06 - 6 Screening and Prevention of Disease

6 Screening and Prevention of Disease

Gary J. Martin

Screening and Prevention

of Disease A primary goal of health care is to prevent disease or detect it early enough that intervention will be more effective. Tremendous progress has been made toward this goal over the past 50 years. Screening tests are available for many common diseases and encompass biochemical (e.g., cholesterol, glucose), physiologic (e.g., blood pressure, growth curves), radiologic (e.g., mammogram, bone densitometry), and cyto­ logic (e.g., Pap smear) approaches. Effective preventive interventions have resulted in dramatic declines in mortality from many diseases, particularly infections. Preventive interventions include counseling about risk behaviors, vaccinations, medications, and, in some relatively uncommon settings, surgery. Preventive services (including screening tests, preventive interventions, and counseling) are different than other medical interventions because they are proactively administered to healthy individuals instead of in response to a symptom, sign, or diag­ nosis. Thus, the decision to recommend a screening test or preventive intervention requires a particularly high bar of evidence that testing and intervention are both practical and effective. Because population-based screening and prevention strategies must be extremely low risk to have an acceptable benefit-to-harm ratio, the ability to target individuals who are more likely to develop disease could enable the application of a wider set of potential approaches and increase efficiency. Currently, there are many types of data that can predict disease incidence in an asymptomatic individual. Germline genomic data have received the most attention to date, at least in part because mutations in high-penetrance genes have clear implications for preventive care (Chap. 480). Women with mutations in either BRCA1 or BRCA2, the two major breast cancer susceptibil­ ity genes identified to date, have a markedly increased risk (five- to twentyfold) of breast and ovarian cancer. Genetic counseling should be provided. Screening and prevention recommendations often include prophylactic oophorectomy and breast magnetic resonance imaging (MRI), both of which are considered to incur too much harm for women at average cancer risk. Some women with BRCA mutations opt for prophylactic mastectomy to greatly reduce their breast cancer risk. Although the proportion of common disease explained by highpenetrance genes appears to be relatively small (5–10% of most dis­ eases), mutations in rare, moderate-penetrance genes and variants in low-penetrance genes also contribute to the prediction of disease risk. Most recently, polygenic risk scores combining information about vari­ ants across hundreds of genes are being evaluated for identifying indi­ viduals at high risk of coronary heart disease and other conditions. The advent of affordable whole exome/whole genome sequencing is likely to speed the dissemination of these tests into clinical practice and may transform the delivery of preventive care. Other forms of “omic” data also have the potential to provide impor­ tant predictive information. Proteomics and metabolomics can provide insight into gene function, but it has proven challenging to develop reliable, predictive measures using these platforms. More recently, it has become possible to measure the presence of mutations in DNA circulating in the bloodstream and in stool, with early promising evidence that these assays can be used to detect cancer before existing screening tests. In addition to “omic” data, imaging data are increasingly being integrated into risk-stratified prevention approaches as evidence grows about the predictive ability of these data. For example, coronary com­ puted tomography (CT) scans are used in many preventive cardiology programs to inform decisions about beginning statin therapy when there is conflicting or uncertain information from other risk assess­ ment approaches. Of course, these data may also be helpful in predict­ ing the risk of harms from screening or prevention, such as the risk of a false-positive mammogram.

