Clinical Fellow, Department of Hematology and Bone charles.ryan@ucsf.edu
Marrow Transplantation, University of California, Cancers of the Genitourinary Tract (in Chapter 39)
San Francisco
References René Salazar, MD
Professor of Medical Education, Assistant Dean for
Kristin S. Raj, MD Diversity, Dell Medical School, The University of Texas
Clinical Instructor, Department of Psychiatry and at Austin
Behavioral Sciences, Stanford University School of rene.salazar@austin.utexas.edu
Medicine, Stanford, California Disease Prevention & Health Promotion
kraj@stanford.edu
Psychiatric Disorders

CMDT 2019 xi
Joshua S. Schindler, MD Michael Sutters, MD, MRCP (UK)

Associate Professor, Department of Otolaryngology, Attending Nephrologist, Virginia Mason Medical Center,
Oregon Health & Science University, Portland, Oregon; Seattle, Washington; Affiliate Assistant Professor of
Medical Director, OHSU-Northwest Clinic for Voice Medicine, Division of Nephrology, University of
and Swallowing Washington School of Medicine, Seattle, Washington
schindlj@ohsu.edu michael.sutters@vmmc.org
Ear, Nose, & Throat Disorders Systemic Hypertension
Brian S. Schwartz, MD Philip Tiso

Associate Professor, Division of Infectious Diseases, Principal Editor, Division of General Internal Medicine,
Department of Medicine, University of California, University of California, San Francisco
San Francisco References
brian.schwartz@ucsf.edu
Bacterial & Chlamydial Infections Judith Walsh, MD, MPH
Professor of Clinical Medicine, Division of General
Rachel K. Scott MD, MPH, FACOG Internal Medicine, Women’s Health Center of
Scientific Director of Women’s Health Research, MedStar Excellence, University of California, San Francisco
Health Research Institute Director, Women’s Center for Judith.Walsh@ucsf.edu
Positive Living, MedStar Washington Hospital Center, CMDT Online—Women’s Health Issues
Department of Women’s and Infants’ Services; Assistant
Professor of Obstetrics and Gynecology, Georgetown Thomas J. Walsh, MD, MS
University School of Medicine, Washington, D.C. Associate Professor, Department of Urology, University of
Rachel.K.Scott@Medstar.net Washington School of Medicine, Seattle, Washington
Gynecologic Disorders walsht@uw.edu
Urologic Disorders
Wayne X. Shandera, MD
Assistant Professor, Department of Internal Medicine, Sunny Wang, MD
Baylor College of Medicine, Houston, Texas Assistant Clinical Professor of Medicine, Division of
shandera@bcm.tmc.edu Hematology/Oncology, University of California,
Viral & Rickettsial Infections San Francisco; San Francisco Veterans Affairs Health
Care System
Samuel A. Shelburne, III, MD, PhD sunny.wang@ucsf.edu
Associate Professor, Department of Infectious Diseases Lung Cancer (in Chapter 39)
and Department of Genomic Medicine, The University
of Texas MD Anderson Cancer Center, Houston, Texas Nolan Williams, MD
sshelburne@mdanderson.org Instructor; Director, Brain Stimulation Laboratory,
Mycotic Infections Department of Psychiatry, Stanford University School
of Medicine, Stanford, California
Kanade Shinkai, MD, PhD nolanw@stanford.edu
Associate Professor, Department of Dermatology, Psychiatric Disorders
Kanade.Shinkai@ucsf.edu CAPT Jason Woo, MD, MPH, FACOG
Dermatologic Disorders Medical Officer, Office of Generic Drugs, Center for Drug
Evaluation and Research, U.S. Food and Drug
Scott Steiger, MD Administration, Silver Spring, Maryland
Associate Professor of Clinical Medicine and Psychiatry, woojjmd@gmail.com
Division of General Internal Medicine, Department of Gynecologic Disorders
Medicine, University of California, San Francisco;
Deputy Medical Director, Opiate Treatment Outpatient Tyler Woodell, MD
Program, Division of Substance Abuse and Addiction Fellow, Division of Nephrology, Oregon Health & Science
Medicine, Department of Psychiatry, Zuckerberg University, Portland Oregon
San Francisco General Hospital woodell@ohsu.edu
scott.steiger@ucsf.edu Kidney Disease
Palliative Care & Pain Management
Wanning Zhao, MD
Resident Physician, Department of Otolaryngology—Head
& Neck Surgery, University of California, San Francisco
References


Preface
Current Medical Diagnosis & Treatment 2019 (CMDT 2019) is the 58th edition of this single-source reference for
practitioners in both hospital and ambulatory settings. The book emphasizes the practical features of clinical diagnosis and
patient management in all fields of internal medicine and in specialties of interest to primary care practitioners and to
subspecialists who provide general care.
Our students have inspired us to look at issues of race and justice, which surely impact people’s health. We have therefore
reviewed the content of our work to ensure that it contains the dignity and equality that every patient deserves.
INTENDED AUDIENCE FOR CMDT

House officers, medical students, and all other health professions students will find the descriptions of diagnostic and
therapeutic modalities, with citations to the current literature, of everyday usefulness in patient care.
Internists, family physicians, hospitalists, nurse practitioners, physician assistants, and all primary care providers will
appreciate CMDT as a ready reference and refresher text. Physicians in other specialties, pharmacists, and dentists will find
the book a useful basic medical reference text. Nurses, nurse practitioners, and physician assistants will welcome the format
and scope of the book as a means of referencing medical diagnosis and treatment.
Patients and their family members who seek information about the nature of specific diseases and their diagnosis and
treatment may also find this book to be a valuable resource.
NEW IN THIS EDITION OF CMDT

• New color figures throughout the book
• Rewritten section on pain management at the end of life
• Updated American College of Cardiology/American Heart Association (ACC/AHA) guidelines for treatment of
valvular heart disease
• ACC consensus document providing decision pathway for use of transcatheter aortic valve replacement
• Extensively revised sections on long QT syndrome; AV block; and sinus arrhythmia, bradycardia, and tachycardia
• Rewritten section on atrial tachycardia
• Substantial revision of ventricular tachycardia management
• New algorithms for managing mitral regurgitation and heart failure with reduced ejjection fraction
• New table outlining management strategies for women with valvular heart disease, complex congenital heart disease,
pulmonary hypertension, aortopathy, and dilated cardiomyopathy
• New ACC/AHA and Hypertension Canada blood pressure guidelines
• New table outlining blood pressure values across a range of measurement methods (ie, home and ambulatory
monitoring)
• New table comparing blood pressure treatment thresholds and targets in the 2017 ACC/AHA guidelines with the 2017
Hypertension Canada guidelines
• New FDA-approved medications for relapsing or refractory forms of leukemia
• Rewritten section on monoclonal gammopathy of uncertain significance
• New FDA-approved direct-acting oral anticoagulant
• Information regarding commercially available freeze-dried capsule fecal formulation for treatment of recurrent and
refractory Clostridium difficile infection
• New FDA-approved medications for treatment of breast cancer
• Cancer Care Ontario and American Society of Clinical Oncology jointly published guidelines outlining adjuvant
therapy plan for postmenopausal breast cancer patients
• Substantial revision of the targeted therapies for hormone receptor–positive metastatic breast cancer
• American College of Obstetricians and Gynecologists support for considering use of low-dose aspirin to prevent
preeclampsia
xiii

xiv CMDT 2019 PREFACE
• Revised recommendations for treating hepatitis C virus–associated kidney disease

• New chronic tubulointerstitial disease called Mesoamerican nephropathy
• Detailed discussion of available treatment options for refractory trigeminal neuralgia
• New classification of epilepsy
• Updated information about treating spinal muscular atrophy
• Substantial revision of Psychiatric Disorders chapter
• New section on incidentally discovered adrenal masses
• Updated treatment section for classic Turner syndrome
• New FDA-approved integrase inhibitor for treatment of HIV-1 infection
• Extensive revision of Viral & Rickettsial Infections chapter
• New FDA-approved medication for gastric adenocarcinoma
• New colon cancer screening recommendations from the US Multi-Society Task Force
OUTSTANDING FEATURES OF CMDT

• Medical advances up to time of annual publication
• Detailed presentation of primary care topics, including gynecology, obstetrics, dermatology, ophthalmology,
otolaryngology, psychiatry, neurology, toxicology, urology, geriatrics, orthopedics, women’s health, preventive medicine,
and palliative care
• Concise format, facilitating efficient use in any practice setting
• More than 1000 diseases and disorders
• Annual update on HIV/AIDS and other newly emerging infections
• Specific disease prevention information
• Easy access to medication dosages, with trade names indexed and costs updated in each edition
• Recent references, with unique identifiers (PubMed, PMID numbers) for rapid downloading of article abstracts and, in
some instances, full-text reference articles
E-CHAPTERS, CMDT ONLINE, & AVAILABLE APPS

E-Chapters mentioned in the table of contents can be accessed at www.AccessMedicine.com/CMDT. The seven online-only
chapters available without need for subscription at www.AccessMedicine.com/CMDT include
• Anti-Infective Chemotherapeutic & Antibiotic Agents
• Diagnostic Testing & Medical Decision Making
• Information Technology in Patient Care
• Integrative Medicine
• Podiatric Disorders
• Women’s Health Issues
• Appendix: Therapeutic Drug Monitoring & Laboratory Reference Intervals, & Pharmacogenetic Testing
Institutional or individual subscriptions to AccessMedicine will also have full electronic access to CMDT 2019.
Subscribers to CMDT Online receive full electronic access to CMDT 2019 as well as
• An expanded, dedicated media gallery
• Quick Medical Diagnosis & Treatment (QMDT)—a concise, bulleted version of CMDT 2019
• Guide to Diagnostic Tests—for quick reference to the selection and interpretation of commonly used diagnostic tests
• CURRENT Practice Guidelines in Primary Care—delivering concise summaries of the most relevant guidelines in

primary care
• Diagnosaurus—consisting of 1000+ differential diagnoses
CMDT 2019, QMDT, Guide to Diagnostic Tests, and Diagnosaurus are also available as individual apps for your smartphone
or tablet and can be found in the Apple App Store and Google Play.

CMDT 2019 xv
SPECIAL RECOGNITION
After preparing his annual contribution for this 2019 edition of CMDT, Dr. Paul Riordan-Eva announced his retirement
from the book. Dr. Riordan-Eva has contributed each year to CMDT for 30 years (since 1989). In addition, he has
contributed to Vaughan & Asbury’s General Ophthalmology since 1989 and has been
its senior editor since 2004.
Dr. Riordan-Eva has had a distinguished career in ophthalmology. He studied at
Cambridge University and St. Thomas Hospital Medical School, London. He then
pursued his ophthalmology training in London, followed by a Fellowship at the
Proctor Foundation in San Francisco. Dr. Riordan-Eva’s first consultant appointment
in 1995 was as Consultant Neuro-Ophthalmologist at Moorfields Eye Hospital and
the National Hospital for Neurology and Neurosurgery. His work there was
combined with Consultant Clinical Scientist at the Medical Research Council Human
Movement and Balance Unit, researching brainstem control of eye movements. In
1999, Dr. Riordan-Eva moved to King’s College Hospital, London, to set up the neuro-
ophthalmology service in the regional neurosciences center. His publications include
46 peer-reviewed original papers and 13 reviews. Dr. Riordan-Eva retired from
clinical practice in 2017. Currently, he is the Chairman of the Medical Defence Union,
the leading medical indemnity provider in the United Kingdom.
On behalf of our readers and the entire staff at McGraw-Hill Education, we send
our warmest congratulations to Paul for his retirement. As his editors, we offer our
heartfelt gratitude for his 30 years of contribution to CMDT. We will sorely miss
working with him each year. Felicitations, Paul!
ACKNOWLEDGMENTS
We wish to thank our associate authors for participating once again in the annual updating of this important book. We are
especially grateful to Natalie J.M. Dailey Garnes, MD, MPH, C. Diana Nicoll, MD, PhD, MPA, and Suzanne Watnick, MD,
who are leaving CMDT this year. We have all benefited from their clinical wisdom and commitment.
Many students and physicians also have contributed useful suggestions to this and previous editions, and we are grateful.
We continue to welcome comments and recommendations for future editions in writing or via electronic mail. The editors’
e-mail addresses are below and author e-mail addresses are included in the Authors section.
Maxine A. Papadakis, MD Michael W. Rabow, MD

