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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

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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.
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10 CMDT 2019 C 1
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» Lipid Disorders (see Chapter 28) U.S. Preventive Services Task Force. Statin use for the primary
»
Higher low-density lipoprotein (LDL) cholesterol concen- prevention of cardiovascular disease in adults: U.S. Preventive
Services Task Force Recommendation Statement. JAMA.
trations and lower high-density lipoprotein (HDL) levels 2016 Nov 15;316(19):1997–2007. [PMID: 27838723]
are associated with an increased risk of CHD. Measurement
of total and high-density lipoprotein cholesterol levels can
help assess the degree of CHD risk. The best age to start » Hypertension (see Chapter 11)
»
screening is controversial, as is its frequency. Cholesterol-
lowering therapy reduces the relative risk of CHD events, Over 67 million adults in the United States have hyperten-
with the degree of reduction proportional to the reduction sion, representing 29% of the adult US population. Hyper-
in LDL cholesterol achieved. The absolute benefits of tension in nearly half of these adults is not controlled (ie,
screening for—and treating—abnormal lipid levels depend less than 140/90 mm Hg). Among those whose hyperten-
on the presence and level of other cardiovascular risk fac- sion is not well controlled, nearly 40% are not aware of
tors, including hypertension, diabetes mellitus, smoking, their elevated blood pressure; almost 16% are aware but not
age, and sex. If other risk factors are present, atherosclerotic being treated; and 45% are being treated but the hyperten-
cardiovascular disease risk is higher and the potential ben- sion is not controlled. In every adult age group, higher
efits of therapy are greater. Patients with known cardiovas- values of systolic and diastolic blood pressure carry greater
cular disease are at higher risk and have larger benefits risks of stroke and heart failure. Systolic blood pressure is a
from reduction in LDL cholesterol. The optimal risk better predictor of morbid events than diastolic blood pres-
threshold for initiating statins for primary prevention sure. Home monitoring is better correlated with target
remains somewhat controversial, although most guidelines organ damage than clinic-based values. Clinicians can
now suggest statin therapy when the 10-year atherosclerotic apply specific blood pressure criteria, such as those of the
cardiovascular risk is greater than 10%. Joint National Committee or American Heart Association
Evidence for the effectiveness of statin-type drugs is guidelines, along with consideration of the patient’s cardio-
better than for the other classes of lipid-lowering agents or vascular risk and personal values, to decide at what levels
dietary changes specifically for improving lipid levels. Mul- treatment should be considered in individual cases. One
tiple large, randomized, placebo-controlled trials have trial suggests additional benefit from more intensive blood
demonstrated important reductions in total mortality, pressure control (goal systolic blood pressure of 120 mm Hg)
major coronary events, and strokes with lowering levels of in patients at higher risk; however, another found no ben-
LDL cholesterol by statin therapy for patients with known efit from more aggressive treatment in patients at interme-
cardiovascular disease. Statins also reduce cardiovascular diate risk.
events for patients with diabetes mellitus. For patients with Primary prevention of hypertension can be accom-
no previous history of cardiovascular events or diabetes, plished by strategies aimed at both the general population
meta-analyses have shown important reductions of cardio- and special high-risk populations. The latter include per-
vascular events. sons with high-normal blood pressure or a family history of
New antilipidemic monoclonal antibody agents (eg, hypertension, blacks, and individuals with various behav-
evolocumab and alirocumab) lower LDL cholesterol by ioral risk factors, such as physical inactivity; excessive con-
50–60% by binding proprotein convertase subtilisin sumption of salt, alcohol, or calories; and deficient intake of
kexin type 9 (PCSK9), which decreases the degradation potassium. Effective interventions for primary prevention
of LDL receptors. PCSK9 inhibitors also decrease Lp(a) of hypertension include reduced sodium and alcohol con-
levels. These new agents are very expensive so are often sumption, weight loss, and regular exercise. Potassium
used mainly when statin therapy does not reduce the supplementation lowers blood pressure modestly, and a diet
LDL cholesterol sufficiently at maximally tolerated doses high in fresh fruits and vegetables and low in fat, red meats,
or when patients are intolerant of statins. So far, few side and sugar-containing beverages also reduces blood pres-
effects have been reported with PCSK9 inhibitor use. To sure. Interventions of unproven efficacy include pill supple-
date, there has been only one large placebo-controlled mentation of potassium, calcium, magnesium, fish oil, or
trial of alirocumab as add-on therapy to maximal statin fiber; macronutrient alteration; and stress management.
doses. Improved identification and treatment of hypertension
Guidelines for statin and PCSK9 therapy are discussed is a major cause of the recent decline in stroke deaths as
in Chapter 28. well as the reduction in incidence of heart failure–related
hospitalizations. Because hypertension is usually asymp-
tomatic, screening is strongly recommended to identify
Cholesterol Treatment Trialists’ (CTT) Collaboration; Fulcher J patients for treatment. Elevated office readings should be
et al. Efficacy and safety of LDL-lowering therapy among men
confirmed with repeated measurements, ideally from
and women: meta-analysis of individual data from 174,000
participants in 27 randomised trials. Lancet. 2015 Apr 11; ambulatory monitoring or home measurements. Despite
385(9976):1397–405. [PMID: 25579834] strong recommendations in favor of screening and treat-
Pagidipati NJ et al. Comparison of recommended eligibility ment, hypertension control remains suboptimal. An inter-
for primary prevention statin therapy based on the U.S. Preven- vention that included both patient and provider education
tive Services Task Force Recommendations vs the ACC/AHA was more effective than provider education alone in
Guidelines. JAMA. 2017 Apr 18;317(15):1563–7. [PMID:
achieving control of hypertension, suggesting the benefits
28418481]
of patient participation; another trial found that home
CMDT19_Ch01_p0001-p0019.indd 10 05/07/18 2:04 PM

monitoring combined with telephone-based nurse support Dehmer SP et al. Aspirin for the primary prevention of cardio-
was more effective than home monitoring alone for blood vascular disease and colorectal cancer: a decision analysis for
pressure control. Pharmacologic management of hyperten- the U.S. Preventive Services Task Force. Ann Intern Med.
sion is discussed in Chapter 11. 2016 Jun 21;164(12):777–86. [PMID: 27064573]
Guirguis-Blake JM et al. Aspirin for the primary prevention of
cardiovascular events: a systematic evidence review for the
Ettehad D et al. Blood pressure lowering for prevention of car- U.S. Preventive Services Task Force [Internet]. 2015 Sep.
diovascular disease and death: a systematic review and meta- Rockville, MD: Agency for Healthcare Research and Quality;
analysis. Lancet. 2016 Mar 5;387(10022):957–67. [PMID: 2015 Sep. http://www.ncbi.nlm.nih.gov/books/NBK321623/
26724178] [PMID: 26491760]
James PA et al. 2014 evidence-based guideline for the manage- Moyer VA et al. Vitamin, mineral, and multivitamin supple-
ment of high blood pressure in adults: report from the panel ments for the primary prevention of cardiovascular disease
members appointed to the Eighth Joint National Committee and cancer: U.S. Preventive Services Task Force recommenda-
(JNC 8). JAMA. 2014 Feb 5;311(5):507–20. Erratum in: tion statement. Ann Intern Med. 2014 Apr 15;160(8):558–64.
JAMA. 2014 May 7;311(17):1809. [PMID: 24352797] [PMID: 24566474]
Lonn EM et al; HOPE-3 Investigators. Blood-pressure lowering
in intermediate-risk persons without cardiovascular disease.
N Engl J Med. 2016 May 26;374(21):2009–20. [PMID: PREVENTION OF OSTEOPOROSIS
27041480]
Piper MA et al. Diagnostic and predictive accuracy of blood See Chapter 26.
pressure screening methods with consideration of rescreen- Osteoporosis, characterized by low bone mineral den-
ing intervals: a systematic review for the U.S. Preventive Ser- sity, is common and associated with an increased risk of
vices Task Force. Ann Intern Med. 2015 Feb 3;162(3):192–204. fracture. The lifetime risk of an osteoporotic fracture is
[PMID: 25531400] approximately 50% for women and 30% for men. Osteopo-
SPRINT Research Group; Wright JT Jr et al. A randomized trial
of intensive versus standard blood-pressure control. N Engl J
rotic fractures can cause significant pain and disability. As
Med. 2015 Nov 26;373(22):2103–16. [PMID: 26551272] such, research has focused on means of preventing osteo-
Weiss J et al. Benefits and harms of intensive blood pressure porosis and related fractures. Primary prevention strategies
treatment in adults aged 60 years or older: a systematic review include calcium supplementation, vitamin D supplementa-
and meta-analysis. Ann Intern Med. 2017 Mar 21;166(6): tion, and exercise programs. The effectiveness of calcium
419–29. [PMID: 28114673] and vitamin D for fracture prevention remain controver-
Whelton PK et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/
ASH/ASPC/NMA/PCNA guideline for the prevention, detec-
sial, particularly in noninstitutionalized individuals.
tion, evaluation, and management of high blood pressure in Screening for osteoporosis on the basis of low bone
adults: a report of the American College of Cardiology/ mineral density is recommended for women over age 65,
American Heart Association Task Force on Clinical Practice based on indirect evidence that screening can identify
Guidelines. Hypertension. 2017 Nov 13. [Epub ahead of women with low bone mineral density and that treatment
print] [PMID: 29133356] of women with low bone density with bisphosphonates is
Yoon SS et al. Trends in blood pressure among adults with
hypertension: United States, 2003 to 2012. Hypertension.
effective in reducing fractures. However, real-world adher-
2015 Jan;65(1):54–61. [PMID: 25399687] ence to pharmacologic therapy for osteoporosis is low:
one-third to one-half of patients do not take their medica-
» Chemoprevention
tion as directed. The effectiveness of screening for osteopo-
»
rosis in younger women and in men has not been

Regular use of low-dose aspirin (81–325 mg) can reduce established. Concern has been raised that bisphosphonates
cardiovascular events but increases gastrointestinal bleed- may increase the risk of certain uncommon atypical types
ing. Aspirin may also reduce the risk of death from several of femoral fractures and rare osteonecrosis of the jaw, mak-
common types of cancer (colorectal, esophageal, gastric, ing consideration of the benefits and risks of therapy
breast, prostate, and possibly lung). The potential benefits important when considering osteoporosis screening.
of aspirin appear to exceed the harms for those at increased
cardiovascular risk, which can be defined as a 10-year risk Black DM et al. Clinical Practice. Postmenopausal osteoporosis.
of greater than 10%. N Engl J Med. 2016 Jan 21;374(3):254–62. [PMID: 26789873]
Results from a meta-analysis suggest that aspirin could Golob AL et al. Osteoporosis: screening, prevention, and man-
agement. Med Clin North Am. 2015 May;99(3):587–606.
also reduce the risk of death from several common types of [PMID: 25841602]
cancer (colorectal, esophageal, gastric, breast, prostate, and
possibly lung). Nonsteroidal anti-inflammatory drugs may PREVENTION OF PHYSICAL INACTIVITY
reduce the incidence of colorectal adenomas and polyps
but may also increase heart disease and gastrointestinal Lack of sufficient physical activity is the second most
bleeding, and thus are not recommended for colon cancer important contributor to preventable deaths, trailing only
prevention in average-risk patients. tobacco use. A sedentary lifestyle has been linked to 28% of
Antioxidant vitamin (vitamin E, vitamin C, and beta- deaths from leading chronic diseases. Sedentary behavior
carotene) supplementation produced no significant reduc- and physical inactivity have also been linked to decreases
tions in the 5-year incidence of—or mortality in midlife cognition. Worldwide, approximately 30% of
from—vascular disease, cancer, or other major outcomes adults are physically inactive. Inactivity rates are higher in
in high-risk individuals with coronary artery disease, other women, in those from high-income countries (such as the
occlusive arterial disease, or diabetes mellitus. Americas), and in aged individuals. Alarmingly, among
CMDT19_Ch01_p0001-p0019.indd 11 05/07/18 2:04 PM

