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Warning:
This site is being maintained for historical purposes, but has had no new entries since October 1998. To find more recent articles, please visit the following:
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Guide To Clinical Preventive Services; An Assessment of the Effectiveness of 169 Interventions
Report of the U.S. Preventive Services Task Force; Williams & Wilkins, (MAY OBTAIN A COPY FOR $30.00. TO ORDER CALL 1-800-638-0672 OR WRITE TO ADDRESS AT THE END OF THIS DOCUMENT)
Publication date: 10/01/1989
Table of Contents
The Periodic Health Examination: Age-Specific Charts
The Periodic Health Examination: Age-Specific Charts
Table 5: Leading Causes of Death, Birth to 18 Months
Table 6: Leading Causes of Death, Ages 2-6
Table 7:Leading Causes of Death, Ages 7-12
Table 8:Leading Causes of Death, Ages 13-18
Table 9:Leading Causes of Death, Ages 19-39
Table 10: Leading Causes of Death, Ages 40 -64
Table 11: Leading Causes of Death, Ages 65 and Over
Table 12: Pregnant Women
REFERENCES
Recommendations for Patient Education and Counseling
References
Screening for Asymptomatic Coronary Artery Disease
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for High Blood Cholesterol
Recommendation
Burden of Suffering
Efficacy of Screening Test
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Hypertension
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Notes
References
Screening for Cerebrovascular Disease
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Peripheral Arterial Disease
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Screening for Breast Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Colorectal Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Cervical Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Test
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Prostate Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
References
Screening for Lung Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Skin Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Testicular Cancer
Recommendation
Burden of Suffering
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Ovarian Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
References
Screening for Pancreatic Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Oral Cancer
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Diabetes Mellitus
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Thyroid Disease
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
References
Screening for Obesity
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Phenylketonuria
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
References
Screening for Hepatitis B
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
Note
References
Screening for Tuberculosis
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
Note
References
Screening for Syphilis
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
Note
References
Screening for Gonorrhea
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Infection with Human Immunodeficiency Virus
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Chlamydial Infection
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Genital Herpes Simplex
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
Note
References
Screening for Asymptomatic Bacteriuria, Hematuria, and Proteinuria
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Note
References
Screening for Anemia
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Hemoglobinopathies
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Lead Toxicity
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
References
Screening for Diminished Visual Acuity
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Glaucoma
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Hearing Impairment
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Intrauterine Growth Retardation
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Preeclampsia
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Rubella
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Rh Incompatibility
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Congenital Birth Defects
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
References
Screening for Fetal Distress
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Postmenopausal Osteoporosis
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Risk of Low Back Injury
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Dementia
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Abnormal Bereavement
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Screening for Depression
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Screening for Suicidal Intent
Recommendation:
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Clinical Intervention
Note
References
Screening for Violent Injuries
Recommendation
Burden of Suffering
Efficacy of Screening
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention:
Note
References
Screening for Alcohol and Other Drug Abuse
Recommendation
Burden of Suffering
Efficacy of Screening Tests
Effectiveness of Early Detection
Recommendations of Others
Discussion
Clinical Intervention
References
Counseling to Prevent Tobacco Use
Recommendation
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Exercise Counseling
Recommendation
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Nutritional Counseling
Recommendation:
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Clinical Intervention
Note
References
Counseling to Prevent Motor Vehicle Injuries
Recommendation
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Counseling to Prevent Household and Environmental Injuries
Recommendation:
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Counseling to Prevent Human Immunodeficiency Virus Infection and OthSexually Transmitted Diseases
Recommendation
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Counseling to Prevent Unintended Pregnancy
Recommendation
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Counseling to Prevent Dental Disease
Recommendation
Burden of Suffering
Efficacy of Risk Reduction
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Childhood Immunizations
Recommendation
Burden of Suffering
Efficacy of Vaccines
Recommendations of Others
Clinical Intervention
Note
References
Adult Immunizations
Recommendation
Burden of Suffering
Efficacy of Vaccines
Recommendations of Others
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Postexposure Prophylaxis
Recommendation
Recommendation
Burden of Suffering
Efficacy of Prophylaxis
Recommendations of Others
Clinical Intervention
Note
References
Estrogen Prophylaxis
Recommendation
Burden of Suffering
Efficacy of Chemoprophylaxis
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
Note
References
Aspirin Prophylaxis
Recommendation
Burden of Suffering
Efficacy of Chemoprophylaxis
Effectiveness of Counseling
Recommendations of Others
Discussion
Clinical Intervention
References
Appendix A; Task Force Ratings
Quality of Evidence
Table 13:Breast Cancer Screening
Table 14:Screening for Diabetes Mellitus
Table 15:Colorectal Cancer Screening
Table 16:Prevention od Sexually Transmitted Diseases
Table 17:Automobile Occupant Protection Counseling
Table 18:Dipstick Urinalysis
Table 19:Smoking Cessation Counseling
Table 20:Physical Activity Counseling
Table 21:dietary Fat Counseling
Table 22:Fall Protection Among Older Adults
Table 23:Prevention of Unwanted Adolescent Pregnancy
Table 24:Preventive Dentistry
Table 25:Immunizations, Immunoprophylaxis, and Chemoprophylaxis to
POINT OF CONTACT FOR THIS DOCUMENT:
Tables
Criteria For Effectiveness
Definition Of Terms
Positive Predictive Value (PPV) And Prevalence
Effect Of Mortality Rate On Total Deaths Prevented
Birth To 18 Months
Ages 2-6
Ages 7-12
Ages 13-18
Ages 19-39
Ages 40-64
Ages 65 And Over
Pregnant Women
Breast Cancer Screening
Screening For Diabetes Mellitus
Colorectal Cancer Screening
Prevention Of Sexually Transmitted Diseases
Automobile Occupant Protection Counseling
Dipstick Urinalysis
Smoking Cessation Counseling
Physical Activity Counseling
Dietary Fat Counseling
Fall Prevention Among Oldr Persons
Prevention Of Unwanted Adolescent Pregnancy
Preventive Dentistry
Immunizations, Immunoprophylaxis, And Chemoprophylaxis To Prevent
Introduction
This report is intended for primary care clinicians: physicians, nurses, nurse practitioners, physicians' assistants, other allied health professionals, and students. It provides recommendations for clinical practice on 169 preventive interventions--screening tests, counseling interventions, immunizations, and chemoprophylactic regimens--for the prevention of 60 target conditions. The patients for whom these services are recommended include asymptomatic individuals of all age groups and risk categories. Thus, the subject matter is relevant to all of the major primary care specialties: family practice, internal medicine, pediatrics, and obstetrics-gynecology. The recommendations in each chapter are based on a standardized review of current scientific evidence and include a summary of published clinical research regarding the clinical effectiveness of each preventive service. A listing of the relevant recommendations of major professional organizations and health agencies is also included for each preventive service.Clinicians have always intuitively understood the value of prevention. Faced daily with the difficult and often unsuccessful task of treating advanced stages of disease, primary care providers have long sought the opportunity to intervene early in the course of disease or even before disease develops. The benefits of incorporating prevention into medical practice have become increasingly apparent over the past 20 to 30 years as previously common and debilitating conditions have declined in incidence following the introduction of effective clinical preventive services. Infectious diseases such as poliomyelitis, which once occurred in regular epidemic waves (over 18,300 cases in 1954), have become rare in the United States as a result of childhood immunization.1 Only five cases of paralytic poliomyelitis were reported in the United States in 1987.1 Before rubella vaccine became available, rubella epidemics occurred regularly in the United States every six to nine years; a 1964 pandemic resulted in over 12 million rubella infections, with over 11,000 fetal losses and about 20,000 infants born with congenital rubella syndrome.2,3 The incidence of rubella has decreased 99% since 1969, when the vaccine first became available.4,5 Similar trends have occurred with diphtheria, pertussis, and other once-common childhood infectious diseases.(1)
Preventive services for the early detection of disease have also been associated with dramatic reductions in morbidity and mortality. Age-adjusted mortality from strokes has decreased by more than 50% since 1972, a trend attributed in part to earlier detection and treatment of hypertension.(6,7) Cervical cancer mortality has fallen by 73% since 1950,(8) due in part to widespread Papanicolaou testing to detect cervical dysplasia.(9,10) Children with metabolic disorders such as phenylketonuria and congenital hypothyroidism, who once suffered severe irreversible mental retardation, now usually retain normal cognitive function as a result of routine newborn screening and treatment.(11-13)
Although immunizations and screening tests remain important preventive services, the most promising role for prevention in current medical practice may lie in changing the personal health behaviors of patients long before clinical disease develops. The importance of this aspect of clinical practice is demonstrated by a growing body of evidence linking a handful of personal health behaviors to the leading causes of death in the United States: heart disease, cancer, cerebrovascular disease, injuries, and chronic obstructive pulmonary disease.(14) Smoking alone contributes to one out of every six deaths in the United States,(15) including 130,000 deaths each year from cancer, 115,000 from coronary artery disease, 27,500 from cerebrovascular disease, and 60,000 from chronic obstructive pulmonary disease.(16) Failure to use safety belts and driving while intoxicated are major contributors to motor vehicle injuries, which accounted for over 47,000 deaths in 1987.(14) Physical inactivity and dietary factors contribute to coronary atherosclerosis, cancer, diabetes, osteoporosis, or other common diseases.(17-20) Certain sexual practices increase the risk of unintended pregnancy, sexually transmitted diseases, and acquired immunodeficiency syndrome.(21,22)
Although there are sound clinical reasons for emphasizing prevention in medicine, studies have shown that physicians often fail to provide recommended clinical preventive services.(23) This is due to a variety of factors, including lack of reimbursement for preventive services.(24) Also, busy clinicians often have insufficient time with patients to deliver the range of preventive services that are recommended. But even when these barriers to implementation are accounted for, clinicians fail to perform preventive services as recommended.(25) One reason for this is uncertainty among clinicians as to which services should be offered.
Part of the uncertainty among clinicians derives from the fact that recommendations come from multiple sources, and these recommendations are often different. Recommendations relating to clinical preventive services are issued regularly by Government health agencies,(6,26-28) medical specialty organizations, (29-35) professional and scientific organizations, (36-38) voluntary associations, (39-41) and individual experts.(42-47)
In addition, a major reason clinicians may be reluctant to perform preventive services is skepticism about their clinical effectiveness. It is often unclear whether performance of certain preventive interventions can significantly reduce morbidity or mortality from the target condition the clinician is attempting to prevent. It is also unclear how to compare the relative effectiveness of different preventive services, making it difficult for busy clinicians to decide which interventions are most important during a brief patient visit. A broader concern is that some maneuvers may ultimately result in more harm than good. While this concern applies to all clinical practices, it is especially important in relation to preventive services because the individuals who receive these interventions are often relatively healthy. Minor complications or rare adverse effects that would be tolerated in the treatment of a severe illness take on greater significance in the asymptomatic population and require careful evaluation to determine whether benefits exceed risks. Moreover, preventive services such as routine screening are often recommended for a large proportion of the population, and there are therefore potentially significant economic implications to implementation.
These uncertainties increasingly have raised questions about the value of the routine health examination of asymptomatic persons, in which the same battery of tests and physical examination procedures are performed as part of a routine checkup. The annual physical examination of healthy persons was first proposed by the American Medical Association in 1922.48 For many years after, it was common practice among health professionals to recommend routine physicals and comprehensive laboratory testing as effective preventive medicine. It is now increasingly clear, however, that while routine visits with the primary care clinician are important, performing the same interventions on all patients and performing them as frequently as every year are not the most clinically effective approaches to disease prevention. Rather, both the frequency and the content of the periodic health examination need to be tailored to the unique health risks of the individual patient and should take into consideration the quality of the evidence that specific preventive services are clinically effective. This approach to the periodic visit was endorsed by the American Medical Association in 1983 in a policy statement that withdrew support for a standard annual physical examination.(36)Current thinking is that the individualized periodic health visit should place greater emphasis on evidence of clinical effectiveness, and thus increased attention is turning to the collection of reliable data on the effectiveness of specific preventive services.
One of the first comprehensive efforts to examine these issues systematically was undertaken by the Canadian government, which in 1976 convened the Canadian Task Force on the Periodic Health Examination. This expert panel adopted a highly organized approach to evaluating the effectiveness of clinical preventive services. Explicit criteria were developed to judge the quality of evidence from published clinical research, and uniform decision rules were used to link the strength of recommendations for or against a given preventive service to the quality of the underlying evidence (see Appendix A). These ratings were intended to provide the clinician with a means of selecting those preventive services supported by the strongest evidence of effectiveness. Using this approach, the Canadian Task Force examined preventive services for 78 target conditions, releasing its recommendations in a monograph published in 1979.(49) In 1982, the Canadian Task Force reconvened and applied its methodology to new evidence as it became available, publishing revised recommendations and evaluations of new topics in 1984, 1986, and 1988.(50-52)
A similar effort was launched in the United States in 1984, when Edward N. Brandt, M.D., Ph.D., the Assistant Secretary for Health of the Department of Health and Human Services, commissioned the U.S. Preventive Services Task Force. This 20-member non-Federal panel included 14 physicians with expertise in primary care medicine (family practice, internal medicine, and pediatrics), clinical epidemiology, and public health. The panel also included a dentist, a nurse, a health services researcher, a health educator, a health economist, and a medical sociologist. Like the Canadian panel, the U.S. Task Force was charged with developing recommendations for clinicians on the appropriate use of preventive interventions, based on a systematic review of evidence of clinical effectiveness.53 A similar methodology was adopted at the outset of the project. This enabled the U.S. and Canadian panels to collaborate in a binational effort to review evidence and develop recommendations on preventive services.
The U.S. Task Force met 14 times between July 1984 and February 1988. Its objective was to develop comprehensive recommendations addressing preventive services for all age groups. The panel members and their scientific support staff, based at the Office of Disease Prevention and Health Promotion of the Department of Health and Human Services, reviewed evidence and developed recommendations on preventive services for 60 target conditions affecting patients from infancy to old age. This report, which summarizes the findings and clinical recommendations of the panel, was prepared by the scientific staff of the Task Force in the final year of the project (1988-1989). Both the meetings of the Task Force and the preparation of this work have been carried out in close collaboration with professional organizations throughout the United States and with U.S. Government agencies that share an interest in prevention.
Several important findings have emerged from the review of evidence in this report. First, the data suggest that among the most effective interventions available to clinicians for reducing the incidence and severity of the leading causes of disease and disability in the United States are those that address the personal health practices of patients. Primary prevention as it relates to such risk factors as smoking, physical inactivity, poor nutrition, and alcohol and other drug abuse holds generally greater promise for improving overall health than many secondary preventive measures such as routine screening for early disease. Although certain screening tests, such as mammography (54) and Papanicolaou smears, (55) can be highly effective in reducing morbidity and mortality, the Task Force found that many others are of unproven effectiveness. Screening tests with inadequate accuracy, when performed routinely without regard to risk factors, often produce large numbers of false-positive results that may result in unnecessary diagnostic testing and treatment. Many tests that lack evidence of improved clinical outcome have the additional disadvantage of being expensive, especially when performed on large numbers of persons in the population.
Thus, the second principal finding of this report is the need for greater selectivity in ordering tests and providing preventive services. In particular, the proper selection of screening tests requires careful consideration of the age, sex, and other individual risk factors of the patient if the clinician is to minimize the risk of adverse effects and unnecessary expenditures due to screening (see Methodology). An appreciation of the risk profile of the patient is also necessary to determine which interventions are most important during the clinical encounter. The need for evaluating risk factors underscores a time-honored principle of medical practice: the importance of a complete medical history and detailed discussion with patients regarding personal health practices.
The third principal finding of the Task Force report is that conventional clinical activities (e.g., diagnostic testing) may be of less value to patients than activities once considered outside the traditional role of the clinician (e.g., counseling and patient education). This suggests a new paradigm in defining the responsibilities of the primary care provider. In the past, the role of the clinician related primarily to the treatment of illnesses; the asymptomatic healthy individual did not need to see the doctor. In addition, personal health behaviors were often not viewed as a legitimate clinical issue. A patient's use of safety belts, for example, would receive less attention from the clinician than the results of a complete blood count (CBC) or a routine chest xray. A careful review of the data, however, suggests that different priorities are in order. Motor vehicle injuries affect nearly 4 million persons each year in the United States; (56) they account for over 45,000 deaths each year and are a leading cause of death in persons aged 5-44.(14) Proper use of safety belts can prevent 40-60% of motor vehicle injuries and deaths.(57,58) In contrast, there is little good evidence that performing routine CBCs or chest x-rays improves clinical outcome, (59,60) and these procedures are associated with increased health care expenditures.
The fourth finding is that the shifting responsibility of clinicians also implies a changing role for patients. The increasing evidence of the importance of personal health behaviors and primary prevention means that patients must assume greater responsibility for their own health. Whereas the clinician is often the key figure in the treatment of acute illnesses and injuries, the patient is the principal effector in primary prevention. In the traditional doctor-patient relationship, the patient adopts a passive role and expects the doctor to assume control of the treatment plan. One of the initial tasks of the clinician practicing primary prevention is shifting the locus of control to the patient. To achieve competence in this task, some clinicians may need to develop new skills in helping to empower patients and in counseling them to change certain health related behaviors.
Fifth, preventive services need not be delivered exclusively during visits devoted entirely to prevention. While preventive checkups often provide more time for counseling and other preventive services, and although healthy individuals may be more receptive to such interventions than those who are sick, the illness visit is an equally important time to practice prevention. In fact, some individuals may see clinicians only when they are ill or injured. The illness visit may provide the only opportunity to reach such individuals who, due to limited access to care, would be otherwise unlikely to receive preventive services. For many conditions, the Task Force found that devising strategies to increase access to preventive services for such individuals is more likely to reduce morbidity and mortality than performing preventive services more frequently on those who are already regular recipients of preventive care and who are often in better health.
Sixth, the gaps in evidence identified by the Task Force underscore the size of the research agenda in preventive medicine. For most topics examined in this report, the Task Force found inadequate evidence to evaluate effectiveness or to determine the optimal frequency of a preventive service. In some cases, the necessary studies have never been performed. But for many other topics, studies have been performed--in some cases, large numbers of studies--but the findings are unreliable because of improper study design or systematic biases. Thus, while it is certainly important to perform more research in preventive medicine, there is an even greater need in prevention and other medical specialties for better quality research in evaluating effectiveness. The studies reviewed in this report suggest that clinical researchers evaluating effectiveness often fail to give adequate attention to potential flaws in the design of their studies. This observation confirms the findings of other reviewers regarding the need to improve the overall methodologic quality of clinical research. (61)
Finally, the process used by the U.S. and Canadian Task Forces to evaluate effectiveness may be as important a contribution to medical policy as are the recommendations themselves. Although only preventive services have been examined in this report, the techniques that have been developed by the U.S. Task Force for the standardized review of evidence and for developing clinical practice recommendations based on documented decision rules are equally applicable to many other medical practices. The availability of such techniques comes at a time when increasing attention is being focused on devising better methods for evaluating effectiveness in clinical practice.(62) The methodology presented in this report may be useful to others who share an interest in using systematic methods for reviewing published clinical research and assessing the overall health effects of clinical practices.
It is hoped that this report will help resolve some of the uncertainties among primary care clinicians regarding the effectiveness of preventive services. A comprehensive approach has been taken to explore issues of prevention for a wide range of disease categories and for patients of all ages. The systematic approach to the review of evidence for each topic should provide clinicians with the means to compare the relative effectiveness of different preventive services and to determine, on the basis of scientific evidence, what is most likely to benefit their patients. Basing such decisions on rigorous research will be an important step forward in the advancement of disease prevention and health promotion in the United States.
References
1. Centers for Disease Control. Summary of notifiable diseases, United States, 1987. MMWR 1988; 36:1-59.
2. Witte JJ, Karchmer AW, Case G, et al. Epidemiology of rubella. Am J Dis Child 1969; 118:107-11.
3. Orenstein WA, Bart KJ, Hinman AR, et al. The opportunity and obligation to eliminate rubella from the United States. JAMA 1984; 251:1988-94. 4. Centers for Disease Control. Rubella and congenital rubella--United States, 1984-1986. MMWR 1987; 36:664.
5. Idem. Rubella and congenital rubella syndrome--New York City. MMWR 1986; 35:770-9.
6. 1988 Joint National Committee. The 1988 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1988; 148:1023-38.
7. Garraway WM, Whisnant JP. The changing pattern of hypertension and the declining incidence of stroke. JAMA 1987; 258:214-7.
8. National Cancer Institute. 1987 annual cancer statistics review, including cancer trends, 1950-1985. Washington, D.C.: Department of Health and Human Services, 1988. (Publication no. DHHS (NIH) 882789.) 9. Yu S, Miller AB, Sherman GJ. Optimising the age, number of tests, and test interval for cervical screening in Canada. J Epi Comm Health 1982; 36:1-10.
10. Miller AB, Visentin T, Howe GR. The effect of hysterectomies and screening on mortality from cancer of the uterus in Canada. Int J Cancer 1981; 27:651-7.
11. Berman PW, Waisman HA, Graham FK. Intelligence in treated phenylketonuric children: a developmental study. Child Develop 1966; 37:731-47.
12. Hudson FP, Mordaunt VL, Leahy I. Evaluation of treatment begun in first three months of life in 184 cases of phenylketonuria. Arch Dis Child 1970; 45:5-12.
13. Williamson ML, Koch R, Azen C, et al. Correlates of intelligence test results in treated phenylketonuric children. Pediatrics 1981; 68:161-7. 14. National Center for Health Statistics. Advance report of final mortality statistics, 1986. Monthly Vital Statistics Report (Suppl), vol. 37, no. 6. Hyattsville, Md.: Public Health Service, 1988. (Publication no. DHHS (PHS) 88-1120.)
15. Centers for Disease Control. Smoking-attributable mortality and years of potential life lost--United States, 1984. MMWR 1987; 36:6937. 16. Department of Health and Human Services. Reducing the health consequences of smoking: 25 years of progress. A report of the Surgeon General. Rockville, Md.: Department of Health and Human Services, 1989. (Publication no. DHHS (PHS) 89-8411.)
17. Bouchard C, Shephard RJ, Stephens T, et al., eds. Exercise, fitness, and health: research and consensus. Proceedings of the International Conference on Exercise, Fitness, and Health. Champaign, Ill.: Human Kinetics Publishers (in press).
18. Department of Health and Human Services. The Surgeon General's report on nutrition and health. Washington, D.C.: Government Printing Office, 1988. (Publication no. DHHS (PHS) 88-50210.)
19. The Lipid Research Clinics Coronary Primary Prevention Trial Results. I. Reduction in incidence of coronary heart disease. JAMA 1984; 251:351-64.
20. The Lipid Research Clinics Coronary Primary Prevention Trial Results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251:365-74.
21. Hatcher RA, Guest F, Stewart F, et al. Contraceptive technology, 1988-1989. Atlanta, Ga.: Printed Matter, Inc., 1988.
22. Curran JW, Jaffe HW, Hardy AM, et al. Epidemiology of HIV infection and AIDS in the United States. Science 1988; 239:610-6.
23. Lewis CE. Disease prevention and health promotion practices of primary care physicians in the United States. Am J Prev Med (Suppl) 1988; 4:9-16.
24. Logsdon DN, Rosen MA. The cost of preventive health services in primary medical care and implications for health insurance coverage. J Ambul Care Man 1984; 46-55.
25. Lurie N, Manning WG, Peterson C, et al. Preventive care: do we practice what we preach? Am J Public Health 1987; 77:801-4.
26. National Cancer Institute. Working guidelines for early cancer detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
27. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med 1988; 148:36-69.
28. Immunization Practices Advisory Committee. New recommended schedule for active immunization of normal infants and children. MMWR 1986; 35:577-9.
29. American College of Physicians. Periodic health examination: a guide for designing individualized preventive health care in the asymptomatic patient. Ann Intern Med 1981; 95:729-32.
30. Idem. Common diagnostic tests: use and interpretation. Philadelphia: American College of Physicians, 1987.
31. American College of Obstetricians and Gynecologists. Standards for obstetric-gynecologic services, 6th ed. Washington, D.C.: American College of Obstetricians and Gynecologists, 1985:17-8.
32. Peter G, Giebink GS, Hall CB, et al., eds. Report of the Committee on Infectious Diseases, 20th ed. Elk Grove Village, Ill.: American Academy of Pediatrics, 1986:266-75.
33. American Academy of Pediatrics. Guide to implementing safety counseling. Elk Grove Village, Ill.: American Academy of Pediatrics, 1985.
34. Idem. Vision screening and eye examination in children. Committee on Practice and Ambulatory Medicine. Pediatrics 1986; 77:918-9. 35. American Academy of Ophthalmology. Infants and children's eye care. Statement by the American Academy of Ophthalmology to the Select Panel for the Promotion of Child Health, Department of Health and Human Services. San Francisco, Calif.: American Academy of Ophthalmology, 1980.
36. American Medical Association. Medical evaluations of healthy persons. Council on Scientific Affairs. JAMA 1983; 249:1626-33.
37. American Dental Association. Accepted dental therapeutics, 39th ed. Chicago, Ill.: American Dental Association, 1982.
38. National Academy of Sciences, Institute of Medicine. Ad Hoc Advisory Group on Preventive Services. Preventive services for the well population. Washington, D.C.: National Academy of Sciences, 1978. 39. American Cancer Society. Report on the cancer-related health checkup. CA 1980; 30:194-240.
40. American Heart Association. Cardiovascular and risk factor evaluation of healthy American adults: a statement for physicians by an ad hoc committee appointed by the steering committee. Circulation 1987; 75:1340A-62A.
41. American Diabetes Association. Physician's guide to non-insulin dependent (type II) diabetes. Diagnosis and treatment. Alexandria, Va.: American Diabetes Association, 1988.
42. Frame PS, Carlson SJ. A critical review of periodic health screening using specific screening criteria. J Fam Pract 1975; 2:283-9. 43. Frame PS. A critical review of adult health maintenance. Part 1. Prevention of atherosclerotic diseases. J Fam Pract 1986; 22:341-6. 44. Idem. A critical review of adult health maintenance. Part 2. Prevention of infectious diseases. J Fam Pract 1986; 22:417-22.
45. Idem. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
46. Idem. A critical review of adult health maintenance. Part 4. Prevention of metabolic, behavioral, and miscellaneous conditions. J Fam Pract 1986; 23:29-39.
47. Breslow L, Somers AR. The lifetime health-monitoring program: a practical approach to preventive medicine. N Engl J Med 1977; 292:601-8.
48. American Medical Association. Periodic health examination: a manual for physicians. Chicago, Ill.: American Medical Association, 1947. 49. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1194-254.
50. Idem. The periodic health examination. 1984 update. Can Med Assoc J 1984; 130:1278-85.
51. Idem. The periodic health examination. 1986 update. Can Med Assoc J 1986; 134:721-9.
52. Idem. The periodic health examination. 1988 update. Can Med Assoc J 1988; 138:617-26.
53. Lawrence RS, Mickalide AD. Preventive services in clinical practice: designing the periodic health examination. JAMA 1987; 257:2205-7. 54. Shapiro S, Venet W, Strax P, et al., eds. Periodic screening for breast cancer. Baltimore, Md.: Johns Hopkins Press, 1988.
55. International Agency for Research on Cancer Working Group on Evaluation of Cervical Cancer Screening Programmes. Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. Br Med J 1986; 293:659-64.
56. National Highway Traffic Safety Administration. National accident sampling system, 1986: a report on traffic crashes and injuries in the United States. Washington, D.C.: Department of Transportation, 1988:x. (Publication no. DOT HS 807-296.)
57. Department of Transportation. Final regulatory impact assessment on amendments to Federal Motor Vehicle Safety Standard 208, Front Seat Occupant Protection. Washington, D.C.: Department of Transportation, 1984. (Publication no. DOT HS 806-572.)
58. Campbell BJ. Safety belt injury reduction related to crash severity and front seated position. J Trauma 1987; 27:733-9.
59. Tape TG, Mushlin AI. The utility of routine chest radiographs. Ann Intern Med 1986; 104:663-70.
60. Shapiro MF, Greenfield S. The complete blood count and leukocyte differential count. Ann Intern Med 1987; 106:65-74.
61. Feinstein AR. Scientific standards in epidemiologic studies of the menace of daily life. Science 1988; 242:1257-63.
62. Institute of Medicine. Assessing medical technologies. Washington, D.C.: National Academy Press, 1985.
Methodology
This report presents a systematic approach to evaluating the effectiveness of clinical preventive services. The recommendations, and the review of evidence from published clinical research on which they are based, are the product of a methodology established at the outset of the project. The intent of this analytic process has been to provide clinicians* with current and scientifically defensible information about the relative effectiveness of different preventive services and the quality of the evidence on which these conclusions are based. This information can help clinicians who have limited time to select the most appropriate preventive services to offer in a periodic health examination for patients of different ages and risk categories. The critical appraisal of evidence is also intended to identify preventive services of uncertain effectiveness as well as those that could result in more harm than good if performed routinely by clinicians.For the content of this report to be useful, and to clarify differences between the U.S. Preventive Services Task Force recommendations and those of other groups, it is important for the reader to be aware of the process by which this report was developed, as well as how it differs from the consensus development process used to derive most clinical practice guidelines. First, the objectives of the review process, including the types of preventive services to be examined and the nature of the recommendations to be developed, were carefully defined early in the process. Second, the Task Force adopted explicit criteria for recommending the performance or exclusion of preventive services and applied these "rules of evidence" systematically to each topic it studied. Third, literature searches and assessments of the quality of individual studies were conducted in accordance with rigorous, predetermined methodologic criteria. Fourth, guidelines were adopted for translating these findings into sound clinical practice recommendations. Finally, these recommendations were reviewed extensively by experts in the United States, Canada, and the United Kingdom. Each of these steps is examined in greater detail below.
(Notes *)The provider of preventive services in primary care is often a physician. The term "clinician" is used in this report, however, to include other primary care providers such as nurses, nurse practitioners, physicians' assistants, and other allied health professionals. Although physicians may be better qualified than other providers to perform certain preventive services or to convince patients to change behavior, some preventive services are more effectively performed by nonphysicians with special training (e.g., nurses, dietitians, smoking cessation counselors, mental health professionals). **The term "asymptomatic person" as used in this report differs from its customary meaning in medical practice. Although "asymptomatic" is often considered synonymous with "healthy," the term is used in this report to describe individuals who lack clinical evidence of the target condition. Signs and symptoms of illnesses unrelated to the target condition may be present without affecting the designation of "asymptomatic." Thus, a 70-year-old man with no genitourinary symptoms who is screened for prostate cancer would be designated asymptomatic for that condition, even if he were hospitalized for (unrelated) congestive heart failure. Preventive services recommended for "asymptomatic patients" therefore need not be delivered only during preventive checkups of healthy persons but apply equally to clinical encounters with patients being seen for other reasons. In fact, the illness visit may provide the clinician with the best opportunity for delivering some preventive services. Persons in need of preventive services who have limited access to care rarely visit clinicians unless they become ill.
Definition of Objectives --
Systematic rules were used to select the target conditions and candidate preventive interventions to be evaluated by the Task Force.
Selection of Target Conditions --
The Task Force began by preparing a list of important diseases and injuries in the United States that might be preventable through clinical intervention. The 60 target conditions were selected on the basis of two important criteria:
Burden of Suffering from the Target Condition -
Conditions that are relatively uncommon in the United States or are of only minor clinical significance were not considered in this report. Thus, consideration was given to both the prevalence (proportion of the population affected) and incidence (number of new cases per year) of the condition. Conditions that were once common but have become rare because of effective preventive interventions (e.g., poliomyelitis) were included in the review.
Potential Effectiveness of the Preventive Intervention -
Conditions were excluded from analysis if the panel could not identify a potentially effective preventive intervention that could be performed by clinicians.
Selection of Preventive Services --
For each target condition, the Task Force used two criteria to select the preventive services to be evaluated. First, in general, only preventive services carried out on asymptomatic persons** were reviewed. Thus, only primary and secondary preventive measures were addressed. Primary preventive measures involve entirely asymptomatic individuals (e.g., routine immunization of healthy children), whereas secondary preventive measures identify and treat asymptomatic persons who have already developed risk factors or preclinical disease but in whom the disease itself has not become clinically apparent. Obtaining a Papanicolaou smear to detect cervical dysplasia before the development of cancer is a form of secondary prevention. Preventive measures in symptomatic patients, such as antibiotic therapy to prevent postoperative wound infection or insulin therapy to prevent the complications of diabetes mellitus, are considered tertiary prevention and are outside the scope of this report.
The second criterion for selecting preventive services for review was that the maneuver had to be performed in the clinical setting. Only those preventive services that would be carried out by clinicians in the context of routine health care were examined. Findings should not be extrapolated to preventive interventions performed in other settings. Screening tests are evaluated in terms of their effectiveness when performed during the clinical encounter (i.e., case-finding). Screening tests performed at schools, worksites, health fairs, and other community locations are not within the scope of this report. Also, preventive interventions performed outside the clinical setting (e.g., health and safety legislation, mandatory screening, community health promotion) are not specifically evaluated, although clinicians can play an important role in promoting such programs and in encouraging the participation of their patients.
After the complete set of target conditions and preventive services were identified, they were divided into three categories: screening tests, counseling interventions, and immunizations and chemoprophylaxis. Screening tests are those preventive services in which a special test or standardized examination procedure is used to identify patients requiring special intervention. Nonstandardized historical questions, such as asking patients whether they smoke, and tests involving symptomatic patients are not considered screening tests. Counseling interventions are those in which the patient receives information and advice regarding personal behaviors (e.g., diet) to reduce the risk of subsequent illness or injury. Counseling regarding the health-related behaviors of persons who have already developed signs and symptoms is specifically excluded. Immunizations discussed in this report include vaccines and immunoglobulins (passive immunization) taken by persons with no evidence of infectious disease. Chemoprophylaxis refers to the use of drugs or biologics taken by asymptomatic persons as primary prevention to reduce the risk of developing a disease.
Criteria for Determining Effectiveness --
Preventive services are required to meet predetermined criteria to be considered effective. The criteria of effectiveness for the three categories of preventive services (Table 1) provided the analytic framework for the evaluation of effectiveness in the 60 chapters in this report. Each of these criteria must be satisfied to evaluate the "causal pathway" of a preventive service, the chain of events that must occur for a preventive maneuver to influence clinical outcome.(1) Thus, a screening test is not considered effective if it lacks sufficient accuracy to detect the condition earlier than without screening or if there is inadequate evidence that early detection improves outcome. Similarly, counseling interventions cannot be considered effective in the absence of firm evidence that changing personal behavior can improve outcome and that clinicians can influence this behavior through counseling. Effective immunization and chemoprophylactic regimens require evidence of biologic efficacy; in the case of chemoprophylactic agents, evidence is also necessary that patients will comply with long-term use of the drug.
The methodologic issues involved in evaluating screening tests require further elaboration. As mentioned above, a screening test must satisfy two major requirements to be considered effective:
These two headings appear in each of the Screening sections in this report.
- The test must be able to detect the target condition earlier than without screening and with sufficient accuracy to avoid producing large numbers of false-positive and false-negative results (efficacy of screening test).
- Persons with disease who are detected early should have a better clinical outcome than those who are detected without screening (effectiveness of early detection).
Efficacy of Screening Test -
In a departure from the conventional definition of "efficacy," the term "efficacy of a screening test" is used in this report to describe accuracy and reliability. Accuracy is measured in terms of four indices: sensitivity, specificity, and positive and negative predictive value (Table 2). Sensitivity refers to the proportion of persons with a condition who correctly test "positive" when screened. A test with poor sensitivity will miss cases (persons with the condition) and will produce a large proportion of false-negative results; true cases will be told incorrectly that they are free of disease. Specificity refers to the proportion of persons without the condition who correctly test "negative" when screened. A test with poor specificity will result in healthy persons being told they have the condition (false positives). An accepted reference standard ("gold standard") is essential to determining sensitivity and specificity, because it provides the means for distinguishing between "true" and "false" test results.
The use of screening tests with poor sensitivity and/or specificity is of special significance to the clinician because of the potentially serious consequences of false-negative and false-positive results. Persons who receive false-negative results may experience important delays in diagnosis and treatment. Some might develop a false sense of security, resulting in inadequate attention to risk reduction and delays in seeking medical care when warning symptoms become present. False-positive results can lead to follow-up testing that may be uncomfortable, expensive, and, in some cases, potentially harmful. If follow-up testing does not disclose the error, the patient may even receive unnecessary treatment. There may also be psychological consequences. Persons informed of an abnormal medical test that is falsely positive may experience unnecessary anxiety until the error is corrected. Labeling may affect behavior; for example, studies have shown that some persons with hypertension identified through screening may experience altered behavior and decreased work productivity.(2,3)
A proper evaluation of a screening test must therefore include a determination of the likelihood of producing false-positive results. This is done by calculating the positive predictive value (PPV) of the test (Table 2) in the population to be screened. The PPV of a screening test is the proportion of positive results that are correct (true positives). A test with low PPV can generate more false-positive than true-positive results, but this depends to a large extent on the type of population in which it is used. The PPV increases and decreases in accordance with the prevalence of the target condition in the screened population. Thus, unlike sensitivity and specificity, the PPV is not a constant performance characteristic of a screening test. If the target condition is sufficiently rare in the screened population, even tests with excellent sensitivity and specificity can have low PPV, generating more false-positive than true-positive results. This mathematical relationship is best illustrated by an example:
A population of 100,000 in which the prevalence of a hypothetical cancer is 1% would have 1000 persons with cancer and 99,000 without cancer. A screening test with 90% sensitivity and 90% specificity would detect 900 of the 1000 cases, but would also mislabel 9900 healthy persons (Table 3). Thus, the PPV (the proportion of persons with positive test results who actually had cancer) would be 900/10,800, or 8.3%. If the same test were performed in a population with a lower cancer prevalence of 0.1%, the PPV would fall to 0.9%, a ratio of 111 false positives for every true case of cancer detected.
Reliability (reproducibility), the ability of a test to obtain the same result when repeated, is another important consideration in the evaluation of screening tests. An accurate test with poor reliability, whether due to differences in results obtained by different individuals or laboratories (interobserver variation) or by the same observer (intraobserver variation), may produce results that vary widely from the correct value, even though the average of the results approximates the true value.
Effectiveness of Early Detection --
Even if the test accurately detects early-stage disease, one must also question whether there is any benefit to the patient in having done so. Early detection should lead to the implementation of clinical interventions that can prevent or delay progression of the disorder. Detection of the disorder is of little clinical value if the condition is not treatable. Thus, treatment efficacy is fundamental for an effective screening test. Even with the availability of an efficacious form of treatment, early detection must offer added benefit over conventional diagnosis and treatment if screening is to improve outcome. The effectiveness of a screening test is questionable if asymptomatic persons detected through screening have the same clinical outcome as those who first present with symptoms.
Lead-Time and Length Bias -
It is often very difficult to determine with certainty whether early detection truly improves outcome. This is a common problem when evaluating cancer screening tests. For most forms of cancer, five-year survival is higher for persons with early-stage disease.(4) Such data are often interpreted as evidence that early detection of cancer is effective, because death due to cancer appears to be delayed as a result of screening and early treatment. Survival data do not constitute true proof of benefit, however, because they are easily influenced by lead-time bias: Survival can appear to be lengthened when screening simply advances the time of diagnosis, lengthening the period of time between diagnosis and death without any true prolongation of life.(5)
Length bias can also result in overestimation of the effectiveness of cancer screening. This refers to the tendency of screening to detect a disproportionate number of cases of slowly progressive disease and to miss aggressive cases that, by virtue of rapid progression, are present in the population only briefly. The "window" between the time a cancer can be detected by screening and the time it will be found because of symptoms is shorter for rapidly growing cancers, so they are less likely to be found by screening. As a result, persons with aggressive malignancies will be underrepresented in the cases detected by screening, and the cases found by screening may do better than average even if the screening itself does not influence outcome. Due to this bias, the calculated survival of persons detected through screening could overestimate the actual effectiveness of screening.(5)
Assessing Population Benefits -
Although these considerations provide necessary information about the clinical effectiveness of preventive services, other factors must often be examined to obtain a broader picture of the potential health impact on the population as a whole. Interventions of only minor effectiveness in terms of relative risk may have significant impact on the population in terms of absolute risk if the target condition is common and associated with significant morbidity and mortality. Under these circumstances, a highly effective intervention (in terms of relative risk) that is applied to a small high-risk group may save fewer lives than one of only modest clinical effectiveness applied to large numbers of affected persons see (Table 4). Failure to consider these epidemiologic characteristics of the target condition can lead to misconceptions about overall effectiveness.
Potential adverse effects of interventions must also be considered in assessing overall health impact, but often these effects receive inadequate attention when effectiveness is evaluated. For example, the widely held belief that early detection of disease is beneficial leads many to advocate screening even in the absence of definitive evidence of benefit. Some may discount the clinical significance of potential adverse effects. A critical examination will often reveal that many kinds of testing, especially among ostensibly healthy persons, have potential adverse effects. Direct physical complications from a test procedure (e.g., colonic perforation during sigmoidoscopy), labeling and diagnostic errors based on test results (see above), and increased economic costs are all potential consequences of screening tests. Resources devoted to costly screening programs of uncertain effectiveness may consume time, personnel, or money needed for other more effective health care services. In this report, potential adverse effects are considered clinically relevant and are always evaluated along with potential benefits in determining whether a preventive service should be recommended.
Methodology for Reviewing Evidence -
In evaluating effectiveness, the Task Force used a systematic approach to collect evidence from published clinical research and to judge the quality of individual studies.
Literature Retrieval Methods --
Studies were obtained for review by computerized literature search of MEDLARS. Keywords used for each topic are available on request. The reference list was supplemented by citations obtained from experts and from reviews of bibliographic listings, textbooks, and other sources. This report was completed in February 1989, and studies published subsequently are not addressed.
Exclusion Criteria -
Many preventive services involve tests or procedures that are not used exclusively in the context of primary or secondary prevention. Sigmoidoscopy, for example, is also performed for purposes other than screening. Thus, studies evaluating the effectiveness of procedures or tests involving patients who are symptomatic or have a history of the target condition are not considered admissible evidence for evaluating effectiveness in asymptomatic persons. Such tests are instead considered diagnostic tests, even if they are described by investigators as "screening tests." Uncontrolled studies, comparisons between time and place (cross-cultural studies, studies with historical controls), descriptive data, and animal studies have also been excluded from the review process when evidence from randomized controlled trials, cohort studies, or case-control studies is available. Etiologic evidence, which demonstrates a causal relationship between a risk factor and a disease, was considered less persuasive than evidence from well-designed intervention studies, which measure the effectiveness of modifying the risk factor. As mentioned above, studies of preventive interventions not performed by clinicians were excluded from review.
Evaluating the Quality of the Evidence -
The methodologic quality of individual studies has received special emphasis in this report. Although all types of evidence were considered, increased weight was given to well-designed studies. Three types of study designs received special emphasis: randomized controlled trials, cohort studies, and case-control studies. In randomized controlled trials, participants are assigned in a randomized fashion to a study group (which receives the intervention) or a control group (which receives a standard treatment, which may be no intervention or a placebo). Randomization enhances the comparability of the two groups and provides a more valid basis for measuring statistical uncertainty. In this manner, differences in outcome can be attributed to the intervention rather than to other differences between groups. In a blinded trial, the investigators, the subjects, or both (double-blind study) are not told to which group subjects have been assigned, so that this knowledge will not influence their assessment of outcome. Controlled trials that are not randomized are subject to a variety of biases, including selection bias: Persons who volunteer or are assigned by investigators to study groups may differ in characteristics other than the intervention itself.