Maxine.Papadakis@ucsf.edu Mike.Rabow@ucsf.edu
Stephen J. McPhee, MD San Francisco, California
Stephen.McPhee@ucsf.edu


From inability to let well alone; from too much zeal for the new and
contempt for what is old; from putting knowledge before wisdom,
science before art and cleverness before common sense; from treating
patients as cases; and from making the cure of the disease more
grievous than the endurance of the same, Good Lord, deliver us.
—Sir Robert Hutchison


CMDT 2019 1
1
Disease Prevention &
Health Promotion
Michael Pignone MD, MPH1
René Salazar, MD
º Patient reasons for nonadherence include simple

GENERAL APPROACH TO THE PATIENT
º
forgetfulness, being away from home, being busy, and
The medical interview serves several functions. It is used to changes in daily routine. Other reasons include psychi-
collect information to assist in diagnosis (the “history” of atric disorders (depression or substance misuse),
the present illness), to understand patient values, to assess uncertainty about the effectiveness of treatment, lack of
and communicate prognosis, to establish a therapeutic knowledge about the consequences of poor adherence,
relationship, and to reach agreement with the patient about regimen complexity, and treatment side effects. The rising
further diagnostic procedures and therapeutic options. It costs of medications, including generic drugs, and the
also serves as an opportunity to influence patient behavior, increase in patient cost-sharing burden, has made adher-
such as in motivational discussions about smoking cessa- ence even more difficult, particularly for those with lower
tion or medication adherence. Interviewing techniques incomes.
that avoid domination by the clinician increase patient Patients seem better able to take prescribed medica-
involvement in care and patient satisfaction. Effective clini- tions than to adhere to recommendations to change their
cian-patient communication and increased patient involve- diet, exercise habits, or alcohol intake or to perform vari-
ment can improve health outcomes. ous self-care activities (such as monitoring blood glucose
levels at home). For short-term regimens, adherence to
» Patient Adherence medications can be improved by giving clear instructions.
»
Writing out advice to patients, including changes in medi-
For many illnesses, treatment depends on difficult funda-
cation, may be helpful. Because low functional health
mental behavioral changes, including alterations in diet,
literacy is common (almost half of English-speaking US
taking up exercise, giving up smoking, cutting down drink-
patients are unable to read and understand standard
ing, and adhering to medication regimens that are often
health education materials), other forms of communica-
complex. Adherence is a problem in every practice; up to
tion—such as illustrated simple text, videotapes, or oral
50% of patients fail to achieve full adherence, and one-third
instructions—may be more effective. For non–English-
never take their medicines. Many patients with medical
speaking patients, clinicians and health care delivery sys-
problems, even those with access to care, do not seek appro-
tems can work to provide culturally and linguistically
priate care or may drop out of care prematurely. Adherence
appropriate health services.
rates for short-term, self-administered therapies are higher
To help improve adherence to long-term regimens, cli-
than for long-term therapies and are inversely correlated
nicians can work with patients to reach agreement on the
with the number of interventions, their complexity and
goals for therapy, provide information about the regimen,
cost, and the patient’s perception of overmedication.
ensure understanding by using the “teach-back” method,
As an example, in HIV-infected patients, adherence to
counsel about the importance of adherence and how to
antiretroviral therapy is a crucial determinant of treatment
organize medication-taking, reinforce self-monitoring,
success. Studies have unequivocally demonstrated a close
provide more convenient care, prescribe a simple dosage
relationship between patient adherence and plasma HIV
regimen for all medications (preferably one or two doses
RNA levels, CD4 cell counts, and mortality. Adherence
daily), suggest ways to help in remembering to take doses
levels of more than 95% are needed to maintain virologic
(time of day, mealtime, alarms) and to keep appoint-
suppression. However, studies show that over 60% of
ments, and provide ways to simplify dosing (medication
patients are less than 90% adherent and that adherence
boxes). Single-unit doses supplied in foil wrappers can
tends to decrease over time.
increase adherence but should be avoided for patients
1
Dr. Pignone is a former member of the US Preventive Services who have difficulty opening them. Medication boxes with
Task Force (USPSTF). The views expressed in this chapter are his compartments (eg, Medisets) that are filled weekly are
and Dr. Salazar’s and not necessarily those of the USPSTF. useful. Microelectronic devices can provide feedback to
CMDT19_Ch01_p0001-p0019.indd 1 05/07/18 2:04 PM

2 CMDT 2019 C 1
hapter
show patients whether they have taken doses as scheduled Choudhry NK et al. Improving adherence to therapy and clinical
or to notify patients within a day if doses are skipped. outcomes while containing costs: opportunities from the
Reminders, including cell phone text messages, are another greater use of generic medications: best practice advice from
effective means of encouraging adherence. The clinician the Clinical Guidelines Committee of the American College of
can also enlist social support from family and friends, Physicians. Ann Intern Med. 2016 Jan 5;164(1):41–9. [PMID:
recruit an adherence monitor, provide a more convenient 26594818]
Thakkar J et al. Mobile telephone text messaging for medication
care environment, and provide rewards and recognition for adherence in chronic disease: a meta-analysis. JAMA Intern
the patient’s efforts to follow the regimen. Collaborative Med. 2016 Mar;176(3):340–9. [PMID: 26831740]
programs that utilize pharmacists to help ensure adherence
are also effective.
Adherence is also improved when a trusting doctor- º
HEALTH MAINTENANCE & DISEASE
º
patient relationship has been established and when
patients actively participate in their care. Clinicians can
PREVENTION
improve patient adherence by inquiring specifically about Preventive medicine can be categorized as primary, sec-
the behaviors in question. When asked, many patients ondary, or tertiary. Primary prevention aims to remove or
admit to incomplete adherence with medication regimens, reduce disease risk factors (eg, immunization, giving up or
with advice about giving up cigarettes, or with engaging not starting smoking). Secondary prevention techniques
only in “safer sex” practices. Although difficult, sufficient promote early detection of disease or precursor states (eg,
time must be made available for communication of health routine cervical Papanicolaou screening to detect carci-
messages. noma or dysplasia of the cervix). Tertiary prevention mea-
Medication adherence can be assessed generally with sures are aimed at limiting the impact of established
a single question: “In the past month, how often did you disease (eg, partial mastectomy and radiation therapy to
take your medications as the doctor prescribed?” Other remove and control localized breast cancer).
ways of assessing medication adherence include pill Tables 1–1 and 1–2 give leading causes of death in the
counts and refill records; monitoring serum, urine, or United States and estimates of deaths from preventable
saliva levels of drugs or metabolites; watching for causes. Recent data suggest increased rates of death, mainly
appointment nonattendance and treatment nonresponse; from suicide and substance misuse, particularly among less
and assessing predictable drug effects, such as weight well-educated middle-aged white adults.
changes with diuretics or bradycardia from beta-blockers. Many effective preventive services are underutilized,
In some conditions, even partial adherence, as with drug and few adults receive all of the most strongly recom-
treatment of hypertension and diabetes mellitus, improves mended services. Several methods, including the use of
outcomes compared with nonadherence; in other cases, provider or patient reminder systems (including interac-
such as HIV antiretroviral therapy or tuberculosis treat- tive patient health records), reorganization of care environ-
ment, partial adherence may be worse than complete ments, and possibly provision of financial incentives to
nonadherence. clinicians (though this remains controversial), can increase
» Guiding Principles of Care

utilization of preventive services, but such methods have
not been widely adopted.
»
Ethical decisions are often called for in medical practice, at
both the “micro” level of the individual patient-clinician
relationship and at the “macro” level of the allocation of Table 1–1. Leading causes of death in the United States,
resources. Ethical principles that guide the successful 2015.
approach to diagnosis and treatment are honesty, benefi-
cence, justice, avoidance of conflict of interest, and the Category Estimate
pledge to do no harm. Increasingly, Western medicine
All causes 2,712,630
involves patients in important decisions about medical
care, eg, which colorectal screening test to obtain or which 1. Diseases of the heart 633,842
modality of therapy for breast cancer or how far to proceed 2. Malignant neoplasms 595,930
with treatment of patients who have terminal illnesses (see 3. Chronic lower respiratory diseases 155,041
Chapter 5).
The clinician’s role does not end with diagnosis and 4. Unintentional injuries 146,571
treatment. The importance of the empathic clinician in 5. Cerebrovascular diseases 140,323
helping patients and their families bear the burden of seri- 6. Alzheimer disease 110,561
ous illness and death cannot be overemphasized. “To cure
7. Diabetes mellitus 79,535
sometimes, to relieve often, and to comfort always” is a
French saying as apt today as it was five centuries ago—as is 8. Influenza and pneumonia 57,062
Francis Peabody’s admonition: “The secret of the care of the 9. Nephritis, nephrotic syndrome, and 49,959

patient is in caring for the patient.” Training to improve nephrosis
mindfulness and enhance patient-centered communication 10. Intentional self-harm (suicide) 44,193
increases patient satisfaction and may also improve clini-
cian satisfaction. Data from National Center for Health Statistics 2016.
CMDT19_Ch01_p0001-p0019.indd 2 05/07/18 2:04 PM

DISEASE PREVENTION & HEALTH PROMOTION CMDT 2019 3
Table 1–2. Deaths from all causes attributable to common preventable risk factors. (Numbers given in the thousands.)
Risk Factor Male (95% CI) Female (95% CI) Both Sexes (95% CI)
Tobacco smoking 248 (226–269) 219 (196–244) 467 (436–500)
High blood pressure 164 (153–175) 231 (213–249) 395 (372–414)
Overweight–obesity (high BMI) 114 (95–128) 102 (80–119) 216 (188–237)
Physical inactivity 88 (72–105) 103 (80–128) 191 (164–222)
High blood glucose 102 (80–122) 89 (69–108) 190 (163–217)
High LDL cholesterol 60 (42–70) 53 (44–59) 113 (94–124)
High dietary salt (sodium) 49 (46–51) 54 (50–57) 102 (97–107)
Low dietary omega-3 fatty acids (seafood) 45 (37–52) 39 (31–47) 84 (72–96)
High dietary trans fatty acids 46 (33–58) 35 (23–46) 82 (63–97)
Alcohol use 45 (32–49) 20 (17–22) 64 (51–69)
Low intake of fruits and vegetables 33 (23–45) 24 (15–36) 58 (44–74)
Low dietary polyunsaturated fatty acids 9 (6–12) 6 (3–9) 15 (11–20)
(in place of saturated fatty acids)
BMI, body mass index; CI, confidence interval; LDL, low-density lipoprotein.
Note: Numbers of deaths cannot be summed across categories.
Used, with permission, from Danaei G et al. The preventable causes of death in the United States: comparative risk assessment of dietary,
lifestyle, and metabolic risk factors. PLoS Med. 2009 Apr 28;6(4):e1000058.
from vaccine-preventable diseases, such as hepatitis A,