TABLE 6-1  Principles of Screening The condition should be an important health problem. There should be a treatment for the condition. Facilities for diagnosis and treatment should be available. CHAPTER 6 There should be a latent stage of the disease. There should be a test or examination for the condition. The test should be acceptable to the population. The natural history of the disease should be adequately understood. There should be an agreed policy on whom to treat. Screening and Prevention of Disease The cost of finding a case should be balanced in relation to overall medical expenditure. Source: Reproduced with permission from The basic principles of screening populations for disease. World Health Organization; 1968. In addition to advances in risk prediction, there are several other reasons that screening and prevention are likely to gain importance in medical care in the near term. New imaging modalities are being developed that promise to detect changes at the cellular and subcellular levels, greatly increasing the probability that early detection improves outcomes. The rapidly growing understanding of the biologic pathways underlying initiation and progression of many common diseases has the potential to transform the development of preventive interventions, including chemoprevention. Furthermore, screening and prevention offer the promise of both improving health and sparing the costs of dis­ ease treatment, an issue that will continue to gain importance as long as health care costs in the United States remain a concern to patients, government agencies, and insurers. This chapter will review the basic principles of screening and pre­ vention in the primary care setting. Recommendations for specific disorders such as cardiovascular disease, diabetes, and cancer are pro­ vided in the chapters dedicated to those topics. ■ ■BASIC PRINCIPLES OF SCREENING The basic principles of screening populations for disease were pub­ lished by the World Health Organization in 1968 (Table 6-1). In general, screening is most effective when applied to relatively common disorders that carry a large disease burden (Table 6-2). The five leading causes of mortality in the United States are heart diseases, malignant neoplasms, chronic obstructive pulmonary dis­ ease, accidents, and cerebrovascular diseases. Thus, many screening strategies are targeted at these conditions. From a global health per­ spective, these conditions are priorities, but malaria, malnutrition, AIDS, tuberculosis, and violence also carry a heavy disease burden (Chap. 485). Having an effective treatment for early disease has proven challeng­ ing for some common diseases. For example, although Alzheimer’s disease is the sixth leading cause of death in the United States, there are no curative treatments and a paucity of data that early treatment improves outcomes. Lack of facilities for diagnosis and treatment is a particular challenge for developing countries and may change screen­ ing strategies, including the development of “see and treat” approaches such as those currently used for cervical cancer screening in some countries. A long latent or preclinical phase where early treatment increases the chance of cure is a hallmark of many cancers; for exam­ ple, polypectomy prevents progression to colon cancer. Similarly, early identification of hypertension or hyperlipidemia allows therapeutic TABLE 6-2  Lifetime Cumulative Risk Breast cancer for women 10% Colon cancer 6% Cervical cancer for womena 2% Domestic violence for women Up to 15% Hip fracture for white women 16% aAssuming an unscreened population without HPV vaccination.

interventions that reduce the long-term risk of cardiovascular or cere­ brovascular events. In contrast, lung cancer screening has historically proven more challenging because most tumors are not curable by the time they can be detected on a chest x-ray. However, the length of the preclinical phase also depends on the level of resolution of the screen­ ing test, and this situation changed with the development of chest CT. Low-dose chest CT scanning can detect tumors earlier and has been demonstrated to reduce lung cancer mortality by 20% in individuals who had at least a 30-pack-year history of smoking. The short interval between the ability to detect disease on a screening test and the devel­ opment of incurable disease also contributes to the limited effective­ ness of mammography screening in reducing deaths from some forms of breast cancer. At the other end of the spectrum, the early detection of prostate cancer may not lead to a difference in the mortality rate because the disease is often indolent and competing morbidities, such as coronary artery disease, may ultimately cause mortality (Chap. 75). This uncertainty about the natural history is also reflected in the contro­ versy about treatment of prostate cancer, further contributing to the challenge of screening in this disease. Finally, screening programs can incur significant economic costs that must be considered in the con­ text of the available resources and alternative strategies for improving health outcomes.