A cohort study differs from a clinical trial in that the investigators do not determine at the outset which persons receive the intervention or exposure. Rather, persons who have already been exposed and controls who have not been exposed are selected by the investigators to be followed longitudinally over time in an effort to observe differences in outcome. The Framingham Heart Study, for example, is a large ongoing cohort study providing longitudinal data on cardiovascular disease in residents of a Massachusetts community in whom potential cardiovascular risk factors were first measured over 30 years ago. Cohort studies are therefore observational, whereas clinical trials are experimental. Cohort studies are more subject to systematic bias than randomized trials because treatments, risk factors, and other covariables may be chosen by patients or physicians on the basis of important (and often unrecognized) factors that are related to outcome. It is therefore especially important for investigators to identify and correct for confounding variables, related factors that may be more directly responsible for clinical outcome than the intervention/exposure in question. For example, increased mortality among persons with low body weight can be due to the confounding variable of underlying illness.
Both cohort studies and clinical trials have the disadvantage of often requiring large sample sizes and/or many years of observation to provide adequate statistical power to measure differences in outcome. Failure to demonstrate a significant effect in such studies may be the result of statistical properties of the study design rather than a true reflection of poor clinical effectiveness. Both clinical trials and cohort studies have the advantage, however, of generally being prospective in design: the clinical outcome is not known at the beginning of the study and therefore is less likely to influence the collection of data.
Large sample sizes and lengthy follow-up periods are often unnecessary in case-control studies. This type of study differs from cohort studies and clinical trials in that the study and control groups are selected on the basis of whether they have the disease (cases) rather than whether they have been exposed to a risk factor or clinical intervention. The design is therefore retrospective, with the clinical outcome already known at the outset. In contrast to the Framingham Heart Study, a case-control study might first identify persons who have suffered myocardial infarction (cases) and those who have not (controls) and evaluate both groups to assess differences in risk factors preceding the onset of clinical disease. Principal disadvantages of this study design are that important confounding variables may be difficult to identify and adjust for, clinical outcome is already known and may influence the measurement and interpretation of data (observer bias), and participants may have difficulty in accurately recalling past medical history and previous exposures (recall bias).
Other types of study designs, such as cross-cultural studies, uncontrolled cohort studies, and case reports, provide useful data but do not generally provide strong evidence for or against effectiveness. Cross-cultural comparisons can demonstrate differences in disease rates between populations or countries, but these may be due to a variety of genetic and environmental factors other than the variable in question. Uncontrolled studies may demonstrate impressive treatment results or better outcomes than have been observed in the past (historical controls), but the absence of internal controls raises the question of whether the results would have occurred even in the absence of the intervention, perhaps as a result of other concurrent medical advances or case-selection. For further background on methodologic issues in evaluating clinical research, the reader is referred to several recent reviews.(5-7)
In summary, claims of effectiveness in published research must be interpreted with careful attention to the type of study design. Impressive findings, even if reported to be statistically significant, may be an artifact of measurement error, the manner in which participants were selected, or other design flaws rather than a reflection of a true effect on clinical outcome. In particular, p-values measure only random variability in results and do not account for bias; thus, even impressively low p-values are of little value when the data may be subject to substantial bias. Conversely, research findings suggesting ineffectiveness may result from low statistical power, inadequate follow-up, and other design limitations.
The quality of the evidence is therefore as important as the results. For these reasons, the U.S. Preventive Services Task Force established a hierarchy of evidence in which greater weight was given to those study designs that are, in general, less subject to bias and misinterpretation. The hierarchy ranked the following designs in decreasing order of importance: randomized controlled trials, nonrandomized controlled trials, cohort studies, case-control studies, comparisons between time and places, uncontrolled experiments, descriptive studies, and expert opinion. For many of the preventive services examined in this report, the Task Force assigned "evidence ratings" reflecting this hierarchy using a five-point scale (I,II-1, etc.) adapted from the scheme developed originally by the Canadian Task Force on the Periodic Health Examination (see Appendix A).(8-11)
Translating Science into Clinical Practice Recommendations -- The strength of recommendations to perform or not perform a preventive service is based on the quality of the evidence that its performance will result in more good than harm. Interventions that have been proved effective in well-designed studies or have demonstrated consistent benefit in a large number of studies of weaker design are generally recommended in this report. Interventions that have been proved to be ineffective or harmful are generally not recommended. Some preventive services are described as "clinically prudent," even though convincing evidence of effectiveness is lacking. This occurs when performance of the maneuver is not associated with significant harm or cost but has the potential of reducing the incidence of a leading cause of death or suffering in the specified group for which it is recommended. Maneuvers are often recommended for high-risk groups even though there is no additional evidence of greater effectiveness in these individuals than in the general population. This policy is based on the recognition that the absence of evidence of effectiveness does not rule out effectiveness; if, in fact, the maneuver is effective, individuals at increased risk of developing the disease are most likely to benefit.
For some preventive services no recommendation is made, because the evidence is inadequate to support a recommendation for or against performing the maneuver. For example, there is generally little scientific evidence regarding the clinical effectiveness of teaching self-examination of the breast, testes, or skin. Under these circumstances, available data are so limited that the clinician is best advised to exercise individual judgment and discretion on a case-by-case basis. Similarly, there are often inadequate data to determine the optimal frequency for performing preventive services. Rather than suggesting an arbitrary interval for testing that is not scientifically defensible, the Task Force generally recommends that clinicians use individual judgment in choosing an appropriate interval based on the patient's medical history and personal circumstances.
Some preventive services are specifically not recommended even though there is no convincing evidence that they are ineffective. This position is taken with those interventions whose potential adverse effects are of clinical concern, as well as those procedures that could generate significant increases in health care costs were they to be performed on a large proportion of the population. For example, even though further research is needed to fully evaluate the effectiveness of ultrasound screening for cancer of the prostate, ovary, or pancreas, this test is specifically not recommended by the Task Force pending the results of these studies. In addition to the potential risks of false-positive labeling, routine ultrasound screening of the general population would be costly and could divert limited resources needed for other more effective health care services. Under these circumstances, the Task Force required evidence of effectiveness before recommending widespread implementation of the preventive service.
In selected situations, even preventive services of proven effectiveness may not be recommended due to concerns about feasibility and compliance. Benefits observed under carefully controlled experimental conditions may not be generalizable to normal medical practice. That is, the preventive service may have proven efficacy but may lack effectiveness. It may be difficult for clinicians to perform the procedure in the same manner as investigators with special expertise and a standardized protocol. Patients may be less willing than research volunteers to comply with interventions that lack widespread acceptability. The cost of the procedure and other logistical considerations may make implementation of the recommendation difficult for the health care system without compromising quality or the delivery of other health care services.
For some preventive services examined by the Task Force, recommendations to perform or exclude the maneuver from the periodic health examination have been assigned a rating from a five-point (A-E) scale developed originally by the Canadian Task Force on the Periodic Health Examination (see Appendix A).(8-11) The rationale for these ratings is outlined in background papers available for review in a separate publication.(12) Background papers on selected preventive services have also been published in the Journal of the American Medical Association.(13-20) For the majority of topics examined in this report, which were not examined in this manner, scientific reviews and evaluations were conducted under Task Force supervision by scientific staff who were recruited by the Task Force and based at the Office of Disease Prevention and Health Promotion in Washington, D.C.
Outside Review Process -
The Task Force recommendations have been reviewed by over 300 experts in Government health agencies, academic medical centers, and medical organizations in the United States, Canada, and the United Kingdom. The report has received extensive review by representatives of the U.S. Public Health Service. Recommendations were modified on the basis of reviewer comments if the reviewer identified relevant studies not examined in the report, misinterpretations of findings, or other issues deserving revision within the constraints of the Task Force methodology. The format of this report was designed in consultation with representatives of medical specialty organizations, including the American Medical Association, the American College of Physicians, the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the American College of Preventive Medicine, the American Dental Association, and the American Osteopathic Association.(21)
Recommendations appearing in this report are intended as guidelines, providing clinicians with information on the proven effectiveness of preventive services in published clinical research. Recommendations for or against performing these maneuvers should not be interpreted as standards of care but rather as statements regarding the quality of the supporting scientific evidence. Clinicians with limited time can use this information to help select the preventive services most likely to benefit patients in selected risk categories. However, sound clinical decision making requires careful consideration of many variables; the science base must be examined along with other important aspects of the medical history and the clinical setting. Departure from these recommendations by clinicians familiar with a patient's individual circumstances is often appropriate and should not necessarily be interpreted by patients or others as compromising quality of care.
References
1. Battista RN, Fletcher SW. Making recommendations on preventive practices: methodological issues. Am J Prev Med Suppl 1988; 4:5367. 2. Lefebvre RC, Hursey KG, Carleton RA. Labeling of participants in high blood pressure screening programs: implications for blood cholesterol screenings. Arch Intern Med 1988; 148:1993-7.
3. MacDonald LA, Sackett DL, Haynes RB, et al. Labelling in hypertension: a review of the behavioral and psychological consequences. J Chron Dis 1984; 37:933-42.
4. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:332. 5. Sackett DL, Haynes RB, Tugwell P. Clinical epidemiology. Boston: Little, Brown, 1985.
6. Fletcher RH, Fletcher SW, Wagner EH. Clinical epidemiology: the essentials. Baltimore, Md.: Williams and Wilkins, 1988.
7. Bailar JC III, Mosteller F, eds. Medical uses of statistics. Waltham, Mass.: NEJM Books, 1986.
8. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1193-254.
9. Idem. The periodic health examination. 1984 update. Can Med Assoc J 1984; 130: 1278-85.
10.Idem. The periodic health examination. 1986 update. Can Med Assoc J 1986; 134: 721-9.
11.Idem. The periodic health examination. 1988 update. Can Med Assoc J 1988; 138: 617-26.
12.Lawrence RS, Goldboom RB, eds. Preventing disease: beyond the rhetoric. New York: Springer-Verlag (in press).
13.O'Malley MS, Fletcher SW. Screening for breast cancer with breast self- examination: a critical review. JAMA 1987; 257:2197-203.
14.LaForce FM. Immunizations, immunoprophylaxis, and chemoprophylaxis to prevent selected infections. JAMA 1987; 257:2464-70.
15.Horsburgh CR, Douglas JM, LaForce FM. Preventive strategies in sexually transmitted diseases for the primary care physician. JAMA 1987; 258:815-21.
16.Kottke TE, Battista RN, DeFriese GH, et al. Attributes of successful smoking cessation interventions in medical practice: a meta-analysis of 39 controlled trials. JAMA 1988; 259:2882-9.
17.Polen MR, Friedman GD. Automobile injury: selected risk factors and prevention in the health care setting. JAMA 1988; 259:76-80. 18.Knight KK, Fielding JE, Battista RN. Occult blood screening for colorectal cancer. JAMA 1989; 261:587-93.
19.Selby JV, Friedman GD. Sigmoidoscopy in the periodic health examination. JAMA 1989; 261:595-602.
20.Harris SS, Caspersen CJ, DeFriese GH, et al. Physical activity counseling for healthy adults as a primary preventive intervention in the clinical setting: report for the US Preventive Services Task Force. JAMA 1989; 261:3590-8.
21.Centers for Disease Control. Chronic disease control activities of medical and dental organizations. MMWR 1988; 37:325-8.
The Periodic Health Examination: Age-Specific Charts
The periodic health visit is an important opportunity for the delivery of clinical preventive services. Determining the specific preventive services that are most appropriate for inclusion in the periodic health examination has been one of the principal objectives of the U.S. Preventive Services Task Force project. The process by which these determinations were made is discussed in detail. This chapter explores the recommended content of the periodic health examination. It includes a series of eight tables that state the specific preventive services that should be considered for patients in different age groups.The Task Force judged it especially important to tailor the content of the periodic examination to the individual needs of the patient and to emphasize those preventive services that have proved to be effective in properly conducted studies. This approach is based on the recognition that the leading causes of illness and injury in an individual patient depend on age, sex, and other risk factors. The clinician whose time with patients is limited is therefore best advised to target preventive measures toward those conditions most likely to significantly influence the health and well-being of the patient being examined. The two most important factors to consider are the leading causes of morbidity and mortality in the patient and the potential effectiveness of clinical interventions in altering the natural history of those diseases.
Leading causes of morbidity and mortality are essential to consider with each patent if the clinician is to determine which conditions are most important to prevent Failure to do so can lead to misplaced priorities when performing the periodic health examination. For example, a clinician wishing to include a preventive measure during the few remaining minutes of an office visit with an adolescent male might consider teaching the patient how to perform testicular self-examination An estimated 350 persons will die from testicular cancer in the United States during 1989 and it is believed that early detection is an important means of improving survival.(1) However, a teenage male is considerably more likely to die from an injury than from cancer or any other disease. Of the 39,929 deaths among young persons (aged 15-24 years)in the United States during 1986, 19,975 were due to injuries (15,227 due to motor vehicles crashes), 5522 were due to homicides, and 5120 were the result of suicide.(2) All forms of cancer combined accounted for only 2115 deaths in this age group.(2) It seems likely on the basis of mortality data alone that a few minutes with an adolescent might be more productively spent by discussing the prevention of unintentional and intentional injuries. Leading causes of morbidity, such as unintended pregnancy, depression, and drug abuse, are also important target conditions.
Clinical efforts directed toward these important conditions may be of limited however, if the preventive intervention does not result in improved outcome. Thus, the second major consideration in setting priorities is effectiveness. Although homicide and suicide are leading causes of death among adolescents, the effectiveness of efforts by clinicians to prevent deaths from intentional injuries has not been established. However, measures to reduce the risk of motor vehicle injuries, the leading cause of death in this age group, are well established Proper use of safety belts has proved to reduce the risk of injury and death from motor vehicle crashes by as much as 40-60%.(3,4) Alcohol intoxication is associated with half of all injury fatalities.(5) With one out of three deaths among young persons occurring in motor vehicle crashes,(2) the busy clinician seeing young patients is best advised to direct attention to the use of safety belts and the dangers of driving while under the influence of alcohol.
Age is only one of many risk factors the clinician must consider in designing an appropriate periodic health examination. Among persons in special high-risk groups, the leading causes of morbidity and mortality may differ considerably from other individuals of the same age and sex. For example, although sexually transmitted diseases and unintended pregnancy are unlikely problems for sexually, abstinent teenagers, they are important sources of morbidity among those who are sexually active. One out of four cases of gonorrhea (195,274 cases) reported in the United States during 1987 occurred among persons aged 10-19.(7) Intravenous drug use is also uncommon in the general population, but among individuals with this history, acquired immunodeficiencY syndrome (AIDS) is the leading cause of death.8 Thus, the most important preventive interventions in the period health examination of an intravenous drug user are counseling to obtain treatment for chemical dependency and education about measures to prevent transmission of infectious disease. These and other methodologic issues in establishing priorities for preforming preventive Services are discussed in greater detail in (see Methodology).
The differences in priorities among individuals in different age groups and risk categories and the effectiveness of some preventive services in only certain populations suggests that a uniform periodic health examination cannot be recommended for all persons. The reader will note that recommendations throughout this report are targeted toward individuals who meet specific risk factor criteria only rarely do they apply universally to all patients. While it is therefore difficult design a periodic health examination that accounts fully for differences among patients, the eight tables that follow identify those recommended preventive services that should be considered for patients in specific age groups.
The reader is urged to refer to appropriate chapters in this report to obtain more detailed information about the proper indications for specific preventive service than can be provided in the tables. The review of evidence in the text also provide the scientific rationale for the recommendations, which are based on a system methodology (see Methodology). The reader can also compare the Task Force recommendations with those of major organizations and Government agencies, who are listed in each chapter under the heading Recommendations of Others. In addition, all chapters include a detailed Clinical Intervention section that provide concise information for the clinician on currently recommended techniques, dos-ages, and other specifics for performing recommended preventive services.
The preventive services examined in this report and appearing in Tables 5-12 have been carefully defined. They include only those preventive services that would be performed by clinicians on asymptomatic persons in the context of routine health care (see Methodology). Preventive measures involving persons with sign symptoms of disease and those performed outside the clinical setting are within the scope of this report or its recommendations.
The tables are not intended to be a complete list of all preventive services should be offered during the periodic health examination. Rather, these recommendations encompass only those preventive services that have been examined in the report and that have been shown to have satisfactory evidence of clinical not effectiveness, based on the methodology discussed in the Methodology Chapter. Since the evaluations were defined by specific preventive services, general procedures such as are the medical history and the physical examination were not examined in their entirety.
The interventions listed are therefore not exhaustive. The periodic health examination performed by most pediatricians, for example, includes a number of maneuvers that were not examined by the Task Force, such as screening for belts developmental disorders and anticipatory guidance, The interested reader should refer to the recommendations of other groups for luther information on such topics. Similarly, recommendations relating to preventive services during pregnancy should not be interpreted as comprehensive guidelines for prenatal care.
Recommendations by the Task Force against performing certain preventive services are not intended to be unconditional. The clinician may judge such maneuvers to be appropriate in light of the medical history of the patient, local standards of care, or other individual circumstances.
Many of the preventive services appearing in Tables 5-12 are recommended Intra only for members of high-risk groups and are not considered appropriate in the routine examination of all persons in the age group. The specific risk groups for which the maneuver is considered appropriate are identified by an annotated high-risk (HR) code accompanying each table. The reader should refer to appropriate chapters in the report for more detailed guidelines to help identify individuals at increased risk. Risk factors that are especially important for clinicians to identify at an early stage but that are not considered appropriate for routine screening are listed under the heading Remain Alert For. Many of the disorders appearing undo risk this heading are often overlooked by clinicians due to failure to recognize suggestive signs or symptoms or the importance of early identification.
A frequency schedule for periodic health visits is recommended in each table. These intervals are considered clinically prudent; however, scientific data are lacking to determine the optimal frequency for such visits. Clinicians should exercise discretion in selecting an appropriate schedule, especially for patients with abnormal signs or symptoms and those with chronic illness. The preventive services listed in each table are not necessarily recommended at every periodic visit. For example, although thyroid function tests may be clinically prudent in more elderly women, they are not recommended annually even though periodic visits in this age group are recommended once a year.
Although the preventive services listed in Tables 5-12 can serve as the basis for Designing periodic checkups devoted entirely to disease prevention, they may also be performed during visits for other reasons (e.g., illness visits, chronic disease checkups) when indicated. For patients with limited access to care, the illness visit In may provide the only realistic opportunity for the clinician to discuss prevent on. It is recognized that busy clinicians may not be able to perform all recommended Preventive services during a single clinical encounter. Indeed, it is not clear that such a grouping is either necessary or clinically effective. Patients suffering from an acute illness or injury may not be receptive to some preventive interventions. The clinician must therefore use discretion in selecting appropriate ate preventive services from these lists and may wish to give special emphasis to those preventive services aimed at the leading causes of illness and disability in the age group. Age-specific leading causes of death are listed in each table to aid the clinician in making this assessment. Recommended preventive services that cannot be Performed by the clinician could be scheduled for a later health visit.
Immunizations appearing in Tables 5-12 are those recommended on a routine basis and do not apply to persons with special exposures to infected individuals. The reader is referred to the Postexposure Prophylaxis Chapter for detailed guidelines on immunization if such circumstances.
The Periodic Health Examination: Age-Specific Charts
The periodic health visit is an important opportunity for the delivery of clinical preventive services. Determining the specific preventive services that are most appropriate for inclusion in the periodic health examination has been one of the principal objectives of the U.S. Preventive Services Task Force project. The process by which these determinations were made is discussed in detail. This chapter explores the recommended content of the periodic health examination. It includes a series of eight tables that state the specific preventive services that should be considered for patients in different age groups.The Task Force judged it especially important to tailor the content of the periodic examination to the individual needs of the patient and to emphasize those preventive services that have proved to be effective in properly conducted studies. This approach is based on the recognition that the leading causes of illness and injury in an individual patient depend on age, sex, and other risk factors. The clinician whose time with patients is limited is therefore best advised to target preventive measures toward those conditions most likely to significantly influence the health and well-being of the patient being examined. The two most important factors to consider are the leading causes of morbidity and mortality in the patient and the potential effectiveness of clinical interventions in altering the natural history of those diseases.
Leading causes of morbidity and mortality are essential to consider with each patent if the clinician is to determine which conditions are most important to prevent Failure to do so can lead to misplaced priorities when performing the periodic health examination. For example, a clinician wishing to include a preventive measure during the few remaining minutes of an office visit with an adolescent male might consider teaching the patient how to perform testicular self-examination An estimated 350 persons will die from testicular cancer in the United States during 1989 and it is believed that early detection is an important means of improving survival.(1) However, a teenage male is considerably more likely to die from an injury than from cancer or any other disease. Of the 39,929 deaths among young persons (aged 15-24 years)in the United States during 1986, 19,975 were due to injuries (15,227 due to motor vehicles crashes), 5522 were due to homicides, and 5120 were the result of suicide.(2) All forms of cancer combined accounted for only 2115 deaths in this age group.(2) It
Table 5: Leading Causes of Death, Birth to 18 Months
(Table 5)Table 6: Leading Causes of Death, Ages 2-6
(Table 6)Table 7:Leading Causes of Death, Ages 7-12
(Table 7)Table 8:Leading Causes of Death, Ages 13-18
(Table 8)Table 9:Leading Causes of Death, Ages 19-39
(Table 9)Table 10: Leading Causes of Death, Ages 40 -64
(Table 10)Table 11: Leading Causes of Death, Ages 65 and Over
(Table 11)Table 12: Pregnant Women
(Table 12)REFERENCES
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:332. 2. National Center for Health Statistics. Advance report of final morality statistics, 1986. Monthly Vital Statistics Report, vol. 37, no. 6. Hyattsville, Md.: Public Health Service, 1988. (Publication no. DHHS (PHS) 88-1120.)
3. Department of Transportation. Final regulatory impact assessment on amendments to Federal Motor Vehicle Safety Standard 208, Front Seat Occupant Protection. Washington, D.C.: Department of Transportation, 1984. (Publication no. DOT HS 806-572.)
4. Campbell BJ. Safety belt injury reduction related to crash severity and front seated position. J Trauma 1987; 27:733-9.
5. Baker SP, O'Neill B, Karpf R. The injury fact book. Lexington, Mass.: DC Heath and Company, 1984.
6. Waller JA. Injury control: a guide to causes and prevention of trauma. Lexington, Mass.: DC Heath and Company, 1985.
7. Centers for Disease Control. Summary of notifiable diseases, United States, 1987. MMWR 1988; 36:10.
8. Curran JW, Jaffe HW, Hardy AM, et al. Epidemiology of HIV infection and AIDS in the United States. Science 1988; 239:610-6.
9. American Academy of Pediatrics. Guidelines for health supervision. Elk Grove Village.III.: American Academy of Pediatrics, 1985. 10.Idem. Recommendations for preventive pediatric health care. Committee on Practice and Ambulatory Medicine. Elk Grove Village, III.:American Academy of Pediatrics, 1987.
Recommendations for Patient Education and Counseling
Empirical research and clinical experience yield certain principles that clinicians can use to induce behavior change among patients. Attention to these key concepts should enhance the effectiveness of physician counseling concerning all behavioral changes recommended in this report.1. Develop a therapeutic alliance. See yourself as an expert consultant available to help patients who remain in control of their own health choices. This perspective facilitates development of a therapeutic alliance in which health is maintained or achieved through a provider-patient partnership.(1,2) Help motivate patients who smoke, abuse alcohol and other drugs, or do not exercise to change these behaviors. Assist them in acquiring the necessary attitudes and skills to succeed in their attempts.
2. Counsel all patients. Most patients are eager for health information and guidance and generally want more than physicians provide.(3) Whites tend to receive more information than blacks and Hispanics,(4,5) and middle class patients tend to receive more than working class patients.(6) Physicians tend to talk more with patients who pose more questions, but those who are quieter are often in greater need of education.(7) Make a concerted effort to respond to the educational needs of all your patients in ways appropriate to their age, race, sex, socioeconomic status, and interpersonal skills.
3. Ensure that patients understand the relationship between behavior and health. Inquire about what your patients already know or believe about the relationship between risk factors and health status. Do not assume that patients understand the health effects of smoking, lack of exercise, poor nutrition, and other lifestyle factors. Explain in simple terms the idea that certain factors can increase the risk of disease and that combinations of factors can sometimes work together to increase risk beyond the sum of their individual contributions. Respond to patients' questions, reinforce key points, and encourage patients to write down questions about risk factors for discussion at the next visit. Bear in mind that knowledge is a necessary, but not a sufficient, stimulus for behavior change.
4. Work with patients to assess barriers to behavior change. Anticipating obstacles to behavior change is fundamental to effective patient education since patients often do not follow physicians' advice concerning medication use or lifestyle changes.(8) According to one well-studied model, three areas of beliefs influence the adoption and maintenance of behavior change: (1) susceptibility to continuing problems if the advice is not followed; (2) severity of problems associated with not following the advice; and (3) the benefits of adopting the advice weighed against the potential risks, costs, side effects, and barriers.(9) Assess those areas and address those beliefs that are not conducive to healthful behaviors. In addition, try to determine other obstacles to change, including lack of skills, motivation, resources, and social support, and help patients determine ways to overcome them.(10)
5. Gain commitment from patients to change. This is a critical step in patient education and counseling because patients typically come into the physician's office expecting to be treated for a condition. If patients do not agree that their behaviors are significantly related to health outcomes, attempts at patient education may be irrelevant.
6. Involve patients in selecting risk factors to change. Do not overwhelm patients by asking them to try to change all their unhealthful behaviors at the same time. Let patient need, patient preference, and your own assessment of relative importance to health dictate your recommendation of which risk factor to tackle first.(11) Patients who achieve success in one effort may attempt other changes, since many behavior patterns tend to be linked.(12) For example, quitting smoking may lead to renewed energy to begin exercising, which in turn may lead to better eating habits. There are situations, however, where it is advisable to address risk factors simultaneously, such as chemical dependence involving several substances.
7. Use a combination of strategies. Educational efforts that integrate individual counseling, group classes, audiovisual aids, written materials, and community resources are far more effective than those employing only one single technique.(13) Be flexible about tailoring programs to individual needs; for example, some patients will not attend group classes, and others may have inflexible work schedules. Ensure that printed materials are accurate, consistent with your views, and at a reading level appropriate to the patient population. Use written materials to strengthen the message, personalizing them by jotting pertinent comments in the margins; this will help to remind patients later of your suggestions. Be wary of excessive use of print materials as a substitute for verbal communication with patients. Multiple studies have demonstrated that clinicians' individual attention and feedback are more useful than media or other communication channels in changing patient knowledge and behavior.(14)
8. Design a behavior modification plan. Patient education should be oriented toward what patients should do, not merely what patients should know.(15) Ask patients if they have ever tried to change the specific behavior before and discuss the methods used, the barriers encountered, and the degree of success. If patients have tried and failed, ask them to identify what they have learned from the attempt. Agree on a specific, time-limited goal to be achieved and record the goal in the medical record.(16) Discuss the behaviors that need to be modified to achieve the goal, paying special attention to patient cultural beliefs and attitudes that might facilitate or impede success. Assist patients in writing action plans, review relevant instructional materials, and stress your willingness to be of continued assistance.(11) Remember, at best patients often recall only about 50% of what they are told by their physicians, and lifestyle recommendations are remembered less than are medication regimens.(17) Close your visit by summarizing your mutual expectations and expressing your confidence that the patient will make a good effort to modify his or her risk factors.
9. Monitor progress through follow-up contact. Once a strategy for behavior change has been developed, schedule a follow-up appointment or telephone call within the next few weeks to evaluate progress in achieving the goal. Reinforce successes through positive verbal feedback. If patients have not followed the plan, work with them to identify and overcome obstacles. Modify the plan if necessary to facilitate successful risk factor reduction. Strategies include referring patients to community agencies or self-help groups and eliciting support for the patient's prescribed regimen from family members or significant individuals in their social networks.(8) Progressively transfer responsibility for self-care to patients by scheduling follow-up contacts with increasingly longer time intervals.(8) Evaluate your office's capacity to monitor patient progress through computerized records or other tracking systems, and make necessary improvements.
10. Involve office staff. Use the team approach to patient education. Share responsibility for patients with nurses, health educators, dietitians, and other allied health professionals, as appropriate. Ask your receptionist to encourage patients to read materials that you have reviewed, approved, and placed in your reception area. Ensure that team members and the office environment communicate consistent positive health messages.(18) Well-meaning comments such as "Well, you know the doctor is a fanatic about exercise,' or "I can't lose weight either" can unintentionally sabotage patient education strategies.(19) If possible, form a patient education committee to generate program ideas and promote staff commitment.(18)
Bear in mind that the physician's own health-promoting behavior should serve as a role model for patients. It is difficult to assist patients to stop smoking, begin exercising, change dietary patterns, reduce alcohol consumption, or manage stress if you need to and do not make these changes in your own behavior. Rene Dubos once said that "to ward off disease or recover from health, men as a rule find it easier to depend on the healers than to attempt the more difficult task of living wisely."(20) Physicians who both practice and preach prudent health behaviors should be better able to foster health within themselves and their patients.(21)
References
1. Rosenstock IM. Adoption and maintenance of lifestyle modifications. Am J Prev Med 1988; 4:349-52.
2. Lipkin M. The medical interview and related skills. In Branch WT, ed. Office practice of medicine, 1st ed. Philadelphia: WB Saunders, 1987:1287-1306.
3. Woo B, Woo B, Cook F, et al. Screening procedures in the asymptomatic adult: comparisons of physicians' recommendations, patients' desires, published guidelines, and actual practice. JAMA 1985; 254:1480-4. 4. Hall JA, Roter DL, Katz NR. Meta-analysis of correlates of provider behavior in medical encounters. Med Care 1988; 26:657-75. 5. Roter DL, Hall JA, Katz NR. Patient-physician communication: a descriptive summary of the literature. Patient Educ Couns 1988; 12:99-119.
6. Waitzkin H. Information giving in medical care. J Health Soc Behav 1985; 26:81-101.
7. Roter DL. Patient participation in the patient-provider interaction. The effects of patient question asking on the quality of interaction, satisfaction, and compliance. Health Educ Monogr 1977; 5:281-315. 8. Green LW. How physicians can improve patients' participation and maintenance in self-care. West J Med 1987; 147:346-9.
9. Janz NK, Becker MH. The health belief model: a decade later. Health Educ Q 1984; 11:1-47.
10.Ockene JK, Sorensen G, Kabat-Zinn J, et al. Benefits and costs of lifestyle change to reduce risk of chronic disease. Prev Med 1988; 17:224-34.
11.Fried RA, Iverson DC, Nagle JP. The clinician's health promotion handbook. Denver, Colo.: Mercy Medical Center, 1985:9-21. 12.Integration of risk factor interventions: two reports to the Office of Disease Prevention and Health Promotion. Washington, D.C.: Department of Health and Human Services, 1986.
13.Kottke TE, Battista RN, DeFriese GH, et al. Attributes of successful smoking cessation interventions in clinical practice: a meta-analysis of 42 controlled trials. JAMA 1988; 259:2882-9.
14.Mullen PD, Green LW, Persinger G. Clinical trials of patient education for chronic conditions: a comparative analysis of intervention types. Prev Med 1985; 14:753-81.
15.Bartlett EE. Introduction: eight principles from patient education research. Prev Med 1985; 14:667-9.
16.Simons-Morton BG, Pate RP, Simons-Morton DG. Prescribing physical activity to prevent disease. Postgrad Med 1988; 83:165-76. 17.Rost K, Roter D. Predictors of recall of medication regimens and recommendations for lifestyle change in elderly patients. Gerontologist 1987; 27:510-5.
18.Vogt HB, Kapp C. Patient education in primary care practice. Postgrad Med 1987; 81:273-8.
19.Richards JW, Blum A. Health promotion. In: Taylor RE, ed. Family medicine: principles and practice, 3rd ed. New York: Springer-Verlag, 1988:94-105.
20.Gutmann MC, Jackson TC. Facilitating behavior change. In: Sheridan DP, Winogrond IR, eds. The preventive approach to patient care. New York: Elsevier, 1987:49-68.
21.Shindell S, Sheridan DP. The healthy physician. In: Sheridan DP, Winogrond IR, eds. The preventive approach to patient care. New York: Elsevier, 1987:69-96.
Screening for Asymptomatic Coronary Artery Disease
Recommendation
Clinicians should emphasize the primary prevention of coronary artery disease (CAD) by periodically screening for high blood pressure and high serum cholesterol and by routinely investigating behavioral risk factors for CAD such as tobacco use, dietary fat and cholesterol intake, and inadequate physical activity. Secondary prevention of CAD (screening) by performing routine electrocardiography to screen asymptomatic persons is not recommended. It may be clinically prudent to perform screening electrocardiograms (ECGs) in certain high-risk groups (see Clinical Intervention). Routine resting or exercise ECG screening before entering athletic programs is not recommended for asymptomatic children, adolescents, or young adults.Burden of Suffering
Coronary artery disease is the leading cause of death in the United States, accounting for about 1.5 million myocardial infarctions and 520,000 deaths each year.(1,2) Acute myocardial infarction is associated with high mortality despite recent advances in resuscitation and cardiac life support techniques; about 15% of patients who reach the hospital after acute myocardial infarction do not survive their hospitalization.(3) In addition, CAD is responsible for significant morbidity and disability among those suffering from angina pectoris and the complications of myocardial infarction. Medical care and lost productivity for cardiovascular diseases cost the United States nearly $80 billion in 1986.(2) Myocardial infarction and sudden death often occur without warning in persons without a history of angina pectoris or other clinical symptoms. The principal modifiable risk factors for CAD are cigarette smoking, hypertension, elevated serum cholesterol, and obesity. Age, sex, and family history are the principal nonmodifiable risk factors.Efficacy of Screening Tests
There are two screening strategies to reduce morbidity and mortality from CAD. The first involves primary prevention by screening for cardiac risk factors, such as hypertension, elevated serum cholesterol, cigarette smoking, and physical inactivity. The second strategy involves secondary prevention through early detection of coronary atherosclerotic disease. The principal tests considered for this form of screening include resting and exercise ECGs, which can provide evidence of previous silent myocardial infarctions. In addition, certain ECG findings may be useful in predicting the long-term risk of experiencing future coronary events. Prospective studies in asymptomatic persons suggest that Q-waves, ST-segment depression, T-wave inversion, left ventricular hypertrophy, and ventricular arrhythmias are associated with increased risk for coronary events and sudden death.(4-12) However, there are important limitations to the sensitivity and specificity of electrocardiography when used as a screening test. A normal ECG does not rule out coronary disease; ECG changes often do not become apparent until atherosclerotic narrowing has become great enough to significantly impede coronary blood flow.(13)Conversely, an abnormal ECG cannot be relied on as conclusive evidence of underlying arterial disease. ST-segment changes, for example, occur commonly in the general population.(14) Thus, routine ECG testing in asymptomatic persons, in whom the probability of having CAD is relatively low, generates a large proportion of false-positive results.(15) Although precise data are lacking on the positive predictive value of the resting ECG, studies of exercise ECG (which has greater sensitivity and specificity than the resting ECG) indicate that most asymptomatic persons with abnormal results do not have underlying CAD. A series of reports have shown that angiographic evidence of significant stenosis (greater than 50% narrowing) is present in only 30-43% of middle-aged asymptomatic persons with abnormal exercise tests.(16-18) Abnormal resting ECG findings, although often associated with increased long-term risk of developing symptomatic disease, are of limited prognostic value. Prospective studies lasting between 5 and 30 years have found that CAD develops in only 3-15% of asymptomatic persons with resting ECG abnormalities.(4,5,9,12,19) An abnormal exercise test is of somewhat larger, but also limited, prognostic value in predicting CAD in asymptomatic persons.(20) Longitudinal studies lasting 3-13 years have shown that, depending on the population being studied and the end points used to define cardiac events, between 5% and 46% (or an average of about 25%) of persons with exercise-induced ST-segment depression developed symptomatic coronary disease such as angina pectoris or myocardial infarction.(21-30)
False-positive electrocardiography results are undesirable for several reasons. Persons with abnormal results often subsequently receive diagnostic procedures such as thallium scintigraphy and, if this is also positive, coronary angiography before it can be determined that the ECG is falsely positive. The initial abnormal ECG as well as the serial tests that follow may produce considerable anxiety among patients. Both the extent and precision of diagnostic testing can be modified to some extent by performing work-ups in accordance with a Bayesian model:(31) testing can be targeted to high-risk groups, such as men with a family history of premature CAD or those persons whose calculated pretest probability of developing CAD is greater than 10%. Nonetheless, even the initial abnormal ECG tracing may disqualify some patients from jobs, insurance eligibility, and other opportunities, although precise data on the magnitude of these problems are lacking.
Effectiveness of Early Detection
Although there is evidence from case-control and cohort studies that asymptomatic persons with selected ECG findings are at increased risk of cardiac death, myocardial infarction, and sudden death,(21,29,30,32-35) there is little evidence that the identification of these individuals through ECG screening and the treatment of their asymptomatic CAD can reduce the incidence of these outcomes. Studies have shown that antianginal drugs such as nitroglycerin, beta-adrenergic blockers, and calcium antagonists can reduce the frequency and the duration of silent ischemic episodes,(36-38) but there is no evidence that this treatment results in lowered incidence of cardiac events in persons with no history of angina or myocardial infarction. Other, more invasive treatment options such as coronary artery bypass grafting and angioplasty may be of benefit to asymptomatic persons with left main coronary or three-vessel disease.(39) For example, three-vessel disease accounts for about 25% of abnormal angiograms in asymptomatic middle-aged men.(40) However, it is unclear from current evidence that the detection of such individuals provides sufficient justification for routine screening of large asymptomatic populations.Some argue that a screening ECG is valuable as a "baseline" to help interpret changes in subsequent ECGs.(41) Such ECG records are clinically useful on occasion, and changes in serial ECGs may help predict future coronary events,11 but studies indicate that in actual practice, most baseline tracings are either unavailable or do not provide information that affects treatment decisions.(42) Even when important differences are noted between the baseline ECG and a subsequent tracing, it is often difficult to determine when during the interval the change occurred. Another argument for electrocardiography screening is that the early identification of persons at increased risk for CAD on the basis of ECG findings may help to modify other important cardiac risk factors such as cigarette smoking, hypertension, and high blood cholesterol.(41) While the efficacy of these behavioral changes is well established, these interventions are recommended independently of the ECG, and there is little evidence to suggest that patients who are aware of their ECG findings are more likely to change behavior or to experience a better outcome than those who do not obtain ECG results.
Periodic ECG screening has also been advocated for persons who might endanger public safety were they to experience myocardial infarction or sudden death at work (e.g., airline pilots, bus and truck drivers, railroad engineers).(43) Cardiac events in such individuals are more likely to affect the safety of a large number of persons, and clinical intervention, either through medical treatment or counseling to change job status, might prevent such catastrophes. There are no available data to confirm the efficacy of these measures, however.
Preliminary exercise ECG testing has been advocated for sedentary persons planning to begin vigorous exercise programs. There is evidence that strenuous exertion may increase the risk of sudden cardiac death,(44,45) usually as a result of underlying hypertrophic cardiomyopathy or congenital coronary anomalies in young persons(46) or CAD in older persons.(45) Cardiac events during exercise in persons without overt heart disease are relatively uncommon, however, and thus the number of cases that are preventable through preexercise testing of asymptomatic persons is limited. In addition, it has not been proved that restricted exertion in asymptomatic persons at risk for heart disease can prevent the occurrence of subsequent cardiac events. In populations at low risk for heart disease, such as healthy young persons engaged in athletic programs or recreational sports, the limited benefits of screening may be outweighed by the harmful effects of labeling and exercise restrictions for the large proportion of persons whose positive ECG results will be falsely positive.
Recommendations of Others
In 1977, a task force sponsored by the American College of Cardiology (ACC) recommended that all adults receive a baseline 12-lead ECG at an unspecified age, followed by periodic ECG testing every five years, or annually in high-risk persons.(47) The American Heart Association (AHA) recommends baseline electrocardiography at age 20 followed by repeated tracings at ages 40 and 60 in normotensive persons.(48) The Institute of Medicine has recommended obtaining a baseline ECG at age 40 or 45.(49) Recommendations against routine electrocardiography have been issued by the Canadian Task Force (50) and a number of reviewers.(51-53) The ACC and AHA recommend exercise electrocardiography testing of asymptomatic males over age 40 under the following circumstances: (a) occupations affecting public safety (e.g., airline pilots, firemen, police officers, bus or truck drivers, railroad engineers); (b) two or more cardiac risk factors (serum cholesterol over 240 mg/dL (6.20 mmol/L), blood pressure greater than 160/90 mm Hg, cigarette smoking, diabetes mellitus, family history of CAD onset before age 55); or (c) sedentary persons planning to begin a vigorous exercise program.(43) The American College of Sports Medicine recommends preliminary exercise ECG testing for all men and women over 45 who plan to begin an exercise program.(54)Discussion
CAD is the leading cause of death in the United States, and thus even preventive interventions of only modest benefit may have large public health implications. The screening ECG has this potential due to its ability to detect previously unrecognized atherosclerotic heart disease and its prognostic value in predicting subsequent illness.However, the ECG is an imperfect screening test. False-positive ECG results are not uncommon in healthy persons, especially when screening is performed routinely in low-risk asymptomatic populations. In these groups, the large majority of persons with abnormal ECG results do not have CAD and are unlikely to develop the disease in the near future. To minimize the physical, psychological, and economic effects of false-positive labeling, ECG screening should be targeted to individuals at increased risk for CAD and to those whose sudden death or incapacitation would endanger the safety of others.
There are major costs associated with the widespread performance of periodic resting ECG on large numbers of asymptomatic persons. Exercise testing is an even more expensive procedure. These expenses would be justified if the incidence of CAD could be significantly lowered in the process, but such evidence is not yet available. Further research is necessary to demonstrate whether early detection and treatment of asymptomatic CAD is effective in lowering morbidity and mortality. In the meantime, the most effective proven means of preventing CAD are the identification and control of major cardiac risk factors such as hypertension, elevated serum cholesterol, and cigarette smoking.
Clinical Intervention
Clinicians should emphasize primary prevention of CAD by periodically screening for hypertension and high serum cholesterol and by routinely investigating behavioral risk factors for CAD such as tobacco use dietary fat and cholesterol intake and inadequate physical activity Secondary prevention (screening) by performing routine electrocardiography in asymptomatic persons is not recommended as an effective strategy to reduce the risk of CAD. It may be clinically prudent to perform screening ECGs on asymptomatic males over age 40 with two or more cardiac risk factors (hypercholesterolemia, hypertension, cigarette smoking, diabetes mellitus, or family history of early-onset CAD); on those who would endanger public safety were they to experience sudden cardiac events (e.g., commercial airline pilots); and as exercise tests for sedentary or high-risk males over age 40 who are planning to begin a vigorous exercise program. Due to the lack of data on the effectiveness of the screening ECG, the optimal interval for such testing is uncertain and is left to clinical discretion. The exercise ECG is a more sensitive and specific screening test than the resting ECG. Routine resting or exercise ECG screening to enter athletic programs is not recommended for children, adolescents, or young adults with no evidence of heart disease.References
1. National Center for Health Statistics. Advance report of final mortality statistics, 1986. Monthly Vital Statistics Report (Suppl), vol. 37, Hyattsville, Md.: Public Health Service, 1988. (Publication no. DHHS (PHS) 88-1120.)