12 CMDT 2019 C 1
hapter
teens aged 13–15, 80% report doing fewer than 60 minutes risks of exercise, prescribe an exercise program appropriate
of physical activity of moderate to vigorous intensity per for each patient, and provide advice to help prevent injuries
day; boys are more active than girls. and cardiovascular complications.
The US Department of Health and Human Services and Although primary care providers regularly ask patients
the CDC recommend that adults (including older adults) about physical activity and advise them with verbal coun-
engage in 150 minutes of moderate-intensity (such as brisk seling, few providers provide written prescriptions or per-
walking) or 75 minutes of vigorous-intensity (such as jog- form fitness assessments. Tailored interventions may
ging or running) aerobic activity or an equivalent mix of potentially help increase physical activity in individuals.
moderate- and vigorous-intensity aerobic activity each Exercise counseling with a prescription, eg, for walking at
week. In addition to activity recommendations, the CDC either a hard intensity or a moderate intensity with a high
recommends activities to strengthen all major muscle frequency, can produce significant long-term improve-
groups (abdomen, arms, back, chest, hips, legs, and shoul- ments in cardiorespiratory fitness. To be effective, exercise
ders) at least twice a week. prescriptions must include recommendations on type, fre-
Patients who engage in regular moderate to vigorous quency, intensity, time, and progression of exercise and
exercise have a lower risk of myocardial infarction, stroke, must follow disease-specific guidelines. Several factors
hypertension, hyperlipidemia, type 2 diabetes mellitus, influence physical activity behavior, including personal,
diverticular disease, and osteoporosis. Evidence supports social (eg, family and work), and environmental (eg, access
the recommended guidelines of 30 minutes of moderate to exercise facilities and well-lit parks). Walkable neighbor-
physical activity on most days of the week in both the pri- hoods around workplaces support physical activity such as
mary and secondary prevention of CHD. walking and bicycling. A community-based volunteer
In longitudinal cohort studies, individuals who report intervention resulted in increased walking activity among
higher levels of leisure-time physical activity are less likely to older women, who were at elevated risk for both inactivity
gain weight. Conversely, individuals who are overweight are and adverse health outcomes.
less likely to stay active. However, at least 60 minutes of daily Broad-based interventions targeting various factors are
moderate-intensity physical activity may be necessary to often the most successful, and interventions to promote
maximize weight loss and prevent significant weight regain. physical activity are more effective when health agencies
Moreover, adequate levels of physical activity appear to be work with community partners, such as schools, businesses,
important for the prevention of weight gain and the develop- and health care organizations. Enhanced community
ment of obesity. Physical activity also appears to have an awareness through mass media campaigns, school-based
independent effect on health-related outcomes, such as devel- strategies, and policy approaches are proven strategies to
opment of type 2 diabetes mellitus in patients with impaired increase physical activity.
glucose tolerance when compared with body weight, suggest-
ing that adequate levels of activity may counteract the nega-
tive influence of body weight on health outcomes. Adlakha D et al. Home and workplace built environment
supports for physical activity. Am J Prev Med. 2015 Jan;
Physical activity can be incorporated into any person’s 48(1):104–7. [PMID: 25442233]
daily routine. For example, the clinician can advise a Bouchard C et al. Less sitting, more physical activity, or higher
patient to take the stairs instead of the elevator, to walk or fitness? Mayo Clin Proc. 2015 Nov;90(11):1533–40. [PMID:
bike instead of driving, to do housework or yard work, to 26422244]
get off the bus one or two stops earlier and walk the rest of Centers for Disease Control and Prevention (CDC). How much
the way, to park at the far end of the parking lot, or to walk physical activity do adults need? 2015 Jun 4. http://www.cdc.
gov/physicalactivity/basics/adults/index.htm
during the lunch hour. The basic message should be the Hoang TD et al. Effect of early adult patterns of physical activity
more the better, and anything is better than nothing. and television viewing on midlife cognitive function. JAMA
To be more effective in counseling about exercise, clini- Psychiatry. 2016 Jan;73(1):73–9. [PMID: 26629780]
cians can also incorporate motivational interviewing tech- Varma VR et al. Effect of community volunteering on physical
niques, adopt a whole-practice approach (eg, use practice activity: a randomized controlled trial. Am J Prev Med.
nurses to assist), and establish linkages with community 2016 Jan;50(1):106–10. [PMID: 26340864]
agencies. Clinicians can incorporate the “5 As” approach:
1. Ask (identify those who can benefit). PREVENTION OF OVERWEIGHT & OBESITY
2. Assess (current activity level). Obesity is now a true epidemic and public health crisis that
3. Advise (individualize plan). both clinicians and patients must face. Normal body
4. Assist (provide a written exercise prescription and sup- weight is defined as a body mass index (BMI), calculated as
port material). the weight in kilograms divided by the height in meters
5. Arrange (appropriate referral and follow-up). squared, of less than 25; overweight is defined as a BMI =
25.0–29.9, and obesity as a BMI greater than 30. Between
Such interventions have a moderate effect on self- 1980 and 2013, there was an 8% increase worldwide in the
reported physical activity and cardiorespiratory fitness, proportion of men and women with a BMI greater than 25.
even if they do not always help patients achieve a predeter- The most recent national data reveal that one-third of
mined level of physical activity. In their counseling, clini- adults in the United States are obese, and prevalence rates
cians should advise patients about both the benefits and are higher in blacks and Hispanics compared to
CMDT19_Ch01_p0001-p0019.indd 12 05/07/18 2:04 PM

non-Hispanic whites. This trend has been linked both to and meat. Only one of four Americans eats the recom-
declines in physical activity and to increased caloric intake. mended five or more fruits and vegetables per day.
Risk assessment of the overweight and obese patient Clinicians can help guide patients to develop personal-
begins with determination of BMI, waist circumference for ized eating plans to reduce energy intake, particularly by
those with a BMI of 35 or less, presence of comorbid condi- recognizing the contributions of fat, concentrated carbohy-
tions, and a fasting blood glucose and lipid panel. Obesity drates, and large portion sizes (see Chapter 29). Patients
is clearly associated with type 2 diabetes mellitus, hyper- typically underestimate caloric content, especially when
tension, hyperlipidemia, cancer, osteoarthritis, cardiovas- consuming food away from home. Providing patients with
cular disease, obstructive sleep apnea, and asthma. In caloric and nutritional information may help address the
addition, almost one-quarter of the US population cur- current obesity epidemic. To prevent the long-term chronic
rently has the metabolic syndrome. disease sequelae of overweight and obesity, clinicians must
Metabolic syndrome is defined as the presence of any work with patients to modify other risk factors, eg, by
three of the following: waist measurement of 40 inches or smoking cessation (see above) and strict blood pressure
more for men and 35 inches or more for women, triglycer- and glycemic control (see Chapters 11 and 27).
ide levels of 150 mg/dL (1.70 mmol/L) or above, HDL Lifestyle modification, including diet, physical activity,
cholesterol level less than 40 mg/dL (less than 1.44 mmol/L) and behavior therapy, has been shown to induce clinically
for men and less than 50 mg/dL (less than 1.80 mmol/L) significant weight loss. Other treatment options for obesity
for women, blood pressure of 130/85 mm Hg or above, and include pharmacotherapy and surgery (see Chapter 29). In
fasting blood glucose levels of 100 mg/dL (5.55 mmol/L) or overweight and obese persons, at least 60 minutes of mod-
above. The relationship between overweight and obesity erate- to high-intensity physical activity per day may be
and diabetes, hypertension, and coronary artery disease is necessary to maximize weight loss and prevent significant
thought to be due to insulin resistance and compensatory weight regain. Counseling interventions or pharmacother-
hyperinsulinemia. apy can produce modest (3–5 kg) sustained weight loss
Obesity is associated with a higher all-cause mortality over 6–12 months. Counseling appears to be most effective
rate. Data suggest an increase among those with grades 2 when intensive and combined with behavioral therapy.
and 3 obesity (BMI more than 35); however, the impact on Pharmacotherapy appears safe in the short term; long-term
all-cause mortality among overweight (BMI 25–30) and safety is still not established. Lorcaserin, a selective
grade 1 obesity (BMI 30–35) is questionable. Persons with 5-hydroxytryptamine 2C (5-HT2C) agonist, has been
a BMI 40 or higher have death rates from cancers that are shown to reduce body weight through a reduction of
52% higher for men and 62% higher for women than the energy intake without influencing energy expenditure. It
rates in men and women of normal weight. Significant was approved by the FDA for adults with a BMI 30 or
trends of increasing risk of death with higher BMIs are higher or adults with a BMI 27 or higher who have at least
observed for cancers of the stomach and prostate in men one obesity-related condition, such as hypertension, type 2
and for cancers of the breast, uterus, cervix, and ovary in diabetes mellitus, or hypercholesterolemia.
women, and for cancers of the esophagus, colon and rec- Commercial weight loss programs are effective in pro-
tum, liver, gallbladder, pancreas, and kidney, non-Hodgkin moting weight loss and weight loss management. A ran-
lymphoma, and plasma cell myeloma (previously called domized controlled trial of over 400 overweight or obese
multiple myeloma) in both men and women. women demonstrated the effectiveness of a free prepared
In the Framingham Heart Study, overweight and obe- meal and incentivized structured weight loss program
sity were associated with large decreases in life expectancy. compared with usual care.
For example, 40-year-old female nonsmokers lost 3.3 years Weight loss strategies using dietary, physical activity, or
and 40-year-old male nonsmokers lost 3.1 years of life behavioral interventions can produce significant improve-
expectancy because of overweight, and 7.1 years and 5.8 years ments in weight among persons with prediabetes and a
of life expectancy, respectively, because of obesity. Obese significant decrease in diabetes incidence. Lifestyle inter-
female smokers lost 7.2 years and obese male smokers lost ventions including diet combined with physical activity are
6.7 years of life expectancy compared with normal-weight effective in achieving weight loss and reducing cardiometa-
smokers, and 13.3 years and 13.7 years, respectively, com- bolic risk factors among patients with severe obesity.
pared with normal-weight nonsmokers. Bariatric surgical procedures, eg, adjustable gastric band,
Prevention of overweight and obesity involves both sleeve gastrectomy, and Roux-en-Y gastric bypass, are
increasing physical activity and dietary modification to reserved for patients with morbid obesity whose BMI exceeds
reduce caloric intake. Adequate levels of physical activity 40, or for less severely obese patients (with BMIs between 35
appear to be important for the prevention of weight gain and 40) with high-risk comorbid conditions such as life-
and the development of obesity. Physical activity programs threatening cardiopulmonary problems (eg, severe sleep
consistent with public health recommendations may pro- apnea, Pickwickian syndrome, and obesity-related cardiomy-
mote modest weight loss (~2 kg); however, the amount of opathy) or severe diabetes mellitus. In selected patients, sur-
weight loss for any one individual is highly variable. Only gery can produce substantial weight loss (10 to 159 kg) over
49% of Americans are physically active at a moderate level 1 to 5 years, with rare but sometimes severe complications.
and 20% at a more vigorous level. In addition, only 3% of Nutritional deficiencies are one complication of bariatric
Americans meet four of the five USDA recommendations surgical procedures and close monitoring of a patient’s meta-
for the intake of grains, fruits, vegetables, dairy products, bolic and nutritional status is essential.
CMDT19_Ch01_p0001-p0019.indd 13 05/07/18 2:04 PM

14 CMDT 2019 C 1
hapter
Finally, clinicians seem to share a general perception important preventable cause of cancer. Primary preven-
that almost no one succeeds in long-term maintenance of tion of skin cancer consists of restricting exposure to
weight loss. However, research demonstrates that approxi- ultraviolet light by wearing appropriate clothing and use
mately 20% of overweight individuals are successful at of sunscreens. Persons who engage in regular physical
long-term weight loss (defined as losing 10% or more of exercise and avoid obesity have lower rates of breast and
initial body weight and maintaining the loss for 1 year or colon cancer. Prevention of occupationally induced cancers
longer). National Weight Control Registry members who involves minimizing exposure to carcinogenic substances,
lost an average of 33 kg and maintained the loss for more such as asbestos, ionizing radiation, and benzene com-
than 5 years have provided useful information about how pounds. Chemoprevention has been widely studied for
to maintain weight loss. Members report engaging in high primary cancer prevention (see above Chemoprevention
levels of physical activity (approximately 60 min/day), eat- section and Chapter 39). Use of tamoxifen, raloxifene,
ing a low-calorie, low-fat diet, eating breakfast regularly, and aromatase inhibitors for breast cancer prevention is
self-monitoring weight, and maintaining a consistent eat- discussed in Chapters 17 and 39. Hepatitis B vaccination
ing pattern from weekdays to weekends. can prevent hepatocellular carcinoma (HCC), and screen-
Clinicians must work to identify and provide the best ing and vaccination programs may be cost effective and
prevention and treatment strategies for patients who are useful in preventing HCC in high-risk groups, such as
overweight and obese. Clinician advice on weight loss can Asians and Pacific Islanders. The use of HPV vaccine to
have a significant impact on patient attempts to adjust prevent cervical and possibly anal cancer is discussed
weight-related behaviors. Unfortunately, many clinicians above. In addition to preventing anogenital cancers,
are poorly prepared to address obesity. Clinician bias and HPV vaccines may have a role in the prevention of HPV-
lack of training in behavior-change strategies impair the related head and neck cancers. Guidelines for optimal
care of obese patients. Strategies to address these issues cancer screening in adults over the age of 75 are unsettled;
should be incorporated into innovative treatment and care- thus, an individualized approach that considers differ-
delivery strategies. ences in disease risk rather than chronological age is
recommended.
Dietz WH et al. Management of obesity: improvement of health-
care training and systems for prevention and care. Lancet.
2015 Jun 20;385(9986):2521–33. [PMID: 25703112] Breslau ES et al. An individualized approach to cancer screening
Evert AB et al. Lifestyle intervention: nutrition therapy and decisions in older adults: a multilevel framework. J Gen
physical activity. Med Clin North Am. 2015 Jan;99(1):69–85. Intern Med. 2016 May;31(5):539–47. [PMID: 26941042]
[PMID: 25456644] Smith RA et al. Cancer screening in the United States, 2016: a
Flegal KM et al. Association of all-cause mortality with over- review of current American Cancer Society guidelines and
weight and obesity using standard body mass index catego- current issues in cancer screening. CA Cancer J Clin. 2016
ries: a systematic review and meta-analysis. JAMA. 2013 Jan 2; Mar–Apr;66(2):96–114. [PMID: 26797525]
309(1):71–82. [PMID: 23280227] Wernli KJ et al. Screening for skin cancer in adults: updated
Guth E. JAMA patient page. Healthy weight loss. JAMA. evidence report and systematic review for the U.S. Preventive
2014 Sep 3;312(9):974. [PMID: 25182116] Services Task Force. JAMA. 2016 Jul 26;316(4):436–47.
Hartmann-Boyce J et al. Self-help for weight loss in overweight [PMID: 27458949]
and obese adults: systematic review and meta-analysis. Am J
» Screening & Early Detection