PART 1 The Profession of Medicine ■ ■METHODS OF MEASURING HEALTH BENEFITS Because screening and preventive interventions are recommended to asymptomatic individuals, they are held to a high standard for demonstrating a favorable risk-benefit ratio before implementation. In general, the principles of evidence-based medicine apply to dem­ onstrating the efficacy of screening tests and preventive interventions, where randomized controlled trials (RCTs) with mortality outcomes are the gold standard. However, because RCTs are often not feasible, observational studies, such as case-control designs, have been used to assess the effectiveness of some interventions such as colonoscopy for colorectal cancer screening. For some strategies, such as Pap smear screening for cervical cancer, the only data available are ecologic data demonstrating dramatic declines in mortality. Irrespective of the study design used to assess the effectiveness of screening, it is critical that disease incidence or mortality is the pri­ mary endpoint rather than length of disease survival. This is important because lead time bias and length time bias can create the appearance of an improvement in disease survival from a screening test when there is no actual effect. Lead time bias occurs because screening identifies a case before it would have presented clinically, thereby creating the perception that a patient lived longer after diagnosis simply by moving the date of diagnosis earlier rather than the date of death later. Length time bias occurs because screening is more likely to identify slowly pro­ gressive disease than rapidly progressive disease. Thus, within a fixed period of time, a screened population will have a greater proportion of these slowly progressive cases and will appear to have better disease survival than an unscreened population. Disease-free survival is an alternative to consider since many metastatic cancers are controllable for many years with newer therapies. Differences in cancer mortality may not be as easily detected, but years of chemotherapy would still be worth avoiding. A variety of endpoints are used to assess the potential gain from screening and preventive interventions.

1. The absolute and relative impact of screening on disease incidence or mortality. The absolute difference in disease incidence or mortality between a screened and nonscreened group allows the comparison of size of the benefit across preventive services. A meta-analysis of Swedish mammography trials (ages 40–70) found that ~1.2 fewer women per 1000 would die from breast cancer if they were screened over a 12-year period. By comparison, at least ~3 lives per 1000 would be saved from colon cancer in a population (aged 50–75) screened with annual fecal occult blood testing (FOBT) over a 13-year period, and an estimated 20–24 lives per 1000 would be saved over the entire 25-year period. Based on this analysis, colon

TABLE 6-3  Estimated Average Increase in Life Expectancy for a Population SCREENING OR PREVENTIVE INTERVENTION AVERAGE INCREASE Mammography:     Women, 40–50 years 0–5 days   Women, 50–70 years 1 month Pap smears, age 18–65 2–3 months Getting a 35-year-old smoker to quit 3–5 years Beginning regular exercise for a 40-year-old man

(30 min, 3 times a week) 9 months–2 years cancer screening may actually save more women’s lives than does mammography. However, the relative impact of FOBT (30% reduc­ tion in colon cancer death) is similar to the relative impact of mam­ mography (14–32% reduction in breast cancer death), emphasizing the importance of both relative and absolute comparisons. 2. The number of subjects screened to prevent disease or death in one individual. The inverse of the absolute difference in mortality is the number of subjects who would need to be screened or receive a preventive intervention to prevent one death. For example, 731 women aged 65–69 would need to be screened by dual-energy x-ray absorptiometry (DEXA) (and treated appropriately) to prevent one hip fracture from osteoporosis. 3. Increase in average life expectancy for a population. Predicted increases in life expectancy for various screening and preventive interventions are listed in Table 6-3. It should be noted, however, that the increase in life expectancy is an average that applies to a population, not to an individual. In reality, the vast majority of the population does not derive any benefit from a screening test. A small subset of patients, however, will benefit greatly. For example, Pap smears do not benefit the 98% of women who never develop cancer of the cervix. However, for the 2% who would have developed cervical cancer, Pap smears may add as much as 25 years to their lives. Some studies suggest that a 1-month gain of life expectancy is a reasonable goal for a population-based screening or prevention strategy. ■ ■ASSESSING THE HARMS OF SCREENING

AND PREVENTION Just as with most aspects of medical care, screening and preventive interventions also incur the possibility of adverse outcomes. These adverse outcomes include side effects from preventive medica­ tions and vaccinations, false-positive screening tests, overdiagnosis of disease from screening tests, anxiety, radiation exposure from some screening tests, and discomfort from some interventions and screening tests. The risk of side effects from preventive medications is analogous to the use of medications in therapeutic settings and is considered in the U.S. Food and Drug Administration (FDA) approval process. Side effects from currently recommended vaccinations are primarily limited to discomfort and minor immune reactions. How­ ever, the concern about associations between vaccinations and serious adverse outcomes continues to limit the acceptance of many vaccina­ tions despite the lack of data supporting the causal nature of these associations. The possibility of a false-positive test occurs with nearly all screen­ ing tests, although the definition of what constitutes a false-positive result often varies across settings. For some tests such as screening mammography and screening chest CT, a false-positive result occurs when an abnormality is identified that is not malignant, requiring either a biopsy diagnosis or short-term follow-up. For other tests such as Pap smears, a false-positive result occurs because the test identifies a wide range of potentially premalignant states, only a small percent­ age of which would ever progress to an invasive cancer. This risk is closely tied to the risk of overdiagnosis in which the screening test identifies dis­ ease that would not have presented clinically in the patient’s lifetime.