2. American Heart Association. 1989 heart facts. Dallas, Tex.: American Heart Association, 1988.
3. Furberg CD. Secondary prevention trials after acute myocardial infarction. Am J Cardiol 1987; 60:28A-32A.
4. Rose G, Baxter PJ, Reid DD, et al. Prevalence and prognosis of electrocardiographic findings in middle aged men. Br Heart J 1978; 40:636-43.
5. Knutsen R, Knutsen SF, Curb JD, et al. The predictive value of resting electrocardiograms for 12-year incidence of coronary heart disease in the Honolulu Heart Program. J Clin Epidemiol 1988; 41:293-302. 6. Cedres BL, Liu K, Stamler J, et al. Independent contribution of electrocardiographic abnormalities to risk of death from coronary heart disease, cardiovascular diseases and all causes: findings of three Chicago epidemiologic studies. Circulation 1982; 65:146-53. 7. Blackburn H, Taylor HL, Keys A. Coronary heart disease in seven countries. XVI. The electrocardiogram in prediction of five-year coronary heart disease incidence among men aged forty through fifty-nine. Circulation (Suppl 1) 1970; 41:154-61.
8. Cullen K, Stenhouse NS, Wearne KL, et al. Electrocardiograms and 13 year cardiovascular mortality in Busselton study. Br Heart J 1982; 47:209-12. 9. Higgins ITT, Kannel WB, Dawber TR. The electrocardiogram in epidemiological studies: reproducibility, validity, and international comparison. Br J Prev Soc Med 1965; 19:53-68.
10. Pooling Project Research Group. Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the Pooling Project. J Chron Dis 1978; 31:201-306.
11. Harlan WR, Cowie CC, Oberman A, et al. Prediction of subsequent ischemic heart disease using serial resting electrocardiograms. Am J Epidemiol 1984; 119:208-17.
12. Kannel WB, Anderson K, McGee DL, et al. Nonspecific electrocardiographic abnormality as a predictor of coronary heart disease: the Framingham Study. Am Heart J 1987; 113:370-6. 13. Detrano R, Froelicher V. A logical approach to screening for coronary artery disease. Ann Intern Med 1987; 106:846-52.
14. Kohli RS, Cashman PM, Lahiri A, et al. The ST segment of the ambulatory electrocardiogram in a normal population. Br Heart J 1988; 60:4-16. 15. Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary artery disease. N Engl J Med 1979; 300:1350-8.
16. Froelicher VF Jr, Yanowitz FG, Thompson AJ, et al. The correlation of coronary angiography and the electrocardiographic response to maximal treadmill testing in 76 asymptomatic men. Circulation 1973; 48:597-604. 17. Borer JS, Brensike JF, Redwood DR, et al. Limitations of the electrocardiographic response to exercise in predicting coronary-artery disease. N Engl J Med 1975;293:367-71.
18. Froelicher VF Jr, Thompson AJ, Wolthuis R, et al. Angiographic findings in asymptomatic aircrewmen with electrocardiographic abnormalities. Am J Cardiol 1977; 39:32-8.
19. Multiple Risk Factor Intervention Trial Research Group. Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial. Am J Cardiol 1985; 55:1-15.
20. Uhl GS, Froelicher V. Screening for asymptomatic coronary artery disease. J Am Coll Cardiol 1983; 1:946-55.
21. Bruce RA, DeRouen TA, Hossack KF. Value of maximal exercise tests in risk assessment of primary coronary heart disease events in healthy men: five years' experience of the Seattle Heart Watch Study. Am J Cardiol 1980; 46:371-8.
22. Aronow WS, Cassidy J. Five-year follow-up of double Master's test, maximal treadmill stress test, and resting and postexercise apex cardiogram in asymptomatic persons. Circulation 1975; 52:616-8. 23. Cumming GR, Samm J, Borysyk L, et al. Electrocardiographic changes during exercise in asymptomatic men: 3-year follow-up. Can Med Assoc J 1975; 112:578-81.
24. Froelicher VF Jr, Thomas MM, Pillow C, et al. Epidemiologic study of asymptomatic men screened by maximal treadmill testing for latent coronary artery disease. Am J Cardiol 1974; 34:770-6.
25. Allen WH, Aronow WS, Goodman P, et al. Five-year follow-up of maximal treadmill stress test in asymptomatic men and women. Circulation 1980; 62:522-7.
26. McHenry PL, O'Donnell J, Morris SN, et al. The abnormal exercise electrocardiogram in apparently healthy men: a predictor of angina pectoris as an initial coronary event during long-term follow-up. Circulation 1984; 70:547-51.
27. MacIntyre NR, Kunkler JR, Mitchell RE, et al. Eight-year follow-up of exercise electrocardiograms in healthy, middle-aged aviators. Aviat Space Environ Med 1981; 52:256-9.
28. Manca C, Dei Cas L, Albertini D, et al. Differential prognostic value of exercise electrocardiogram in men and women. Cardiology 1978; 63:312-9.
29. Giagnoni E, Secchi MB, Wu SC, et al. Prognostic value of exercise EKG testing in asymptomatic normotensive subjects: a prospective matched study. N Engl J Med 1983; 309:1085-9.
30. Gordon DJ, Ekelund LG, Karon JM, et al. Predictive value of the exercise tolerance test for mortality in North American men: the Lipid Research Clinics Mortality Follow-Up Study. Circulation 1986; 74:525-61.
31. Detrano R, Yiannikas J, Salcedo EE, et al. Bayesian probability analysis: a prospective demonstration of its clinical utility in diagnosing coronary disease. Circulation 1984; 69:541-7. 32. Erikssen J, Thaulow E. Follow-up of patients with asymptomatic myocardial ischemia. In: Rutishauser W, Roskamm H, eds. Silent myocardial ischemia. Berlin: Springer-Verlag, 1984:156-64. 33. Multiple Risk Factor Intervention Trial Research Group. Exercise electrocardiogram and coronary heart disease mortality in the Multiple Risk Factor Intervention Trial. Am J Cardiol 1985; 55:16-24. 34. Hickman JR Jr, Uhl GS, Cook RI, et al. A natural history study of asymptomatic coronary disease. Am J Cardiol 1980; 45:422. 35. Cohn PF. Silent myocardial ischemia. Ann Intern Med 1988; 109:312-7. 36. Shell WE, Kivowitz CF, Rubins SB, et al. Mechanisms and therapy of silent myocardial ischemia: the effect of transdermal nitroglycerin. Am Heart J 1986; 112:222-9.
37. Frishman W, Teicher M. Antianginal drug therapy for silent myocardial ischemia. Am Heart J 1987; 114:140-7.
38. Pepine CJ, Hill JA, Imperi GA, et al. Beta-adrenergic blockers in silent myocardial ischemia. Am J Cardiol 1988; 61:18B-21B. 39. Epstein SE, Quyyumi AA, Bonow RO. Myocardial ischemia: silent or symptomatic. N Engl J Med 1988; 318:1038-43.
40. Erikssen J, Enge I, Forfang K, et al. False positive diagnostic tests and coronary angiographic findings in 105 presumably healthy males. Circulation 1978; 54:371-6.
41. Collen MF. The baseline screening electrocardiogram: is it worthwhile? An affirmative view. J Fam Pract 1987; 25:393-6.
42. Rubenstein L, Greenfield S. The baseline ECG in the evaluation of acute cardiac complaints. JAMA 1980; 224:2536-9.
43. American College of Cardiology. Guidelines for exercise testing: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Cardiovascular Procedures (Subcommittee on Exercise Testing). J Am Coll Cardiol 1986; 8:725-38.
44. Cobb LA, Weaver WD. Exercise: a risk for sudden death in patients with coronary artery disease. J Am Coll Cardiol 1986; 7:215-9. 45. Amsterdam EA, Laslett L, Holly R. Exercise and sudden death. Cardiol Clin 1987; 5:337-43.
46. Epstein SE, Maron BJ. Sudden death and the competitive athlete: perspectives on preparticipation screening studies. J Am Coll Cardiol 1986; 7:220-30.
47. Resnekov L, Fox S, Selzer A, et al. Task Force IV: use of electrocardiograms in practice. Am J Cardiol 1978; 41:170-5. 48. American Heart Association. Cardiovascular and risk factor evaluation of healthy American adults: a statement for physicians by an ad hoc committee appointed by the steering committee, American Heart Association. Circulation 1987; 75:1340A-62A.
49. National Academy of Sciences, Institute of Medicine. Ad Hoc Advisory Group on Preventive Services. Preventive services for the well population. Washington, D.C.: National Academy of Sciences, 1978. 50. Canadian Task Force on the Periodic Health Examination. The periodic health examination: 1984 update. Can Med Assoc J 1984; 130:2-15. 51. Frame PS. A critical review of adult health maintenance. Part 1. prevention of atherosclerotic diseases. J Fam Pract 1986; 22:341-6. 52. Goldberger AL, O'Konski M. Utility of the routine electrocardiogram before surgery and on general hospital admission: critical review and new guidelines. Ann Intern Med 1986; 105:552-7.
53. Estes EH. Baseline screening electrocardiogram: an opposing view. J Fam Pract 1987; 25:395-6.
54. American College of Sports Medicine. Guidelines for exercise testing and prescription, 3rd ed. Philadelphia: Lea & Febiger, 1986.
Screening for High Blood Cholesterol
Recommendation
Periodic measurement of total serum cholesterol is most important for middle-aged men, and it may also be clinically prudent in young men, women, and the elderly (see Clinical Intervention). All patients should receive periodic counseling regarding dietary intake of fat (especially saturated fat) and cholesterol.Burden of Suffering
High blood cholesterol, cigarette smoking, and hypertension are the principal modifiable risk factors for coronary artery disease (CAD), the leading cause of death in the United States.(1) About 1.5 million myocardial infarctions (MIs) and over 520,000 deaths from ischemic heart disease occur each year in the United States.(1,2) These cardiac events often occur without warning in persons with no previous history of angina pectoris or other clinical symptoms. The 30-day case-fatality rate for persons in whom MI is the initial manifestation of CAD is about 30%.(3) CAD is also associated with significant morbidity; the discomfort and exertional restrictions of angina pectoris and MI can limit productivity, functional independence, and quality of life. Cardiovascular diseases cost the United States about $80 billion each year.(2)Efficacy of Screening Test
The principal screening test for high blood cholesterol is the measurement of total serum cholesterol in specimens obtained by either venipuncture or finger-stick. Due to biological variation and measurement error, such measurements may not always reflect the patient's true cholesterol level. Serum cholesterol levels normally undergo substantial physiologic fluctuations related to gender, stress, and season,(4) and therefore a single blood test may not always be representative. Repeated measurements on the same individual have a standard deviation of about 18 mg/dL (0.45 mmol/L), so that the 95% confidence interval for a typical adult whose blood cholesterol is 220 mg/dL (5.70 mmol/L) would be +/-36 mg/dL (0.95 mmol/L), or 184-256 mg/dL (4.75-6.65 mmol/L).(5,6) Due to this variation, a single cholesterol measurement should not be relied on and the average of multiple tests should be used for therapeutic decisions.In addition to biological variation, different laboratory instruments for measuring serum cholesterol are subject to systematic bias and random sources of error.(7) A number of instruments in routine use consistently overestimate (positive bias) or underestimate (negative bias) the true cholesterol value by about 2-7%.(4,7-11) More extreme errors have also been reported. One study found that a serum cholesterol concentration of 250 mg/dL (6.45 mmol/L) was reported by one instrument as 285 mg/dL (7.35 mmol/L) (14% positive bias) and by another as 301 mg/dL (7.80 mmol/L) (20% positive bias).(4) Nearly half of all laboratory cholesterol results vary by 5% or more from the correct value.(12) Another potential source of error is poor precision (e.g., producing different results on the same specimen), although it is generally less of a problem than bias.(12) This accounts for about 3-4% of variation in the results of conventional clinical laboratory equipment(5,10) and desk-top office analyzers.(7,13-16) There is also significant variation between clinical laboratories (about 6%) and within individual laboratories (about 3.5%).(12)
Capillary sample measurements are often less accurate than analyses of venipuncture specimens. Inadequate training and the use of improper techniques in operating the equipment can introduce additional sources of error.(16) This is especially important in relation to desk-top chemical analyzers.(12) Further research is needed to fully evaluate these devices, and programs should be developed to assure acceptable performance standards before desk-top instruments are recommended for widespread screening.(12) Since clinical decisions regarding treatment are affected by the report of a cholesterol level above a "desirable" level, there are potentially important clinical consequences resulting from laboratory underestimation or overestimation of the actual cholesterol level. Persons with high blood cholesterol requiring intervention may be advised incorrectly that their serum lipid levels are in the desirable range and thus not be retested for some time. Conversely, persons who receive falsely elevated test results may undergo the inconvenience and cost of follow-up testing. In some cases, erroneous cholesterol test results may generate unnecessary office visits to health care providers. Some patients may experience anxiety and the effects of labeling that have been observed in hypertension screening, such as absenteeism and psychological symptoms.(17) Finally, patients receiving inadequate follow-up testing may be exposed unnecessarily to treatment with cholesterol-lowering drugs.
To minimize the adverse effects of misclassification resulting from biological variance or laboratory error, an average of at least two blood test results is often recommended to provide a more accurate measure of the true concentration of total cholesterol; three tests are recommended if the difference between the first two tests is greater than 30 mg/dL (0.80 mmol/L).(18) In addition, rigorous standards for improving accuracy and precision in clinical laboratories are being developed and implemented by the College of American Pathologists, the Centers for Disease Control, and the National Cholesterol Coordinating Committee Laboratory Standardization Panel.(12,19) These groups have proposed the goal of improving standards for accuracy and precision in clinical laboratory measurement from the current range of +/-5% to less than 3% by 1992.
Effectiveness of Early Detection
Early detection of high blood cholesterol in asymptomatic persons allows identification of an important modifiable risk factor for CAD. A large body of evidence gathered over several decades, including epidemiologic, pathologic, animal, genetic, and metabolic studies, supports the "lipid hypothesis," the causal relationship between serum cholesterol levels and the development of coronary atherosclerosis.(20-23)The question of whether the lowering of serum cholesterol can achieve a significant reduction in the incidence of CAD in asymptomatic persons has been of major clinical interest. Early efforts to answer this question involved controlled clinical trials in which asymptomatic middle-aged men with selected cardiac risk factors were given low-fat or modified-fat diets.(24-32) Such diets lowered serum cholesterol levels by about 10-15%, and in most trials, this was associated with a reduction in the incidence of cardiac events (e.g., myocardial infarction (24,25,28-30,32) These early studies, however, suffered from a variety of design limitations, such as small sample size, selection bias in the recruitment of study groups and controls, confounding variables, inappropriate statistical analyses, and limited generalizability.(33,34) Probably due to inadequate sample size, most of these studies did not find a significant difference in either CAD or overall mortality between intervention and control groups.(24-27)
The ability of cholesterol-lowering drugs to reduce the incidence of CAD in asymptomatic persons has been demonstrated in three well-designed randomized controlled trials involving asymptomatic middle-aged men with high blood cholesterol. In the WHO Cooperative Trial, which involved over 15,000 men, subjects receiving clofibrate experienced a statistically significant 20% reduction in the overall rate of MI and 25% reduction in nonfatal MI when compared with controls receiving olive oil capsules.(35-37) The incidence of fatal MI was similar in both groups. The Lipid Research Clinics (LRC) Coronary Primary Prevention Trial, a multicenter study of cholestyramine involving 3806 men, reported an incidence of cardiac events of 7.0% in persons receiving cholestyramine and 8.6% in those receiving placebo.(38-42) This 19% reduction in the incidence of CAD was also statistically significant. Nonfatal MI and CAD mortality were 19% and 24% lower, respectively, in the group taking cholestyramine, and the incidence of angina, positive exercise tests, and coronary bypass surgery was also reduced. The Helsinki Heart Study, a trial involving 4081 asymptomatic men, reported a statistically significant 34% reduction in the incidence of cardiac events (nonfatal MI and cardiac death) in men receiving gemfibrozil.(43)
Taken together, these studies provide compelling evidence that the incidence of nonfatal MI and fatal cardiac disease can be reduced by lowering serum cholesterol. The randomized controlled trials that provide the strongest evidence, however, used drugs rather than diet to achieve this effect and involved a select population group, primarily white men aged 35-59 with serum cholesterol values above 255-265 mg/dL (6.60-6.85 mmol/L).(38,43) A current focus of interest is the extent to which this evidence is generalizable to other population groups (i.e., women, young men, the elderly, persons with less marked elevation of serum cholesterol) or to dietary measures.
Women, young men, and the elderly presumably benefit to some extent from lowering serum cholesterol. There are uncertainties, however, regarding the magnitude of benefit from screening these populations since elevated blood cholesterol is either a weaker risk factor or a less common abnormality in these(34,44-47) Persons with borderline high cholesterol (200-240 mg/dL (5.15-6.20 mmol/L)), lacking the high blood cholesterol levels required of participants in the above trials, may benefit less by lowering cholesterol. A cohort study involving over 350,000 men(48,49) and 30-year longitudinal data from the Framingham Study(50) provide evidence that CAD risk increases in a continuous and graded fashion beginning with serum cholesterol levels as low as 180 mg/dL (4.65 mmol/L).(51) The risk rises sharply above 220-240 mg/dL (5.70-6.20 mmol/L), reaching a fourfold increase for levels above 260 mg/dL (6.70 mmol/L), which is the 90th percentile of middle-aged men. It follows that reductions in persons with borderline high cholesterol would be of less substantial benefit than for persons with severe elevations; a 50 mg/dL (1.30 mmol/L) reduction lowers absolute risk by about 50% in persons with a serum cholesterol of 300 mg/dL (7.75 mmol/L) but only by 25% at a level of 250 mg/dL (6.45 mmol/L) and only 7.5% at 200 mg/dL (5.15 mmol/L).(22)
Cardiac risk factors other than high blood cholesterol are also important determinants of the benefits that can be expected from lowering blood cholesterol. Persons at increased risk for CAD because of a history of MI or angina, or asymptomatic persons with other cardiac risk factors, are thought to experience a greater reduction in risk for any given reduction in blood cholesterol than persons without these risk factors.(18,52) These risk factors include male sex, family history of premature CAD, cigarette smoking, hypertension, low high-density lipoprotein (HDL) cholesterol (less than 35 mg/dL (0.90 mmol/L)), diabetes mellitus, cerebrovascular or peripheral vascular disease, and severe obesity.
Another question concerns the magnitude of benefit associated with dietary measures. Animal studies, epidemiological data, and metabolic research support a beneficial effect from diets low in fat, primarily saturated fat. Clinical trials in which diet was the sole intervention have provided encouraging but not conclusive evidence of a significant reduction in the incidence of CAD.(21,22,44,53,54) The lack of conclusive evidence is due at least in part to design limitations (see above). It is reasonable to extrapolate from the drug trial findings that dietary restrictions, if successful in achieving significant reductions in serum cholesterol, can also lower the risk of CAD. Meta-analyses and other reviews of data pooled from dietary trials suggest that the dose-response relationship between dietary reduction of serum cholesterol and the risk of CAD is similar to that observed in data analyzed from drug trials.(55)
The ability of patients to achieve and maintain reductions in dietary fat is still under study. Low-fat diets that have been shown in experimental research to achieve significant reductions in serum cholesterol may not be adopted as readily by all members of the general population.(34,56) Thus, the more modest reductions in serum cholesterol level that result from ordinary fat-controlled diets may produce only modest reductions in CAD. Nonetheless, when compared with pharmacologic regimens to lower serum cholesterol, dietary measures are safer, less expensive, and may obviate the need for prescribing cholesterol-lowering drugs.
In summary, the magnitude of benefit of detecting high blood cholesterol may be reduced in women, young men, and the elderly; persons with borderline high cholesterol; and persons who use dietary measures that do not lower serum cholesterol significantly. Lowering serum cholesterol in low-risk populations may result in only minor changes in population-wide life expectancy.(47) On the other hand, low-risk individuals account for a large proportion of the population. It has been argued from a public health perspective that even modest benefits multiplied across large numbers of individuals can have significant public health implications.(57) Even a modest 5% reduction in the incidence of CAD would prevent about 75,000 MIs each year in the United States.(2)
It is also important to consider the potential health risks associated with lowering serum cholesterol. Long-term use of cholesterol-lowering drugs, such as nicotinic acid, clofibrate, and cholestyramine, is associated with a number of unpleasant and potentially serious side effects.(22,58,59) New classes of lipid-lowering drugs, such as lovastatin, also have adverse effects(60) and have not been in use for sufficient time to establish their long-term safety. The three major clinical trials involving lipid-lowering drugs each reported an increase in non-CAD deaths in intervention groups. An increase in violent deaths (accidents, suicide, homicide) reported in two of the three trials was not statistically significant and was attributed to chance by the investigators,(38,43) but the findings have raised concern among others.(61) The third trial reported a statistically significant 44% increase in all-cause mortality in men taking clofibrate.(35-37) Because clofibrate also causes gallstones,(35) its use for lowering cholesterol to prevent CAD is no longer recommended. Studies have reported associations between decreased levels of serum cholesterol and cancer(24,62-65) and gastrointestinal disease.(24,35,43) Evidence from a large longitudinal study, however, indicates that the association with cancer may represent an effect of preclinical cancer on blood cholesterol rather than an effect of low cholesterol on the development of the disease.(66) An increased incidence of cancer was also not apparent in the three drug trials discussed above.
Cholesterol screening during childhood has received increased attention in recent years. The detection of high blood cholesterol during childhood is of potential value in identifying those children who are at increased risk for developing CAD as adults and who might benefit from more intensive dietary interventions and follow-up than would be offered in the course of routine well-child care. Studies have shown that children with increased intake of dietary fat and cholesterol are at increased risk of having high blood cholesterol,(67) and children with high blood cholesterol are more likely than other children to have elevated cholesterol levels as adults.(68) Dietary habits learned in childhood may persist into adult life, and parents of children with high cholesterol levels are more likely to experience CAD.(69) High blood cholesterol may produce early atherosclerotic changes before adulthood; postmortem studies have demonstrated fatty streaks lining the aortas of children and adolescents with high blood cholesterol levels.(70) Autopsy studies have also noted evidence of CAD in adolescent and young adult war casualties.(71) It is unclear how strongly these pathologic changes are associated with subsequent CAD, however. A relationship between lowering cholesterol during childhood and decreased incidence of CAD during later life has yet to be demonstrated in controlled studies, in part due to the difficulty of performing such studies. This lack of evidence is of concern because it is currently unclear whether a policy of routine cholesterol screening of the 50-60 million children(72) in the United States would achieve sufficient clinical benefit in later years to justify the costs and potential adverse effects of widespread testing. Due to the low prevalence of high blood cholesterol in children, routine screening is likely to generate a large proportion of false positives. There is little information on the potential psychological effects on children of being "labeled" as having high blood cholesterol. Also, some pediatricians have expressed concern that dietary restrictions during childhood may affect the child's source of calories, calcium, and iron.(73) The issue is still under active study.
Recommendations of Others
The National Heart, Lung, and Blood Institute has issued recommendations on cholesterol screening in the clinical setting in the report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.(18) These recommendations were endorsed by the National Cholesterol Coordinating Committee, which includes representatives from the leading national medical organizations. The report recommends routine measurement of nonfasting serum cholesterol in all adults aged 20 and above at least once every five years and provides a detailed protocol to guide follow-up of test results. The protocol sets a lower treatment threshold for persons with CAD or who are at high risk for CAD and recommends averaging two to three separate measurements of total cholesterol and low-density lipoprotein (LDL) cholesterol to help guide drug treatment decisions. Specific recommendations to improve the effectiveness of public screening for high blood cholesterol have been issued through a workshop sponsored by the National Heart, Lung, and Blood Institute.(74) The American Academy of Pediatrics recommends regular elective testing for high blood cholesterol only for children over age 2 who have a family history of hyperlipidemia or early MI.(75) Others have recently recommended universal cholesterol screening for all children.(76) Recommendations on public screening outside the medical setting are currently being prepared by the National Cholesterol Coordinating Committee.Discussion
Serum cholesterol testing of adults in the United States has the potential of achieving a significant reduction in the nationwide incidence of CAD. Care is, however, required for any program targeting more than 150 million people(72) for testing and follow-up to guard against unnecessary health care expenditures and adverse personal consequences. In particular, the use of inaccurate laboratory or desk-top instruments for screening can lead to large numbers of both false-negative and false-positive results. The former can delay needed clinical intervention and the latter can lead to considerable inconvenience, costs, and adverse psychological and medical consequences in persons not needing intervention. It is therefore important for clinicians to exercise discretion in selecting accurate and reliable methods of obtaining blood specimens in the clinical setting, to use clinical laboratories that adhere to accepted standards of quality control, and to properly design treatment strategies based on results confirmed by repeated tests.Discretion is especially important in the use of cholesterol-lowering drugs. The efficacy of such drugs in preventing CAD has been demonstrated most convincingly in middle-aged men with serum cholesterol levels above 255-265 mg/dL (6.60-6.85 mmol/L).(38,43) The effect on CAD of using lipid-lowering drugs in young men, women, or elderly persons, or in those with only mild to moderate elevations in blood cholesterol, has not been studied in clinical trials of asymptomatic persons. It is therefore reasonable to limit the exposure of low- or moderate-risk individuals to the unpleasant side effects of lipid-lowering drugs, the inconvenience of daily, long-term administration, and the potential health risks of agents for which long-term safety has yet to be established. There are also economic implications to prescribing lipid-lowering drugs in light of their expense and the quantities required for long-term therapy. Some studies examining the economic benefits of preventing CAD have questioned the cost- effectiveness of routine drug therapy for elevations in blood cholesterol.(77-80)
It has been shown that a low level of HDL cholesterol is an independent predictor of CAD. Persons whose HDL cholesterol level is at the 20th percentile have two to four times the risk of developing CAD as persons whose level is at the 80th percentile.(81,82) Lipid-fractionation studies, which enable the calculation of HDL and LDL levels, can therefore provide more meaningful information on CAD risk and the effectiveness of therapy than can total cholesterol measurement. Concerns that total blood cholesterol measurements may fail to detect persons at increased risk due to low HDL cholesterol (despite a normal total cholesterol level) have led to recent recommendations to perform lipoprotein analysis routinely on all persons with borderline or high total blood cholesterol.(83)
There are substantial economic considerations in the performance of fractionation studies as a routine follow-up to finding elevated total cholesterol. For example, examining lipid profiles on all adults with high blood cholesterol (240 mg/dL (6.20 mmol/L) or greater) would require performing a $20-$40 test on nearly one-quarter of the 150 million adults in the United States.(72,84) Although it is likely that the information would be useful to clinicians, further research is necessary to determine the exact prevalence of low HDL cholesterol, the efficacy of measures to raise HDL cholesterol, and whether the added information provided by routine lipoprotein analysis results in an overall improvement in clinical outcome. Until this evidence becomes available, lipid fractionation studies may be best reserved for the smaller group of persons for whom the information is most important, such as those being considered for drug therapy and those being monitored for response to treatment with cholesterol-lowering drugs.
Clinical Intervention
All patients should receive periodic counseling regarding dietary intake of fat (especially saturated fat) and cholesterol (see Nutrition). Periodic measurement of total serum cholesterol (nonfasting) is most important for middle-aged men, and it may also be clinically prudent in young men, women, and the elderly. The optimal frequency for cholesterol measurement in asymptomatic persons has not been determined on the basis of scientific evidence and is left to clinical discretion; an interval of every five years (and more frequently for persons with previous evidence of elevated cholesterol) has been recommended on the basis of expert opinion.(18) Cholesterol tests should be performed on venous blood samples analyzed by an accredited laboratory that meets current standards of accuracy and reliability. Abnormal results should be confirmed by a second measurement of nonfasting total cholesterol, and the mean of both results should be used for subsequent therapeutic decisionmaking.All adults with high blood cholesterol (at or above 240 mg/dL (6.20 mmol/L)) and those persons with borderline high cholesterol (200-239 mg/dL (5.15-6.15 mmol/L)) who have known CAD or two or more cardiac risk factors should receive information about the meaning of results, intensive dietary counseling, and follow-up evaluation. The most important cardiac risk factors to be considered include male gender, premature CAD in a first-degree relative, smoking, hypertension, serum HDL cholesterol less than 35 mg/dL (0.90 mmol/L) (when this information is available), diabetes mellitus, previous stroke or peripheral vascular disease, and severe obesity. The recommended two-step dietary program to lower serum cholesterol has been described in detail elsewhere.(18) The primary objective of the Step-One diet is to reduce all dietary fat intake to less than 30% of total calories (with saturated fat contributing less than 10% of total calories) and to reduce dietary cholesterol intake to less than 300 mg/day. The Step-Two diet, which is recommended if the goals of therapy are not achieved after three months, differs from the first by further restricting intake of saturated fats (to 7% of total calories) and dietary cholesterol (200 mg/day).
Cholesterol-lowering drugs should be considered in middle-aged men in whom blood cholesterol remains significantly elevated after a thorough six-month trial of dietary intervention. A suggested threshold for drug treatment is 240 mg/dL (6.20 mmol/L) or greater in persons with CAD or at least two cardiac risk factors and 265 mg/dL (6.85 mmol/L) or greater in persons without risk factors. The patient should receive information on the potential benefits and risks of long-term therapy before beginning treatment on cholesterol-lowering drugs. It is clinically prudent to perform lipid fractionation studies on persons being considered for drug treatment and those being monitored for response to drug therapy over time.
References
1. National Center for Health Statistics. Advance report of final mortality statistics, 1985. Monthly Vital Statistics Report (Suppl), vol. 37, no. 6. Hyattsville, Md.: Public Health Service, 1988. (Publication no. DHHS (PHS) 88-1120.)
2. American Heart Association. 1989 heart facts. Dallas, Texas: American Heart Association, 1988.
3. Elveback LR, Connolly DC, Melton LJ III. Coronary heart disease in residents of Rochester, Minnesota. Incidence, 1950 through 1982. Mayo Clin Proc 1986; 61:896-900.
4. Blank DW, Hoeg JM, Kroll MH, et al. The method of determination must be considered in interpreting blood cholesterol levels. JAMA 1986; 256:2767-70.
5. Jacobs DR, Barrett-Connor E. Retest reliability of plasma cholesterol and triglyceride: the Lipid Research Clinics Prevalence Study. Am J Epidemiol 1982; 116:878-85.
6. Wyngaarden JB. Variability in individual cholesterol level clouds risk assessment. JAMA 1988; 260:759.
7. Burke JJ II, Fischer PM. A clinician's guide to the office measurement of cholesterol. JAMA 1988; 259:3444-8.
8. Koch TR, Mehta U, Lee H, et al. Bias and precision of cholesterol analysis by physician's office analyzers. Clin Chem 1987; 33:2262-7. 9. Kroll MH, Lindsey H, Greene J, et al. Bias between enzymatic methods and the reference method for cholesterol. Clin Chem 1988; 34:131-5. 10. Rastam L, Admire JB, Frantz ID, et al. Measurement of blood cholesterol with the Reflotron analyzer evaluated. Clin Chem 1988; 34:426.
11. Lasater TM, Lefebvre RC, Assaf AR, et al. Rapid measurement of blood cholesterol: evaluation of a new instrument. Am J Prev Med 1987; 3:311-6.
12. Laboratory Standardization Panel of the National Cholesterol Education Program. Current status of blood cholesterol measurement in clinical laboratories in the United States. Clin Chem 1988; 34:193-201. 13. Hicks JM, Iosefsohn M. Another physician's office analyzer: the Abbott "Vision" evaluated. Clin Chem 1987; 33:817-9.
14. Nanji AA, Sincennes F, Poon R, et al. Evaluation of the Boehringer Mannheim "Reflotron" analyzer. Clin Chem 1987; 33:1254-5. 15. von Schenck H, Treichl L, Tilling B, et al. Laboratory and field evaluation of three desktop instruments for assay of cholesterol and triglyceride. Clin Chem 1987; 33:1230-2.
16. Belsey R, Vandenbark M, Goitein RK, et al. Evaluation of a laboratory system intended for use in physicians' offices. II. Reliability of results produced by health care workers without formal or professional training. JAMA 1987; 258:357-61.
17. Lefebvre RC, Hursey KG, Carleton RA. Labeling of participants in high blood pressure screening programs: implications for blood cholesterol screenings. Arch Intern Med 1988; 148:1993-7.
18. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med 1988; 148:36-69.
19. Cotton P. CAP moves to improve lipid tests. Medical World News, June 1988:55.
20. Stamler J. Lifestyles, major risk factors, proof and public policy. Circulation 1978; 58:3-19.
21. Stallones RA. Ischemic heart disease and lipids in blood and diet. Ann Rev Nutr 1983; 3:155-85.
22. Grundy SM. Cholesterol and coronary heart disease: a new era. JAMA 1986; 256:2849-58.
23. National Institutes of Health. Lowering blood cholesterol to prevent heart disease. JAMA 1985; 253:2080-6.
24. Dayton S, Pearce ML, Hashimoto S, et al. A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis. Circulation (Suppl II) 1969; 40:II-1-63. 25. Hjermann I, Velve Byre K, Holme I, et al. Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomized trial in healthy men. Lancet 1981; 2:1303-10.
26. Multiple Risk Factor Intervention Trial Research Group. Multiple risk factor intervention trial: risk factor changes and mortality results. JAMA 1982; 248:1465-77.
27. World Health Organization European Collaborative Group. European collaborative trial of multifactorial prevention of coronary heart disease: final report on the 6-year results. Lancet 1986; 1:869-72. 28. Rinzler S. Primary prevention of coronary heart disease by diet. Bull NY Acad Med 1968; 44:936-49.
29. Turpeinen O, Karvonen MJ, Pekkarinen M, et al. Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. Int J Epidemiol 1979; 8:99-118.
30. Miettinen M, Turpeinen O, Karvonen MJ, et al. Effect of cholesterol- lowering diet on mortality from coronary heart disease and other causes. Lancet 1972; 2:835-8.
31. Stamler J. Acute myocardial infarction, progress in primary prevention. Br Heart J 1971; 33:145-64.
32. Frantz ID, Dawson EA, Kuba K. The Minnesota Coronary Survey: effect of diet on cardiovascular events and deaths. Circulation (Suppl II) 1975; 52:II-4.
33. Borhani NO. Primary prevention of coronary heart disease: a critique. Am J Card 1977; 40:251-9.
34. Ahrens EH. The diet-heart question in 1985; has it really been settled? Lancet 1985; 1:1085-7.
35. Report from the Committee of Principal Investigators. A cooperative trial in the primary prevention of ischaemic heart disease using clofibrate. Br Heart J 1978; 40:1069-118.
36. Report of the Committee of Principal Investigators. W.H.O. cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up. Lancet 1980; 2:379-85.
37. Idem. W.H.O. cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Lancet 1984; 2:600-4.
38. The Lipid Research Clinics Coronary Primary Prevention Trial Results. I. Reduction in incidence of coronary heart disease. JAMA 1984; 251:351-64.
39. The Lipid Research Clinics Coronary Primary Prevention Trial Results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251:365-74. 40. The Lipid Research Clinics Program. The coronary primary prevention trial: design and implementation. J Chron Dis 1979; 32:609-31. 41. Idem. Pre-entry characteristics of participants in the Lipid Research Clinics Coronary Primary Prevention Trial. J Chron Dis 1983; 36:467-79.
42. Idem. Participant recruitment to the Coronary Primary Prevention Trial. J Chron Dis 1983; 36:451-65.
43. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317:1237-45.
44. Kronmal RA. Commentary on the published results of the Lipid Research Clinics Coronary Primary Prevention Trial. JAMA 1985; 253:2091-3. 45. Rahimtoola SH. Some unexpected lessons from large multicenter randomized clinical trials. Circulation 1985; 72:449-55. 46. Borhani NO. Prevention of coronary heart disease in practice: implications of the results of recent clinical trials. JAMA 1985; 254:257-62.
47. Taylor WC, Pass TM, Shepard D, et al. Cholesterol reduction and life expectancy: a model incorporating multiple risk factors. Ann Intern Med 1987; 106:605-14.
48. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? JAMA 1986; 256:2823-8.
49. Martin MJ, Hulley SB, Browner WS, et al. Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men. Lancet 1986; 2:933-6.
50. Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham Study. JAMA 1987; 257:2176-80. 51. Neaton JD, Kuller LH, Wentworth D, et al. Total and cardiovascular mortality in relation to cigarette smoking, serum cholesterol concentration, and diastolic blood pressure among black and white males followed up for five years. Am Heart J 1984; 108:759-70. 52. Siegel D, Grady D, Browner WS, et al. Risk factor modification after myocardial infarction. Ann Intern Med 1988; 109:213-8.
53. Rahimtoola SH. Cholesterol and coronary heart disease: a perspective. JAMA 1985; 253:2094-5.
54. Kaplan RM. Behavioral epidemiology, health promotion, and health services. Med Care 1985; 23:564-83.
55. Tyroler HA. Review of lipid-lowering clinical trials in relation to observational epidemiologic studies. Circulation 1987; 76:515-22. 56. Hulley SB, Lo B. Choice and use of blood lipid tests: an epidemiologic perspective. Arch Intern Med 1983; 143:667-73.
57. Blackburn H. Public policy and dietary recommendations to reduce population level of blood cholesterol. Am J Prev Med 1985; 1:3-11. 58. Oliver MF. Risks of correcting the risks of coronary disease and stroke with drugs. N Engl J Med 1982; 306:297-8.
59. Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987; 2:10-32.
60. Lovastatin for hypercholesterolemia. Medical Letter 1987; 29:99-101. 61. Kolata G. Heart panel's conclusions questioned. Science 1985; 227:40-1.
62. Rose G, Shipley MJ. Plasma lipids and mortality: a source of error. Lancet 1980; 1:523-6.
63. Neugut AI, Johnsen CM, Fink DJ. Serum cholesterol levels in adenomatous polyps and cancer of the colon: a case-control study. JAMA 1986; 255:365-7.
64. International Collaborative Group. Circulating cholesterol level and risk of death from cancer in men aged 40 to 69 years. JAMA 1982; 248:2853-9.
65. Williams RR, Sorlie PD, Feinleib M, et al. Cancer incidence by levels of cholesterol. JAMA 1981; 245:247-52.
66. Sherwin RW, Wentworth DN, Cutler JA, et al. Serum cholesterol levels and cancer mortality in 361,662 men screened for the Multiple Risk Factor Intervention Trial. JAMA 1987; 257:943-8.
67. Nicklas TA, Farris RP, Smoak CG, et al. Dietary factors relate to cardiovascular risk factors in early life. Arteriosclerosis 1988; 8:193-9.
68. Lauer RM, Lee J, Clarke WR. Factors affecting the relationship between childhood and adult cholesterol levels: the Muscatine Study. Pediatrics 1988; 82:309-18.
69. Croft JB, Cresanta JL, Webber LS, et al. Cardiovascular risk in parents of children with extreme lipoprotein cholesterol levels: the Bogalusa Heart Study. South Med J 1988; 81:341-9.
70. Berenson GS, Srinivasan SR, Nicklas TA, et al. Cardiovascular risk factors in children and early prevention of heart disease. Clin Chem 1988; 34:B115-22.
71. Enos WF, Holmes RH, Beyer J. Coronary disease among United States soldiers killed in action in Korea. JAMA 1953; 152:1090-3. 72. National Center for Health Statistics. Health, United States, 1988. Washington D.C.: Government Printing Office, 1989:41. (Publication no. DHHS (PHS) 89-1232.)
73. American Academy of Pediatrics. Prudent lifestyle for children: dietary fat and cholesterol. Pediatrics 1986; 78:521-5. 74. National Heart, Lung, and Blood Institute. Recommendations regarding public screening for measuring blood cholesterol: summary of a National Heart, Lung, and Blood Institute workshop. Bethesda, Md.: National Heart, Lung, and Blood Institute, 1988.
75. American Academy of Pediatrics. Indications for cholesterol testing in children. Pediatrics 1989; 83:141-2.
76. Merz B. New studies fuel controversy over universal cholesterol screening during childhood. JAMA 1989; 261:814.
77. Oster G, Epstein AM. Cost-effectiveness of antihyperlipemic therapy in the prevention of coronary heart disease: the case of cholestyramine. JAMA 1987; 258:2381-7.
78. Kinosian BP, Eisenberg JM. Cutting into cholesterol: cost-effective alternatives for treating hypercholesterolemia. JAMA 1988; 259:2249-54.
79. Weinstein MC, Stason WB. Cost effectiveness of interventions to prevent or treat coronary heart disease. Ann Rev Public Health 1985; 6:41-63.
80. Himmelstein DU, Woolhandler S. Costs and effects: the lipid research trial and the Rand experiment. N Engl J Med 1985; 311:1512-3. 81. Castelli WP, Garrison RJ, Wilson PW, et al. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA 1986; 256:2835-8.
82. Wilson PW, Abbott RD, Castelli WP. High density lipoprotein cholesterol and mortality: the Framingham Heart Study. Arteriosclerosis 1988; 8:737-41.
83. Merz B. Is it time to include lipoprotein analysis in cholesterol screening? JAMA 1989; 261:497-8.
84. Herman M, Health Care Financing Administration. Personal communication, February 1989.
Screening for Hypertension
Recommendation
Blood pressure should be measured regularly in all persons aged 3 and above (see Clinical Intervention).Burden of Suffering
Hypertension may occur in as many as 58 million Americans.(1) It is a leading risk factor for coronary artery disease, congestive heart failure, stroke, renal disease, and retinopathy. These complications of hypertension are among the most common and serious diseases in the United States, and successful efforts to lower blood pressure could thus have substantial impact on population morbidity and mortality. Heart disease is the leading cause of death in the United States, accounting for over 765,000 deaths each year, and cerebrovascular disease, the third leading cause of death, accounts for 150,000 deaths each year.(2) Hypertension is more common in blacks and the elderly.(1)Efficacy of Screening Tests
The most accurate devices for measuring blood pressure (e.g., intraarterial catheters) are not appropriate for routine screening because of their invasiveness, technical limitations, and cost. Office sphygmomanometry (the blood pressure cuff) remains the most appropriate screening test for hypertension in the asymptomatic population. Although this test is highly accurate when performed correctly, false-positive and false-negative results (i.e., recording a blood pressure that is not representative of the patient's mean blood pressure) do occur in clinical practice.(3) A recent study found that 21% of persons diagnosed as mildly hypertensive based on office sphygmomanometry had no evidence of hypertension when 24-hour ambulatory recordings were obtained.(4)Errors in measuring blood pressure may result from instrument, observer, and/or patient factors.(5) Examples of instrument error include manometer dysfunction, pressure leaks, stethoscope defects, and bladders of incorrect width and length for the patient's arm size. The observer can introduce errors due to sensory impairment (difficulty hearing Korotkoff sounds or reading the manometer), inattention, inconsistency in recording Korotkoff sounds (e.g., Phase IV vs. Phase V), and subconscious bias (e.g., digit preference for numbers ending with zero or preconceived notions of normal pressures).