Case A et al. Rising morbidity and mortality in midlife among
white non-Hispanic Americans in the 21st century. Proc Natl hepatitis B, influenza, and pneumococcal infections, con-
Acad Sci U S A. 2015 Dec 8;112(49):15078–83. [PMID: tinue to occur among adults. Increases in the number of
26575631] vaccine-preventable diseases in the United States highlight
Forman-Hoffman VL et al. Disability status, mortality, and lead- the need to understand the association of vaccine refusal
ing causes of death in the United States community popula- and the epidemiology of these diseases.
tion. Med Care. 2015 Apr;53(4):346–54. [PMID: 25719432] Evidence suggests annual influenza vaccination is safe
García MC et al. Potentially preventable deaths among the five
leading causes of death—United States, 2010 and 2014. and effective with potential benefit in all age groups, and
MMWR Morb Mortal Wkly Rep. 2016 Nov 18;65(45):1245–55. the Advisory Committee on Immunization Practices
[PMID: 27855145] (ACIP) recommends routine influenza vaccination for all
Levine DM et al. The quality of outpatient care delivered to persons aged 6 months and older, including all adults.
adults in the United States, 2002 to 2013. JAMA Intern Med. When vaccine supply is limited, certain groups should be
2016 Dec 1;176(12):1778–90. [PMID: 27749962] given priority, such as adults 50 years and older, individuals
Ma J et al. Temporal trends in mortality in the United States,
1969–2013. JAMA. 2015 Oct 27;314(16):1731–9. [PMID: with chronic illness or immunosuppression, and pregnant
26505597] women. An alternative high-dose inactivated vaccine is
Murphy SL et al. Deaths: final data for 2015. National Vital available for adults 65 years and older. Adults 65 years and
Statistics Reports. Hyattsville, MD. 2017 Nov 27;66(6):1–76. older can receive either the standard-dose or high-dose
National Center for Health Statistics. Health, United States, vaccine, whereas those younger than 65 years should
2015: with special feature on racial and ethnic health dispari- receive a standard-dose preparation.
ties. Hyattsville, MD. 2016 May. [PMID: 27308685]
The ACIP recommends two doses of measles, mumps,
and rubella (MMR) vaccine in adults at high risk for expo-
PREVENTION OF INFECTIOUS DISEASES sure and transmission (eg, college students, health care
workers). Otherwise, one dose is recommended for adults
Much of the decline in the incidence and fatality rates of aged 18 years and older. Physician documentation of dis-
infectious diseases is attributable to public health mea- ease is not acceptable for evidence of MMR immunity.
sures—especially immunization, improved sanitation, and Routine use of 13-valent pneumococcal conjugate vac-
better nutrition. cine (PCV13) is recommended among adults aged 65 and
Immunization remains the best means of preventing older. Individuals 65 years of age or older who have never
many infectious diseases. Recommended immunization received a pneumococcal vaccine should first receive
schedules for children and adolescents can be found PCV13 followed by a dose of 23-valent pneumococcal
online at http://www.cdc.gov/vaccines/schedules/hcp/ polysaccharide vaccine (PPSV23) 6–12 months later. Indi-
child-adolescent.html, and the schedule for adults is at viduals who have received more than one dose of PPSV23
http://www.cdc.gov/vaccines/schedules/hcp/adult.html should receive a dose of PCV13 more than 1 year after the
(see also Chapter 30). Substantial morbidity and mortality last dose of PPSV23 was administered.
CMDT19_Ch01_p0001-p0019.indd 3 05/07/18 2:04 PM

4 CMDT 2019 C 1
hapter
The ACIP recommends routine use of a single dose of vitro T-cell interferon-gamma release in response to two
tetanus, diphtheria, and 5-component acellular pertussis antigens (one, the enzyme-linked immunospot [ELISpot],
vaccine (Tdap) for adults aged 19–64 years to replace the [T-SPOT.TB], and the other, a quantitative ELISA [Quan-
next booster dose of tetanus and diphtheria toxoids tiFERON-TBGold] test). These T-cell–based assays have
vaccine (Td). Due to increasing reports of pertussis in the an excellent specificity that is higher than tuberculin skin
United States, clinicians may choose to give Tdap to per- testing in BCG-vaccinated populations.
sons aged 65 years and older (particularly to those who The US Preventive Services Task Force (USPSTF) rec-
might risk transmission to at-risk infants who are most ommends behavioral counseling for adolescents and adults
susceptible to complications, including death), despite lim- who are sexually active and at increased risk for sexually
ited published data on the safety and efficacy of the vaccine transmitted infections. Sexually active women aged 24 years
in this age group. or younger and older women who are at increased risk for
Both hepatitis A vaccine and immune globulin pro- infection should be screened for chlamydia. Screening
vide protection against hepatitis A; however, administra- HIV-positive men or men who have sex with men for
tion of immune globulin may provide a modest benefit syphilis every 3 months is associated with improved syphilis
over vaccination in some settings. Hepatitis B vaccine detection.
administered as a three-dose series is recommended for all HIV infection remains a major infectious disease prob-
children aged 0–18 years and high-risk individuals (ie, lem in the world. The CDC recommends universal HIV
health care workers, injection drug users, people with end- screening of all patients aged 13–64, and the USPSTF rec-
stage renal disease). Adults with diabetes are also at ommends that clinicians screen adolescents and adults
increased risk for hepatitis B infection. The ACIP recom- aged 15 to 65 years. Clinicians should integrate biomedical
mends vaccination for hepatitis B in diabetic patients aged and behavioral approaches for HIV prevention. In addition
19–59 years. The hepatitis B vaccine should also be consid- to reducing sexual transmission of HIV, initiation of anti-
ered in diabetic persons age 60 and older. retroviral therapy reduces the risk for AIDS-defining
Human papillomavirus (HPV) virus-like particle events and death among patients with less immunologi-
(VLP) vaccines have demonstrated effectiveness in pre- cally advanced disease.
venting persistent HPV infections and thus may impact the Daily preexposure prophylaxis (PrEP) with the fixed-
rate of cervical intraepithelial neoplasia (CIN) II–III. The dose combination of tenofovir disoproxil 300 mg and
ACIP recommends routine HPV vaccination (with three emtricitabine 200 mg (Truvada) should be considered for
doses of the 9-valent [9vHPV], 4-valent [4vHPV], or people who are HIV-negative but at substantial of risk for
2-valent [2vHPV] vaccine) for girls aged 11–12 years. The HIV infection. Studies of men who have sex with men sug-
ACIP also recommends that all unvaccinated girls and gest that PrEP is very effective in reducing the risk of con-
women through age 26 years receive the three-dose HPV tracting HIV. Patients taking PrEP should be encouraged
vaccination. Studies suggest that one dose of vaccine may to use other prevention strategies, such as consistent con-
be as effective as three. The ACIP also recommends the dom use and choosing less risky sexual behaviors (eg, oral
routine vaccination with three doses of the 4vHPV or sex), to maximally reduce their risk. Postexposure prophy-
9vHPV vaccine for boys aged 11 or 12 years, males through laxis (PEP) with combinations of antiretroviral drugs is
age 21 years, and men who have sex with men and immu- widely used after occupational and nonoccupational con-
nocompromised men (including those with HIV infec- tact, and may reduce the risk of transmission by approxi-
tion) through age 26 years. Vaccination of males with mately 80%. PEP should be initiated within 72 hours of
HPV may lead to indirect protection of women by reducing exposure.
transmission of HPV and may prevent anal intraepithelial In immunocompromised patients, live vaccines are
neoplasia and squamous cell carcinoma in men who have contraindicated, but many killed or component vaccines
sex with men. are safe and recommended. Asymptomatic HIV-infected
Persons traveling to countries where infections are patients have not shown adverse consequences when given
endemic should take the precautions described in Chapter live MMR and influenza vaccinations as well as tetanus,
30 and at http://wwwnc.cdc.gov/travel/destinations/list. hepatitis B, H influenza type b, and pneumococcal vaccina-
Immunization registries—confidential, population-based, tions—all should be given. However, if poliomyelitis
computerized information systems that collect vaccination immunization is required, the inactivated poliomyelitis
data about all residents of a geographic area—can be used vaccine is indicated. In symptomatic HIV-infected patients,
to increase and sustain high vaccination coverage. live-virus vaccines, such as MMR, should generally be
Until recently, the rate of tuberculosis in the United avoided, but annual influenza vaccination is safe.
States had been declining. The Centers for Disease Control Herpes zoster, caused by reactivation from previous
and Prevention (CDC) reports that after 2 decades of prog- varicella zoster virus infection, affects many older adults
ress toward tuberculosis elimination—with annual and people with immune system dysfunction. It can cause
decreases of greater than or equal to 0.2 case per 100,000 postherpetic neuralgia, a potentially debilitating chronic
persons—its incidence in the United States plateaued at pain syndrome. Two vaccines are available for the preven-
approximately 3.0 cases per 100,000 persons during 2013– tion of herpes zoster, a live virus vaccine (Zostavax) and a
2015. Two blood tests, which are not confounded by prior herpes zoster subunit vaccine (HZ/su; Shingrix) (approved
bacillus Calmette-Guérin (BCG) vaccination, have been by the US Food and Drug Administration [FDA] in
developed to detect tuberculosis infection by measuring in October 2017). The ACIP recommends the HZ/su vaccine
CMDT19_Ch01_p0001-p0019.indd 4 05/07/18 2:04 PM

be used for the prevention of herpes zoster and related Several risk factors increase the risk for coronary disease
complications in immunocompetent adults age 50 and and stroke. These risk factors can be divided into those that
older and in individuals who previously received Zostavax. are modifiable (eg, lipid disorders, hypertension, cigarette
The ACIP prefers the use of the new HZ/su vaccine over smoking) and those that are not (eg, age, sex, family history
the older live virus vaccine. of early coronary disease). Impressive declines in age-specific
In May 2015, the World Health Organization reported mortality rates from heart disease and stroke have been
the first local transmission of Zika virus in the Western achieved in all age groups in North America during the
Hemisphere. Zika virus spreads to people primarily past two decades, in large part through improvement of
through mosquito bites but can also spread during sex by a modifiable risk factors: reductions in cigarette smoking,
person infected with Zika to his or her partner. Although improvements in lipid levels, and more aggressive detec-
clinical disease is usually mild, Zika virus infections in tion and treatment of hypertension. This section considers
women infected during pregnancy have been linked to fetal the role of screening for cardiovascular risk and the use of
microcephaly and loss, and newborn and infant blindness effective therapies to reduce such risk. Key recommenda-
and other neurologic problems (see Chapter 32). Pregnant tions for cardiovascular prevention are shown in Table 1–3.
women should consider postponing travel to areas where Guidelines encourage regular assessment of global cardio-
Zika virus transmission is ongoing. vascular risk in adults 40–79 years of age without known
cardiovascular disease.
American Academy of Family Practitioners. ACIP recommends
new herpes zoster subunit vaccine. 2017 Oct 31. http://www Goff DC Jr et al. 2013 ACC/AHA guideline on the assessment of
.aafp.org/news/health-of-the-public/20171031acipmeeting cardiovascular risk: a report of the American College of Car-
.html diology/American Heart Association Task Force on Practice
Basta NE et al. Immunogenicity of a meningococcal B vaccine Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S49–73.
during a university outbreak. N Engl J Med. 2016 Jul 21; [PMID: 24222018]
375(3):220–8. [PMID: 27468058] Gómez-Pardo E et al. A comprehensive lifestyle peer group-
Blackstock OJ et al. A cross-sectional online survey of HIV pre- based intervention on cardiovascular risk factors: the ran-
exposure prophylaxis adoption among primary care physi- domized controlled fifty-fifty program. J Am Coll Cardiol.
cians. J Gen Intern Med. 2017 Jan;32(1):62–70. [PMID: 2016 Feb 9;67(5):476–85. Erratum in: J Am Coll Cardiol. 2016
27778215] Mar 22;67(11):1385. [PMID: 26562047]
Cantor AG et al. Screening for syphilis: updated evidence Jin J. JAMA patient page. Counseling on healthy living to pre-
report and systematic review for the U.S. Preventive Services vent cardiovascular disease in adults without risk factors.
Task Force. JAMA. 2016 Jun 7;315(21):2328–37. [PMID: JAMA. 2017 Jul 11;318(2):210. [PMID: 28697255]
27272584] Kavousi M et al. Comparison of application of the ACC/AHA
Centers for Disease Control and Prevention (CDC). Adult guidelines, Adult Treatment Panel III guidelines, and Euro-
Immunization Schedules: United States, 2016. http://www pean Society of Cardiology guidelines for cardiovascular dis-
.cdc.gov/vaccines/schedules/hcp/adult.html ease prevention in a European cohort. JAMA. 2014 Apr 9;
Centers for Disease Control and Prevention (CDC). Pertussis 311(14):1416–23. [PMID: 24681960]
outbreak trends, 2015. http://www.cdc.gov/pertussis/out- U.S. Preventive Services Task Force. Behavioral counseling to
breaks/trends.html promote a healthful diet and physical activity for cardiovascu-
Centers for Disease Control and Prevention (CDC). HIV/AIDS, lar disease prevention in adults without cardiovascular risk
2017. http://www.cdc.gov/hiv/basics/index.html factors: U.S. Preventive Services Task Force Recommendation
Centers for Disease Control and Prevention (CDC). Zika virus. Statement. JAMA. 2017 Jul 11;318(2):167–74. [PMID:
http://www.cdc.gov/zika/index.html 28697260]
Jin J. JAMA patient page. Screening for syphilis. JAMA. 2016
Jun 7;315(21):2367. [PMID: 27272600]
» Abdominal Aortic Aneurysm

Mayer KH et al. Antiretroviral preexposure prophylaxis: oppor-
tunities and challenges for primary care physicians. JAMA. »
2016 Mar 1;315(9):867–8. [PMID: 26893026]