Assessing the degree of overdiagnosis from a screening test is very difficult given the need for long-term follow-up of an unscreened population to determine the true incidence of disease over time. Recent estimates suggest that as much as 15–40% of breast cancers identified by mammography screening and 15–37% of prostate cancers identified by prostate-specific antigen testing may never have presented clinically. Screening tests also have the potential to create unwarranted anxiety, particularly in conjunction with false-positive findings. Although multiple studies have documented increased anxiety through the screening process, there are few data suggesting this anxiety has longterm adverse consequences, including subsequent screening behavior. Screening tests that involve radiation (e.g., mammography, chest CT) add to the cumulative radiation exposure for the screened individual. The absolute amount of radiation is very small from any of these tests, but the overall impact of repeated exposure from multiple sources is still being determined. Some preventive interventions (e.g., vaccina­ tions) and screening tests (e.g., mammography) may lead to discomfort at the time of administration, but again, there is little evidence of longterm adverse consequences. ■ ■WEIGHING THE BENEFITS AND HARMS The decision to implement a population-based screening and preven­ tion strategy requires weighing the benefits and harms, including the economic impact of the strategy. The costs include not only the expense of the intervention but also time away from work, down­ stream costs from false-positive results, “incidentalomas” or adverse events, and other potential harms. Cost-effectiveness is typically assessed by calculating the cost per year of life saved, with adjustment TABLE 6-4  Screening Tests Recommended by the U.S. Preventive Services Task Force for Average-Risk Adults DISEASE TEST POPULATION FREQUENCY CHAPTER Abdominal aortic aneurysm Ultrasound Men 65–75 who have ever smoked Once   Alcohol misuse Alcohol Use Disorders Identification Test All adults Unknown

Breast cancer Mammography with or without clinical breast examination Cervical cancer Pap smear Women 21–65 Every 3 years

Pap smear and/or HPV testing Women 30–65 Every 5 years if HPV negative   Chlamydia/gonorrhea Nucleic acid amplification test on urine or cervical swab Colorectal cancer Fecal occult blood testing 45–75 Every year 75, 86   Fecal immunochemical-DNA 45–75 Every 1–3 years     Sigmoidoscopy 45–75 Every 5 years     Colonoscopy (or occult blood testing combined with sigmoidoscopy) Depression+anxiety Screening questions All adults Periodically   Diabetes Fasting blood glucose or HgbA1c Adults overweight, obese, or with hypertension Hepatitis C Anti-HCV antibody followed by confirmatory PCR HIV Reactive immunoassay or rapid HIV followed by confirmatory test Hyperlipidemia Cholesterol 40–75 Unknown

Hypertension Blood pressure All adults Periodically

Intimate partner violence Screening questions Women of childbearing age Unknown Lung cancer Low-dose computed tomography Adults 50–80 years who have a 20-pack-year smoking history and currently smoke or have quit within the past 15 years Obesity Body mass index All adults Unknown

Osteoporosis DEXA Women >65 or >60 with risk factors Unknown

Abbreviations: DEXA, dual-energy x-ray absorptiometry; HCV, hepatitis C virus; HPV, human papillomavirus; PCR, polymerase chain reaction. Source: Adapted from the U.S. Preventive Services Task Force, https://www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics/uspstf-a-and-b-recommendations.

for the quality of life impact of different interventions and disease states (i.e., quality-adjusted life-year). Typically, strategies that cost $50,000–100,000 per quality-adjusted year of life saved are considered “cost-effective” (Chap. 4).