The patient can be the source of misleading readings due to posture and biological factors. Posture (i.e., lying, standing, sitting) and arm position in relation to the heart can affect results by as much as 10 mm Hg.(5) Biological factors include anxiety, meals, tobacco, temperature changes, exertion, and pain. Due to these limitations in the test-retest reliability of blood pressure measurement, it is commonly recommended that hypertension be diagnosed only after more than one elevated reading is obtained on each of three separate visits.(1)
Additional factors affect accuracy when performing sphygmomanometry on children; these difficulties are especially common when testing infants and toddlers under age 3.(6) First, there is increased variation in arm circumference, requiring greater care in the selection of cuff sizes. Second, the examination is more frequently complicated by the anxiety and restlessness of the patient. Third, the disappearance of Korotkoff sounds (Phase V) is often difficult to hear in children and Phase IV values are often substituted. Fourth, erroneous Korotkoff sounds can be produced inadvertently by the pressure of the stethoscope diaphragm against the antecubital fossa. Finally, the definition of pediatric hypertension has itself been uncertain because of confusion over normal values during childhood. Previous criteria using population data to define the 95th percentile at different ages were erroneously high.(7) Revised criteria for pediatric hypertension, based on data from over 70,000 children, have recently been published (6) (see Clinical Intervention).
Effectiveness of Early Detection
There is a direct relationship between the magnitude of blood pressure elevation and the benefit of lowering pressure. In persons with malignant hypertension, the benefits of intervention are most dramatic; treatment increases five-year survival from near zero (data from historical controls) to 75%.(8) The efficacy of treating moderate hypertension (diastolic blood pressure above 104 mm Hg) is also clear, as demonstrated in the Veterans Administration Cooperative Study on Antihypertensive Agents.(9-11) In this randomized double-blind controlled trial, middle-aged men with diastolic blood pressure above 104 mm Hg experienced a significant reduction in cardiovascular events after treatment with antihypertensive medication.Persons with mild hypertension (diastolic blood pressure of 90-104 mm Hg) also benefit from treatment. This was confirmed in the Hypertension Detection and Follow-Up Program, a randomized controlled trial involving nearly 11,000 hypertensives.(12) The intervention group received standardized pharmacologic treatment (stepped care) while the control group was referred for community medical care. There was a statistically significant 17% reduction in five-year all-cause mortality in the group receiving standardized drug therapy; the subset with mild hypertension experienced a 20% reduction in mortality.(12) Deaths due to cerebrovascular disease, ischemic heart disease, and other causes were also significantly reduced in the stepped care group.(13) Similar results have been reported in other studies, such as the Australian National Blood Pressure Study (14) and the Medical Research Council trial.(15) Although treatment of hypertension is associated with multiple benefits, the greatest effect appears to be in the prevention of cerebrovascular disease.(16) Improved treatment of high blood pressure has been credited with the greater than 50% reduction in age-adjusted stroke mortality that has been observed since 1972.(1,17)
Although the efficacy of antihypertensive treatment has been well established in clinical research, certain factors may influence the magnitude of benefit achieved in actual practice. First, the benefits of treatment may be less significant or less well proven in certain population groups, such as children. Second, nonpharmacologic first-line therapy (e.g., weight reduction, exercise, sodium restriction, decreased alcohol intake) may be less effective than drug therapy in achieving significant and consistent blood pressure reductions. Although it is known that weight reduction and sodium restriction can lower blood pressure,(18,19) the magnitude and duration of reduction in actual practice may be limited by biological factors (e.g., hypertensives who are not salt-sensitive) and the difficulties of maintaining behavioral changes (e.g., weight loss). Finally, compliance with drug therapy may be limited by the inconvenience, side effects, and cost of these agents.(20,21)
Recommendations of Others
Revised recommendations for adults from the National Heart, Lung, and Blood Institute were issued recently by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure,(1) and similar recommendations have been issued by the American Heart Association.(22) These call for routine blood pressure measurement at least once every two years for persons with a diastolic blood pressure below 85 mm Hg and a systolic pressure below 140 mm Hg. Measurements are recommended annually for persons with a diastolic blood pressure of 85-89 mm Hg. Persons with higher blood pressures require more frequent measurements. The Canadian Task Force recommends that all persons aged 25 and over receive a blood pressure measurement during any visit to a physician.(23) The American Academy of Pediatrics and the National Heart, Lung, and Blood Institute recommend that children and adolescents receive annual blood pressure measurements from ages 3-20.(6)Discussion
It is clear from several large clinical trials that lowering blood pressure is beneficial and that the population incidence of several leading causes of death can be reduced through the detection and treatment of high blood pressure. An average diastolic blood pressure reduction of 6-8 mm Hg across the population could reduce the incidence of coronary artery disease by 25% and the incidence of strokes by 50%.(24) At the same time, it is important for clinicians to minimize the potential harmful effects of detection and treatment. For example, if performed incorrectly, sphygmomanometry can produce misleading results. Some hypertensive patients thereby escape detection (false negatives) and some normotensive persons receive inappropriate labeling (false positives), which may have certain psychological, behavioral, and even financial consequences.(25) Treatment of hypertension can also be harmful as a result of medical complications, especially related to drugs. Clinicians can minimize these effects by using proper technique when performing sphygmomanometry, making appropriate use of nonpharmacologic methods, and prescribing antihypertensive drugs with careful adherence to current guidelines.Clinical Intervention
Blood pressure should be measured regularly in all persons aged 3 and above. The optimal interval for blood pressure screening has not been determined and is left to clinical discretion. Current expert opinion is that persons thought to be normotensive should receive blood pressure measurements at least once every two years if their last diastolic and systolic blood pressure readings were below 85 mm Hg and 140 mm Hg, respectively, and annually if the last diastolic blood pressure was 85-89 mm Hg.(1) Sphygmomanometry should be performed in accordance with recommended technique.(*1) Hypertension should not be diagnosed on the basis of a single measurement; elevated readings(**) should be confirmed on more than one reading at each of three separate visits. Once confirmed, patients should receive counseling regarding exercise, weight reduction, dietary sodium intake, and alcohol consumption.(1) Other cardiovascular risk factors, such as smoking and elevated serum cholesterol, should also be discussed. Antihypertensive drugs should be prescribed in accordance with recent guidelines(1) and with attention to current techniques for improving compliance.(20,21)Notes
* Guidelines for Sphygmomanometry
(**) In adults, current blood pressure criteria for the diagnosis are a diastolic pressure of 90 mm Hg or greater or a systolic pressure of 140 mm Hg or greater. (1) In children, the criteria vary with age:(6)
- Patient should be seated with arm bared, supported, and positioned at heart level.
- Patient should have refrained from smoking or ingesting caffeine within 30 minutes before measurement.
- Measurement should begin after five minutes of quiet rest.
- An appropriate cuff size (child, adult, large adult) should be selected; the rubber bladder should encircle at least two thirds of the arm. - Measurements should be taken with a mercury sphygmomanometer, a recently calibrated aneroid manometer, or a validated electronic device.
- Both systolic and diastolic pressures should be recorded; the disappearance of sound (Phase V) indicates the diastolic pressure. - Two or more readings should be averaged; if the first two differ by more than 5 mm Hg, additional readings should be obtained.
Pediatric Blood Pressure Age (Yrs) Diastolic (mm Hg) Systolic (mm Hg) --------------------------------------------------- 0-2 74 112 3-5 76 116 6-9 78 122 10-12 82 126 13-15 86 136References
1. 1988 Joint National Committee. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1988; 148:1023-38.
2. National Center for Health Statistics. Advance report of final mortality statistics, 1986. Monthly Vital Statistics Report (Suppl), vol. 37, Hyattsville, Md.: Public Health Service, 1988. (Publication no. DHHS (PHS) 88-1120.)
3. Tifft CP. Are the days of the sphygmomanometer past? Arch Intern Med 1988; 148:518-9.
4. Pickering TG, James GD, Boddie C, et al. How common is white coat hypertension? JAMA 1988; 259:225-8.
5. Kirkendall WM, Feinleib M, Freis ED, et al. Recommendations for human blood pressure determination by sphygmomanometers. Subcommittee of the AHA Postgraduate Education Committee. Circulation 1980; 62:1146A-55A. 6. Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children--1987. Pediatrics 1987; 79:1-25.
7. Mehta SK. Pediatric hypertension: a challenge for pediatricians. Am J Dis Child 1987; 141:893-4.
8. Hansson L. Current and future strategies in the treatment of hypertension. Am J Cardiol 1988; 61:2C-7C.
9. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. III. Influence of age, diastolic pressure, and prior cardiovascular disease: further analysis of side effects. Circulation 1972; 45:991-1004. 10. Idem. Effects of treatment on morbidity in hypertension: results in patients with diastolic pressures averaging 115 through 129 mm Hg. JAMA 1967; 202:1028-34.
11. Idem. Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic pressures averaging 90 through 114 mm Hg. JAMA 1970; 213:1143-52.
12. Hypertension Detection and Follow-Up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-Up Program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA 1979;242:
13. Idem. Persistence of reduction in blood pressure and mortality of participants in the Hypertension Detection and Follow-Up Program. JAMA 1988; 259:2113-22.
14. Management Committee of the Australian National Blood Pressure Study. The Australian therapeutic trial in mild hypertension. Lancet 1980; 1:1261-7.
15. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. Br Med J 1985; 291:97-104. 16. MacMahon SW, Cutler JA, Furberg CD, et al. The effects of drug treatment for hypertension on morbidity and mortality from cardiovascular disease: a review of randomized, controlled trials. Prog Cardiovasc Dis (Suppl) 1986; 29:99-118. and the declining incidence of stroke. JAMA 1987; 258:214-7.
17. Garraway WM, Whisnant JP. The changing pattern of hypertension and the declining incidence of stroke. JAMA 1987; 258:214-7.
18. Nonpharmacological approaches to the control of high blood pressure. Final report of the Subcommittee on Nonpharmacological Therapy of the 1984 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 1986; 8:444-67.
19. Stamler J, Stamler R. Intervention for the prevention and control of hypertension and atherosclerotic diseases: United States and international experience. Am J Med 1984; 76:13-36.
20. McClellan WM, Hall WD, Brogan D, et al. Continuity of care in hypertension: an important correlate of blood pressure control among aware hypertensives. Arch Intern Med 1988; 148:525-8.
21. National Institutes of Health. The physician's guide: improving adherence among hypertensive patients. Working Group on Health Education and High Blood Pressure Control. Bethesda, Md.: Department of Health and Human Services, 1987.
22. Grundy SM, Greenland P, Herd A, et al. Cardiovascular and risk factor evaluation of healthy American adults. A statement for physicians by an ad hoc committee appointed by the Steering Committee, American Heart Association. Circulation 1987; 75:1340A-62A.
23. Canadian Task Force on the Periodic Health Examination. 1984 update. Can Med Assoc J 1984; 130:2-15.
24. Blackburn H. Public policy and dietary recommendations to reduce the population level of blood cholesterol. Am J Prev Med 1985; 1:3-11. 25. MacDonald LA, Sackett DL, Haynes RB, et al. Labelling in hypertension: a review of the behavioral and psychological consequences. J Chron Dis 1984; 37:933-42.
Screening for Cerebrovascular Disease
Recommendation
There is currently insufficient evidence to recommend for or against auscultation for carotid bruits or noninvasive testing for carotid stenosis as effective screening strategies to prevent cerebrovascular disease in asymptomatic persons. It may be clinically prudent to include cervical auscultation in the physical examination of patients with established risk factors for cerebrovascular or cardiovascular disease (see Clinical Intervention). All patients should be screened for hypertension, and some persons should be tested for high blood cholesterol. Clinicians should also provide counseling about smoking.Burden of Suffering
Cerebrovascular disease is the third leading cause of death in the United States, accounting for nearly 150,000 deaths in 1986.(1) Strokes can result in substantial neurologic deficits as well as serious medical and psychological complications. This illness places an enormous burden on family members and caretakers, and it often necessitates skilled care in an institutional setting. The cost of stroke care in the United States has been estimated at $5 billion per year.(2) The principal risk factors for ischemic stroke are increased age, hypertension, smoking, coronary artery disease, atrial fibrillation, and diabetes.(3-5) Of these, the most important modifiable risk factor is hypertension. Improved treatment of high blood pressure has been credited with the greater than 50% reduction in age-adjusted stroke mortality that has been observed since 1972.(6,7)Efficacy of Screening Tests
Population-based cohort studies have established that persons with carotid artery stenosis are at substantially increased risk for subsequent stroke, myocardial infarction, and death.(8,9) The risk is greater for persons with neurologic symptoms such as transient ischemic attacks. Even in asymptomatic persons, however, it has been proposed that stroke can be prevented by identifying individuals with carotid stenosis and performing endarterectomy on these vessels. Two methods are used to detect carotid artery stenosis: clinical auscultation for carotid bruits and noninvasive studies of the artery. Neck auscultation is an inadequate screening test for carotid stenosis. There is considerable interobserver variation among clinicians in the interpretation of the key auditory characteristics--intensity, pitch, and duration--of importance in predicting stenosis.(10) In addition, a cervical bruit can be heard in 4% of the population over age 40, but the finding is not specific for significant carotid artery stenosis. Between 40% and 75% of arteries with asymptomatic bruits do not have significant compromise in blood flow;(11) similar sounds can also be produced by anatomic variation and tortuosity, venous hum, goiter, and transmitted cardiac murmur.(10,12-14) Finally, hemodynamically significant stenotic lesions may exist in the absence of an audible bruit.(10,12,15)Persons with cervical bruits can be further evaluated with greater accuracy by noninvasive study of the carotid arteries. Techniques include the evaluation of auditory or visual features (spectral analysis phonoangiography, continuous-wave or pulsed Doppler ultrasound, B-mode real-time ultrasound, and duplex scanning combining the latter two) and tests of blood flow in ophthalmic and cranial tributaries of the carotid arteries (oculoplethysmography, ophthalmodynamometry, periorbital directional Doppler ultrasound, and thermography).(12,16) Several of these tests compare favorably with conventional angiography, the reference standard for confirming carotid artery disease.(12) Continuous-wave Doppler ultrasound, for example, has a sensitivity of 87% and a specificity of 91% when angiography is used as the reference criterion.(17) Duplex scanning is also reported to have good agreement with angiographic results.(18)
Effectiveness of Early Detection
The rationale for testing for carotid artery stenosis is that persons with asymptomatic bruits are at increased risk for cerebrovascular disease and myocardial infarction;(8,9,19) thus, information about the degree of stenosis may facilitate interventions to help prevent subsequent stroke. An awareness of the diagnosis may motivate patients to modify other risk factors (e.g., high blood pressure, smoking, hypercholesterolemia, physical inactivity) and to notify clinicians when they first become aware of symptoms of transient ischemic attack. Moreover, performing carotid endarterectomy in some individuals may prevent subsequent cerebral infarction distal to the obstruction.Rigorous evidence that these interventions improve outcome in asymptomatic persons is lacking. It has not been proved, for example, that asymptomatic persons with stenoses detected through screening have a better outcome than do those who first present with symptoms. The proportion of persons with asymptomatic bruits who will experience stroke is relatively small; the annual incidence of stroke (unheralded by transient ischemic attacks) in this population is only 1-3%.(8,9,13,19-21) In those persons who will suffer a stroke, it is unclear from current evidence whether the degree of carotid stenosis provides meaningful information on the risk of infarction(13,19,22) or its location.(8,9) Carotid artery lesions may be less a predictor of thromboembolic strokes than of generalized atherosclerotic disease; persons with carotid artery disease are considerably more likely to die from ischemic heart disease than from a cerebrovascular event.(8,9) Finally, no controlled studies have examined changes in the behavior of patients on learning the results of carotid artery examinations.
Nonetheless, the performance of carotid endarterectomy for lesions detected through screening may provide an important means of preventing subsequent stroke. Reliable data about the benefits and risks of performing this procedure on asymptomatic persons are lacking. Two studies reporting improved outcomes after endarterectomy suffered from selection biases and inconsistent measurement criteria.(14,23) Other trials often involved persons with neurologic symptoms (e.g., transient ischemic attacks) and do not provide compelling evidence of substantial benefit.(24-26) In response to the need for more reliable data, four large multicenter trials are currently under way.(27,28) They are expected to provide results in coming years on the efficacy of endarterectomy in both asymptomatic and symptomatic persons.
In the meantime, data from a number of studies have generated some concern that the risks associated with carotid endarterectomy, especially when performed at centers with high complication rates, may exceed potential benefits in asymptomatic persons with bruits, who have a relatively low risk of subsequent stroke even without treatment (see above). A number of studies have reported a perioperative mortality of about 3%,(29-31) and a perioperative stroke rate ranging between 2% and 24%, depending on the surgical expertise of the center.(11,30-35) However, these studies suffer from important methodologic problems, and definitive data on the risk-benefit ratio await the completion of the trials in progress. Until this information becomes available, it remains uncertain whether the detection of asymptomatic carotid artery stenoses through screening results in improved outcome.
Recommendations of Others
Although auscultation of the carotid arteries is widely considered a routine component of the physical examination, the Canadian Task Force(36) and other reviewers(15,37) have argued against routine screening for carotid bruits in asymptomatic persons. A consensus panel has recently recommended a baseline noninvasive study of the carotid arteries in persons considered at high risk for extracranial carotid arterial disease.(38)Discussion
The most effective interventions to prevent stroke are recommended even in the absence of cerebrovascular disease: the identification and treatment of hypertension, smoking cessation, and lowering of serum cholesterol.(32) By comparison, the relative effectiveness of screening for carotid artery disease is less certain. Although the auscultation of bruits can detect some cases of carotid artery stenosis and noninvasive testing can confirm the presence of significant obstructive lesions, the detection of these lesions may be of limited clinical value if the diagnosis cannot be followed by an intervention that prevents subsequent stroke. Until evidence regarding carotid endarterectomy becomes available from ongoing clinical trials, the effectiveness of screening for carotid artery disease remains in question. Nonetheless, there is little evidence of harm from cervical auscultation, a procedure widely considered a routine component of the physical examination, and the auscultatory findings may provide especially useful risk assessment information for patients with other risk factors for cerebrovascular and cardiovascular disease. This is especially important for persons with a history of transient ischemic attacks. In the absence of careful questioning by the clinician about previous neurologic symptoms, elderly patients are often presumed erroneously to be "asymptomatic."Although noninvasive testing can provide more accurate information on the degree of stenosis, economic considerations preclude routine noninvasive testing of the general population. About 1 million Americans have carotid bruits, and it is estimated that it would cost as much as $200 million to perform noninvasive testing on all of them.(15) The costs of carotid endarterectomy are also an important consideration. Over 100,000 carotid endarterectomies were performed in 1985,(39) making it the third most common operation in the United States.(40) In light of the substantial costs associated with the treatment and support of stroke victims, the expense of diagnostic testing and surgery are justified if these procedures prove to be effective in preventing stroke, but evidence of this awaits the results of ongoing research.
As an alternative to screening, antiplatelet therapy with aspirin offers a possible method of reducing the risk of stroke in asymptomatic persons. Most clinical trials to date, however, have examined the role of aspirin only as a secondary prevention strategy (i.e., in persons with previous transient ischemic attacks or strokes) and have often failed to demonstrate a statistically significant effect on subsequent strokes.(41-44) A recent meta-analysis of 25 trials of antiplatelet therapy concluded that antiplatelet treatment of low-risk persons may be of some benefit in preventing subsequent disease, but only if the risk of serious side effects (e.g., cerebral hemorrhage) remains quite low.(45) A stronger body of evidence exists for the role of aspirin in the primary prevention of coronary artery disease.
Clinical Intervention
There is currently insufficient evidence to recommend for or against auscultation for carotid bruits and noninvasive testing for carotid stenosis as an effective screening strategy to prevent cerebrovascular disease in asymptomatic persons. It may be clinically prudent to include cervical auscultation in the physical examination of asymptomatic patients with established risk factors for cerebrovascular or cardiovascular disease (e.g., increased age, hypertension, smoking, coronary artery disease, atrial fibrillation, diabetes) and in all patients with neurologic symptoms (e.g., transient ischemic attacks) or a previous history of cerebrovascular disease. Elderly patients should be asked whether they have experienced previously the symptoms of transient ischemic attack or other neurologic illnesses. All patients should receive routine screening for hypertension and some persons should be tested for high blood cholesterol. Clinicians should provide counseling to stop smoking, to engage in regular exercise, and to decrease intake of dietary fat.References
1. National Center for Health Statistics. Advance report of final mortality statistics, 1986. Monthly Vital Statistics Report, vol. 37, no. 6. Hyattsville, Md.: Public Health Service, 1988. (Publication no. DHHS (PHS) 88-1120.)
2. Hodgson TA, Kopstein AN. Health care expenditures for major diseases in 1980. Health Care Fin Rev 1984; 5:1-12.
3. Schoenberg BS. Epidemiology of cerebrovascular disease. South Med J 1979; 72:331-6.
4. Davis PH, Dambrosia JM, Schoenberg DG, et al. Risk factors for ischemic stroke: a prospective study in Rochester, Minnesota. Ann Neurol 1987; 22:319-27.
5. Wolf PA, D'Agostino RB, Kannel WB, et al. Cigarette smoking as a risk factor for stroke: the Framingham Study. JAMA 1988; 259:1025-9. 6. 1988 Joint National Committee. The 1988 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1988; 148:1023-38.
7. Garraway WM, Whisnant JP. The changing pattern of hypertension and the declining incidence of stroke. JAMA 1987; 258:214-7.
8. Heyman A, Wilkinson WE, Heyden S, et al. Risk of stroke in asymptomatic persons with cervical arterial bruits: a population study in Evans County, Georgia. N Engl J Med 1980; 302:838-41.
9. Wolf PA, Kannel WB, Sorlie P, et al. Asymptomatic carotid bruit and risk of stroke: the Framingham study. JAMA 1981; 245:1442-5.
10. Chambers BR, Norris JW. Clinical significance of asymptomatic neck bruits. Neurology 1985; 35:742-5.
11. Quinones-Baldrich WJ, Moore WS. Asymptomatic carotid stenosis: rationale for management. Arch Neurol 1985; 42:378-82.
12. Caplan LR. Carotid-artery disease. N Engl J Med 1986; 315:886-8. 13. Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med 1986; 315:860-5.
14. Thompson JE, Patman RD, Talkington CM. Asymptomatic carotid bruit: long-term outcome of patients having endarterectomy compared with unoperated controls. Ann Surg 1978; 188:308-16.
15. Kuller LH, Sutton KC. Carotid artery bruit: is it safe and effective to auscultate the neck? Stroke 1984; 15:944-7.
16. Solomon S. Recent developments in the diagnosis and management of stroke. Bull NY Acad Med 1986; 62:250-61.
17. D'Alton JG, Norris JW. Carotid Doppler evaluation in cerebrovascular disease. Can Med Assoc J 1983; 129:1184-9.
18. Stavenow L, Bjerre P, Lindgarde F. Experiences of duplex ultrasonography of carotid arteries performed by clinicians: correlation to angiography. Acta Med Scand 1987; 222:31-6. 19. Bogousslavsky J, Despland PA, Regli F. Asymptomatic tight stenosis of the internal carotid artery: long-term prognosis. Neurology 1986; 36:861-3.
20. Meissner I, Wiebers DO, Whisnant JP, et al. The natural history of asymptomatic carotid artery lesions. JAMA 1987; 258:2704-7. 21. Hennerici M, Hulsbomer HB, Hefter H, et al. Natural history of asymptomatic extracranial arterial disease: results of a long-term prospective study. Brain 1987; 110:777-91.
22. Yatsu FM, Fields WS. Asymptomatic carotid bruit: stenosis or ulceration, a conservative approach. Arch Neurol 1985; 42:383-5. 23. Busuttil RW, Baker JD, Davidson RK, et al. Carotid artery stenosis: hemodynamic significance and clinical course. JAMA 1981; 245:1438-41. 24. Fields WS, Maslenikov V, Meyer JS, et al. Joint study of extracranial arterial occlusion. V. Progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions. JAMA 1970; 211:1993-2003. 25. Bauer RB, Meyer JS, Gotham JE, et al. A controlled study of surgical treatment of cerebrovascular disease: forty-two months' experience with 183 cases. In: Millikan CH, Siekert RG, Whisnant JP, eds. Cerebral vascular diseases. New York: Grune and Stratton, 1966.
26. Shaw DA, Venables GS, Cartlidge NEP, et al. Carotid endarterectomy in patients with transient cerebral ischemia. J Neurol Sci 1984; 64:45-53. 27. Walker MD, National Institute of Neurological and Communicative Disorders and Stroke. Personal communication, February 1988. 28. Callow AD, Caplan LR, Correll JW, et al. Carotid endarterectomy: what is its current status? Am J Med 1988; 85:835-8.
29. Dyken ML, Pokras R. The performance of endarterectomy for disease of the extracranial arteries of the head. Stroke 1984; 15:948-50. 30. Brott T, Labutta RJ, Kempozinski RF. Changing patterns in the practice of carotid endarterectomy in a large metropolitan area. JAMA 1986; 255:2609-12.
31. Slavish LG, Nicholas GG, Gee W. Review of a community hospital experience with carotid endarterectomy. Stroke 1984; 15:956-9. 32. Grotta JC. Current medical and surgical therapy for cerebrovascular disease. N Engl J Med 1987; 317:1505-16.
33. Warlow C. Carotid endarterectomy: does it work? Stroke 1984; 15:1068-76.
34. Rubin JR, Pitluk HC, King TA, et al. Carotid endarterectomy in a metropolitan community: the early results after 8535 operations. J Vasc Surg 1988; 7:256-60.
35. Zurbruegg HR, Seiler RW, Grolimund P, et al. Morbidity and mortality of carotid endarterectomy: a literature review of the results in the last 10 years. Acta Neurochir (Wien) 1987; 84:3-12.
36. Canadian Task Force on the Periodic Health Examination. 1984 update. Can Med Assoc J 1984; 130:1-16.
37. Frame PS. A critical review of adult health maintenance. Part 1. Prevention of atherosclerotic diseases. J Fam Pract 1986; 22:341-6. 38. Toole JF, Adams H Jr, Dyken M, et al. Evaluation for asymptomatic carotid artery atherosclerosis: a multidisciplinary consensus statement. South Med J 1988; 81: 1549-52.
39. Winslow CM, Solomon DH, Chassin MR, et al. The appropriateness of carotid endarterectomy. N Engl J Med 1988; 318:721-7.
40. Barnett HJM, Plum F, Walton JN. Carotid endarterectomy: an expression of concern. Stroke 1984; 15:941-3.
41. Fields WS, Lemak NA, Frankowski RF, et al. Controlled trial of aspirin in cerebral ischemia. Circulation 1980; 62:V90-6.
42. Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med 1978; 299:53-9. 43. Bousser MG, Eschwege E, Haguenau M, et al. "AICLA" controlled trial of aspirin and dipyrimadole in the secondary prevention of atherothrombotic cerebral ischemia. Stroke 1983; 14:5-14. 44. UK-TIA Study Group. United Kingdom transient ischemic attack (UK-TIA) aspirin trial: interim results. Br Med J 1988; 296:316-20. 45. Antiplatelet Trialists' Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J 1988; 296:320-31.
Screening for Peripheral Arterial Disease
Recommendation
Routine screening for peripheral arterial disease in asymptomatic persons is not recommended. Clinicians should be alert to signs of peripheral arterial disease in persons at increased risk (see Clinical Intervention) and should thoroughly evaluate those patients with clinical evidence of vascular disease.Burden of Suffering
Peripheral arterial disease (PAD) becomes increasingly common with age; it is estimated that 12-15% of the population over age 50 have this disease.(1-3) Increased mortality has been documented in patients with PAD, a disease that is strongly associated with coronary artery disease and that shares many of the same risk factors.(1,2,4-7) Although only a small proportion of individuals with PAD and intermittent claudication develop skin breakdown or limb loss, pain and associated disability often restrict ambulation and the overall quality of life.(1,4,7) Persons at increased risk for PAD include cigarette smokers and persons with diabetes mellitus or hypertension.(1,4,7) Diabetic PAD is responsible for about one-half of all amputations.(1)Efficacy of Screening Tests
There is evidence that a history of intermittent claudication and the palpation of peripheral pulses are unreliable techniques for the detection of PAD.(1,3,6,8) In one study, a battery of noninvasive tests for PAD were administered to 624 hyperlipidemic subjects aged 38-82.(5) In this population, the positive predictive value and sensitivity of a classic history of claudication were only 54.5% and 9.2%, respectively, when compared with the results of formal noninvasive testing. The sensitivity of an abnormal posterior tibial pulse was 71.2%, the positive predictive value was 48.7%, and the specificity was 91.3%. An abnormal dorsalis pedis pulse had a sensitivity of only 50%; this artery is congenitally absent in 10-15% of the population.(8) The authors concluded that symptoms and abnormal pulses are not pathognomonic for PAD.(5) Greater accuracy has been achieved with noninvasive testing using Doppler ankle-arm pressure ratios, measurement of reactive hyperemia after exercise, pulse reappearance time, ultrasound duplex scanning, and plethysmography.(1,9,10) At present, however, additional data on sensitivity, specificity, and positive predictive value in asymptomatic populations are needed before noninvasive testing can be considered for routine screening.Effectiveness of Early Detection
The rationale for the early detection of PAD is that risk factor modification following detection might lower subsequent morbidity and mortality from PAD and systemic atherosclerotic disease. By virtue of its strong association with coronary atherosclerosis, the early diagnosis of PAD might also lead to the detection of asymptomatic coronary artery disease. Firm evidence of these benefits is lacking, however; there has been little research to examine whether asymptomatic persons with PAD have lower morbidity or mortality with treatment than do symptomatic patients. It is clear that certain interventions are beneficial in symptomatic persons. There is evidence, for example, that patients who stop smoking have marked improvement in PAD symptoms and reduced overall cardiovascular mortality.(1,7,11) Certain antithrombotic drugs may also be of benefit.(12) These and other measures used in the treatment of PAD symptoms may also be effective preventive interventions in asymptomatic persons, but the evidence is less rigorous.(1,4) Examples include walking programs, control of weight and blood pressure, correction of elevated serum lipids and glucose, proper foot care, and certain drugs.Recommendations of Others
There are no official recommendations for physicians to screen asymptomatic persons for PAD, although inspection of the skin and palpation of peripheral pulses are often included in the physical examination of the extremities.Discussion
There is insufficient evidence that routine screening for PAD in asymptomatic persons is effective in reducing morbidity or mortality from this disease. However, many of the behavioral interventions that are prescribed after detecting PAD--smoking cessation blood pressure control, and exercise -- can be recommended even in the absence of screening and are of proven value in the prevention of other atherosclerotic conditions, such as coronary artery and cerebrovascular disease.Clinical Intervention
Routine screening for peripheral arterial disease in asymptomatic persons is not recommended. Clinicians should be alert to signs of PAD in persons at increased risk (persons over age 50, smokers, diabetics) and should thoroughly evaluate those patients with clinical evidence of vascular disease. Clinicians should screen for hypertension and hypercholesterolemia, and they should provide appropriate counseling regarding the use of tobacco products, exercise, and nutritional risk factors for atherosclerotic disease.References
1. Strandness DE, Didisheim P, Clowes AW, et al, eds. Vascular diseases: current research and clinical applications. Orlando, Fla.: Grune and Stratton, Inc., 1987.
2. Criqui MH, Fronek A, Barrett-Connor E, et al. The prevalence of peripheral arterial disease in a defined population. Circulation 1985; 71:510-5.
3. Lombardi G, Polotti R, Polizzi N, et al. Prevalence of asymptomatic peripheral vascular disease in a group of patients older than 50. J Am Geriatr Soc 1986; 34:551-2.
4. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham study. J Am Geriatr Soc 1985; 33:13-8.
5. Criqui MH, Fronek A, Klauber MR, et al. The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from noninvasive testing in a defined population. Circulation 1985; 71:516-22.
6. Criqui MH, Coughlin SS, Fronek A. Noninvasively diagnosed peripheral arterial disease as a predictor of mortality: results from a prospective study. Circulation 1985; 72:768-73.
7. Rutherford RB, ed. Vascular surgery, 2nd ed. Philadelphia: WB Saunders Company, 1984:553.
8. Kappert A, Winsor T. Diagnosis of peripheral vascular diseases. Philadelphia: FA Davis Company, 1972:26.
9. Barnes RW. Noninvasive diagnostic techniques in peripheral vascular disease. Am Heart J 1979; 97:241-4.
10.Moneta GL, Strandness DE. Peripheral arterial duplex scanning. J Clin Ultrasound 1987; 15:645-51.
11.Jonason T, Bergstrom R. Cessation of smoking in patients with intermittent claudication: effects of the risk of peripheral vascular complications, myocardial infarction and mortality. Acta Med Scand 1987; 221:253-60.
12.Arcan JC, Blanchard J, Boissel JP, et al. Multicenter double-blind study of ticlopidine in the treatment of intermittent claudication and the prevention of its complications. Angiology 1988; 39:802-11.
Screening for Breast Cancer
Recommendation
All women over age 40 should receive an annual clinical breast examination. Mammography every one to two years is recommended for all women beginning at age 50 and concluding at approximately age 75 unless pathology has been detected. It may be prudent to begin mammography at an earlier age for women at high risk for breast cancer (see Clinical Intervention). Although the teaching of breast self-examination is not specifically recommended at this time, there is insufficient evidence to recommend any change in current breast self-examination practices.Burden of Suffering
In the United States in 1989, an estimated 142,000 new cases of breast cancer will occur in women, and 43,000 women will die of this disease.(1) Breast cancer accounts for 28% of all newly diagnosed cancers in women and 18% of female cancer deaths.(1) The age-adjusted mortality rate from breast cancer has been almost unchanged over the past 10 years. Breast cancer is the leading contributor to premature cancer mortality in women.(2) Because women of the "baby boom" generation are now reaching age 40, the number of breast cancer cases and deaths will increase substantially over the next 40 years unless age-specific incidence and mortality rates decline.Important risk factors for breast cancer include sex, geographic location, and age. Breast cancer is much more common in women than men,(1) and the highest rates of breast cancer exist in North America and northern Europe. In American women, the annual incidence of breast cancer increases rapidly with age, from approximately 20 per 100,000 at age 30 to 180 per 100,000 at age 50.(3) The risk for women with a family history of premenopausally diagnosed breast cancer in a first-degree relative is about two to three times that of the average woman of the same age in the general population.(3-5) Women with previous breast cancer are at increased risk, as are women with a history of benign breast disease.(3,4,6) Other factors with some clinical or statistical association with breast cancer include first pregnancy after age 30, menarche before age 12, menopause after age 50, obesity, high socioeconomic status, and a history of ovarian or endometrial cancer.(3,4,7)
Efficacy of Screening Tests
The three screening tests usually considered for breast cancer are clinical examination of the breast, x-ray mammography, and breast self- examination (BSE). The sensitivity and specificity of clinical examination of the breast varies with the skill and experience of the examiner and with the characteristics of the individual breast being examined. Over the five years of the Breast Cancer Detection Demonstration Project (BCDDP), the estimated sensitivity of clinical examination alone was 45%.(8) Data from studies using manufactured breast models show that mean sensitivity among registered nurses was 65% compared with 55% for untrained women.(8,9) Detection by physicians was 87% for lumps 1.0 cm in diameter, a size comparable to that used in the studies involving nurses and women.(8,10)Estimates of the sensitivity of mammography depend on a number of factors, including the size of the lesion, the age of the patient, and the extent of follow-up to determine the proportion of "negative" masses that are later found to be malignant (i.e., false negatives). The average sensitivity of the combined clinical examination and mammography in the five years of the BCDDP was 75%. The estimated sensitivity for mammography alone was 71%.(8) A recent report from a multicenter trial estimated the sensitivity of an initial mammographic examination to be about 75%.(11) In a study of 499 women, mammography had an overall sensitivity of 78%, but it was reduced to 70% when only lesions under 1.0 cm in diameter were considered.(12) Sensitivity for all breast cancers in women over 50 was 87%, while sensitivity in women under 51 was 56%. In the 10-year follow-up of a Dutch study, the sensitivity of mammography was 80% for women aged 50 and above and 60% for those under 50.(13)
The specificity of mammography is about 94-99%.(11,13) Even with this excellent specificity, however, false positives can occur frequently if the test is performed routinely in populations with a low prevalence of breast cancer. Thus, most abnormal results of mammograms performed on young women without known risk factors for breast cancer are likely to be false positives. BCDDP data show that only 10% of women with positive (mammography and clinical examination) screening results were found to have cancer,(14) and a recent multicenter trial reported a positive predictive value of only 7% for initial mammographic examinations.(11) There is no study that shows that the sensitivity or specificity of mammography is increased when "baseline" mammograms are available for comparison.
Studies of mammography have shown large variations in observer (radiologist interpreter) performance.(15-17) In a study using 100 xeroradiographic mammograms, including 10 of women with proven cancers, the number of lesions identified as "suspicious for cancer" by 9 radiologists ranged from 10 to 45.(15) In a large breast cancer screening study in Canada, agreement was poor between radiologists at five screening centers and a single reference radiologist.(16)
Because exposure to ionizing radiation can be carcinogenic, widespread testing by mammography has the potential of producing some cases of radiation-induced cancer. However, radiation exposure from mammography has decreased dramatically with the development of dedicated mammography equipment and low-dose techniques.(18,19) Radiation exposure varies with breast size as well as with the specific equipment and technique used.(17-19) Thus, it is important for operators to use low-dose equipment and proper technique to limit unnecessary exposure to ionizing radiation during mammography.
Self-examination of the breast appears to be a less sensitive form of screening than clinical examination, and its specificity remains uncertain. Using reasonable assumptions applied to data from the BCDDP, the estimated overall sensitivity of BSE alone was found to be 26% in women also screened by mammography and physical examination.(8) Estimated BSE sensitivity in the BCDDP varied by age group; it was most sensitive for women 35-39 years of age (41%) and least sensitive for women aged 60-74 (21%).(8) Among participants in a breast cancer registry, BSE was reported to detect 34% of cancers.(8,20)
In a study of women's ability to detect breast lumps, untrained volunteers were able to detect 25% of lumps ranging in size from 0.25 to 3.0 cm in diameter.(8,21) The study showed that the sensitivity of BSE can be improved by training. A 30-minute training session increased the mean lump detection rate to 50%.(21) Although training sessions have increased detection rates, they also increase false-positive rates. False-positive BSE may result in unnecessary physician visits, heightened anxiety levels in women, and increased radiographic and surgical procedures. No study yet reported has directly compared the sensitivity or specificity of self-examination with that of clinical examination and mammography, in part due to the methodologic difficulties with properly designing such a study.
Effectiveness of Early Detection
The results of several large studies have convincingly demonstrated the effectiveness of clinical examination and mammographic screening for breast cancer in women aged 50 and older. The Health Insurance Plan of Greater New York (HIP) in 1963 began a randomized prospective study of clinical examination and mammography in 62,000 women.(22) The follow-up of this group now exceeds 18 years. In women who were over age 50 at the time of entry into the study, mortality from breast cancer in the screened group was more than 50% lower than in the unscreened group at five years. This effect has gradually decreased to about 21% after 18 years.In the Swedish "two county study," a randomized controlled trial was begun in 1977 using single-view mammograms to screen about 78,000 women every 20 to 36 months.(23) After six years of follow-up, the group of women who were over age 50 at the time of entry showed a significant decrease in breast cancer mortality. A recently reported randomized controlled trial in Malmo, Sweden, found that in 8.8 years of follow-up women aged 55 and older who received periodic mammographic screening had a significant reduction in mortality from breast cancer.(24) In the Netherlands, a screening program of single-view mammography every two years for women over age 35 was introduced in 1975.(25) After seven years, this case-control study showed that mammography significantly reduced the risk of mortality from breast cancer in women 50 and over. A case-control study in Italy also reported a strong inverse relationship between mortality from breast cancer and mammographic screening in women aged 50 and older.(26)
More than 280,000 women in the United States were screened with a combination of clinical examination and mammography during the Breast Cancer Detection Demonstration Project.(27) This demonstration project was not designed as a research study, however, and lacked a control group. Effectiveness was inferred by comparing the outcome among BCDDP participants with that observed in national cancer surveillance programs. These comparisons showed that BCDDP participants had higher survival rates than those of breast cancer cases in national sample groups.(27) The finding of increased five-year survival was confirmed in a recent analysis of the BCDDP data, which also demonstrated that cumulative mortality from breast cancer was 80% of that expected of BCDDP participants without diagnosed breast cancer at the start of the study.(28) Due to the absence of internal controls in the original design of this study, however, it is unclear to what extent these differences were due to selection bias, lead-time bias, and other sources of bias.(29)
Although most authorities agree on the benefits of screening women aged 50 and over for breast cancer, there has been some uncertainty about the effectiveness of mammographic screening in women between the ages of 40 and 49.(29-31) Mammography for women under 50 has not been shown to be effective in reducing breast cancer mortality in the Swedish "two county trial"(23) or the Dutch study,(25) although the follow-up period may not have been of sufficient duration to detect an effect on mortality. The Malmo, Sweden, trial also reported no benefit for women under age 55, but the mean follow-up period was less than 9 years; moreover, 24% of women in the control group are thought to have received mammography outside of the screening program and as many as 26% of women in the intervention program did not attend screening.(24)
Follow-up data from the HIP study suggest that women aged 40-49 who receive periodic mammography and clinical examination may experience a reduction of about 25% in breast cancer mortality, but the investigators and others have not found this difference to be statistically significant.(22,32) Interpretations of statistical significance when analyzing these data are influenced by a number of factors, some of which include the definition of the 40-49 age group (i.e., age at entry into study vs. age at diagnosis), the length of follow-up, and the denominator chosen to calculate mortality (women entering the study vs. cases of breast cancer). The difference in mortality is statistically significant when cases of breast cancer are used as the denominator and age at entry defines the age group.(33) Statistical significance may, however, be less a consideration than clinical significance. Although nearly 28,000 women aged 40-49 entered the HIP trial, after over 18 years there were only 16 fewer breast cancer deaths among screened women (61 deaths) than in the control group (77 deaths), a difference of about 12 in 10,000 women screened.(33,34)
There are few data regarding the optimal frequency of mammography or the age at which to discontinue screening in the asymptomatic elderly. Although an annual interval is widely recommended, a recent analysis of data from the Swedish "two county" study found little evidence that an annual interval conferred greater benefit than screening every two years.(35) Although there are no reliable data on the optimal age to conclude mammographic screening, there are uncertainties regarding the effectiveness of screening beyond age 75 in asymptomatic women with consistently normal results on previous examinations. The incidence of new disease in this population may be relatively low and thus the effectiveness of screening may be limited, but reliable data are lacking.
Although no large study has quantitated the effectiveness of breast cancer screening for women in high-risk groups, it is apparent that these women have a greater probability of developing the disease.(30) If screening can reduce the risk of mortality from breast cancer, there may be a greater effect from screening those in high-risk groups, but studies confirming this effect are lacking. Further, established risk factors are present in less than one-quarter of women with breast cancer, so that a screening program restricted to high-risk groups is likely to miss the majority of cases.
Retrospective studies of the effectiveness of BSE have produced mixed results, and BSE has not been studied in a prospective controlled trial with mortality as an outcome.(8) A recent meta-analysis of pooled data from 12 studies found that women who practiced BSE before their illness were less likely to have a tumor of 2.0 cm or more in diameter or to have evidence of extension to lymph nodes.(36) The studies from which these data were obtained, however, suffer from important design limitations and provide little information on clinical outcome (e.g., breast cancer mortality).