Phadke VK et al. Association between vaccine refusal and
One-time screening for abdominal aortic aneurysm (AAA)
vaccine-preventable diseases in the United States: a review of by ultrasonography in men aged 65–75 years is associated
measles and pertussis. JAMA. 2016 Mar 15;315(11):1149–58. with a relative reduction in odds of AAA-related mortality
Erratum in: JAMA. 2016 May 17;315(19):2125. [PMID: of almost 50% and possibly a small reduction in all-cause
26978210] mortality. Women do not appear to benefit from screening,
PrEP (preexposure prophylaxis), 2017. http://www.cdc.gov/hiv/ and most of the benefit in men appears to accrue among
basics/prep.html
PEP (postexposure prophylaxis), 2017. http://www.cdc.gov/hiv/
current or former smokers. Screening men aged 65 years
basics//pep.html. and older is highly cost effective.
Sultan B et al. Current perspectives in HIV post-exposure
prophylaxis. HIV AIDS (Auckl). 2014 Oct 24;6:147–58.
[PMID: 25368534] Canadian Task Force on Preventive Health Care. Recommen-
dations on screening for abdominal aortic aneurysm in
primary care. CMAJ. 2017 Sep 11;189(36):E1137–45. [PMID:
PREVENTION OF CARDIOVASCULAR DISEASE 28893876]
Wanhainen A et al; Swedish Aneurysm Screening Study Group
Cardiovascular diseases, including coronary heart disease (SASS). Outcome of the Swedish nationwide abdominal
(CHD) and stroke, represent two of the most important aortic aneurysm screening program. Circulation. 2016 Oct 18;
134(16):1141–8. [PMID: 27630132]
causes of morbidity and mortality in developed countries.
CMDT19_Ch01_p0001-p0019.indd 5 05/07/18 2:04 PM

6 CMDT 2019 C 1
hapter
Table 1–3. Expert recommendations for cardiovascular risk prevention methods: US Preventive Services Task Force
(USPSTF).1
Prevention Method Recommendation/[Year Issued]

Screening for abdominal Recommends one-time screening for AAA by ultrasonography in men aged 65–75 years who have ever
aortic aneurysm (AAA) smoked. (B)
Selectively offer screening for AAA in men aged 65–75 years who have never smoked. (C)
Current evidence is insufficient to assess the balance of benefits and harms of screening for AAA in women
aged 65–75 years who have ever smoked. (I)
Recommends against routine screening for AAA in women who have never smoked.
(D) [2014]
Aspirin use Recommends initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and
colorectal cancer (CRC) in adults aged 50–59 years who have a 10% or greater 10-year CVD risk, are not at
increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose
aspirin daily for at least 10 years. (B)
The decision to initiate low-dose aspirin use for the primary prevention of CVD and CRC in adults aged
60–69 years who have a 10% or greater 10-year CVD risk should be an individual one. Persons who are
not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take
low-dose aspirin daily for at least 10 years are more likely to benefit. Persons who place a higher value on
the potential benefits than the potential harms may choose to initiate low-dose aspirin. (C)
The current evidence is insufficient to assess the balance of benefits and harms of initiating aspirin use for the
primary prevention of CVD and CRC in adults younger than 50 years or older than age 70. (I)
[2016]
Blood pressure screening The USPSTF recommends screening for high blood pressure in adults aged 18 years or older. The USPSTF rec-
ommends obtaining measurements outside of the clinical setting for diagnostic confirmation before start-
ing treatment. (A)
[2015]
Serum lipid screening and The USPSTF recommends that adults without a history of CVD use a low- to moderate-dose statin for the
use of statins for prevention of CVD events and mortality when all of the following criteria are met: (1) they are aged
prevention 40–75 years; (2) they have one or more CVD risk factors (ie, dyslipidemia, diabetes mellitus, hypertension, or
smoking); and (3) they have a calculated 10-year risk of a cardiovascular event of 10% or greater.
Identification of dyslipidemia and calculation of 10-year CVD event risk requires universal lipids screening in
adults aged 40–75 years. See the “Clinical Considerations” section of the USPSTF recommendations2 for more
information on lipids screening and the assessment of cardiovascular risk. (B)
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of
initiating statin use for the primary prevention of CVD events and mortality in adults aged 76 years and older
without a history of heart attack or stroke. (I)
[2016]
Counseling about health- Recommends offering or referring adults who are overweight or obese and have additional CVD risk factors to
ful diet and physical intensive behavioral counseling interventions to promote a healthful diet and physical activity for CVD
activity for CVD prevention. (B)
prevention [2014]
Recommends that primary care professionals individualize the decision to offer or refer adults without obesity
who do not have hypertension, dyslipidemia, abnormal blood glucose levels, or diabetes to behavioral
counseling to promote a healthful diet and physical activity. (C)
[2017]
Screening for diabetes Recommends screening for abnormal blood glucose as part of cardiovascular risk assessment in adults aged
mellitus 40–70 years who are overweight or obese. Clinicians should offer or refer patients with abnormal blood
glucose to intensive behavioral counseling interventions to promote a healthful diet and physical activity. (B)
[2015]
Screening for smoking and Recommends that clinicians ask all adults about tobacco use, advise them to stop using tobacco, and provide
counseling to promote behavioral interventions and US Food and Drug Administration (FDA)–approved pharmacotherapy for
cessation cessation to adults who use tobacco. (A)
[2015]
1
Recommendation A: The USPSTF strongly recommends that clinicians routinely provide the service to eligible patients. (The USPSTF found
good evidence that the service improves important health outcomes and concludes that benefits substantially outweigh harms.)
Recommendation B: The USPSTF recommends that clinicians routinely provide the service to eligible patients. (The USPSTF found at least
fair evidence that the service improves important health outcomes and concludes that benefits substantially outweigh harms.)
Recommendation C: The USPSTF makes no recommendation for or against routine provision of the service.
Recommendation D: The USPSTF recommends against routinely providing the service to asymptomatic patients. (The USPSTF found at
least fair evidence that the service is ineffective or that harms outweigh benefits.)
Recommendation I: The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing the service.
2
http://www.uspreventiveservicestaskforce.org/BrowseRec/Index/browse-recommendations
CMDT19_Ch01_p0001-p0019.indd 6 05/07/18 2:04 PM

» Cigarette Smoking
»
year in the United States are attributable to environmental
Cigarette smoking remains the most important cause of tobacco smoke.
preventable morbidity and early mortality. In 2015, there Smoking cessation reduces the risks of death and of
were an estimated 6.4 million premature deaths in the myocardial infarction in people with coronary artery dis-
world attributable to smoking and tobacco use; smoking is ease; reduces the rate of death and acute myocardial infarc-
the second leading cause of disability adjusted life years tion in patients who have undergone percutaneous
lost. Cigarettes are responsible for one in every five deaths coronary revascularization; lessens the risk of stroke; and is
in the United States. From 2005 to 2009, more than associated with improvement of COPD symptoms. On
480,000 deaths per year (more than 278,000 in men and average, women smokers who quit smoking by age 35 add
more than 201,000 in women) were attributable to smok- about 3 years to their life expectancy, and men add more
ing. Annual cost of smoking-related health care is approxi- than 2 years to theirs. Smoking cessation can increase life
mately $130 billion in the United States, with another expectancy even for those who stop after the age of 65.
$150 billion in productivity losses. Fortunately, US smoking Although tobacco use constitutes the most serious
rates are declining; in 2015, 15.1% of US adults were smok- common medical problem, it is undertreated. Almost 40%
ers. Global direct health care costs from smoking in 2012 of smokers attempt to quit each year, but only 4% are suc-
were estimated at $422 billion, with total costs of over cessful. Persons whose clinicians advise them to quit are
$1.4 trillion. 1.6 times as likely to attempt quitting. Over 70% of smokers
Nicotine is highly addictive, raises brain levels of dopa- see a physician each year, but only 20% of them receive any
mine, and produces withdrawal symptoms on discontinua- medical quitting advice or assistance.
tion. Smokers die 5–8 years earlier than never-smokers. Factors associated with successful cessation include
They have twice the risk of fatal heart disease; 10 times the having a rule against smoking in the home, being older,
risk of lung cancer; and several times the risk of cancers of and having greater education. Several effective interven-
the mouth, throat, esophagus, pancreas, kidney, bladder, tions are available to promote smoking cessation, including
and cervix; a twofold to threefold higher incidence of counseling, pharmacotherapy, and combinations of the
stroke and peptic ulcers (which heal less well than in non- two. The five steps for helping smokers quit are summa-
smokers); a two- to fourfold greater risk of fractures of the rized in Table 1–4.
hip, wrist, and vertebrae; four times the risk of invasive Common elements of supportive smoking cessation
pneumococcal disease; and a twofold increase in cataracts. treatments are reviewed in Table 1–5. A system should be
In the United States, over 90% of cases of chronic obstruc- implemented to identify smokers, and advice to quit should
tive pulmonary disease (COPD) occur among current or be tailored to the patient’s level of readiness to change. All
former smokers. patients trying to quit should be offered pharmacotherapy
Both active smoking and passive smoking are associ- except those with medical contraindications, women who
ated with deterioration of the elastic properties of the aorta are pregnant or breast-feeding, and adolescents. Weight
(increasing the risk of aortic aneurysm) and with progres- gain occurs in most patients (80%) following smoking ces-
sion of carotid artery atherosclerosis. Smoking has also sation. Average weight gain is 2 kg, but for some (10–15%),
been associated with increased risks of leukemia, of colon major weight gain—over 13 kg—may occur. Planning for
and prostate cancers, of breast cancer among postmeno- the possibility of weight gain, and means of mitigating it,
pausal women who are slow acetylators of N-acetyltrans- may help with maintenance of cessation.
ferase-2 enzymes, of osteoporosis, and of Alzheimer Several pharmacologic therapies have been shown to
disease. In cancers of the head and neck, lung, esophagus, be effective in promoting cessation. Nicotine replacement
and bladder, smoking is linked to mutations of the P53 therapy doubles the chance of successful quitting. The
gene, the most common genetic change in human cancer. nicotine patch, gum, and lozenges are available over the
Patients with head and neck cancer who continue to counter and nicotine nasal spray and inhalers by prescrip-
smoke during radiation therapy have lower rates of tion. The sustained-release antidepressant drug bupro-
response than those who do not smoke. Olfaction and taste pion (150–300 mg/day orally) is an effective smoking
are impaired in smokers, and facial wrinkles are increased. cessation agent and is associated with minimal weight
Heavy smokers have a 2.5 greater risk of age-related macu- gain, although seizures are a contraindication. It acts by
lar degeneration. boosting brain levels of dopamine and norepinephrine,
The children of smokers have lower birth weights, are mimicking the effect of nicotine. More recently, vareni-
more likely to be mentally retarded, have more frequent cline, a partial nicotinic acetylcholine-receptor agonist,
respiratory infections and less efficient pulmonary func- has been shown to improve cessation rates; however, its
tion, have a higher incidence of chronic ear infections than adverse effects, particularly its effects on mood, are not
children of nonsmokers, and are more likely to become completely understood and warrant careful consideration.
smokers themselves. In addition, exposure to environmen- No single pharmacotherapy is clearly more effective than
tal tobacco smoke has been shown to increase the risk of others, so patient preferences and data on adverse effects
cervical cancer, lung cancer, invasive pneumococcal dis- should be taken into account in selecting a treatment.
ease, and heart disease; to promote endothelial damage and Combination therapy is more effective than a single phar-
platelet aggregation; and to increase urinary excretion of macologic modality. The efficacy of e-cigarettes in smok-
tobacco-specific lung carcinogens. The incidence of breast ing cessation has not been well evaluated, and some users
cancer may be increased as well. Over 41,000 deaths per may find them addictive.
CMDT19_Ch01_p0001-p0019.indd 7 05/07/18 2:04 PM

8 CMDT 2019 C 1
hapter
Table 1–4. Actions and strategies for the primary care clinician to help patients quit smoking.
Action Strategies for Implementation

