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a LANGE medical book

2021
CURRENT
Medical Diagnosis
& Treatment
SIXTIETH 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
Department of Medicine
University of California, San Francisco

Associate Editor

Michael W. Rabow, MD
Professor of Medicine and Urology
Division of Palliative Medicine
Department of Medicine
University of California, San Francisco

With Associate Authors

Mc
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 Contents
Authors v 13. Blood Disorders 512
Preface xiii
Lloyd E. Damon, MD, & Charalambos Babis
1. Disease Prevention & Health Promotion 1 Andreadis, MD, MSCE

Michael Pignone, MD, MPH, & Rene Salazar, MD
2. Common Symptoms
Paul L. Nadler, MD, & Ralph Gonzales, MD, MSPH
14. Disorders of Hemostasis, Thrombosis, &
Antithrombotic Therapy 558
16
Andrew D. Leavitt, MD, Erika Leemann Price, MD,
MPH, & Tracy Minichiello, MD

3. Preoperative Evaluation & Perioperative 15. Gastrointestinal Disorders 592

Management 44
Kenneth R. McQuaid, MD
Hugo Q. Cheng, MD
16. Liver, Biliary Tract, & Pancreas
4. Geriatric Disorders 54 Disorders 693
G. Michael Harper, MD, C. Bree Johnston, Lawrence S. Friedman, MD
MD, MPH, & C. Seth Landefeld, MD
17. Breast Disorders 758
5. Palliative Care & Pain Management 70
Armando E. Giuliano, MD, FACS, FRCSEd, &
Michael 1/1/. Rabow, MD, Steven Z. Pantilat, MD, Sara A. Hurvitz, MD, FACP
Ann Cai Shah, MD, Lawrence Poree, MD, MPH, PhD,
& Scott Steiger, MD 18. Gynecologic Disorders 785

6. Dermatologic Disorders 102 Jason Woo, MD, MPH, FACOG, &

Jill Long, MD, MPH, MHS, FACOG
Kanade Shinkai, MD, PhD, & Lindy P. Fox, MD
19. Obstetrics & Obstetric Disorders 820
7. Disorders of the Eyes & Lids 173
Vanessa L. Rogers, MD, & Scott W. Roberts, MD
Jacque L. Duncan, MD, Neeti B. Parikh, MD, &
Gerami D. Seitzman, MD 20. Rheumatologic, Immunologic,
& Allergic Disorders 849
8. Ear, Nose, & Throat Disorders 210
Jinoos Yazdany, MD, MPH, Rebecca Manno, MD,
Lawrence R. Lustig, MD, & Joshua S. Schindler, MD MHS, David B. Hellmann, MD, MACP, &John B.
Imboden Jr., MD
9. Pulmonary Disorders 251
Asha N. Chesnutt, MD, Mark S. Chesnutt, MD, 21. Electrolyte & Acid-Base Disorders 909
Niall T. Prendergast, MD, & Nayan Arora, MD, &J. Ashley Jefferson, MD
Thomas J. Prendergast, MD
22. Kidney Disease 938
10. Heart Disease 334
Tonja C. Dirkx, MD, & Tyler B. Woodell, MD, MCR
Thomas M. Bashore, MD, Christopher B. Granger,
MD, Kevin P. Jackson, MD, & Manesh R. Patel, MD 23. Urologic Disorders 980
11. Systemic Hypertension 453 Mathew Sorensen, MD, MS, FACS, Thomas J. Walsh,
MD, MS, & Kevin A. Ostrowski, MD
Michael Sutters, MD, MRCP (UK)
24. Nervous System Disorders 1005
12. Blood Vessel & Lymphatic Disorders 485
Vanja C. Douglas, MD, &
Warren J. Gasper, MD, James C. lannuzzi, MD, MPH, Michael J. Aminoff, MD, DSc, FRCP
& Meshell D. Johnson, MD

iii
 iv CMDT2021 CONTENTS

25. Psychiatric Disorders 1082 39. Cancer 1654

Kristin S. Raj, MD, Nolan Williams, MD, & Sunny Wang, MD, Tiffany 0. Dea, PharmD, BCOP,
Charles DeBattista, DMH, MD Patricio A. Cornett, MD, Lawrence S. Friedman, MD,
Carling Ursem, MD, Kenneth R. McQuaid, MD, &
26. Endocrine Disorders 1138 George R. Schade, MD
Paul A. Fitzgerald, MD
40. Genetic & Genomic Disorders 1721
27. Diabetes Mellitus & Hypoglycemia 1242 Reed E. Pyeritz, MD, PhD
Umesh Moshorani, MB, BS, MRCP (UK)
41. Sports Medicine & Outpatient
Orthopedics 1730
28. Lipid Disorders 1288
Anthony Luke, MD, MPH, &C. Benjamin Mo, MD
Michael J. Blaha, MD, MPH
42. Sexual & Gender Minority Health 1765
29. Nutritional Disorders 1299
Juno Obedln-Mallver, MD, MPH, MAS,
Katherine H. Sounders, MD, &
Patricio A. Robertson, MD, Kevin L. Arc/, MD, MPH,
Leon I. lgel, MD, FACP, FTOS Kenneth H. Moyer, MD, &Madeline B. Deutsch,
MD, MPH
30. Common Problems in lnfedious
Diseases & Antimicrobial Therapy 1320 e1. Anti-lnfedive Chemotherapeutic &
Peter V. Chin-Hong, MD, & Antibiotic Agents Online*
B. Joseph Guglielmo, PharmD Katherine Gruenberg, PharmD, &
B. Joseph Guglielmo, PhormD
31. HIV Infection & AIDS 1361
Mitchell H. Katz, MD e2. Diagnostic Testing & Medical
Decision Making Online*
32. Viral & Rickettsial Infections 1403 Chuonyi Mark Lu, MD
Eva Clark. MD, PhD, & Wayne X. Shandera, MD
e3. Information Technology in Patient
33. Baderlal& Chlamydlallnfectlons 1490 Care Online*
Bryn A. Boslett, MD, & Brion S. Schwartz, MD Russ Cue/no, MD, MS

34. Spirochetal Infections 1535 e4. Integrative Medicine Online*

Susan S. Philip, MD, MPH Dorshon Mehta, MD, MPH

35. Protozoal& Helminthic Infections 1552 e5. Podiatric Disorders Online*

Philip J. Rosenthal, MD Monara Dlnl, DPM, & Charles B. Parks, DPM

36. Mycotic Infections 1593 e6. Women's Health Issues Online*

Stacey R. Rose, MD, & Richard J. Hamill, MD Brigid Dolan, MD, MEd, & Judith Walsh, MD, MPH

37. Disorders Related to Environmental e7. Appendix: Therapeutic Drug Monitoring,

Emergencies 1608 Laboratory Reference Intervals, &
Pharmacogenetic Tests Online*
Jacqueline A. Nemer, MD, FACEP, &
Marianne A. Juarez. MD Chuanyi Mark Lu, MD

Index 1787
38. Poisoning 1624
Craig Smollin, MD, & Kent R. Olson, MD

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

 Preface
Current Medical Diagnosis & Treatment 2021 (CMDT 2021) is the 60th 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 peoples 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 quickly referencing medical diagnosis and treatment modalities.
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

• INNOVATIVE TABLE highlighting the “Year in Review: Key Clinical Updates in CMDT 2021,” individually listed with
page numbers and reference citations, for easy access to significant changes in this edition
• New section on SARS-CoV-2 virus and COVID-19 infection
• Extensive revision of the Viral & Rickettsial Infections chapter, including new section on acute flaccid myelitis as well
as updates on measles, mumps, and Zika virus
• 140 NEW online images in the Heart Disease, Gastrointestinal Disorders, and Cancer chapters
• Addition of the 2019 European guidelines for treating pulmonary embolism
• New table outlining agents to consider for reversing anticoagulant effect during life-threatening bleeding based on the
Anticoagulation Forum and American Society of Hematology 2019 guidelines
• Bedaquiline considered first-line medication for multidrug-resistant tuberculosis
• Lefamulin, a new commercially available medication for treating community-acquired bacterial pneumonia
• New information on the combination of emtricitabine/tenofovir alafenamide as antiretroviral treatment for preexposure
prophylaxis among men
• A two-drug regimen, dolutegravir plus lamivudine, included in the top recommended HIV antiretroviral regimens
• Recommendation from the Advisory Committee on Immunization Practices for shared clinical decision-making
regarding HPV vaccination for adults aged 26-45 years
• Substantial revision of the Sexual & Gender Minority Health chapter
• Bempedoic acid, a new FDA-approved pharmacologic option for lowering LDL cholesterol in patients who cannot toler­
ate statins
• FDA approval of various closed loop systems that adjust basal insulin delivery for diabetic patients
• Eculizumab, a newly FDA-approved medication for both myasthenia gravis and neuromyelitis optica
• FDA approval of lasmiditan, a new pharmacologic option that can safely be given to migraine sufferers with cardiovas­
cular risk factors
• The sodium-glucose linked transporter (SGLT) inhibitors slow progression of early diabetic nephropathy in addition to
their having cardioprotective effects
• The US Preventive Services Task Force recommendation for hepatitis C screening of asymptomatic adults between ages
18 and 79 years

xiii
 XIV CMDT 2021 PREFACE

• FDA approval of adjuvant trastuzumab emtansine for patients with HER2-positive breast cancer with residual disease
after standard trastuzumab-containing neoadjuvant therapy
• Data from HER2CLIMB, a phase III trial, expected to lead to FDA approval of a new therapy for breast cancer patients
with pretreated HER2-positive advanced disease
• Promising results from phase 3 clinical trials of gene therapy for hemophilia A and B
• Information on bremelanotide, a second FDA-approved medication for hypoactive sexual desire disorder in premeno­
pausal women
• Mepolizumab, newly FDA approved for the treatment of eosinophilic granulomatosis with polyangiitis

OUTSTANDING FEATURES OF CMDT

• Medical advances up to time of annual publication
• Detailed presentation of internal medicine disciplines, plus primary care topics in gynecology, obstetrics, dermatology,
ophthalmology, otolaryngology, psychiatry, neurology, toxicology, urology, geriatrics, orthopedics, womens health,
sexual and gender minority 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

Seven e-chapters listed in the Table of Contents can be accessed at www.AccessMedicine.com/CMDT. These online-only
chapters (available without need for subscription) include
• Anti-Infective Chemotherapeutic & Antibiotic Agents
• Diagnostic Testing & Medical Decision Making
• Information Technology in Patient Care
• Integrative Medicine
• Podiatric Disorders
• Womens Health Issues
• Appendix: Therapeutic Drug Monitoring, Laboratory Reference Intervals, & Pharmacogenetic Tests
Institutional or individual subscriptions to AccessMedicine also have full electronic access to CMDT 2021.
Subscribers to CMDT Online receive full electronic access to CMDT 2021 as well as
• An expanded, dedicated media gallery
• Quick Medical Diagnosis & Treatment (QMDT)—a concise, bulleted version of CMDT 2021
• 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 2021, 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.

Disease Prevention &
Health Promotion
Michael Pignone, MD, MPH1
Rene Salazar, MD
GENERAL APPROACH TO THE PATIENT
The medical interview serves several functions. It is used to
collect information to assist in diagnosis (the “history” of
the present illness), to understand patient values, to assess
and communicate prognosis, to establish a therapeutic
relationship, and to reach agreement with the patient about
further diagnostic procedures and therapeutic options. It
also serves as an opportunity to influence patient behavior,
such as in motivational discussions about smoking cessa­
tion or medication adherence. Interviewing techniques
that avoid domination by the clinician increase patient
involvement in care and patient satisfaction. Effective
clinician-patient communication and increased patient
involvement can improve health outcomes.
Patient Adherence
For many illnesses, su ccessfu l prevention and treatment
depends on difficu lt fu ndamental behavioral changes,
including altering diet, taking up exercise, giving up smok­
ing, cu tting down drinking, and adhering to medication
regimens that are often complex. Adherence is a problem in
every practice; up to 50% of patients fail to achieve full
adherence, and one-third never take their medicines. Many
patients with medical problems, even those with access
to care, do not seek appropriate care or may drop out of
care prematu rely. Adherence rates for short-term, self­
administered therapies are higher than for long-term
therapies and are inversely correlated with the number of
interventions, their complexity and cost, and the patients
perception of overmedication.
As an example, in HIV-infected patients, adherence to
antiretroviral therapy is a crucial determinant of treatment
success. Studies have unequivocally demonstrated a close
relationship between patient adherence and plasma HIV
RNA levels, CD4 cell counts, and mortality. Adherence
levels of more than 95% are needed to maintain virologic
suppression. However, studies show that over 60% of
1Dr. Pignone is a former member of the US Preventive Services
Task Force (USPSTF). The views expressed in this chapter are
his and Dr. Salazar's and not necessarily those of the USPSTF.
CMDT 2021
patients are less than 90% adherent and that adherence
tends to decrease over time.
Patient reasons for suboptimal adherence include sim­
ple forgetfulness, being away from home, being busy, and
changing daily routine. Other reasons include psychiatric
disorders (depression or substance misuse), uncertainty
about the effectiveness of treatment, lack of knowledge
about the consequences of poor adherence, regimen com­
plexity, and treatment side effects. The rising costs of medi­
cations, including generic drugs, and the increase in
patient cost-sharing burden, has made adherence even
more difficult, particularly for those with lower incomes.
Patients seem better able to take prescribed medications
than to adhere to recommendations to change their diet,
exercise habits, or alcohol intake or to perform various self-
care activities (such as monitoring blood glucose levels at
home). For short-term regimens, adherence to medications
can be improved by giving clear instructions. Writing out
advice to patients, including changes in medication, may
be helpful. Because low functional health literacy is com­
mon (almost half of English-speaking US patients are
unable to read and understand standard health education
materials), other forms of communication—such as illus­
trated simple text, videotapes, or oral instructions—may be
more effective. For non-English-speaking patients, clini­
cians and health care delivery systems can work to provide
culturally and linguistically appropriate health services.
To help improve adherence to long-term regimens, cli­
nicians can work with patients to reach agreement on the
goals for therapy, provide information about the regimen,
ensure understanding by using the “teach-back” method,
counsel about the importance of adherence and how to
organize medication-taking, reinforce self-monitoring,
provide more convenient care, prescribe a simple dosage
regimen for all medications (preferably one or two doses
daily), suggest ways to help in remembering to take doses
(time of day, mealtime, alarms) and to keep appointments,
and provide ways to simplify dosing (medication boxes).
Single-unit doses supplied in foil wrappers can increase
adherence but should be avoided for patients who have dif­
ficulty opening them. Medication boxes with compart­
ments (eg, Medisets) that are filled weekly are useful.
Microelectronic devices can provide feedback to show
 CMDT 2021 CHAPTER 1
patients whether they have taken doses as scheduled or to
notify patients within a day if doses are skipped. Reminders,
including cell phone text messages, are another effective
means of encouraging adherence. The clinician can also
enlist social support from family and friends, recruit an
adherence monitor, provide a more convenient care envi­
ronment, and provide rewards and recognition for the
patients efforts to follow the regimen. Collaborative pro­
grams in which pharmacists help ensure adherence are also
effective. Motivational interviewing techniques can be
helpful when patients are ambivalent about their therapy.
Adherence is also improved when a trusting doctor­
patient relationship has been established and when patients
actively participate in their care. Clinicians can improve
patient adherence by inquiring specifically about the behav­
iors in question. When asked, many patients admit to
incomplete adherence with medication regimens, with
advice about giving up cigarettes, or with engaging only in
“safer sex” practices. Although difficult, sufficient time must
be made available for communication of health messages.
Medication adherence can be assessed generally with a
single question: “In the past month, how often did you take
your medications as the doctor prescribed?” Other ways of
assessing medication adherence include pill counts and
refill records; monitoring serum, urine, or saliva levels of
drugs or metabolites; watching for appointment nonatten­
dance and treatment nonresponse; and assessing predict­
able drug effects, such as weight changes with diuretics or
bradycardia from beta-blockers. In some conditions, even
partial adherence, as with drug treatment of hypertension
and diabetes mellitus, improves outcomes compared with
nonadherence; in other cases, such as HIV antiretroviral
therapy or tuberculosis treatment, partial adherence may
be worse than complete nonadherence.
Guiding Principles of Care
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
resources. Ethical principles that guide the successful
approach to diagnosis and treatment are honesty, benefi­
cence, justice, avoidance of conflict of interest, and the
pledge to do no harm. Increasingly, Western medicine
involves patients in important decisions about medical
care, eg, which colorectal screening test to obtain or which
modality of therapy for breast cancer or how far to proceed
with treatment of patients who have terminal illnesses (see
Chapter 5).
The clinician’s role does not end with diagnosis and
treatment. The importance of the empathic clinician in
helping patients and their families bear the burden of seri­
ous illness and death cannot be overemphasized. “To cure
sometimes, to relieve often, and to comfort always” is a
French saying as apt today as it was five centuries ago—as
is Francis Peabody’s admonition: “The secret of the care of
the patient is in caring for the patient.” Training to improve
mindfulness and enhance patient-centered communica­
tion increases patient satisfaction and may also improve
clinician satisfaction.
Cutler RL et al. Economic impact of medication non-adherence
by disease groups: a systematic review. BMJ Open. 2018 Jan
21;8(l):e016982. [PMID: 29358417]
Kini V et al. Interventions to improve medication adherence:
a review. JAMA. 2018 Dec 18;320(23):2461-73. [PMID:
30561486]
HEALTH MAINTENANCE & DISEASE
PREVENTION
Preventive medicine can be categorized as primary, sec­
ondary, or tertiary. Primary prevention aims to remove or
reduce disease risk factors (eg, immunization, giving up or
not starting smoking). Secondary prevention techniques
promote early detection of disease or precursor states (eg,
routine cervical Papanicolaou screening to detect carci­
noma or dysplasia of the cervix). Tertiary prevention mea­
sures are aimed at limiting the impact of established
disease (eg, partial mastectomy and radiation therapy to
remove and control localized breast cancer).
Tables 1-1 and 1-2 give leading causes of death in the
United States and estimates of deaths from preventable
causes. Recent data suggest increased mortality rates,
driven by increases in suicide and substance misuse and its
sequelae. Unintentional injuries, including deaths from
opioid-related overdoses, have become the third leading
cause of death in the United States. Non-Hispanic whites
with a high school education or less have suffered
disproportionately.
Many effective preventive services are underutilized,
and few adults receive all of the most strongly recom­
mended services. Several methods, including the use of
provider or patient reminder systems (including interac­
tive patient health records), reorganization of care environ­
ments, and possibly provision of financial incentives to
Table 1-1. Leading causes of death in the United States,
2017.
Category Estimate
All causes 2,179,857
1. Diseases of the heart 647,457
2. Malignant neoplasms 599,108
3. Unintentional injuries 169,936
4. Chronic lower respiratory 160,201
diseases
5. Cerebrovascular diseases 146,383
6. Alzheimer disease 121,404
7. Diabetes mellitus 83,564
8. Influenza and pneumonia 55,672
9. Nephritis, nephrotic syndrome, 50,633
and nephrosis
10. Intentional self-harm (suicide) 47,173
Data from National Center for Health Statistics 2019.
 DISEASE PREVENTION & HEALTH PROMOTION CMDT2021