Recommendations of Others
The American Cancer Society(37) and the National Cancer Institute(38) recommend monthly BSE and regular clinical examination of the breast for all women; baseline mammography between ages 35 and 40, followed by annual or biennial mammograms from ages 40-49; and annual mammograms beginning at age 50. These recommendations have been supported by other groups such as the American Medical Association,(39) the American College of Obstetricians and Gynecologists,(40) and the American College of Radiology.(41) A joint statement on screening for breast cancer involving many of these organizations is currently being developed under the organization of the American College of Radiology.(42)In contrast, the Canadian Task Force,(43) American College of Physicians,(44) and other authorities(45,46) support annual clinical breast examinations for all women starting at age 40 but do not recommend beginning yearly mammography until age 50.
The World Health Organization states that there is insufficient evidence that BSE is effective in reducing mortality from breast cancer.(47) Thus, it does not recommend BSE screening programs as public health policy, although it finds equally insufficient evidence to change such programs where they already exist.
Discussion
At this time, there is little doubt that breast cancer screening by clinical examination and mammography has the potential of reducing mortality from breast cancer for women aged 50 and above. Most studies have not shown a clear benefit from mammography in women aged 40-49. Studies that will provide important information on this topic are in progress.(48) In the meantime, it is unclear whether the effects on breast cancer mortality achieved by screening women aged 40-49 are of sufficient magnitude to justify the costs and potential adverse effects from false-positive results that may occur as a result of widespread screening.(34) Until more definitive data become available, it is reasonable to concentrate the large effort and expense associated with mammography on women in the age group for which benefit has been most clearly demonstrated: those aged 50 and above. Annual clinical breast examination is a prudent recommendation for women aged 40-49.Conclusions about the cost-effectiveness of mammography have not been universally accepted. Charges vary greatly in the United States, but in 1984 they averaged about $80-$100 per procedure.(30) For screening mammography to be widely used, it is likely that this charge would have to be reduced to $50 or less.(49) Even if only $50 were charged per mammogram, surveying all of the women in the United States over 40 years of age would cost more than $2 billion a year.(50) Others have drawn attention to the additional costs of biopsies performed on the basis of false-positive mammography results.(30) There are also concerns about the availability of the large numbers of trained radiologists needed to interpret additional screening examinations.(50,51)
Wide variation is found in the quality and consistency of mammography, as well as in the accuracy of interpretation, radiation exposure, and cost.(15-18,30) Radiation exposure during routine mammography is frequently much higher than the optimal doses or the minimal achievable doses usually quoted.(17-19) All of the above caveats about mammography argue for caution in the recommendation of mammographic screening, as well as for the selection of mammographers who maintain only the highest standards of quality.
The accuracy of BSE as currently practiced appears to be considerably inferior to that of the combination of clinical breast examination and mammography. False-positive BSE, especially among younger women in whom breast cancer is uncommon, can lead to needless anxiety and expense. With the present state of knowledge, it is difficult to make a recommendation about the inclusion or exclusion of teaching BSE during the periodic health examination. The WHO policy, neither recommending new BSE teaching programs nor changing existing ones, appears to be a prudent interim approach pending new data.(47)
Clinical Intervention
Annual clinical breast examination is recommended for all women aged 40 and above. Mammography every one to two years is recommended for all women beginning at age 50 and concluding at approximately age 75 unless pathology is detected. Obtaining "baseline" mammograms before age 50 is not recommended. For the special category of women at high risk because of a family history of premenopausally diagnosed breast cancer in first-degree relatives, it may be prudent to begin regular clinical breast examination and mammography at an earlier age (e.g., age 35). Clinicians should refer patients to mammographers who use low-dose equipment and adhere to high standards of quality control. Although teaching BSE is not specifically recommended at this time, there is insufficient evidence to recommend any change in current BSE practices.Note
See Appendix A for the U.S. Preventive Services Task Force Table of Ratings for this topic. See also the relevant Task Force background paper: O'Malley MS, Fletcher SW. U.S. Preventive Services Task Force: screening for breast cancer with breast self-examination: a critical review. JAMA 1987; 257:2196-203.References
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 2. Leads from MMWR. Premature mortality due to breast cancer--United States, 1984. JAMA 1987; 3:229-31.
3. McLellan GL. Screening and early diagnosis of breast cancer. J Fam Pract 1988; 26:561-8.
4. Kelsey JL, Hildreth NG, Thompson WD. Epidemiological aspects of breast cancer. Radiol Clin North Am 1983; 21:3-12.
5. Kelsey JL. A review of the epidemiology of human breast cancer. Epidemiol Rev 1979; 1:74-109.
6. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985; 312:146-51. 7. Seidman H, Stellman SD, Mushinski MH. A different perspective on breast cancer risk factors: some implications of nonattributable risk. CA 1982; 32:301-13.
8. O'Malley MS, Fletcher SW. Screening for breast cancer with breast self examination. JAMA 1987; 257:2197-293.
9. Haughey BP, Marshall JR, Mettlin C, et al. Nurses' ability to detect nodules in silicone breast models. Oncol Nurs Forum 1984; 1:37-42. 10. Fletcher SW, O'Malley MS, Bunce LA. Physicians' abilities to detect lumps in silicone breast models. JAMA 1985; 253:2224-8.
11. Baines CJ, McFarlane DV, Miller AB. Sensitivity and specificity of first screen mammography in 15 NBSS centres. Can Assoc Radiol J 1988; 39:273-6.
12. Eideiken S. Mammography and palpable cancer of the breast. Cancer 1988; 61:263-5.
13. Peeters PH, Verbeck AL, Hendricks JH, et al. The predictive value of positive test results in screening for breast cancer by mammography in the Nijmegen programme. Br J Cancer 1987; 56:667-71.
14. Wright CJ. Breast cancer screening: a different look at the evidence. Surgery 1986; 100:594-8.
15. Boyd NF, Wolfson C, Moskowitz M, et al. Observer variation in the interpretation of xeromammograms. JNCI 1982; 68:357-63.
16. Baines CJ, McFarlane DV, Wall C. Audit procedures in the national breast screening study: mammography interpretation. J Can Assoc Radiol 1986; 37:256-60.
17. Gadkin BM, Feig SA, Muir HD. The technical quality of mammography in centers participating in a regional breast cancer awareness program. Radiographics 1988; 8:133-45.
18. Kimme-Smith C, Bassett LW, Gold RH. Evaluation of radiation dose, focal spot, and automatic exposure of newer film-screen mammography units. AJR 1987; 149:913-7.
19. Prado KL, Rakowski JT, Barragan F, et al. Breast radiation dose in film/screen mammography. Health Physics 1988; 55:81-3.
20. Gould-Martin K, Paganini-Hill A, Cassagrande C, et al. Behavioral and biological determinants of surgical stage of breast cancer. Prev Med 1982; 11:441-53.
21. Hall DC, Adams CK, Stein GH, et al. Improved detection of human breast lesions following experimental training. Cancer 1980; 46:408-11.
22. Shapiro S, Venet W, Strax P, et al., eds. Periodic screening for breast cancer. Baltimore, Md.: Johns Hopkins Press, 1988.
23. Tabar L, Fagerberg CJG, Gad A, et al. Reduction in mortality from breast cancer after mass screening with mammography: randomised trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare. Lancet 1985; 1:829-32.
24. Andersson I, Aspegren K, Janzon L, et al. Mammographic screening and mortality from breast cancer: the Malmo Mammographic Screening Trial. Br Med J 1988; 297:943-8.
25. Verbeek ALM, Hendricks JHCL, Hollan PR, et al. Reduction of breast cancer mortality through mass screening with modern mammography: first results of the Nijmegen Project, 1975-1981. Lancet 1984; 1:1222-4. 26. Palli D, Del Turco MR, Buiatti E, et al. A case-control study of the efficacy of a non-randomized breast cancer screening program in Florence (Italy). Int J Cancer 1986; 38:501-4.
27. Seidman H, Gelb SK, Silverberg E, et al. Survival experience in the breast cancer detection demonstration project. CA 1987; 37:258-90. 28. Morrison AS, Brisson J, Khalid N. Breast cancer incidence and mortality in the Breast Cancer Detection Demonstration Project. JNCI 1988; 80:1540-7.
29. Bailar JC. Mammography before age 50 years? An editorial. JAMA 1988; 259:1548-9.
30. Eddy DM, Hasselblad V, McGivney W, et al. The value of mammography screening in women under age 50 years. JAMA 1988; 259:1512-9. 31. Dodd GD, Taplin S. Is screening mammography routinely indicated for women between 40 and 50 years of age? J Fam Pract 1988; 27:313-20. 32. Day NE, Baines CJ, Chamberlain J, et al. UICC project on screening for cancer: report of the workshop on screening for breast cancer. Int J Cancer 1986; 38:303-8.
33. Chu KC, Smart CR, Tarone RE. Analysis of breast cancer mortality and stage distribution by age for the Health Insurance Plan clinical trial. JNCI 1988; 80:1125-32.
34. Eddy DM. Breast cancer screening (letter). JNCI 1989; 81:234-5. 35. Tabar L, Faberberg G, Day NE, et al. What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial. Int J Cancer 1987; 55:547-51.
36. Hill D, White V, Jolley D, et al. Self examination of the breast: is it beneficial? Meta-analysis of studies investigating breast self examination and extent of disease in patients with breast cancer. Br Med J 1988; 297:271-5.
37. American Cancer Society. Summary of current guidelines for the cancer- related checkup: recommendations. New York: American Cancer Society, 1988.
38. National Cancer Institute. Working guidelines for early detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
39. American Medical Association. Mammography screening in asymptomatic women 40 years and older (Resolution 93, I-87). Report of the Council on Scientific Affairs, Report F (A-88). Chicago, Ill.: American Medical Association, 1988.
40. American College of Obstetricians and Gynecologists. Standards for obstetric-gynecologic services, 6th ed. Washington, D.C.: American College of Obstetricians and Gynecologists, 1985.
41. American College of Radiology. Policy statement: guidelines for mammography. Reston, Va.: American College of Radiology, 1982. 42. Dodd GD, American College of Radiology. Personal communication, February 1989.
43. Canadian Task Force on the Periodic Health Examination. The periodic health examination: 2. 1985 update. Can Med Assoc J 1986; 134:724-9. 44. American College of Physicians. The use of diagnostic tests for screening and evaluating breast lesions. Ann Intern Med 1985; 103:147-51.
45. Baines CJ. Breast-cancer screening: current evidence on mammography and implications for practice. Can Fam Physician 1987; 33:915-22. 46. Frame PS. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
47. World Health Organization. Self-examination in the early detection of breast cancer. Bull WHO 1984; 62:861-9.
48. Miller AB. Screening for breast cancer. Breast Cancer Res Treat 1983; 3:143-56.
49. Sickles EA, Weber WN, Galvin HB, et al. Mammographic screening: how to operate successfully at low cost. Radiology 1986; 160:95-7. 50. Dodd GD. The history and present status of radiographic screening for breast carcinoma. Cancer (Suppl 7) 1987; 1:1671-4.
51. Bassett LW, Diamond JJ, Gold RH, et al. Survey of mammography practices. AJR 1987; 149:1149-52.
Screening for Colorectal Cancer
Recommendation
There is insufficient evidence to recommend for or against fecal occult blood testing or sigmoidoscopy as effective screening tests for colorectal cancer in asymptomatic persons. There are also inadequate grounds for discontinuing this form of screening where it is currently practiced or for withholding it from persons who request it. It may be clinically prudent to offer screening to persons aged 50 and older with known risk factors for colorectal cancer (see Clinical Intervention).Burden of Suffering
Colorectal cancer is the second most common form of cancer in the United States and has the second highest mortality rate, accounting for over 150,000 new cases and 61,000 deaths each year.(1) On average, clinically diagnosed colorectal cancer deprives its victims of about six to seven years of life.(2) Estimated 10-year survival is 74% in persons with localized disease, 36% in persons with regional metastases, and only 5% in those with disseminated disease.(3) In addition to the mortality associated with colorectal cancer, this disease and its treatment can produce significant morbidity; surgical resection, colostomies, chemotherapy, and radiotherapy can cause considerable discomfort and disruption of lifestyle. Principal risk factors for colorectal cancer include a family history of colorectal cancer, familial polyposis coli, or cancer family syndrome; a personal history of endometrial, ovarian, or breast cancer; and a history of longstanding ulcerative colitis, adenomatous polyps, or previous colorectal cancer.Efficacy of Screening Tests
The principal screening tests for detecting colorectal cancer in asymptomatic persons are the digital rectal examination, fecal occult blood testing, and sigmoidoscopy. The digital rectal examination is of limited value as a screening test for colorectal cancer. The examining finger, which is only 7-8 cm long, has limited access even to the rectal mucosa, which is 11 cm in length.(4) It is estimated that less than 10% of colorectal cancers can be palpated by digital rectal examination.(4)A second screening maneuver is fecal occult blood testing. Positive reactions on guaiac-impregnated cards, the most common form of testing, can signal the presence of bleeding from premalignant adenomas and early-stage colorectal cancers. The guaiac test can also produce false-positive results, however. The ingestion of foods containing peroxidases,(5) iron compounds,(6) and gastric irritants such as salicylates and other anti- inflammatory agents(7,8) can produce false-positive test results for neoplasia. Gastrointestinal bleeding can be caused by conditions other than colorectal adenomas or cancer, such as hemorrhoids, diverticulosis, and peptic ulcers. As a result, when occult blood testing is performed on asymptomatic persons, the majority of positive reactions are falsely positive for neoplasia. When fecal occult blood testing is performed in groups of asymptomatic persons over age 50, the positive predictive value is only about 5-10% for carcinoma and 30% for adenomas.(9-14) This large proportion of false-positive results is an important concern because of the discomfort, cost, and occasional complications associated with follow-up diagnostic tests, such as barium enema and colonoscopy.(15)
Fecal occult blood testing can also miss cases, especially small adenomas and colorectal malignancies that do not bleed or bleed only intermittently.(16,17) About 20 mL of daily blood loss is necessary to produce consistently positive results on guaiac cards.(18-20) Other causes of false-negative results include nonuniform distribution of blood in feces,(21) antioxidants such as ascorbic acid that interfere with test reagents,(22) and extended delays in testing stool samples.(18) Rehydration of stored slides can improve sensitivity, but this also increases the number of false-positive reactions.(23) The exact sensitivity of fecal occult blood testing in asymptomatic persons is not known; reported sensitivities of 50-92% are based on studies of persons with known colorectal malignancies(16,24-27) and are not applicable to the general population. The reported sensitivity in asymptomatic persons ranges from 20-25% in some studies (which were not properly designed to measure sensitivity)(14,28) to about 75% in preliminary data from ongoing clinical trials.(29,30)
HemoQuant (SmithKline Diagnostics, Sunnyvale, CA), a test for quantitative measurement of hemoglobin in the stool, has been suggested as a more sensitive and specific screening test for occult blood loss.(31-33) In addition to providing quantitative information, the test may be less influenced by dietary peroxidases, specimen storage, hydration, ascorbic acid, and upper gastrointestinal bleeding. The increased sensitivity and specificity for blood, however, may come at the expense of decreased specificity for neoplasia.(34) Also, the test is considerably more expensive than conventional guaiac cards.(34,35) Since specific cut-point criteria for defining a positive test have yet to be developed, the HemoQuant test is not ready for widespread clinical use.
The third screening test for colorectal cancer is sigmoidoscopy. Sigmoidoscopic screening in asymptomatic persons detects approximately 1-4 cancers per 1000 examinations.(36,37) However, the sensitivity and diagnostic yield of this form of screening varies with the type of instrument: the rigid (25 cm) sigmoidoscope, the short (35 cm) flexible fiberoptic sigmoidoscope, and the long (60 cm or 65 cm) flexible fiberoptic sigmoidoscope. Since only 30% of colorectal cancers occur in the distal 20 cm of bowel, and only 50-60% occur in or distal to the sigmoid colon,(38-41) the length of the sigmoidoscope has a direct effect on case detection.(42-46) The rigid sigmoidoscope, which has an average depth of insertion of about 20 cm(42-48) and allows examination to just above the rectosigmoid junction,(49) can detect only about 25-30% of colorectal cancers. The 35 cm flexible sigmoidoscope, however, can visualize about 50-75% of the sigmoid colon. Longer 60 cm and 65 cm instruments can reach the proximal end of the sigmoid in 80% of examinations(50,51) and thus can detect 50-60% of colorectal cancers. Researchers have recently examined the feasibility of introducing the 105 cm flexible sigmoidoscope into the family practice setting,(52) but it is as yet unclear whether the added length substantially increases the rate of detection of premalignant or malignant lesions.
Sigmoidoscopy can also produce "false-positive" results, primarily by detecting polyps that are unlikely to become malignant during the patient's lifetime. Autopsy studies have shown that as many as 10-33% of older adults have colonic polyps at death,(53) but only 2-3% have colorectal cancer.(54-56) Depending on the type of adenomatous polyp, an estimated 5-40% eventually become malignant,(57) a process that takes an average of 10-15 years.(58,59) It follows that the majority of asymptomatic persons with colonic polyps discovered on routine sigmoidoscopic examination will not develop clinically significant malignancy during their lifetime. For these persons, interventions that typically follow such a discovery (i.e., biopsy, polypectomy, frequent colonoscopy), procedures that are costly, anxiety provoking, and potentially harmful, are unlikely to be of significant clinical benefit.
Effectiveness of Early Detection
Persons with early-stage colorectal cancer on diagnosis appear to have longer survival than persons with advanced disease. The estimated 10-year survival is 74% for localized lesions (Dukes' A or B), 36% for tumors with regional invasion (Dukes' C) and 5% for disseminated disease (Dukes' D).(3) There is little information, however, on the extent to which lead-time and length biases account for these differences, or whether asymptomatic persons detected through screening have lower mortality than cases detected without screening. Two controlled trials in the United States(9-12) and three additional clinical trials under way in Europe(29,30,60) are expected to provide this information, primarily for fecal occult blood testing, but final results will not be available for several years.A randomized controlled trial of multiphasic health examinations has often been cited as evidence that sigmoidoscopic screening can lower mortality from colon cancer.(61-63) Study group participants were urged annually to schedule a multiphasic checkup; controls received no such urging. Among the many interventions in the multiphasic checkup, persons aged 40 and older were encouraged to receive a rigid sigmoidoscopic examination. After 16 years of follow-up, the investigators found that the study group had significantly lower mortality from colorectal cancer, one-half the incidence of cancer of the distal bowel, a greater proportion of localized tumors, and a lower case-fatality rate.(64) The investigators have urged that these results be interpreted cautiously, however, since the trial was not designed specifically to examine the effect of sigmoidoscopy, but rather the multiphasic checkup as a whole. In addition, the role of sigmoidoscopy has been questioned by the investigators after a recent data analysis revealed little difference between study and control groups in the proportion of subjects receiving sigmoidoscopy or in the rate of detection or removal of polyps.(64)
The results of two large screening programs have also been cited in support of sigmoidoscopic screening.(65-67) Both studies found that persons receiving periodic rigid sigmoidoscopic examinations had less advanced disease and better survival from colon cancer than was typical of the general population. One program, which performed 21,150 initial examinations and 92,650 subsequent sigmoidoscopies, reported an incidence of colorectal cancer that was 85% less than that of the general population within the state.(65,66) The participants in both studies, however, were recruited in a nonrandomized fashion and may not have been entirely comparable to the general population in terms of risk for colorectal cancer. Since neither study included internal controls, it is difficult to conclude with certainty that the favorable outcomes observed in the studies were due to sigmoidoscopic screening rather than to other characteristics of the screening program or participants. Other methodologic concerns relating to the designs of these investigations have been outlined in recent reviews.(64,68)
An important consideration in assessing the effectiveness of sigmoidoscopic screening is the potential iatrogenic risk associated with the procedure. Complications from sigmoidoscopy are relatively rare in asymptomatic persons but can be potentially serious. Perforations occur in approximately 1 out of 5000-7000 rigid sigmoidoscopic examinations.(36,69) Although there are fewer data available on flexible sigmoidoscopy, the complication rate appears to be less than or equal to that observed for rigid sigmoidoscopy.
Even if screening is effective in reducing colorectal cancer mortality, there is little information on the optimal age to begin screening or the frequency with which it should be performed. Theoretically, the potential yield from screening increases beyond age 50 since the incidence of colorectal cancer after this age doubles every seven years.(3) In the absence of direct evidence from clinical studies, some have attempted to evaluate the effectiveness of different screening schedules through mathematical modeling. One such study suggested that delaying the onset of screening from age 40 to age 50 would reduce effectiveness by about 5-10% in persons with a family history of colon cancer.(2) The same study estimated that a screening interval of three to five years would preserve 70-90% of the effectiveness of annual screening in persons with a family history of colon cancer.(2) Another modeling study found that an interval of two to four years would allow detection of 95% of all polypoid lesions greater than 13 mm in diameter.(70)
Recommendations of Others
The American Cancer Society recommends annual digital rectal examination for all adults beginning at age 40 and annual stool occult blood testing beginning at age 50. Sigmoidoscopy every three to five years is recommended beginning at age 50.(71) Similar recommendations have been issued by the National Cancer Institute,(72) the American Gastroenterological Association,(73) the American Society for Gastrointestinal Endoscopy,(73) and other groups. The Canadian Task Force makes no mention of sigmoidoscopy but recommends annual stool occult blood testing for high-risk persons over age 45.(74) Other experts on the periodic health examination have advised against routine sigmoidoscopy but advocate fecal occult blood testing every two years between ages 40 and 50 and annually thereafter.(37,75)Discussion
An important limitation to the effectiveness of screening for colorectal cancer is the ability of patients and clinicians to comply with testing. Patients may not comply with fecal occult blood testing for a variety of reasons,(60,76) but compliance rates are generally higher than for sigmoidoscopy. Although the introduction of flexible fiberoptic instruments has made sigmoidoscopy more acceptable to patients,(77) the procedure remains uncomfortable, embarrassing, and expensive, and therefore many patients may be reluctant to agree to this test. A recent survey of patients over age 50 found that only 13% indicated a desire to receive sigmoidoscopy after being informed of recommendations that they should receive the test every three to five years;(71) the most common reasons cited by the patients for declining the test were cost (31%), discomfort (12%), and fear (9%).(78) In a study in which sigmoidoscopy was repeatedly recommended, only 31% of participants consented to the procedure,(61-63) but this study was performed during years when the rigid sigmoidoscope was typically used for the procedure. Compliance rates as low as 6-12% have been reported.(37) Physicians may also be reluctant to perform screening sigmoidoscopy on asymptomatic persons. It has been estimated that a typical family physician with 3000 active patients (one-third aged 50 or older) would have to perform five sigmoidoscopies daily to initially screen the population and two daily procedures for subsequent screening.(37) In addition, examinations using the more effective long (60 cm or 65 cm) flexible sigmoidoscopes are more time-consuming(39-43) and require more extensive training(79-81) than do those using shorter instruments.Another limitation to screening is cost. Although a formal cost- effectiveness analysis of screening for colorectal cancer is beyond the scope of this chapter, it should be noted that the economic implications associated with the widespread performance of fecal occult blood testing and sigmoidoscopy are not insignificant. A single flexible sigmoidoscopic examination costs between $100 and $200.(2,15,82) A policy of routine occult blood and sigmoidoscopic screening of all persons in the United States over age 50 (about 62 million persons) would be expected to cost over $1 billion per year in direct charges.(82) Others have calculated that Hemoccult (SmithKline Diagnostics, Sunnyvale, CA) screening alone could cost the United States and Canada between $500 million and $1 billion each year.(83) The costs of performing screening tests on a large proportion of the U.S. population may be justified if morbidity and mortality from colorectal cancer can be prevented through screening, but firm evidence to this effect is not yet available.
In summary, whether screening asymptomatic persons will significantly reduce mortality from colorectal cancer remains uncertain and awaits the results of ongoing clinical trials. In the absence of such evidence, widespread screening of asymptomatic persons for colonic polyps or colorectal cancer appears to be premature. The logistical difficulties of performing fecal occult blood tests and sigmoidoscopy on a large proportion of the U.S. population are not insignificant, due to the limited acceptability of the tests and the expense of performing screening and follow-up on a large proportion of the population. Moreover, the tests have potential adverse effects that must be considered, such as false-positive results that lead to expensive and potentially harmful diagnostic procedures. Screening of persons at increased risk for colorectal cancer may be justified on the basis of clinical prudence, but direct evidence that screening of this population is effective is also lacking.
Clinical Intervention
There is insufficient evidence to recommend for or against fecal occult blood testing or sigmoidoscopy as effective screening tests for colorectal cancer in asymptomatic persons. There are also inadequate grounds for discontinuing this form of screening where it is currently practiced or for withholding it from persons who request it. It may be clinically prudent to offer screening to persons aged 50 and older who have first-degree relatives with colorectal cancer; a personal history of endometrial, ovarian, or breast cancer; or a previous diagnosis of inflammatory bowel disease, adenomatous polyps, or colorectal cancer. These patients should receive current information regarding the benefits, risks, and uncertainties of both occult blood tests and sigmoidoscopy. Fecal occult blood testing should adhere to current guidelines for dietary preparation, sample collection, and storage.84 Sigmoidoscopy should be performed by a trained examiner. The instrument should be selected on the basis of examiner expertise and patient comfort. The optimal interval for colorectal cancer screening is uncertain and is left to clinical discretion. Periodic colonoscopy is recommended for all persons with a family history of familial polyposis coli or cancer family syndrome.Note
See Appendix A for the U.S. Preventive Services Task Force Table of Ratings for this topic. See also the relevant Task Force background papers: Knight KK, Fielding JE, Battista RN. Occult blood screening for colorectal cancer. JAMA 1989; 261:587-93; and Selby JV, Friedman GD. Sigmoidoscopy in the periodic health examination of asymptomatic adults. JAMA 1989; 261:595-601.References
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 2. Eddy DM, Nugent FW, Eddy JF, et al. Screening for colorectal cancer in a high-risk population: results of a mathematical model. Gastroenterology 1987; 92:682-92.
3. National Cancer Institute. Surveillance, epidemiology and end-results: incidence and mortality data, 1973-77. National Cancer Institute Monograph No. 57. Bethesda, Md.: National Cancer Institute, 1981. 4. Schottenfeld D, Winawer SJ. Large intestine. In: Schottenfeld D, Sherlock P, eds. Colorectal cancer: prevention, epidemiology, and screening. New York: Raven Press, 1980:175-80.
5. Illingworth DG. Influence of diet on occult blood tests. Gut 1965; 6:595-8.
6. Lifton LJ, Kreiser J. False-positive stool occult blood tests caused by iron preparations: a controlled study and review of the literature. Gastroenterology 1982; 83:860-3.
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8. Rees WD, Turnberg LA. Reappraisal of the effects of aspirin on the stomach. Lancet 1980; 2:410-3.
9. Winawer SJ, Andrews M, Flehinger B, et al. Progress report on controlled trial of fecal occult blood testing for the detection of colorectal neoplasia. Cancer 1980; 45:2959-64.
10. Gilbertsen VA, Church TR, Grewe FJ. The design of a study to assess occult-blood screening for colon cancer. J Chron Dis 1980; 33:107-14. 11. Gilbertsen VA, McHugh RB, Schuman LM, et al. The earlier detection of colorectal cancers: a preliminary report of the results of the occult blood study. Cancer 1980; 45:2899-901.
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13. Windeler J, Kobberling J. Colorectal cancer and Haemoccult. A study of its value in mass screening using meta-analysis. Int J Color Dis 1987; 2:223-8.
14. Bang KM, Tillett S, Hoar SK, et al. Sensitivity of fecal Hemoccult testing and flexible sigmoidoscopy for colorectal cancer screening. J Occup Med 1986; 28:709-13.
15. Brandeau ML, Eddy DM. The workup of the asymptomatic patient with a positive fecal occult blood test. Med Decis Making 1987; 7:32-46. 16. Crowley ML, Freeman LD, Mottet MD, et al. Sensitivity of guaiac- impregnated cards for the detection of colorectal neoplasia. J Clin Gastroenterology 1983; 5:127-30.
17. Griffith CDM, Turner DJ, Saunders JH. False-negative results of Hemoccult test in colorectal cancer. Br Med J 1981; 283:472. 18. Morris DW, Hansell JR, Ostrow D, et al. Reliability of chemical tests for fecal occult blood in hospitalized patients. Dig Dis 1976; 21:845-52.
19. Heinrich HC, Icagic F. Comparative studies on the "in vivo" sensitivity of four commercial pseudoperoxidase-based faecal occult blood tests in relation to actual blood losses as calculated from measured whole body 59Fe-elimination rates. Klin Wochenschr 1980; 58:1283-97. 20. Stroehlein JR, Fairbanks VF, McGill DB, et al. Hemoccult detection of fecal occult blood quantitated by radioassay. Dig Dis 1976; 21:841-4. 21. Rosenfield RE, Kochwa S, Kaczera Z, et al. Nonuniform distribution of occult blood in feces. Am J Clin Pathol 1979; 71:204-9.
22. Jaffe RM, Kasten B, Young DS, et al. False-negative stool occult blood tests caused by ingestion of ascorbic acid (vitamin C). Ann Intern Med 1975; 83:824-6.
23. Wells HJ, Pagano JF. "Hemoccult" (TM) test-reversal of false-negative results due to storage. Gastroenterology 1977; 72:1148.
24. Doran J, Hardcastle JD. Bleeding patterns in colorectal cancer: the effect of aspirin and the implications for faecal occult blood testing. Br J Surg 1982; 69:711-3.
25. Macrae FA, St John DJB. Relationship between patterns of bleeding and Hemoccult sensitivity in patients with colorectal cancers or adenomas. Gastroenterology 1982; 82:891-8.
26. Ribet A, Frexinos J, Escourrou J, et al. Occult blood tests and colorectal tumours. Lancet 1980; 1:417.
27. Applegate WB, Spector MH. Colorectal cancer screening. J Commun Health 1981; 7:138-51.
28. Rozen P, Ron E, Fireman Z, et al. The relative value of fecal occult blood tests and flexible sigmoidoscopy in screening for large bowel neoplasia. Cancer 1987; 60:2553-8.
29. Kewenter J, Bjork S, Haglind E, et al. Screening and rescreening for colorectal cancer: a controlled trial of fecal occult blood testing in 27,700 subjects. Cancer 1988; 62:645-51.
30. Hardcastle JD, Armitage NC, Chamberlain J, et al. Fecal occult blood screening for colorectal cancer in the general population: results of a controlled trial. Cancer 1986; 58:397-403.
31. Schwartz S, Dahl J, Ellefson M, et al. The "HemoQuant" test: a specific and quantitative determination of heme (hemoglobin) in feces and other materials. Clin Chem 1983; 29:2061-7.
32. Ahlquist DA, McGill DB, Schwartz S, et al. HemoQuant, a new quantitative assay for fecal hemoglobin: comparison with Hemoccult. Ann Intern Med 1984; 101:297-302.
33. Idem. Fecal blood levels in health and disease: a study using HemoQuant. N Engl J Med 1985; 312:1422-8.
34. Joseph AM, Crowson TW, Rich EC. Cost effectiveness of HemoQuant versus Hemoccult for colorectal cancer screening. J Gen Intern Med 1988; 3:132-8.
35. Peterson WL, Fordtran JS. Quantitating the occult. N Engl J Med 1985; 312:1448-9.
36. Bolt RJ. Sigmoidoscopy in detection and diagnosis in the asymptomatic individual. Cancer 1971; 28:121-2.
37. Frame PS. Screening flexible sigmoidoscopy: is it worthwhile? An opposing view. J Fam Pract 1987; 25:604-7.
38. Cady N, Persson AV, Monson DO, et al. Changing patterns of colorectal carcinoma. Cancer 1974; 33:422-6.
39. Rhodes JB, Holmes FF, Clark GM. Changing distribution of primary cancers in the large bowel. JAMA 1977; 238:1641-3.
40. Abrams JS, Reines HD. Increasing incidence of right-sided lesions in colorectal cancer. Am J Surg 1979; 137:522-6.
41. Greene FL. Distribution of colorectal neoplasms. A left-to-right shift of polyps and cancer. Am J Surg 1983; 49:62-5.
42. Winnan G, Berci G, Panish J, et al. Superiority of the flexible to the rigid sigmoidoscope in routine proctosigmoidoscopy. N Engl J Med 1980; 302:1011-2.
43. Bohlman TW, Katon RM, Lipshutz GR, et al. Fiberoptic pansigmoidoscopy: an evaluation and comparison with rigid sigmoidoscopy. Gastroenterology 1977; 72:644-9.
44. Winawer SJ, Leidner SD, Boyle C, et al. Comparison of flexible sigmoidoscopy with other diagnostic techniques in the diagnosis of rectocolon neoplasia. Dig Dis Sci 1979; 24:277-81.
45. Marks G, Boggs HW, Castro AF, et al. Sigmoidoscopic examinations with rigid and flexible fiberoptic sigmoidoscopes in the surgeon's office. Dis Col Rect 1979; 22:162-9.
46. Protell RL, Buenger N, Gilbert DA, et al. The short colonoscope: preliminary analysis of a comparison with rigid sigmoidoscopy and Hemoccult testing. Gastrointest Endosc 1978; 24:208.
47. Nivatvongs S, Fryd DS. How far does the proctosigmoidoscope reach? N Engl J Med 1980; 303:380-2.
48. Nicholls RJ, Dube S. The extent of examination by rigid sigmoidoscopy. Br J Surg 1982; 69:438.
49. Shatz BA, Freitas EL. Area of colon visualized through the sigmoidoscope. JAMA 1954; 156:717-9.
50. Gillespie PE, Chambers TJ, Chan KW, et al. Colonic adenomas: a colonoscopic survey. Gut 1979; 20:240-5.
51. Lehman GA, Buchner DM, Lappas JC. Anatomical extent of fiberoptic sigmoidoscopy. Gastroenterology 1983; 84:803-8.
52. Dervin JV. Feasibility of 105-cm flexible sigmoidoscopy in family practice. J Fam Pract 1986; 23:341-4.
53. Correa P, Strong JP, Reif A, et al. The epidemiology of colorectal polyps: prevalence in New Orleans and international comparisons. Cancer 1977; 39:2258-64.
54. Hughes LE. The incidence of benign and malignant neoplasms of the colon and rectum: a post mortem study. NZ J Surg 1968; 38:30-5. 55. Rickert RR, Auerback O, Garfinke L, et al. Adenomatous lesions of the large bowel: an autopsy survey. Cancer 1979; 43:1847-57. 56. Williams AR, Balasooriy BAW, Day DW. Polyps and cancer of the large bowel: a necropsy study in Liverpool. Gut 1982; 23:835-42. 57. Muto T, Bussey HJR, Morson BC. The evolution of cancer of the colon and rectum. Cancer 1975; 36:2251-70.
58. Morson BC. Evolution of cancer of the colon and rectum. Cancer 1974; 34:845-9.
59. Idem. The evolution of colorectal carcinoma. Clin Radiol 1984; 35:425-31.
60. Kronborg O, Fenger C, Sndergaard O, et al. Initial mass screening for colorectal cancer with fecal occult blood test. A prospective randomized study at Funen in Denmark. Scan J Gastroenterol 1987; 22:677-86.
61. Cutler JL, Ramcharan S, Feldman R, et al. Multiphasic checkup evaluation study. 1. Methods and population. Prev Med 1973; 2:197-206. 62. Dales LG, Friedman GD, Collen MF. Evaluating periodic multiphasic health checkups: a controlled trial. J Chronic Dis 1979; 32:385-404. 63. Friedman GD, Collen MF, Fireman BH. Multiphasic health checkup evaluation: a 16-year follow-up. J Chronic Dis 1986; 39:453-63. 64. Selby JV, Friedman GD, Collen MF. Sigmoidoscopy and mortality from colorectal cancer: the Kaiser Permanente Multiphasic Evaluation Study. J Clin Epidemiol 1988; 41:427-34.
65. Gilbertsen VA. Proctosigmoidoscopy and polypectomy in reducing the incidence of rectal cancer. Cancer 1974; 34:936-9.
66. Gilbertsen VA, Nelms JM. The prevention of invasive cancer of the rectum. Cancer 1978; 41:1137-9.
67. Hertz REL, Deddish MR, Day E. Value of periodic examinations in detecting cancer of the colon and rectum. Postgrad Med 1960; 27:290-4. 68. Morrison A. Screening in chronic disease. New York: Oxford University Press, 1985.
69. Nelson RL, Abcarian H, Prasad ML. Iatrogenic perforation of the colon and rectum. Dis Colon Rectum 1982; 25:305-8.
70. Carroll RLA, Klein M. How often should patients be sigmoidoscoped? A mathematical perspective. Prev Med 1980; 9:741-6.
71. American Cancer Society. Guidelines for the cancer-related checkup: guidelines and rationale. CA 1980; 30:194-240.
72. National Cancer Institute. Working guidelines for early cancer detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
73. Fleischer DE, Goldberg SB, Browning TH, et al. Detection and surveillance of colorectal cancer. JAMA 1989; 261:580-5. 74. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 1193-1254.
75. Frame PS. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
76. Blalock SJ, DeVellis BM, Sandler RS. Participation in fecal occult blood screening: a critical review. Prev Med 1987; 16:9-18. 77. Winawer SJ, Miller C, Lightdale C, et al. Patient response to sigmoidoscopy: a randomized, controlled trial of rigid and flexible sigmoidoscopy. Cancer 1987; 60:1905-8.
78. Petravage J, Swedberg J. Patient response to sigmoidoscopy recommendations via mailed reminders. J Fam Pract 1988; 27:387-9. 79. Shapiro M. Flexible fiberoptic sigmoidoscopy: the long and the short of it. Gastrointest Endosc 1984; 30:114-6.
80. Griffin JW. Flexible fiberoptic sigmoidoscopy: longer may not be better for the "nonendoscopist." Gastrointest Endosc 1985; 31:347-8. 81. Weissman GS, Winawer SJ, Baldwin MP, et al. Multicenter evaluation of training of non-endoscopists in flexible sigmoidoscopy. CA 1987; 37:26-30.
82. Clayman CB. Mass screening for colorectal cancer: are we ready? JAMA 1989; 261:609.
83. Frank JW. Occult-blood screening for colorectal carcinoma: the yield and the costs. Am J Prev Med 1985; 1:18-24.
84. Gnauck R, Macrae FA, Fleisher M. How to perform the fecal occult blood test. CA 1984; 34:134-7.
Screening for Cervical Cancer
Recommendation
Regular Papanicolaou (Pap) testing is recommended for all women who are or have been sexually active (see Clinical Intervention). Pap smears should begin with the onset of sexual activity and should be repeated every one to three years at the physician's discretion. They may be discontinued at age 65 if previous smears have been consistently normal.Burden of Suffering
Approximately 13,000 new cases of cervical cancer are diagnosed each year, and about 7000 women die from this disease annually.(1) Although the five-year survival rate is about 90% for persons with localized cervical cancer, it is considerably lower (about 40%) for persons with advanced disease.(1) The incidence of invasive cervical cancer has decreased significantly over the last 40 years, due in large part to organized early detection programs.(2) Although all sexually active women are at risk for cervical cancer, the disease is more common among women of low socioeconomic status and those with a history of multiple sexual partners or early onset of sexual intercourse.(3-5)Efficacy of Screening Test
The principal screening test for cervical cancer is the Pap smear. Precise data on the sensitivity and specificity of this test are lacking due to methodologic problems. Depending on study design, false-negative rates of 1-80% have been reported;(6,7) a range of 20-45% has been most frequently quoted, primarily in studies comparing normal test results with subsequent smears.(8-12) Although reliable data are lacking, specificity is probably greater than 90%(7) and may be as high as 99%.(12) The test-retest reliability of Pap smears is also influenced by variations in the expertise and procedures of different cytopathology laboratories. A significant proportion of diagnostic errors may be attributable to laboratory error. In one study of over 300 laboratories given slides with known cytologic diagnoses, false-negative diagnoses were made in 7.5% of smears with moderate dysplasia or frank malignancy, and false-positive diagnoses were made in 8.9% of smears with no more than benign atypia.(6)There are important potential adverse effects associated with errors in the interpretation of Pap smears. False-negative results are of significance because carcinoma in situ or more invasive lesions may escape detection and progress to more advanced disease during the period between tests. The potential adverse effects of false-positive results include patient anxiety regarding the risk of cervical cancer, as well as the unnecessary inconvenience, discomfort, and expense of follow-up diagnostic procedures.
Effectiveness of Early Detection
Early detection of cervical neoplasia provides an opportunity to prevent or delay progression to invasive cancer by performing clinical interventions such as colposcopy, conization, localized excision, and, when necessary, hysterectomy.(13) There is evidence that early detection through routine Pap testing and treatment of precursor cervical intraepithelial neoplasia can lower mortality from cervical cancer. Correlational studies in the United States, Canada, and several European countries comparing cervical cancer data over time have shown dramatic reductions in the incidence of invasive disease following the implementation of cervical screening programs.(14-19) Case-control studies have shown a strong negative association between screening and invasive disease, also suggesting that screening is protective.(20-23) These observational studies do not constitute direct evidence that screening was responsible for the findings,(24) and randomized controlled trials to provide such evidence have not been performed. Nonetheless, the large body of supportive evidence accumulated to date has prompted the adoption of routine cervical cancer screening in many countries and makes performance of a controlled trial of Pap smears unlikely for ethical reasons.The effectiveness of cervical cancer screening increases when Pap testing is performed more frequently.(2,21) Aggressive dysplastic and premalignant lesions are less likely to escape detection when the interval between smears is short. There are, however, diminishing returns as frequency is increased.(2,20,25) Although studies have shown that reducing the interval between Pap smears from 10 years to 5 years is likely to achieve a significant reduction in the risk of invasive cervical cancer, case-control studies and mathematical modeling have demonstrated that increasing to a 2- to 3-year interval offers only slight added benefit.(2,5,20) There is little evidence that women who receive annual screening are at significantly lower risk for invasive cervical cancer than are women who are tested every three to five years. These findings were confirmed in a major study of eight cervical cancer screening programs in Europe and Canada involving over 1.8 million women.(26) According to this report, the cumulative incidence of invasive cervical cancer was reduced 64.1% when the interval between Pap tests was 10 years, 83.6% at 5 years, 90.8% at 3 years, 92.5% at 2 years, and 93.5% at 1 year. These estimates were for women aged 35-64 who had at least one screen before age 35, and they are based on the assumption of 100% compliance.
Recommendations of Others
Although inconsistent guidelines on Pap testing have been issued in the past, a consensus recommendation was adopted recently by the American Cancer Society, the National Cancer Institute, the American College of Obstetricians and Gynecologists, the American Medical Association, the American Nurses Association, the American Academy of Family Physicians, and the American Medical Women's Association.(27) It recommends annual Pap smears for all women who are or have been sexually active or have reached age 18. The recommendation permits Pap testing less frequently once three or more annual smears have been normal and if recommended by the physician. The organizations did not recommend an age to discontinue Pap testing.The 1980 National Institutes of Health Consensus Conference on Cervical Cancer Screening(3) and the 1982 Canadian Task Force on Cervical Cancer Screening Programs(28) recommended that Pap testing begin when a woman becomes sexually active or reaches age 18, and that it be discontinued at age 60 if previous screening has been adequate and Pap smears have been consistently negative. The consensus conference recommended an interval of one to three years after two normal annual smears. The Canadian Task Force recommended annual Pap testing until age 35 followed by rescreening every five years.