Public Health. 2015 Mar;105(3):e43–57. [PMID: 25602873]
Jin J. JAMA patient page. Obesity and the heart. JAMA. 2013
»
Nov 20;310(19):2113. [PMID: 24240948]
Ng M et al. Global, regional, and national prevalence of over- Screening prevents death from cancers of the breast, colon,
weight and obesity in children and adults during 1980–2013: and cervix. Current cancer screening recommendations
a systematic analysis for the Global Burden of Disease Study from the USPSTF are shown in Table 1–6. Despite an
2013. Lancet. 2014 Aug 30;384(9945):766–81. Erratum in: increase in rates of screening for breast, cervical, and colon
Lancet. 2014 Aug 30;384(9945):746. [PMID: 24880830] cancer over the last decade, overall screening for these
Ogden CL et al. Prevalence of childhood and adult obesity in the
cancers is suboptimal. Interventions effective in promoting
United States, 2011–2012. JAMA. 2014 Feb 26;311(8):806–14.
[PMID: 24570244] recommended cancer screening include group education,
Rose SA et al. Physician weight loss advice and patient weight one-on-one education, patient reminders, reduction of
loss behavior change: a literature review and meta-analysis of structural barriers, reduction of out-of-pocket costs, and
survey data. Int J Obes (Lond). 2013 Jan;37(1):118–28. provider assessment and feedback.
[PMID: 22450855] Evidence from randomized trials suggests that screen-
Swift DL et al. The role of exercise and physical activity in weight
ing mammography has both benefits and downsides. A
loss and maintenance. Prog Cardiovasc Dis. 2014 Jan–Feb;
56(4):441–7. [PMID: 24438736] 2011 Cochrane review estimated that screening with mam-
mography led to a reduction in breast cancer mortality of
15% but resulted in 30% overdiagnosis and overtreatment.
CANCER PREVENTION
Currently, the appropriate form and frequency of screening
» Primary Prevention
for breast cancer remains controversial, and screening
guidelines vary. Clinicians should discuss the risks and
»
Cancer mortality rates continue to decrease in the benefits with each patient and consider individual patient
United States; part of this decrease results from reduc- preferences when deciding when to begin screening (see
tions in tobacco use, since cigarette smoking is the most Chapters 17 and e6).
CMDT19_Ch01_p0001-p0019.indd 14 05/07/18 2:04 PM

Table 1–6. Cancer screening recommendations for average-risk adults: US Preventive Services Task Force (USPSTF).1
Test USPSTF Recommendation/[Year Issued]

Breast self-examination Recommends against teaching breast self-examination. (D)
[2009]
Clinical breast examination Insufficient evidence to recommend for or against clinical breast examination. (I)
[2009]
Mammography Recommends biennial screening mammography for women aged 50–74 years. (B)
The decision to start screening mammography in women prior to age 50 years should be an individ-
ual one. Women who place a higher value on the potential benefit than the potential harms may
choose to begin biennial screening between the ages of 40 and 49 years. (C)
[2016]
Cervical cancer screening Recommends screening for cervical cancer in women aged 21–65 years with cytology (Pap smear)
every 3 years or, for women aged 30–65 years who want to lengthen the screening interval,
screening with a combination of cytology and human papillomavirus (HPV) testing every 5 years. (A)
Recommends against screening for cervical cancer in women younger than 21 years. (D)
Recommends against screening for cervical cancer in women older than 65 years who have had
adequate prior screening and are not otherwise at high risk for cervical cancer. (D)
Recommends against screening for cervical cancer in women who have had a hysterectomy with
removal of the cervix and who do not have a history of a high-grade precancerous lesion
(ie, cervical intraepithelial neoplasia [CIN] grade 2 or 3) or cervical cancer. (D)
[2017]
Colorectal cancer (CRC) screening Recommends screening for CRC starting at age 50 years and continuing until age 75 years. (A)
The decision to screen for CRC in adults aged 76–85 years should be an individual one, taking into
account the patient’s overall health and prior screening history. (C)
[2016]
Characteristics of colorectal Reviews the following tests: fecal occult blood tests (gFOBT, FIT) every year; FIT-DNA every 1 or
cancer screening strategies 3 years; colonoscopy every 10 years; CT colonography every 5 years; flexible sigmoidoscopy
every 5 years; flexible sigmoidoscopy every 10 years plus FIT every 1 year.
Lung cancer screening Recommends annual lung cancer screening using low-dose CT in current smokers aged 55–80 years
with a 30-pack-year smoking history, or in smokers who quit within the past 15 years. (B)
Recommends stopping screening once a person has not smoked for 15 years or a health problem
that significantly limits life expectancy has developed.
[2013]
Prostate cancer screening Recommends that clinicians inform men ages 55–69 years about the potential benefits and harms of
prostate-specific antigen (PSA)–based screening for prostate cancer. (C)
Recommends against prostate specific antigen PSA–based screening for prostate cancer in men age
70 years and older. (D)
[2017]
Testicular cancer screening Recommends against screening for testicular cancer in adolescent or adult males.
[2011]
1
United States Preventive Services Task Force recommendations available at http://www.uspreventiveservicestaskforce.org/BrowseRec/
Index/browse-recommendations.
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 recommends against routinely providing the service. There may be considerations that support providing
the service in an individual patient. There is at least moderate certainty that the net benefit is small.
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.
http://www.uspreventiveservicestaskforce.org/BrowseRec/Index/browse-recommendations
Digital mammography is more sensitive in women high risk (20–25% or more), including those with a
with dense breasts and younger women; however, studies strong family history of breast or ovarian cancer. Screen-
exploring outcomes are lacking. MRI is not currently ing with both MRI and mammography might be superior
recommended for general screening, and its impact on to mammography alone in ruling out cancerous lesions
breast cancer mortality is uncertain; nevertheless, the in women with an inherited predisposition to breast
American Cancer Society recommends it for women at cancer.
CMDT19_Ch01_p0001-p0019.indd 15 05/07/18 2:04 PM

16 CMDT 2019 C 1
hapter
All current recommendations call for cervical and recommended in women who test positive for types 16 or
colorectal cancer screening. Screening for testicular cancers 16/18. Women with atypical squamous cells of undeter-
among asymptomatic adolescent or adult males is not rec- mined significance (ASCUS) on cytology and a negative
ommended by the USPSTF. Prostate cancer screening HPV test result should continue routine screening as per
remains controversial, since no completed trials have age-specific guidelines.
answered the question of whether early detection and In a randomized, controlled trial, transvaginal ultra-
treatment after screen detection produce sufficient benefits sound combined with serum cancer antigen 125 (CA-125)
to outweigh harms of treatment. A 2013 Cochrane system- as screening tools to detect ovarian cancer did not reduce
atic review revealed that prostate cancer screening with mortality. Furthermore, complications were associated with
PSA testing did not decrease all-cause mortality and may diagnostic evaluations to follow up false-positive screening
not decrease prostate cancer–specific mortality. Any bene- test results. Thus, screening for ovarian cancer with trans-
fits in terms of reduction in prostate cancer–related mor- vaginal ultrasound and CA-125 is not recommended.
tality would take more than 10 years to become evident. Evidence suggests that chest CT is significantly more
Men with less than 10–15 years’ life expectancy should be sensitive than chest radiography in identifying small
informed that screening for prostate cancer is unlikely to asymptomatic lung cancers; however, controversy exists
be beneficial. In 2017, the USPSTF recommended against regarding the efficacy and cost-effectiveness of low-dose
PSA-based prostate cancer screening for men older than CT screening in high-risk individuals. In the United States,
age 70 years (grade D recommendation). the National Lung Screening Trial (NLST), a randomized
Annual or biennial fecal occult blood testing reduces clinical trial of over 53,000 individuals at high risk for lung
mortality from colorectal cancer by 16–33%. Fecal immu- cancer, revealed a 20% relative reduction and 6.7% absolute
nochemical tests (FIT) are superior to guaiac-based fecal reduction in lung cancer mortality in those who were
occult blood tests (gFOBT) in detecting advanced adeno- screened with annual low-dose CTs for 3 years compared
matous polyps and colorectal cancer, and patients are more with those who had chest radiographs. There were a
likely to favor FIT over gFOBT. Randomized trials using greater number of false-positive results in the low-dose CT
sigmoidoscopy as the screening method found 20–30% group compared with those in the radiography group
reductions in mortality from colorectal cancer. Colonos- (23.3% vs 6.5%) (see Chapter 39). In Italy, the Multicentric
copy has also been advocated as a screening examination. Italian Lung Detection (MILD) study, a randomized trial of
It is more accurate than flexible sigmoidoscopy for detect- over 4000 participants comparing annual or biennial low-
ing cancer and polyps, but its value in reducing colon dose CT with observation revealed no evidence of a protec-
cancer mortality has not been studied directly. CT colo- tive effect with annual or biennial low-dose CT screening.
nography (virtual colonoscopy) is a noninvasive option in The USPSTF recommends annual lung cancer screening
screening for colorectal cancer. It has been shown to have a with low-dose CT in current smokers aged 55 to 80 years
high safety profile and performance similar to colonos- with a 30-pack-year smoking history or smokers who quit
copy. The American College of Physicians (ACP) recom- within the past 15 years. Screening should stop once a per-
mends clinicians stop screening for colorectal cancer in son has not smoked for 15 years or a health problem that
individuals over the age of 75 years or with a life expec- significantly limits life expectancy has developed. Screening
tancy of less than 10 years. The USPSTF recommends should not be viewed as an alternative to smoking
screening for colorectal cancer starting at age 50 years and cessation.
continuing until age 75 years (grade A recommendation)
but says that the decision to screen for colorectal cancer in Hayes JH et al. Screening for prostate cancer with the prostate-
adults aged 76–85 years should be an individual one, taking specific antigen test: a review of current evidence. JAMA.
2014 Mar 19;311(11):1143–9. [PMID: 24643604]
into account the patient’s overall health and prior screening Holme Ø et al. Effect of flexible sigmoidoscopy screening on
history (grade C recommendation). colorectal cancer incidence and mortality: a randomized
The USPSTF recommends screening for cervical cancer clinical trial. JAMA. 2014 Aug 13;312(6):606–15. [PMID:
in women aged 21–65 years with a Papanicolaou smear 25117129]
(cytology) every 3 years or, for women aged 30–65 years Jin J. JAMA patient page. Screening tests for colorectal cancer.
who desire longer intervals, screening with cytology and JAMA. 2016 Jun 21;315(23):2636. [PMID: 27305292]
Lieberman D et al. Screening for colorectal cancer and evolving
HPV testing every 5 years. The USPSTF recommends issues for physicians and patients: a review. JAMA. 2016
against screening in women younger than 21 years of age Nov 22;316(20):2135–45. [PMID: 27893135]
and average-risk women over 65 with adequate negative Melnikow J et al. Supplemental screening for breast cancer in
prior screenings. Receipt of HPV vaccination has no women with dense breasts: a systematic review for the U.S.
impact on screening intervals. Preventive Services Task Force. Ann Intern Med. 2016
In 2012, the American Cancer Society, the American Feb 16;164(4):268–78. [PMID: 26757021]
Moyer VA; U.S. Preventive Services Task Force. Screening for
Society for Colposcopy and Cervical Pathology, and the lung cancer: U.S. Preventive Services Task Force recommen-
American Society for Clinical Pathology published updated dation statement. Ann Intern Med. 2014 Mar 4;160(5):330–8.
guidelines for management of abnormal results. Women [PMID: 24378917]
whose cervical specimen HPV tests are positive but cytol- Nelson HD et al. Effectiveness of breast cancer screening: sys-
ogy results are otherwise negative should repeat co-testing tematic review and meta-analysis to update the 2009 U.S.
in 12 months (option 1) or undergo HPV-genotype–specific Preventive Services Task Force Recommendation. Ann Intern
Med. 2016 Feb 16;164(4):244–55. [PMID: 26756588]
testing for types 16 or 16/18 (option 2). Colposcopy is
CMDT19_Ch01_p0001-p0019.indd 16 05/07/18 2:04 PM