The U.S. Preventive Services Task Force (USPSTF) is an indepen­ dent panel of experts in preventive care that provides evidence-based recommendations for screening and preventive strategies based on an assessment of the benefit-to-harm ratio (Tables 6-4 and 6-5). Because there are multiple advisory organizations providing rec­ ommendations for preventive services, the agreement among the organizations varies across the different services. For example, all advisory groups support screening for hyperlipidemia and colorectal cancer, whereas consensus is lower for breast cancer screening among women in their forties and for prostate cancer screening. Because the guidelines are only updated periodically, differences across advisory organizations may also reflect the data that were available when the guideline was issued. CHAPTER 6 Screening and Prevention of Disease For many screening tests and preventive interventions, the balance of benefits and harms may be uncertain for the average-risk population but more favorable for individuals at higher risk for disease. Although age is the most commonly used risk factor for determining screen­ ing and prevention recommendations, the USPSTF also recommends some screening tests in populations based upon the presence of other risk factors for the disease. In addition, being at increased risk for the disease often supports initiating screening at an earlier age than that recommended for the average-risk population. For example, when there is a significant family history of colon cancer, it is prudent to initiate screening 10 years before the age at which the youngest family member was diagnosed with cancer. Women (40?) 50–75 Every 2 years

Sexually active women <25 Unknown

45–75 Every 10 years   Every 3 years

18–79 Once

15–65 At least once

Yearly

TABLE 6-5  Preventive Interventions Recommended for Average-Risk Adults INTERVENTION DISEASE POPULATION FREQUENCY CHAPTER Adult immunization       127, 129   COVID-19    Tetanus-diphtheria  

18 18 PART 1 The Profession of Medicine   Varicella   Susceptibles only, >18 Two doses     Measles-mumps-rubella   Women, childbearing age One dose     Pneumococcal   64 20 valent option or 15/23     Influenza   18 Yearly     Human papillomavirus   Up to age 27 If not done prior     Zoster   60 Once   Chemoprevention           Aspirin Cardiovascular disease Aged 40–59 years with a ≥10% 10-year cardiovascular disease risk (bleeding risk may = benefit for some groups)   Folic acid Neural tube defects in baby Women planning or capable of pregnancy       Tamoxifen/raloxifene Breast cancer Women at high risk for breast cancer       Vitamin D Fracture/falls 64 at increased risk for falls     Although informed consent is important for all aspects of medi­ cal care, shared decision-making may be a particularly important approach to decisions about preventive services when the benefit-toharm ratio is uncertain for a specific population. For example, many expert groups, including the American Cancer Society, recommend an individualized discussion about prostate cancer screening because the decision-making process is complex and relies heavily on personal issues. Some men may decline screening, whereas others may be more willing to accept the risks of an early detection strategy. Another example of shared decision-making involves the choice of techniques for colon cancer screening (Chap. 75). In controlled studies, the use of annual FOBT reduces colon cancer deaths by 15–30%. Flexible sig­ moidoscopy reduces colon cancer deaths by ~40–60%. Colonoscopy appears to offer a greater benefit than flexible sigmoidoscopy with a reduction in risk of ~50–70% under optimal conditions of adherence and adenoma detection rates, but its use incurs additional costs and risks. These screening procedures have not been compared directly in the same population, but models suggest that appropriate frequen­ cies of each technique may be associated with similar numbers of lives saved and cost to society per life saved ($10,000–25,000). Thus, although one patient may prefer the ease of preparation and less time disruption of a DNA-based stool test, others may prefer the sedation, thoroughness, and time interval of colonoscopy. ■ ■COUNSELING ON HEALTHY BEHAVIORS In considering the impact of preventive services, it is important to recognize that tobacco and alcohol use, diet, and exercise constitute the vast majority of factors that influence preventable deaths in developed countries. Perhaps the single greatest preventive health care measure is to help patients quit smoking (Chap. 465). However, efforts in these areas frequently require behavior changes (e.g., weight loss, exercise) or the management of addictive conditions (e.g., tobacco and alcohol use) that are often recalcitrant to intervention. Although these are chal­ lenging problems, evidence strongly supports the role of counseling by health care providers (Table 6-6) in effecting health behavior change. Educational campaigns, public policy changes, and community-based interventions have also proven to be important parts of a strategy for addressing these factors in some settings. Although the USPSTF found that the evidence was conclusive to recommend a relatively small set of counseling activities, counseling in areas such as physical activity and injury prevention (including seat belts and bicycle and motorcycle helmets) has become a routine part of primary care practice. Prevent­ ing and treating excess weight is also a top priority given the multiple complications of obesity (Chap. 414).