Discussion
There are important economic considerations to performing Pap tests every year, rather than every two to three years, since this policy could double or triple the total number of smears taken on over 77 million American women at risk.(29) Although there is at least some epidemiologic data to support Pap testing as frequently as every two to three years,(5,20) annual testing appears to be of only limited added benefit in lowering mortality.(26) It has been estimated that screening women aged 20-64 every three years reduces cumulative incidence of invasive cervical cancer by 91%, requires about 15 tests per woman, and yields 96 cases for every 100,000 Pap smears. Annual screening reduces incidence by 93%, but requires 45 tests and yields only 33 cases for every 100,000 tests.(26)Annual testing, however, is common. A survey of recently trained gynecologists found that 97% recommend a Pap test at least once a year.(30) The preference of many clinicians for performing annual Pap smears is based on concerns that less frequent testing may result in more harm than good, but reliable scientific data to support these opinions are lacking. Specifically, advocates of annual testing have expressed concerns that data demonstrating little added value to annual testing are based on retrospective studies and mathematical models that are subject to biases and invalid assumptions; that an interval longer than one year may permit aggressive, rapidly growing cancers to escape early detection; that the public may obtain Pap smears at a lower frequency than that publicized in recommendations; that a longer interval might affect compliance among high- risk women, a group with poor coverage even with an annual testing policy; that repeated testing may offset the false-negative rate of the Pap smear; that the test is inexpensive and safe; and that a large proportion of women believe it is important to have an annual Pap test and, while visiting the clinician, may receive other preventive interventions.(31) Definitive evidence to support these concerns is lacking.
Women who do not engage in sexual intercourse are not at risk for cervical cancer and therefore do not require screening.(3,4,28) In addition, screening of women who have only recently become sexually active (e.g., adolescents) is likely to have low yield. The incidence of invasive cancer in women under age 25 is only about 1-3 per 100,000, a rate that is much lower than that of older age groups.(12) One study found that most women with cervical intraepithelial neoplasia who had become sexually active at age 18 were not diagnosed with severe dysplasia or carcinoma in situ until age 30.(4)
Although invasive cervical cancer is uncommon at young ages, a number of authorities advocate starting screening with the onset of sexual activity.(3,27,28) This policy is based in part on the concern that a proportion of young women with cervical intraepithelial neoplasia may have an aggressive cell type that can progress rapidly and undetected if screening is delayed to a later age. The exact incidence and natural history of aggressive disease in young women remains uncertain, however. Another reason given for early screening is the concern that the incidence of cervical dysplasia occurring in young women appears to be on the rise, coincident with the increasing sexual activity of adolescents. On these grounds, testing should begin by age 18, since about 60% of American teenagers are sexually active by this age.(32) Screening in the absence of a history of sexual intercourse may be justified if the credibility of the sexual history is in question.
When screening is initiated, it is frequently recommended that the first two to three smears be obtained one year apart as a means of detecting aggressive tumors at a young age. There is little evidence to suggest, however, that young women whose first two tests are separated by two or three years, rather than one, have a greater mortality or person-years life lost.(2) Recommendations to perform these first tests annually are based primarily on expert opinion.
Elderly women do not appear to benefit from Pap testing if repeated cervical smears have consistently been normal.(2,4,28) Many older women have had inadequate screening, however; nearly half of women over age 65 have never received a Pap test and 75% have not received regular screening.(33,34) Further screening in this group of older women is important(2,34) and has been shown to be cost-effective.(35)
The effectiveness of cervical cancer screening is more likely to be improved by extending testing to women who are not currently being screened and by improving the accuracy of Pap smears than by efforts to increase the frequency of testing. Studies suggest that those at greatest risk for cervical cancer are the very women least likely to have access to testing.(33,36) Inadequate Pap testing is most common among blacks, the poor, uninsured persons, the elderly, and persons living in rural areas. In addition, many women who are tested receive inaccurate results due to interpretative or reporting errors by cytopathology laboratories or specimen collection errors by clinicians.(37) The failure of some physicians to provide adequate follow-up for abnormal Pap smears is another source of delay in the management of cervical dysplasia.(37)
Clinical Intervention
Regular Papanicolaou tests are recommended for all women who are or have been sexually active. Testing should begin at the age when the woman first engages in sexual intercourse. Adolescents whose sexual history is thought to be unreliable should be presumed to be sexually active at age 18. Pap tests are appropriately performed at an interval of one to three years, to be recommended by the physician based on the presence of risk factors (e.g., early onset of sexual intercourse, history of multiple sexual partners, low socioeconomic status). Pap smears may be discontinued at age 65, but only if the physician can document previous Pap screening in which smears have been consistently normal. Physicians should submit specimens to laboratories having adequate quality control measures to ensure optimal accuracy in the interpretation and reporting of results. Thorough follow-up of test results should also be ensured.References
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 2. Yu S, Miller AB, Sherman GJ. Optimising the age, number of tests, and test interval for cervical screening in Canada. J Epidemiol Community Health 1982; 36:1-10.
3. Cervical cancer screening: summary of an NIH consensus statement. Br Med J 1980; 281:1264-6.
4. Wright VC, Riopelle MA. Age at time of intercourse v. chronologic age as a basis for Pap smear screening. Can Med Assoc J 1982; 127:127-31. 5. Brinton LA, Tashima KT, Lehman HF, et al. Epidemiology of cervical cancer by cell type. Cancer Res 1987; 47:1706-11.
7. Tawa K, Forsythe A, Cove JK, et al. A comparison of the Papanicolaou smear and the cervigram: sensitivity, specificity, and cost analysis. Obstet Gynecol 1988; 71:229-35.
8. Foltz AM, Kelsey JL. The annual Pap test: a dubious policy success. Milbank Mem Fund Q 1978; 56:426-62.
9. Coppleson LW, Brown B. Estimation of the screening error rate from the observed detection rates in repeated cervical cytology. Am J Obstet Gynecol 1974; 119:953-8.
10. Benoit AG, Krepart GV, Lotocki RJ. Results of prior cytologic screening in patients with a diagnosis of Stage I carcinoma of the cervix. Am J Obstet Gynecol 1984; 148:690-4.
11. Jones DE, Creasman WT, Dombroski RA, et al. Evaluation of the atypical Pap smear. Am J Obstet Gynecol 1987; 157:544-9.
12. Boyes DA, Morrison B, Knox EG, et al. A cohort study of cervical cancer screening in British Columbia. Clin Invest Med 1982; 5:1-29. 13. American College of Obstetricians and Gynecologists. Cervical cytology: evaluation and management of abnormalities. ACOG Technical Bulletin No.Gynecologists, 1984.
- Washington, D.C.: American College of Obstetricians and
14. Cramer DW. The role of cervical cytology in the declining morbidity and mortality of cervical cancer. Cancer 1974; 34:2018-27.
15. Miller AB, Lindsay J, Hill GB. Mortality from cancer of the uterus in Canada and its relationship to screening for cancer of the cervix. Int J Cancer 1976; 17:602-12.
16. Anderson GH, Boyes DA, Benedet JL, et al. Organisation and results of the cervical cytology screening programme in British Columbia, 1955-85. Br Med J 1988; 296:975-8.
17. Johanneson G, Geirsson G, Day N. The effect of mass screening in Iceland, 1965-1974, on the incidence and mortality of cervical carcinoma. Int J Cancer 1978; 21:418-25.
18. Hakama M. Mass screening for cervical cancer in Finland. In: Miller AB, ed. Screening in cancer: a report of a UICC workshop in Toronto. UICC Technical Report Series Vol. 40. Geneva: UICC, 1978.
19. Laara E, Day NE, Hakama M. Trends in mortality from cervical cancer in the Nordic countries: association with organized screening programmes. Lancet 1987; 1:1247-9.
20. La Vecchia C, Decarli A, Gentile A, et al. Pap smear and the risk of cervical neoplasia: quantitative estimates from a case-control study. Lancet 1984; 2:779-82.
21. Clarke EA, Anderson TW. Does screening by Pap smears help prevent cervical cancer? A case-control study. Lancet 1979; 2:1-4. 22. Aristizabal N, Cuello C, Correa P, et al. The impact of vaginal cytology on cervical cancer risks in Cali, Colombia. Int J Cancer 1984; 34:5-9.
23. Berrino F, Gatta G, d'Alto M, et al. Efficacy of screening in preventing invasive cervical cancer: a case-control study in Milan, Italy. IARC Sci Publ 1986; 76:111-23.
24. Skrabanek P. Cervical cancer screening. Lancet 1987; 1:1432-3. 25. Miller AB, Visentin T, Howe GR. The effect of hysterectomies and screening on mortality from cancer of the uterus in Canada. Int J Cancer 1981; 27:651-7.
26. International Agency for Research on Cancer Working Group on Evaluation of Cervical Cancer Screening Programmes. Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. Br Med J 1986; 293:659-64.
27. Fink DJ. Change in American Cancer Society checkup guidelines for detection of cervical cancer. CA 1988; 38:127-8.
28. Canadian Task Force on Cervical Cancer Screening Programs. Cervical cancer screening programs: summary of the 1982 Canadian task force report. Can Med Assoc J 1982; 127:581-9.
29. National Center for Health Statistics. Health United States 1986. Washington, D.C.:Department of Health and Human Services, 1986:72 (Publication no. DHHS (PHS) 87-1232.)
30. Weisman CS, Celentano DD, Hill MN, et al. Pap testing: opinion and practice among young obstetricians-gynecologists. Prev Med 1986; 15:342-51.
31. American College of Obstetricians and Gynecologists. Periodic cancer screening for women: statement of the Task Force on Periodic Cancer Screening for Women. Washington, D.C.: American College of Obstetricians and Gynecologists, 1980.
32. Idem. The adolescent obstetric-gynecologic patient. ACOG Technical Bulletin No. 94. Washington, D.C.: American College of Obstetricians and Gynecologists, 1986.
33. Kleinman JC, Kopstein A. Who is being screened for cervical cancer? Am J Public Health 1981; 71:73-5.
34. Mandelblatt J, Gopaul I, Wistreich M. Gynecologic care of elderly women: another look at Papanicolaou smear testing. JAMA 1986; 256:367-71.
35. Mandelblatt JS, Fahs MC. The cost-effectiveness of cervical cancer screening for low-income elderly women. JAMA 1988; 259:2409-13. 36. Hayward RA, Shapiro MF, Freeman HE, et al. Who gets screened for cervical and breast cancer? Results from a new national survey. Arch Intern Med 1988; 148:1177-81.
37. Koss LG. The Papanicolaou test for cervical cancer detection: a triumph and a tragedy. JAMA 1989; 261:737-43.
Screening for Prostate Cancer
Recommendation
There is insufficient evidence to recommend for or against routine digital rectal examinations as an effective screening test for prostate cancer in asymptomatic men. Transrectal ultrasound and serum tumor markers are not recommended for routine screening in asymptomatic men.Burden of Suffering
Prostate cancer is the most common cancer in American men and has the third highest cancer mortality rate.(1) It has the second highest cancer mortality rate in men over age 75.(1) Prostate cancer will account for an estimated 103,000 new cases and 28,500 deaths in the United States in 1989.(1) There has been no improvement in the age-adjusted death rate from this disease since 1949.(2) Risk increases with age, beginning at ages 55-60. After age 80, the incidence is as high as 1000 cases per 100,000 men.(3) Because local extension beyond the capsule of the prostate rarely produces symptoms, between 35% and 75% of patients already have metastases to the bones or lymph nodes at the time of diagnosis.(4,5) Survival is substantially decreased at this stage.(4)Efficacy of Screening Tests
The principal screening tests for detecting prostate cancer in asymptomatic men are the digital rectal examination, transrectal ultrasound, and serum tumor markers. The digital rectal examination is limited in sensitivity because the examining finger can palpate only the posterior and lateral aspects of the gland. Studies have shown that tumors often occur in portions of the prostate not accessible to the examining finger.(5-7) In addition, Stage A tumors by definition are nonpalpable. The digital rectal examination also has limited specificity, producing a large proportion of false-positive results. Several studies involving largely asymptomatic populations have shown that only 26-34% of men with suspicious findings on digital rectal examination have histological evidence of prostate cancer on needle biopsy.(8-10) The exact sensitivity and specificity of digital palpation are, however, unknown because biopsies are rarely performed on persons with normal rectal examinations. Studies in which a battery of other diagnostic tests were performed along with the rectal examination found the examination to have a sensitivity of 69-73% and a specificity of 77-89%, but these data were obtained in men with urinary obstructive symptoms and presumably are not generalizable to asymptomatic men.(11,12) A study in asymptomatic men found a digital rectal examination to have a sensitivity of only 33%.(13) It has recently been suggested that the actual sensitivity of the digital rectal examination may be as low as 2-9% in detecting cancer.(14)Transrectal ultrasonography is a second means of identifying prostate cancer, but there are as yet few data on the performance characteristics of this test in asymptomatic persons. Most sensitivity and specificity data for transrectal ultrasound derive from studies involving patients with suspected or confirmed prostate cancer, in which ultrasound is generally performed on a selected group of patients.(15-17) In one study, for example, transrectal ultrasound was performed on men with abnormal digital rectal examinations; the sonographers correctly identified cancer in 19 out of 28 (68%) men with biopsy-proven cancers and correctly ruled out cancer in 26 of 60 (43%) patients without histologic evidence of cancer.(15) In a recent prospective study, digital rectal examination and transrectal ultrasound were performed on nearly 800 community volunteers; biopsies were taken if either test was positive.(10) The positive predictive value of ultrasound in this study was 31%. The large proportion of false positives is due in part to the similarity in sonographic appearance between prostatic carcinoma and benign inflammatory conditions such as prostatitis and prostatic infarction.(18)
Serum tumor markers such as prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) are often elevated in persons with prostate cancer, but they do not appear to be useful screening tests for the detection of preclinical disease. The reported sensitivity of PAP is between 20% and 45%.(11,19) PSA is highly sensitive but lacks specificity (about 38-56%), in part because of difficulties in distinguishing between cancer and benign prostatic inflammation.(19,20)
Effectiveness of Early Detection
There is little direct evidence that early detection of prostate cancer improves outcome. Survival appears to be longer for persons with early disease; five-year survival is 85% for Stage A tumors, 77% for Stage B, 65% for Stage C, and 29% for Stage D.(21) It is not known, however, to what extent lead-time and length biases account for these differences. Autopsy studies indicate that prostate cancer is present in nearly half of older men, suggesting that a large proportion of occult cancers detected through screening would not manifest themselves during the patient's lifetime. In these persons, the detection of slow-growing malignancies through screening, followed by potentially unpleasant or harmful therapeutic interventions, might offer little clinical benefit.It is estimated that only 1 in 380 men with histologic evidence of prostate cancer die from the disease.(9) Even in these individuals there is little evidence that treatment can significantly alter the course of the disease. Stage C and Stage D disease are generally resistant to intervention, and the efficacy of treatment for Stage B prostatic cancer remains in question. The major randomized controlled trial comparing treatment of prostate cancer with no treatment found that radical prostatectomy was no better than placebo in altering five-year survival.(22) Finally, the morbidity associated with complications from invasive diagnostic/staging procedures (e.g., needle biopsy, lymphadenectomy) and treatment (e.g., radical prostatectomy) must also be considered in assessing the overall benefits of clinical intervention.
Prospective studies are needed to provide evidence that persons with prostate cancer detected through screening have a better outcome than those who are not screened. A multicenter trial, the National Prostatic Cancer Ultrasound Detection Project, is currently under way to compare the effectiveness of different screening protocols, but this study does not include a control group in which screening is not offered.(23) Published evidence to date on the benefits of screening are largely descriptive uncontrolled studies that lack conclusive evidence of clinical benefit. In a frequently cited screening program, for example, annual digital rectal examinations were performed on nearly 6000 men over the course of 21 years, resulting in the detection of 75 cases of prostate cancer.(24) Five-year survival for these patients was 77%, and the investigators noted that the subgroup receiving total prostatectomies experienced a higher five-year survival rate (91%) than men of the same age in the general population (83%). Other centers have reported that screened cohorts are more likely to have localized (Stage A and B) disease on diagnosis, but there is no direct evidence of improved clinical outcome.(8,9,25) There is also reason to question the accuracy of the clinical staging of these Stage A and Stage B cancers; several studies have shown that two-thirds of patients classified clinically as Stage A or Stage B are subsequently found to have Stage C or Stage D disease when staging lymphadenectomy is performed.(8,9,25) Mathematical modeling studies have suggested modest benefit
from screening by digital rectal examination, but these findings are sensitive to certain assumptions about the natural history of the disease and the efficacy of treatment.(26)
Recommendations of Others
The American Cancer Society(27) and the National Cancer Institute(28) recommend an annual digital rectal examination for both prostate and colorectal cancer beginning at age 40. The Canadian Task Force(29) and other experts(30) on the periodic health examination have advised against routine screening for prostate cancer. A technology assessment panel convened by the American Medical Association recently concluded that the role of transrectal ultrasound in screening for prostate cancer is investigational.(31) Similar recommendations have been issued by other experts.(32,33)Clinical Intervention
There is insufficient evidence to recommend for or against routine digital rectal examination as an effective screening test for prostate cancer in asymptomatic men. Transrectal ultrasound and serum tumor markers are not recommended for routine screening in asymptomatic men.References
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 2. Idem. Cancer facts and figures. New York: American Cancer Society, 1985. 3. Young JL Jr, Percy CL, Asire AJ (eds). SEER Program: incidence and mortality, 1973-77. National Cancer Institute Monograph 57. Washington, D.C.: Government Printing Office, 1981.
4. Chodak GW, Schoenberg HW. Early detection of prostate cancer by routine screening. JAMA 1984; 252:3261-4.
5. Resnick MI. Background for screening: epidemiology and cost effectiveness. Prog Clin Biol Res 1988; 269:111-20.
6. Spigelman SS, McNeal JE, Freiha FS, et al. Rectal examination in volume determination of carcinoma of the prostate: clinical and anatomical correlations. J Urol 1986; 136:1228-30.
7. McNeal JE, Price HM, Redwine EA, et al. Stage A versus Stage B adenocarcinoma of the prostate: morphological comparison and biological significance. J Urol 1988; 139:61-5.
8. Thompson IM, Ernst JJ, Gangai MP, et al. Adenocarcinoma of the prostate: results of routine urological screening. J Urol 1984; 132:690-2. 9. Chodak GW, Keller P, Schoenberg H. Routine screening for prostate cancer using the digital rectal examination. Prog Clin Biol Res 1988; 269:87-98.
10. Lee F, Littrup PJ, Torp-Pedersen ST, et al. Prostate cancer: comparison of transrectal US and digital rectal examination for screening. Radiology 1988; 168:389-94.
11. Guinan P, Bush I, Ray V, et al. The accuracy of the rectal examination in the diagnosis of prostatic carcinoma. N Engl J Med 1980; 303:499-503.
12. Guinan P, Ray P, Bhatti R, et al. An evaluation of five tests to diagnose prostate cancer. Prog Clin Biol Res 1987; 243A:551-8. 13. Vihko P, Kontturi O, Ervast J, et al. Screening for carcinoma of the prostate: rectal examination and enzymatic radioimmunologic measurements of serum acid phosphatase compared. Cancer 1985; 56:173-7. 14. Stamey TA. Cancer of the prostate. Monographs Urol 1983; 4:65-132. 15. Chodak GW, Wald V, Parmer E, et al. Comparison of digital examination and transrectal ultrasonography for the diagnosis of prostatic cancer. J Urology 1986; 135:951-4.
16. Clements R, Griffiths GJ, Peeling WB, et al. How accurate is the index finger? A comparison of digital and ultrasound examination of the prostatic nodule. Clin Radiol 1988; 39:87-9.
17. Brooman PJC, Peeling WB, Griffiths GJ, et al. A comparison between digital examination and per-rectal ultrasound in the evaluation of the prostate. Br J Urol 1981; 53:617-20.
18. Kadmon D. Methods of detecting prostatic tumors. In: Ratliff TL, Catalona WJ, eds. Genitourinary cancer. Boston, Mass.: Martinus Nijhoff, 1987:77-93.
19. Stamey TA, Yan N, Hay AR, et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317:909-16.
20. Huber PR, Schnell Y, Hering F, et al. Prostate-specific antigen: experimental and clinical observations. Scand J Urol Nephrol 1987; 104:33-9.
21. Mettlin C, Natarajan N. End results for urologic cancers: trends and interhospital differences. Cancer 1987; 60:474-9.
22. Byar DK, Corle DK. VACURG randomized trial of radical prostatectomy for Stages I and II prostate cancer. Veterans Administration Cooperative Urological Research Group. Urol (Suppl) 1981; 17:7-11.
23. Murphy GP. Screening for prostatic carcinoma: useful or not? Prog Clin Biol Res 1988; 269:131-7.
24. Gilbertsen VA. Cancer of the prostate gland: results of early diagnosis and therapy undertaken for cure of the disease. JAMA 1971; 215:81-4. 25. Thompson IM, Rounder JB, Teague JL, et al. Impact of routine screening for adenocarcinoma of the prostate on stage distribution. J Urol 1987; 137:424-6.
26. Love RR, Fryback DG, Kimbrough SR. A cost-effectiveness analysis of screening for carcinoma of the prostate by digital examination. Med Decis Making 1985; 5:263-78.
27. American Cancer Society. Guidelines for the cancer-related checkup: recommendations and rationale. CA 1980; 30:4.
28. National Cancer Institute. Working guidelines for early cancer detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
29. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1194-254.
30. Frame PS. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
31. Diagnostic and Therapeutic Technology Assessment (DATTA). Transrectal ultrasonography in prostatic cancer. JAMA 1988; 259:2757-9. 32. McClellan BL. Transrectal US of the prostate: is the technology leading the science? Radiology 1988; 168:571-5.
33. Chodak GW. Transrectal ultrasonography: is it ready for routine use? JAMA 1988; 259:2744-5.
Screening for Lung Cancer
Recommendation
Screening asymptomatic persons for lung cancer by performing routine chest radiography or sputum cytology is not recommended.Burden of Suffering
Cancer of the lung is the leading cause of deaths from cancer in the United States.(1) It is responsible for over 140,000 deaths annually; 155,000 new cases will be diagnosed in 1989.(1) The five-year survival rate is only 13%, representing the poorest prognosis for any cancer site other than the pancreas, liver, and esophagus.(1) Important risk factors for lung cancer include the use of tobacco and occupational exposure to certain carcinogens.(2) Tobacco alone is responsible for over 90% of all cases of cancer of the lung, trachea, and bronchus.(2)Efficacy of Screening Tests
Although the chest radiograph and the sputum cytological examination are capable of detecting lung cancer in its early stages, they lack sufficient accuracy to be used as routine screening tests in asymptomatic persons. The accuracy of the chest radiograph is limited by the capabilities of the technology and observer variation among radiologists. Suboptimal technique, insufficient exposure, and poor positioning and cooperation of the patient can obscure pulmonary nodules or introduce artifacts into the film.(3) Once the x-ray is taken, there can be significant inconsistencies in the interpretations made by different radiologists. The extent of this problem is difficult to measure in terms of sensitivity and specificity because of the absence of a "gold standard" to confirm the accuracy of the radiologist's report.(3) Studies do indicate, however, that radiologists frequently disagree on the interpretation of chest radiographs and that over 40% of these are significant or potentially significant.(4) Most errors are false-negative interpretations, and about 10-20% are incorrect radiologic diagnoses and "indeterminate" results that require follow-up testing for clarification.(4) Interpretation of chest x-rays by primary care physicians may be less accurate than those of radiologists.(5)Furthermore, the yield of screening chest radiography to detect cancer is low, largely due to the low prevalence of lung cancer in the general population and even among asymptomatic smokers. Of the initial 31,360 screening radiographs performed on asymptomatic smokers in the National Cancer Institute Cooperative Early Lung Cancer Detection Program, only 256 (0.82%) were interpreted as "suspicious for cancer," and only 121 of these patients (0.39% of the screened population) were ultimately diagnosed as having lung cancer.(6) Other studies have confirmed the low yield of performing chest radiographs on asymptomatic persons.(7,8)
Data from the same studies suggest that sputum cytology is a less effective screening test than chest radiography. The investigators found that, of the 160 lung cancers detected by administering both tests, 123 (77%) would have been detected by x-ray alone and 67 (42%) would have been detected by cytological examination alone.(6) In addition, the majority of incident cases detected in subsequent screenings were detected by x-ray.(9)
Effectiveness of Early Detection
Lung cancers first detected when symptomatic usually present at an advanced stage for which the treatment outcome is poor. Overall five-year survival for lung cancer is less than 13%.(1) If therapy is initiated early, while the tumor is still localized (Stage I), five-year survival is about 27-33%,(1) and under optimal conditions Stage I cases can have a five-year survival of 60-75%.(9-11) Once tumors have metastasized, however, the benefits of resection are limited.(10) Early detection of Stage I tumors through screening might therefore provide an opportunity to improve survival. However, there is little convincing evidence that screening programs using radiography or cytology, either alone or in combination, actually succeed in reducing lung cancer mortality.The efficacy of chest x-ray screening for lung cancer was first investigated in the 1960s. A controlled prospective study involving over 55,000 persons found that those receiving chest radiographs every six months had a larger proportion of resectable tumors but the same mortality from lung cancer when compared with controls who received x-rays at the beginning and end of the trial.(12) Similar findings were reported in the Philadelphia Pulmonary Neoplasm Research Project(13) and, more recently, in a case-control study.(14) In addition, the results of one of the three centers participating in the National Cancer Institute Cooperative Early Lung Cancer Detection Program (see below) provide indirect evidence of the limited efficacy of x-ray screening. In this study, persons receiving chest radiography and sputum cytology every four months had the same outcome (lung cancer mortality) as persons receiving advice to obtain annual testing.(15) However, no study to date has compared chest x-ray screening for lung cancer with no screening in a prospective design with adequate follow-up time. Thus, although the efficacy of chest x-ray screening can be questioned on the basis of the preceding studies, conclusive evidence that chest radiography screening does not lower lung cancer mortality is not available.
Three large clinical trials published by the National Cancer Institute Cooperative Early Lung Cancer Detection Program have examined the efficacy of dual screening (chest x-ray and sputum cytology) in over 30,000 male smokers.(6,9,16-21) Two trials comparing annual dual screening with annual radiographic screening tested the incremental benefit of adding sputum cytology to x-ray screening.(17,18) The third trial, which compared dual screening every four months with advice to receive the same tests annually, examined the benefit of frequent dual screening compared with usual medical care.(19) In each study, lung cancer mortality did not differ between experimental groups and control groups. Although early-stage, resectable tumors were more common and five-year survival significantly higher in groups receiving regular dual screening, lead-time and length biases may have been responsible for these findings. A recent randomized prospective trial of dual screening in Czechoslovakia produced similar results; the investigators found no substantial difference in the number or causes of death between groups.(22)
Recommendations of Others
There is a consensus that current evidence is insufficient to support routine screening for lung cancer among asymptomatic persons. This is the official policy of the American Cancer Society,(23) the National Cancer Institute,(24) the Food and Drug Administration,(25) the American College of Radiology,(26) the Royal College of Radiologists,(27) and the World Health Organization.(28) Recent reviews of the evidence by the Canadian Task Force(29) and others(3,30) have reached the same conclusion. Some experts defend screening smokers even in the face of the limited evidence because of the poor prognosis of lung cancer patients who present with symptoms.(31) There are no official recommendations to screen nonsmokers. All authorities strongly endorse the value of smoking cessation in the prevention of lung cancer.Discussion
Although lung cancer is the leading cause of cancer deaths and early detection might improve survival, there is little rigorous evidence that screening programs can lower mortality from this disease. To the weakness of the evidence for screening must be added the substantial cost of routine population testing. It is estimated that $1.5 billion is spent annually for screening chest radiographs,(8) and it is known that false-positive results from these films lead to unnecessary expense and morbidity in follow-up procedures.(32) Primary prevention may be a more effective strategy than screening to reduce the morbidity and mortality of lung cancer. Cigarette smoking is responsible for over 90% of all lung cancers(2) and should therefore serve as the principal focus of clinical efforts to help prevent this disease.Clinical Intervention
Screening asymptomatic persons for lung cancer by performing routine chest radiography or sputum cytology is not recommended. All persons should be counseled about the use of tobacco products (see Counseling to Prevent Tobacco Use).References
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 2. Department of Health and Human Services. Reducing the health consequences of smoking: 25 years of progress. A report of the Surgeon General. Rockville, Md.: Department of Health and Human Services, 1989. (Publication no. DHHS (PHS) 89-8411.)
3. Tape TG, Mushlin AI. The utility of routine chest radiographs. Ann Intern Med 1986; 104:663-70.
4. Herman PG, Gerson DE, Hessel SJ, et al. Disagreements in chest roentgen interpretation. Chest 1975; 68:278-82.
5. Kuritzky L, Haddy RI, Curry RW Sr. Interpretation of chest roentgenograms by primary care physicians. South Med J 1987; 80:1347-51. 6. The National Cancer Institute Cooperative Early Lung Cancer Detection Program. Summary and conclusions. Am Rev Resp Dis 1984; 130:565-7. 7. Rucker L, Frye EB, Staten MA. Usefulness of screening chest roentgenograms in preoperative patients. JAMA 1983; 250:3209-11. 8. Hubbel FA, Greenfield S, Tyler JL, et al. The impact of routine admission chest x-ray films on patient care. N Engl J Med 1985; 312:209-13.
9. Melamed MR, Flehinger BJ, Zaman MB, et al. Screening for early lung cancer: results of the Memorial Sloan-Kettering study in New York. Chest 1984; 86:44-53.
10. Wright JL, Coppin C, Mullen BJ, et al. Surgical treatment of lung cancer: promise and problems of early diagnosis. Can J Surg 1986; 29:205-8.
11. Moores DW, McKneally MF. Treatment of Stage I lung cancer (T1N0M0, T2N0M0). Surg Clin North Am 1987; 67:937-43.
12. Brett GZ. The value of lung cancer detection by six-monthly chest radiographs. Thorax 1968; 23:414-20.
13. Weiss W. Survivorship among men with bronchogenic carcinoma: three studies in populations screened every six months. Arch Environ Health 1971;22:168-73.
14. Ebeling K, Nischan P. Screening for lung cancer: results from a case- control study. Int J Cancer 1987; 40:141-4.
15. Sanderson DR. Lung cancer screening: the Mayo study. Chest 1986; 89:324S.
16. Berlin NI, Buncher CR, Fontana RS, et al. The National Cancer Institute Cooperative Early Lung Cancer Detection Program: results of the initial screen (prevalence): introduction. Am Rev Resp Dis 1984; 130:545-9. 17. Flehinger BJ, Melamed MR, Zaman MB, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Memorial Sloan-Kettering study. Am Rev Resp Dis 1984; 130:555-60.
18. Frost JK, Ball WC Jr, Levin ML, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Resp Dis 1984; 130:549-54. 19. Fontana RS, Sanderson DR, Taylor WF, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Resp Dis 1984; 130:561-5. 20. Fontana RS. Screening for lung cancer: recent experience in the United States. In: Hansen HH, ed. Lung cancer. Boston, Mass.: Martinus Nijhoff, 1986:91-111.
21. Tockman MS, Frost JK, Stitik FP, et al. Screening and detection of lung cancer. In: Aisner J, ed. Lung cancer. New York: Churchill Livingston, 1985:25-40.
22. Kubik A, Polak J. Lung cancer detection: results of a randomized prospective study in Czechoslovakia. Cancer 1986; 57:2427-37. 23. American Cancer Society. Guidelines for the cancer-related check-up. CA 1980; 30:199-207.
24. National Cancer Institute. Cancer control objectives for the nation: 1985-2000. Washington, D.C.: Public Health Service, 1986. (Publication no. DHHS (NIH) 86-2880.)
25. National Center for Devices and Radiologic Health. The selection of patients for x-ray examinations: chest x-ray screening examinations. Rockville, Md.: Food and Drug Administration, 1983. (Publication no. DHHS (FDA) 83-8204.)
26. American College of Radiology. Policy statement: referral criteria for chest x-ray examinations. Chicago, Ill.: American College of Radiology, 1982.
27. Royal College of Radiologists Working Party on the Effective Use of Diagnostic Radiology. Preoperative chest radiology: national study by the Royal College of Radiologists. Lancet 1979; 2:83-6.
28. WHO Scientific Group on the Indications for and Limitations of Major X- Ray Diagnostic Investigations. A rational approach to radiodiagnostic investigations. WHO Technical Report Series No. 689. Geneva: World Health Organization, 1983:7-28.
29. Morrison B. Lung cancer: report for the Canadian Task Force on the Periodic Health Examination. Can Med Assoc J (in press). 30. Frame PS. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
31. Melamed MR, Flehinger BJ. Screening for lung cancer. Chest 1984; 86:2-3.
32. Bailar JC. Screening for lung cancer: where are we now? Am Rev Resp Dis 1984; 130:541-2.
Screening for Skin Cancer
Recommendation
Routine screening for skin cancer is recommended for persons at high risk (see Clinical Intervention). Clinicians should advise all patients with increased outdoor exposure to use sunscreen preparations and other measures to protect their skin from ultraviolet rays. Currently there is no evidence for or against counseling patients to perform skin self- examination.Burden of Suffering
Over 500,000 new cases of skin cancer are diagnosed each year.(10 Most of these are basal cell and squamous cell carcinomas, which are highly treatable and rarely metastasize. These tumors can, however, be disfiguring if they are not detected early, and they account for over 2000 deaths each year.(2) The most serious form of skin cancer is malignant melanoma, which accounts for 74% of all skin cancer deaths.(3) An estimated 27,000 new cases of malignant melanoma will occur in the United States in 1989, and 6000 persons will die of this disease.(2) An increasing number of new cases and deaths from malignant melanoma are being reported in the United States.(3) Malignant melanoma usually presents in persons over age 40 and is uncommon in young persons.(3) The principal risk factors are precursor lesions (e.g., dysplastic nevi,certain congenital nevi) and a family history of malignant melanoma.(3,4) A number of other risk factors for malignant melanoma have also been identified.(5)Efficacy of Screening Tests
The principal screening test for skin cancer is physical examination of the skin. Detection of a suspicious lesion constitutes a positive screening test, which then should be confirmed by skin biopsy. There are few studies evaluating the accuracy of the skin examination, however, and most suffer from important design flaws. Estimates of sensitivity and specificity (33-98% and 45-95%, respectively) vary with the type of skin cancer being sought.(6-9) A randomized community study found that the positive predictive value of a suspicious skin lesion is limited; biopsy- proven carcinoma was present in only 38-59% of lesions identified as suspicious for skin cancer by expert dermatologists.(7) Primary care physicians and others lacking specialized training in dermatology would be expected to have greater difficulty in evaluating skin lesions.(10-12) In one study, in which skin photographs were shown to dermatologists and nondermatologists, five of the six photographs of malignant melanoma were correctly identified by 69% of the dermatologists but only by 12% of the nondermatologists.(10) Both of the two photographs of dysplastic nevi were recognized by most of the dermatologists, but only 31% of the nondermatologists were able to identify one.(10)Other factors affecting the yield of screening for skin cancer are the proportion of the body surface examined and the frequency of the examination. Only 20% of malignant melanomas occur on normally exposed body surfaces (in contrast to 85-90% of basal cell and squamous cell carcinomas); many melanomas occur on the back and legs.(13) Dermatologists estimate the detection of malignant melanoma is over six times as likely with a total-body skin examination.(13) A second factor affecting yield is the frequency of the examination. If the interval between examinations is too long, new cancers may not be detected before they have progressed to an advanced stage. There are no data, however, with which to determine the optimal frequency of examination, and therefore annual or biennial intervals have been recommended on the basis of clinical judgment.
Patient self-examination would be expected to be less accurate than physician examination in evaluating skin lesions. There are no data, however, on the accuracy of skin self-examination, the efficacy of self- examination instructions in reducing errors, or the proportion of lesions brought to medical attention that would be benign (false positives). It is known that persons who detect malignant lesions often delay seeking medical care until the lesion becomes symptomatic. In one study, patients with malignant melanoma reported seeking medical attention 11-18 months after the melanoma was first detected.(14) Symptomatic lesions were seen by clinicians within 2-6 months but were more advanced on presentation.(14)
Effectiveness of Early Detection
Although there is little proven reduction in mortality associated with the early diagnosis of basal and squamous cell cancers, early treatment may reduce morbidity and disfigurement. In the case of malignant melanoma, there is stronger evidence that survival is directly related to the stage of the disease. Five-year survival for Stage I melanoma is greater than 80-90%, but it is only 27-57% with Stage II disease.(15) In more advanced cases of disseminated metastatic melanoma, for which there is no effective treatment,(4) the median survival time is about 5-9 months.(16) The likelihood of recurrence after resection is also related to the thickness of the melanoma. A lesion thickness less than 0.76 mm is associated with a 10-year disease-free survival rate in excess of 99%.(3,17) The rate is only 48% for lesions greater than 3 mm in thickness.(3) Although it is possible that lead-time and length biases account for some of these differences, the data suggest that persons in whom malignant melanoma is detected early may experience a better outcome than those detected with more advanced disease.Recommendations of Others
The American Academy of Dermatology(18) and others(3) recommend annual, complete skin examination by a physician, to be supplemented by monthly self-examinations of the skin. The American Cancer Society(19) and the National Cancer Institute(20) recommend including a complete skin examination as part of the routine periodic health examination. The Canadian Task Force advises against routine screening but recommends skin examinations for those in high-risk groups, such as persons with dysplastic nevi and their relatives, outdoor workers, and persons exposed to chemical skin carcinogens.(21) Others have advised physicians not to screen for skin cancer but to instruct patients to perform self-examinations.(22) Most dermatologists recommend examining the entire body; some recommend performing complete skin examinations only on those patients with a history of actinic lesions, skin cancer, and extensive or obscure dermatologic disorders.(23) The American Academy of Dermatology also recommends advising patients to limit sun exposure and to use sunscreens and protective clothing when exposed to sunlight.(18) Others emphasize the importance of counseling parents to use sunscreens and other measures to prevent skin damage in children.(24)Discussion
Although screening for skin cancer is of some value in detecting basal cell and squamous cell carcinoma, its principal benefit lies in discovering and treating early-stage malignant melanoma. This disease is, however, relatively uncommon in the general population (lifetime risk of 0.7%).(3) Since over 99% of patients who would be examined under routine screening would never have malignant melanoma, it is important to consider the potential adverse effects of routine skin examinations. Medical expenses, for example, might be increased; physician office visits would be lengthened by performing a thorough skin examination and teaching self-examination.(23) A total-body examination may be embarrassing for some patients;(23) skin biopsy may be uncomfortable and may increase physician charges ($36-$125 or more per procedure);(25) and patient anxiety may be generated by lesions that ultimately prove to be benign (false positives). In light of these concerns, a more prudent approach might be to limit screening by total-body examination to population groups at increased risk for skin cancer.As an alternative to early detection, many authorities have advocated primary prevention of skin cancer by limiting exposure to sunlight and by applying sunscreen preparations rated 15 SPF (Sun-Protective Factor) or more. These maneuvers are more clearly relevant to preventing nonmelanomatous skin cancers (e.g., basal cell and squamous cell carcinoma) for which ultraviolet rays are an established risk factor. Malignant melanoma may be linked to certain patterns of sunlight exposure, such as sunburns or exposure at young ages, but the association remains uncertain.(26-29) There have been few studies examining the effectiveness of counseling patients to protect themselves from sunlight in reducing the incidence of skin cancer. It is known that sunscreen agents can block carcinogenic ultraviolet rays(30) and can reduce the incidence of skin tumors in laboratory animals.(31,32) There is also some evidence that public education can increase knowledge about the health risks of sunlight.(33) At the same time, it is not certain that patients act on this information, perhaps due to the perceived personal benefits of sunbathing or obtaining a suntan.(34) A recent survey found that although 54% of adults and 37% of adolescents are aware of the risks of sun exposure, 30% of adults and 50% of adolescents continue to engage in suntanning. Fully 23% of adults and 33% of adolescents failed to use protective measures while engaged in suntanning.(35)
Clinical Intervention
Routine screening by complete skin examination is recommended for persons with a family or personal history of skin cancer, clinical evidence of precursor lesions (e.g., dysplastic nevi, certain congenital nevi), and those with increased occupational or recreational exposure to sunlight. The optimal frequency of such examinations has not been determined and is left to clinical discretion. Although routine screening for skin cancer is not recommended for the general population, clinicians should be alert to skin lesions with malignant features when examining patients for other reasons. When examining pigmented lesions, a malignant appearance should be judged by established dermatologic criteria (i.e., asymmetry, border irregularity, color variability, diameter greater than 6 mm). Appropriate biopsy specimens should be taken of suspicious lesions. Clinicians should advise patients with increased occupational or recreational exposure to sunlight to use sunscreen preparations, protective clothing, and other measures to limit exposure to ultraviolet rays. Currently, there is no evidence for or against counseling patients to perform periodic self-examination of the skin.References
1. American Cancer Society. Cancer facts and figures--1987. New York: American Cancer Society, 1987.
2. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 3. Friedman RJ, Rigel DS, Kopf AW. Early detection of malignant melanoma: the role of physician examination and self-examination of the skin. CA 1985; 35:130-51.
4. Fitzpatrick TB, Rhodes AR, Sober AJ. Prevention of malignant melanoma by recognition of its precursors. N Engl J Med 1985; 312:115-6. 5. Evans RD, Kopf AW, Lew RA, et al. Risk factors for the development of malignant melanoma. I. Review of case-control studies. J Dermatol Surg Oncol 1988; 14:393-408.
6. Lightstone AC, Kopf AW, Garfinkel L. Diagnostic accuracy: a new approach to its evaluation. Arch Dermatol 1965; 91:497-502.
7. Green A, Leslie D, Weedon D. Diagnosis of skin cancer in the general population: clinical accuracy in the Nambour survey. Med J Aust 1988; 148:447-50.
8. Kopf AW, Mintzis M, Bart RS. Diagnostic accuracy in malignant melanoma. Arch Dermatol 1975; 111:1291-2.
9. Presser SE, Taylor JR. Clinical diagnostic accuracy of basal cell carcinoma. J Am Acad Dermatol 1987; 16:988-90.
10. Cassileth BR, Clark WH, Lusk EJ. How well do physicians recognize melanoma and other problem lesions? J Am Acad Dermatol 1986; 14:555-60. 11. Ramsey DL, Fox AB. The ability of primary care physicians to recognize the common dermatoses. Arch Dermatol 1981; 117:620-2.
12. Wanger RF, Wagner D, Tomich JM, et al. Diagnoses of skin diseases: dermatologists vs. nondermatologists. J Dermatol Surg Oncol 1985; 11:476-9.
13. Rigel DS, Friedman RJ, Kopf AW, et al. Importance of complete cutaneous examination for the detection of malignant melanoma. J Am Acad Dermatol 1986; 14:857-60.
14. Cassileth BR, Lusk EJ, Guerry D, et al. "Catalyst" symptoms in malignant melanoma. J Gen Intern Med 1987; 2:1-4.
15. Hartley JW, Fletcher WS. Improved survival of patients with Stage II melanoma of the extremity using hyperthermic isolation perfusion with 1-phenylalanine mustard. J Surg Oncol 1987; 36:170-4.
16. Hena MA, Emrich LJ, Nambisan RN, et al. Effect of surgical treatment on Stage IV melanoma. Am J Surg 1987; 153:270-5.
17. Veronesi U, Cascinelli N, Adamus J, et al. Thin Stage I primary cutaneous malignant melanoma: comparison of excision with margins of 1 or 3 cm. N Engl J Med 1988; 318:1159-62.