kicked you, or otherwise physically hurt you?”—can

Soung MC. Screening for cancer: when to stop? A practical
guide and review of the evidence. Med Clin North Am. increase identification of this common problem. Assess-
2015 Mar;99(2):249–62. [PMID: 25700582] ment for abuse and offering of referrals to community
Tanoue LT et al. Lung cancer screening. Am J Respir Crit Care resources create the potential to interrupt and prevent
Med. 2015 Jan 1;191(1):19–33. [PMID: 25369325] recurrence of domestic violence and associated trauma.
Wood DE. National Comprehensive Cancer Network (NCCN) Clinicians should take an active role in following up with
clinical practice guidelines for lung cancer screening. Thorac patients whenever possible, since intimate partner vio-
Surg Clin. 2015 May;25(2):185–97. [PMID: 25901562]
lence screening with passive referrals to services may not
be adequate. Evaluation of services available to patients
PREVENTION OF INJURIES & VIOLENCE after identification of intimate partner violence should be
a priority.
Injuries remain the most important cause of loss of poten- Physical and psychological abuse, exploitation, and
tial years of life before age 65. Homicide and motor vehicle neglect of older adults are serious, underrecognized prob-
accidents are a major cause of injury-related deaths among lems; they may occur in up to 10% of elders. Risk factors
young adults, and accidental falls are the most common for elder abuse include a culture of violence in the family;
cause of injury-related death in older adults. Approxi- a demented, debilitated, or depressed and socially isolated
mately one-third of all injury deaths include a diagnosis of victim; and a perpetrator profile of mental illness, alcohol
traumatic brain injury. Other causes of injury-related or drug abuse, or emotional and/or financial dependence
deaths include suicide and accidental exposure to smoke, on the victim. Clues to elder mistreatment include the
fire, and flames. patient’s ill-kempt appearance, recurrent urgent-care visits,
Although motor vehicle accident deaths per miles missed appointments, suspicious physical findings, and
driven have declined in the United States, there has been implausible explanations for injuries.
an increase in motor vehicle accidents related to distracted
driving (using a cell phone, texting, eating). Evidence also Centers for Disease Control and Prevention (CDC). CDC Grand
suggests that motorists’ use of sleeping medications (such Rounds: reducing severe traumatic brain injury in the United
as zolpidem) almost doubles the risk of motor vehicle acci- States. MMWR Morb Mortal Wkly Rep. 2013 Jul 12; 62(27):
dents. Clinicians should discuss this risk when selecting a 549–52. [PMID: 23842444]
sleeping medication. For 16- and 17-year-old drivers, the Dicola D et al. Intimate partner violence. Am Fam Physician.
risk of fatal crashes increases with the number of 2016 Oct 15;94(8):646–51. [PMID: 27929227]
Ellsberg M et al. Prevention of violence against women and girls:
passengers. what does the evidence say? Lancet. 2015 Apr 18;385(9977):
Each year in the United States, more than 500,000 1555–66. [PMID: 25467575]
people are nonfatally injured while riding bicycles. The rate Haegerich TM et al. Prevention of injury and violence in the
of helmet use by bicyclists and motorcyclists is significantly USA. Lancet. 2014 Jul 5;384(9937):64–74. [PMID: 24996591]
increased in states with helmet laws. Young men appear Hansen RN et al. Sedative hypnotic medication use and the risk
most likely to resist wearing helmets. of motor vehicle crash. Am J Public Health. 2015 Aug;
105(8):e64–9. [PMID: 26066943]
Males aged 16–35 are at especially high risk for serious Keall MD et al. Home modifications to reduce injuries from falls
injury and death from accidents and violence, with blacks in the Home Injury Prevention Intervention (HIPI) study: a
and Latinos at greatest risk. Deaths from firearms have cluster-randomised controlled trial. Lancet. 2015 Jan 17;
reached epidemic levels in the United States. In 2015, a 385(9964):231–8. [PMID: 25255696]
total of 13,286 people were killed in the United States in a Lachs MS et al. Elder abuse. N Engl J Med. 2015 Nov 12;
gun homicide, unintentional shooting, or murder/suicide. 373(20):1947–56. [PMID: 26559573]
Lyons BH et al. Surveillance for violent deaths—National Violent
Having a gun in the home increases the likelihood of Death Reporting System, 17 States, 2013. MMWR Surveill
homicide nearly threefold and of suicide fivefold. Educat- Summ. 2016 Aug 19;65(10):1–42. [PMID: 27537325]
ing clinicians to recognize and treat depression as well as Moyer VA. Screening for intimate partner violence and abuse of
restricting access to lethal methods have been found to elderly and vulnerable adults: U.S. Preventive Services Task
reduce suicide rates. Force recommendation statement. Ann Intern Med. 2013
In addition, clinicians should try to educate their Mar 19;158(6):478–86. [PMID: 23338828]
National Center for Statistics and Analysis. Distracted Driving:
patients about always wearing seat belts and safety helmets, 2013 Data, in Traffic Safety Research Note. DOT HS 812 132.
about the risks of using cellular telephones or texting while April 2015, National Highway Traffic Safety Administration:
driving, of drinking and driving—or of using other intoxi- Washington, D.C. http://www.distraction.gov/downloads/
cants (including marijuana) or long-acting benzodiaze- pdfs/Distracted_Driving_2013_Research_note.pdf
pines and then driving—and about the risks of having guns Riley CL et al; Society of Critical Care Medicine. Critical
in the home. violent injury in the United States: a review and call to
action. Crit Care Med. 2015 Nov;43(11):2460–7. [PMID:
Clinicians have a critical role in the detection, preven- 26327199]
tion, and management of intimate partner violence (see Stowe JD et al. A randomized crash injury prevention trial of
Chapter e6.). The USPSTF recommends screening women transitioning high-risk elders from driving. J Trauma Acute
of childbearing age for intimate partner violence and Care Surg. 2015 Jul;79(1):132–7. [PMID: 26091326]
providing or referring women to intervention services Sumner SA et al. Violence in the United States: status, challenges,
when needed. Inclusion of a single question in the medi- and opportunities. JAMA. 2015 Aug 4;314(5):478–88. [PMID:
26241599]
cal history—”At any time, has a partner ever hit you,
CMDT19_Ch01_p0001-p0019.indd 17 05/07/18 2:04 PM

18 CMDT 2019 C 1
hapter
PREVENTION OF SUBSTANCE ABUSE: As with cigarette use, clinician identification and coun-
ALCOHOL & ILLICIT DRUGS seling about alcohol misuse is essential. An estimated
15–30% of hospitalized patients have problems with alco-
Substance abuse is a major public health problem in the hol abuse or dependence, but the connection between
United States, where approximately 51% of adults 18 years patients’ presenting complaints and their alcohol use is
and older are current regular drinkers (at least 12 drinks in often missed. The USPSTF recommends screening adults
the past year). Maximum recommended consumption for aged 18 years and older for alcohol misuse.
adult women and those older than 65 years is three or The Alcohol Use Disorder Identification Test (AUDIT)
fewer drinks per day (seven per week), and for adult men, consists of questions on the quantity and frequency of
four or fewer drinks per day (14 per week). The spectrum alcohol consumption, on alcohol dependence symptoms,
of alcohol misuse includes risky drinking (alcohol con- and on alcohol-related problems (Table 1–7). The AUDIT
sumption above the recommended daily, weekly, or per- questionnaire is a cost-effective and efficient diagnostic
occasion amounts), harmful use (a pattern causing damage tool for routine screening of alcohol use disorders in
to health), alcohol abuse (a pattern leading to clinically primary care settings. Brief advice and counseling with-
significant impairment or distress), and alcohol depen- out regular follow-up and reinforcement cannot sustain
dence (defined as three or more of the following: tolerance, significant long-term reductions in unhealthy drinking
withdrawal, increased consumption, desire to cut down behaviors.
use, giving up social activities, increased time using alcohol Time restraints may prevent clinicians from using the
or recovering from use, continued use despite known AUDIT to screen patients, but single-question screening
adverse effects). Underdiagnosis and under-treatment of tests for unhealthy alcohol use may help increase the fre-
alcohol misuse is substantial, both because of patient quency of subsequent AUDIT screening in primary care
denial and lack of detection of clinical clues. Treatment settings. The National Institute on Alcohol Abuse and
rates for alcohol dependence have slightly declined over Alcoholism recommends the following single-question
the last several years. Only a quarter of alcohol-dependent screening test (validated in primary care settings): “How
patients have ever been treated. many times in the past year have you had X or more drinks
Table 1–7. Screening for alcohol abuse using the Alcohol Use Disorder Identification Test (AUDIT).
(Scores for response categories are given in parentheses. Scores range from 0 to 40, with a cutoff score of 5 or more indicating
hazardous drinking, harmful drinking, or alcohol dependence.)
1. How often do you have a drink containing alcohol?
(0) Never (1) Monthly or less (2) Two to four times a month (3) Two or three times a week (4) Four or more times a week
2. How many drinks containing alcohol do you have on a typical day when you are drinking?
(0) 1 or 2 (1) 3 or 4 (2) 5 or 6 (3) 7 to 9 (4) 10 or more
3. How often do you have six or more drinks on one occasion?
(0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily
4. How often during the past year have you found that you were not able to stop drinking once you had started?
5. How often during the past year have you failed to do what was normally expected of you because of drinking?
6. How often during the past year have you needed a first drink in the morning to get yourself going after a heavy drinking session?
7. How often during the past year have you had a feeling of guilt or remorse after drinking?
8. How often during the past year have you been unable to remember what happened the night before because you had been drinking?
9. Have you or has someone else been injured as a result of your drinking?
(0) No (2) Yes, but not in the past year (4) Yes, during the past year
10. Has a relative or friend or a doctor or other health worker been concerned about your drinking or suggested you cut down?
(0) No (2) Yes, but not in the past year (4) Yes, during the past year
Adapted, with permission, from BMJ Publishing Group Ltd. and Piccinelli M et al. Efficacy of the alcohol use disorders identification test as
a screening tool for hazardous alcohol intake and related disorders in primary care: a validity study. BMJ. 1997 Feb 8;314(7078):420–4.
CMDT19_Ch01_p0001-p0019.indd 18 05/07/18 2:04 PM

in a day?” (X is 5 for men and 4 for women, and a response options to make naloxone more available to treat opioid
of more than 1 time is considered positive.) overdose. (See Chapter 5.)
Clinicians should provide those who screen positive for Use of illegal drugs—including cocaine, methamphet-
hazardous or risky drinking with brief behavioral counsel- amine, and so-called designer drugs—either sporadically
ing interventions to reduce alcohol misuse. Use of screen- or episodically remains an important problem. Lifetime
ing procedures and brief intervention methods (see prevalence of drug abuse is approximately 8% and is gener-
Chapter 25) can produce a 10–30% reduction in long-term ally greater among men, young and unmarried individuals,
alcohol use and alcohol-related problems. Native Americans, and those of lower socioeconomic sta-
Several pharmacologic agents are effective in reducing tus. As with alcohol, drug abuse disorders often coexist
alcohol consumption. In acute alcohol detoxification, long- with personality, anxiety, and other substance abuse disor-
acting benzodiazepines are preferred because they can be ders. Abuse of anabolic-androgenic steroids has been asso-
given on a fixed schedule or through “front-loading” or ciated with use of other illicit drugs, alcohol, and cigarettes
“symptom-triggered” regimens. Adjuvant sympatholytic and with violence and criminal behavior.
medications can be used to treat hyperadrenergic symp- As with alcohol abuse, the lifetime treatment rate for
toms that persist despite adequate sedation. Three drugs drug abuse is low (8%). The recognition of drug abuse
are FDA approved for treatment of alcohol dependence: presents special problems and requires that the clinician
disulfiram, naltrexone, and acamprosate. Disulfiram, an actively consider the diagnosis. Clinical aspects of sub-
aversive agent, has significant adverse effects and conse- stance abuse are discussed in Chapter 25.
quently, compliance difficulties have resulted in no clear Buprenorphine has potential as a medication to amelio-
evidence that it increases abstinence rates, decreases relapse rate the symptoms and signs of withdrawal from opioids
rates, or reduces cravings. Compared with placebo, naltrex- and has been shown to be effective in reducing concomi-
one can lower the risk of treatment withdrawal in alcohol- tant cocaine and opioid abuse. The risk of overdose is lower
dependent patients, and the long-acting intramuscular with buprenorphine than methadone and it is preferred for
formulation of naltrexone has been found to be well toler- patients at high risk for methadone toxicity (see Chapter 5).
ated and to reduce drinking significantly among treat- Rapid opioid detoxification with opioid antagonist induc-
ment-seeking alcoholics over a 6-month period. In a tion using general anesthesia has emerged as an approach
randomized, controlled trial, patients receiving medical to treat opioid dependence. However, a randomized com-
management with naltrexone, a combined behavioral parison of buprenorphine-assisted rapid opioid detoxifica-
intervention, or both, fared better on drinking outcomes, tion with naltrexone induction and clonidine-assisted
whereas acamprosate showed no evidence of efficacy with opioid detoxification with delayed naltrexone induction
or without combined behavioral intervention. Persons who found no significant differences in rates of completion of
receive short-term treatment with naltrexone have a lower inpatient detoxification, treatment retention, or propor-
chance of alcoholism relapse. Topiramate is a promising tions of opioid-positive urine specimens, and the anesthe-
treatment for alcohol dependence. A 6-month randomized sia procedure was associated with more potentially
trial of topiramate versus naltrexone revealed a greater life-threatening adverse events. Finally, cognitive-behavior
reduction of alcohol intake and cravings in participants therapy, contingency management, couples, and family
receiving topiramate. Topiramate’s side effect profile is therapy, and other types of behavioral treatment have been
favorable, and its benefits appear to increase over time. shown to be effective interventions for drug addiction.
Clinicians should be aware that although topiramate
appears to be an effective treatment for alcohol depen-
dence, the manufacturer has not pursued FDA approval for Berger D et al. Primary care management of alcohol misuse.
this indication. Med Clin North Am. 2015 Sep;99(5):989–1016. [PMID:
Over the last decade, the rate of prescription drug abuse 26320043]
Delker E et al. Alcohol consumption in demographic subpopula-
has increased dramatically, particularly at both ends of the
tions: an epidemiologic overview. Alcohol Res. 2016;38(1):7–15.
age spectrum. The most commonly abused classes of medi- [PMID: 27159807]
cations are pain relievers, tranquilizers, stimulants, and Dowell D et al. CDC guideline for prescribing opioids for
sedatives. Opioid-based prescription drug abuse, misuse, chronic pain—United States, 2016. JAMA. 2016 Apr
and overdose has reached epidemic proportions in the 19;315(15):1624–45. [PMID: 26977696]
United States. Deaths due to prescription opioid overdose Moyer VA; U.S. Preventive Services Task Force. Screening and
behavioral counseling interventions in primary care to reduce
have dramatically increased. Opioid risk mitigation strate-
alcohol misuse: U.S. Preventive Services Task Force recom-
gies include use of risk assessment tools, treatment agree- mendation statement. Ann Intern Med. 2013 Aug 6;159(3):
ments (contracts), and urine drug testing. Additional 210–8. [PMID: 23698791]
strategies include establishing and strengthening prescrip- U.S. Food and Drug Administration. FDA supports greater access
tion drug monitoring programs, regulating pain manage- to naloxone to help reduce opioid overdose deaths. 2016
ment facilities, and establishing dosage thresholds requiring August 10. http://blogs.fda.gov/fdavoice/index.php/2016/08/
fda-supports-greater-access-to-naloxone-to-help-reduce-
consultation with pain specialists. The FDA supports
opioid-overdose-deaths/
greater access to naloxone and is currently exploring
CMDT19_Ch01_p0001-p0019.indd 19 05/07/18 2:04 PM