the United States (eg, regional epidemics) highlight the need

Table 1-2. Leading preventable causes of death in the to understand the association of vaccine refusal and disease
United States, 2017. epidemiology.
Evidence suggests annual influenza vaccination is safe
Category Estimate
and effective with potential benefit in all age groups, and
Dietary risks 503,390 the Advisory Committee on Immunization Practices
High systolic blood pressure 454,346 (ACIP) recommends routine influenza vaccination for all
persons aged 6 months and older, including all adults.
Tobacco 437,706
When vaccine supply is limited, certain groups should be
High fasting plasma glucose 420,192 given priority, such as adults 50 years and older, individuals
High BMI 408,831 with chronic illness or immunosuppression, and pregnant
women. An alternative high-dose inactivated vaccine is
High LDL cholesterol 221,557
available for adults 65 years and older. Adults 65 years and
Impaired kidney function 173,378 older can receive either the standard-dose or high-dose
Air pollution 107,506 vaccine, whereas those younger than 65 years should
Alcohol use 104,536 receive a standard-dose preparation.
The ACIP recommends two doses of measles, mumps,
Drug use 104,440
and rubella (MMR) vaccine in adults at high risk for expo­
Low physical activity 70,844 sure and transmission (eg, college students, health care
Occupational risks 63,580 workers). Otherwise, one dose is recommended for adults
aged 18 years and older. Physician documentation of dis­
BMI, body mass index; LDL, low-density lipoprotein. ease is not acceptable evidence of MMR immunity.
Data from the US Burden of Disease Collaborators, 2019. Routine use of 13-valent pneumococcal conjugate
vaccine (PCV13) is recommended among adults aged 65
clinicians (though this remains controversial), can increase and older. Individuals 65 years of age or older who have
utilization of preventive services, but such methods have never received a pneumococcal vaccine should first receive
not been widely adopted. PCV13 followed by a dose of 23-valent pneumococcal
polysaccharide vaccine (PPSV23) 6-12 months later.
Borsky A et al. Few Americans receive all high-priority, appro­ Individuals who have received more than one dose of
priate clinical preventive services. Health Aff. (Millwood). PPSV23 should receive a dose of PCV13 more than 1 year
2018 Jun;37(6):925-8. [PMID: 29863918] after the last dose of PPSV23 was administered.
Heron M. Deaths: leading causes for 2017. Natl Vital Stat Rep.
The ACIP recommends routine use of a single dose of
2019 Jun 24;68(6)l-77. https://www.cdc.gov/nchs/data/nvsr/
nvsr68/nvsr68_06-508.pdf
tetanus, diphtheria, and five-component acellular pertussis
Levine DM et al. Quality and experience of outpatient care in the vaccine (Tdap) for adults aged 19-64 years to replace the
United States for adults with or without primary care. JAMA next booster dose of tetanus and diphtheria toxoids
Intern Med. 2019 Mar l;179(3):363-72. Erratum in: JAMA vaccine (Td). Due to increasing reports of pertussis in the
Intern Med. 2019 Jun 1;179(6):854. [PMID: 30688977] United States, clinicians may choose to give Tdap to per­
US Burden of Disease Collaborators. The state of US health,
sons aged 65 years and older (particularly to those who
1990-2016: burden of diseases, injuries, and risk factors
among US states. JAMA. 2018 Apr 10;319(14):1444-72.
might risk transmission to at-risk infants who are most
[PMID: 29634829] susceptible to complications, including death), despite lim­
Woolf SH et al. Life expectancy and mortality rates in the United ited published data on the safety and efficacy of the vaccine
States, 1959-2017. JAMA. 2019 Nov 26;322(20):1996-2016. in this age group.
[PMID: 31769830] Both hepatitis A vaccine and immune globulin pro­
vide protection against hepatitis A; however, administra­
PREVENTION OF INFECTIOUS DISEASES tion of immune globulin may provide a modest benefit
over vaccination in some settings. Hepatitis B vaccine
Much of the decline in the incidence and fatality rates of administered as a three-dose series is recommended for all
infectious diseases is attributable to public health children aged 0-18 years and high-risk individuals (ie,
measures—especially immunization, improved sanitation, health care workers, injection drug users, people with end­
and better nutrition. stage renal disease). Adults with diabetes are also at
Immunization remains the best means of preventing increased risk for hepatitis B infection. The ACIP recom­
many infectious diseases. Recommended immunization mends vaccination for hepatitis B in diabetic patients
schedules for children and adolescents can be found online at aged 19-59 years. The hepatitis B vaccine should also be
http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent. considered in diabetic persons age 60 and older.
html, and the schedule for adults is at http://www.cdc.gov/ Human papillomavirus (HPV) virus-like particle
vaccines/schedules/hcp/adult.html (see also Chapter 30). (VLP) vaccines have demonstrated effectiveness in pre­
Substantial morbidity and mortality from vaccine-preventable venting persistent HPV infections and thus may impact
diseases, such as hepatitis A, hepatitis B, influenza, and pneu­ the rate of cervical intraepithelial neoplasia (CIN) II—III.
mococcal infections, continue to occur among adults. The ACIP recommends routine HPV vaccination for
Increases in the number of vaccine-preventable diseases in children and adults aged 9-26 years. Though routinely
 CMDT 2021 CHAPTER 1
recommended at age 11 or 12 years, vaccination can be
given starting at 9 years of age. Catch-up HPV vaccination
is recommended for all persons not adequately vaccinated
through age 26 years. Catch-up vaccination is not recom­
mended for all adults older than 26 years. Shared clinical
decision-making regarding HPV vaccination is recom­
mended for some individuals between 27 and 45 years of
age (vaccine is not licensed for adults older than 45 years).
Persons traveling to countries where infections are
endemic should take the precautions described in Chapter 30
and at https://wwwnc.cdc.gov/travel/destinations/list.
Immunization registries—confidential, population-based,
computerized information systems that collect vaccination
data about all residents of a geographic area—can be used
to increase and sustain high vaccination coverage.
The US Preventive Services Task Force (USPSTF) rec­
ommends behavioral counseling for adolescents and adults
who are sexually active and at increased risk for sexually
transmitted infections. Sexually active women aged
24 years or younger and older women who are at increased
risk for infection should be screened for chlamydia and
gonorrhea. Screening HIV-positive men or men who have
sex with men for syphilis every 3 months is associated with
improved syphilis detection.
HIV infection remains a major infectious disease prob­
lem in the world. The CDC recommends universal HIV
screening of all patients aged 13-64, and the USPSTF rec­
ommends that clinicians screen adolescents and adults
aged 15-65 years. Clinicians should integrate biomedical
and behavioral approaches for HIV prevention. In addition
to reducing sexual transmission of HIV, initiation of anti­
retroviral therapy reduces the risk for AIDS-defining
events and death among patients with less immunologi­
cally advanced disease.
Daily preexposure prophylaxis (PrEP) with the fixed-
dose combination of tenofovir disoproxil 300 mg and
emtricitabine 200 mg (Truvada) should be considered for
people who are HIV-negative but at substantial risk for
HIV infection. Studies of men who have sex with men sug­
gest that PrEP is very effective in reducing the risk of
contracting HIV. Patients taking PrEP should be encour­
aged to use other prevention strategies, such as consistent
condom use and choosing less risky sexual behaviors (eg,
oral sex), to maximally reduce their risk. Postexposure
prophylaxis (PEP) with combinations of antiretroviral
drugs is widely used after occupational and nonoccupa-
tional contact, and may reduce the risk of transmission
by approximately 80%. PEP should be initiated within
72 hours of exposure.
In immunocompromised patients, live vaccines are
contraindicated, but many killed or component vaccines
are safe and recommended. Asymptomatic HIV-infected
patients have not shown adverse consequences when given
live MMR and influenza vaccinations as well as tetanus,
hepatitis B, Haemophilus influenzae type b, and pneumo­
coccal vaccinations—all should be given. However, if
poliomyelitis immunization is required, the inactivated
poliomyelitis vaccine is indicated. In symptomatic HIV-
infected patients, live-virus vaccines, such as MMR, should
generally be avoided, but annual influenza vaccination is
safe.
Herpes zoster, caused by reactivation from previous
varicella zoster virus infection, affects many older adults
and people with immune system dysfunction. It can cause
postherpetic neuralgia, a potentially debilitating chronic
pain syndrome. The ACIP recommends the herpes zoster
subunit vaccine (HZ/su; Shingrix) be used for the preven­
tion of herpes zoster and related complications in immu­
nocompetent adults age 50 and older and in individuals
who previously received Zostavax.
Zika virus spreads to people primarily through mos­
quito bites but can also spread during sex by a person
infected with Zika to his or her partner. Although clinical
disease is usually mild, Zika virus infections in women
infected during pregnancy have been linked to fetal micro­
cephaly and loss, and newborn and infant blindness and
other neurologic problems (see Chapter 32). Pregnant
women should consider postponing travel to areas where
Zika virus transmission is ongoing.
Blackstock OJ et al. A cross-sectional online survey of HIV pre­
exposure prophylaxis adoption among primary care physicians.
J Gen Intern Med. 2017 Jan;32(l):62-70. [PMID: 27778215]
Centers for Disease Control and Prevention (CDC). HIV/AIDS,
2019. https://www.cdc.gov/hiv/basics/index.html
Centers for Disease Control and Prevention (CDC). PEP
(postexposure prophylaxis), 2018. https://www.cdc.gov/hiv/
risk/pep/index.html
Centers for Disease Control and Prevention (CDC). PrEP
(preexposure prophylaxis), 2019. https://www.cdc.gov/hiv/
basics/prep.html
Centers for Disease Control and Prevention (CDC). Recom­
mended Adult Immunization Schedules: United States, 2019.
https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html
Centers for Disease Control and Prevention (CDC). Zika virus,
2019. https://www.cdc.gov/zika/index.html
Meites E et al. Human papillomavirus vaccination for adults:
updated recommendations of the Advisory Committee on
Immunization Practices. MMWR Morb Mortal Wkly Rep.
2019 Aug 16;68(32):698-702. [PMID: 31415491]
Riddell J 4th et al. HIV preexposure prophylaxis: a review. JAMA.
2018 Mar 27;319(12):1261-8. [PMID: 29584848]
Short MD et al. Which patients should receive the herpes zoster
vaccine? JAAPA. 2019 Sep;32(9):18-20. [PMID: 31460969]
PREVENTION OF CARDIOVASCULAR DISEASE
Cardiovascular diseases (CVDs), including coronary heart
disease (CHD) and stroke, represent two of the most
important causes of morbidity and mortality in developed
countries. Several risk factors increase the risk for coronary
disease and stroke. These risk factors can be divided into
those that are modifiable (eg, lipid disorders, hypertension,
cigarette smoking) and those that are not (eg, age, sex, fam­
ily history of early coronary disease). Impressive declines
in age-specific mortality rates from heart disease and
stroke have been achieved in all age groups in North
America during the past two decades, in large part through
improvement of modifiable risk factors: reductions in ciga­
rette smoking, improvements in lipid levels, and more
aggressive detection and treatment of hypertension. This
section considers the role of screening for cardiovascular
risk and the use of effective therapies to reduce such risk.
Key recommendations for cardiovascular prevention
are shown in Table 1-3. Guidelines encourage regular
 DISEASE PREVENTION & HEALTH PROMOTION CMDT2021

Table 1-3. Expert recommendations for cardiovascular risk prevention methods: US Preventive Services Task Force
(USPSTF).1

Prevention Method Recommendation/[Year Issued]

Screening for Recommends one-time screening for AAA by ultrasonography in men aged 65-75 years who have ever smoked. (B)
abdominal aortic Selectively offer screening for AAA in men aged 65-75 years who have never smoked. (C)
aneurysm (AAA) 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 or have a family history of AAA. (1)
Recommends against routine screening for AAA in women who have never smoked and have no family history of
AAA. (D)
[2019]
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 The USPSTF recommends screening for high blood pressure in adults aged 18 years or older. The USPSTF
screening recommends obtaining measurements outside of the clinical setting for diagnostic confirmation before starting
treatment. (A)
[2015]
Serum lipid screening The USPSTF recommends that adults without a history of CVD use a low- to moderate-dose statin for the prevention
and use of statins of CVD events and mortality when all of the following criteria are met: (1) they are aged 40-75 years; (2) they have
for prevention 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 recommendations1 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 initiat­
ing 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 Recommends offering or referring adults who are overweight or obese and have additional CVD risk factors to inten­
healthful diet and sive behavioral counseling interventions to promote a healthful diet and physical activity for CVD prevention. (B)
physical activity for [2014]
CVD prevention 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 Recommends screening for abnormal blood glucose as part of cardiovascular risk assessment in adults aged
diabetes 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 Recommends that clinicians ask all adults about tobacco use, advise them to stop using tobacco, and provide
and counseling to behavioral interventionsand US Food and Drug Administration (FDA)-approved pharmacotherapy for cessation
promote cessation to adults who use tobacco. (A)
[2015]

1US Preventive Services Task Force recommendations available at http://www.uspreventiveservicestaskforce.org/BrowseRec/lndex/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 makes no recommendation for or against routine provision of the service.
Recommendation D: The USPSTF recommends against routinely p roviding the service to asymp tomatic p atients. (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.
 CMDT 2021 CHAPTER 1
assessment of global cardiovascular risk in adults
40-79 years of age without known CVD, using standard
cardiovascular risk factors. The role of nontraditional risk
factors for improving risk estimation remains unclear.
Lin JS et al. Nontraditional risk factors in cardiovascular disease
risk assessment: a systematic evidence report for the US
Preventive Services Task Force [Internet]. Rockville, MD:
Agency for Healthcare Research and Quality (US); 2018 Jul.
https://www.ncbi.nlm.nih.gov/books/NBK525925/ [PMID:
30234933]
Wall HK et al. Vital signs: prevalence of key cardiovascular
disease risk factors for Million Hearts 2022—United States,
2011-2016. MMWR Morb Mortal Wkly Rep. 2018 Sep 7;
67(35):983-91. [PMID: 30188885]
Yadlowsky S et al. Clinical implications of revised pooled cohort
equations for estimating atherosclerotic cardiovascular
disease risk. Ann Intern Med. 2018 Jul 3; 169( 1 ):20—9. [PMID:
29868850]
Abdominal Aortic Aneurysm
One-time screening for abdominal aortic aneurysm (AAA)
by ultrasonography is recommended by the USPSTF
(B recommendation) in men aged 65-75 years who have
ever smoked. One-time screening for AAA is associated
with a relative reduction in odds of AAA-related mortality
over 12-15 years (odds ratio [OR] 0.65 [95% confidence
interval [CI] 0.57-0.74]) and a similar reduction in AAA-
related ruptures (OR 0.62 [95% CI 0.55-0.70]). Women
who have never smoked and who have no family history
of AAA do not appear to benefit from such screening (D
recommendation); the current evidence for women who
have ever smoked or who have a family history of AAA is
insufficient to assess the balance of risks versus benefits (I
recommendation) (Table 1-3).
Guirguis-Blake JM et al. Primary care screening for abdominal
aortic aneurysm: updated evidence report and systematic
review for the US Preventive Services Task Force. JAMA. 2019
Dec 10;322(22):2219-38. [PMID: 31821436]
US Preventive Services Task Force, Owens DK et al. Screening
for abdominal aortic aneurysm: US Preventive Services Task
Force Recommendation Statement. JAMA. 2019 Dec
10;322(22):2211—8. [PMID: 31821437]
Ying AJ et al. Abdominal aortic aneurysm screening: a system­
atic review and meta-analysis of efficacy and cost. Ann Vase
Surg. 2019 Jan;54:298-303.e3. [PMID: 30081169]
Cigarette Smoking
Cigarette smoking remains the most important cause of
preventable morbidity and early mortality. In 2015, there
were an estimated 6.4 million premature deaths in the
world attributable to smoking and tobacco use; smoking is
the second leading cause of disability-adjusted life-years
lost. Cigarettes are responsible for one in every five deaths
in the United States, or over 480,000 deaths annually.
Annual cost of smoking-related health care is approxi­
mately $130 billion in the United States, with another $150
billion in productivity losses. Fortunately, US smoking
rates have been declining; in 2015,15.1% of US adults were
smokers, and by 2018, 13.7% were smokers. Global direct
health care costs from smoking in 2012 were estimated at
$422 billion, with total costs of over $1.4 trillion.
Over 41,000 deaths per year in the United States are
attributable to environmental tobacco smoke.
Smoking cessation reduces the risks of death and of
myocardial infarction in people with coronary artery
disease; reduces the rate of death and acute myocardial
infarction in patients who have undergone percutaneous
coronary revascularization; lessens the risk of stroke; and is
associated with improvement of chronic obstructive pul­
monary disease symptoms. On average, women smokers
who quit smoking by age 35 add about 3 years to their life
expectancy, and men add more than 2 years to theirs.
Smoking cessation can increase life expectancy even for
those who stop after the age of 65.
Although tobacco use constitutes the most serious
common medical problem, it is undertreated. Almost 40%
of smokers attempt to quit each year, but only 4% are suc­
cessful. Persons whose clinicians advise them to quit are
1.6 times as likely to attempt quitting. Over 70% of smokers
see a physician each year, but only 20% of them receive any
medical quitting advice or assistance.
Factors associated with successful cessation include
having a rule against smoking in the home, being older,
and having greater education. Several effective clinical
interventions are available to promote smoking cessation,
including counseling, pharmacotherapy, and combinations
of the two.
Helpful counseling strategies are shown in Table 1-4.
Additionally, a system should be implemented to identify
smokers, and advice to quit should be tailored to the
patients level of readiness to change. All patients trying to
quit should be offered pharmacotherapy (Table 1-5) except
those with medical contraindications, women who are
pregnant or breast-feeding, and adolescents. Weight gain
occurs in most patients (80%) following smoking cessa­
tion. Average weight gain is 2 kg, but for some (10-15%),
major weight gain—over 13 kg—may occur. Planning for
the possibility of weight gain, and means of mitigating it,
may help with maintenance of cessation.
Several pharmacologic therapies shown to be effective
in promoting cessation are summarized in Table 1-5. Nico­
tine replacement therapy doubles the chance of successful
quitting. The nicotine patch, gum, and lozenges are avail­
able over the counter and nicotine nasal spray and inhalers
by prescription. The sustained-release antidepressant drug
bupropion (150-300 mg/day orally) is an effective smoking
cessation agent and is associated with minimal weight gain,
although seizures are a contraindication. It acts by boosting
brain levels of dopamine and norepinephrine, mimicking
the effect of nicotine. Varenicline, a partial nicotinic acetyl -
choline-receptor agonist, has been shown to improve ces­
sation rates; however, its adverse effects, particularly its
effects on mood, are not completely understood and war­
rant careful consideration. No single pharmacotherapy is
clearly more effective than others, so patient preferences
and data on adverse effects should be taken into account in
selecting a treatment. Combination therapy is more effec­
tive than a single pharmacologic modality. The efficacy of
 DISEASE PREVENTION & HEALTH PROMOTION CMDT2021

Table 1-4. Inquiries to help in support of smoking cessation.