18. Martin G, American Academy of Dermatology. Personal communication, January 1989.
19. American Cancer Society. Guidelines for the cancer-related checkup: recommendations and rationale. New York: American Cancer Society, 1980. 20. National Cancer Institute. Working guidelines for early cancer detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
21. Canadian Task Force on the Periodic Health Examination. The periodic health examination: 2. 1984 update. Can Med Assoc J 1984; 130:2-16. 22. Frame PS. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
23. Epstein E. Crucial importance of the complete skin examination (letter). J Am Acad Dermatol 1985; 13:151-3.
24. Stern RS, Weinstein MC, Baker SG. Risk reduction for nonmelanoma skin cancer with childhood sunscreen use. Arch Dermatol 1986; 122:537-45. 25. Fewkes JL, Sober AJ. Skin biopsy: the four types and how best to do them. Primary Care and Cancer 1988; March:11-6.
26. Lew RA, Sober AJ, Cook N, et al. Sun exposure habits in patients with cutaneous malignant melanoma: a case control study. J Dermatol Surg Oncol 1983; 9:981-6.
27. Holman CD, Armstrong BK, Heenan PJ. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. JNCI 1986; 76:403-14. 28. MacKie RM. The role of sunlight in the etiology of cutaneous malignant melanoma. Clin Exp Dermatol 1981; 6:407-10.
29. MacKie RM, Aitchison T. Severe sunburn and subsequent risk of primary cutaneous malignant melanoma in Scotland. Br J Cancer 1982; 46:955-60. 30. Pathak MA. Sunscreens and their use in the preventive treatment of sunlight-induced skin damage. J Dermatol Surg Oncol 1987; 13:739-50. 31. Wulf HC, Poulsen T, Brodthagen H, et al. Sunscreens for delay of ultraviolet induction of skin tumors. J Am Acad Dermatol 1982; 7:194-202.
32. Kligman LH, Akin FJ, Kligman AM. Sunscreens prevent ultraviolet photocarcinogenesis. J Am Acad Dermatol 1980; 3:30-5.
33. Putnam GL, Yanagisako KL. Skin cancer comic book: evaluation of a public educational vehicle. Cancer Det Prev 1982; 5:349-56. 34. Keesling B, Friedman HS. Psychosocial factors in sunbathing and sunscreen use. Health Psychol 1987; 6:477-93.
35. Public awareness of the effects of sun on skin. A survey conducted for the American Academy of Dermatology. Princeton, N.J.: Opinion Research Corporation, 1987.
Screening for Testicular Cancer
Recommendation
Periodic screening for testicular cancer by testicular examination is recommended for men with a history of cryptorchidism, orchiopexy, or testicular atrophy. There is insufficient evidence of clinical benefit or harm to recommend for or against routine screening of other asymptomatic men for testicular cancer. Clinicians should advise adolescent and young adult males to seek prompt medical attention for testicular symptoms such as pain, swelling, or heaviness. Currently, there is insufficient evidence for or against counseling patients to perform periodic self-examination of the testicles (see Clinical Intervention).Burden of Suffering
Testicular cancer is the most common form of cancer in young men.(1) It will account for an estimated 5700 new cases and 350 deaths in the United States in 1989.(2) Diagnostic techniques and therapeutic interventions, while successful in reducing the previously high mortality of this disease, nonetheless produce considerable morbidity. Orchiectomy, for example, is frequently required for diagnostic purposes; lymph node dissection often results in ejaculatory dysfunction; and effective chemotherapeutic agents, such as cis-platin and bleomycin, are associated with a variety of serious side effects.(3) Testicular cancer is most common in white adolescents and young adults, in whom the annual incidence is about 1 per 10,000.(4) Leading risk factors for testicular cancer are a history of cryptorchidism, orchiopexy, or testicular atrophy.(5)Efficacy of Screening Tests
The principal screening test for testicular cancer is palpation of the testes by an examiner. Detection of a suspicious testicular mass constitutes a positive test, and accuracy is confirmed by pathological examination of tissue. There is little information on the sensitivity, specificity, or positive predictive value of the testicular examination in asymptomatic persons. Sensitivity, which depends in large part on the palpability of the mass, would be expected to be poor in detecting small testicular tumors or when an improper examination technique is used.(6,7) Even when the physician is aware of a testicular mass or symptoms, however, sensitivity may be poor in recognizing cancer because of the variety of other causes of symptomatic testicular masses. There is evidence that between 26% and 56% of patients presenting initially to their physician with testicular cancer are first diagnosed as having epididymitis, testicular trauma, hydrocele, or other benign disorders,(8-10) and they often receive treatment for these conditions before the cancer is diagnosed.(6,9,11) An alternative means of screening for testicular cancer is instructing patients to periodically examine themselves for testicular masses. Reliable information on the accuracy of testicular self-examination is not available. There have been few studies of whether counseling men to perform self-examination motivates them to adopt this practice or to perform it correctly. Research to date has demonstrated only that education about testicular cancer and self-examination may enhance knowledge and self-reported claims of performing testicular examination.(12,13) One study found that men who reviewed an educational checklist on how to perform self-examination were able to demonstrate greater skill when self- examination was performed moments later, and they were able to recall the contents of the checklist in a telephone survey months later.(14) Few studies, however, have examined whether education or self-examination instructions actually increase the performance of self-examination. It is also unclear whether persons who detect testicular abnormalities seek medical attention promptly. Patients with testicular symptoms may wait as long as several months before contacting a physician.(8) Finally, no studies have proved that persons who perform testicular self-examination are more likely to detect early-stage tumors or have improved survival than those who do not practice self-examination.(15) Rather, published evidence that self-examination can detect testicular cancer in asymptomatic persons is limited to a small number of anecdotal reports.(16)
Effectiveness of Early Detection
The outcome of treatment is considerably better in patients with Stage I testicular cancer than in those with more advanced disease. The current five-year survival for Stage I seminoma treated with radiotherapy is 91-99%.(3) Stage I nonseminomatous cancers (e.g., teratomas, embryonal carcinoma) treated with radical retroperitoneal lymph node dissection have a reported 3-5-year survival approaching 90%.(3) With the advent of cisplatin-based chemotherapeutic regimens, a 3-year survival of 90-100% has been reported.(3) Reported survival in patients with disseminated testicular cancer, however, is lower (about 60-75%), and these persons require intensive treatment with chemotherapeutic agents that produce a variety of systemic side effects.(17,18)Although lead-time and length biases may account for part of the improved survival observed for persons with early-stage testicular cancer, it is likely that the prognosis is, in fact, better for persons with less advanced disease. There is, however, no evidence that screening (i.e., detection of testicular cancer in asymptomatic persons) is effective in improving the detection of Stage I testicular cancer or its outcome. Even without screening, 60-80% of seminomas present as Stage I disease.(3) There is evidence that once testicular symptoms have appeared, diagnostic delays are associated with more advanced disease and lower survival.(8,9,19) But there is no evidence to date that diagnosis before symptoms appear (i.e., through screening) is of benefit in improving outcome.
Recommendations of Others
The American Cancer Society(20) and the National Cancer Institute(21) recommend that testicular examination be included as part of the periodic health examination of men. The Canadian Task Force, however, recommends that screening should be performed only on patients with a history of cryptorchidism, testicular atrophy, or ambiguous sex.(22) Recommendations differ on whether patients should be counseled to perform testicular self- examination. The American Cancer Society(23) and the National Cancer Institute(24) recommend that all postpubertal males should perform monthly testicular self-examination. Physicians have been advised to instruct male patients on how to perform this examination,(25) and some authorities believe the technique should be reviewed at every periodic health visit beginning with puberty and continuing throughout life.(26) Others, citing the lack of evidence that self-examination is effective, have advised physicians against routinely devoting time to discussing testicular self- examination.(15,27)Discussion
Although screening for testicular cancer may be beneficial, conclusive evidence of benefit is lacking. It is also clear from the rarity of this disease that a program of routine screening of all asymptomatic males would have low yield. Testicular cancer accounts for less than 1% of all male neoplasms, and the lifetime probability of a white male (the race at greatest risk for the disease) developing this disease is 0.2%.(18) Thus, the vast majority of men would have normal examinations; of those with suspicious masses, most would have benign disease (false positives). Many of these cases, however, would require referral to urologists, radiographic studies, or invasive procedures (e.g., orchiectomy, inguinal exploration) before malignancy could be ruled out.(3) Similarly, routine performance of self-examination by all males would detect some malignancies, but the vast majority of findings would be benign. The discovery by patients of testicular masses might generate anxiety and increased physician office visits, but data supporting such adverse effects are lacking. Finally, some authors have expressed concern about the cost of physician time to teach self-examination.(8)Clinical Intervention
Periodic screening for testicular cancer by testicular examination is recommended for men with a history of cryptorchidism, orchiopexy, or testicular atrophy. The optimal frequency of such examinations has not been determined and is left to clinical discretion. There is insufficient evidence of clinical benefit or harm to recommend for or against routine screening of other asymptomatic men for testicular cancer. Clinicians should advise adolescent and young adult males to seek prompt medical attention for testicular symptoms such as pain, swelling, or heaviness. Currently, there is insufficient evidence for or against counseling patients to perform periodic self-examination of the testicles.References
1. Davies JM. Testicular cancer in England and Wales: some epidemiological aspects. Lancet 1981; 1:928-32.
2. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 3. Fung CY, Garnick MB. Clinical stage I carcinoma of the testis: a review. J Clin Oncol 1988; 6:734-50.
4. Edson M. Testis cancer: the pendulum swings. Experience in 430 patients. J Urol 1979; 122:763-5.
5. Henderson BE, Benton B, Jing J, et al. Risk factors for cancer of the testes in young men. Cancer 1979; 23:598-602.
6. Prout GR, Griffin PP. Testicular tumors: delay in diagnosis and influence on survival. Am Fam Physician 1984; 29:205-9.
7. Peterson LJ, Catalona WJ, Koehler RE. Ultrasonic localization of a non- palpable testis tumor. J Urol 1979; 122:843-4.
8. Bosl GJ, Vogelzang NJ, Goldman A, et al. Impact of delay in diagnosis on clinical stage of testicular cancer. Lancet 1981; 2:970-2. 9. Field TE. Common errors occurring in the diagnosis of testicular neoplasms and the effect of these errors on prognosis. J R Army Med Corps 1964; 110:152-5.
10. Patton JF, Hewitt CB, Mallis N. Diagnosis and treatment of tumors of the testis. JAMA 1959; 171:2194-8.
11. Earlier diagnosis of testicular tumors (editorial). Br Med J 1980; 280:961.
12. Marty PJ, McDermott RJ. Three strategies for encouraging testicular self-examination among college-aged males. J Am Coll Health 1986; 34:253-8.
13. Ostwald SK, Rothenberger J. Development of a testicular self- examination program for college men. J Am Coll Health 1985; 33:234-9. 14. Friman PC, Finney JW, Glasscock SG, et al. Testicular self-examination: validation of a training strategy for early cancer detection. J Appl Behav Anal 1986; 19:87-92.
15. Westlake SJ, Frank JW. Testicular self-examination: an argument against routine teaching. Fam Pract 1987; 4:143-8.
16. Garnick MB, Mayer RJ, Richie JP. Testicular self-examination (letter). N Engl J Med 1980; 302:297.
17. Einhorn LH, Williams SD. Chemotherapy of disseminated testicular cancer. Cancer 1980; 46:1339-44.
18. Paulson DF. Testicular carcinoma. Curr Prob Cancer 1982; 6:1-44. 19. Post GJ, Belis JA. Delayed presentation of testicular tumors. South Med J 1980; 73:33-5.
20. American Cancer Society. Guidelines for the cancer-related checkup: recommendations and rationale. New York: American Cancer Society, 1980. 21. National Cancer Institute. Working guidelines for early cancer detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
22. Canadian Task Force on the Periodic Health Examination. The periodic health examination, 1984 update. Can Med Assoc J 1984; 130:2-16. 23. American Cancer Society. For men only--testicular cancer and how to do testicular self examination. New York: American Cancer Society, 1984. 24. National Cancer Institute. Testicular self-examination. Washington, D.C.: Government Printing Office, 1986. (Publication no. DHHS (NIH) 87-2636.)
25. Frame PS. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
26. Goldenring JM. Equal time for men: teaching testicular self- examination. J Adol Health Care 1986; 7:273-4.
27. Goldbloom RB. Self-examination by adolescents. Pediatrics 1985; 76:126-8.
Screening for Ovarian Cancer
Recommendation
Screening of asymptomatic women for ovarian cancer is not recommended. It is prudent to examine the uterine adnexa when performing gynecologic examinations for other reasons.Burden of Suffering
Ovarian cancer is the fifth leading cause of cancer deaths among U.S. women(1) and has the highest mortality of any of the gynecologic cancers.(2) It will account for about 20,000 new cases and 12,000 deaths in 1989.(1) It is estimated that 1 in every 70-100 American women is destined to die from this disease.(3,4) The overall five-year survival rate is about 30-35%3,5 and decreases to 4% in women diagnosed with advanced disease.(5) Symptoms usually do not become apparent until the tumor compresses or invades adjacent structures, ascites develops, or metastases become clinically evident.(2) As a result, two-thirds of women with ovarian cancer have advanced (Stage III or IV) disease at the time of diagnosis.(5,6) Carcinoma of the ovary is most common in women over age 60.7 Other important risk factors include increased ovulatory activity (nulliparity, late first pregnancy, late menopause) and a family history of ovarian cancer.(8,9)Efficacy of Screening Tests
Potential screening tests for ovarian cancer include the bimanual pelvic examination, the Papanicolaou (Pap) smear, cytologic examination of peritoneal lavage, tumor markers, and ultrasound imaging. The pelvic examination, which can detect a variety of gynecologic disorders, is of unknown sensitivity and specificity in detecting ovarian cancer. However, small, early-stage ovarian tumors are often not detected by palpation, due to the deep anatomic location of the ovary. Thus, ovarian cancers detected by pelvic examination are generally advanced(7,8,10,11) and associated with poor survival.(8) The pelvic examination may also produce false positives when benign adnexal masses (e.g., functional cysts) are found.(4,8)The Pap smear may occasionally reveal malignant ovarian cells,(12) but it is not considered a reliable screening test for ovarian
carcinoma.(3,8,10,11,13) Studies indicate that the Pap smear has a sensitivity of only 40% in detecting ovarian cancer,(12) and some authors report even lower values (10-30%).(8) Another potential test for ovarian cancer, cytologic examination of peritoneal lavage obtained by culdocentesis, is also considered inappropriate for routine screening. This procedure is impractical in primary care, technically difficult, uncomfortable for patients, and has poor sensitivity in detecting early-stage disease.(4,8,13,14) In one study,(15) only 36% of patients with Stage Ia ovarian cancer had positive cytology when culdocentesis was performed prior to diagnostic laparotomy. This study also demonstrated the poor positive predictive value of the test: only 5.4% of women with positive cytology were subsequently shown to have ovarian cancer.
Serum tumor markers are often elevated in women with ovarian cancer. Examples of these markers include carcinoembryonic antigen, ovarian cystadenocarcinoma antigen, and CA-125 tumor-associated antigen. CA-125 is elevated in 82% of women with advanced (Stage III or IV) ovarian cancer,(16) and it is also elevated, although less frequently, in women with earlier stage disease.(17) Measurements taken prior to diagnostic laparoscopy indicate that CA-125 is elevated in one-half of women with Stage I tumors;18-20 preoperative elevations are more common in women with nonmucinous tumors.(20) These cases are not representative of asymptomatic women in the general population, however. It is not known whether tumor markers become elevated early enough in the natural history of occult ovarian cancer to provide adequate sensitivity for screening. A recent study found that elevated CA-125 levels (greater than 30 U/mL) were present in 24% of blood specimens obtained from women five or more years before ovarian cancer was diagnosed.(17) However, further research is needed to provide more reliable data on the sensitivity of this and other tumor markers in detecting early-stage ovarian cancer in asymptomatic women.
Tumor markers may have limited specificity. It has been reported that CA-125 is elevated in 1% of healthy women, 6-40% of women with benign masses (e.g., uterine fibroids, endometriosis, pancreatic pseudocyst, pulmonary hamartoma), and 29% of women with nongynecologic cancers (e.g., pancreas, stomach, colon, breast).(16,21) It may be possible to improve the specificity of CA-125 measurement by selective screening of postmenopausal women,(22) through modifications in the assay technique,(23) or by combining CA-125 measurement with ultrasound (see below). However, prospective studies involving asymptomatic women are needed to provide definitive data on the performance characteristics of these techniques when used as screening tests.
Ultrasound imaging has also been evaluated as a screening test for ovarian cancer, since it is able to accurately estimate ovarian size, detect masses as small as 1 cm, and distinguish solid lesions from cysts.(10,24) Studies have shown, however, that routine ultrasound testing of asymptomatic women has a low yield in detecting ovarian cancer and generates a large proportion of false-positive results that often require diagnostic laparotomy or laparoscopy. In one study, ultrasound screening of 805 high- risk women led to 39 laparotomies, which revealed one ovarian carcinoma, two borderline tumors, one cancer of the cecum, and five cystadenomas.(25) In a larger study, ultrasound was performed routinely on 5678 asymptomatic female volunteers over age 45 or with a history of previous breast or gynecologic cancer.(14) Two Stage I ovarian cancers were detected in a total of 6920 scans performed over two years. A recent preliminary report from the same center indicated that 14,356 ultrasound examinations performed over three years on 5489 asymptomatic women over age 45 detected five ovarian cancers.(26) Although the sensitivity and specificity of the test were excellent (100% and 94.6%, respectively), the positive predictive value in this low-risk study population was only 2.6%. It has been calculated from these results and other data that ultrasound screening of 100,000 women over age 45 would detect 40 cases of ovarian cancer, but at a cost of 5398 false positives and over 160 complications from diagnostic laparoscopy.(27)
It may be possible to improve accuracy by combining ultrasound with other screening tests, such as the measurement of CA-125. This approach has been shown to be a useful method of discriminating between benign and malignant adnexal masses in preoperative patients.(28) Further research is needed, however, to determine the sensitivity, specificity, and positive predictive value of performing these tests in combination to screen asymptomatic women. One prospective study(29) screened 1010 asymptomatic postmenopausal women over age 45 with pelvic examination and CA-125 measurement; those with abnormal results received an ultrasound examination. Although one ovarian cancer was detected (all three screening tests were positive in this woman), the study demonstrated poor positive predictive value with each of the three screening tests. No abnormality was discovered in 28 of the 31 women with elevated CA-125. Fibroids and benign cysts were responsible for over half of the 28 abnormal pelvic examinations. There were 13 abnormal ultrasound examinations; 12 of these women consented to laparotomy, which revealed six benign ovarian cysts, two fimbrial cysts, two women with no surgical findings, one woman with adhesions, and the ovarian cancer.
Effectiveness of Early Detection
There is no direct evidence from prospective studies that women with early-stage ovarian cancer detected through screening have lower mortality from ovarian cancer than do women with more advanced disease. A large body of indirect evidence, however, suggests that this is the case. Although lead-time and length biases may be responsible, it is known that survival from ovarian cancer is related to stage at diagnosis. The five-year survival rate is 66.4% at Stage I, 45% at Stage II, 13.3% at Stage III, and only 4.1% at Stage IV.(5) Studies have shown that the most important prognostic factor in patients with advanced ovarian cancer is the size of residual tumor after treatment.(2,6) Surgical debulking, abdominal radiotherapy, and chemotherapy for ovarian cancer appear to be more effective in reducing the size of residual tumor when ovarian cancer is detected early.(2) Although these observations provide suggestive evidence that early detection may be beneficial, conclusive proof will require properly conducted prospective studies comparing long-term mortality from ovarian cancer between screened and non-screened cohorts.Recommendations of Others
Although some authors have advocated selective screening for ovarian cancer by ultrasound,(10,30) and even by culdocentesis in certain high-risk groups,(4,8) there are no official recommendations to screen for ovarian cancer in asymptomatic women. The pelvic examination is, however, mentioned in a recent consensus recommendation on Pap testing issued by the American Cancer Society, National Cancer Institute, American College of Obstetricians and Gynecologists, American Medical Association, American Nurses Association, American Academy of Family Physicians, and the American Medical Women's Association.(31) Specifically, the pelvic examination (and Pap smear) are recommended annually for all women who are or have been sexually active or have reached age 18. Although Pap testing may be performed less frequently once three annual smears have been normal, the organizations did not specifically recommend reducing the frequency of pelvic examinations. An annual pelvic examination has been advocated in the past by the American College of Obstetricians and Gynecologists(32) and the American Cancer Society.(3) The pelvic examination is considered by the National Cancer Institute(33) and others(8,11) to be a necessary component of the complete physical examination. Recently, however, a number of authors have advised against performing periodic pelvic examinations to detect ovarian cancer.(34,35) There are no recommendations to perform routine ultrasound examinations to detect ovarian cancer.Clinical Intervention
Screening of asymptomatic women for ovarian cancer is not recommended. It is clinically prudent to examine the uterine adnexa when performing gynecologic examinations for other reasons.References
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 2. Slotman BJ, Rao BR. Ovarian cancer: etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy. Anticancer Res 1988; 8:417-34.
3. American Cancer Society. Cancer facts and figures, 1987. New York: American Cancer Society, 1987.
4. Griffiths CT. Carcinoma of the ovary and fallopian tube. In: Holland JF, Frei E, eds. Cancer medicine. Philadelphia: Lea and Febiger, 1982:1958-69.
5. Richardson GS, Scully RE, Nikrui N, et al. Common epithelial cancer of the ovary. N Engl J Med 1985; 312:415-24.
6. Young RC. Ovarian cancer treatment: progress or paralysis. Semin Oncol 1984; 11:327-9.
7. Young JL, Percy CL, Asire AJ, eds. SEER Program: incidence and mortality, 1973-1977. National Cancer Institute, Monograph 57. Washington, D.C.: Government Printing Office, 1981:75.
8. Smith LH, Oi RH. Detection of malignant ovarian neoplasm: a review of the literature. 1. Detection of the patient at risk; clinical, radiological and cytological detection. Obstet Gynecol Surv 1984; 39:313-28.
9. Hildreth NG, Kelsey JL, LiVolsi VA, et al. An epidemiological study of epithelial carcinoma of the ovary. Am J Epidemiol 1981; 114:398-405. 10. Lynch HT, Albano WA, Lynch JF, et al. Surveillance and management of patients at high genetic risk for ovarian carcinoma. Obstet Gynecol 1982; 59:589-96.
11. Hall DJ, Hurt WG. The adnexal mass. J Fam Pract 1982; 14:135-40. 12. Graham JB, Graham RM, Schueller EF. Preclinical detection of ovarian cancer. Cancer 1964; 17:1414.
13. Rubin P, Bennett JM. Ovarian cancer. In: Bakeman RP, ed. Clinical oncology for medical students and physicians: a multidisciplinary approach, 5th ed. New York: American Cancer Society, 1978:114-20.
14. Goswamy RK, Campbell S. Screening for ovarian cancer. IARC Sci Publ 1986; 76: 305-9.
15. Keettel WC, Pixley EE, Buckshaum HJ. Experience with peritoneal cytology in management of gynecologic malignancies. Am J Obstet Gynecol 1974; 120:174.
16. Bast RC, Klug TL, St John E, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian carcinoma. N Engl J Med 1983; 309:883-7.
17. Zurawski VR Jr, Orjaseter H, Andersen A, et al. Elevated serum CA 125 levels prior to diagnosis of ovarian cancer neoplasia: relevance for early detection of ovarian cancer. Int J Cancer 1988; 42:677-80. 18. Jacobs I. Screening for ovarian cancer by CA-125 measurement. Lancet 1988; 1:889.
19. Mann WJ, Patsner B, Cohen H, et al. Preoperative serum CA-125 levels in patients with surgical stage I invasive ovarian adenocarcinoma. JNCI 1988; 80:208-9.
20. Zurawski VR Jr, Knapp RC, Einhorn N, et al. An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma. Gynecol Oncol 1988; 30:7-14.
21. Di-Xia C, Schwartz P, Xinguo L, et al. Evaluation of CA 125 levels in differentiating malignant from benign tumors in patients with pelvic masses. Obstet Gynecol 1988; 72:23-7.
22. Zurawski VR Jr, Broderick SF, Pickens P, et al. Serum CA 125 levels in a group of nonhospitalized women: relevance for the early detection of ovarian cancer. Obstet Gynecol 1987; 69:606-11.
23. Klug TL, Green PJ, Zurawski VR Jr, et al. Confirmation of a false- positive result in CA 125 immunoradiometric assay caused by human anti- idiotypic immunoglobulin. Clin Chem 1988; 34:1071-6.
24. Campbell S, Goessens L, Goswamy R, et al. Real-time ultrasound for determination of ovarian morphology and volume: a possible early screening test for ovarian cancer? Lancet 1982; 1:425-6. 25. Andolf E, Svalenius E, Astedt B. Ultrasonography for early detection of ovarian carcinoma. Br J Obstet Gynecol 1986; 93:1286-9.
26. Campbell S, Bhan V, Royston J, et al. Screening for early ovarian cancer. Lancet 1988; 1:710-1.
27. Jacobs I. Screening for early ovarian cancer. Lancet 1988; 2:171-2. 28. Finkler NJ, Benacerraf B, Lavin PT, et al. Comparison of serum CA 125, clinical impression, and ultrasound in the preoperative evaluation of ovarian masses. Obstet Gynecol 1988; 72:659-64.
29. Jacobs I, Stabile I, Bridges J, et al. Multimodal approach to screening for ovarian cancer. Lancet 1988; 1:268-71.
30. Ferrucci JT Jr. Screening for ovarian cancer. JAMA 1986; 255:3169. 31. Fink DJ. Change in American Cancer Society checkup guidelines for detection of cervical cancer. CA 1988; 38:127-8.
32. American College of Obstetricians and Gynecologists. Standards for obstetric-gynecologic services, 6th ed. Washington, D.C.: American College of Obstetricians and Gynecologists, 1985:53-5.
33. National Cancer Institute, Division of Cancer Prevention and Control. Working guidelines for early detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
34. Frame PS. A critical review of adult health maintenance. Part 3. Prevention of cancer. J Fam Pract 1986; 22:511-20.
35. Ganiats TG. Screening for ovarian cancer. JAMA 1986; 256:1892.
Screening for Pancreatic Cancer
Recommendation
Routine screening for pancreatic cancer in asymptomatic persons is not recommended.Burden of Suffering
Pancreatic cancer is the fifth leading cause of cancer deaths in the United States, accounting for 25,000 deaths in 1989.(1) The age-adjusted incidence and mortality of pancreatic cancer have been increasing since the 1930s.(2,3) Since initial symptoms are usually nonspecific and are frequently disregarded, about 85% of symptomatic patients have regional and distant metastases by the time they are diagnosed.(4) At this stage, the disease is usually inoperable.(5) Only 4% of the 26,000 new cases of pancreatic cancer diagnosed annually live more than three years after diagnosis.(6) Pancreatic cancer is more common in older persons (80% of cases occur between ages 60 and 80), blacks, and cigarette smokers.(2,3,6)Efficacy of Screening Tests
There are no reliable screening tests for detecting pancreatic cancer in asymptomatic persons. The deep anatomic location of the pancreas makes detection of small localized tumors unlikely during the routine abdominal examination. Even in patients with confirmed pancreatic cancer, an epigastric mass is palpable in only 12-20% of cases.(5,7) The most accurate tests for pancreatic cancer, such as computerized axial tomography and endoscopic retrograde cholangio-pancreatography, are inappropriate for routine screening due to their cost and invasiveness. A noninvasive screening test, ultrasonography, can detect some tumors in the head of the pancreas, where cancers are more resectable.(8) Although ultrasound has a reported sensitivity of 79% and a specificity of 94%,(9) data from most ultrasound studies are based on examinations of symptomatic patients with suspected disease. They thus provide little information on the efficacy of abdominal ultrasound as a screening test in asymptomatic persons.Persons with pancreatic cancer often have elevated levels of certain serologic markers. These include carcinoembryonic antigen, carbohydrate antigen 19-9, pancreatic oncofetal antigen, tissue polypeptide antigen, inhibited leukocyte adherence, galactosyl transferase isoenzyme II, and a number of other peptides and hormones. Although studies suggest that serologic markers are elevated in most patients with pancreatic cancer,(8-13) no single marker has achieved acceptance as a suitable screening test for asymptomatic persons. This is because most tests have only been studied in high-risk populations, such as symptomatic patients with suspected or confirmed pancreatic cancer. Many of these tests lack adequate sensitivity and specificity, and some serologic markers are elevated only after the tumor has progressed to an advanced stage. Also, routine testing for serologic markers in asymptomatic persons would generate a large proportion of false-positive results, due to the low prevalence of pancreatic cancer in the general population.(10) Studies indicate that 15-50% of elevations of various serologic markers are due to benign gastrointestinal diseases or malignancies other than pancreatic cancer.(8-13)
Effectiveness of Early Detection
There is little conclusive evidence that early detection can lower morbidity or mortality from pancreatic cancer. The current five-year survival for localized disease is 5%, only slightly higher than five-year survival with regional (4%) and distant (1%) metastases.(6) There is some evidence to suggest that surgically treated patients with resectable tumors survive longer than those with more advanced disease,(14,15) but the designs of most studies of surgical outcome suffer from lead-time, length, and selection biases.(15) Surgery is performed in less than 10% of patients with pancreatic cancer,(15) and it is not without risk; estimates of perioperative mortality range between 3% and 20%.(16)Recommendations of Others
There are no official recommendations to perform routine screening for pancreatic cancer in asymptomatic persons, and some authors(15) have specifically advised against the practice.Discussion
Primary prevention of pancreatic cancer may be possible through clinical efforts directed at the use of tobacco products. Studies suggest that cigarette smoking is an important risk factor for this disease.(2) Although the causal relationship between smoking and pancreatic cancer requires further study, counseling patients to discontinue smoking (see Counseling to Prevent Tobacco Use) is easily justified by its established efficacy in preventing other malignancies (e.g., lung cancer), coronary artery disease, and other serious disorders.Clinical Intervention
Routine screening for pancreatic cancer in asymptomatic persons is not recommended. All patients should be counseled regarding the use of tobacco products.References
1. American Cancer Society. Cancer statistics, 1988. CA 1989; 39:3-20. 2. Gordis L, Gold EB. Epidemiology of pancreatic cancer. World J Surg 1984; 8:808-21.
3. Levin DL, Connelly RR, Devesa SS. Demographic characteristics of cancer of the pancreas: mortality, incidence, survival. Cancer 1981; 47:1456-68.
4. Go VLW, Taylor WF, DiMagno EP. Efforts at early diagnosis of pancreatic cancer: the Mayo Clinic experience. Cancer 1981; 47:1698-703. 5. Macdonald JS, Widerlite L, Schein PS. Current diagnosis and management of pancreatic carcinoma. JNCI 1976; 56:1093-9.
6. American Cancer Society. Cancer facts and figures, 1987. New York: American Cancer Society, 1987.
7. Gudjonsson B, Livstone EM, Spiro HM. Cancer of the pancreas: diagnostic accuracy and survival statistics. Cancer 1978; 42:2494-506. 8. Moossa AR, Levin B. The diagnosis of "early" pancreatic cancer: the University of Chicago experience. Cancer 1981; 47:1688-97. 9. Wang TH, Lin JT, Chen DS, et al. Noninvasive diagnosis of advanced pancreatic cancer by real-time ultrasonography, carcinoembryonic antigen, and carbohydrate antigen 19-9. Pancreas 1986; 1:219-23. 10. Podolsky DK. Serologic markers in the diagnosis and management of pancreatic carcinoma. World J Surg 1984; 8:822-30.
11. Evaluation of CA 19-9 as a serum tumour marker in pancreatic cancer. Br J Cancer 1986; 53:197-202.
12. Basso D, Fabris C, Del Favero G, et al. Combined determination of serum CA 19-9 and tissue polypeptide antigen: why not improvement in pancreatic cancer diagnosis? Oncology 1988; 45:24-9.
13. Podolsky DK, McPhee MS, Alpert E, et al. Galactosyltransferase isoenzyme II in the detection of pancreatic cancer: comparison with radiologic, endoscopic, and serologic tests. N Engl J Med 1981; 304:1313-8.
14. Cancer of the Pancreas Task Force. Staging of cancer of the pancreas. Cancer 1981; 47:1631-7.
15. Early diagnosis and screening for pancreatic cancer. Lancet 1986; 2:785-6.
16. Trede M. The surgical treatment of pancreatic carcinoma. Surgery 1985; 97:28-35.
Screening for Oral Cancer
Recommendation
Routine screening of asymptomatic persons for oral cancer by primary care clinicians is not recommended. It may be prudent for clinicians to perform careful examinations for cancerous lesions of the oral cavity in patients who use tobacco or excessive amounts of alcohol, as well as in those with suspicious symptoms or lesions detected through self- examination. All patients should be counseled to receive regular dental examinations, to discontinue the use of all forms of tobacco, and to limit consumption of alcohol. Persons with increased exposure to sunlight should be advised to take protective measures to protect their lips and skin from the harmful effects of ultraviolet rays.Burden of Suffering
Oral cancer will account for over 30,000 new cases and about 8600 deaths in the United States in 1989.(1) Since over half of these cancers have metastasized or become invasive at the time of diagnosis,(2,3) overall five-year survival from this form of cancer is poor (30-50%).(1,4) Carcinoma of the tongue, the most frequent site of oral cancer (excluding the lip), has an overall five-year survival of less than 15%.(2) About half of all oropharyngeal cancers and the majority of deaths from this disease occur in persons over age 65.(5) In addition to age, other major risk factors include the use of tobacco (smoking of cigarettes, pipes, or cigars; smokeless tobacco, i.e., chewing tobacco or snuff) and the excessive consumption of alcohol.(5)Efficacy of Screening Tests
The principal screening test for oropharyngeal cancer in asymptomatic persons is inspection and palpation of the oral cavity. Studies indicate that many oral cancers occur on the floor of the mouth, the ventral and lateral regions of the tongue, and the soft palate, anatomic sites that may be inaccessible to routine visual inspection.(3,5) The recommended examination technique involves a careful exploration of the oral cavity with a gloved hand and a gauze pad, retraction of the tongue to expose ventral and posterolateral surfaces and the floor of the mouth, and bidigital palpation for masses.(2,6) There is little information, however, on the sensitivity of this procedure in detecting oral cancer or on the frequency of false-positive results when a lesion is found. In addition, it may be impractical for physicians to perform a complete examination in this manner on all patients. The abbreviated oral inspection that is more typical of the routine physical examination is also of unknown accuracy and predictive value. Some studies suggest that dentists are more effective than physicians in routinely performing a complete mouth examination and detecting early-stage oral cancer.(7) Unfortunately, older Americans, the population at greatest risk for oral cancer, visit the dentist infrequently (an average of less than once every five years); physician visits are six times as common at this age.(2)Alternative screening tests for oral cancer have been proposed, such as tolonium chloride rinses to stain suspicious lesions,(8) but further research is needed to evaluate the accuracy and acceptability of these techniques before routine use in the general population can be considered.
Effectiveness of Early Detection
There is evidence that persons with early-stage oral cancer have a better prognosis than those diagnosed with more advanced disease. In one study, overall five-year survival was 63% for persons with localized disease, 30% for those with regional extension, and 17% for persons with cancers with distant metastases.(7) Similar findings have been published in other series. However, the role of lead-time bias, length bias, and other factors in the interpretation of these data has not been fully considered; some authors have questioned the effectiveness of early detection in improving prognosis.(9) Further research is needed to demonstrate in a prospective fashion that the outcome of oral cancer is improved when lesions are detected in asymptomatic persons.Recommendations of Others
The Canadian Task Force recommends that an annual visual inspection of the mouth include an examination for oral cancer in males and in all smokers.(10) Similarly, the National Cancer Institute(11) and the American Cancer Society(12) recommend that a complete oral examination for cancer be included in the periodic health examination.Discussion
Available screening tests for oral cancer are limited to the physical examination of the mouth, a test of undetermined sensitivity, specificity, and positive predictive value. The primary care physician faces logistical difficulties in performing a thorough mouth examination on every patient. There is also inadequate evidence that early detection of oral cancer necessarily improves outcome. Although direct evidence of benefit is lacking, examinations for oral cancer in asymptomatic persons may be clinically prudent in persons at significantly increased risk for the disease (i.e., persons with a smoking or alcohol history, or those with suspicious lesions). It is also appropriate to refer patients for regular visits to the dentist, for whom complete examination of the oral cavity is often more feasible (see Counseling to Prevent Dental Disease).Primary prevention strategies, such as counseling patients regarding the use of tobacco and alcohol, may have a greater impact on the morbidity and mortality associated with oral cancer than measures aimed at early detection. There is good evidence that smoking and excessive consumption of alcohol are both independent and synergistic risk factors for oral cancer.(5) Over 90% of oropharyngeal cancer deaths are associated with smoking.(13) In addition to smoking and alcohol, oral cancer is also associated with the use of snuff and chewing tobacco.(14,15) Smokeless tobacco is used by over 10 million Americans(14,16) and a growing number of young persons under the age of 21 (currently estimated at 3 million).(16) Between 8% and 36% of male high school and college students are regular users of smokeless tobacco, and there is evidence that young children (aged 8-13) may also have significant exposure in some geographic areas.(15) Young people who use smokeless tobacco may be more likely to switch to cigarette smoking as they grow older.(17) Efforts by patients to reduce or eliminate exposure to these substances will have benefits that extend beyond the prevention of oral cancer. Smoking is a leading risk factor for lung cancer, atherosclerosis, and a number of other serious diseases (see Counseling to Prevent Tobacco Use), and alcohol abuse is associated with addictive behavior, medical disorders, and increased risk of injuries (Screening for Alcohol and Other Drug Abuse). Finally, measures to reduce outdoor exposure to sunlight may reduce the risk of lip cancer, along with other forms of skin cancer.
Clinical Intervention
Routine screening examinations for oral cancer by primary care clinicians are not recommended for all asymptomatic persons. It may be clinically prudent to include an examination for cancerous and precancerous lesions of the oral cavity in the periodic health examination of persons with exposure to tobacco and excessive amounts of alcohol, as well as in persons with suspicious symptoms or lesions detected through self- examination. All patients, especially those over age 65, should be advised to receive a complete dental examination on a regular basis (see Counseling to Prevent Dental Disease). All adolescent and adult patients should be asked to describe their use of tobacco (Counseling to Prevent Tobacco Use) and alcohol (Screening for Alcohol and Other Drug Abuse). Appropriate counseling should be offered to those persons who smoke cigarettes, pipes, or cigars, those who use chewing tobacco or snuff, and those who have evidence of alcohol abuse. Persons with increased exposure to sunlight should be advised to take protective measures when outdoors to protect their lips and skin from the harmful effects of ultraviolet rays (Screening for Skin Cancer).Note: See Appendix A for the U.S. Preventive Services Task Force Table of Ratings for this topic. See also the relevant Task Force background paper: Greene JC. Preventive dentistry. In: Goldbloom RB, Lawrence RS, eds. Preventing disease: beyond the rhetoric. New York: Springer-Verlag (in press).
References
1. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 2. Chiodo GT, Eigner T, Rosenstein DI. Oral cancer detection: the importance of routine screening for prolongation of survival. Postgrad Med 1986; 80:231-6.
3. Mashberg A, Meyers H. Anatomical site and size of 222 early asymptomatic oral squamous carcinomas. Cancer 1976; 37:2149-57.
4. Orlian AI. Cancer of the soft tissues of the oral cavity. NY State Dent J 1983; 49:704-9.
5. Baden E. Prevention of cancer of the oral cavity and pharynx. CA 1987; 37:49-62.
6. Hahn W. Clinical signs for the early recognition of cancer of the oral cavity. Int Dent J 1977; 27:165-71.
7. Elwood JM, Gallagher RP. Factors influencing early diagnosis of cancer of the oral cavity. Can Med Assoc J 1985; 133:651-6.
8. Mashberg A. Final evaluation of tolonium chloride rinse for screening of high-risk patients with asymptomatic squamous carcinoma. J Am Dent Assoc 1983; 106:319-23.
9. William RG. The early diagnosis of carcinoma of the mouth. Ann R Coll Surg Engl 1981; 63:423-5.
10. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1-45.
11. National Cancer Institute. Working guidelines for early cancer detection: rationale and supporting evidence to decrease mortality. Bethesda, Md.: National Cancer Institute, 1987.
12. American Cancer Society. Guidelines for the cancer-related checkup: recommendations and rationale. CA 1980; 30:4-50.
13. Department of Health and Human Services. Reducing the health consequences of smoking: 25 years of progress. A report of the Surgeon General. Rockville, Md.: Department of Health and Human Services, 1989. (Publication no. DHHS (PHS) 89-8411.)
14. Idem. The health consequences of smokeless tobacco: a report of the advisory committee to the Surgeon General. Washington, D.C.: Government Printing Office, 1986. (Publication no. DHHS (PHS) 86-2874.) 15. Connoly GN, Winn DM, Hecht SS, et al. The reemergence of smokeless tobacco. N Engl J Med 1986; 314:1020-7.
16. National Institutes of Health. Consensus development conference statement: health implications of smokeless tobacco use. Bethesda, Md.: National Institutes of Health, 1986.
17. Glover ED, Laflin M, Edwards SW. Age of initiation and switching patterns between smokeless tobacco and cigarettes among college students in the United States. Am J Public Health 1989; 79:207-8.
Screening for Diabetes Mellitus
Recommendation
An oral glucose tolerance test for gestational diabetes mellitus is recommended for all pregnant women between 24 and 28 weeks of gestation. Routine screening for diabetes in asymptomatic nonpregnant adult patients, using plasma glucose measurement or urinalysis, is not recommended for the general population, but it may be appropriate in selected high-risk groups (see Clinical Intervention).Burden of Suffering
Approximately 11 million persons in the United States have diabetes mellitus, and about 5 million of them have not been diagnosed.(1,2) Diabetes can cause life-threatening metabolic complications, and it is an important risk factor for other leading causes of death, such as coronary artery disease, congestive heart failure, and cerebrovascular disease. Diabetes is the seventh leading cause of death in the United States, accounting for over 130,000 deaths each year.(3,4) It is an important contributor to deaths from other causes as well.(4) Diabetes is a leading cause of neuropathy, which develops in at least 50% of patients within 25 years of diagnosis.(5) Diabetic peripheral vascular disease accounts for about 50,000 amputations each year.(6) Diabetic microvascular disease can lead to renal failure and blindness. Diabetic nephropathy, a complication in about 10% of cases, accounts for one-quarter of all new dialysis patients.(1) Diabetes is the leading cause of blindness in adults, with about 5800 people each year losing their sight as a result of this disease.(7) Infants born of diabetic women are at increased risk of prematurity, perinatal mortality, macrosomia, congenital malformations, and metabolic derangements.(8,9) Direct and indirect costs of diabetes in the United States total at least $14 billion per year.(10)About 90% of all cases of diabetes are Type II, or noninsulin-dependent diabetes mellitus (NIDDM).(2) This form of diabetes generally occurs in adults and is increasingly common after age 40. About 2 million older Americans have diabetes.(11) NIDDM is more common in blacks, Hispanics, and Native Americans. About 1 million black Americans have diabetes.(12) Other important risk factors for NIDDM include family history, obesity, and a history of gestational diabetes. Type I diabetes, or insulin-dependent diabetes mellitus (IDDM), accounts for about 10% of all cases of diabetes and characteristically has an acute onset during childhood or adolescence.