20 CMDT 2019
2
Common Symptoms
Paul L. Nadler, MD
Ralph Gonzales, MD, MSPH
COUGH and sore throat help confirm this diagnosis. Dyspnea (at
rest or with exertion) may reflect a more serious condition,
and further evaluation should include assessment of oxy-
ESSENTIAL INQUIRIES genation (pulse oximetry or arterial blood gas measure-
ment), airflow (peak flow or spirometry), and pulmonary
parenchymal disease (chest radiography). The timing and
» Age, tobacco or cannabis use, occupational history, character of the cough are not very useful in establishing
»
environmental exposures, and duration of cough. the cause of acute cough syndromes, although cough-
» Dyspnea (at rest or with exertion). variant asthma should be considered in adults with promi-
»
» Vital signs (heart rate, respiratory rate, body nent nocturnal cough, and persistent cough with phlegm
»
temperature). increases the likelihood of chronic obstructive pulmonary
»
disease (COPD). The presence of posttussive emesis or
Chest examination.
inspiratory whoop in adults modestly increases the likeli-
»
» Chest radiography when unexplained cough lasts hood of pertussis, and the absence of paroxysmal cough
»
more than 3–6 weeks. and the presence of fever decreases its likelihood. Uncom-
mon causes of acute cough should be suspected in those
» General Considerations
with heart disease (heart failure) or hay fever (allergic rhinitis)
and those with occupational risk factors (such as
»
Cough is the most common symptom for which patients farmworkers).
seek medical attention. Cough adversely affects personal
and work-related interactions, disrupts sleep, and often 2. Persistent and chronic cough—Cough due to acute
causes discomfort of the throat and chest wall. Most people respiratory tract infection resolves within 3 weeks in the
seeking medical attention for acute cough desire symptom vast majority (more than 90%) of patients. Pertussis should
relief; few are worried about serious illness. Cough results be considered in adolescents and adults with persistent or
from stimulation of mechanical or chemical afferent nerve severe cough lasting more than 3 weeks, and in selected
receptors in the bronchial tree. Effective cough depends on geographic areas where its prevalence approaches 20%
an intact afferent–efferent reflex arc, adequate expiratory (although its exact prevalence is difficult to ascertain due
and chest wall muscle strength, and normal mucociliary to the limited sensitivity of diagnostic tests).
production and clearance. When angiotensin-converting enzyme (ACE) inhibitor
therapy, acute respiratory tract infection, and chest radio-
» Clinical Findings graph abnormalities are absent, most cases of persistent and
chronic cough are due to (or exacerbated by) postnasal drip
»
A. Symptoms (upper airway cough syndrome), asthma, or gastroesopha-
geal reflux disease (GERD), or some combination of these
Distinguishing acute (less than 3 weeks), persistent
three entities. Approximately 10% of cases are caused by
(3–8 weeks), and chronic (more than 8 weeks) cough illness
nonasthmatic eosinophilic bronchitis. A history of nasal or
syndromes is a useful first step in evaluation. Postinfec-
sinus congestion, wheezing, or heartburn should direct sub-
tious cough lasting 3–8 weeks has also been referred to as
sequent evaluation and treatment, though these conditions
subacute cough to distinguish this common, distinct
frequently cause persistent cough in the absence of typical
clinical entity from acute and chronic cough.
symptoms. Dyspnea at rest or with exertion is not com-
1. Acute cough—In healthy adults, most acute cough syn- monly reported among patients with persistent cough; dys-
dromes are due to viral respiratory tract infections. Addi- pnea requires assessment for chronic lung disease, HF,
tional features of infection such as fever, nasal congestion, anemia, pulmonary embolism, or pulmonary hypertension.
CMDT19_Ch02_p0020-p0045.indd 20 18/06/18 4:15 PM

COMMON SYMPTOMS CMDT 2019 21
Bronchogenic carcinoma is suspected when cough is

accompanied by unexplained weight loss, hemoptysis, and Table 2–1. Positive and negative likelihood ratios for
fevers with night sweats, particularly in persons with sig- history, physical examination, and laboratory findings
nificant tobacco or occupational exposures (asbestos, in the diagnosis of pneumonia.
radon, diesel exhaust, and metals). Persistent and chronic
Positive Negative
cough accompanied by excessive mucus secretions
Likelihood Likelihood
increases the likelihood of COPD, particularly among Finding Ratio Ratio
smokers, or of bronchiectasis if accompanied by a history
of recurrent or complicated pneumonia; chest radiographs Medical history
are helpful in diagnosis. Fever 1.7–2.1 0.6–0.7
Chills 1.3–1.7 0.7–0.9
B. Physical Examination Physical examination
Examination can direct subsequent diagnostic testing for Tachypnea (RR > 25 breaths/min) 1.5–3.4 0.8
acute cough. Pneumonia is suspected when acute cough is Tachycardia (> 100 beats/min 1.6–2.3 0.5–0.7
accompanied by vital sign abnormalities (tachycardia, in two studies or
tachypnea, fever). Findings suggestive of airspace consoli- > 120 beats/min in one study)
dation (rales, decreased breath sounds, fremitus, egoph-
Hyperthermia (> 37.8°C) 1.4–4.4 0.6–0.8
ony) are significant predictors of community-acquired
pneumonia but are present in the minority of cases. Puru- Chest examination
lent sputum is associated with bacterial infections in Dullness to percussion 2.2–4.3 0.8–0.9
patients with structural lung disease (eg, COPD, cystic Decreased breath sounds 2.3–2.5 0.6–0.8
fibrosis), but it is a poor predictor of pneumonia in the
otherwise healthy adult. Wheezing and rhonchi are fre- Crackles 1.6–2.7 0.6–0.9
quent findings in adults with acute bronchitis and do not Rhonchi 1.4–1.5 0.8–0.9
indicate consolidation or adult-onset asthma in most cases. Egophony 2.0–8.6 0.8–1.0
Examination of patients with persistent cough should
Laboratory findings
look for evidence of chronic sinusitis, contributing to post-
nasal drip syndrome or asthma. Chest and cardiac signs Leukocytosis (> 11 × 109/L in 1.9–3.7 0.3–0.6
may help distinguish COPD from HF. In patients with one study or ≥ 10.4 × 109/L
in another study)
cough and dyspnea, a normal match test (ability to blow
out a match from 25 cm away) and maximum laryngeal RR, respiratory rate.
height greater than 4 cm (measured from the sternal notch
to the cricoid cartilage at end expiration) substantially
decrease the likelihood of COPD. Similarly, normal jugular patients have effective respiratory compensation. During
venous pressure and no hepatojugular reflux decrease the documented outbreaks, clinical diagnosis of influenza has
likelihood of biventricular HF. a positive predictive value of ~70%; this usually obviates
the need for rapid diagnostic tests.
C. Diagnostic Studies
2. Persistent and chronic cough—Chest radiography is
1. Acute cough—Chest radiography should be considered indicated when ACE inhibitor therapy–related and postin-
for any adult with acute cough whose vital signs are abnor- fectious cough are excluded. If pertussis is suspected, poly-
mal or whose chest examination suggests pneumonia. The merase chain reaction testing should be performed on a
relationship between specific clinical findings and the nasopharyngeal swab or nasal wash specimen—although
probability of pneumonia is shown in Table 2–1. A large, the ability to detect pertussis decreases as the duration of
multicenter randomized clinical trial found that elevated cough increases. When the chest film is normal, postnasal
serum C-reactive protein (levels greater than 30 mg/dL) drip, asthma, or GERD are the most likely causes. The
improves diagnostic accuracy of clinical prediction rules presence of typical symptoms of these conditions directs
for pneumonia in adults with acute cough; procalcitonin further evaluation or empiric therapy, though typical
added no clinically relevant information. A meta-analysis symptoms are often absent. Definitive tests for determin-
found that lung ultrasonography had better accuracy than ing the presence of each are available (Table 2–2). However,
chest radiography for the diagnosis of adult community- empiric treatment with a maximum-strength regimen for
acquired pneumonia. Lung ultrasonography had a pooled postnasal drip, asthma, or GERD for 2–4 weeks is one rec-
sensitivity of 0.95 (95% confidence interval [CI], 0.93–0.97) ommended approach since documenting the presence of
and a specificity of 0.90 (95% CI, 0.86–0.94). Chest radiog- postnasal drip, asthma, or GERD does not mean they are
raphy had a pooled sensitivity of 0.77 (95% CI, 0.73–0.80) the cause of the cough. Alternative approaches to identify-
and a specificity of 0.91 (95% CI, 0.87–0.94). In patients ing patients who have asthma with its corticosteroid-
with dyspnea, pulse oximetry and peak flow help exclude responsive cough include examining induced sputum for
hypoxemia or obstructive airway disease. However, a nor- increased eosinophil counts (greater than 3%) or providing
mal pulse oximetry value (eg, greater than 93%) does not an empiric trial of prednisone, 30 mg daily orally for 2 weeks.
rule out a significant alveolar–arterial (A–a) gradient when Spirometry may help identify large airway obstruction in
CMDT19_Ch02_p0020-p0045.indd 21 18/06/18 4:15 PM

22 CMDT 2019 Cha e 2
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r
Chlamydophila- or Mycoplasma-documented infection or
Table 2–2. Empiric treatments or tests for persistent outbreaks, first-line antibiotics include erythromycin or
cough. doxycycline. However, antibiotics do not improve cough
severity or duration in patients with uncomplicated acute
Suspected Step 1 ( mpiric Step 2 (Definitive
bronchitis. In patients with bronchitis and wheezing,
E
Condition Therapy) Testing)
inhaled beta-2-agonist therapy reduces severity and dura-
Postnasal drip Therapy for allergy or Sinus CT scan; tion of cough. In patients with acute cough, treating the
chronic sinusitis ENT referral accompanying postnasal drip (with antihistamines, decon-
Asthma Beta-2-agonist Spirometry; consider gestants, or nasal corticosteroids) can be helpful. A
methacholine chal- Cochrane review (n = 163) found codeine to be no more
lenge if normal effective than placebo in reducing cough symptoms.
GERD Lifestyle and diet Esophageal pH
modifications with monitoring
B. Persistent and Chronic Cough
or without proton
pump inhibitors Evaluation and management of persistent cough often
require multiple visits and therapeutic trials, which fre-
ENT, ear, nose, and throat; GERD, gastroesophageal reflux disease.
quently lead to frustration, anger, and anxiety. When per-
tussis infection is suspected early in its course, treatment
patients who have persistent cough and wheezing and who with a macrolide antibiotic (see Chapter 33) is appropriate
are not responding to asthma treatment. When empiric to reduce organism shedding and transmission. When
treatment trials are not successful, additional evaluation pertussis has lasted more than 7–10 days, antibiotic treat-
with pH manometry, endoscopy, barium swallow, sinus ment does not affect the duration of cough, which can last
CT, or high-resolution chest CT may identify the cause. up to 6 months. Early identification, revaccination with
» Differential Diagnosis
Tdap, and treatment of adult patients who work or live with
persons at high risk for complications from pertussis (preg-
»
A. Acute Cough nant women, infants [particularly younger than 1 year],
and immunosuppressed individuals) are encouraged.
Acute cough may be a symptom of acute respiratory tract Table 2–2 outlines empiric treatments for persistent
infection, asthma, allergic rhinitis, and HF, as well as many cough. There is no evidence to guide how long to continue
less common causes. treatment for persistent cough due to postnasal drip,
asthma, or GERD. Studies have not found a consistent
B. Persistent and Chronic Cough benefit of inhaled corticosteroid therapy in adults with
Causes of persistent cough include environmental expo- persistent cough. Eight weeks of thrice-weekly azithromy-
sures (cigarette smoke, air pollution), occupational expo- cin did not improve cough in patients without asthma.
sures, pertussis, postnasal drip, asthma (including When empiric treatment trials fail, consider other
cough-variant asthma), GERD, COPD, bronchiectasis, causes of chronic cough such as obstructive sleep apnea,
eosinophilic bronchitis, tuberculosis or other chronic infec- tonsillar or uvular enlargement, and environmental fungi.
tion, interstitial lung disease, and bronchogenic carcinoma. The small percentage of patients with idiopathic chronic
COPD is a common cause of persistent cough among cough should be managed in consultation with an otolar-
patients older than 50 years. Persistent cough may also be yngologist or a pulmonologist; consider a high-resolution
due to somatic cough syndrome (previously called “psycho- CT scan of the lungs. Treatment options include nebulized
genic cough”) or tic cough (previously called “habit cough”). lidocaine therapy and morphine sulfate, 5–10 mg orally
twice daily. Sensory dysfunction of the laryngeal branches
» Treatment of the vagus nerve may contribute to persistent cough syn-
dromes and may help explain the effectiveness of gabapen-
»
A. Acute Cough tin in patients with chronic cough. Speech pathology
Treatment of acute cough should target the underlying therapy combined with pregabalin has some benefit in
etiology of the illness, the cough reflex itself, and any addi- chronic refractory cough. In patients with reflex cough
tional factors that exacerbate the cough. Cough duration is syndrome, therapy aimed at shifting the patient’s atten-
typically 1–3 weeks, yet patients frequently expect cough to tional focus from internal stimuli to external focal points
last fewer than 10 days. Limited studies on the use of dex- can be helpful. Proton pump inhibitors are not effective on
tromethorphan suggest a minor or modest benefit; dextro- their own; most benefit appears to come from lifestyle
methorphan should be avoided in children and adolescents modifications and weight reduction.
because of concerns about misuse.
When influenza is diagnosed (including H1N1 influ- » When to Refer
enza), oral oseltamivir or zanamivir or intravenous pera-
»
mivir are equally effective (1 less day of illness) when • Failure to control persistent or chronic cough following
initiated within 30–48 hours of illness onset; treatment is empiric treatment trials.
recommended regardless of illness duration when patients • Patients with recurrent symptoms should be referred to
have severe influenza requiring hospitalization. In an otolaryngologist, pulmonologist, or gastroenterologist.
CMDT19_Ch02_p0020-p0045.indd 22 18/06/18 4:15 PM

COMMON SYMPTOMS CMDT 2019 23
» When to Admit
»
presents in patients: rate of onset, previous dyspnea, medi-
cations, comorbidities, psychological profile, and severity
• Patient at high risk for tuberculosis for whom compli- of underlying disorder.
ance with respiratory precautions is uncertain.
» Clinical Findings
• Need for urgent bronchoscopy, such as suspected for-
eign body. »
• Smoke or toxic fume inhalational injury. A. Symptoms