Step 1. Ask—Systematically Identify All Tobacco Users at Every Visit
Implement an officewide system that ensures Expand the vital signs to include tobacco use.
that for every patient at every clinic visit, Data should be collected by the health care team.
tobacco-use status is queried and The action should be implemented using preprinted progress note paper that includes
documented1 the expanded vital signs, a vital signs stamp or, for computerized records, an item
assessing tobacco-use status.
Alternatives to the vital signs stamp are to place tobacco-use status stickers on all
patients’ charts or to indicate smoking status using computerized reminder systems.
Step 2. Advise—Strongly Urge All Smokers to Quit
In a clear, strong, and personalized Advice should be
manner, urge every smoker to quit Clear: “I think it is important for you to quit smoking now, and I will help you. Cutting
down while you are ill is not enough.”
Strong: “As your clinician, I need you to know that quitting smoking is the most impor-
tant thing you can do to protect your current and future health.”
Personalized: Tie smoking to current health or illness and/or the social and economic
costs of tobacco use, motivational level/readiness to quit, and the impact of smoking
on children and others in the household.
Encourage clinic staff to reinforce the cessation message and support the patient’s quit
attempt.
Step 3. Attempt—Identify Smokers Willing to Make a Quit Attempt
Ask every smoker if he or she is willing to make a If the patient is willing to make a quit attempt at this time, provide assistance
quit attempt at this time (see step 4).
If the patient prefers a more intensive treatment or the clinician believes more
intensive treatment is appropriate, refer the patient to interventions adminis-
tered by a smoking cessation specialist and follow up with him or her regarding
quitting (see step 5).
If the patient clearly states he or she is not willing to make a quit attempt at this time,
provide a motivational intervention.
Step 4. Assist—Aid the Patient in Quitting
A. Help the patient with a quit plan Set a quit date. Ideally, the quit date should be within 2 weeks, taking patient prefer-
ence into account.
Help the patient prepare for quitting. The patient must:
Inform family, friends, and coworkers of quitting and request understanding and
support.
Prepare the environment by removing cigarettes from it. Prior to quitting, the patient
should avoid smoking in places where he or she spends a lot of time (eg, home, car).
Review previous quit attempts. What helped? What led to relapse?
Anticipate challenges to the planned quit attempt, particularly during the critical first
few weeks.
B. Encourage nicotine replacement therapy except Encourage the use of the nicotine patch or nicotine gum therapy for smoking cessation.
in special circumstances
C. Give key advice on successful quitting Abstinence: Total abstinence is essential. Not even a single puff after the quit date.
Alcohol: Drinking alcohol is highly associated with relapse. Those who stop smoking
should review their alcohol use and consider limiting or abstaining from alcohol use
during the quit process.
Other smokers in the household: The presence of other smokers in the household,
particularly a spouse, is associated with lower success rates. Patients should consider
quitting with their significant others and/or developing specific plans to maintain
abstinence in a household where others still smoke.
D. Provide supplementary materials Source: Federal agencies, including the National Cancer Institute and the Agency for
Health Care Policy and Research; nonprofit agencies (American Cancer Society,
American Lung Association, American Heart Association); or local or state health
departments.
Selection concerns: The material must be culturally, racially, educationally, and age
appropriate for the patient.
Location: Readily available in every clinic office.
(continued )
CMDT19_Ch01_p0001-p0019.indd 8 05/07/18 2:04 PM

Table 1–4. Actions and strategies for the primary care clinician to help patients quit smoking. (continued)
Action Strategies for Implementation

Step 5. Arrange—Schedule Follow-Up Contact
Schedule follow-up contact, either in person Timing: Follow-up contact should occur soon after the quit date, preferably during the
or via telephone first week. A second follow-up contact is recommended within the first month.
Schedule further follow-up contacts as indicated.
Actions during follow-up: Congratulate success. If smoking occurred, review the cir-
cumstances and elicit recommitment to total abstinence. Remind the patient that a
lapse can be used as a learning experience and is not a sign of failure. Identify the
problems already encountered and anticipate challenges in the immediate future.
Assess nicotine replacement therapy use and problems. Consider referral to a more
intense or specialized program.
1
Repeated assessment is not necessary in the case of the adult who has never smoked or not smoked for many years and for whom the
information is clearly documented in the medical record.
Adapted and reproduced, with permission, from The Agency for Health Care Policy and Research. Smoking Cessation Clinical Practice
Guideline. JAMA. 1996 Apr 24;275(16):1270–80. Copyright © 1996 American Medical Association. All rights reserved.
Clinicians should not show disapproval of patients who Individualized or group counseling is very cost effec-
failed to stop smoking or who are not ready to make a quit tive, even more so than in treating hypertension. Smoking
attempt. Thoughtful advice that emphasizes the benefits of cessation counseling by telephone (“quitlines”) and text
cessation and recognizes common barriers to success can messaging–based interventions have both proved effective.
increase motivation to quit and quit rates. An intercurrent An additional strategy is to recommend that any smoking
illness or hospitalization may motivate even the most take place outdoors to limit the effects of passive smoke on
addicted smoker to quit. housemates and coworkers. This can lead to smoking
reduction and quitting.
The clinician’s role in smoking cessation is summarized
Table 1–5. Common elements of supportive smoking in Tables 1–4 and 1–5. Public policies, including higher
treatments. cigarette taxes and more restrictive public smoking laws,
have also been shown to encourage cessation, as have
Component Examples financial incentives directed to patients.
Encouragement of Note that effective cessation treatments
the patient in the are now available. GBD 2015 Risk Factors Collaborators. Global, regional, and
quit attempt Note that half the people who have ever national comparative risk assessment of 79 behavioural, envi-
smoked have now quit. ronmental and occupational, and metabolic risks or clusters of
Communicate belief in the patient’s ability risks, 1990–2015: a systematic analysis for the Global Burden of
to quit. Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1659–724.
[PMID: 27733284]
Communication of Ask how the patient feels about quitting. Goodchild M et al. Global economic cost of smoking-
caring and Directly express concern and a willingness attributable diseases. Tob Control. 2018 Jan;27(1):58–64.
concern to help. [PMID: 28138063]
Be open to the patient’s expression of fears Jamal A et al. Current cigarette smoking among adults—United
of quitting, difficulties experienced, and States, 2005–2015. MMWR Morb Mortal Wkly Rep. 2016
ambivalent feelings. Nov 11;65(44):1205–11. [PMID: 27832052]
Encouragement of Ask about: Martín Cantera C et al. Effectiveness of multicomponent inter-
ventions in primary healthcare settings to promote continu-
the patient to talk Reasons that the patient wants to quit.
ous smoking cessation in adults: a systematic review. BMJ
about the quitting Difficulties encountered while quitting.
Open. 2015 Oct 1;5(10):e008807. [PMID: 26428333]
process Success the patient has achieved. Mons U et al. Impact of smoking and smoking cessation on
Concerns or worries about quitting. cardiovascular events and mortality among older adults:
Provision of basic Inform the patient about: meta-analysis of individual participant data from prospective
information about The nature and time course of cohort studies of the CHANCES Consortium. BMJ. 2015
smoking and withdrawal. Apr 20;350:h1551. [PMID: 25896935]
successful quitting The addictive nature of smoking. Rahman MA et al. E-cigarettes and smoking cessation: evidence
The fact that any smoking (even a single from a systematic review and meta-analysis. PLoS One. 2015
puff) increases the likelihood of full Mar 30;10(3):e0122544. [PMID: 25822251]
Rostron BL et al. Estimation of cigarette smoking-attributable
relapse.
morbidity in the United States. JAMA Intern Med. 2014 Dec;
174(12):1922–8. [PMID: 25317719]
Adapted, with permission, from The Agency for Health Care Policy
Stead LF et al. Combined pharmacotherapy and behavioural
and Research. Smoking Cessation Clinical Practice Guideline.
interventions for smoking cessation. Cochrane Database Syst
JAMA. 1996 Apr 24;275(16):1270–80. Copyright © 1996 American Rev. 2016 Mar 24;3:CD008286. [PMID: 27009521]
Medical Association. All rights reserved.
CMDT19_Ch01_p0001-p0019.indd 9 05/07/18 2:04 PM