Component Helpful Clinician Statements and Inquiries

Communicate your caring and concern
Encourage the patient to talk about the
quitting process
Provide basic information about smoking
(eg, its addictive nature) and successful
quitting (eg, nature and time course of
withdrawal)
Encourage the patient to make a quit attempt
"1 am concerned about the effects of smoking on your health...
• and want you to know that 1 am willing to help you to quit."
• and so how do you feel about quitting?"
• do you have any fears or ambivalent feelings about quitting?"
"Tell me...
• why do you want to quit smoking?"
• when you tried quitting smoking in the past, what sort of difficulties did you
encounter?"
• were you able to succeed at all, even for a while?"
• what concerns or worries do you have about quitting now?"
"Did you know that...
• the nicotine in cigarette smoke is highly addictive?"
• within a day of stopping, you will notice nicotine withdrawal symptoms, such as
irritability and craving?"
• after you quit, any smoking (even a single puff) makes it likely that you will fully
relapse into smoking again?"
"1 want you to reassure you that...
• as your clinician, 1 believe you are going to be able to quit."
• there are now available many effective smoking cessation treatments."
• more than half the people who have ever smoked have now successfully quit."

e-cigarettes in smoking cessation has not been well evalu­

ated, and some users may find them addictive. Recent
reports of “vaping-related” lung disease should prompt
additional caution in the use of unregulated nicotine deliv­
ery devices for smoking cessation (see Chapter 9).
Clinicians should not show disapproval of patients who
fail to stop smoking or who are not ready to make a quit
attempt. Thoughtful advice that emphasizes the benefits of
cessation and recognizes common barriers to success can
increase motivation to quit and quit rates. An upcoming
medical procedure or intercurrent illness or hospitalization
may motivate even the most addicted smoker to quit.
Individualized or group counseling is very cost effec­
tive, even more so than treating hypertension. Smoking
cessation counseling by telephone (“quitlines”) and text
messaging-based interventions have both proved effective.
An additional strategy is to recommend that any smoking
take place outdoors to limit the effects of passive smoke on
housemates and coworkers. This can lead to smoking
reduction and quitting.
Public policies, including higher cigarette taxes and
more restrictive public smoking laws, have also been
shown to encourage cessation, as have financial incentives
directed to patients.
Anonymous. Drugs for smoking cessation. Med Lett Drugs
Ther. 2019 Jul 15;61(1576): 105-10. [PMID: 31381546]
Centers for Disease Control and Prevention (CDC). Current
cigarette smoking among adults in the United States in 2017.2019
November 18. https://www.cdc.gov/tobacco/data_statistics/
fact_sheets/adult_data/cig_smoking/index.htm
Goodchild M et al. Global economic cost of smoking-attributable
diseases. Tob Control. 2018 Jan;27(l):58-64. [PMID:
28138063]
Hollands GJ et al. Interventions to increase adherence to medi­
cations for tobacco dependence. Cochrane Database Syst Rev.
2019 Aug 16;8:CD009164. [PMID: 31425618]
Ma J et al. Smoking-attributable mortality by state in 2014, U.S.
Am J Prev Med. 2018 May;54(5):661-70. [PMID: 29551325]
Tibuakuu M et al. National trends in cessation counseling,
prescription medication use, and associated costs among US
adult cigarette smokers. JAMA Netw Open. 2019 May 3;
2(5):el94585. [PMID: 31125108]
Lipid Disorders
Higher low-density lipoprotein (LDL) cholesterol concen­
trations and lower high-density lipoprotein (HDL) levels are
associated with an increased risk of CHD (see Chapter 28).
Measurement of total and high-density lipoprotein choles­
terol levels can help assess the degree of CHD risk. The best
age to start screening is controversial, as is its frequency.
Cholesterol-lowering therapy reduces the relative risk of
CHD events, with the degree of reduction proportional to
the reduction in LDL cholesterol achieved, at least at LDL
levels greater than 100 mg/dL. The absolute benefits of
screening for—and treating—abnormal lipid levels depend
on the presence and level of other cardiovascular risk fac­
tors, including hypertension, diabetes mellitus, smoking,
age, and sex. If other risk factors are present, atherosclerotic
CVD risk is higher and the potential benefits of therapy are
greater. Patients with known CVD are at higher risk and
have larger benefits from reduction in LDL cholesterol. The
optimal risk threshold for initiating statins for primary pre­
vention remains somewhat controversial, although most
guidelines now suggest statin therapy when the 10-year
atherosclerotic cardiovascular risk is greater than 10%.
Evidence for the effectiveness of statin-type drugs is
better than for the other classes of lipid-lowering agents
 CMDT 2021 CHAPTER 1

Table 1-5. Medications for tobacco dependence and smoking cessation.

Cost3
Drug Some Formulations Usual Adult Dosage1,2 30 days

Nicotine Replacement Therapies (NRTs]

Nicotine transdermal patch4 - generic 7,14,21 mg/24 hr patches 1 patch/day5 $54.90
(NicoDerm CQ)
Nicotine polacrilex gum4 - generic 2,4 mg/pieces 8-24 pieces/day5,6,7 $70.40
(Nicorette gum)
Nicotine polacrilex lozenge4,8 - generic 2,4 mg/lozenges 8-20 lozenges/day5,6,9 $81.47
(Nicorette Lozenge)

Nicotine oral inhaler - Nicotrol 10 mg cartridges10 4-16 cartridges/day5 $524.87

Nicotine nasal spray - Nicotrol NS 200 sprays/10 mL bottles (0.5 mg/spray) 2 sprays 8-40x/day (max 10 sprays/hr)4 $551.11
(4-bottle
package)
Dopaminergic-Noradrenergic Reuptake Inhibitor
Bupropion SR - generic 100,150,200 mg SR tablets11 150 mg orally once daily x 3 days, then $116.00
150 mg orally twice daily
Nicotinic Receptor Partial Agonist
Varenicline tartrate - Chantix 0.5,1 mg tablets 0.5 mg orally once daily x 3 days, then $568.80
0.5 mg twice daily on days 4-7, then
1 mg twice daily

SR, sustained-release.
1 Dosage reductions may be needed for liver or kidney impairment.

2Patients should receive a minimum of 3-6 months of effective therap y. In general, the dosage of NRTs can be tap ered at the end of

treatment; bup rop ion SR and varenicline can usually be stop p ed without a gradual dosage reduction, but some clinicians recommend
a taper.
3Cost for 30 days treatment.

4Available over-the-counter for persons >18 years old.

5See expanded table for dosage titration instructions, available at: medicalletter.org/TML-article-1576c.

6Eating or drinking within 15 minutes of using a gum or lozenge should be avoided.

7 A second piece of gum can be used within 1 hour. Continuously chewing one piece after another is not recommended.

8Also available in a mini-lozenge.

9Maximum of 5 lozenges in 6 hours or 20 lozenges/day. Use of more than 1 lozenge at a time or continuously using one after another is

not recommended.
10Each cartridge delivers 4 mg of nicotine.

11Only the generic 150-mg SR tablets are FDA-approved as a smoking cessation aid.

Modified, with permission, from Drugs for smoking cessation. Med L ett Drugs Ther. 2019 Jul 15;61 (1576): 105-10. http://www.medicalletter
•org.