• Gas exchanged is impaired by cough. The duration, severity, and periodicity of dyspnea influ-
• Patients at high risk for barotrauma (eg, recent ence the tempo of the clinical evaluation. Rapid onset or
pneumothorax). severe dyspnea in the absence of other clinical features
should raise concern for pneumothorax, pulmonary embo-
lism, or increased left ventricular end-diastolic pressure
Gibson P et al; CHEST Expert Cough Panel. Treatment of unex- (LVEDP). Spontaneous pneumothorax is usually accompa-
plained chronic cough: CHEST Guideline and Expert Panel nied by chest pain and occurs most often in thin, young
Report. Chest. 2016 Jan;149(1):27–44. [PMID: 26426314]
Kahrilas PJ et al; CHEST Expert Cough Panel. Chronic cough males and in those with underlying lung disease. Pulmo-
due to gastroesophageal reflux in adults: CHEST guideline nary embolism should always be suspected when a patient
and expert panel report. Chest. 2016 Dec;150(6):1341–60. with new dyspnea reports a recent history (previous 4
[PMID: 27614002] weeks) of prolonged immobilization or surgery, estrogen
Michaudet C et al. Chronic cough: evaluation and management. therapy, or other risk factors for deep venous thrombosis
Am Fam Physician. 2017 Nov 1;96(9):575–80. [PMID: (DVT) (eg, previous history of thromboembolism, cancer,
29094873]
Moore A et al. Clinical characteristics of pertussis-associated obesity, lower extremity trauma) and when the cause of
cough in adults and children: a diagnostic systematic review dyspnea is not apparent. Silent myocardial infarction,
and meta-analysis. Chest. 2017 Aug;152(2):353–67. [PMID: which occurs more frequently in diabetic persons and
28511929] women, can result in increased LVEDP, acute HF, and
Smith JA et al. Chronic cough. N Engl J Med. 2016 Oct 20; dyspnea.
375(16):1544–51. [PMID: 27797316] Accompanying symptoms provide important clues to
Tarlo SM et al. Evaluation of occupational and environmental
factors in the assessment of chronic cough in adults: a system- causes of dyspnea. When cough and fever are present, pul-
atic review. Chest. 2016 Jan;149(1):143–60. [PMID: 26501943] monary disease (particularly infection) is the primary
Teepe J et al; GRACE Consortium. Predicting the presence of concern; myocarditis, pericarditis, and septic emboli can
bacterial pathogens in the airways of primary care patients present in this manner. Chest pain should be further char-
with acute cough. CMAJ. 2016 Oct 24. [Epub ahead of print] acterized as acute or chronic, pleuritic or exertional.
[PMID: 27777252] Although acute pleuritic chest pain is the rule in acute
pericarditis and pneumothorax, most patients with pleu-
DYSPNEA ritic chest pain in the outpatient clinic have pleurisy due to
acute viral respiratory tract infection. Periodic chest pain
that precedes the onset of dyspnea suggests myocardial
ESSENTIAL INQUIRIES ischemia or pulmonary embolism. When associated with
wheezing, most cases of dyspnea are due to acute bronchi-
» Fever, cough, and chest pain. tis; however, other causes include new-onset asthma, for-
eign body, and vocal cord dysfunction. Interstitial lung
»
» Vital sign measurements; pulse oximetry. disease and pulmonary hypertension should be considered
»
» »
Cardiac and chest examination. in patients with symptoms (or history) of connective tissue
» »
Chest radiography and arterial blood gas mea- disease.
surement in selected patients. When a patient reports prominent dyspnea with mild
or no accompanying features, consider noncardiopulmo-
nary causes of impaired oxygen delivery (anemia, methe-
» General Considerations moglobinemia, cyanide ingestion, carbon monoxide),
metabolic acidosis, panic disorder, neuromuscular disor-
»
Dyspnea is a subjective experience or perception of uncom- ders, and chronic pulmonary embolism.
fortable breathing. There is a lack of empiric evidence on Platypnea-orthodeoxia syndrome is characterized by
the prevalence, etiology, and prognosis of dyspnea in gen- dyspnea and hypoxemia on sitting or standing that
eral practice. The relationship between level of dyspnea improves in the recumbent position. It may be caused by
and the severity of underlying disease varies widely among an intracardiac shunt, pulmonary vascular shunt, or venti-
individuals. Dyspnea can result from conditions that lation-perfusion mismatch.
increase the mechanical effort of breathing (eg, COPD,
restrictive lung disease, respiratory muscle weakness), con-
ditions that produce compensatory tachypnea (eg, hypox- B. Physical Examination
emia, acidosis), primary pulmonary vasculopathy A focused physical examination should include evaluation
(pulmonary hypertension), or psychogenic conditions. The of the head and neck, chest, heart, and lower extremities.
following factors play a role in how and when dyspnea Visual inspection of the patient can suggest obstructive
CMDT19_Ch02_p0020-p0045.indd 23 18/06/18 4:15 PM

24 CMDT 2019 Cha e 2
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none is present, there is a very low probability (less than
Table 2–3. Clinical findings suggesting obstructive 10%) of increased LVEDP, but when two or more are pres-
airway disease. ent, there is a very high probability (greater than 90%) of
increased LVEDP.
djusted Likelihood Ratios
A
C. Diagnostic Studies
Factor Present Factor bsent
Causes of dyspnea that can be managed without chest radi-
A
> 40 pack-years 11.6 0.9 ography are few: ingestions causing lactic acidosis, anemia,
smoking
methemoglobinemia, and carbon monoxide poisoning.
Age ≥ 45 years 1.4 0.5 The diagnosis of pneumonia should be confirmed by chest
Maximum laryngeal 3.6 0.7 radiography in most patients, and elevated blood levels of
height ≤ 4 cm procalcitonin or C-reactive protein can support the diag-
All three factors 58.5 0.3 nosis of pneumonia in equivocal cases or in the presence of
interstitial lung disease. Conversely, a low procalcitonin
Reproduced, with permission, from Straus SE et al. The accuracy of can help exclude pneumonia in dyspneic patients present-
patient history, wheezing, and laryngeal measurements in diag- ing with HF. Lung ultrasonography is more accurate than
nosing obstructive airway disease. CARE-COAD1 Group. Clinical chest radiography for the diagnosis of pneumonia in
Assessment of the Reliability of the Examination—Chronic patients admitted to an acute geriatric ward. Chest radiog-
Obstructive Airways Disease. JAMA. 2000 Apr 12;283(14):1853–7. raphy is fairly sensitive and specific for new-onset HF
© 2000 American Medical Association. All rights reserved.
(represented by redistribution of pulmonary venous circu-
lation) and can help guide treatment of patients with other
airway disease (pursed-lip breathing, use of accessory cardiac diseases. NT-proBNP can assist in the diagnosis of
respiratory muscles, barrel-shaped chest), pneumothorax HF; the Acute Diagnostic Cut-Offs in the Emergency
(asymmetric excursion), or metabolic acidosis (Kussmaul Department study defines best diagnostic cutoff points.
respirations). Patients with impending upper airway End-expiratory chest radiography enhances detection of
obstruction (eg, epiglottitis, foreign body) or severe small pneumothoraces.
asthma exacerbation sometimes assume a tripod position. A normal chest radiograph has substantial diagnostic
Focal wheezing raises the suspicion for a foreign body or value. When there is no physical examination evidence of
other bronchial obstruction. Maximum laryngeal height COPD or HF and the chest radiograph is normal, the major
(the distance between the top of the thyroid cartilage and remaining causes of dyspnea include pulmonary embolism,
the suprasternal notch at end expiration) is a measure of Pneumocystis jirovecii infection (initial radiograph may be
hyperinflation. Obstructive airway disease is virtually normal in up to 25%), upper airway obstruction, foreign
nonexistent when a nonsmoking patient younger than 45 body, anemia, and metabolic acidosis. If a patient has tachy-
years has a maximum laryngeal height greater than 4 cm cardia and hypoxemia but a normal chest radiograph and
(Table 2–3). Absent breath sounds suggest a pneumotho- electrocardiogram (ECG), then tests to exclude pulmonary
rax. An accentuated pulmonic component of the second emboli, anemia, or metabolic acidosis are warranted. High-
heart sound (loud P2) is a sign of pulmonary hypertension resolution chest CT is particularly useful in the evaluation
and pulmonary embolism. of interstitial and alveolar lung disease. Helical (“spiral”) CT
Table 2–4 shows clinical predictors of increased LVEDP is useful to diagnose pulmonary embolism since the images
in dyspneic patients with no prior history of HF. When are high resolution and require only one breathhold by the
patient, but to minimize unnecessary testing and radiation
exposure, the clinician should first consider a clinical deci-
Table 2–4. Clinical findings suggesting increased left sion rule (with or without D-dimer testing) to estimate the
ventricular end-diastolic pressure. pretest probability of a pulmonary embolism. It is appropri-
ate to forego CT scanning in patients with very low proba-
Tachycardia bility of pulmonary embolus when other causes of dyspnea
Systolic hypotension are more likely (see Chapter 9).
Jugular venous distention (> 5–7 cm H2O)1
Table 2–4 shows clinical findings suggesting increased
Hepatojugular reflux (> 1 cm)2
Crackles, especially bibasilar
LVEDP. Elevated serum or B-type natriuretic peptide (BNP
Third heart sound3 or NT-proBNP) levels are both sensitive and specific for
Lower extremity edema increased LVEDP in symptomatic persons. BNP has been
Radiographic pulmonary vascular redistribution or cardiomegaly1 shown to reliably diagnose severe dyspnea caused by HF
1
and to differentiate it from dyspnea due to other conditions.
These findings are particularly helpful. However, systematic use of BNP in evaluation of dyspnea in
2
Proper abdominal compression for evaluating hepatojugular
the emergency department does not appear to have a clini-
reflux requires > 30 seconds of sustained right upper quadrant
abdominal compression. cally significant impact on patient or system outcomes, and
3
Auscultation of the heart at 45-degree angle in left lateral decubi- it does not conclusively affect hospital mortality rates.
tus position doubles the detection rate of third heart sounds. Newer cardiac biomarkers such as ST2 may have better
Data from Badgett RG et al. Can the clinical examination diagnose prognostic value for mortality and may help titrate medical
left-sided heart failure in adults? JAMA. 1997 Jun 4;277(21):1712–9. therapy.
CMDT19_Ch02_p0020-p0045.indd 24 18/06/18 4:15 PM

Another random document with
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Boghead were deposited under water as members of a regular
sequence of sedimentary strata. The yellow bodies which form so
great a part of the beds are practically all of the same type.
Reinschia and Pila cannot always be distinguished, and it would
seem that there are no adequate grounds for instituting two distinct
genera and referring them to different families of recent algae.
Stated briefly, my conclusion is that the algae of the French
authors may be definite organic bodies, but it is unwise to attempt to
determine their affinities within such narrow limits as have been
referred to in the above résumé. The structure of the bituminous
deposits is worthy of careful study, and it is by no means impossible
that further research might lead us to accept the view of the earlier
investigators, that the brightly coloured organic-like bodies may be
inorganic in origin.
D. RHODOPHYCEAE. (Florideae. Red Algae.)

The thallus of the members of this group assumes various forms,
and consists of branched cell-filaments of a more or less complex
structure. Cells of the thallus contain a red colouring matter in
addition to the green chlorophyll. The reproduction is asexual and
sexual; the formation of asexual reproductive cells (tetraspores) in
groups of four in sporangia is a characteristic method of
reproduction. Sexual reproduction is effected by means of distinct
male and female cells.
With the exception of a few fresh-water genera all the red algae
are marine. The Rhodophyceae, like the Cyanophyceae and
Chlorophyceae, include a shell-boring form which has been found in
the common razor-shell[343]. Several genera live as endophytes in the
tissues of other algae. The recent species of this section of algae are
characteristic of temperate and tropical seas. One subdivision of the
red algae, the Corallinaceae, is extremely important from a
geological point of view and must be dealt with in some detail.
Corallinaceae.
The thallus is usually encrusted with carbonate of lime; it is of a
branched cylindrical form in the well-known Corallina officinalis, Linn.
of the British coasts, of an encrusting and foliaceous type, in the
genus Lithophyllum, and of a more coral-like form in the genus
Lithothamnion. The reproductive organs occur in conceptacles,
having the form of small depressed cavities in the thallus, or
projecting as warty swellings above the surface of the plant. Asexual
reproduction is by means of tetraspores formed in conceptacles
resembling those containing the sexual cells. The Corallinaceae may
be subdivided into the two families Melobesieae and Corallineae[344].
Melobesieae. Thallus encrusting, leaf- or coral-like; unsegmented.
(Melobesia, Lithophyllum, Lithothamnion.)
Corallineae. Cylindrical filamentous and segmented thallus.
(Amphiroa and Corallina.)
The genus Corallina is the best known British representative of the
Corallinaceae. With other members of the group it was long
regarded as a coralline animal, and it is only comparatively recently
that the plant-nature of these forms has been generally admitted.
Lithophyllum, Lithothamnion, Melobesia, and other genera of the
Corallinaceae and some of the Siphoneae play a very important part
in the building and cementing of coral-reefs. The pink or rose-
coloured calcareous thallus of some of these calcareous algae or
Nullipores imparts to coral-reefs a characteristic appearance. In
some cases, indeed, the coral-reefs are very largely composed of
algae. Saville Kent[345] describes the Corallines or Nullipores of the
Australian Barrier-reef as furnishing a considerable quota towards
the composition of the coral rock. Mr Stanley Gardiner, who
accompanied the coral-boring expedition to the island of Funafuti,
has kindly allowed me to quote the following extract from his notes,
which affords an interesting example of the importance of calcareous
algae as reef-building organisms. “It is quite a misnomer to speak of
the outer edge of a reef like this (Rotuma Island) as being formed of
coral. It would be far better to call it a Nullipore reef, as it is
completely encrusted by these algae, while outside in the perfectly
clear water, 10 to 15 fathoms in depth, the bottom has a most
brilliant appearance from masses of red, white and pink Nullipores,
with only a stray coral here and there.”
Agassiz[346] has given an account of the occurrence of immense
masses of Nullipores (Udotea, Halimeda etc.) in the Florida reefs; his
description is illustrated by good figures of these algae.
In the Mediterranean there are true Nullipore reefs, which are
interesting geologically as well as botanically. Walther[347] has
described one of these limestone-banks in the Gulf of Naples which
occurs about 1 kilometre from the coast and 30 metres below the
surface of the water. Every dredging, he says, brings up numberless
masses of Lithothamnion fasciculatum (Lamarck), and L. crassum
(Phil.). Between the branches of the algae, gasteropods and other
animals become completely enclosed by the growing plants, while
diatoms, foraminifera, and other forms of life are abundant. Water
percolating through the mass gradually destroys the structure of the
algal thalli, and in places reduces the whole bank to a compact
structureless limestone.
The same author[348] has also called attention to the importance of
Lithophyllum as a constructive element in the coral-reefs off the Sinai
peninsula.
Lithothamnion a typical genus of the Corallinaceae may be briefly
described.
Lithothamnion. Fig. 37.