Another random document with
no related content on Scribd:
to factions as irreconcilable as Montagues and Capulets, had broken
into civil war on the advent of Queen Joanna as regent; the powerful
family of the Agramonts welcoming her eagerly; while the
Beaumonts, their rivals, out of favour at Court and wild with
jealousy, called hourly upon Charles to avenge their wrongs and his
own. His mother’s will, leaving Navarre to her husband during his
lifetime, had, they declared, been made null and void by the King’s
subsequent remarriage. Not only was it the duty of a son to resist
such unlawful tyranny, but it was folly to refuse with imprisonment
or a poison cup lurking in the background.
The latter argument was convincing; but never was rebellion
undertaken with a heavier heart. The Prince of Viana was a student
and philosopher who, like the Clerk of Oxenford, would have
preferred a shelf of Aristotle’s books at his bed’s head to the richest
robes, or fiddle, or psaltery. The quiet of a monastery library, with its
smell of dust and parchment, thrilled him more than any trumpet-
call; and he would gladly have exchanged his birthright for the
monk’s garb of peace. Fortune willed otherwise, laying on his
shoulders in pitiless mockery the burden of the man of action; and
the result was the defeat that is the usual reward of half-heartedness.
His uncle’s Court at Naples proved a temporary asylum for him in
his subsequent enforced exile; and also the island of Sicily, where he
soon won the affection of the people, and lived in happiness, till
Alfonso’s death awoke him rudely from his day-dreams. He was
overwhelmed by fear for his own future; though, had he been a
different man, he might have wrested away the sceptre of Sicily. In
Aragon itself public opinion had been growing steadily in his favour,
and not only in Navarre were there murmurs at his absence, but up
and down the streets of Barcelona, where the new King was far from
popular, and his haughty Castilian wife an object of dislike.
Prudence dictated to King John a policy of reconciliation; and after
prolonged negotiations the exile returned; but the cold forgiveness
he received from his father and stepmother for the wrongs they had
done him was in marked contrast to the joyous welcome of the
nation. No outward ceremony of a loving father pardoning a prodigal
son could mask the lack of confidence that still denied the Prince his
recognition as rightful heir, and drove him to enter into a secret
alliance with Henry IV. of Castile.
As a result of these negotiations, a marriage was arranged between
Charles and the Infanta Isabel. That the suggested bride was only ten
and the bridegroom nearing forty was a discrepancy not even
considered; and the messengers, who went to Arévalo to report on
the appearance of the Princess, returned to her suitor, as the
chroniclers expressed it, “very well content.” Far different were the
feelings of the King of Aragon, when he learned of the intended
match from his father-in-law, the Admiral of Castile. Isabel had been
destined for his favourite son, and, in spite of the conspiracy to
which he had lent his aid, this alliance still held outwardly good. It
did not need the jealous insinuations of his wife to inflame afresh his
hatred of his first-born; and the Prince of Viana soon found himself
in prison, accused of no less a crime than plotting against his father’s
life.
Unfortunately for King John, popular belief ran in a contrary
direction, and his son’s release was soon demanded by all parts of the
kingdom. In Barcelona, the citizens rose, tore down the royal
standard and took the Governor prisoner. Revolt flamed through the
land; but even more alarming was the sudden declaration of war by
Henry IV., who, taking advantage of the King of Aragon’s
embarrassments, hastily dispatched a force to invade Navarre, where
the Beaumonts were already in the field.
It was a bitter moment for King John. Realizing his critical
position, he agreed to his son’s release; and Charles of Viana passed
in triumph to Barcelona. For once, almost without his intervention,
Fortune had smiled on him; but it proved only a gleam before the
final storm. Three months after he had been publicly proclaimed as
his father’s heir, the news of his sudden illness and death fell on his
supporters with paralysing swiftness.
Nothing, on the other hand, could have been more opportune for
King John and his Queen; and their joy can be gauged by the haste
with which they at once proclaimed the ten-year-old Ferdinand heir
to the throne, demanding from the national Cortes of the three
kingdoms the oath they had so long denied his elder brother. Yet
Queen Joanna’s maternal ambitions were not to be satisfied by this
easy assumption of victory. Charles of Viana dead was to prove an
even more potent foe than Charles of Viana living.
Gentle and unassuming, yet with a melancholy dignity that
accorded well with his misfortunes, he had been accepted as a
national hero by the impulsive Catalans; and after death they
translated the rather negative qualities of his life into the attributes
of a saint. Only the halo of martyrdom was required to fire the
general sympathy into religious fervour; and this rumour supplied
when it maintained that his tragic end had been due to no ordinary
fever, but to poison administered by his stepmother’s orders.
The supposition was not improbable; and the inhabitants of
Barcelona did not trouble to verify the very scanty evidence for the
actual fact. They preferred to rest their accusations on the tales of
those who had seen the Prince’s unhappy spirit, like Hamlet’s father,
walking abroad at midnight demanding revenge. Soon his tomb
became a shrine for pilgrims, and there the last touch of sanctity was
added. He who in life had suffered acutely from ill-health became in
death a worker of miracles, a healer whom no absence of papal
sanction could rob of popular canonization.
The effect upon the public mind was to fan smouldering rebellion
into flames; and when Queen Joanna, having gained the recognition
of her son as heir to the throne by the Aragonese Cortes at Calatayud,
proceeded with the same object to Barcelona, the citizens rose and
drove her from their gates. Only the timely intervention of some
French troops, which Louis XI. had just hired out to King John,
saved her and Ferdinand from falling into the hands of their furious
subjects.
This foreign assistance had contributed not a little to the bitterness
of the Catalans, for the French King had secretly encouraged their
turbulence and disaffection, promising them his support.
“As for peace he could hardly endure the thought of it,” wrote
Philip de Commines of his master, Louis XI. That monarch, like King
John of Aragon, had studied the art of “making trouble,” and in this
truly mediæval pursuit excelled all rivals. It suited his purpose
admirably that his ambitious neighbour should be involved in civil
war, just as it fitted in with his schemes that his troops should
prevent that conflict from going too far. The question was all part
and parcel of his policy of French aggrandizement; the ultimate
object of his design nothing less than the kingdom of Navarre, that
semi-independent state, nominally Spanish, but projecting in a
tantalizing wedge across the Pyrenees.
With Charles of Viana the male line of Evreux had come to an end,
and the claims on Navarre had passed to his sister Blanche. On
Blanche’s death, and Louis in his schemes leapt to the possibility of
such a fortunate accident, the next heir would be Eleanor, her
younger sister, wife of a French Count, Gaston de Foix. It would be
well for France to establish a royal family of her own nationality on
the throne of Navarre. It would be even better for that family to be
closely connected with the House of Valois; and, calculating on the
possibilities, Louis gave his sister Madeleine in marriage to the
young Gaston de Foix, Eleanor’s son and the heir to her ambitions.
It only remained to turn the possible into the certain: to make sure
that Blanche’s claims should not prejudice those of her younger
sister. At this stage in his plans Louis found ready assistance in the
King of Aragon, who included in his hatred of Charles of Viana a still
more unnatural dislike of his gentle elder daughter, whose only sins
were that she had loved her brother in his misfortunes and proved
too good a wife for Henry of Castile.
Thus the tragedy was planned. Blanche must become a nun or pass
into the care of her brother-in-law in some mountain fortress of
Navarre. Then the alternative was whittled away. Nunneries and
vows were not so safe as prison walls and that final silence, whose
only pleading is at God’s judgment-bar. Eleanor, fierce and vindictive
as her father, was determined there should be no loophole of escape,
no half-measures by which she might miss her coveted inheritance.
John of Aragon went himself to fetch his elder daughter to her
fate, assuring her of his intention of marrying her to a French prince,
once they had crossed the Pyrenees; but his victim was not deceived.
Powerless to resist, as she had been in bygone days to help her
brother, Blanche made one last desperate appeal before the gates of
the castle of Orthez closed for ever behind her. On the 30th of April,
1462, she wrote a letter to Henry IV. of Castile, ceding to him her
claims on Navarre, and beseeching him by the closeness of the tie
that had once united them, and by his love for her dead brother, to
accept what she offered and avenge her wrongs.
It was in vain. Even before Charles of Viana’s death, Henry IV.,
repenting of his rash invasion of Navarre, had come to terms with
the Aragonese King, regardless of his ally’s plight; while just at the
climax of Blanche’s misfortunes, an event happened in Castile that
was to make all but domestic affairs slide into the background.
In March, 1462, Queen Joanna gave birth to a daughter in the
palace at Madrid. The King had at last an heir. Great were the
festivities and rejoicings at Court, many the bull-fights and jousts in
honour of the occasion. Below all the sparkle of congratulation and
rejoicing, however, ran an undercurrent of sneering incredulity. It
was nearly seven years since the Queen came a bride to Cordova, and
for thirteen before that had Henry been married to the virtuous
Blanche of Navarre, yet neither by wife nor mistress had he been
known to have child.
“Enrique El Impotente,” his people had nicknamed him, and now,
recalling the levity of the Queen’s life and her avowed leaning
towards the hero of the famous “Passage of Arms,” they dubbed the
little Princess in mockery “Joanna La Beltraneja.”
Was the King blind? or why was the handsome Beltran de La
Cueva created at this moment, almost it seemed in celebration of the
occasion, Count of Ledesma, and received into the innermost royal
councils? There were those who did not hesitate to affirm that Henry
was indifferent to his own honour, so long as his anxiety for an heir
was satisfied.
Whatever the doubts and misgivings as to her parentage, there was
no lack of outward ceremony at the Infanta’s baptism, in the royal
chapel eight days after her birth. The Primate himself, the
Archbishop of Toledo, performed the rites, and Isabel, who with her
brother Alfonso, had been lately brought up to court, was one of the
godmothers, the other, the Marquesa de Villena, wife of the
favourite. Two months later, a Cortes, composed of prelates, nobles,
and representatives of the Third Estate, assembled at Madrid, and, in
response to the King’s command, took an oath to the Infanta Joanna
as heir to the throne; Isabel and her brother being the first to kneel
and kiss the baby’s hand.
The Christmas of 1462 found Henry and his Queen at Almazon;
and thither came messengers from Barcelona with their tale of
rebellion and the fixed resolution they had made never to submit to
King John’s yoke. Instead the citizens offered their allegiance to
Castile, imploring help and support in the struggle before them.
Henry had been unmoved by Blanche’s appeal, for he knew the
difficulties of an invasion of Navarre, but the present project
flattered his vanity. He would merely dispatch a few troops to
Barcelona, as few as he could under the circumstances, and the
Catalans in return would gain him, at best an important harbour on
the Mediterranean, at worst would act as a thorn in the side of his
ambitious neighbour. He graciously consented therefore to send
2500 horse, under the leadership of one of the Beaumonts, as
earnest of his good intentions; but almost before this force had
reached Barcelona, those intentions had already changed, and he had
agreed to the mediation of the King of France in the disputes
between him and the King of Aragon.
Louis XI., “the universal spider,” as Chastellain called him, had
been spreading his web of diplomacy over the southern peninsula. By
the Treaty of Olito, signed by him and King John in April, 1462, he
had promised to lend that monarch seven hundred lances, with
archers, artillery, and ammunition, in return for two hundred
thousand gold crowns to be paid him on the reduction of Barcelona.
Whether he would ever receive this sum was perhaps a doubtful
matter; but Louis had accepted the pledge of the border counties of
Roussillon and Cerdagne, that commanded the eastern Pyrenees,
should the money fail, and would have been more annoyed than
pleased by prompt repayment. According to his own calculations he
stood to gain in either case; and in the meantime he was well content
to increase his influence by posing as the arbiter of Spanish politics.
After a preliminary conference at Bayonne, it was arranged that
the Kings of Castile and France should meet for a final discussion of
the proposed terms of peace on the banks of the Bidassoa, the
boundary between their two territories. It is a scene that Philip de
Commines’ pen has made for ever memorable; for though he himself
was not present he drew his vivid account from distinguished eye-
witnesses on both sides. Through his medium and that of the
Spanish chroniclers we can see the showy luxury of the Castilian
Court, the splendour of the Moorish guards by whom Henry was
surrounded, the favourite Beltran de La Cueva in his boat, with its
sail of cloth-of-gold dipping before the wind, his very boots as he
stepped on shore glittering with precious stones. Such was the model
to whom Castilian chivalry looked, the man, who with the
Archbishop of Toledo and the Marquis of Villena dictated to their
master his every word.
It is small wonder if Louis XI. had for the ruler of Castile “little
value or esteem,” or that Commines himself, summing up the
situation, caustically dismisses Henry as “a person of no great sense.”
There could not have been a stronger contrast between the two
kings: Henry with his pale blue eyes and mass of reddish hair, his
awkwardly-built frame, overdressed and loaded with jewels,
towering above his meagre companion; Louis, sardonic and self-
contained, well aware of the smothered laughter his appearance
excited amongst Castilian courtiers, but secretly conscious that his
badly cut suit of French homespun and queer shaped hat, its sole
ornament an image of the Virgin, snubbed the butterfly throng about
him.
“The convention broke up and they parted,” says Commines, “but
with such scorn and contempt on both sides, that the two kings never
loved one another heartily afterwards.”
The result of the interview, May, 1463, was soon published. In
return for King John’s future friendship, and in compensation for
her expenses as an ally of Charles of Viana, a few years before, Castile
found herself the richer for the town of Estella in Navarre, a gain so
small that it was widely believed the Archbishop of Toledo and his
fellow-politicians had allowed themselves to be bribed.
If the Castilians were bitter at this decision, still more so were the
Catalans, deserted by their ally and offered nothing save the
unpalatable advice that they should return to King John’s allegiance.
The messengers from Barcelona quitted Fuenterrabia as soon as they
heard, openly uttering their contempt for Castile’s treachery.
“It is the hour,” they exclaimed, “of her shame and of her King’s
dishonour!”
They could not realize to the full the truth of their words, nor to
what depths Henry was shortly to fall and drag the fortunes of his
country with him.
CHAPTER III
THE REIGN OF HENRY IV.: CIVIL WAR AND
ANARCHY
1464–1474
Henry IV. had been merely a figurehead at the meeting of