  Every 10 years       ■ ■IMPLEMENTING DISEASE PREVENTION

AND SCREENING The implementation of disease prevention and screening strategies in practice is challenging. A number of techniques can assist physicians with the delivery of these services. An appropriately configured elec­ tronic health record can provide reminder systems that make it easier for physicians to track and meet guidelines. Some systems give patients secure access to their medical records, providing an additional means to enhance adherence to routine screening. Systems that provide nurses and other staff with standing orders are effective for immunizations. The USPSTF has developed flow sheets and electronic tools to assist clinicians (https://www.uspreventiveservicestaskforce.org/uspstf/aboutuspstf/task-force-resources). Many of these tools use age categories to help guide implementation. Age-specific recommendations for screen­ ing and counseling are summarized in Table 6-7. Many patients see a physician for ongoing care of chronic ill­ nesses, and this visit provides an opportunity to include a “measure of prevention” for other health problems. For example, a patient seen for management of hypertension or diabetes can have breast cancer screening incorporated into one visit and a discussion about colon cancer screening at the next visit. Other patients may respond more favorably to a clearly defined visit that addresses all relevant screening and prevention interventions. Because of age or comorbidities, it may be appropriate with some patients to abandon certain screening and prevention activities, although there are fewer data about when to “sunset” these services. For many screening tests, the benefit of screen­ ing does not accrue until 5–10 years of follow-up, and there are gener­ ally few data to support continuing screening for most diseases past age 75. In addition, for patients with advanced diseases and limited life expectancy, there is considerable benefit from shifting the focus from screening procedures to the conditions and interventions more likely to affect quality and length of life. TABLE 6-6  Preventive Counseling Recommended by the

U.S. Preventive Services Task Force (USPSTF) TOPIC CHAPTER REFERENCE Alcohol and drug use 464, 467, 468 Genetic counseling for BRCA1/2 testing among women at increased risk for deleterious mutations 84, 480 Nutrition and diet 343, 344 Sexually transmitted infections 141, 208 Sun exposure

Tobacco use

TABLE 6-7  Age-Specific Causes of Mortality and Corresponding Preventive Options LEADING CAUSES OF