Philippi[349] was the first writer to describe this and other genera as
plants. He gave the following definition of Lithothamnion:
“Stirps calcarea rigida, e ramis cylindricis vel compressiusculis dichotoma ramosis
constans.”
The thallus of Lithothamnion grows attached to the face of a rock

or other foundation, and forms a hard, stony mass, assuming various
coralline shapes. The exposed face may have the form of numerous
short branches or of an irregular warty surface.
In section (fig. 37, A.) the lower part of the thallus is seen to be
made up of rows of cells radiating out from a central point, and the
upper portion consists of vertical and horizontal rows of cells. The
whole body is divided up into a large number of small cells by
anticlinal and periclinal walls, and possesses an evident cellular as
distinct from a tubular structure. Conceptacles containing
reproductive organs are either sunk in the thallus or project above
the surface. The two types of structure in a single thallus are shown
in fig. 37, A, also a conceptacle containing tetraspores.
Fig. 37, A. Section of a recent Lithothamnion (after Rosanoff[350], × 200).

B. Section of Lithothamnion suganum, Roth (after Rothpletz[351], × 100).
C. A conceptacle with tetraspores from a Tertiary Lithothamnion (after
Früh[352], × 300). D. Sphaerocodium Bornemanni Roth, (after Rothpletz,
× 150).
In the closely allied Lithophyllum the thallus is encrusting, and in
section it presents the same appearance as the lower part of a
Lithothamnion thallus.
Species of Lithothamnion occur in the Mediterranean Sea, and are
abundant in the arctic regions[353], while on the British coasts the
genus is represented by four species[354]. Some large specimens of
Lithothamnion and Lithophyllum are exhibited in one of the show-
cases in the botanical department of the British Museum. For the
best figures and descriptions of recent species reference should be
made to the works of Hauck, Rosanoff, Rosenvinge, Kjellman and
Solms-Laubach[355].
It is to be expected that such calcareous algae as Lithothamnion
should be widely represented by fossil forms. In addition to the
botanical importance of the data furnished by the fossil species as to
the past history of the Corallinaceae, there is much of geological
interest to be learnt from a study of the manner of occurrence of both
the fossil and recent representatives. As agents of rock-building the
coralline algae are especially important. The late Prof. Unger[356] in
1858 gave an account of the so-called Leithakalk of the Tertiary
Vienna basin, and recognised the importance of fossil algae as rock-
forming organisms. The Miocene Leithakalk, which is widely used in
Vienna as a building stone[357], consists in part of limestone rocks
consisting to a large extent of Lithothamnion.
Since the publication of Unger’s work several writers have
described numerous fossil species of Lithothamnion from various
geological horizons. A few examples will suffice to illustrate the
range and structure of this and other genera of the Corallinaceae. In
dealing with the fossil species it is often impossible to make use of
those characters which are of primary importance in the recognition
of recent species. The fossil thallus is usually too intimately
associated with the surrounding rock to admit of any use being made
of external form as a diagnostic feature. The size and form of the
cells must be taken as the chief basis on which to determine specific
differences. In the absence of conceptacles or reproductive organs it
is not always easy to distinguish calcareous algae from fossil
Hydrozoa or Bryozoa. In many instances, however, apart from the
nature and size of the elements composing the thallus, the
conceptacles afford a valuable aid to identification. An example of a
fossil conceptacle containing tetraspores is shown in fig. 37, C; it is
from a Tertiary species of Lithothamnion, described by Früh from
Montévraz in Switzerland.
• • • • •
1. Lithothamnion mamillosum Gümb. Fig. 32, A (i) and (ii). (p.
155.) This species was first recorded by Gümbel[358] from the Upper
Cretaceous (Danian) rocks of Petersbergs, near Maëstricht, on the
Belgian frontier. It was originally described as a Bryozoan. The
thallus has the form of an encrusting calcareous structure bearing on
its upper surface thick nodular branches, as shown in fig. 32, A (ii); in
section, A (i), the thallus consists of a regular series of rectangular
cells.
The specific name mamillosum has also been given to a recent
species by Hauck[359], but probably in ignorance of the existence of
Gümbel’s Cretaceous species.
• • • • •
2. Lithothamnion suganum Roth. Fig. 37, B. The section of this
form given in fig. 37, B shows three oval conceptacles filled with
crystalline material. The two lower conceptacles originally
communicated with the surface of the thallus, but as in recent
species the deeper portions of the algal body became covered over
by additions to the surface, forming merely dead foundations for new
and overlying living tissues.
The cells of the thallus have a breadth of 7–9µ, and a length of 9–
12µ.
The specimen was obtained from a Lithothamnion bank, probably
of Upper Oligocene age, in Val Sugana[360], in the Austrian Tyrol.
Numerous other species of Jurassic, Cretaceous and Tertiary age
might be quoted, but the above may suffice to illustrate the general
characters and mode of occurrence of the genus. It is important that
the student should become familiar with the Lithothamnion and
Lithophyllum types of thallus, in view of their frequent occurrence in
crystalline limestone rocks and in such comparatively recent
deposits as those of upraised coral-reefs. The coral-rock of
Barbados and other West-Indian islands affords a good illustration of
the manner of occurrence of fossil coralline algae in association with
corals and other organisms[361].
In the fossil species of Lithothamnion hitherto recorded there do
not appear to be any important features in which they differ from
recent forms; the geological history of the genus so far as it is
known, favours the view that the generic characters are of
considerable antiquity.
Solenopora. Fig. 38.

Mr A. Brown[362], of Aberdeen, has recently brought forward good
evidence for including various calcareous fossils, described by
several authors under different names and referred to various
genera of fossil animals, in the genus Solenopora, which he places
among the coralline algae.
Species of this genus have been described from England,
Scotland, Esthonia, Russia, and other countries. The geological
range of Solenopora appears to be from Ordovician to Jurassic
rocks; in some cases it is an important constituent of beds of
limestone.
• • • • •
Solenopora compacta (Billings). Fig. 38. This species was
originally described by Billings as Stromatopora compacta, and
afterwards defined by Nicholson and Etheridge. The thallus forms
sub-spheroidal masses, from the size of a hemp-seed to that of an
orange. The external surface is lobulate; the fractured surface has a
porcellaneous and sometimes a fibrous appearance, and is usually
white or light brown in colour. In vertical section (fig. 38, B) the cells
are elongated and arranged in a radiating and parallel fashion; they
often occur in concentric layers. The cells have a diameter of about
¹⁄₁₇ mm. and possess distinctly undulating walls, as seen in a
tangential section (fig. 38, A). Brown describes certain larger cells in
the thallus (fig. 38, A) as sporangia[363], but it is difficult to recognise
any distinct sporangial cavities in the drawing. The example figured
is from the Trenton limestone of Canada; a variety of the same
species has been recorded from the Ordovician rocks of Girvan in
Ayrshire. There appear to be good reasons for accepting Brown’s
conclusion that Solenopora belongs to the Corallinaceae rather than
to the Hydrozoa, among which it was originally included. After
comparing Solenopora with recent genera of Florideae, Brown
concludes that “the forms of the cells and cell-walls, the method of
increase, and the arrangement of the tissue cells in the various
species of Solenopora bear strong evidence of relationship between
that genus and the calcareous algae[364].”
Fig. 38. Solenopora compacta (Billings). A. Tangential section. × 100. B.

Vertical section. × 50. (After Brown.)
The importance of the calcareous Rhodophyceae has been
frequently emphasised by recent researches, and our knowledge of
the rock-building forms is already fairly extensive. We possess
evidence of the existence of species of different genera in
Ordovician seas, as well as in those of the Silurian, Triassic,
Jurassic, and more recent periods. It is reasonable to prophesy that
further researches into the structure of ancient limestones will
considerably extend our knowledge of the geological and botanical
history of the Corallinaceae.
Numerous fossils have been described as examples of other
genera[365] of Rhodophyceae than those included in the
Corallinaceae, but these possess little or no scientific value and
need not be considered.
E. PHAEOPHYCEAE (Brown Algae).