or dietary changes specifically for improving lipid levels.
Multiple large, randomized, placebo-controlled trials
have demonstrated important reductions in total mortal­
ity, major coronary events, and strokes with lowering
levels of LDL cholesterol by statin therapy for patients
with known CVD. Statins also reduce cardiovascular
events for patients with diabetes mellitus. For patients
with no previous history of cardiovascular events or dia­
betes, meta-analyses have shown important reductions of
cardiovascular events.
Newer antilipidemic monoclonal antibody agents (eg,
evolocumab and alirocumab) lower LDL cholesterol by
50-60% by binding proprotein convertase subtilisin kexin
type 9 (PCSK9), which decreases the degradation of LDL
receptors. PCSK9 inhibitors also decrease Lp(a) levels. These
newer agents are very expensive so are often used mainly in
high-risk patients when statin therapy does not reduce the
LDL cholesterol sufficiently at maximally tolerated doses
or when patients are intolerant of statins. So far, few side
effects have been reported with PCSK9 inhibitor use.
Guidelines for statin and PCSK9 therapy are discussed
in Chapter 28.
Navarese EP et al. Association between baseline LDL-C level and
total and cardiovascular mortality after LDL-C lowering: a
systematic review and meta-analysis. JAMA. 2018 Apr
17;319(15):1566-79. [PMID: 29677301]
Pagidipati NJ et al. Comparison of recommended eligibility for
primary prevention statin therapy based on the US Preventive
Services Task Force Recommendations vs the ACC/AHA
Guidelines. JAMA. 2017 Apr 18;317(15):1563-7. [PMID:
28418481]
 DISEASE PREVENTION & HEALTH PROMOTION
US Preventive Services Task Force. Statin use for the primary
prevention of cardiovascular disease in adults: US Preventive
Services Task Force Recommendation Statement. JAMA.
2016 Nov 15;316( 19): 1997-2007. [PMID: 27838723]
Hypertension
Over 67 million adults in the United States have hyperten­
sion, representing 29% of the adult US population (see
Chapter 11). Hypertension in nearly half of these adults is
not controlled (ie, less than 140/90 mm Hg). Among those
whose hypertension is not well controlled, nearly 40% are
not aware of their elevated blood pressure; almost 16% are
aware but not being treated; and 45% are being treated but
the hypertension is not controlled. In every adult age group,
higher values of systolic and diastolic blood pressure carry
greater risks of stroke and heart failure. Systolic blood pres­
sure is a better predictor of morbid events than diastolic
blood pressure. Home monitoring is better correlated with
target organ damage than clinic-based values. Clinicians
can apply specific blood pressure criteria, such as those of
the Joint National Committee or American Heart Associa­
tion guidelines, along with consideration of the patients
cardiovascular risk and personal values, to decide at what
levels treatment should be considered in individual cases.
Primary prevention of hypertension can be accom­
plished by strategies aimed at both the general population
and special high-risk populations. The latter include per­
sons with high-normal blood pressure or a family history
of hypertension, blacks, and individuals with various
behavioral risk factors, such as physical inactivity; exces­
sive consumption of salt, alcohol, or calories; and deficient
intake of potassium. Effective interventions for primary
prevention of hypertension include reduced sodium and
alcohol consumption, weight loss, and regular exercise.
Potassium supplementation lowers blood pressure mod­
estly, and a diet high in fresh fruits and vegetables and low
in fat, red meats, and sugar-containing beverages also
reduces blood pressure. Interventions of unproven efficacy
include pill supplementation of potassium, calcium, mag­
nesium, fish oil, or fiber; macronutrient alteration; and
stress management.
Improved identification and treatment of hypertension
is a major cause of the recent decline in stroke deaths as
well as the reduction in incidence of heart failure-related
hospitalizations. Because hypertension is usually asymp­
tomatic, screening is strongly recommended to identify
patients for treatment. Elevated office readings should be
confirmed with repeated measurements, ideally from
ambulatory monitoring or home measurements. Despite
strong recommendations in favor of screening and treat­
ment, hypertension control remains suboptimal. An inter­
vention that included both patient and provider education
was more effective than provider education alone in
achieving control of hypertension, suggesting the benefits
of patient participation; another trial found that home
monitoring combined with telephone-based nurse support
was more effective than home monitoring alone for blood
pressure control. Pharmacologic management of hyperten­
sion is discussed in Chapter 11.
CMDT2021
Bundy JD et al. Comparison of the 2017 ACC/AH A Hyperten­
sion Guideline with earlier guidelines on estimated reduc­
tions in cardiovascular disease. Curr Hypertens Rep. 2019
Aug 31;21(10):76. [PMID: 31473837]
Fryar CD et al. Hypertension prevalence and control among
adults: United States, 2015-2016. NCHS Data Brief. 2017
Oct;(289):l-8. [PMID: 29155682]
Weiss J et al. Benefits and harms of intensive blood pressure
treatment in adults aged 60 years or older: a systematic review
and meta-analysis. Ann Intern Med. 2017 Mar 21;166(6):
419-29. [PMID: 28114673]
Whelton PK et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/
ASH/ASPC/NMA/PCNA guideline for the prevention, detec­
tion, evaluation, and management of high blood pressure in
adults: a report of the American College of Cardiology/
American Heart Association Task Force on Clinical Practice
Guidelines. Hypertension. 2018 Jun;71(6):1269-324. [PMID:
29133354]
Chemoprevention
Regular use of low-dose aspirin (81-325 mg) can reduce
cardiovascular events but increases gastrointestinal bleed­
ing. Aspirin may also reduce the risk of death from several
common types of cancer (colorectal, esophageal, gastric,
breast, prostate, and possibly lung). The potential benefits
of aspirin may exceed the possible adverse effects among
middle-aged adults who are at increased cardiovascular
risk, which can be defined as a 10-year risk of greater than
10%, and who do not have an increased risk of bleeding. A
newer trial in older healthy adults did not find clear benefit
from aspirin for reduction of cardiovascular events and
saw an increase in all-cause mortality with aspirin. There­
fore, aspirin should not be routinely initiated in healthy
adults over age 70.
Nonsteroidal anti-inflammatory drugs may reduce the
incidence of colorectal adenomas and polyps but may also
increase heart disease and gastrointestinal bleeding, and
thus are not recommended for colon cancer prevention in
average-risk patients.
Antioxidant vitamin (vitamin E, vitamin C, and
beta-carotene) supplementation produced no significant
reductions in the 5-year incidence of—or mortality from—
vascular disease, cancer, or other major outcomes in high-
risk individuals with coronary artery disease, other
occlusive arterial disease, or diabetes mellitus.
Gaziano JM. Aspirin for primary prevention: clinical consider­
ations in 2019. JAMA. 2019 Jan 22;321(3):253-55. [PMID:
30667488]
Huang WY et al. Frequency of intracranial hemorrhage with low-
dose aspirin in individuals without symptomatic cardiovascular
disease: a systematic review and meta-analysis. JAMA Neurol.
2019 May 13. [Epub ahead of print] [PMID: 31081871]
McNeil JJ et al; ASPREE Investigator Group. Effect of aspirin on
cardiovascular events and bleeding in the healthy elderly.
N Engl J Med. 2018 Oct 18;379( 16): 1509-18. [PMID: 30221597]
Patrono C et al. Role of aspirin in primary prevention of cardio­
vascular disease. Nat Rev Cardiol. 2019 Nov;16(ll):675-86.
[PMID: 31243390]
Zheng SL et al. Association of aspirin use for primary prevention
with cardiovascular events and bleeding events: a systematic
review and meta-analysis. JAMA. 2019 Jan 22;321 (3):277-87.
[PMID: 30667501]
 1 CMDT 2021 CHAPTER 1
PREVENTION OF OSTEOPOROSIS
See Chapter 26.
Osteoporosis, characterized by low bone mineral den­
sity, is common and associated with an increased risk of
fracture. The lifetime risk of an osteoporotic fracture is
approximately 50% for women and 30% for men. Osteopo­
rotic fractures can cause significant pain and disability. As
such, research has focused on means of preventing osteo­
porosis and related fractures. Primary prevention strategies
include calcium supplementation, vitamin D supplementa­
tion, and exercise programs. The effectiveness of calcium
and vitamin D for fracture prevention remain controver­
sial, particularly in noninstitutionalized individuals.
Screening for osteoporosis on the basis of low bone
mineral density is recommended for women over age 65,
based on indirect evidence that screening can identify
women with low bone mineral density and that treatment
of women with low bone density with bisphosphonates is
effective in reducing fractures. However, real-world adher­
ence to pharmacologic therapy for osteoporosis is low:
one-third to one-half of patients do not take their medica­
tion as directed. Screening for osteoporosis is also recom­
mended in younger women who are at increased risk. The
effectiveness of screening in men has not been established.
Concern has been raised that bisphosphonates may
increase the risk of certain uncommon atypical types of
femoral fractures and rare osteonecrosis of the jaw, making
consideration of the benefits and risks of therapy impor­
tant when considering osteoporosis screening.
US Preventive Services Task Force. Screening for osteoporosis to
prevent fractures: US Preventive Services Task Force recom­
mendation statement. JAMA. 2018 Jun 26;319(24):2521-31.
[PMID: 29946735]
US Preventive Services Task Force. Vitamin D, calcium, or com­
bined supplementation for the primary prevention of frac­
tures in community-dwelling adults: US Preventive Services
Task Force recommendation statement. JAMA. 2018 Apr
17;319(15):1592-9. [PMID: 29677309]
Yedavally-Yellayi S et al. Update on osteoporosis. Prim Care.
2019 Mar;46(l):175-90. [PMID: 30704657]
PREVENTION OF PHYSICAL INACTIVITY
Lack of sufficient physical activity is the second most
important contributor to preventable deaths, trailing only
tobacco use. The US Department of Health and Human
Services and the CDC recommend that adults (including
older adults) engage in 150 minutes of moderate-intensity
(such as brisk walking) or 75 minutes of vigorous-intensity
(such as jogging or running) aerobic activity or an equiva­
lent mix of moderate- and vigorous-intensity aerobic activ­
ity each week. In addition to activity recommendations, the
CDC recommends activities to strengthen all major muscle
groups (abdomen, arms, back, chest, hips, legs, and shoul­
ders) at least twice a week.
Patients who engage in regular moderate to vigorous
exercise have a lower risk of myocardial infarction, stroke,
hypertension, hyperlipidemia, type 2 diabetes mellitus,
diverticular disease, and osteoporosis. Evidence supports
the recommended guidelines of 30 minutes of moderate
physical activity on most days of the week in both the pri­
mary and secondary prevention of CHD.
In longitudinal cohort studies, individuals who report
higher levels of leisure-time physical activity are less likely
to gain weight. Conversely, individuals who are overweight
are less likely to stay active. However, at least 60 minutes of
daily moderate-intensity physical activity may be necessary
to maximize weight loss and prevent significant weight
regain. Moreover, adequate levels of physical activity
appear to be important for the prevention of weight gain
and the development of obesity. Physical activity also
appears to have an independent effect on health-related
outcomes, such as development of type 2 diabetes mellitus
in patients with impaired glucose tolerance when com­
pared with body weight, suggesting that adequate levels of
activity may counteract the negative influence of body
weight on health outcomes. Compared to individuals with­
out CVD, those with CVD may benefit from physical activ­
ity to a greater extent.
Physical activity can be incorporated into any person’s
daily routine. For example, the clinician can advise a
patient to take the stairs instead of the elevator, to walk or
bike instead of driving, to do housework or yard work, to
get off the bus one or two stops earlier and walk the rest of
the way, to park at the far end of the parking lot, or to walk
during the lunch hour. The basic message should be the
more the better, and anything is better than nothing.
To be more effective in counseling about exercise, clini­
cians can also incorporate motivational interviewing tech­
niques, adopt a whole-practice approach (eg, use practice
nurses to assist), and establish linkages with community
agencies. Clinicians can incorporate the “5 As” approach:
1. Ask (identify those who can benefit).
2. Assess (current activity level).
3. Advise (individualize plan).
4. Assist (provide a written exercise prescription and sup­
port material).
5. Arrange (appropriate referral and follow-up).
Such interventions have a moderate effect on self­
reported physical activity and cardiorespiratory fitness,
even if they do not always help patients achieve a predeter­
mined level of physical activity. In their counseling, clini­
cians should advise patients about both the benefits and
risks of exercise, prescribe an exercise program appropriate
for each patient, and provide advice to help prevent injuries
and cardiovascular complications.
Although primary care providers regularly ask patients
about physical activity and advise them with verbal coun­
seling, few providers provide written prescriptions or per­
form fitness assessments. Tailored interventions may
potentially help increase physical activity in individuals.
Exercise counseling with a prescription, eg, for walking at
either a hard intensity or a moderate intensity with a high
frequency, can produce significant long-term improve­
ments in cardiorespiratory fitness. To be effective, exercise
prescriptions must include recommendations on type, fre­
quency, intensity, time, and progression of exercise and
 DISEASE PREVENTION & HEALTH PROMOTION
must follow disease-specific guidelines. Several factors
influence physical activity behavior, including personal,
social (eg, family and work), and environmental (eg, access
to exercise facilities and well-lit parks) factors. Walkable
neighborhoods around workplaces support physical activ­
ity such as walking and bicycling. A community-based
volunteer intervention resulted in increased walking activ­
ity among older women, who were at elevated risk for both
inactivity and adverse health outcomes.
Broad-based interventions targeting various factors are
often the most successful, and interventions to promote
physical activity are more effective when health agencies
work with community partners, such as schools, businesses,
and health care organizations. Enhanced community
awareness through mass media campaigns, school-based
strategies, and policy approaches are proven strategies to
increase physical activity.
Giroir BP et al. Physical activity guidelines for health and pros­
perity in the United States [Viewpoint]. JAMA. 2018 Nov
20;320(19): 1971-2. [PMID: 30418473]
Jeong SW et al. Mortality reduction with physical activity in
patients with and without cardiovascular disease. Eur Heart J.
2019 Nov 14;40(43):3547-55. [PMID: 31504416]
Kennedy AB et al. Tools clinicians can use to help get patients
active. Curr Sports Med Rep. 2018 Aug;17(8):271-6. [PMID:
30095547]
Piercy KL et al. The physical activity guidelines for Americans.
JAMA. 2018 Nov 20;320(19):2020-8. [PMID: 30418471]
PREVENTION OF OVERWEIGHT & OBESITY
Obesity is now a true epidemic and public health crisis that
both clinicians and patients must face. Normal body
weight is defined as a body mass index (BMI), calculated as
the weight in kilograms divided by the height in meters
squared, of less than 25; overweight is defined as a BMI =
25.0-29.9, and obesity as a BMI greater than 30. BMI is
often miscategorized as overweight, when it is in fact in the
obese range.
Risk assessment of the overweight and obese patient
begins with determination of BMI, waist circumference for
those with a BMI of 35 or less, presence of comorbid condi­
tions, and a fasting blood glucose and lipid panel. Obesity
is clearly associated with type 2 diabetes mellitus, hyper­
tension, hyperlipidemia, cancer, osteoarthritis, cardiovas­
cular disease, obstructive sleep apnea, and asthma.
Obesity is associated with a higher all-cause mortality
rate. Data suggest an increase among those with grades 2
and 3 obesity (BMI more than 35); however, the impact on
all-cause mortality among overweight (BMI 25-30) and
grade 1 obesity (BMI 30-35) is questionable. Persons with
a BMI of 40 or higher have death rates from cancers that
are 52% higher for men and 62% higher for women than
the rates in men and women of normal weight.
Prevention of overweight and obesity involves both
increasing physical activity and dietary modification to
reduce caloric intake. Adequate levels of physical activity
appear to be important for the prevention of weight gain
and the development of obesity. Physical activity programs
consistent with public health recommendations may
CMDT 2021
promote modest weight loss (~2 kg); however, the amount
of weight loss for any one individual is highly variable.
Clinicians can help guide patients to develop personal­
ized eating plans to reduce energy intake, particularly by
recognizing the contributions of fat, concentrated carbohy­
drates, and large portion sizes (see Chapter 29). Patients
typically underestimate caloric content, especially when
consuming food away from home. Providing patients with
caloric and nutritional information may help address the
current obesity epidemic. To prevent the long-term chronic
disease sequelae of overweight and obesity, clinicians must
work with patients to modify other risk factors, eg, by
smoking cessation (see previous section on cigarette smok­
ing) and strict blood pressure and glycemic control (see
Chapters 11 and 27).
Lifestyle modification, including diet, physical activity,
and behavior therapy, has been shown to induce clinically
significant weight loss. Other treatment options for obesity
include pharmacotherapy and surgery (see Chapter 29).
Counseling interventions or pharmacotherapy can produce
modest (3-5 kg) sustained weight loss over 6-12 months.
Counseling appears to be most effective when intensive
and combined with behavioral therapy. Pharmacotherapy
appears safe in the short term; long-term safety is still not
established.
Commercial weight loss programs are effective in pro­
moting weight loss and weight loss management. A ran­
domized controlled trial of over 400 overweight or obese
women demonstrated the effectiveness of a free prepared
meal and incentivized structured weight loss program
compared with usual care.
Weight loss strategies using dietary, physical activity, or
behavioral interventions can produce significant improve­
ments in weight among persons with prediabetes and a
significant decrease in diabetes incidence. Lifestyle inter­
ventions including diet combined with physical activity are
effective in achieving weight loss and reducing cardiometa-
bolic risk factors among patients with severe obesity.
Bariatric surgical procedures, eg, adjustable gastric
band, sleeve gastrectomy, and Roux-en-Y gastric bypass,
are reserved for patients with morbid obesity whose BMI
exceeds 40, or for less severely obese patients (with BMIs
between 35 and 40) with high-risk comorbid conditions
such as life-threatening cardiopulmonary problems (eg,
severe sleep apnea, Pickwickian syndrome, and obesity-
related cardiomyopathy) or severe diabetes mellitus. In
selected patients, surgery can produce substantial weight
loss (10-159 kg) over 1-5 years, with rare but sometimes
severe complications. Nutritional deficiencies are one com­
plication of bariatric surgical procedures and close moni­
toring of a patients metabolic and nutritional status is
essential.
Finally, clinicians seem to share a general perception
that almost no one succeeds in long-term maintenance of
weight loss. However, research demonstrates that approxi­
mately 20% of overweight individuals are successful at long­
term weight loss (defined as losing 10% or more of initial
body weight and maintaining the loss for 1 year or longer).
Clinicians must work to identify and provide the best
prevention and treatment strategies for patients who are
 CMDT 2021 CHAPTER 1
overweight and obese. Clinician advice on weight loss can
have a significant impact on patient attempts to adjust
weight-related behaviors. Unfortunately, many clinicians
are poorly prepared to address obesity. Clinicians are more
likely to give advice as BMI increases, missing opportuni­
ties to discuss weight with overweight patients. Clinician
bias and lack of training in behavior-change strategies
impair the care of obese patients. Strategies to address
these issues should be incorporated into innovative treat­
ment and care-delivery strategies (see Chapter 29).
Ryan DH et al. Guideline recommendations for obesity manage­
ment. Med Clin North Am. 2018 Jan;102(l):49-63. [PMID:
29156187]
Walsh K et al. Health advice and education given to overweight
patients by primary care doctors and nurses: a scoping
literature review. Prev Med Rep. 2019 Jan 25;14:100812.
[PMID: 30805277]
CANCER PREVENTION
Primary Prevention
Cancer mortality rates continue to decrease in the United
States; part of this decrease results from reductions in
tobacco use, since cigarette smoking is the most important
preventable cause of cancer. Primary prevention of skin
cancer consists of restricting exposure to ultraviolet light
by wearing appropriate clothing, and use of sunscreens.
Persons who engage in regular physical exercise and avoid
obesity have lower rates of breast and colon cancer. Preven­
tion of occupationally induced cancers involves minimiz­
ing exposure to carcinogenic substances, such as asbestos,
ionizing radiation, and benzene compounds. Chemopre­
vention has been widely studied for primary cancer pre­
vention (see earlier Chemoprevention section and Chapter
39). Use of tamoxifen, raloxifene, and aromatase inhibitors
for breast cancer prevention is discussed in Chapters 17
and 39. Hepatitis B vaccination can prevent hepatocellular
carcinoma (HCC), and screening and vaccination pro­
grams may be cost effective and useful in preventing HCC
in high-risk groups, such as Asians and Pacific Islanders.
Screening and treatment of hepatitis C is another strategy
to prevent HCC (see Chapter 16). The use of HPV vaccine
to prevent cervical and possibly anal cancer is discussed
earlier in this chapter. HPV vaccines may also have a role
in the prevention of HPV-related head and neck cancers.
The USPSTF recommends genetic counseling and, if indi­
cated after counseling, genetic testing for women whose
family or personal history is associated with an increased
risk of harmful mutations in the BRCA 1/2 gene. Guide­
lines for optimal cancer screening in adults over the age of
75 are unsettled; thus, an individualized approach that
considers differences in disease risk rather than chrono­
logical age alone is recommended.
US Preventive Services Task Force; Owens DK et al. Risk assess­
ment, genetic counseling, and genetic testing for BRCA-
related cancer: US Preventive Services Task Force
Recommendation Statement. JAMA. 2019 Aug 20;322(7):
652-65. [PMID: 31429903]
Wernli KJ et al. Screening for skin cancer in adults: updated
evidence report and systematic review for the US Preventive
Services Task Force. JAMA. 2016 Jul 26;316(4):436-47.
[PMID: 27458949]
Screening & Early Detection
Screening prevents death from cancers of the breast, colon,
and cervix. Current cancer screening recommendations
from the USPSTF are available online at https://www.
uspreventiveservicestaskforce.org/BrowseRec/Index/
browse-recommendations. Despite an increase in rates of
screening for breast, cervical, and colon cancer over the last
decade, overall screening for these cancers is suboptimal.
Interventions effective in promoting recommended cancer
screening include group education, one-on-one education,
patient reminders, reduction of structural barriers, reduc­
tion of out-of-pocket costs, and provider assessment and
feedback.
Though breast cancer mortality is generally reduced
with mammography screening, evidence from randomized
trials suggests that screening mammography has both ben­
efits and downsides. Clinicians should discuss the risks and
benefits with each patient and consider individual patient
preferences when deciding when to begin screening (see
Chapters 17 and e6).
Digital mammography is more sensitive in women with
dense breasts and in younger women; however, studies
exploring outcomes are lacking. MRI is not currently rec­
ommended for general screening, and its impact on breast
cancer mortality is uncertain; nevertheless, the American
Cancer Society recommends it for women at high risk
(20-25% or more), including those with a strong family
history of breast or ovarian cancer. Screening with both
MRI and mammography might be superior to mammogra­
phy alone in ruling out cancerous lesions in women with
an inherited predisposition to breast cancer. Digital breast
tomosynthesis (three-dimensional mammography) inte­
grated with digital mammography increases cancer detec­
tion rates compared to digital mammography alone;
however, the extent of improved detection and impact on
assessment outcomes need further exploration.
All current recommendations call for cervical and
colorectal cancer screening. Screening for testicular can­
cers among asymptomatic adolescent or adult males is not
recommended by the USPSTF. Prostate cancer screening
remains controversial, since no completed trials have
answered the question of whether early detection and
treatment after screen detection produce sufficient benefits
to outweigh harms of treatment. For men between the ages
of 55 and 69, the decision to screen should be individual­
ized and include a discussion of its risks and benefits with
a clinician. The USPSTF recommends against PSA-based
prostate cancer screening for men older than age 70 years
(grade D recommendation).
Annual or biennial fecal occult blood testing reduces
mortality from colorectal cancer. Fecal immunochemical
tests (FIT) are superior to guaiac-based fecal occult blood
tests (gFOBT) in detecting advanced adenomatous polyps
and colorectal cancer, and patients are more likely to favor
 DISEASE PREVENTION & HEALTH PROMOTION
FIT over gFOBT. Randomized trials using sigmoidoscopy
as the screening method found 20-30% reductions in mor­
tality from colorectal cancer. Colonoscopy has also been
advocated as a screening examination. It is more accurate
than flexible sigmoidoscopy for detecting cancer and pol­
yps, but its value in reducing colon cancer mortality has
not been studied directly. CT coIonography (virtual colo­
noscopy) is a noninvasive option in screening for colorectal
cancer. It has been shown to have a high safety profile and
performance similar to colonoscopy.
The USPSTF recommends screening for cervical cancer
in women aged 21-65 years with a Papanicolaou smear
(cytology) every 3 years or, for women aged 30-65 years
who desire longer intervals, screening with cytology and
HPV testing every 5 years. The USPSTF recommends
against screening in women younger than 21 years of age
and average-risk women over 65 with adequate negative
prior screenings. Receipt of HPV vaccination has no
impact on screening intervals.
Women whose cervical specimen HPV tests are positive
but cytology results are otherwise negative should repeat
co-testing in 12 months (option 1) or undergo HPV-
genotype-specific testing for types 16 or 16/18 (option 2).
Colposcopy is recommended in women who test positive
for types 16 or 16/18. Women with atypical squamous cells
of undetermined significance (ASCUS) on cytology and a
negative HPV test result should continue routine screening
as per age-specific guidelines.
In a randomized, controlled trial, transvaginal ultra­
sound combined with serum cancer antigen 125 (CA-125)
as screening tools to detect ovarian cancer did not reduce
mortality. Furthermore, complications were associated with
diagnostic evaluations to follow up false-positive screening
test results. Thus, screening for ovarian cancer with trans­
vaginal ultrasound and CA-125 is not recommended.
The USPSTF recommends offering annual lung cancer
screening with low-dose CT to current smokers aged 55 to
80 years with a 30-pack-year smoking history or to smokers
who quit within the past 15 years. Screening should stop
once a person has not smoked for 15 years or a health prob­
lem that significantly limits life expectancy has developed.
Screening should not be viewed as an alternative to smok­
ing cessation but rather as a complementary approach.
Geneve N et al. Colorectal cancer screening. Prim Care. 2019
Mar;46(l):135-48. [PMID: 30704654]
Li T et al. Digital breast tomosynthesis (3D mammography) for
breast cancer screening and for assessment of screen-recalled
findings: review of the evidence. Expert Rev Anticancer Ther.
2018 Aug;18(8):785-91. [PMID: 29847744]
Qaseem A et al. Screening for breast cancer in average-risk
women: a guidance statement from the American College of
Physicians. Ann Intern Med. 2019 Apr 16;170(8):547-60.
[PMID: 30959525]
Qaseem A et al. Screening for colorectal cancer in asymptomatic
average-risk adults: a guidance statement from the American
College of Physicians. Ann Intern Med. 2019 Nov 5;171 (9):
643-54. [PMID: 31683290]
US Preventive Services Task Force; Grossman DC et al. Screening
for ovarian cancer: US Preventive Services Task Force recom­
mendation statement. JAMA. 2018 Feb 13;319(6):588-94.
[PMID: 29450531]
CMDT 2021 3
US Preventive Services Task Force; Grossman DC et al. Screening
for prostate cancer: US Preventive Services Task Force recom­
mendation statement. JAMA. 2018 May 8;319(18):1901-13.
Erratum in: JAMA. 2018 Jun 19;319(23):2443. [PMID: 29801017]
US Preventive Services Task Force; Curry SJ et al. Screening for
cervical cancer: US Preventive Services Task Force recommen­
dation statement. JAMA. 2018 Aug 21;320(7):674-86. [PMID:
30140884]
PREVENTION OF INJURIES & VIOLENCE
Injuries remain the most important cause of loss of poten­
tial years of life before age 65. Homicide and motor vehicle
accidents are a major cause of injury-related deaths among
young adults, and accidental falls are the most common
cause of injury-related death in older adults. Approxi­
mately one-third of all injury deaths include a diagnosis of
traumatic brain injury, which has been associated with an
increased risk of suicide.
Although motor vehicle accident deaths per miles driven
have declined in the United States, there has been an increase
in motor vehicle accidents related to distracted driving (using
a cell phone, texting, eating). Evidence also suggests that
motorists’ use of sleeping medications (such as zolpidem)
almost doubles the risk of motor vehicle accidents. Clinicians
should discuss this risk when selecting a sleeping medication.
For 16- and 17-year-old drivers, the risk of fatal crashes
increases with the number of passengers.
Men ages 16-35 are at especially high risk for serious
injury and death from accidents and violence, with blacks
and Latinos at greatest risk. Deaths from firearms have
reached epidemic levels in the United States. Having a gun
in the home increases the likelihood of homicide nearly
threefold and of suicide fivefold. Educating clinicians to
recognize and treat depression as well as restricting access
to lethal methods have been found to reduce suicide rates.
In addition, clinicians should try to educate their patients
about always wearing seat belts and safety helmets, about the
risks of using cellular telephones or texting while driving and
of drinking and driving—or of using other intoxicants
(including marijuana) or long-acting benzodiazepines and
then driving—and about the risks of having guns in the home.
Clinicians have a critical role in the detection, preven­
tion, and management of intimate partner violence (see
Chapter e6). The USPSTF recommends screening women
of childbearing age for intimate partner violence and pro­
viding or referring women to intervention services when
needed. Inclusion of a single question in the medical
history—“At any time, has a partner ever hit you, kicked
you, or otherwise physically hurt you?”—can increase
identification of this common problem. Assessment for
abuse and offering of referrals to community resources cre­
ate the potential to interrupt and prevent recurrence of
domestic violence and associated trauma. Clinicians
should take an active role in following up with patients
whenever possible, since intimate partner violence screen­
ing with passive referrals to services may not be adequate.
Evaluation of services available to patients after identifica­
tion of intimate partner violence should be a priority.
Physical and psychological abuse, exploitation, and
neglect of older adults are serious, underrecognized
 CMDT 2021 CHAPTER 1

problems; they may occur in up to 10% of elders. Risk fac­
tors for elder abuse include a culture of violence in the
family; a demented, debilitated, or depressed and socially
isolated victim; and a perpetrator profile of mental illness,
alcohol or drug abuse, or emotional and/or financial
dependence on the victim. Clues to elder mistreatment
include the patient’s ill-kempt appearance, recurrent
urgent-care visits, missed appointments, suspicious physi­
cal findings, and implausible explanations for injuries.
Feltner C et al. Screening for intimate partner violence, elder
abuse, and abuse of vulnerable adults: evidence report and
systematic review for the US Preventive Services Task Force.
JAMA. 2018 Oct 23;320(16):1688—701. [PMID: 30357304]
Jin J. JAMA Patient Page. Screening for intimate partner vio­
lence, elder abuse, and abuse of vulnerable adults. JAMA.
2018 Oct 23;320(16):1718. [PMID: 30357300]
Lutgendorf MA. Intimate partner violence and women's health.
Obstet Gynecol. 2019 Sep;134(3):470-80. [PMID: 31403968]
PREVENTION OF SUBSTANCE USE DISORDER:
ALCOHOL & ILLICIT DRUGS
Unhealthy alcohol use is a major public health problem in
the United States, where approximately 51% of adults
18 years and older are current regular drinkers (at least 12
drinks in the past year). The 2015-2020 US Dietary Guide­
lines for Americans recommends that if alcohol is con­
sumed, it should be consumed in moderation—up to one
drink per day for women and two drinks per day for men—
and only by adults of legal drinking age. The spectrum of
alcohol use disorders includes alcohol dependence, harm­
ful pattern use of alcohol, and entities such as alcohol
intoxication, alcohol withdrawal, and several alcohol-
induced mental disorders. The ICD-11 includes a new
category: hazardous alcohol use. Categorized as a risk fac­
tor, hazardous alcohol use is a pattern of alcohol use that
appreciably increases the risk of physical or mental health
harmful consequence to the user.
Underdiagnosis and undertreatment of alcohol misuse
is substantial, both because of patient denial and lack of
detection of clinical clues.
As with cigarette use, clinician identification and
counseling about unhealthy alcohol use are essential. The
USPSTF recommends screening adults aged 18 years and
older for unhealthy alcohol use.
The Alcohol Use Disorder Identification Test (AUDIT)
consists of questions on the quantity and frequency of alco­
hol consumption, on alcohol dependence symptoms, and
on alcohol-related problems (Table 1-6). The AUDIT
questionnaire is a cost-effective and efficient diagnostic