Fuenterrabia, a rôle to which with his habitual lethargy he had no
objection. When, however, he attempted to obtain possession of the
town of Estella and failed to do so in spite of Villena’s outwardly
strenuous efforts, he began at last to suspect that he had been also a
dupe, and that French and Aragonese money had bribed his
ministers to his own undoing.
He could not make up his mind to break openly with the Marquis
and his uncle, the Archbishop of Toledo; but a perceptible coldness
appeared in his manner where they were concerned, in contrast to
the ever-increasing favour that he now bestowed on Beltran de La
Cueva, Count of Ledesma. The latter’s share in the conferences had
been mainly ornamental. Indeed his talents had lain hitherto rather
in the ballroom or the lists than in the world of practical politics; but
success had stirred his ambitions, and especially his marriage with
the daughter of the Marquis de Santillana, head of the powerful
family of Mendoza. With this connection at his back he might hope
to drive Villena and his relations from Court, and with the Queen’s
aid control the destinies of Castile.
In the struggle between the rival favourites, the Princess Isabel
was regarded as a useful pawn on their chess-board. She and her
brother had been summoned to Court at Villena’s suggestion that
“they would be better brought up and learn more virtuous customs
than away from his Majesty’s presence.” Whether irony were
intended or no, Henry had accepted the statement seriously; and
while Alfonso was handed over to a tutor, his sister joined the
Queen’s household.
There were hopes at this time of another heir to the crown; and the
King, foreseeing in the prospect of a son the means to raise his fallen
dignity, was anxious to gratify his wife’s wishes. When she pleaded
therefore for an alliance with her own country, to be cemented by the
marriage of her brother Alfonso, then a widower, with the twelve-
year-old Isabel, he readily agreed. The scheme was the more pleasing
that it ran counter to the union of Isabel and Ferdinand of Aragon,
still strongly advocated by King John. Villena, who had been bribed
into assisting the latter negotiation, received the first real intimation
that his ascendancy was shaken, when he learned that the King and
Court had set off to the south-western province of Estremadura
without consulting him.
Through the medium of the Queen and Count of Ledesma, the
Portuguese alliance was successfully arranged; and Alfonso V. was so
impressed by the young Princess that he gallantly protested his wish
that the betrothal could take place at once. Isabel replied with her
strange unchildlike caution, that she could not be betrothed save
with the consent of the National Cortes, an appeal to Cæsar that
postponed the matter for the time being. Perhaps she knew her
brother well enough to doubt his continued insistence that “she
should marry none save the King of Portugal”; or she may thus early
have formed a shrewd and not altogether flattering estimate of the
volatile and uncertain Alfonso.
In the meantime the Marquis of Villena was plotting secretly with
his brother, the Master of Calatrava, the Archbishop of Toledo, the
Admiral of Castile, and other nobles how he might regain his old
influence. After a series of attempts on his rival’s life, from which
Beltran de La Cueva emerged scatheless with the additional honour
of the coveted Mastership of Santiago, he and his fellow-conspirators
retired to Burgos, where they drew up a schedule of their grievances.
Secret measures having failed they were determined to browbeat
Henry into submission by playing on his well-known fears of civil
war.
The King’s hopes of an undisputed succession had been shattered
by the premature birth of a still-born son; and thus the question of
the Infanta Joanna’s legitimacy remained as a convenient weapon for
those discontented with the Crown. Nor had the gifts and honours
heaped on Beltran de La Cueva encouraged the loyalty of the
principal nobles. The new favourite was rapacious and arrogant,
while even more intolerable to courtiers of good family and wealth
was the rise of an upstart nobility, that threatened to monopolize the
royal favour.
Louis XI. was astute enough to develop such a policy to his own
advantage; but the feeble Henry IV. was no more able to control his
new creations than their rivals. Almost without exception they
betrayed and sold him for their own ends, poisoning his mind
against the few likely to remain faithful, and making his name odious
amongst his poorer subjects by their selfishness and the corruption
of their rule.
The conspirators of Burgos were thus enabled to pose as the
defenders of national liberties; and their insolent letter of censure
took the colouring most likely to appeal to popular prejudice.
Complaints of the King’s laxity in religious matters, of the unchecked
violence of his Moorish guard, of the debasement of the coinage, and
of the incompetence and venality of the royal judges—these were
placed in the foreground, but the real crux of the document came
later. It lay in two petitions that were veiled threats, first that the
King would deprive the Count of Ledesma of the Mastership of
Santiago, since it belonged of right to the Infante Alfonso, and next
that the said Alfonso should be proclaimed as heir to the throne. The
illegitimacy of the Princess Joanna was openly affirmed.
Henry received this letter at Valladolid, and, calling together his
royal council, laid it before them. He expressed neither resentment at
its insolence nor a desire for revenge; and when the aged Bishop of
Cuenca, who had been one of his father’s advisers, bade him have no
dealings with the conspirators save to offer them battle, he replied
with a sneer that “those who need not fight nor lay hands on their
swords were always free with the lives of others.”
Peace at all costs was his cry, and the old Bishop, exasperated,
forgot prudence in his anger. “Henceforth,” he exclaimed, “you will
be thought the most unworthy King Spain ever knew; and you will
repent it, Señor, when it is too late to make amends.”
Already knights and armed men were flocking to the royal
standard, as they heard of the rebels’ ultimatum. Many of them were
genuinely shocked at the attack on the dignity of the Crown, but for
the greater number Henry’s reckless prodigality of money and
estates was not without its attractions.
The King, however, proved deaf alike to warnings and scorn. After
elaborate discussions he and the Marquis of Villena arranged a
temporary peace, known as the Concord of Medina del Campo. Its
terms were entirely favourable to the conspirators, for Henry,
heedless of the implied slur on his honour, agreed to acknowledge
Alfonso as his heir, on the understanding that he should later marry
the Infanta Joanna. With incredible shortsightedness he also
consented to hand his brother over to the Marquis; and on the 30th
of November, 1464, the oath to the new heir to the throne was
publicly taken. This was followed by the elevation of the Count of
Ledesma, who had resigned the Mastership of Santiago in favour of
the young Prince, to the rank of Duke of Alburquerque.
The question of the misgovernment of the country and its cure was
to be referred to a committee of five leading nobles, two to be
selected by either party, while the Prior-General of the Order of San
Geronimo was given a casting vote. This “Junta of Medina del
Campo,” held in January, 1465, proved no lasting settlement, for the
King’s representatives allowed themselves to be won over to the
views of the league, with disastrous results for their own master.
“They straitened the power of the King to such an extent,” says a
chronicler, “that they left him almost nothing of his dominion save
the title of King, without power to command or any pre-eminence.”
Henry was roused at last, but it was only to fall a victim to fresh
treachery.
Two of the most prominent members of the league in its
beginnings had been Don Alonso Carrillo, Archbishop of Toledo,
uncle of the Marquis of Villena, and the Admiral of Castile, Don
Fadrique Enriquez. The former had little of his nephew’s suave
charm and adaptability, and his haughty, irascible nature was more
suited to the camp than the Primacy of the Castilian Church.
“He was a great lover of war,” says Pulgar in his Claros Varones,
“and while he was praised on the one side for his open-handedness
he was blamed on the other for his turbulence, considering the
religious vows by which he was bound.”
At the time of the Concord of Medina del Campo, he and the
Admiral of Castile had professed themselves weary of the consistent
disloyalty of their colleagues, and had returned to Court with the
King. They now denounced the “Junta” and advised their master to
revoke his agreement to the Concord, and to demand that the Infante
Alfonso should be instantly restored to his power. As might be
expected, the league merely laughed at this request. They declared
that they held the young Prince as a guarantee of their safety, and
that, since the King had determined to persecute them, they must
renounce his service.
Not a few of those at Court suspected the Archbishop and Admiral
of a share in this response, but Henry refused to take a lesson from
the ill-results of past credulity. Instead he submitted entirely to his
new advisers, surrendering at their request two important
strongholds. This achieved, Don Fadrique and the Archbishop
deserted to the league without further pretence; and when the royal
messengers discovered the latter in full fighting gear, on his way to
one of his new possessions, and ventured to remind him that the
King awaited him, that warlike prelate replied with an air of fury:
“Go, tell your King that I have had enough of him and his affairs.
Henceforward he shall see who is the true Sovereign of Castile.”
This insult with its cryptic threat was explained almost
immediately by messengers hurrying from Valladolid, who brought
word that the Admiral had raised the standard of revolt, proclaiming
in the market-place, “Long live the King—Don Alfonso!”
From defiance in words the rebel leaders proceeded to show their
scorn of Henry IV. in action. On June 5th of the same year, they
commanded a wooden scaffold to be set up on the plain outside the
city of Avila, so that it could be clearly seen from all the surrounding
neighbourhood. On it was placed an effigy of the King, robed in
heavy black and seated in a chair of state. On his head was a crown,
before him he held a sword, and in his right hand a sceptre—
emblems of the sovereignty he had failed to exercise. Mounting the
scaffold, the chief members of the league read aloud their grievances,
declaring that only necessity had driven them to the step they were
about to take. Then the Archbishop of Toledo removed the crown
and others of the league the sword and sceptre. Having stripped the
effigy of its royal robes, they threw it on the ground, spurning it from
them with their feet.
Immediately it had fallen and their jests and insults had died away,
the eleven-year-old Alfonso ascended the scaffold, and when he had
been invested with the insignia of majesty, the nobles knelt, and
kissed his hand, and took the oath of allegiance. Afterwards they
raised him on their shoulders, shouting, “Castile for the King, Don
Alfonso!”
Messengers soon brought Henry news of his mock dethronement;
and reports of risings in different parts of the land followed in quick
succession. Valladolid and Burgos had risen in the north; there were
factions in the important city of Toledo; a revolt had blazed up in
Andalusia, where Don Pedro Giron, Master of Calatrava, had long
been busy, sowing the seeds of disaffection.
“Naked I came from my mother’s womb, and naked shall the earth
receive me,” exclaimed the King when he was told, and he found a
melancholy satisfaction in quotations from Isaiah concerning the
ingratitude of a chosen people. The tide had, however, turned in his
favour. Even in Avila, amid the shouts of triumph and rejoicing,
when Henry’s effigy was thrown to the ground, some of those present
had sobbed aloud with horror. More practical assistance took the
shape of an army that rapidly collected in response to Henry’s
summons, “eager,” as the chronicler expressed it, “to come to blows
with those tyrants who had thus dishonoured their natural lord.”
Villena who much preferred diplomacy to the shock of warfare had
in the meanwhile induced his master to agree to a personal
interview, with the result that the King broke up his camp,
compensating his troops for their inaction by large gifts of money.
The league, it was understood, would return to Henry’s allegiance
within a certain time; but its leaders had fallen out amongst
themselves, and at length Villena thought it as well that he and his
family should seek advantageous terms on their own account.
He demanded with incredible insolence that Henry should give his
sister Isabel in marriage to Don Pedro Giron, Master of Calatrava. In
return the Master would pay into the impoverished royal treasury an
enormous sum of money, amassed by fraud and violence, besides
entering the royal service with the 3000 lances, with which he was
just then engaged in harrying the fields of Andalusia. By way of
securing future peace, the Infante Alfonso was to be restored to his
brother, and the Duke of Alburquerque and his brother-in-law, the
Bishop of Calahorra, banished.
For all his folly and weakness, it is difficult to believe that Henry
would consent to such terms, but so low were the straits in which he
found himself that he immediately expressed his satisfaction,
sending word to Don Pedro Giron to come as quickly as he could.
Isabel on her part was aghast and, finding entreaties and
remonstrances of no avail, she spent days and nights upon her knees,
praying that God would either remove the man or herself, before
such a marriage should take place. Her favourite lady-in-waiting,
Doña Beatriz de Bobadilla, moved by her distress, assured her that
neither God nor she would permit such a crime, and, showing her a
dagger that she wore hidden, swore to kill the Master, if no other way
of safety should present itself.
Help, indeed, seemed far away, for the bridegroom, having
obtained from Rome a dispensation from his ill-kept vow of celibacy,
was soon on his way to Madrid at the head of a large company of
knights and horsemen. His only reply to those who told him of the
Infanta’s obstinate refusal of his suit was that he would win her, if
not by gentleness then by force.
At Villa Real, where he halted for the night, the unexpected
happened, for, falling ill of an inflammation of the throat, he died a
few days later.
“He was suddenly struck down by the hand of God,” says Enriquez
del Castillo; while Alonso de Palencia describes how at the end “he
blasphemously accused God of cruelty in not permitting him to add
forty days to his forty and three years.”
Both the King and the Marquis of Villena were in consternation at
the news. The latter had begun to lose his influence with the league,
who justly suspected him of caring more for his own interests than
theirs; and, while he bargained and negotiated with a view to
securing for himself the Mastership of Santiago, a position that he no
longer considered belonged to the young Alfonso “of right,” the
Archbishop of Toledo and the Admiral were bent on bringing matters
to an issue by open war.
Henry was forced to collect his loyalists once more; and on the
20th of August, 1467, a battle took place on the plain of Olmedo, just
outside the city. The King’s army had the advantage in numbers;
indeed he had been induced to advance on the belief that the enemy
would not dare to leave the shelter of their walls, and by the time
they appeared it was too late to sound the retreat. Conspicuous
amongst the rebels were the Infante Alfonso clad, notwithstanding
his youth, in full mail armour, and the fiery Archbishop of Toledo in
his surcoat of scarlet emblazoned with a white cross. The latter was
wounded in his left arm early in the fight but not for that ceasing to
urge on his cavalry to the attack. On the other side the hero of the
day was Beltran de La Cueva, whose death forty knights had sworn to
accomplish, but whose skill and courage were to preserve him for
service in a better cause.
Alone, amongst the leading combatants, Henry IV. cut but a poor
figure, for, watching the action from a piece of rising ground, he fled
at the first sign of a reverse, persuaded that the battle was lost. Late
that evening a messenger, primed with the news of victory,
discovered him hiding in a neighbouring village, and he at last
consented to return to the camp.
The royalists succeeded in continuing their march, but since the
enemy remained in possession of the larger number of banners and
prisoners, both armies were able to claim that they had won.
The battle of Olmedo was followed by the treacherous surrender to
the league of the King’s favourite town of Segovia. Here he had left
the Queen and his sister; but while the former sought refuge in the
Alcazar, which still held out for her husband, Isabel preferred to
remain in the palace with her ladies-in-waiting. She had not suffered
such kindness at the hands of Henry IV. as would make her rate
either his love or his power of protection highly; and, when the rebels
entered the town she surrendered to them with a very goodwill.
Henceforward her fortunes were joined to those of Alfonso; but
death which had saved her from marriage with a man she loathed,
was soon to rob her of her younger brother. It is difficult to form a
clear estimate of either Alfonso’s character or abilities from the
scanty references of the chroniclers; but already, at the age of
fourteen, he had proved himself a better soldier than Henry IV.; and
we are told that those who knew him personally judged him more
upright. The news of his death, on July 5, 1468, was therefore
received with general dismay. His death had been ostensibly the
result of swollen glands, but it was widely believed that the real cause
of its seriousness was a dish of poisoned trout prepared for him by a
secret ally of the King.
With his disappearance from the political chess-board, the whole
balance of affairs in Castile was altered; and Isabel emerged from
comparative obscurity into the prominent position she was
afterwards to hold. Would she take Alfonso’s place as puppet of the
league? or would she be reconciled to her elder brother? In the latter
case, how would the King decide between her claims and those of
Joanna “La Beltraneja”? These were the questions on whose answers
depended the future of the land.
The principal members of the league had no doubts at all as to her
complete acquiescence in their plans, and in the town of Avila they
made her a formal offer of the throne, inviting her to assume the title
of Queen of Castile and Leon. Isabel received the suggestion with her
usual caution; for though but a girl of seventeen, she had few
illusions as to the glories of sovereignty. She knew, moreover, that
several prominent insurgents had taken the opportunity of
reconciling themselves at Court, while the Marquis of Villena, now
acknowledged Master of Santiago, was once more hand in glove with
the King. She therefore replied that while her brother lived she could
neither take the government nor call herself Queen, but that she
would use every effort to secure peace in the land.
ALFONSO, BROTHER OF ISABEL OF
CASTILE
FROM “ICONOGRAFIA ESPAÑOLA” BY