Olive-brown algae, thallus often leathery in texture, composed of
cell-filaments or parenchymatous tissue, in some cases exhibiting a
considerable degree of internal differentiation. The sexual
reproductive organs may be either in the form of passive egg-cells
and motile antherozoids or of motile cells showing no external sexual
difference.
With one or two exceptions all the genera are marine. They have a
wide distribution at the present day, and are especially characteristic
of far northern and extreme southern latitudes. The gigantic forms
Lessonia, Macrocystis and others already alluded to, belong to this
group; also the genus Sargassum, of which the numberless floating
plants constitute the characteristic vegetation of the Sargasso Sea.
Palaeobotanical literature is full of descriptions of supposed fossil
representatives of the brown algae, but only a few of the recorded
species possess more than a very doubtful value; most of them are
worthless as trustworthy botanical records. Many of the numerous
impressions referred to as species of Fucoides and other genera
present a superficial resemblance to the thallus of the common
Bladder-wrack and other brown seaweeds. Such similarity of form,
however, in the case of flat and branched algal-like fossils is of no
scientific value. In many instances the impressions are probably
those of an alga, but they are of no botanical interest. The flat and
forked type of thallus of Fucus, Chondrus crispus (L.) and other
members of the Phaeophyceae is met with also among the red and
green algae, to say nothing of its occurrence in the group of thalloid
Liverworts, or of the almost identical form of various members of the
animal kingdom. The variety of form of the thallus in one species is
well illustrated by the common Chondrus crispus (L.). This alga was
described by Turner[366] in his classic work on the Fuci under the
name of Fucus crispus as “a marine Proteus.” It affords an
interesting example of the different appearance presented by the
same species under different conditions, and at the same time it
furnishes another proof of the futility of relying on imperfectly
preserved external features as taxonomic characters of primary
importance.
An example of a supposed Jurassic Fucus is shown in fig. 49, and
briefly described in the Chapter dealing with fossil Bryophytes.
Several species of Flysch Algae have recently been referred by
Rothpletz[367] to the Phaeophyceae under the provisional generic
name Phycopsis, but they are of no special botanical interest.
The extremely interesting genus Nematophycus has lately been
assigned by a Canadian author[368] to a position in the
Phaeophyceae. Although the particular points on which he chiefly
relies are not perhaps thoroughly established, there are certain
considerations which lead us to include Nematophycus as a doubtful
member of the present group of algae.
Nematophycus.
The stem attains a diameter of between 2 and 3 feet in the largest
specimens; it is made up either of comparatively wide and loosely
arranged tubes pursuing a slightly irregular vertical course
accompanied by a plexus of much narrower tubes, or of tubes
varying in diameter but not divisible into two distinct types. Rings of
growth occur in some forms but not in others. Radially elongated or
isodiametric spaces occur in the stem tissues in which the tubes are
less abundant.
Reproductive organs unknown, with the possible exception of
some very doubtful bodies described as spores.
In 1856 Sir William Dawson proposed the generic name
Prototaxites for some large silicified trunks discovered in the Lower
and Middle Devonian rocks of Canada. A few years later the same
writer[369] published a detailed account of the new fossils and arrived
at the conclusion that the Devonian stem showed definite points of
affinity with the recent genus Taxus, and the generic name suggests
that he regarded it as the type of Coniferous trees belonging to the
sub-family Taxineae. The reasons for this determination were
afterwards shown by Carruthers to be erroneous. Dawson thought
he recognised pits and spiral thickenings in the walls of the tubular
elements, as well as pointed ends in some of the latter. The spiral
markings were in reality small hyphal tubes passing obliquely across
the face of the wider tubes, and the apparent ends of the supposed
tracheids were deceptive appearances due to the fact that the tubes
had in some cases been cut through in an oblique direction. In 1870
Carruthers[370] expressed the opinion that Dawson’s Prototaxites was
a “colossal fossil seaweed” and not a coniferous plant. The same
author[371] in 1872 published a full and able account of the genus,
and conclusively proved that Prototaxites could not be accepted as a
Phanerogam; he brought forward almost convincing evidence in
favour of including the genus among the algae. The name
Prototaxites was now changed for that of Nematophycus. Carruthers
compares the rings of growth in the fossil stems with those in the
large Antarctic Lessonia stems, but he regards the histological
characters as pointing to the Siphoneae as the most likely group of
recent algae in which to include the Palaeozoic genus.
We may pass over various notes and additional contributions by
Dawson, who did not admit the corrections to his original
descriptions which Carruthers’ work supplied. In 1889 an important
memoir appeared by Penhallow[372] of Montreal in which he
confirmed Carruthers’ decision as to the algal nature of Prototaxites;
he contributed some new facts to the previous account by
Carruthers, and expressed himself in favour of regarding the fossil
plant as a near ally of the recent Laminariae. The next addition to our
botanical knowledge of this genus was made by Barber[373] who
described a new specific type of Nematophycus—N. Storriei—found
by Storrie in beds of Wenlock limestone age near Cardiff. Solms-
Laubach[374], in a recent memoir on Devonian plants, recorded the
occurrence of another species of this genus in Middle Devonian
rocks near Gräfrath on the Lower Rhine. Lastly Penhallow[375], in
describing a new species, lays stress on the resemblance of some of
the tubular elements in the stem to the sieve-hyphae of the recent
seaweeds Macrocystis and Laminaria. He concludes that the new
facts he records make it clear that Nematophycus “is an alga, and of
an alliance with the Laminarias.” The recent evidence brought
forward by Penhallow is not entirely satisfactory; the drawings and
descriptions of the supposed trumpet-shaped sieve-hyphae are not
conclusive. On the whole it is probably the better course to speak of
Nematophycus as a possible ally of the brown algae rather than as
an extinct type of the Siphoneae, but until our knowledge is more
complete it is practically impossible to decide the exact position of
this Siluro-Devonian genus.
Solms-Laubach[376] has suggested that the generic name
Nematophyton, used by Penhallow in preference to Carruthers’ term
Nematophycus, is the more suitable as being a neutral designation
and not one which assumes a definite botanical position. In view of
the nature of the evidence in favour of the algal affinities of the fossil,
the reasons for discarding Carruthers’ original name are hardly
sufficient.
Before discussing more fully the distribution and botanical position
of Nematophycus we may describe at length one of the best known
species, and give a short account of some other forms.
• • • • •
1. Nematophycus Logani (Daws.). Fig. 39, A–E. The stem
possesses well marked concentric rings of growth due to a periodic
difference in size of the large tubular elements. The tissues consist
of two distinct kinds of tubular elements, the larger tubes loosely
arranged and pursuing a fairly regular longitudinal course, and
having a diameter of 13–35µ; the smaller tubes, with a diameter of
5–6µ, ramify in different directions and form a loose plexus among
the larger and more regularly disposed elements. Branching occurs
in both kinds of tubes; septa have been recognised only in the
smaller tubes. Irregular and discontinuous radial spaces traverse the
stem tissues, having a superficial resemblance in their manner of
occurrence to the medullary rays of the higher plants.
The best specimens of this species were obtained by Sir William
Dawson from the Devonian Sandstones of Gaspé in New Brunswick.
The largest stems had a diameter of 3 feet and reached a length of
several feet[377]; in some examples Dawson found lateral
appendages attached to the stem which he described as “spreading
roots.” Externally the specimens were occasionally covered with a
layer of friable coal, and internally the tissues were found to be more
or less perfectly preserved by the infiltration of a siliceous solution.
Most of the examples of Nematophycus from Britain and Germany
are much smaller and less perfectly preserved than those from
Canada. The Peter Redpath Museum, Montreal, contains several
very large blocks of Nematophycus, in many of which one sees the
concentric rings of growth clearly etched out by weathering agents in
a cross section of a large stem.
In fig. 39, A, a sketch is given of a thin transverse section of a
stem, drawn natural size. The lines of growth are clearly seen, and
as in coniferous stems the breadth of the concentric zones varies
considerably. The short lines traversing the tissues in a radial
direction represent the medullary-ray-like spaces referred to in the
specific diagnosis. A transverse section examined under a low-
power objective presents the appearance of a number of thick-walled
and comparatively wide tubes loosely arranged; they may be in
contact or separated from one another. If the microscope be carefully
focussed through the thickness of the section the transversely-cut
tubes appear to move laterally, producing a curiously dazzling effect
if the objective is raised or lowered rapidly. This lateral movement is
due to the undulating vertical course of the tubes. Under a higher
power the lighter-coloured matrix in which the tubes are embedded
shows a number of very much smaller and thinner-walled hyphal
elements; some of these are cut across transversely, others more or
less obliquely and others again longitudinally. These smaller tubes
constitute an irregular plexus surrounding and ramifying between the
larger elements. The diameter of the larger tubes decreases for a
certain distance in a radial direction as seen in a transverse section,
and this change in size gives rise to the appearance of concentric
lines indicating periodic changes in growth.
Fig. 39. Nematophycus Logani (Daws.). A. Part of a transverse section
from a specimen in the British Museum. (Nat. size.) B. Transverse
section from specimens in Mr Barber’s possession. C. Longitudinal
section. (B and C × 160.) D. Transverse section showing a radial space.
E. Transverse section; a few ‘cells’ more highly magnified. D and E from
a specimen in the British Museum.
The radial spaces are characterised by the partial absence of the
larger tubes, and as seen in longitudinal sections these spaces
constitute regions in which the smaller tubes branch very freely. Fig.
39, B, represents a small piece of a transverse section seen under a
fairly high power. In fig. 39, C, the tubes are seen in longitudinal
section. The larger elements are unseptate and not very regular in
their vertical course through the stem; the smaller elements are seen
as fine tubes lying between and across the larger tubes. In the
sections I have examined no undoubted transverse septa were
detected in any of the tubular elements.
The question as to the possible connection between the larger and
smaller elements is one which is not as yet satisfactorily disposed of.
Penhallow[378] regards the finer hyphal elements as branches of the
larger tubes, but Barber[379], who has carefully examined good
material of Nematophycus Logani, was unable to detect any organic
connection between the two. My own observations are in accord with
those of Barber. Further details and numerous figures of this species
of Nematophycus will be found in the memoirs of Carruthers,
Penhallow and Barber.
• • • • •
Some specimens of silicified Nematophycus stems afford
particularly instructive examples of the state of preservation or
method of mineralisation as a source of error in histological work.
The sketches reproduced in fig. 39, D and E, were made from a
section of a large specimen of Nematophycus in the British Museum.
In fig. D we have one of the radial spaces containing some indistinct
small elements, the tissue surrounding the space appears to consist
of polygonal cells suggesting ordinary parenchymatous tissue. In fig.
E a few of these ‘cells’ are seen more clearly, they have black and
ragged walls, and often contain very small and faint circles of which
the precise nature is uncertain. The true interpretation of this form of
structure was first supplied by Penhallow[380]. The black network
simulating parenchymatous tissue consists of the substance of
Nematophycus tubes which has been completely redistributed during
fossilisation and collected along fairly regular lines, as seen in figs. D
and E. The original structure has been almost completely destroyed,
and the material composing the walls of the large tubes has finally
been rearranged as a network, interrupted here and there by the
characteristic radial spaces which remain as evidence of the original
Nematophycus characters. It is possible in some cases to trace
every gradation from sections exhibiting the normal structure through
those having the appearance shown in figs. D and E to others in
which the structure is completely lost. Penhallow describes this
method of fossilisation in N. crassus (Daws.); an examination of
several specimens in the National Collection leads me to entirely
confirm his general conclusions, and also to the opinion that N.
Logani shows exactly the same manner of mineralisation as N.
crassus. The chief point of interest as regards this method of
preservation lies in the fact that a fossil described by Dawson[381] as
Celluloxylon primaevum, and referred to as a probable conifer, is
undoubtedly a badly preserved Nematophycus. Penhallow examined
Dawson’s specimens and obtained convincing evidence of their
identity with certain forms of highly altered Nematophycus stems.
• • • • •
2. Nematophycus Storriei Barber. Fig. 40. The specimens on
which Barber[382] founded this species were obtained by Mr Storrie
from the Tymawr quarry near Cardiff, in beds of Wenlock age. The
fragmentary nature of the material is largely compensated for by the
excellence of the preservation. We may briefly define the species as
follows:
The stem consists of separate interlacing undivided and usually
unbranched tubes of varying diameter. Spaces more or less
isodiametric in dimensions are scattered through the tissue. The
spaces constitute regions in which the tubular elements branch
freely.
The main distinguishing features of this British species are (i) the
absence of two distinct and well-defined forms of tubular elements.
The main part of the stem consists of thick walled tubes similar to
those of N. Logani, but the spaces between them are occupied by
thinner-walled and smaller tubes varying considerably in diameter;
(ii) the form of the spaces which are not radially elongated as in N.
Logani.
Fig. 40. Nematophycus Storriei Barb. Longitudinal section, from a
photograph by Mr C. A. Barber. × 45.
Fig. 40 shows the undulating course of the tubes as seen in a
longitudinal section; the black colour of some of the elements is due
to the fact that the surface of the wall is seen, while in the lighter-
coloured portions of the tubes the wall has been cut through. The
lighter patch about the middle of the figure shows the form of one of
the spaces in which the tubes are freely branched.
In addition to the two species already described six others have
been recorded, but with these we need not concern ourselves in
detail. One of these species, N. Hicksi, was found by Dr Hicks[383] in
the Denbighshire grits quarry of Pen-y-Glog near Corwen in North
Wales. The position of these beds has recently been determined by
Mr Lake[384] as corresponding to that of the Wenlock limestone. This
species and N. Storriei are both Silurian examples of the genus. It is
possible, as Barber has suggested, that the specimens described
under these two names should be referred to one species. The
specimens found by Hicks were small and imperfectly preserved
fragments; Etheridge has given a full description of their structure,
and Barber has subsequently examined the material. The
preservation is not such as will admit of any very precise specific
diagnosis; the fragments are correctly referred to Nematophycus, but
their specific characters cannot be clearly determined.
Solms-Laubach[385] has described some fragments of another
species of Nematophycus from the Devonian rocks of the Lower
Rhine. His specimens are chiefly interesting as extending the
geographical range of the genus, and as affording examples of a
curious method of preservation. The specimens obtained were small
fragments, flattened and very dark brown in colour. The tubular
elements consisted of an external membrane of black coal,
enclosing a central core of dark red iron-oxide. On burning the
fragment on a piece of platinum foil the coal composing the wall of
the tubes was removed and the deep-red casts of the tube-cavities
remained[386]. The investigation of the structural characters of this
imperfect material was conducted by reflected light. Under certain
conditions, when it is impossible to obtain thin sections for
examination by transmitted light, it is possible to accomplish much,
as shown by Solms-Laubach’s work, by means of observation with
direct light.
The last species to be noticed is Nematophycus Ortoni recently
described by Penhallow. There are no concentric rings of growth, no
radial spaces and no smaller hyphae in the tissues of this type of
stem. In longitudinal section, the tubes show occasional local
expansions of the lumen which Penhallow compares with the
‘trumpet-hyphae’ of some recent brown algae. No actual sieve-plates
or transverse walls have been detected, but the general appearance
of the tubes is considered to afford distinct evidence of the original
existence of such walls. The figures accompanying the description
do not carry conviction as to the correctness of the reference of the
tubes to imperfectly preserved sieve-hyphae.
The following list, taken, with a few alterations, from Penhallow’s
memoir[387], shows the geographical and geological range of the
species of Nematophycus hitherto recorded.
Nematophycus Logani (Daws.) Lower Devonian of Gaspé.
Silurian [Wenlock] of England.
Silurian of New Brunswick.
N. Hicksi (Eth.) Silurian. (Wenlock) of N. Wales.
N. crassus (Daws.)[388] Middle Devonian of Gaspé and New York.
N. laxus (Daws.) Lower Devonian of Gaspé.
N. tenuis (Daws.) Lower Devonian of Gaspé.
N. Storriei (Barb.) Silurian (Wenlock) of Wales (Cardiff).
N. dechenianus (Pied.) Upper Devonian of Germany (Gräfrath).
N. Ortoni (Pen.) Upper Erian of Ohio.
In summing up our information as to the structure of

Nematophycus we find there are certain points not definitely settled,
and which are of considerable importance. The few recorded
instances of spore-like bodies by Penhallow and Barber are not
satisfactory; we are still ignorant of the nature of the reproductive
organs. Such instances of lateral appendages as have been referred
to do not throw much light on the habit of the plant. So far as we
know at present the stem of Nematophycus was not differentiated
internally into a cortical and central region. It may be that the
specimens have been only partially preserved, and the coaly layer
which occasionally surrounds a stem may represent a carbonised
cortex which has never been petrified. The large and loosely
arranged tubes constitute the chief characteristic feature of the
genus; in some cases (N. Logani) there is an accompanying plexus
of smaller hyphae, in others (N. Storriei) there is no definite division
of the tissue into two sets of tubes of uniform size, and in N. Ortoni
the tubular elements are all of the large type.
Penhallow has recognised the branching of large tubes in N.
Logani and N. crassus giving rise to the small hyphal elements. In
most specimens, however, no such mode of origin of the smaller
tubes can be detected. The spaces which interrupt the homogeneity
of the tissues in some forms have been described as branching
depots, on account of the frequent occurrence in these areas of
much branched hyphae. The function of these spaces (fig. 39, D,
and fig. 40) may be connected with aeration of the stem-tissues.
As Carruthers first pointed out the unseptate nature of the
elements and the occurrence of large and small tubes forming a
comparatively lax tissue suggested affinities with such recent genera
as Penicillus, Halimeda, Udotea and other members of the
Siphoneae. In those fossil stems which possess tubes of two distinct
sizes, we cannot as a rule trace any organic connection between the
two sets of tubular elements. Transverse septa have been detected
in the tubes of some specimens of N. Logani. These considerations
and the large size and habit of growth of the stem leave one
sceptical as to the wisdom of assigning the fossil genus to the
Siphoneae. On the other hand, apart from the doubtful sieve-hyphae
of Penhallow, the manner of growth of the plant, the concentric rings,
marked by a decrease in the diameter of the tubes, the lax
arrangement and irregular course of the elements, afford points of
agreement with some recent Phaeophyceae. The stem of a
Laminaria (fig. 29) or of a Lessonia are the most obvious structures
with which to compare Nematophycus. The medullary region of a
Laminaria or Fucus and of other genera presents a certain
resemblance to the tissues of the fossil stems. On the whole we may
be content to leave Nematophycus for the present as probably an
extinct type of alga, more closely allied to the large members of the
Phaeophyceae than to any other recent seaweeds.
Pachytheca.
(A fossil of uncertain affinity.)
There is another fossil occasionally associated with
Nematophycus and referred by many writers to the Algae, which
calls for a brief notice. Pachytheca is too doubtful a genus to justify a
detailed treatment in the present work. Although, as I have
elsewhere suggested[389], we are hardly in a position to speak with
any degree of certainty as to its affinity, it is not improbable that it
may eventually be shown to be an alga.
Without attempting a full diagnosis of the genus, we may briefly
refer to its most striking characters.
Pachytheca usually occurs in the form of small spherical bodies,
about ·5 cm. in diameter, in Old Red Sandstone or Silurian rocks. In
section a single sphere is found to consist of two well marked
regions; in the centre, of a number of ramifying and irregularly placed

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

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—Sir Robert Hutchison

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º Patient reasons for nonadherence include simple

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