Table 1-6. 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?
(0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily
5. How often during the past year have you failed to do what was normally expected of you because of drinking?
(0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily
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?
(0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily
7. How often during the past year have you had a feeling of guilt or remorse after drinking?
(0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily
8. How often during the past year have you been unable to remember what happened the night before because you had been
drinking?
(0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily
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 BaborTF, Higgins-Biddle JC, Saunders JB, Montiero MG. AUDIT. The Alcohol Use Disorders Identification Test.
Guidelines for Use in Primary Health Care, 2nd ed. Geneva, Switzerland: World Health Organization; 2001.
 DISEASE PREVENTION & HEALTH PROMOTION
tool for routine screening of alcohol use disorders in pri­
mary care settings. Brief advice and counseling without
regular follow-up and reinforcement cannot sustain sig­
nificant long-term reductions in unhealthy drinking
behaviors.
Time restraints may prevent clinicians from using the
full AUDIT to screen patients, but single-question screen­
ing tests for unhealthy alcohol use may help increase the
frequency of subsequent AUDIT screening in primary care
settings. The National Institute on Alcohol Abuse and
Alcoholism recommends the following single-question
screening test (validated in primary care settings): “How
many times in the past year have you had X or more drinks
in a day?” (X is 5 for men and 4 for women, and a response
of more than 1 time is considered positive.)
Clinicians should provide those who screen positive for
hazardous or risky drinking with brief behavioral counsel­
ing interventions to reduce alcohol misuse. Use of screen­
ing procedures and brief intervention methods (see
Chapter 25) can produce a 10-30% reduction in long-term
alcohol use and alcohol-related problems.
Several pharmacologic agents are effective in reducing
alcohol consumption. In acute alcohol detoxification, long-
acting benzodiazepines are preferred because they can be
given on a fixed schedule or through “front-loading” or
“symptom-triggered” regimens. Adjuvant sympatholytic
medications can be used to treat hyperadrenergic symp­
toms that persist despite adequate sedation. Three drugs
are FDA approved for treatment of alcohol dependence:
disulfiram (500 mg orally daily), naltrexone (50 mg orally
daily), and acamprosate (666 mg orally three times daily).
Prescription and nonprescription opioid-based drug
abuse, misuse, and overdose has reached epidemic propor­
tions in the United States. Deaths due to opioid overdose
have dramatically increased. Opioid risk mitigation strate­
gies include use of risk assessment tools, treatment agree­
ments (contracts), and urine drug testing. Additional
strategies include establishing and strengthening prescrip­
tion drug monitoring programs, regulating pain manage­
ment facilities, and establishing dosage thresholds requiring
consultation with pain specialists. Medication-assisted
treatment, the use of medications with counseling and
behavioral therapy, is effective in the prevention of opioid
overdose and substance abuse disorders. Methadone,
buprenorphine, and naltrexone are FDA approved for use
in medication-assisted treatment. Buprenorphine has
potential as a medication to ameliorate the symptoms and
CMDT 2021 5
signs of withdrawal from opioids and is effective in reduc­
ing concomitant cocaine and opioid abuse. The risk of
overdose is lower with buprenorphine than methadone,
and it is preferred for patients at high risk for methadone
toxicity (see Chapter 5). The FDA supports greater access
to naloxone and is currently exploring options to make
naloxone more available to treat opioid overdose. (See
Chapter 5.)
Use of illegal drugs—including cocaine, methamphet­
amine, and so-called designer drugs—either sporadically
or episodically remains an important problem. Lifetime
prevalence of drug abuse is approximately 8% and is gener­
ally greater among men, young and unmarried individuals,
Native Americans, and those of lower socioeconomic sta­
tus. As with alcohol, drug abuse disorders often coexist
with personality, anxiety, and other substance abuse disor­
ders. Abuse of anabolic-androgenic steroids has been asso­
ciated with use of other illicit drugs, alcohol, and cigarettes
and with violence and criminal behavior.
Clinical aspects of substance abuse are discussed in
Chapter 25.
Hepner KA et al. Rates and impact of adherence to recom­
mended care for unhealthy alcohol use. J Gen Intern Med.
2019 Feb;34(2):256-63. [PMID: 30484101]
Kaner EF et al. Effectiveness of brief alcohol interventions in
primary care populations. Cochrane Database Syst Rev. 2018
Feb 24;2:CD004148. [PMID: 29476653]
Pace CA et al. Addressing unhealthy substance use in primary
care. Med Clin North Am. 2018 Jul;102(4):567-86. [PMID:
29933816]
Peglow SL et al. Preventing opioid overdose in the clinic and
hospital: analgesia and opioid antagonists. Med Clin North
Am. 2018 Jul;102(4):621-34. [PMID: 29933819]
Saunders JB et al. Alcohol use disorders in ICD-11: past, present,
and future. Alcohol Clin Exp Res. 2019 Aug;43(8):1617-31.
[PMID: 31194891]
Substance Abuse and Mental Health Services Administration
(SAMHSA). Medication-Assisted Treatment (MAT), https://
www.samhsa.gov/medication-assisted-treatment
US Food and Drug Administration. FDA approves first generic
naloxone nasal spray to treat opioid overdose. 2019 Apr 19.
https://www.fda.gov/news-events/press-announcements/
fda-approves-first-generic-naloxone-nasal-spray-treat-
opioid-overdose
US Preventive Services Task Force, Curry SJ et al. Screening and
behavioral counseling interventions to reduce unhealthy
alcohol use in adolescents and adults: US Preventive Services
Task Force Recommendation Statement. JAMA. 2018 Nov
13;320(18):1899-909. [PMID: 30422199]
 CMDT 2021
Common Symptoms
Paul L. Nadler, MD
Ralph Gonzales, MD, MSPH
COUGH
ESSENTIAL INQUIRIES
► Age, tobacco use, e-cigarette vaping, cannabis use,
occupational history, environmental exposures,
and duration of cough.
► Dyspnea (at rest or with exertion).
► Vital signs (heart rate, respiratory rate, body
temperature).
► Chest examination.
► Chest radiography when unexplained cough lasts
more than 3-6 weeks.
General Considerations
Cough is the most common symptom for which patients
seek medical attention. Cough adversely affects personal
and work-related interactions, disrupts sleep, and often
causes discomfort of the throat and chest wall. Most people
seeking medical attention for acute cough desire symptom
relief; few are worried about serious illness. Cough results
from stimulation of mechanical or chemical afferent nerve
receptors in the bronchial tree. Effective cough depends on
an intact afferent-efferent reflex arc, adequate expiratory
and chest wall muscle strength, and normal mucociliary
production and clearance.
Clinical Findings
A. Symptoms
Distinguishing acute (less than 3 weeks), persistent
(3-8 weeks), and chronic (more than 8 weeks) cough ill­
ness syndromes is a useful first step in evaluation. Postin-
fectious cough lasting 3-8 weeks has also been referred to
as subacute cough to distinguish this common, distinct
clinical entity from acute and chronic cough.
1. Acute cough—In healthy adults, most acute cough
syndromes are due to viral respiratory tract infections.
Additional features of infection such as fever, nasal conges­
tion, and sore throat help confirm this diagnosis. Dyspnea
(at rest or with exertion) may reflect a more serious condi­
tion, and further evaluation should include assessment of
oxygenation (pulse oximetry or arterial blood gas measure­
ment), airflow (peak flow or spirometry), and pulmonary
parenchymal disease (chest radiography). The timing and
character of the cough are not very useful in establishing
the cause of acute cough syndromes, although cough­
variant asthma should be considered in adults with promi­
nent nocturnal cough, and persistent cough with phlegm
increases the likelihood of chronic obstructive pulmonary
disease (COPD). The presence of posttussive emesis or
inspiratory whoop in adults modestly increases the likeli­
hood of pertussis, and the absence of paroxysmal cough
and the presence of fever decrease its likelihood. Uncom­
mon causes of acute cough should be suspected in those
with heart disease (heart failure [HF]) or hay fever (allergic
rhinitis) and those with occupational risk factors (such as
farmworkers).
2. Persistent and chronic cough—Cough due to acute
respiratory tract infection resolves within 3 weeks in the
vast majority (more than 90%) of patients. Pertussis should
be considered in adolescents and adults who have persis­
tent or severe cough lasting more than 3 weeks, who have
not recently been boosted with Tdap, and who have been
exposed to a person with confirmed pertussis. It should
also be considered in selected geographic areas where its
prevalence approaches 20% (although its exact prevalence
is difficult to ascertain due to the limited sensitivity of
diagnostic tests).
When angiotensin-converting enzyme (ACE) inhibitor
therapy, acute respiratory tract infection, and chest radio­
graph abnormalities are absent, most cases of persistent
and chronic cough are due to (or exacerbated by) postna­
sal drip (upper airway cough syndrome), asthma, or gas­
troesophageal reflux disease (GERD), or some combination
of these three entities. Approximately 10% of cases are
caused by nonasthmatic eosinophilic bronchitis. A history
of nasal or sinus congestion, wheezing, or heartburn
should direct subsequent evaluation and treatment,
though these conditions frequently cause persistent cough
 COMMON SYMPTOMS CMDT 2021 7