AGE-SPECIFIC MORTALITY SCREENING PREVENTION INTERVENTIONS TO CONSIDER FOR EACH SPECIFIC POPULATION AGE GROUP 15–24

1. Accident
2. Homicide
3. Suicide
4. Malignancy
5. Heart disease • Counseling on routine seat belt use, bicycle/motorcycle/ATV helmets (1) • Counseling on diet and exercise (5) • Discuss dangers of alcohol use while driving, swimming, boating (1) • Assess and update vaccination status (tetanus, diphtheria, hepatitis B, MMR, rubella, varicella, meningitis, HPV, COVID-19) • Ask about gun use and/or gun possession (2,3) • Assess for substance abuse history including alcohol (2,3) • Screen for domestic violence (2,3) • Screen for depression and/or suicidal/homicidal ideation (2,3) • Pap smear for cervical cancer screening after age 21 (4) • Discuss skin, breast awareness, and testicular self-examinations (4) • Recommend UV light avoidance and regular sunscreen use (4) • Measurement of blood pressure, height, weight, and body mass index (5) • Discuss health risks of tobacco use, consider emphasis on cosmetic and economic issues to improve quit rates for younger smokers (4,5) • Chlamydia and gonorrhea screening and contraceptive counseling for sexually active females, discuss STD prevention • Hepatitis B, and syphilis testing if there is high-risk sexual behavior(s) or any prior history of sexually transmitted disease • Hepatitis C screening starting at age 18 to 79 • HIV testing • Continue annual influenza vaccination 25–44
6. Accident
7. Malignancy
8. Heart disease
9. Suicide
10. Homicide
11. HIV As above plus consider the following: • Readdress smoking status, encourage cessation at every visit (2,3) • Obtain detailed family history of malignancies and begin early screening/prevention program if patient is at significant increased risk (2) • Assess all cardiac risk factors (including screening for diabetes and hyperlipidemia); consider statin therapy for higher-risk patients • Assess for chronic alcohol abuse, risk factors for viral hepatitis, or other risks for development of chronic liver disease • Consider individualized breast cancer screening with mammography at age 40 (2) 45–64
12. Malignancy
13. Heart disease
14. Accident
15. Diabetes mellitus
16. Cerebrovascular disease
17. Chronic lower respiratory • Consider prostate cancer screen with annual PSA and digital rectal examination at age 50 (or possibly earlier in African Americans or patients with family history) (1) • Begin colorectal cancer screening at age 45 or 50 with fecal occult blood testing, stool DNA testing, flexible sigmoidoscopy, or colonoscopy (1) • Reassess and update vaccination status at age 50 and vaccinate all smokers against Streptococcus pneumoniae at age 50 (6) • Consider screening for coronary disease in higher-risk patients (2,5) • Zoster vaccination at age 60 • Begin mammography screening by age 50 • Lung cancer screening at age 50–80 years if a 20-pack-year smoking history and currently smoke or have quit disease
18. Chronic liver disease and cirrhosis
19. Suicide within the past 15 years, yearly ≥65
20. Heart disease
21. Malignancy
22. Cerebrovascular disease
23. Chronic lower respiratory As above plus consider the following: • Readdress smoking status, encourage cessation at every visit (1,2,3,4) • One-time ultrasound for AAA in men 65–75 who have ever smoked • Consider pulmonary function testing for all long-term smokers to assess for development of chronic obstructive disease
24. Alzheimer’s disease
25. Influenza and pneumonia
26. Diabetes mellitus
27. Kidney disease
28. Accidents
29. Septicemia pulmonary disease (4,6) • Screen all postmenopausal women (and all men with risk factors) for osteoporosis • Continue annual influenza vaccination and vaccinate against S. pneumoniae at age 65 (4,6) • Screen for visual and hearing problems, home safety issues, and elder abuse (9) • Consider fall prevention exercise intervention if at higher risk (9) Note: The numbers in parentheses refer to areas of risk in the mortality column affected by the specified intervention. Abbreviations: AAA, abdominal aortic aneurysm; ATV, all-terrain vehicle; HPV, human papillomavirus; MMR, measles-mumps-rubella; PSA, prostate-specific antigen;

STD, sexually transmitted disease; UV, ultraviolet. Acknowledgment The author is grateful to Dr. Katrina A. Armstrong for contributions to this chapter in prior editions of Harrison’s. ■ ■FURTHER READING Bretthauer M et al: Effect of colonoscopy screening on risks of colorectal cancer and related death. N Engl J Med 387:1547, 2022.

CHAPTER 6 Screening and Prevention of Disease Davidson KW et al: Screening for colorectal cancer: US Preventive Ser­ vices Task Force recommendation statement. JAMA 325:1965, 2021. Hugosson J et al: Mortality results from the Goteborg randomized popu­ lation-based prostate-cancer screening trial. Lancet Oncol 11:725, 2010. Woloshin S et al: The new USPSTF mammography recommendations—a dissenting view. N Engl J Med 389:1061, 2023.