VALENTIN CARDERERA Y SOLANO
This answer deprived the league of any legitimate excuse for

rebellion; and they therefore sent letters to the King, declaring their
willingness to return to his service, if he would acknowledge Isabel as
heir to the throne. The Marquis of Villena also pressed the
suggestion, thinking by this means to re-establish his influence
completely; since his enemies, the House of Mendoza, and especially
its cleverest representative Pedro Gonsalez, Bishop of Siguenza, who
had been promoted from the See of Calahorra, had taken up the
cause of Queen Joanna and her daughter.
Henry, anxious for peace, no matter what the price, fell in with
Villena’s schemes. On the 19th of September, 1468, a meeting was
held at the Toros de Guisandos near Avila; and there, in the presence
of the Papal Legate, Henry swore away for a second time the honour
of his so-called daughter, and recognized Isabel as legitimate heir to
the throne and Princess of Asturias. By the terms of an agreement
previously drawn up, he also promised that his sister should not be
compelled to marry against her will, while she in return agreed to
obtain his consent; furthermore he declared that he would divorce
and send back to her own land his wife, whose lax behaviour had
now become a byword.
Isabel’s own position had materially improved; and there were no
lack of suitors for this eligible heiress. Amongst them was a brother
of Edward IV. of England, but whether the Duke of Clarence or
Richard of Gloucester, the chroniclers do not say. The English
alliance was never very seriously considered, whereas a veritable war
of diplomacy was to be waged around the other proposals.
The Infanta’s chief adviser at this time was the Archbishop of
Toledo, though it does not appear that she was as much under his
thumb, as Enriquez de Castillo would have us believe. There is
evidence of considerable independence of judgment both in her
refusal of the crown on Alfonso’s death, and in her willingness to
meet her brother at the Toros de Guisandos, in spite of the
Archbishop’s violent opposition. Throughout the negotiations, the
Archbishop had been on the watch for evidence of some hidden plot,
and only Isabel’s tact and firmness had induced him to accompany
her to the meeting.
Nevertheless it was natural that a girl of her age should rely
considerably on the judgment of a man so well versed in the politics
of the day, especially as the alliance that he urged appealed in every
way to her own inclinations. Ferdinand of Aragon, the Archbishop’s
protégé, was her junior by eleven months; a slight disparity in
comparison with the age of former suitors such as Charles of Viana,
Alfonso of Portugal, and the Master of Calatrava, all her seniors by at
least twenty years.
In modern reckoning, Ferdinand would be called a boy, but his
childhood had been spent amidst surroundings of war and rebellion,
from which he had emerged as his father’s right hand; and John II.,
in token of his love and confidence, had created this son of his old
age King of Sicily to mark his dignity and independence. Shrewd,
practical, and brave, Ferdinand united to a well-set-up, manly,
appearance all those qualities that Henry IV. so conspicuously
lacked. It was little wonder then if he found grace in the Infanta
Isabel’s eyes, not only as an eligible husband, but as a fitting consort
with whose help she might subdue the turbulence of Castile.
It can be imagined that Ferdinand found no grace at all in the eyes
of the Marquis of Villena, to whom opportunities for turbulence were
as the breath of life, and whose affection for the House of Aragon had
never been sincere.
Policy dictated to him a counter-alliance and at first the
importunate Alfonso of Portugal won support. Villena had re-
established his old influence over his master, and at this time formed
an ambitious scheme, by which his son should marry the Infanta
Joanna; the idea being to draw up a new settlement, settling the
crown on his own descendants, if Isabel and her Portuguese husband
had no children.
At Ocaña, where Henry IV. and his sister held a meeting of the
Cortes in 1468, a magnificent embassy appeared from Alfonso V.,
with the Archbishop of Lisbon at its head, seeking the betrothal of
their master to the Infanta Isabel.
“They thought it an easy matter to bring about the marriage,” says
Alonso de Palencia; but they were destined to return to their own
land, with their mission unfulfilled. Isabel had never been attracted
to the Portuguese King; and her coldness was hardened into
antipathy by the Archbishop of Toledo, who sent her secret warnings
that the alliance was a plot to ruin her prospects. Once married, she
would become a foreigner in the eyes of Castile, and while her
children could not hope to succeed to the throne of Portugal, since
Alfonso had already an heir, the Infanta Joanna would be preferred
to her in her own land. Isabel, moved both by these arguments and
her own feelings, thereupon gave a secret promise to marry her
cousin Ferdinand, returning a steady refusal to her brother’s
persuasions and threats.
Henry now made an attempt to capture her, with a view to
imprisoning her in the Alcazar at Madrid; but the attitude of the
principal knights of Ocaña, who loved neither Villena nor the
Portuguese, was so threatening that he quickly changed his manner.
Assuring the Archbishop of Lisbon that some other means would be
found to placate the Princess, whose opposition would only be
increased by violence, he sent him and his fellow-ambassadors away,
not altogether despairing but with their confidence somewhat
shaken.
In the meanwhile the fires of rebellion were alight once more in
Andalusia and burnt so furiously, that it was felt only the King in
person could hope to allay them. With great reluctance he left his
sister in Ocaña, but he dared not risk further unpopularity by using
force. At the Master of Santiago’s suggestion he demanded that she
should promise to take no new steps about her marriage until his
return, thinking in this way to place her in an equivocal position.
Either she would refuse, in which case she would stand self-
convicted of some secret plot, or she would take the oath,
condemning herself as a perjurer if she broke it.
Isabel, appreciating the situation, gave her promise. Even the
Master of Santiago, for all his vigilance, did not know that her
consent to the Aragonese alliance was of previous date, and therefore
arrangements concerned with it could be argued not to fall under the
heading “new.” As soon as Henry IV. and his favourite had gone
southwards, she herself left Ocaña, with the ostensible object of
taking her brother Alfonso’s body to be buried in state at Avila, and
from there went to Madrigal her birthplace, where her mother was
living. It was her hope that here she would be able to complete her
negotiations with King John and his son, undetected; but she found
the Bishop of Burgos, a nephew of the Master of Santiago, in the
town ready to spy on all her actions.
The King had by now planned for his sister a new match, with
Charles, Duke of Berri, brother and heir-presumptive to Louis XI.
Not only would this alliance cement the customary friendship of
Castile and France, but Isabel’s close connection with the French
throne would remove her very thoroughly from the danger zone of
Castilian affairs. When the Cardinal of Arras arrived in Andalusia he
was therefore encouraged by Henry to go to Madrigal in person and
urge the Duke’s suit.
Nothing doubting the success of his mission, for he was a man
famed for his oratory, the Cardinal, having gained admittance to the

ebook download Current Medical Diagnosis &amp; Treatment 2019 58th Edition - eBook PDF all chapter

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

ebook download Current Medical Diagnosis &amp; Treatment 2019 58th Edition - eBook PDF all chapter

Uploaded by

Copyright:

Available Formats

Current Medical Diagnosis & Treatment

2019 58th Edition - eBook PDF

CURRENT Medical Diagnosis and Treatment 2023 (Current

CURRENT Medical Diagnosis & Treatment 2020 59th

CURRENT Medical Diagnosis and Treatment 2021 60th

(eBook PDF) CURRENT Medical Diagnosis and Treatment

Current medical diagnosis & treatment - 2021 60th

Current Medical Diagnosis & Treatment 2020 59th Edition

CURRENT Diagnosis & Treatment Pediatrics 24th Edition

Current Diagnosis & Treatment Obstetrics & Gynecology,

CMDT2019_FM_pi-xx.indd 1 05/07/18 2:02 PM

CMDT2019_FM_pi-xx.indd 2 05/07/18 2:02 PM

With Associate Authors

CMDT2019_FM_pi-xx.indd 1 05/07/18 2:02 PM

eBook conversion by codeMantra

CMDT2019_FM_pi-xx.indd 3 05/07/18 2:02 PM

26. Endocrine Disorders 1119 39. Cancer 1611

42. Lesbian, Gay, Bisexual, & Transgender

Bryn A. Boslett, MD, & e3. Information Technology in

34. Spirochetal Infections 1493 Russ Cucina, MD, MS

Susan S. Philip, MD, MPH e4. Integrative Medicine Online*

Kent R. Olson, MD Index 1743

*Free access to online chapters at www.accessmedicine.com/cmdt

CMDT2019_FM_pi-xx.indd 4 05/07/18 2:02 PM

Kevin L. Ard, MD, MPH Bryn A. Boslett, MD

CMDT2019_FM_pi-xx.indd 5 05/07/18 2:02 PM

Thomas D. Chi, MD Charles DeBattista, DMH, MD

Russ Cucina, MD, MS Vanja C. Douglas, MD

Tiffany O. Dea, PharmD, BCOP

CMDT2019_FM_pi-xx.indd 6 05/07/18 2:02 PM

Lawrence S. Friedman, MD Richard J. Hamill, MD

B. Joseph Guglielmo, PharmD Meshell D. Johnson, MD

CMDT2019_FM_pi-xx.indd 7 05/07/18 2:02 PM

C. Bree Johnston, MD, MPH Chuanyi Mark Lu, MD

Bhavika Kaul, MD Lawrence R. Lustig, MD

C. Seth Landefeld, MD Anne Mardy, MD

CMDT2019_FM_pi-xx.indd 8 05/07/18 2:02 PM

Megan McNamara, MD, MSc Jacqueline A. Nemer, MD, FACEP

Paul L. Nadler, MD Manesh R. Patel, MD

Ramana K. Naidu, MD Susan S. Philip, MD, MPH

CMDT2019_FM_pi-xx.indd 9 05/07/18 2:02 PM

Michael Pignone, MD, MPH Joseph H. Rapp, MD

CMDT2019_FM_pi-xx.indd 10 05/07/18 2:02 PM

Joshua S. Schindler, MD Michael Sutters, MD, MRCP (UK)

Brian S. Schwartz, MD Philip Tiso

CMDT2019_FM_pi-xx.indd 11 05/07/18 2:02 PM

CMDT2019_FM_pi-xx.indd 12 05/07/18 2:02 PM

INTENDED AUDIENCE FOR CMDT

NEW IN THIS EDITION OF CMDT

CMDT2019_FM_pi-xx.indd 13 05/07/18 2:02 PM

• Revised recommendations for treating hepatitis C virus–associated kidney disease

OUTSTANDING FEATURES OF CMDT

E-CHAPTERS, CMDT ONLINE, & AVAILABLE APPS

CMDT2019_FM_pi-xx.indd 14 05/07/18 2:02 PM

Maxine A. Papadakis, MD Michael W. Rabow, MD

CMDT2019_FM_pi-xx.indd 15 05/07/18 2:02 PM

CMDT2019_FM_pi-xx.indd 16 05/07/18 2:02 PM

—Sir Robert Hutchison

CMDT2019_FM_pi-xx.indd 17 05/07/18 2:02 PM

CMDT2019_FM_pi-xx.indd 18 05/07/18 2:02 PM

º Patient reasons for nonadherence include simple

CMDT19_Ch01_p0001-p0019.indd 1 05/07/18 2:04 PM

» Guiding Principles of Care

CMDT19_Ch01_p0001-p0019.indd 2 05/07/18 2:04 PM

ebook download Current Medical Diagnosis & Treatment 2019 58th Edition - eBook PDF all chapter

ebook download Current Medical Diagnosis & Treatment 2019 58th Edition - eBook PDF all chapter