in the absence of typical symptoms. Dyspnea at rest or

with exertion is not commonly reported among patients Table 2-1. Positive and negative likelihood ratios for
with persistent cough; dyspnea requires assessment for history, physical examination, and laboratory findings
chronic lung disease, HF, anemia, pulmonary embolism, in the diagnosis of pneumonia.
or pulmonary hypertension.
Positive Negative
Bronchogenic carcinoma is suspected when cough is
Likelihood Likelihood
accompanied by unexplained weight loss, hemoptysis, and Finding Ratio Ratio
fevers with night sweats, particularly in persons with sig­
nificant tobacco or occupational exposures (asbestos, Medical history
radon, diesel exhaust, and metals). Persistent and chronic Fever 1.7-2.1 0.6-0.7
cough accompanied by excessive mucus secretions Chills 1.3-1.7 0.7-0.9
increases the likelihood of COPD, particularly among
Physical examination
smokers, or of bronchiectasis if accompanied by a history
of recurrent or complicated pneumonia; chest radiographs Tachypnea (RR > 25 1.5-3.4 0.8
are helpful in diagnosis. Chronic cough with dry eyes may breaths/min)
represent Sjogren syndrome. A chronic dry cough may be Tachycardia (> 100 beats/ 1.6-2.3 0.5-0.7
the first symptom of idiopathic pulmonary fibrosis. min in two studies or
> 120 beats/min in one
study)
B. Physical Examination
Hyperthermia (> 37.8°C) 1.4-4.4 0.6-0.8
Examination can direct subsequent diagnostic testing for
Chest examination
acute cough. Pneumonia is suspected when acute cough is
accompanied by vital sign abnormalities (tachycardia, Dullness to percussion 2.2-4.3 0.8-0.9
tachypnea, fever). Findings suggestive of airspace consoli­ Decreased breath sounds 2.3-2.5 0.6-0.8
dation (crackles, decreased breath sounds, fremitus,
Crackles 1.6-2.7 0.6-0.9
egophony) are significant predictors of community-
acquired pneumonia but are present in a minority of cases. Rhonchi 1.4-1.5 0.8-0.9
Purulent sputum is associated with bacterial infections in Egophony 2.0-8.6 0.8-1.0
patients with structural lung disease (eg, COPD, cystic Laboratory findings
fibrosis), but it is a poor predictor of pneumonia in the
Leukocytosis (> 11 x 109/L 1.9-3.7 0.3-0.6
otherwise healthy adult. Wheezing and rhonchi are fre­
in one study or > 10.4 x
quent findings in adults with acute bronchitis and do not
109/L in another study)
indicate consolidation or adult-onset asthma in most cases.
Examination of patients with persistent cough should RR, respiratory rate.
look for evidence of chronic sinusitis, contributing to post­
nasal drip syndrome or asthma. Chest and cardiac signs
may help distinguish COPD from HF. In patients with [CI], 0.93-0.97) and a specificity of 0.90 (95% CI, 0.86-0.94).
cough and dyspnea, a normal match test (ability to blow Chest radiography had a pooled sensitivity of 0.77 (95% CI,
out a match from 25 cm away) and maximum laryngeal 0.73-0.80) and a specificity of 0.91 (95% CI, 0.87-0.94). In
height greater than 4 cm (measured from the sternal notch patients with dyspnea, pulse oximetry and peak flow help
to the cricoid cartilage at end expiration) substantially exclude hypoxemia or obstructive airway disease. How­
decrease the likelihood of COPD. Similarly, normal jugular ever, a normal pulse oximetry value (eg, greater than 93%)
venous pressure and no hepatojugular reflux decrease the does not rule out a significant alveolar-arterial (A-a) gra­
likelihood of biventricular HF. dient when patients have effective respiratory compensa­
tion. During documented outbreaks, clinical diagnosis of
C. Diagnostic Studies influenza has a positive predictive value of -70%; this
usually obviates the need for rapid diagnostic tests. No
1. Acute cough—Chest radiography should be considered
evidence exists to assess whether the initial evaluation of
for any adult with acute cough whose vital signs are abnor­
cough in immunocompromised patients should differ
mal or whose chest examination suggests pneumonia. The
from immunocompetent patients, but expert recommen­
relationship between specific clinical findings and the
dations suggest that tuberculosis be considered in HIV-
probability of pneumonia is shown in Table 2-1. A large,
infected patients in areas with a high prevalence of
multicenter randomized clinical trial found that elevated
tuberculosis regardless of radiographic findings.
serum C-reactive protein (levels greater than 30 mg/dL)
improves diagnostic accuracy of clinical prediction rules 2. Persistent and chronic cough—Chest radiography is
for pneumonia in adults with acute cough; procalcitonin indicated when ACE inhibitor therapy-related and postin-
added no clinically relevant information. A meta-analysis fectious cough are excluded. If pertussis is suspected, poly­
found that lung ultrasonography had better accuracy merase chain reaction testing should be performed on a
than chest radiography for the diagnosis of adult nasopharyngeal swab or nasal wash specimen—although
community-acquired pneumonia. Lung ultrasonography the ability to detect pertussis decreases as the duration of
had a pooled sensitivity of 0.95 (95% confidence interval cough increases. When the chest film is normal, postnasal
 CMDT 2021 CHAPTER 2
Table 2-2. Empiric therapy or definitive testing for
persistent cough.
Suspected Step 1 (Empiric Step 2 (Definitive
Condition Therapy) Testing)
Postnasal drip Therapy for allergy or Sinus CT scan;
chronic sinusitis ENT referral
Asthma Beta-2-agonist Spirometry; consider
methacholine
challenge if normal
GERD Lifestyle and diet mod­ Esophageal pH
ifications with or monitoring
without proton
pump inhibitors
ENT, ear, nose, and throat; GERD, gastroesophageal reflux disease.
drip, asthma, or GERD are the most likely causes. The
presence of typical symptoms of these conditions directs
further evaluation or empiric therapy, though typical
symptoms are often absent. Definitive tests for determin­
ing the presence of each are available (Table 2-2).
However, empiric treatment with a maximum-strength
regimen for postnasal drip, asthma, or GERD for
2-4 weeks is one recommended approach since docu­
menting the presence of postnasal drip, asthma, or GERD
does not mean they are the cause of the cough. Alterna­
tive approaches to identifying patients who have asthma
with its corticosteroid-responsive cough include examin­
ing induced sputum for increased eosinophil counts
(greater than 3%) or providing an empiric trial of predni­
sone, 30 mg daily orally for 2 weeks. Spirometry may help
identify large airway obstruction in patients who have
persistent cough and wheezing and who are not respond­
ing to asthma treatment. When empiric treatment trials are
not successful, additional evaluation with pH manometry,
endoscopy, barium swallow, sinus CT, or high-resolution
chest CT may identify the cause.
Differential Diagnosis
A. Acute Cough
Acute cough may be a symptom of acute respiratory tract
infection, asthma, allergic rhinitis, HF, and ACE inhibitor
therapy, as well as many less common causes.
B. Persistent and Chronic Cough
Causes of persistent cough include environmental expo­
sures (cigarette smoke, air pollution), occupational expo­
sures, pertussis, postnasal drip, asthma (including
cough-variant asthma), GERD, COPD, chronic aspiration,
bronchiectasis, eosinophilic bronchitis, tuberculosis or
other chronic infection, interstitial lung disease, and bron­
chogenic carcinoma. COPD is a common cause of persis­
tent cough among patients older than 50 years. Persistent
cough may also be due to somatic cough syndrome (previ­
ously called “psychogenic cough”) or tic cough (previously
called “habit cough”).
Treatment
A. Acute Cough
Treatment of acute cough should target the underlying
etiology of the illness, the cough reflex itself, and any addi­
tional factors that exacerbate the cough. Cough duration is
typically 1-3 weeks, yet patients frequently expect cough to
last fewer than 10 days. Limited studies on the use of dex­
tromethorphan suggest a minor or modest benefit.
When influenza is diagnosed (including H1N1 influ­
enza), oral oseltamivir or zanamivir or intravenous pera-
mivir are equally effective (1 less day of illness) when
initiated within 30-48 hours of illness onset; treatment is
recommended regardless of illness duration when patients
have severe, complicated, or progressive influenza and in
patients requiring hospitalization. In Chlamydophila- or
Mycoplasma-documented infection or outbreaks, first-line
antibiotics include erythromycin or doxycycline. Antibiot­
ics do not improve cough severity or duration in patients
with uncomplicated acute bronchitis. In patients with
bronchitis and wheezing, inhaled beta-2-agonist therapy
reduces severity and duration of cough. In patients with
acute cough, treating the accompanying postnasal drip
(with antihistamines, decongestants, saline nasal irrigation,
or nasal corticosteroids) can be helpful. A Cochrane review
(n = 163) found codeine to be no more effective than pla­
cebo in reducing cough symptoms.
B. Persistent and Chronic Cough
Evaluation and management of persistent cough often
require multiple visits and therapeutic trials, which fre­
quently lead to frustration, anger, and anxiety. When per­
tussis infection is suspected early in its course, treatment
with a macrolide antibiotic (see Chapter 33) is appropriate
to reduce organism shedding and transmission. When
pertussis has lasted more than 7-10 days, antibiotic treat­
ment does not affect the duration of cough, which can last
up to 6 months. Early identification, revaccination with
Tdap, and treatment of adult patients who work or live with
persons at high risk for complications from pertussis (preg­
nant women, infants [particularly younger than 1 year],
and immunosuppressed individuals) are encouraged.
Table 2-2 outlines empiric treatments for persistent
cough. There is no evidence to guide how long to continue
treatment for persistent cough due to postnasal drip,
asthma, or GERD. Studies have not found a consistent
benefit of inhaled corticosteroid therapy in adults with
persistent cough. Eight weeks of thrice-weekly azithromy­
cin did not improve cough in patients without asthma.
When empiric treatment trials fail, consider other
causes of chronic cough such as obstructive sleep apnea,
tonsillar or uvular enlargement, and environmental fungi.
The small percentage of patients with idiopathic chronic
cough should be managed in consultation with an otolar­
yngologist or a pulmonologist; consider a high-resolution
CT scan of the lungs. Treatment options include nebu­
lized lidocaine therapy and morphine sulfate, 5-10 mg
orally twice daily. Sensory dysfunction of the laryngeal
branches of the vagus nerve may contribute to persistent
 COMMON SYMPTOMS
cough syndromes and may help explain the effectiveness of
gabapentin in patients with chronic cough. Speech pathol­
ogy therapy combined with pregabalin has some benefit in
chronic refractory cough. In patients with reflex cough
syndrome, therapy aimed at shifting the patients atten-
tional focus from internal stimuli to external focal points
can be helpful. Proton pump inhibitors are not effective on
their own; most benefit appears to come from lifestyle
modifications and weight reduction.
When to Refer
• Failure to control persistent or chronic cough following
empiric treatment trials.
• Patients with recurrent symptoms should be referred to an
otolaryngologist, pulmonologist, or gastroenterologist.
When to Admit
• Patient at high risk for tuberculosis for whom compli­
ance with respiratory precautions is uncertain.
• Need for urgent bronchoscopy, such as suspected for­
eign body.
• Smoke or toxic fume inhalational injury.
• Gas exchanged is impaired by cough.
• Patients at high risk for barotrauma (eg, recent
pneumothorax).
Hill AT et al; CHEST Expert Cough Panel. Adult outpatients
with acute cough due to suspected pneumonia or influenza:
CHEST Guideline and Expert Panel Report. Chest. 2019 Jan;
155(l):155-67. [PMID: 30296418]
Moore A et al; CHEST Expert Cough Panel. Clinically diagnosing
pertussis-associated cough in adults and children: CHEST
Guideline and Expert Panel Report. Chest. 2019 Jan; 155(1):
147-54. [PMID: 30321509]
Sinharay R et al. Respiratory and cardiovascular responses to
walking down a traffic-polluted road compared with walking
in a traffic-free area in participants aged 60 years and older
with chronic lung or heart disease and age-matched healthy
controls: a randomised, crossover study. Lancet. 2018 Jan 27;
391(10118):339-49. [PMID: 29221643]
Smith SM et al. Antibiotics for acute bronchitis. Cochrane
Database SystRev. 2017 Jun 19;6:CD000245. [PMID: 28626858]
DYSPNEA
ESSENTIAL INQUIRIES
► Fever, cough, and chest pain.
► Vital sign measurements; pulse oximetry.
► Cardiac and chest examination.
► Chest radiography and arterial blood gas mea­
surement in selected patients.
General Considerations
Dyspnea is a subjective experience or perception of uncom­
fortable breathing. There is a lack of empiric evidence on
CMDT 2021 9
the prevalence, etiology, and prognosis of dyspnea in gen­
eral practice. The relationship between level of dyspnea
and the severity of underlying disease varies widely among
individuals. Dyspnea can result from conditions that
increase the mechanical effort of breathing (eg, asthma,
COPD, restrictive lung disease, respiratory muscle weak­
ness), conditions that produce compensatory tachypnea
(eg, hypoxemia, acidosis), primary pulmonary vasculopa­
thy (pulmonary hypertension), or psychogenic conditions.
The following factors play a role in how and when dyspnea
presents in patients: rate of onset, previous dyspnea, medi­
cations, comorbidities, psychological profile, and severity
of underlying disorder.
Clinical Findings
A. Symptoms
The duration, severity, and periodicity of dyspnea influence
the tempo of the clinical evaluation. Rapid onset or severe
dyspnea in the absence of other clinical features should
raise concern for pneumothorax, pulmonary embolism, or
increased left ventricular end-diastolic pressure (LVEDP).
Spontaneous pneumothorax is usually accompanied by
chest pain and occurs most often in thin, young males and
in those with underlying lung disease. Pulmonary embo­
lism should always be suspected when a patient with new
dyspnea reports a recent history (previous 4 weeks) of
prolonged immobilization or surgery, estrogen therapy, or
other risk factors for deep venous thrombosis (DVT) (eg,
previous history of thromboembolism, cancer, obesity,
lower extremity trauma) and when the cause of dyspnea is
not apparent. Silent myocardial infarction, which occurs
more frequently in diabetic persons and women, can result
in increased LVEDP, acute HF, and dyspnea.
Accompanying symptoms provide important clues to
causes of dyspnea. When cough and fever are present, pul­
monary disease (particularly infection) is the primary
concern; myocarditis, pericarditis, and septic emboli can
present in this manner. Chest pain should be further char­
acterized as acute or chronic, pleuritic or exertional.
Although acute pleuritic chest pain is the rule in acute
pericarditis and pneumothorax, most patients with pleu­
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
ischemia or pulmonary embolism. When associated with
wheezing, most cases of dyspnea are due to acute bronchi­
tis; however, other causes include new-onset asthma, for­
eign body, and vocal cord dysfunction. Interstitial lung
disease and pulmonary hypertension should be considered
in patients with symptoms (or history) of connective tissue
disease. Pulmonary lymphangitis carcinomatosis should be
considered if a patient has a malignancy, especially breast,
lung, or gastric cancer.
When a patient reports prominent dyspnea with mild
or no accompanying features, consider noncardiopulmo-
nary causes of impaired oxygen delivery (anemia, methe­
moglobinemia, cyanide ingestion, carbon monoxide
poisoning), metabolic acidosis, panic disorder, neuromus­
cular disorders, and chronic pulmonary embolism.
 1 CMDT 2021 CHAPTER 2
Platypnea-orthodeoxia syndrome is characterized by
dyspnea and hypoxemia on sitting or standing that
improves in the recumbent position. It may be caused by
an intracardiac shunt, pulmonary vascular shunt (includ­
ing hepatopulmonary syndrome), or ventilation-perfusion
mismatch. Hyperthyroidism can cause dyspnea from
increased ventilatory drive, respiratory muscle weakness,
or pulmonary hypertension.
B. Physical Examination
A focused physical examination should include evaluation
of the head and neck, chest, heart, and lower extremities.
Visual inspection of the patient can suggest obstructive
airway disease (pursed-lip breathing, use of accessory
respiratory muscles, barrel-shaped chest), pneumothorax
(asymmetric excursion), or metabolic acidosis (Kussmaul
respirations). Patients with impending upper airway
obstruction (eg, epiglottitis, foreign body) or severe asthma
exacerbation sometimes assume a tripod position. Focal
wheezing raises the suspicion for a foreign body or other
bronchial obstruction. Maximum laryngeal height (the
distance between the top of the thyroid cartilage and the
suprasternal notch at end expiration) is a measure of
hyperinflation. Obstructive airway disease is virtually non­
existent when a nonsmoking patient younger than age
45 years has a maximum laryngeal height greater than 4 cm.
Factors increasing the likelihood of obstructive airway
disease include patient history of more than 40 pack-years
smoking (adjusted likelihood ratio [LRJ + 11.6; LR- 0.9),
patient age 45 years or older (LR+ 1.4; LR- 0.5), and maxi­
mum laryngeal height greater than or equal to 4 cm (LR+
3.6; LR- 0.7). With all three of these factors present, the
LR+ rises to 58.5 and the LR- falls to 0.3.
Absent breath sounds suggest a pneumothorax. An
accentuated pulmonic component of the second heart
sound (loud P2) is a sign of pulmonary hypertension and
pulmonary embolism.
Clinical predictors of increased LVEDP in dyspneic
patients with no prior history of HF include tachycardia,
systolic hypotension, jugular venous distention, hepato­
jugular reflux, bibasilar crackles, third heart sound, lower
extremity edema, and chest film findings of pulmonary
vascular redistribution or cardiomegaly. When none is
present, there is a very low probability (less than 10%) of
increased LVEDP, but when two or more are present, there
is a very high probability (greater than 90%) of increased
LVEDP.
C. Diagnostic Studies
Causes of dyspnea that can be managed without chest radi­
ography are few: ingestions causing lactic acidosis, anemia,
methemoglobinemia, and carbon monoxide poisoning.
The diagnosis of pneumonia should be confirmed by chest
radiography in most patients, and elevated blood levels of
procalcitonin or C-reactive protein can support the diag­
nosis of pneumonia in equivocal cases or in the presence of
interstitial lung disease. Conversely, a low procalcitonin
can help exclude pneumonia in dyspneic patients present­
ing with HF.
Chest radiography is fairly sensitive and specific for
new-onset HF (represented by redistribution of pulmonary
venous circulation) and can help guide treatment of
patients with other cardiac diseases. NT-proBNP can assist
in the diagnosis of HF.
Lung ultrasonography is superior to chest radiography
in detecting pulmonary edema due to acute decompen­
sated HF among adult patients presenting with dyspnea
and in the diagnosis of pneumonia in patients admitted to
an acute geriatric ward. End-expiratory chest radiography
enhances detection of small pneumothoraces.
A normal chest radiograph has substantial diagnostic
value. When there is no physical examination evidence of
COPD or HF and the chest radiograph is normal, the
major remaining causes of dyspnea include pulmonary
embolism, Pneumocystis jirovecii infection (the initial
radiograph may be normal in up to 25%), upper airway
obstruction, foreign body, anemia, and metabolic acidosis.
If a patient has tachycardia and hypoxemia but a normal
chest radiograph and electrocardiogram (ECG), then tests
to exclude pulmonary emboli, anemia, or metabolic acido­
sis are warranted. High-resolution chest CT is particularly
useful in the evaluation of interstitial and alveolar lung
disease. Helical (“spiral”) CT is useful to diagnose pulmo­
nary embolism since the images 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 decision rule (with or with­
out D-dimer testing) to estimate the pretest probability of
a pulmonary embolism. It is appropriate to forego CT
scanning in patients with very low probability of pulmo­
nary embolus when other causes of dyspnea are more likely
(see Chapter 9).
Laboratory findings suggesting increased LVEDP
include elevated serum B-type natriuretic peptide (BNP or
NT-proBNP) levels. BNP has been shown to reliably diag­
nose severe dyspnea caused by HF and to differentiate it
from dyspnea due to other conditions.
Arterial blood gas measurement may be considered if
clinical examination and routine diagnostic testing are
equivocal. With two notable exceptions (carbon monoxide
poisoning and cyanide toxicity), arterial blood gas mea­
surement distinguishes increased mechanical effort causes
of dyspnea (respiratory acidosis with or without hypox­
emia) from compensatory tachypnea (respiratory alkalosis
with or without hypoxemia or metabolic acidosis) and
from psychogenic dyspnea (respiratory alkalosis). An
observational study, however, found that arterial blood gas
measurement had little value in determining the cause of
dyspnea in patients presenting to the emergency depart­
ment. Carbon monoxide and cyanide impair oxygen deliv­
ery with minimal alterations in Po2; percent
carboxyhemoglobin identifies carbon monoxide toxicity.
Cyanide poisoning should be considered in a patient with
profound lactic acidosis following exposure to burning
vinyl (such as a theater fire or industrial accident). Sus­
pected carbon monoxide poisoning or methemoglobin­
emia can also be confirmed with venous carboxyhemoglobin
or methemoglobin levels. Venous blood gas testing is also
an option for assessing respiratory and acid-base status by
 COMMON SYMPTOMS
measuring venous pH and Pco2 but is unable to provide
information on oxygenation status. To correlate with arte­
rial blood gas values, venous pH is typically 0.03-0.05 units
lower, and venous Pco2 is typically 4-5 mm Hg higher than
arterial samples.
Because arterial blood gas testing is impractical in most
outpatient settings, pulse oximetry has assumed a central
role in the office evaluation of dyspnea. Oxygen saturation
values above 96% almost always correspond with a Po2
greater than 70 mm Hg, whereas values less than 94% may
represent clinically significant hypoxemia. Important
exceptions to this rule include carbon monoxide toxicity,
which leads to a normal oxygen saturation (due to the
similar wavelengths of oxyhemoglobin and carboxyhemo­
globin), and methemoglobinemia, which results in an
oxygen saturation of about 85% that fails to increase with
supplemental oxygen. A delirious or obtunded patient with
obstructive lung disease warrants immediate measurement
of arterial blood gases to exclude hypercapnia and the need
for intubation, regardless of the oxygen saturation. If a
patient reports dyspnea with exertion, but resting oximetry
is normal, assessment of desaturation with ambulation (eg,
a brisk walk around the clinic) can be useful for confirming
impaired gas exchange.
A study found that for adults without known cardiac or
pulmonary disease reporting dyspnea on exertion, spirom­
etry, NT-proBNP, and CT imaging were the most informa­
tive tests.
Episodic dyspnea can be challenging if an evaluation
cannot be performed during symptoms. Life-threatening
causes include recurrent pulmonary embolism, myocardial
ischemia, and reactive airway disease. When associated
with audible wheezing, vocal cord dysfunction should be
considered, particularly in a young woman who does not
respond to asthma therapy. Spirometry is very helpful in
further classifying patients with obstructive airway disease
but is rarely needed in the initial or emergent evaluation of
patients with acute dyspnea.
Differential Diagnosis
Urgent and emergent conditions causing acute dyspnea
include pneumonia, COPD, asthma, pneumothorax, pul­
monary embolism, cardiac disease (eg, HF, acute myocar­
dial infarction, valvular dysfunction, arrhythmia,
intracardiac shunt), pleural effusion, diffuse alveolar hem­
orrhage, metabolic acidosis, cyanide toxicity, methemoglo­
binemia, and carbon monoxide poisoning. The etiology of
dyspnea secondary to e-cigarette vaping is being actively
studied. Chronic dyspnea may be caused by interstitial
lung disease, pulmonary hypertension, or pulmonary
alveolar proteinosis.
Treatment
The treatment of urgent or emergent causes of dyspnea
should aim to relieve the underlying cause. Pending diag­
nosis, patients with hypoxemia should be immediately
provided supplemental oxygen unless significant hyper­
capnia is present or strongly suspected pending arterial
blood gas measurement. Dyspnea frequently occurs in
CMDT 2021 21
patients nearing the end of life. Opioid therapy, anxiolytics,
and corticosteroids can provide substantial relief indepen­
dent of the severity of hypoxemia. However, inhaled opi­
oids are not effective. Oxygen therapy is most beneficial to
patients with significant hypoxemia (Pao2 less than 55 mm
Hg) (see Chapter 5). In patients with severe COPD and
hypoxemia, oxygen therapy improves exercise perfor­
mance and mortality. Pulmonary rehabilitation programs
are another therapeutic option for patients with moderate
to severe COPD or interstitial pulmonary fibrosis. Nonin-
vasive ventilation may be considered for patients with
dyspnea caused by an acute COPD exacerbation, but the
efficacy of this treatment is still uncertain.
When to Refer
• Following acute stabilization, patients with advanced
COPD should be referred to a pulmonologist, and
patients with HF or valvular heart disease should be
referred to a cardiologist.
• Cyanide toxicity or carbon monoxide poisoning should
be managed in conjunction with a toxicologist.
• Lung transplantation can be considered for patients
with advanced interstitial lung disease.
When to Admit
• Impaired gas exchange from any cause or high risk of
pulmonary embolism pending definitive diagnosis.
• Suspected cyanide toxicity or carbon monoxide
poisoning.
Freund Y et al; PROPER Investigator Group. Effect of the Pul­
monary Embolism Rule-Out Criteria on subsequent throm­
boembolic events among low-risk emergency department
patients: the PROPER randomized clinical trial. JAMA. 2018
Feb 13;319(6):559-66. [PMID: 29450523]
Layden JE et al. Pulmonary illness related to e-cigarette use in
Illinois and Wisconsin—preliminary report. N Engl J Med.
2020 Mar 5;382(10):903-16. [PMID: 31491072]
Maw AM et al. Diagnostic accuracy of point-of-care lung
ultrasonography and chest radiography in adults with
symptoms suggestive of acute decompensated heart failure: a
systematic review and meta-analysis. JAMA Netw Open. 2019
Mar l;2(3):el90703. [PMID: 30874784]
Sendama W et al. Decision-making with D-dimer in the diagnosis
of pulmonary embolism. Am J Med. 2018 Dec 131(12):
1438-43. [PMID: 30125536]
HEMOPTYSIS
ESSENTIAL INQUIRIES
► Fever, cough, and other symptoms of lower respi­
ratory tract infection.
► Smoking history.
► Nasopharyngeal or gastrointestinal bleeding.
► Chest radiography and complete blood count
(and, in some cases, INR).
 CMDT 2021 CHAPTER 2
General Considerations
Hemoptysis is the expectoration of blood that originates
below the vocal cords. It is commonly classified as trivial,
mild, or massive—the latter defined as more than 200-600 mL
(about 1-2 cups) in 24 hours. Massive hemoptysis can be
usefully defined as any amount that is hemodynamically
significant or threatens ventilation. Its in-hospital mortal­
ity was 6.5% in one study. The initial goal of management
of massive hemoptysis is therapeutic, not diagnostic.
The causes of hemoptysis can be classified anatomically.
Blood may arise from the trachea due to malignant inva­
sion, and from the airways in COPD, bronchiectasis, bron­
chial Dieulafoy disease, and bronchogenic carcinoma; from
the pulmonary vasculature in left ventricular failure, mitral
stenosis, pulmonary embolism, pulmonary arterial hyper­
tension, and arteriovenous malformations; or from the
pulmonary parenchyma in pneumonia, fungal infections,
inhalation of crack cocaine, or granulomatosis with poly­
angiitis. Diffuse alveolar hemorrhage—manifested by alve­
olar infiltrates on chest radiography—is due to small vessel
bleeding usually caused by autoimmune or hematologic
disorders, or rarely precipitated by warfarin. Most cases of
hemoptysis presenting in the outpatient setting are due to
infection (eg, acute or chronic bronchitis, pneumonia,
tuberculosis, aspergillosis). Hemoptysis due to lung cancer
increases with age, causing up to 20% of cases among older
adults. Less commonly (less than 10% of cases), pulmonary
venous hypertension (eg, mitral stenosis, pulmonary
embolism) causes hemoptysis. Most cases of hemoptysis
that have no visible cause on CT scan or bronchoscopy will
resolve within 6 months without treatment, with the nota­
ble exception of patients at high risk for lung cancer (smok­
ers older than 40 years). Iatrogenic hemorrhage may follow
transbronchial lung biopsies, anticoagulation, or pulmo­
nary artery rupture due to distal placement of a balloon­
tipped catheter. Obstructive sleep apnea may be a risk
factor for hemoptysis. Amyloidosis of the lung can cause
hemoptysis. No cause is identified in up to 15-30% of
cases.
Clinical Findings
A. Symptoms
Blood-tinged sputum in the setting of an upper respiratory
tract infection in an otherwise healthy, young (age under
40 years) nonsmoker does not warrant an extensive diag­
nostic evaluation if the hemoptysis subsides with resolu­
tion of the infection. However, hemoptysis is frequently a
sign of serious disease, especially in patients with a high
prior probability of underlying pulmonary pathology.
Hemoptysis is the only symptom found to be a specific
predictor of lung cancer. There is no value in distinguish­
ing blood-streaked sputum and cough productive of blood
during evaluation; the goal of the history is to identify
patients at risk for one of the disorders listed earlier. Perti­
nent features include duration of symptoms, presence of
respiratory infection, and past or current tobacco use.
Nonpulmonary sources of hemorrhage—from the sinuses
or the gastrointestinal tract—must be excluded.
B. Physical Examination
Elevated pulse, hypotension, and decreased oxygen satura­
tion suggest large-volume hemorrhage that warrants emer­
gent evaluation and stabilization. The nares and oropharynx
should be carefully inspected to identify a potential upper
airway source of bleeding. Chest and cardiac examination
may reveal evidence of HF or mitral stenosis.
C. Diagnostic Studies
Diagnostic evaluation should include a chest radiograph
and complete blood count. Kidney function tests, urinaly­
sis, and coagulation studies are appropriate in specific cir­
cumstances. Hematuria that accompanies hemoptysis may
be a clue to Goodpasture syndrome or vasculitis. Flexible
bronchoscopy reveals endobronchial cancer in 3-6% of
patients with hemoptysis who have a normal (non-lateral-
izing) chest radiograph. Nearly all of these patients are
smokers over the age of 40, and most will have had symp­
toms for more than 1 week. High-resolution chest CT scan
complements bronchoscopy; it can visualize unsuspected
bronchiectasis and arteriovenous malformations and will
show central endobronchial cancers in many cases. It is the
test of choice for suspected small peripheral malignancies.
Helical CT pulmonary angiography is the initial test of
choice for evaluating patients with suspected pulmonary
embolism, although caution should be taken to avoid large
contrast loads in patients with even mild chronic kidney
disease (serum creatinine greater than 2.0 g/dL or rapidly
rising creatinine in normal range). Helical CT scanning
can be avoided in patients who are at “unlikely” risk for
pulmonary embolism using the Wells score or PERC rule
for pulmonary embolism and the sensitive D-dimer test.
Echocardiography may reveal evidence of HF or mitral
stenosis.
Treatment
Management of mild hemoptysis consists of identifying
and treating the specific cause. Massive hemoptysis is life­
threatening. The airway should be protected with endotra­
cheal intubation, ventilation ensured, and effective
circulation maintained. If the location of the bleeding site
is known, the patient should be placed in the decubitus
position with the involved lung dependent. Uncontrollable
hemorrhage warrants rigid bronchoscopy and surgical
consultation. In stable patients, flexible bronchoscopy may
localize the site of bleeding, and angiography can embolize
the involved bronchial arteries. Embolization is effective
initially in 85% of cases, although rebleeding may occur in
up to 20% of patients during the following year. The ante­
rior spinal artery arises from the bronchial artery in up to
5% of people, and paraplegia may result if it is inadver­
tently cannulated and embolized.
One double-blind, randomized controlled trial compared
treatment with inhalations of tranexamic acid (an antifibri-
nolytic drug) versus placebo (normal saline) in patients
hospitalized with mild hemoptysis (less than 200 mL of
expectorated blood per 24 hours). Compared to patients
receiving placebo (normal saline), more patients treated
 COMMON SYMPTOMS
with tranexamic acid experienced resolution of hemoptysis
within 5 days of admission (96% versus 50%; P < 0.0005).
In addition, mean hospital length of stay was shorter for
the tranexamic acid group and fewer patients required
invasive procedures (interventional bronchoscopy, angio­
graphic embolization) to control the hemorrhage.
When to Refer
• Patients should be referred to a pulmonologist when
bronchoscopy of the lower respiratory tract is needed.
• Patients should be referred to an otolaryngologist when
an upper respiratory tract bleeding source is identified.
• Patients with severe coagulopathy complicating man­
agement should be referred to a hematologist.
When to Admit
• To stabilize bleeding process in patients at risk for or
experiencing massive hemoptysis.
• To correct disordered coagulation (using clotting fac­
tors or platelets, or both) or to reverse anticoagulation.
• To stabilize gas exchange.
Davidson K et al. Managing massive hemoptysis. Chest. 2020
Jan;157(l):77-88. [PMID: 31374211]
Ittrich H et al. The diagnosis and treatment of hemoptysis. Dtsch
Arztebl Int. 2017 Jun 5;114(21):371-81. [PMID: 28625277]
Nasser M et al. Alveolar hemorrhage in vasculitis (primary and
secondary). Semin Respir Crit Care Med. 2018 Aug;39(4):
482-93. [PMID: 30404115]
Wand O et al. Inhaled tranexamic acid for hemoptysis treatment:
a randomized controlled trial. Chest. 2018 Dec; 154(6):
1379-84. [PMID: 30321510]
CHEST PAIN
ESSENTIAL INQUIRIES
► Pain onset, character, location/size, duration, peri­
odicity, and exacerbators; shortness of breath.
► Vital signs; chest and cardiac examinations.
► Electrocardiography and biomarkers of myocar­
dial necrosis in selected patients.
General Considerations
Chest pain (or chest discomfort) is a common symptom
that can occur as a result of cardiovascular, pulmonary,
pleural, or musculoskeletal disease; esophageal or other
gastrointestinal disorders; herpes zoster; cocaine use; or
anxiety states. The frequency and distribution of life­
threatening causes of chest pain, such as acute coronary
syndrome (ACS), pericarditis, aortic dissection, vasospas­
tic angina, pulmonary embolism, pneumonia, and esopha­
geal perforation, vary substantially between clinical
settings. Systemic lupus erythematosus, rheumatoid
CMDT 2021
arthritis, reduced estimated glomerular filtration rate, and
HIV infection are conditions that confer a strong risk of
coronary artery disease. Precocious ACS may represent
acute thrombosis independent of underlying atheroscle­
rotic disease. In patients aged 35 years or younger, risk
factors for ACS are obesity, hyperlipidemia, and smoking.
Chest pain characteristics that can lead to early diagno­
sis of acute myocardial infarction do not differ in fre­
quency or strength of association between men and
women. Because pulmonary embolism can present with a
wide variety of symptoms, consideration of the diagnosis
and rigorous risk factor assessment for venous thrombo­
embolism (VTE) is critical. Classic VTE risk factors
include cancer, trauma, recent surgery, prolonged immobi­
lization, pregnancy, oral contraceptives, and family history
and prior history of VTE. Other conditions associated with
increased risk of pulmonary embolism include HF and
COPD. Sickle cell anemia can cause acute chest syndrome.
Patients with this syndrome often have chest pain, fever,
and cough.
Clinical Findings
A. Symptoms
Myocardial ischemia is usually described as a dull, aching
sensation of “pressure,” “tightness,” “squeezing,” or “gas,”
rather than as sharp or spasmodic. Ischemic symptoms
usually subside within 5-20 minutes but may last longer.
Progressive symptoms or symptoms at rest may represent
unstable angina. Prolonged chest pain episodes might rep­
resent myocardial infarction, although up to one-third of
patients with acute myocardial infarction do not report
chest pain. When present, pain due to myocardial ischemia
is commonly accompanied by a sense of anxiety or uneasi­
ness. The location is usually retrosternal or left precordial.
Because the heart lacks somatic innervation, precise local­
ization of pain due to cardiac ischemia is difficult; the pain
is commonly referred to the throat, lower jaw, shoulders,
inner arms, upper abdomen, or back. Ischemic pain may be
precipitated or exacerbated by exertion, cold temperature,
meals, stress, or combinations of these factors and is usu­
ally relieved by rest. However, many episodes do not con­
form to these patterns, and atypical presentations of ACS
are more common in older adults, women, and persons
with diabetes mellitus. Other symptoms that are associated
with ACS include shortness of breath; dizziness; a feeling of
impending doom; and vagal symptoms, such as nausea and
diaphoresis. In older persons, fatigue is a common present­
ing complaint of ACS.
There are gender differences in the perception and pre­
senting symptoms of young patients with myocardial
infarction. Women were more likely than men to present
with three or more associated symptoms (eg, epigastric
symptoms, palpitations, and pain or discomfort in the jaw,
neck, arms, or between the shoulder blades; 61.9% for
women versus 54.8% for men, P < 0.001). In adjusted
analyses, women with an ST-segment-elevation acute myo­
cardial infarction were more likely than men to present
without chest pain (odds ratio, 1.51; 95% CI, 1.03-2.22). In
comparison with men, women were more likely to perceive
 CMDT 2021 CHAPTER 2
symptoms as stress/anxiety (20.9% versus 11.8%, P < 0.001)
but less likely to attribute symptoms to muscle pain (15.4%
versus 21.2%, P = 0.03.)
One analysis found the following clinical features to be
associated with acute myocardial infarction: (1) from the
history: chest pain that radiates to the left, right, or both
arms (LR+ 2.3, 2.9, 7.1); diaphoresis (LR+ 2.0); and nausea
and vomiting (LR+1.9); (2) from the physical examination:
third heart sound (LR+ 3.2), systolic blood pressure less than
or equal to 80 mm Hg (LR +3.1), pulmonary crackles
(LR+ 2.1); and (3) from the electrocardiogram: any ST-segment
elevation greater than or equal to 1 mm (LR+ 11.2), any ST
depression (LR 3.2), any Q wave (LR+ 3.9), any conduction
defect (LR+ 2.7), and new conduction defect (LR+ 6.3).
A meta-analysis found the clinical findings and risk fac­
tors most suggestive of ACS were prior abnormal stress test
(specificity, 96%; LR, 3.1 [95% CI, 2.0-4.7]), peripheral
arterial disease (specificity, 97%; LR, 2.7 [95% CI, 1.5-4.8]),
and pain radiation to both arms (specificity, 96%; LR, 2.6
[95% CI, 1.8-3.7]). The ECG findings associated with ACS
were ST-segment depression (specificity, 95%; LR, 5.3 [95%
CI, 2.1-8.6]) and any evidence of ischemia (specificity,
91%; LR, 3.6 [95% CI, 1.6-5.7]). Risk scores derived from
both the History, Electrocardiogram, Age, Risk Factors,
Troponin (HEART) and Thrombolysis in Myocardial
Infarction (TIMI) trials performed well in detecting ACS
(LR, 13 [95% CI, 7.0-24] for HEART score of 7-10, and
LR, 6.8 [95% CI, 5.2-8.9] for TIMI score of 5-7).
Hypertrophy of either ventricle or aortic stenosis may
also give rise to chest pain with less typical features. Peri­
carditis produces pain that may be greater when supine
than upright and increases with respiration, coughing, or
swallowing. Pleuritic chest pain is usually not ischemic,
and pain on palpation may indicate a musculoskeletal
cause. Aortic dissection classically produces an abrupt
onset of tearing pain of great intensity that often radiates to
the back; however, this classic presentation occurs in a
small proportion of cases. Anterior aortic dissection can
also lead to myocardial or cerebrovascular ischemia.
Pulmonary embolism has a wide range of clinical pre­
sentations, with chest pain present in about 75% of cases.
The chief objective in evaluating patients with suspected
pulmonary embolism is to assess the patients clinical risk
for VTE based on medical history and associated symp­
toms and signs (see above and Chapter 9). Rupture of the
thoracic esophagus iatrogenically or secondary to vomiting
is another cause of chest pain.
B. Physical Examination
Findings on physical examination can occasionally yield
important clues to the underlying cause of chest pain; how­
ever, a normal physical examination should never be used
as the sole basis for ruling out most diagnoses, particularly
ACS and aortic dissection. Vital signs (including pulse
oximetry) and cardiopulmonary examination are always
the first steps for assessing the urgency and tempo of the
subsequent examination and diagnostic workup.
Although chest pain that is reproducible or worsened
with palpation strongly suggests a musculoskeletal cause,
up to 15% of patients with ACS will have reproducible
chest wall tenderness. Pointing to the location of the pain
with one finger has been shown to be highly correlated
with nonischemic chest pain. Aortic dissection can result
in differential blood pressures (greater than 20 mm Hg),
pulse amplitude deficits, and new diastolic murmurs.
Although hypertension is considered the rule in patients
with aortic dissection, systolic blood pressure less than
100 mm Hg is present in up to 25% of patients.
A cardiac friction rub represents pericarditis until
proven otherwise. It can best be heard with the patient sit­
ting forward at end-expiration. Tamponade should be
excluded in all patients with a clinical diagnosis of pericar­
ditis by assessing pulsus paradoxus (a decrease in systolic
blood pressure during inspiration greater than 10 mm Hg)
and inspection of jugular venous pulsations. Subcutaneous
emphysema is common following cervical esophageal per­
foration but present in only about one-third of thoracic
perforations (ie, those most commonly presenting with
chest pain).
The absence of abnormal physical examination findings
in patients with suspected pulmonary embolism usually
serves to increase the likelihood of pulmonary embolism,
although a normal physical examination is also compatible
with the much more common conditions of panic/anxiety
disorder and musculoskeletal disease.
C. Diagnostic Studies
Unless a competing diagnosis can be confirmed, an ECG is
warranted in the initial evaluation of most patients with
acute chest pain to help exclude ACS. ST-segment elevation
is the ECG finding that is the strongest predictor of acute
myocardial infarction; however, up to 20% of patients with
ACS can have a normal ECG. In the emergency depart­
ment, patients with suspected ACS can be safely removed
from cardiac monitoring if they are pain-free at initial
physician assessment and have a normal or nonspecific
ECG. This decision rule had 100% sensitivity for serious
arrhythmia (95% CI, 80-100%). Clinically stable patients
with cardiovascular disease risk factors, normal ECG, nor­
mal cardiac biomarkers, and no alternative diagnoses (such
as typical GERD or costochondritis) should be followed up
with a timely exercise stress test that includes perfusion
imaging. However, more than 25% of patients with stable
chest pain referred for noninvasive testing will have normal
coronary arteries and no long-term clinical events. The
ECG can also provide evidence for alternative diagnoses,
such as pericarditis and pulmonary embolism. Chest radi­
ography is often useful in the evaluation of chest pain, and
is always indicated when cough or shortness of breath
accompanies chest pain. Findings of pneumomediastinum
or new pleural effusion are consistent with esophageal
perforation. Stress echocardiography is useful in risk strati­
fying patients with chest pain, even among those with sig­
nificant obesity.
Diagnostic protocols using a single high-sensitivity
troponin assay combined with a standardized clinical
assessment are an efficient strategy to rapidly determine
whether patients with chest pain are at low risk and may be
discharged from the emergency department. Six estab­
lished risk scores are (1) the modified Goldman Risk Score,
Another random document with
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 Chapter XI
I left the hospital before Peter. My injuries, indeed, were of so slight a
nature that I was confined only a few days, while his were so serious
that the physicians despaired of his life, and he was forced to keep
to his bed for several months. Following my early discharge, I made
daily visits of inquiry to the hospital but it was not until June, 1914,
that I was assured that he would recover. With this good news, came
a certain sense of relief, and I made plans for another voyage to
Europe. The incidents of that voyage—I was in Paris at the
beginning of the war—are of sufficient interest so that I may recount
them in another place, but they bear no relationship to the present
narrative.
Subsequent to his recovery, I have learned since from the physician
who attended him during his protracted illness, Peter returned to
Toledo with his mother. It is probable that he made further literary
experiments. It has even occurred to me that the pivot of his being,
the explanation for his whole course of action may have escaped
me. Although, from the hour of our first meeting, my interest in and
my affection for Peter were deep, assuredly I never imagined that I
should be writing down the history of his life. For the greater part of
the term of our friendship, indeed, I was a writer only in a very
modest sense. I was not on the lookout for the kind of "copy" his
affairs and ideas offered, for at this period I was a reporter of music
and the drama. Even later, when I began to set down my thoughts in
what is euphemistically called a more permanent form, the notion of
using Peter as a subject never presented itself to me, and if he had
asked me to do so during his lifetime, urging me to put aside a pile of
unfinished work in his behalf, the request would have astounded me.
I made, therefore, no special effort to ferret out his secrets. When it
was convenient for both of us we met and, largely by accident, I was
a silent witness of three of his literary experiments. How many others
he may have made, I do not know. It is possible that at some time or
other he may have been inspired by the religious school, the Tolstoy
theory of art, or he may have followed the sensuous lead of Gozzoli
and Debussy, artists whose work intrigued him enormously, or in
another æsthetic avatar, he may have believed that true art is
degrading or coldly classic. There is even the possibility, by no
means remote, that he may have fallen under the influence of the
small-town and psychoanalytic schools. Except in a general way,
however, in a conversation which I shall record at the end of this
chapter, he never mentioned further experiments. It is possible that
others may have evidence bearing on this point. Martha Baker might
make a good witness, but she died in 1911. Mrs. Whiffle knew
nothing of any importance whatever about her son. Since his death I
have interrogated her in vain. She was, indeed, very much
astonished at the little I told her and she will read this book, I think,
with real amazement. The report of Clara Barnes, too, was
negligible. Edith Dale has supplied me with a few facts which I have
inserted where they chronologically belong. Most of my other friends,
Phillip Moeller, Alfred Knopf, Edna Kenton, Pitts Sanborn, Avery
Hopwood, Freddo Sides, Joseph Hergesheimer, even my wife, Fania
Marinoff, never met Peter. Louis Sherwin walked up Fifth Avenue
with us one day, but Peter was unusually silent and after he had left
us at the corner of Fifty-seventh Street, Louis was not sufficiently
curious to ask any questions concerning him. I doubt if Louis could
even recall the incident today. I have inserted advertisements in the
Paris, New York, and Toledo newspapers, begging any one with
pertinent facts or letters in his possession to communicate with me,
but as yet I have received no replies. I have never seen a
photograph of my friend and his mother informs me that she doubts
if he ever sat for one.
The record, therefore, of Peter's literary life, at the conclusion of this
chapter, will be as complete as I can make it. I have tried to set down
the truth as I saw it, leaving out nothing that I remember, even at the
danger of becoming unnecessarily garrulous and rambling. I have
written down all I know because, after all, I may have misunderstood
or misinterpreted, and some one else, with the facts before him, may
be better able to reconstruct the picture of this strange life.
Our next meeting occurred in January, 1919, and his first remark
was, Thank God, you're not shot up! From that time, until the day of
his death, nearly a year later, Peter never mentioned the war to me
again, although I saw him frequently enough, nor did he speak of his
writing, save once, on an occasion which shall be reported in its
proper place.
When we came together for the first time, after the long interval—he
had just returned to New York from Florida—I was surprised at and
even shocked by the purely physical change, which, to be sure, had
a psychical significance, for his face had grown more spiritual. He
had always been slender, but now he was thin, almost emaciated. To
describe his appearance a little later, I might use the word haggard.
His coat, which once fitted his figure snugly, rather hung from his
shoulders. There were white patches in the blue-black of his hair,
deep circles under his eyes, and hollows in his cheeks. But his eyes,
themselves, seemed to shine with a new light, seemed to see
something which I could not even imagine. He had rid himself of
many excrescences and externalities, the purely adscititious
qualities, charming though they might be, which masked his
personality. He had, indeed, discovered himself, although I never
knew how clearly until our last conversation. Peter, without
appearing to be particularly aware of it, had become a mystic. His
emancipation had come through suffering. He was quieter, less
restless, less excitable, still enthusiastic, but with more balance,
more—I do not wish to be misunderstood—irony. He had found life
very satisfying and very hard, very sweet, with something of a bitter
after-taste. He seemed almost holy to me, reminding me at times of
those ascetic monks who crawl two thousand miles on their bellies to
worship at some shrine, or of those Hindu fakirs who lie in one
tortured position for years, their bodies slowly consuming, while their
souls gain fire. That he was ill, very ill, I surmised at once, although,
like everything else I have noted here, this was an impression. He
made no admissions, never spoke of his malady; indeed, for Peter,
he talked astonishingly little about himself. He was pathetic and at
the same time an object for admiration.
Afterwards, I learned from his mother that he suffered from an
incurable disease, the disease that killed him late in 1919. But he
never spoke of this to me and he never complained, unless his
occasional confession that he was tired might be construed as a
complaint.
We had fine times together, of a new kind. The tables, in a sense,
were turned. I had become the writer, however humble, and his
ambition had not been realized. His sympathy with my work, with
what I was trying to do, which he saw almost immediately, saw,
indeed, in the beginning, more clearly than I saw it myself, was
complete. He was never weary of talking about it, at any rate he
never showed me that he was weary, and naturally this drew us very
closely together, for an author is fondest of those men who talk the
most about his work. But this is not the place to publish his opinions
of me, although some of them were so curious and far-seeing—they
were not all flattering by any means—that I shall undoubtedly recur
to them in my autobiography. Fortunately for me, his sympathy grew
as my work progressed, and it seemed amazing to me later, looking
over the book after a period of years, that he had found anything
pleasant to report of Music After the Great War. He had, indeed,
seen something in it, and when I recalled what he had said it was
impossible to feel that he had overstated the case in the interests of
friendship. He had seen the germ, the root of what was to come; he
had seen a suggestion of a style, undeveloped ideas, which he felt
would later be developed, as indeed, to a limited extent, they were.
His plea, to put it concisely, had been for a more personal
expression. He was always asking me, after this or that remark or
anecdote in conversation, why I did not write it, just as I had said it or
told it, and it was a great pleasure for him to perceive in The Merry-
Go-Round and In the Garret (of which he read the proofs just before
his death) some signs of growth in this direction.
You are becoming freer, he would say. You are loosening your
tongue; your heart is beating faster. In time you may liberate those
subconscious ideas which are entangled in your very being. It is only
your conscious self that prevents you from becoming a really
interesting writer. Let that once be as free as the air and the other
will be free too. You must walk boldly and proudly and without fear.
You must search the heart; the mind is negligible in literature as in all
other forms of art. Try to write just as you feel and you will discover
that your feeling is greater than your knowledge of it. The words that
appear on the paper will at first seem strange to you, almost like
hermetic symbols, and it is possible that in the course of time you will
be able to say so much that you yourself will not understand what
you are writing. Do not be afraid of that. Let the current flow freely
when you feel that it is the true current that is flowing.
That is the lesson, he continued, that the creative or critical artist can
learn from the interpreter, the lesson of the uses of personality. The
great interpreters, Rachel, Ristori, Mrs. Siddons, Duse, Bernhardt,
Réjane, Ysaye, Paderewski, and Mary Garden are all big, vibrant
personalities, that the deeper thing, call it God, call it IT, flows
through and permeates. You may not believe this now, but I know it
is true, and you will know it yourself some day. And if you cannot
release your personality, what you write, though it be engraved in
letters an inch deep on stones weighing many tons, will lie like snow
in the street to be melted away by the first rain.
We talked of other writers. Peter drew my attention, for instance, to
the work of Cunninghame Graham, that strange Scotch mystic who
turned his back on civilization to write of the pampas, the arid plains
of Africa, India, and Spain, only to find irony everywhere in every
work of man. But, observed Peter, he could not hate civilization so
intensely had he not lived in it. It is all very well to kick over the
ladder after you have climbed it and set foot on the balcony. Like all
lovers of the simple life, he is very complex. And we discussed
James Branch Cabell, who, Peter told me, was originally a
"romantic." He wrote of knights and ladyes and palfreys with
sympathetic picturesqueness. Of late, however, continued Peter, he,
too, seems to have turned over in bed. Romanticism still appears in
his work but it is undermined by a biting and disturbing irony. He
asks: Are any of the manifestations of modern civilization worthy of
admiration? and like Graham, he seems to answer, No. It is possible
that the public disregard for his earlier and simpler manner may have
produced this metamorphosis. Many a man has become bitter with
less reason. Then he spoke of the attributed influence of Maurice
Hewlett and Anatole France on the work of Cabell. Bernard Shaw,
said Peter, once lost all patience with those critics who insisted that
he was a son of Ibsen and Nietzsche and asserted that it was their
ignorance that prevented them from realizing the debt he owed to
Samuel Butler. Cabell might, with justice, voice a similar complaint,
for if he ever had a literary father it was Arthur Machen. In that
author's The Chronicle of Clemendy, issued in 1888, may be
discovered the same confusion of irony and romance that is to be
traced in the work of Cabell. Moreover, like The Soul of Melicent, the
book purports to be a translation from an old chronicle. I might
further speak of the relationship between Hieroglyphics and Beyond
Life, The Hill of Dreams and The Cream of the Jest, although in each
case the treatment and the style are entirely dissimilar. Machen even
preceded Cabell in his use of unfavourable reviews (Vide the
advertising pages of Beyond Life) in his preface to the 1916 edition
of The Great God Pan. Perhaps, added Peter, Cabell has also read
Herman Melville's Mardi to some advantage. But he is no plagiarist; I
am speaking from the point of view of literary genealogy. Peter, at
my instigation, read a novel or two of Joseph Hergesheimer's. Linda
Condon, he reported, is as evanescent as the spirit of God. Only
those who have encountered Lady Beauty among the juniper trees in
the early dawn will feel this book, and only those who feel will
understand. For Hergesheimer has worked a miracle; he has
brought marble to life, created a vibrant chastity. He has described
ice in words of flame!
One night, quite accidentally, we saw the name of Clara Barnes on a
poster in front of the Metropolitan Opera House. She was singing the
rôle of the Priestess in Aida. We purchased two general admission
tickets and slipped in to hear her. The Priestess, those who have
heard Aida will remember, officiates in the temple scene of the first
act but, like the impersonator of the Bird in Siegfried, she is invisible.
Clara's voice sounded tired and worn, as indeed, it should sound
after those long years of study.
We must go back to see her, Peter urged.
We found a changed and broken Clara. She was dressing alone, but
on the third floor, and the odour of Cœur de Jeannette persisted.
She burst into tears when she saw us.
I can't do it, she moaned. Why did you ever come? I can't do it. I can
only sing with my music in front of me. I shall never be able to sing a
part which appears and there are so few rôles in opera, which permit
you to sing back of the scenery! I can't remember. Now she was
wailing. As fast as I learn one part I forget another.
As we walked away on Fortieth Street, Peter began to relate an
incident he had once read in Plutarch; There was a certain magpie,
belonging to a barber at Rome, which could imitate any word he
heard. One day, a company of passing soldiers blew their trumpets
before the shop and for the next forty-eight hours the magpie was
not only mute but also pensive and melancholy. It was generally
believed that the sound of the trumpets had stunned the bird and
deprived it of both voice and hearing. It appeared, however, that this
was not the case for, says Plutarch, the bird had all the time been
occupied in profound meditation, studying how to imitate the sound
of the trumpets, and when at last master of the trick, he astonished
his friends by a perfect imitation of the flourish on those instruments
it had heard, observing with the greatest exactness all the
repetitions, stops, and changes. This lesson, however, had
apparently been learned at the cost of the whole of its intelligence,
for it made it forget everything it had learned before.
We visited many out-of-the-way places together, Peter and I, the
Negro dance-halls near 135th Street, and the Italian and the Yiddish
Theatres. Peter once remarked that he enjoyed plays more in a
foreign language with which he was unfamiliar. What he could
imagine of plot and dialogue far transcended the actuality. We often
dined at a comfortable Italian restaurant on Spring Street, on the
walls of which birds fluttered through frescoed arbours, trailing with
fruits and flowers, and where the spaghetti was too good to be eaten
without prayer. In an uptown café, we had a strange adventure with a
Frenchwoman, La Tigresse, which I have related elsewhere.[4] Peter
refused, in these last months, to go to concerts, especially in
Carnegie Hall, the atmosphere of which, he said, made it impossible
to listen to music. The bare walls, the bright lights, the sweating
conductors, and the silly, gaping crowd oppressed his spirit. He
envied Ludwig of Bavaria who could listen to music in a darkened
hall in which he was the only auditor. Conditions were more
favourable in the moving picture theatres. The bands, perhaps, did
not play so well but the auditoriums were more subtly lighted, so that
the figures of the audience did not intrude.
Peter was more of a recluse than ever. It had been impossible to
persuade him to meet anybody since the Edith Dale days (Edith
herself was now living in New Mexico and, owing to a slight
misunderstanding, I had not seen or heard from her in five years).
He was even sensitive and morbid on the subject. He made me
promise, as a matter of fact, after the Louis Sherwin episode, that in
case we encountered any of my friends in a restaurant or at a
theatre, I would not introduce him. There was, I assured myself, a
good reason for this. In these last days, Peter faded out in a crowd.
He lost a good deal of his personality even in the presence of a third
person. I begged him to go with me to Florine Stettheimer's studio to
see her pictures, which I was sure would please him, but he refused.
He liked to stroll around with me in odd places and he read and
played the piano a good deal, but he seemed to have few other
interests. He was absolutely ignorant of such matters as politics and
government. He never voted and I have heard him refer to the
president, and not in jest, as Abraham Wilson. Sports did not amuse
him either, but occasionally we went together to see the wrestlers at
Madison Square Garden, especially when Stanislaus Zbyszko was
announced to appear.
He never went to Europe again although, shortly before he died, he
talked of a voyage to Spain. He visited his mother at Toledo several
times and he had planned a trip to Florida, the climate of which he
found particularly soothing to his malady, in January, 1920.
Occasionally he just disappeared, returning again, somewhat
mysteriously, without any explanation, without, indeed, any
admission that he had been away. I knew him too well to ask
questions and, to say truth, there was something very sweet about
these little mystifications. Privacy was so dear a privilege to him that
even with his nearest friends, of which, assuredly, I was one,
perhaps the nearest in this last year, it was essential to his
happiness that he should maintain a certain restraint, a certain
reserve, I had almost said, a certain mystery, but, curiously, there
was nothing theatrical about Peter, even in his most theatrical
performances. Just as by the fineness of his taste, Rembrandt
softened the hideousness of a lurid subject in his Anatomy Lesson,
so the exquisite charm of Peter's personality overcame any possible
repugnance to anything he might choose to do.
During this last year in New York, he lived in an old house on
Beekman Place, that splendid row, just two blocks long, of mellow
brown-stone dwellings, with flights of steps, which back upon the
East River at Fiftieth Street. We often sat on the balcony, looking
over towards the span of the Queensboro Bridge, Blackwell's Island,
with its turreted and battlemented castles so like the Mysteries of
Udolpho, watching the gulls sweep over the surface of the water, the
smoke wreathe from the factory chimneys, and the craft on the river,
with cargoes "of Tyne coal, road-rails, pig-lead, fire-wood, iron-ware,
and cheap tin trays," of the city, but seemingly away from it, with our
backs to it, literally, indeed, while life ebbed by. And, at my side, too,
I saw it slowly ebbing.
The interior, one of those fine old New York interiors, with high
ceilings, bordered with plaster guilloches, white carved marble fire-
places, sliding doors, and huge crystal chandeliers, whose pendants
jingled when some one walked on the floor above, it had been his
happy fancy to decorate in the early Victorian manner. The furniture,
to be sure, was mostly Chippendale, Sheraton, and Heppelwhite, but
there were also heavy carved walnut chairs, upholstered in lovely
figured glazed chintzes. The mirrors were framed in four inches of
purple and red engraved glass. The highboys were littered with
ornaments, Staffordshire china dogs and shepherdesses, splendid
feather and shell flowers, and ormolu clocks stood under glass bells
on the mantel-shelves. He had found a couple of rather worn, but still
handsome, Aubusson carpets, with garlands of huge roses of a pale
blush colour. One of these was in the drawing-room, the other in the
library. An old sampler screen framed the fire-place in the latter
room. The books were curious. Peter was now interested in byways
of literature. I remember such volumes as Thomas Mann's Der Tod
in Venedig, Paterne Berrichon's Life of Arthur Rimbaud, Alfred
Jarry's Ubu Roi, with music by Claude Terrasse, Jean Lorrain's La
Maison Philibert, Richard Garnett's The Twilight of the Gods, the
Comte de Lautréamont's Les Chants de Maldoror, Leolinus
Siluriensis's The Anatomy of Tobacco, Binet-Valmer's Lucien,
Haldane MacFall's The Wooings of Jezebel Pettyfer, James Morier's
Hajji Baba of Ispahan, Robert Hugh Benson's The Necromancers,
André Gide's L'Immoraliste, and various volumes by Guillaume
Apollinaire. The walls of the drawing-room were hung with a French
eighteenth century, rose cotton print, the design of which showed, on
one side, Cupid rowing lustily, while listless old Time sat in the bow
of the boat, with the motto: l'Amour fait passer le Temps; and, on the
other side, Time propelling the boat, while a saddened Cupid, his
face buried in his hands, was the downcast passenger, with the
motto: Le Temps fait passer l'Amour. In the centre, beside a
charming Greek temple, a nymph toyed with a spaniel, and the motto
read: l'Amitié ne craint pas le Temps! There were, therefore, no
pictures on these walls, but, elsewhere, where the walls were white,
or where they were hung with rich crimson Roman damask, as in the
library, there were a few steel engravings and mezzotints and an
early nineteenth century lithograph or two. Over his night-table, at
the side of his bed, he had pinned a photograph of a detail of
Benozzo Gozzoli's frescoes in the Palazzo Riccardi, the detail of the
three youths, and there was also a large framed photograph of
Cranach's naïve Venus in this room. The piano stood in the drawing-
room, near one of the windows, looking over the river. It was always
open and the rack was littered with modern music: John Ireland's
London Pieces, Béla Bartok's Three Burlesques, Gerald Tyrwhitt's
Three Little Funeral Marches, music by Erik Satie, Darius Milhaud,
Georges Auric, and Zoltan Kodaly. I remember one day he asked me
to look at Theodor Streiche's Sprüche and Gedichte, with words by
Richard Dehmel, the second of which he averred was the shortest
song ever composed, consisting of but four bars.
It was a lovely house to lie about in, to talk in, to dream in. It was
restful and quaint, offering a pleasing contrast to the eccentric
modernity of the other homes I visited at this period. There was no
electricity. The chandeliers burned gas but the favourite illumination
was afforded by lamps with round glass globes of various colours,
through which the soft light filtered.
On an afternoon in December, 1919, we were lounging in the
drawing-room. Peter had curled himself into a sort of knot on a broad
sofa with three carved walnut curves at the back. He had spread a
knitted coverlet over his feet, for it was a little chilly, in spite of the
fact that a wood fire was smouldering in the grate. On the table
before him there was a highball glass, half-full of the proper
ingredients, and sprawling beside him on the sofa, a magnificent
blue Persian cat, which he called Chalcedony. George Moore and
George Sand had long since perished of old age and Lou Matagot
had been a victim of the laboratory explosion. There was a certain
melancholy implicit in their absence. Nothing reminds us so
irresistibly of the passing of time as the short age allotted on this
earth to our dear cats. The pinchbottle and several bottles of soda, a
bowl of cracked ice and a bowl of Fatima cigarettes, which both of us
had grown to prefer, reposed conveniently on the table between us. I
remember the increasing silence as the twilight fell and, how, at last,
Peter began to talk.
I wanted to do so much, he began, and for a long time, during these
past four years, it seemed to me that I had done so little. I
remembered Zola's phrase: Mon œuvre, alors, c'était l'Arche, l'Arche
immense! Hélas! ce que l'on rêve, et puis, après, ce que l'on
exécute! At the beginning of the war, I was so very miserable, so
unhappy, so alone. It seemed to me that I had been a complete
failure, that I had accomplished nothing....
I must have raised a protesting hand, for he interjected, No, don't
interrupt me. I am not complaining or asking for sympathy. I am
explaining how I felt, not how I feel. I never spoke of it, of course,
while I felt that way. I am only talking about it now because I have
gone beyond, because, in a sense, at least, I understand. I am
happier now, happier, perhaps, than I have ever been before, for in
the past four years I have left behind my restlessness and achieved
something like peace. I no longer feel that I have failed. Of course, I
have failed, but that was because I was attempting to do something
that I had no right to attempt. My cats should have taught me that. It
is necessary to do only what one must, what one is forced by nature
to do. Samuel Butler has said, and how truly, Nothing is worth doing
or well done which is not done fairly easily, and some little deficiency
of effort is more pardonable than any perceptible excess, for virtue
has ever erred rather on the side of self-indulgence than of
asceticism.... And so, in the end, and after all I am still young, I have
learned that I cannot write. Is a little experience too much to pay for
learning to know oneself? I think not, and that is why, now, I feel
more like a success than a failure, because, finally, I do know myself,
and because I have left no bad work. I can say with Macaulay: There
are no lees in my wine. It is all the cream of the bottle....
I have tried to do too much and that is why, perhaps, I have done
nothing. I wanted to write a new Comédie Humaine. Instead, I have
lived it. And now, I have come to the conclusion that that was all
there was for me to do, just to live, as fully as possible. Sympathy
and enthusiasm are something, after all. I must have communicated
at least a shadow of these to the ideas and objects and people on
whom I have bestowed them. Benozzo Gozzoli's frescoes—now,
don't laugh at what I am going to say, because it is true when you
understand it—are just so much more precious because I have loved
them. They will give more people pleasure because I have given
them my affection. This is something; indeed, next to the creation of
the frescoes, perhaps it is everything.
There are two ways of becoming a writer: one, the cheaper, is to
discover a formula: that is black magic; the other is to have the urge:
that is white magic. I have never been able to discover a new
formula; I have worked with the formulæ of other artists, only to see
the cryptogram blot and blur under my hands. My manipulation of the
mystic figures and the cabalistic secrets has never raised the right
demons....
What is there anyway? All expression lifts us further away from
simplicity and causes unhappiness.... Material, scientific expression:
flying-machines, moving pictures, and telegraphy are simply
disturbing. They add nothing valuable to human life. Any novelist
who invokes the aid of science dies a swift death. Zola's novels are
stuffed with theories of heredity but ideas about heredity change
every day. The current craze is for psychoanalytic novels, which are
not half so psychoanalytic as the books of Jane Austen, as posterity
will find out for itself.... Art in this epoch is too self-conscious.
Everybody is striving to do something new, instead of writing or
painting or composing what is natural.... Even the disturbing irony
and pessimism of Anatole France and Thomas Hardy add nothing to
life. We shall be happier if we go back to the beginning....
The great secret is the cat's secret, to do what one has to do. Let IT
do it, let IT, whatever IT is, flow through you. The writer should say,
with Sancho Panza, De mis viñas vengo, no sé nada. Labanne, in Le
Chat Maigre, cries: Art declines in the degree that thought develops.
In Greece, in the time of Aristotle, there were only sculptors. Artists
are inferior beings. They resemble pregnant women; they give birth
without knowing why. And again, to quote my beloved Samuel Butler,
No one understands how anything is done unless he can do it
himself; and even then he probably does not know how he has done
it. I might add that very often he does not know what he has done.
Sterne wrote Tristram Shandy to ridicule his personal enemies.
Dickens began Pickwick to give the artist, Seymour, an opportunity
to draw Cockney sportsmen and he concluded it in high moral
fervour, with the ambition to wipe out bribery and corruption at
elections, unscrupulous attorneys, and Fleet Prison. To Cervantes,
Don Quixote was a burlesque of the high-flown romantic literature of
his period. To the world, it is one of the great romances of all time....
You see, I am beginning to understand why I haven't written, why I
cannot write.... That is why I am unhappy no longer, why I am more
peaceful, why I do not suffer. But, and now a strange, quavering note
sounded in his voice, if I had found a new formula, who knows what I
might have done?
He turned his face away from me towards the back of the sofa. The
cat was purring heavily, almost like the croupy breathing of a child. It
was quite dark outside, and there was no light in the room save for
the flicker that came from the dying embers. There was a long
silence. In trying afterwards to reckon its length, I judged it must
have been fully half an hour before I spoke. It was a noise that broke
the charm of the stillness. The dead end of the log split over the
andirons and fell into the grate.
Peter, I began.
He did not move.
Peter.... I rose and bent over him. The clock struck six. The cat
stirred uneasily, rose, stretched his enormous length; then gave a
faint but alarmingly portentous mew and leaped from the couch.
Peter!
He did not answer me.
April 29, 1921
New York.

FOOTNOTES:
[4] In the Garret.

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