Gestational diabetes, the development of impaired glucose tolerance during pregnancy in nondiabetic women, occurs in about 3% of pregnancies. This condition is a risk factor for fetal macrosomia and may also be associated with other maternal and neonatal complications. Although macrosomia by itself is not a morbid condition, it is associated with increased risk of birth trauma from skull and clavicular fracture, shoulder dystocia, and peripheral nerve injury.(13-16) As mentioned, a history of gestational diabetes is also a maternal risk factor for the development of NIDDM, and it may be an indicator of long-standing impaired glucose tolerance.(17)
Efficacy of Screening Tests
Although a number of techniques are available to test for diabetes (e.g., hemoglobin A1c), the principal screening test for asymptomatic persons is blood glucose measurement. Glucose can be measured at random, after the patient has fasted, following a meal (postprandial), or at specified intervals after the administration of a known oral dose of glucose (oral glucose tolerance test (GTT)). These tests are used to detect impaired glucose tolerance, a condition that is present in diabetes but that can also occur before diabetes develops. To be classified as having diabetes rather than impaired glucose tolerance alone, an individual must have a fasting plasma glucose of 140 mg/dL (7.8 mmol/L) or greater, an elevated plasma glucose following a 75 g oral glucose tolerance test (200 mg/dL (11.1 mmol/L) or greater at both the 2-hour test and between 0 and 2 hours), or the presence of classic symptoms such as polyuria, polydypsia, and ketonuria.(18) (A higher, 100 g dose and different threshold criteria have been used since the 1960s for the detection of gestational diabetes in pregnant women.)(19) An individual is thought to have impaired glucose tolerance in the absence of diabetes if plasma glucose is between 140 mg/dL (7.8 mmol/ L) and 200 mg/dL (11.1 mmol/L) two hours after a 75 g challenge and the plasma glucose prior to two hours equals or exceeds 200 mg/dL (11.1 mmol/L).(18)The need for such complex criteria is due in part to the difficulty of using a single glucose value as a basis for screening for diabetes. No specific glucose level discriminates completely between persons with impaired glucose tolerance or diabetes and the normal population. There is a wide overlap in the range of blood glucose concentrations within such populations. Even within individuals, there is considerable temporal variation in blood glucose in relation to meals. Thus, adopting a low threshold criteria for defining hyperglycemia will result in high sensitivity but poor specificity for impaired glucose tolerance and diabetes. Conversely, a blood glucose above 200 mg/dL (11.1 mmol/L) is considered an unequivocal sign of impaired glucose tolerance,(20) but many cases would be overlooked if this high threshold value were adopted for screening.
There are advantages and disadvantages to the various glucose screening tests. Fasting glucose measurement is less practical for routine screening than random measurement because the patient must not eat for 8 to 10 hours before the test, but it is generally more accurate. Nonetheless, its sensitivity as a screening test is limited; in one survey, only 25% of persons with undiagnosed diabetes had fasting glucose levels greater than 140 mg/dL (7.8 mmol/L).(21) Postprandial testing (levels above 200 mg/dL (11.1 mmol/L) 90-120 minutes after a meal) may be more convenient for patients and more sensitive in detecting impaired glucose tolerance, but it is not ideal for screening purposes due to the time constraints. The 75 g oral GTT provides the greatest accuracy, but the test is not suited for routine screening due to the inconvenience and cost associated with glucose administration and multiple venipunctures over a period of several hours. Rather than being used as a routine screening test, the GTT is often used as a confirmatory test once diabetes is suspected.
A shorter (one hour) and lower dose (50 g) GTT is now used as a routine screening test for gestational diabetes. A level of 140 mg/dL (7.8 mmol/L) or greater one hour after the 50 g glucose challenge has a reported sensitivity of 83% and a specificity of 87% when compared with the 100 g GTT.(22) Assuming a prevalence of 3% for gestational diabetes, routine use of the 50 g test in pregnant women would generate five false positives for every case of gestational diabetes detected. The test may also have limited reproducibility; up to 75% of patients with a positive GTT have been found to be negative on subsequent testing.(23,24) The high false-positive rate is of significance because mislabeled patients may experience anxiety and inconvenience from follow-up diagnostic testing. Dietary restrictions and unnecessary fetal monitoring and operative deliveries may also result if the error is not disclosed in subsequent testing. There are, however, few reliable data regarding the magnitude of these problems.
Urine testing for glucosuria is considered a poor screening test for diabetes, primarily because the concentration of glucose in urine is variable and because glucosuria may occur at normal blood glucose levels in persons with a low renal threshold for glucose.(25) Urine glucose measurement has been reported to have a sensitivity of less than 30%.(26) In addition, urinalysis is subject to inaccuracies caused by improper specimen collection and testing. Even in persons with known diabetes, urinalysis is being replaced by self-monitoring of blood glucose as a more effective technique for daily assessment of glycemic control.(27,28)
Effectiveness of Early Detection
The detection of impaired glucose tolerance or diabetes in asymptomatic persons provides an opportunity to attempt to prevent or delay the complications of diabetes through dietary and pharmacologic measures to achieve euglycemia. The presumed benefits of early detection are based on evidence that many of the complications of diabetes are directly related to the duration and severity of hyperglycemia.(29-32) There is little direct evidence that asymptomatic persons benefit from the detection and treatment of impaired glucose tolerance in the absence of overt diabetes.(33,34) Most asymptomatic persons with impaired glucose tolerance do not develop diabetes even in the absence of treatment; longitudinal data suggest that only 15-30% of such cases progress to frank diabetes.(35-37) Among persons with impaired glucose tolerance who are destined to develop diabetes, there is conflicting evidence regarding the ability of early hypoglycemic therapy to prevent the progression of the disease. One prospective trial found that dietary and pharmacologic treatment did reduce progression to diabetes,(35) but other prospective studies have reported no beneficial effect.(36-38) Thus, although impaired glucose tolerance is an important risk factor for diabetes, it is not by itself an established indication for treatment.It is also unclear whether treatment reduces the risk of long-term complications after diabetes (IDDM or NIDDM) has developed. Aggressive clinical maneuvers to maintain euglycemia ("tight control") are efficacious in achieving normal plasma glucose levels and reducing the risk of metabolic derangements. Longitudinal studies demonstrate a correlation between the level of glucose control and the incidence of microvascular complications (e.g., diabetic nephropathy and retinopathy).(39-42) However, the benefits of tightened control have been difficult to demonstrate with certainty under controlled experimental conditions. Two controlled trials that examined the efficacy of continuous subcutaneous insulin infusion in reducing progression of microvascular disease in IDDM were unable to demonstrate significant slowing of retinal deterioration within the first year of treatment. In fact, tightened control produced an early acceleration in retinal deterioration.(43,44) Follow-up data from both research groups suggest that reduced progression of retinopathy may become more apparent two years after treatment, but the data are inconclusive due to limitations in study design.(45,46) Both groups also reported that renal function, as measured by urinary albumin excretion, was improved in those who received continuous insulin treatment.(45,47) Another controlled trial, which found that progression of retinopathy and neuropathy was reduced after two years of treatment with continuous insulin infusion, suffered from small sample size and other design limitations.(48)
Macrovascular benefits from treatment, such as reduced cardiovascular disease, have also been presumed but not proved convincingly in clinical trials. Although a large trial reported that glucose control in patients with NIDDM did not appear to lower the rate of vascular complications or deaths in over 12 years of observation, there is substantial controversy regarding the design of this study.(49,50) A clear association between glucose control and overall mortality has also been difficult to demonstrate in longitudinal studies.(51) A multicenter randomized trial is currently under way to provide further data on the health benefits of maintaining euglycemia in patients with IDDM.(52)
In women with IDDM who become pregnant, glycemic control may have a direct effect on maternal and neonatal outcome. A temporal relationship between metabolic control during certain periods of pregnancy and the incidence of maternal and fetal complications has been demonstrated in a number of studies.(53) Women with IDDM who are enrolled in intensive programs to maintain euglycemia during pregnancy appear to have better outcomes than matched controls, although selection biases in these studies may contribute to some of these differences.(54) Historical data demonstrate a dramatic decline in the rate of maternal deaths and neonatal complications (e.g., perinatal death, macrosomia, congenital malformations, postpartum metabolic derangements) in the years following the introduction of insulin.(55,56) Factors other than strict glycemic control, such as closer monitoring of both mother and fetus and vigorous management of the infant after delivery, may have also contributed significantly to this trend.
In addition to instituting hypoglycemic therapy, another possible argument for routine screening is the identification of candidates for laser photocoagulation therapy, which can slow the progression of diabetic retinopathy.(57) However, retinopathy requiring treatment is rare early in the course of the disease,(58,59) and therefore it is unlikely that screening would result in increased benefit from the procedure. Since diabetes is often associated with other serious diseases (e.g., coronary artery disease, peripheral vascular disease), the discovery of diabetes might lead to early detection and treatment of these other conditions. There are, however, few data regarding the accuracy and efficiency of using diabetes screening as a means of detecting other diseases. In addition, more sensitive and specific screening tests are available for most of the conditions associated with diabetes.
Pregnant women with an abnormal oral GTT are at significantly increased risk of macrosomia, preeclampsia, and other complications.(60) The early detection and treatment of gestational diabetes to achieve euglycemia has been associated in observational studies with significantly lower neonatal mortality and morbidity (macrosomia, birth trauma, operative delivery).(61-66) However, the designs of these studies, which are often nonrandomized and lack proper controls, do not permit the conclusion that the treatment of gestational diabetes (rather than other components of prenatal care) was by itself responsible for the improved outcome. Two controlled trials have provided stronger evidence of treatment efficacy.(67,68) In both studies, diet and insulin treatment of gestational diabetes were associated with a significant decrease in the incidence of macrosomia; no differences were reported in neonatal mortality or other outcome measures. In a more recent randomized controlled trial, there were no differences in outcome between women treated with diet and insulin and those treated with diet alone.(69)
Thus, the principal benefit of screening for gestational diabetes that has been proved under controlled experimental conditions is the prevention of macrosomia, a condition associated with increased risk of birth trauma and operative delivery.(13-16) The majority of macrosomic infants are born to women without gestational or insulin-dependent diabetes;(70) other factors such as maternal obesity may be more important. In a study of 574 macrosomic infants, gestational diabetes was present in only 5% of the mothers, whereas 45% were overweight (greater than 90 kg).(71) It is therefore unclear whether the overall incidence of macrosomia in the population will be affected significantly by early detection of gestational diabetes or whether the effect will be of sufficient magnitude and clinical value to justify routine screening of all pregnant women.
Recommendations of Others
Recommendations against routine screening for diabetes in nonpregnant adults have been issued by the Canadian Task Force(72) and other experts on the periodic health examination.(73) The American Diabetes Association (ADA) recommends screening high-risk groups by performing fasting or random blood glucose measurements.(74) The Canadian Task Force recommends screening pregnant women for gestational diabetes by assessing risk factors and by repeated urine glucose testing.(72) In 1985, the Second International Workshop-Conference on Gestational Diabetes Mellitus recommended that all pregnant women receive a 50 g oral glucose tolerance test between 24 and 28 weeks of gestation; women with a one-hour plasma glucose level of 140 mg/dL (7.8 mmol/L) or greater should then receive the 100 g oral glucose tolerance test.(75) This is also the official recommendation of the ADA.(76) The American College of Obstetricians and Gynecologists recommends screening for gestational diabetes in all pregnant women over age 30 and in those with glucosuria, hypertension, or a risk factor for gestational diabetes.(77) The ADA and the American College of Physicians are currently preparing revised recommendations on screening for diabetes.(78)Discussion
Screening for diabetes in the clinical setting suffers from two important limitations: the lack of a screening test that combines accuracy with practicality, and the absence of adequate evidence that early detection and treatment improve outcome in asymptomatic persons. The uncertainties regarding the benefits of early treatment of asymptomatic persons must be weighed against the potential adverse effects of screening (e.g., false-positive labeling) and treatment (e.g., dietary restrictions, insulin injections). In high-risk groups (see Clinical Intervention), in which the prevalence of diabetes is increased, the frequency of false- positive results from screening is likely to be lower. Proponents of screening emphasize that the implications of false-positive labeling can be minimized through subsequent diagnostic testing; moreover, the principal forms of treatment, dietary modification and exercise, are of low cost and of considerable health benefit for numerous target conditions.(78)A stronger scientific rationale exists for screening pregnant women for gestational diabetes, but there are important limitations to this evidence as well. It has not been demonstrated in properly conducted controlled trials (as opposed to observational studies) that treatment can prevent most of the health risks associated with gestational diabetes (perinatal mortality, neonatal metabolic derangements, congenital anomalies). The ability to prevent macrosomia has been proved, but it is uncertain to what extent screening would reduce the overall incidence of birth trauma and operative delivery. Nonetheless, since treatment is unlikely to result in significant maternal or fetal harm, routine screening for gestational diabetes may be a reasonable measure.
In persons who are not pregnant, primary prevention rather than screening may be an important means of preventing diabetes and its complications. Among the many benefits of exercise and weight reduction, for example, are improved glucose tolerance and reduced obesity, important risk factors for diabetes as well as for other serious chronic diseases (Screening for Obesity). A number of dietary interventions (e.g., increased dietary fiber) have also been examined in the prevention and treatment of NIDDM.(79) Since these healthy behaviors are widely recommended even in the absence of diabetes, patients should be encouraged to adopt these behaviors independently of diabetes screening (see Exercise Counseling and Nutrition Counseling).
Clinical Intervention
A 50 g oral glucose tolerance test for gestational diabetes is recommended for all pregnant women between 24 and 28 weeks of gestation. Women with a one-hour plasma glucose level of 140 mg/dL (7.8 mmol/L) or greater should receive a confirmatory three-hour 100 g oral glucose tolerance test. Routine screening for diabetes in asymptomatic nonpregnant adults, using plasma glucose measurement or urinalysis, is not recommended. Periodic fasting plasma glucose measurements may be appropriate in persons at high risk for diabetes mellitus, such as the markedly obese, persons with a family history of diabetes, or women with a history of gestational diabetes.Note
See Appendix A for the U.S. Preventive Services Task Force Table of Ratings for this topic. See also the relevant Task Force background paper: Singer DE, Samet JH, Coley CM, et al. Screening for diabetes mellitus. In: Goldbloom RB, Lawrence RS, eds. Preventing disease: beyond the rhetoric. New York: Springer-Verlag (in press).References
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2. Harris MI. Prevalence of non-insulin-dependent diabetes and impaired glucose tolerance. In: National Diabetes Data Group. Diabetes in America: diabetes data compiled 1984. Washington, D.C.: Department of Health and Human Services, 1985:VI-1 to VI-31. (Publication no. DHHS (NIH) 85-1468.)
3. Kovar MG, Harris MI, Hadden WC. The scope of diabetes in the United States population. Am J Public Health 1987; 77:1549-50.
4. Centers for Disease Control. Trends in diabetes mellitus mortality. MMWR 1988; 37:769-73.
5. Harati Y. Diabetic peripheral neuropathies. Ann Intern Med 1987; 107:546-59.
6. Bild D, Selby JV, Sinnock P, et al. Lower extremity amputation in persons with diabetes: epidemiology and prevention. Diabetes Care 1989; 12:24-31.
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8. Miodonovik M, Mimouni F, Dignan PSJ, et al. Major malformations in infants of IDDM women: vasculopathy and early-trimester poor glycemic control. Diabetes Care 1988; 11:713-8.
9. Mimouni F, Miodonovik M, Siddiqi TA, et al. High spontaneous premature labor rate in insulin-dependent diabetic pregnant women: an association with poor glycemic control and urogenital infection. Obstet Gynecol 1988; 72:175-80.
10. Entmacher PS, Sinnock P, Bostic E, et al. Economic impact of diabetes. In: National Diabetes Data Group. Diabetes in America: diabetes data compiled 1984. Washington, D.C.: Department of Health and Human Services, 1985:XXXII-1 to XXXII-13. (Publication no. DHHS (NIH) 85-1468.)
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12. National Center for Health Statistics. Prevalence of known diabetes among black Americans. Advance Data from Vital and Health Statistics, no. 130. Hyattsville, Md.: Public Health Service, 1987. (Publication no. DHHS (PHS) 87-1250.)
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37. Jarrett RJ, Keen H, McCartney P. The Whitehall Study: ten year follow- up report on men with impaired glucose tolerance with reference to worsening of diabetes and predictors of death. Diabetic Med 1984; 1:279-83.
38. Jarrett RJ, Keen H, Fuller JH, et al. Treatment of borderline diabetes: controlled trial using carbohydrate restriction and phenformin. Br Med J 1977; 2:861-5.
39. Chase HP, Jackson WE, Hoops SL, et al. Glucose control and the renal and retinal complications of insulin-dependent diabetes. JAMA 1989; 261:1155-60.
40. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care 1978; 1:168-88, 252-63.
41. Miki E, Fukuda M, Kuzuya T, et al. Relation of the course of retinopathy to control of diabetes, age, and therapeutic agents in diabetic Japanese patients. Diabetes 1969; 18:773-80.
42. Takazakura E, Nakamoto Y, Hayakawa H, et al. Onset and progression of diabetic glomerulosclerosis: a prospective study based on serial renal biopsies. Diabetes 1975; 24:1-9.
43. Kroc Collaborative Study Group. Blood glucose control and the evolution of diabetic retinopathy and albuminuria: a preliminary multicenter trial. N Engl J Med 1984; 311: 365-72.
44. Lauritzen T, Frost-Larsen K, Larsen HW, et al. Effect of 1 year of near-normal blood glucose levels on retinopathy in insulin-dependent diabetics. Lancet 1983; 1:200-4.
45. Kroc Collaborative Study Group. Diabetic retinopathy after two years of intensified insulin treatment: follow-up of the Kroc Collaborative Study. JAMA 1988; 260:37-41.
46. Lauritzen T, Frost-Larsen K, Larsen HW, et al. The Steno Study Group: two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. Diabetes (Suppl 3) 1985; 34:74-9.
47. Feldt-Rasmussen B, Mathiesen ER, Deckert T. Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet 1986; 2:1300-4.
48. Dahl-Jorgensen K, Brinchmann-Hansen O, Hanssen KF, et al. Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo Study. Br Med J 1986; 293:1195-9.
49. Knatterud GL, Klimt CR, Levin ME, et al. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII: Mortality and selected nonfatal events with insulin treatment. JAMA 1978; 240:37-42.
50. University Group Diabetes Program. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VIII. Evaluation of insulin therapy: final report. Diabetes (Suppl 5) 1982; 31:1-81.
51. Hadden DR, Blair AR, Wilson EA, et al. Natural history of diabetes presenting age 40-69 years: a prospective study of the influence of intensive dietary therapy. Q J Med 1986; 59:579-98.
52. The DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study. Diabetes Care 1987; 10:1-19. 53. Mimouni F, Tsang RC. Pregnancy outcome in insulin-dependent diabetes: temporal relationships with metabolic control during specific pregnancy periods. Am J Perinatol 1988; 5:334-8.
54. Jovanovic L, Druzin M, Peterson CM. Effect of euglycemia on the outcome of pregnancy in insulin-dependent diabetic women as compared with normal control subjects. Am J Med 1981; 71:921-7.
55. O'Sullivan JB, Harris MI, Mills JL. Maternal diabetes in pregnancy. In: National Diabetes Data Group. Diabetes in America: diabetes data compiled 1984. Washington, D.C.: Department of Health and Human Services, 1985:XX-1 to XX-17. (Publication no. DHHS (NIH) 85-1468.) 56. Mills JL, O'Sullivan JB. The infant of the diabetic mother. In: National Diabetes Data Group. Diabetes in America: diabetes data compiled 1984. Washington, D.C.: Department of Health and Human Services, 1985:XXI-1 to XXI-19. (Publication no. DHHS (NIH) 85-1468.) 57. Diabetic Retinopathy Research Group. Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol 1976; 81:383-96. 58. Dorf A, Ballantine EJ, Bennett PH, et al. Retinopathy in Pima Indians: relationship to glucose level, duration of diabetes, age at diagnosis of diabetes, and age at examination in a population with a high prevalence of diabetes mellitus. Diabetes 1976; 25:554-60. 59. Dwyer MS, Melton LJ III, Ballard DJ, et al. Incidence of diabetic retinopathy and blindness: a population-based study in Rochester, Minnesota. Diabetes Care 1985; 8:316-22.
60. Lindsay MK, Graves W, Klein L. The relationship of one abnormal glucose tolerance test value and pregnancy complications. Obstet Gynecol 1989; 73:103-6.
61. Gyves MT, Rodman HM, Little AB, et al. A modern approach to management of pregnant diabetics: a two-year analysis of perinatal outcomes. Am J Obstet Gynecol 1977; 128:606-16.
62. Roversi GD, Gargiulo M, Nicolini U, et al. A new approach to the treatment of diabetic women: report of 479 cases seen from 1963 to 1975. Am J Obstet Gynecol 1979; 135:567-76.
63. Adashi EY, Pinto H, Tyson JE. Impact of maternal euglycemia on fetal outcome in diabetic pregnancy. Am J Obstet Gynecol 1979; 133:268-74. 64. Coustan DR, Imarah J. Prophylactic insulin treatment of gestational diabetes reduces the incidence of macrosomia, operative delivery, and birth trauma. Am J Obstet Gynecol 1984; 150:836-42.
65. Karlsson K, Kjellmer I. The outcome of diabetic pregnancies in relation to the mother's blood sugar level. Am J Obstet Gynecol 1972; 112:213-20.
66. Gabbe SG, Mestman JH, Freeman RK, et al. Management and outcome of class A diabetes mellitus. Am J Obstet Gynecol 1977; 127:475-9. 67. O'Sullivan JB, Gellis SS, Dandrow RV, et al. The potential diabetic and her treatment in pregnancy. Obstet Gynecol 1966; 27:683-9. 68. Coustan DR, Lewis SB. Insulin therapy for gestational diabetes. Obstet Gynecol 1978; 51:306-10.
69. Persson B, Stangenberg M, Hansson U, et al. Gestational diabetes mellitus (GDM): comparative evaluation of two treatment regimens, diet versus insulin and diet. Diabetes (Suppl 2) 1985; 34:101-5. 70. Braveman P, Showstack J, Browner W, et al. Evaluating outcomes of pregnancy in diabetic women: epidemiologic considerations and recommended indicators. Diabetes Care 1988; 11:281-7.
71. Spellacy WN, Miller S, Winegar A, et al. Macrosomia--maternal characteristics and infant complications. Obstet Gynecol 1985; 66:158-61.
72. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1193-254.
73. Frame PS. A critical review of adult health maintenance. Part 4. Prevention of metabolic, behavioral, and miscellaneous conditions. J Fam Pract 1986; 23:29-39.
74. American Diabetes Association. Physician's guide to non-insulin dependent (type II) diabetes. Diagnosis and Treatment. Alexandria, Va.: American Diabetes Association, 1988.
75. Summary and Recommendations of the Second International Workshop- Conference on Gestational Diabetes Mellitus. Diabetes 1985; 34:123-6. 76. American Diabetes Association. Gestational diabetes mellitus. Ann Intern Med 1986; 105:461.
77. American College of Obstetricians and Gynecologists. Management of diabetes mellitus in pregnancy. ACOG Technical Bulletin No. 92. Washington, D.C.: American College of Obstetricians and Gynecologists, 1986.
78. Stolar MH, American Diabetes Association. Personal communication, March 1989.
79. National Institutes of Health Consensus Development Conference. Diet and exercise in noninsulin-dependent diabetes mellitus. Bethesda, Md.: National Institutes of Health, 1986.
Screening for Thyroid Disease
Recommendation
Screening for congenital hypothyroidism is recommended for all neonates during the first week of life (see Clinical Intervention). Routine screening for thyroid disorders is otherwise not warranted in asymptomatic adults or children. Persons with a history of upper-body irradiation may benefit from regular physical examination of the thyroid.Burden of Suffering
The thyroid disorders for which screening is most often considered, hyperthyroidism, hypothyroidism, and thyroid cancer, account for significant morbidity and mortality in the United States. About 2-3% of the U.S. population have either hypothyroidism or hyperthyroidism, conditions that are especially common in women and the elderly.(1) The diverse symptoms that are characteristic of these diseases can have significant impact on the health and behavior of victims. Hyperthyroidism, for example, can cause restlessness, emotional lability, insomnia, heat intolerance, dyspnea, palpitations, ophthalmopathy, diarrhea, muscle atrophy, weakness, tremors, and tachycardia. Hypothyroidism can produce lethargy, confusion, poor memory, cold intolerance, weight gain, constipation, alopecia, dyspnea, myalgias, and paresthesias. Thyroid dysfunction may even lead to death; examples include thyroid storm in hyperthyroidism and myxedema coma in hypothyroidism. The nonspecific nature of many thyroid symptoms introduces added difficulties for patients, especially for those with hypothyroidism, because many thyroid symptoms are easily confused with those of other medical and psychiatric conditions. The patient may receive an incorrect diagnosis or none at all, and this may delay the initiation of appropriate treatment.Congenital hypothyroidism occurs each year in about 1 out of every 3500-4000 newborns.(2) Most children who do not receive prompt treatment for this condition develop irreversible mental retardation and a variety of neuropsychological deficits comprising the syndrome of cretinism.(2) These complications have become less common in recent years following the introduction of routine neonatal screening and early treatment with I-thyroxine.
Thyroid cancer will account for an estimated 11,300 new cases and 1000 deaths in the United States in 1989.(3) Current five-year survival with treatment is over 90%.(3) Persons at increased risk for thyroid cancer, in addition to those with characteristic symptoms (e.g., neck mass, hoarseness), include women, persons with a family history of multiple endocrine neoplasia syndrome II, and the estimated 1 million Americans who have received low-dose upper-body irradiation during infancy, childhood, or adolescence. It has been calculated that at least 90,000 of these persons have irradiation-related cancers.(4,5)
Efficacy of Screening Tests
Many different thyroid function tests can provide useful information in the evaluation of persons with symptoms of thyroid disease, but the yield is considerably less when these tests are performed routinely for screening purposes in asymptomatic individuals or those with nonspecific symptoms. This has been apparent when thyroid function tests are included as a routine component of the periodic health examination. When this was done in one study, total T4 or free T4 levels were abnormal in 5-6% of persons, and over two-thirds of these persons were found to be euthyroid on further testing.(6) The positive predictive value of an abnormal total T4, total T3, or free T4 was between 15% and 26%.(6) In another study, only 1.5% of the population had an abnormal free T4 index and nearly a third of these were false positives.(7) Similar results have been reported in other studies.(8) In a study of hospitalized patients, where 9.4% had an abnormal serum T4 screening test, only 0.6% were found to have newly discovered thyroid disease after further testing.(9)This is, in part, because the serum levels of thyroid hormones that are characteristic of hypothyroidism and hyperthyroidism are not uniform and are often influenced by a variety of biological and diagnostic factors. Thus, although T4 is usually elevated in hyperthyroidism, sole reliance on this hormone to detect the disease may produce false-negative results because 15-25% of cases have normal levels of T4 but an elevated T3 (T3 toxicosis).(10) Conversely, false-positive elevations in T4 and T3 can be produced by increased levels of serum thyroid hormone-binding proteins, certain drugs, and pregnancy.(10) The presence of nonthyroidal illness can produce spuriously low levels of T3 and T4 ("euthyroid sick syndrome") or may raise thyroid-stimulating hormone (TSH) and T4 levels.(10-12) Also, psychiatric diseases may produce transient increases in thyroid hormones that later revert to normal during recovery.(10) For these reasons, estimates of the sensitivity and specificity of thyroid function tests vary with the type of test and the type of thyroid dysfunction being sought. For thyroid tests commonly recommended for screening purposes (total T4, free T4, and free T4 index), specificity is in excess of 90% but sensitivity ranges between 32% and 100%.(6,7,13,14)
A new method of measuring TSH offers promise as a more accurate first-line screening test for thyroid disease. For many years viewed as an important means of evaluating hypothyroidism, TSH is now of potential value in detecting hyperthyroidism as well because of recent advances in immunoradiometric assays that permit measurement of low serum levels of TSH. Its use as a first-line test of thyroid function has been widely investigated.(15-19) One group of investigators, reporting a sensitivity and specificity for this technique in excess of 90% in detecting thyroid disease, has recommended that this test be used for routine screening.(20) Other researchers, however, have raised concerns about its predictive value when used as a first-line test in the general population.(21)
Screening for congenital hypothyroidism in neonates involves the radioimmunoassay of T4 and/or TSH from heel-prick specimens applied to filter paper. These tests have been used routinely for many years throughout the United States and other countries.(22) In the United States, T4 is measured initially on all specimens and TSH is then measured if the T4 level is low; in Europe and elsewhere, TSH is measured first. Currently in the United States, only 1 out of 120 neonates with congenital hypothyroidism escapes detection, usually as a result of biological factors or screening errors.(23) False-positive results are not uncommon, occurring at a ratio of 24-44 for every proven case, but they are easily corrected with follow-up testing.(22) Nonetheless, some investigators have called attention to the evidence that families receiving false-positive results from thyroid function tests may suffer increased anxiety and long-term effects years after the error is corrected.(24)
Screening tests for the detection of thyroid cancer include palpation to detect nodules and diagnostic procedures such as scintigraphy, ultrasonography, and thin-needle aspiration with cytology. With the exception of neck palpation, these tests are generally reserved for persons with evidence of nodular disease or goiter, and they are not recommended as screening tests for asymptomatic persons. There is little information on the accuracy of neck palpation in detecting thyroid disease. Accuracy varies with the technique of the examiner and the size of the mass. Other factors affect the sensitivity and specificity of the examination; for example, autopsy studies have shown that most thyroid nodules are not palpable and those that are palpable are usually benign.(25) Scintigraphy, as mentioned, is generally not performed on asymptomatic individuals without evidence of nodular or diffuse disease, but this test has been recommended to screen asymptomatic persons with a history of upper-body irradiation during childhood. In programs combining scintigraphy with a complete physical examination, nodular disease (benign and malignant) is discovered in as many as 30% of these high-risk participants.(26)
Effectiveness of Early Detection
The early detection of thyroid disease with thyroid function tests and the prompt initiation of treatment is thought to be of value in preventing the steady progression of symptoms that is typical of thyroid dysfunction. The results of thyroid screening tests may also benefit the patient by providing an explanation for nonspecific and insidious symptoms attributed mistakenly to other medical or psychiatric causes.(13) This is especially important in older persons, a population in which the classic clinical presentation of hypothyroidism and hyperthyroidism is often masked. Although the elderly are at increased risk for hypothyroidism, less than a third display the typical signs and symptoms.(27) Many older persons with hyperthyroidism experience "apathetic hyperthyroidism,"(10) lacking the goiter, ophthalmopathy, and signs of sympathetic nervous system overactivity that are typically seen in younger age groups.(28)It has not been proved, however, that adults with thyroid dysfunction who are identified early and receive treatment prior to the appearance of symptoms have a better outcome than those who receive treatment after symptoms become apparent.(8) Although it is known that treatment of hypothyroid persons with I-thyroxine can improve thyroid function test results and certain indices of cardiac function,(29) there is limited evidence that these alterations result in meaningful health benefits for persons with subclinical hypothyroidism.(30,31) Evidence supporting early treatment comes primarily from a randomized placebo-controlled trial of 33 persons with subclinical hypothyroidism.(29) When compared with controls, those persons treated with I-thyroxine had milder symptoms and improved myocardial con tractility; there were no differences in other outcome measures such as basal metabolic rate, pulse, body weight, and skin texture.(29) Although persons with subclinical hypothyroidism are known to have higher levels of serum cholesterol,(32) there was no significant decrease in serum lipids with treatment.(29) Similar questions exist about the efficacy of treating subclinical hyperthyroidism. These uncertainties about treatment benefits are important because of the costs and potential health effects of antithyroid medications, radioactive iodine ablation, and subtotal thyroidectomy.(30)
In contrast, there is good evidence that early treatment of congenital hypothyroidism is effective. It has been known for many years that delay of treatment for this disorder beyond the first few months of life is likely to result in irreversible mental retardation.(2,33) With the advent of early detection and treatment, longitudinal studies have shown that children who receive treatment within the first weeks of life have normal or near-normal intellectual performance when tested at ages 4 to 7.(33-36) These children may have lower IQ scores than their siblings, and many continue to manifest subtle deficits in language, perception, and fine motor skills;(35,37,38) however, the reduced incidence of severe neuropsychological effects observed with early treatment has prompted most Western governments to require routine screening for all neonates.
The benefits of early detection of thyroid cancer are not well defined. Five-year survival is currently over 90%,(3) but it has not been determined whether asymptomatic persons receiving treatment have a better outcome than those who present with symptoms or physical findings. In addition, there is reason to believe that many cancers detected through screening are not destined to manifest themselves clinically during the life of the patient.(4) Autopsy studies(39,40) indicate that 3-36% of the population have occult thyroid carcinoma, but the incidence of overt disease is only about 11,000 cases per year.(3) One group more likely to benefit from early detection of thyroid cancer are those persons with a history of upper-body irradiation during infancy, childhood, or adolescence, since 12% of this population does develop palpable thyroid disease.(4)
Recommendations of Others
Newborn screening for congenital hypothyroidism is mandatory in all states(41) and is recommended by most authorities, including the Canadian Task Force(42) and the American Academy of Pediatrics and American Thyroid Association.(43) There is disagreement about the role of thyroid function tests in screening asymptomatic adults. In its 1979 report, the Canadian Task Force found little scientific evidence to screen for hyperthyroidism but recommended clinical examination of postmenopausal women for hypothyroidism.(42) Others have recommended routine thyroid screening of the elderly,(30) and some authors have advocated routine screening of all asymptomatic persons.(7) Recommendations against any form of screening for thyroid disease in adults have also been made.(44) Routine screening for thyroid cancer has not been recommended for the general population, but annual examinations for thyroid nodules have been advocated for persons with a history of upper-body irradiation during infancy, childhood, or adolescence.(4,26)Clinical Intervention
Screening for congenital hypothyroidism is recommended for all neonates during the first week of life. Heel-prick specimens for T4 and TSH should be obtained, preferably between days 3 and 6. Testing procedures and follow-up treatment for abnormal results should follow current guidelines.(43) Routine thyroid function testing is otherwise not recommended for asymptomatic children or adults. Thyroid screening in the absence of symptoms, however, may be clinically prudent for populations at increased risk, such as older persons, especially women. The specific tests most frequently recommended as first-line screening tests are the serum T4 or the free T4 index (FTI);(7,9,11,14,45,46) further investigation is needed into the role of new, sensitive thyroid-stimulating hormone assays as a first-line test. It may be prudent to perform regular physical examinations of the thyroid in persons with a history of upper-body irradiation.References
1. Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol 1977; 7:481-93. 2. Postellon DC, Abdallah A. Congenital hypothyroidism: diagnosis, treatment, and prognosis. Compr Ther 1986; 12:67-71.
3. American Cancer Society. Cancer statistics, 1989. CA 1989; 39:3-20. 4. Stockwell RM, Barry M, Davidoff F. Managing thyroid abnormalities in adults exposed to upper body irradiation in childhood: a decision analysis. Should patients without palpable nodules be scanned and those with scan defects be subjected to subtotal thyroidectomy? J Clin Endocrinol Metab 1984; 58:804-12.
5. Krenning EP, Ausema L, Bruining HA, et al. Clinical and radiodiagnostic aspects in the evaluation of thyroid nodules with respect to thyroid cancer. Eur J Cancer Clin Oncol 1988; 24:299-304.
6. Fukazawa H, Sakurada T, Yoshida K, et al. Free thyroxine estimation for the screening of hyper- and hypothyroidism in an adult population. Tohoku J Exp Med 1986; 148:411-20.
7. dos Remedios LV, Weber PM, Feldman R, et al. Detecting unsuspected thyroid dysfunction by the free thyroxine index. Arch Intern Med 1980; 140:1045-9.
8. White GH, Walmsley RN. Can the initial assessment of thyroid function be improved? Lancet 1978; 2:933-5.
9. Nolan JP, Tarsa NJ, DiBenedetto G. Case-finding for unsuspected thyroid disease: costs and health benefits. Am J Clin Pathol 1985; 83:346-55. 10. Gavin LA. The diagnostic dilemmas of hyperthyroxinemia and hypothyroxinemia. Adv Intern Med 1988; 33:185-204.
11. Wong ET, Steffes MW. A fundamental approach to the diagnosis of diseases of the thyroid gland. Clin Lab Med 1984; 4:655-70. 12. Wilke TJ. Estimation of free thyroid hormone concentrations in the clinical laboratory. Clin Chem 1986; 32:585-92.
13. Ericsson UB, Thorell JI. A prospective critical evaluation of in vitro thyroid function tests. Acta Med Scand 1986; 220:47-56.
14. Wilke TJ, Eastment HT. Discriminative ability of tests for free and total thyroid hormones in diagnosing thyroid disease. Clin Chem 1986; 32:1746-50.
15. Klee GG, Hay ID. Sensitive thyrotropin assays: analytic and clinical performance criteria. Mayo Clin Proc 1988; 63:1123-32.
16. Ross DS. New sensitive immunoradiometric assays for thyrotropin. Ann Intern Med 1986; 104:718-21.
17. Alexander WD, Kerr DJ, Ferguson MM. First-line test of thyroid function. Lancet 1984; 2:647.
18. Roddis MJ, Burrin JM, Johannssen A, et al. Serum thyrotropin: a first- line discriminatory test of thyroid function. Lancet 1985; 1:277-8. 19. Hershman JM, Pekary AE, Smith VP, et al. Evaluation of five high- sensitivity thyrotropin assays. Mayo Clin Proc 1988; 63:1133-9. 20. Caldwell G, Kellett HA, Gow SM, et al. A new strategy for thyroid function testing. Lancet 1985; 1:1117-9.
21. Ericsson UB, Fernlund P, JI Thorell. Evaluation of the usefulness of a sensitive immunoradiometric assay for thyroid stimulating hormone as a first-line thyroid function test in an unselected patient population. Scan J Clin Lab Invest 1987; 47:215-21.
22. Fisher DA. Effectiveness of newborn screening programs for congenital hypothyroidism: prevalence of missed cases. Pediatr Clin North Am 1987; 34:881-90.
23. Holtzman C, Slazyk WE, Cordero JF, et al. Descriptive epidemiology of missed cases of phenylketonuria and congenital hypothyroidism. Pediatrics 1986; 78:553-8.
24. Fyro K, Bodegard G. Four-year follow-up of psychological reactions to false positive screening tests for congenital hypothyroidism. Acta Paediatr Scand 1987; 76:107-14.
25. Mortensen JB, Woolner LB, Bennett WA. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955; 15:1270-80.
26. Shimaoka K, Bakri K, Sciascia M, et al. Thyroid screening program: follow-up evaluation. NY State J Med 1982; 82:1184-7.
27. Bahemuka M, Hodkinson HM. Screening for hypothyroidism in elderly inpatients. Br Med J 1975; 2:601-3.
28. Feit H. Thyroid function in the elderly. Clin Ger Med 1988; 4:151-61. 29. Cooper DS, Halpern R, Wood LC, et al. L-thyroxine therapy in subclinical hypothyroidism: a double-blind, placebo-controlled trial. Ann Intern Med 1984; 101:18-24.
30. Screening for thyroid disease (editorial). Lancet 1981; 2:128-30. 31. Fraser WD, Biggart EM, O'Reilly DJ, et al. Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? Br Med J 1986; 293:808-10.
32. Althaus BU, Staub JJ, Ryff-De Leche A, et al. LDL/HDL changes in subclinical hypothyroidism: possible risk factors for coronary heart disease. Clin Endocrinol 1988; 28:157-63.
33. Glorieux J, Dussault JH, Letarte J, et al. Preliminary results on the mental development of hypothyroid infants detected by the Quebec Screening Program. J Pediatr 1983; 102:19-22.
34. New England Congenital Hypothyroidism Collaborative. Effects of neonatal screening for hypothyroidism: prevention of mental retardation by treatment before clinical manifestations. Lancet 1981; 2:1095-8. 35. Glorieux J, Dussault JH, Morisette J, et al. Follow-up at ages 5 and 7 years on mental development in children with hypothyroidism detected by Quebec Screening Program. J Pediatr 1985; 107:913-5.
36. Ilicki A, Larsson A. Psychomotor development of children with congenital hypothyroidism diagnosed by neonatal screening. Acta Paediatr Scan 1988; 77:142-7.
37. Rovet JF. A prospective investigation of children with congenital hypothyroidism identified by neonatal thyroid screening in Ontario. Can J Public Health (Suppl 1) 1986; 77:164-73.
38. Murphy G, Hulse JA, Jackson D, et al. Early treated hypothyroidism: development at 3 years. Arch Dis Child 1986; 61:761-5.39.Holm LE, Lowhagen T, Silfversward C. The reliability of malignant thyroid tumor diagnosis in the Swedish cancer registry. Acta Pathol Microbiol Scand A 1980; 88:251-4.
40. Franssila KO, Harach R. Occult papillary carcinoma of the thyroid in children and young adults. Cancer 1986; 58:715-9.
41. Stevens MB, Rigilano JC, Wilson CC. State screening for metabolic disorders in newborns. Am Fam Physician 1988; 37:223-8.
42. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1-45.
43. American Academy of Pediatrics, American Thyroid Association. Newborn screening for congenital hypothyroidism: recommended guidelines. Pediatrics 1987; 80:745-9.
44. Frame PS. A critical review of adult health maintenance. Part 4. Prevention of metabolic, behavioral, and miscellaneous conditions. J Fam Pract 1986; 23:29-39.
45. Schultz AL. Thyroid function tests: selective use for cost containment. Postgrad Med 1986; 80:219-28.
46. Penney MD, O'Sullivan DJ. Total or free thyroxin as a primary test of thyroid function. Clin Chem 1987; 33:170-1.
Screening for Obesity
Recommendation
All children and adults should receive periodic height and weight measurements (see Clinical Intervention).Burden of Suffering
Obesity has been defined as being 20% or more above desirable body weight.(1) Increasingly, body mass index (body weight in kilograms divided by the square of height in meters) and other parameters are replacing crude weight measurements in the definition of obesity. About 32 million American adults (aged 25-74) are obese.(2) The prevalence of obesity among children is uncertain, but it is estimated to be between 5% and 25%.3 There are reports that the prevalence of childhood obesity is increasing.(4) There is also evidence that childhood obesity may be a significant risk factor for adult obesity and that this risk becomes greater when obesity occurs among older children and adolescents.(1,5)Increased mortality in adults has been clearly documented as a result of morbid obesity, weight that is at least twice (or 100 pounds over) the desirable weight.(1,6) In the case of moderate obesity, however, experts differ on whether the observed decrease in longevity is due to the effect of obesity alone or to the effect of closely related variables such as smoking, concurrent diseases,physical inactivity, socioeconomic status, or diet.(7-12) It is known, however, that the overweight are more likely to have diabetes, hypertension, and risk factors for other diseases.(1) The prevalence of diabetes and hypertension is three times higher in overweight persons(13) than in those of normal weight. Research has established a clear association between obesity and hypercholesterolemia and a possible independent relationship between obesity and coronary artery disease.(1,3,9,10,13,14) Obesity may influence the risk of cancer of the colon, rectum, prostate, gallbladder, biliary tract, breast, cervix, endometrium, and ovary.(1) Finally, obesity affects the quality of life through social discrimination and by limiting mobility, physical endurance, and other functional measures.(1)
Efficacy of Screening Tests
Extremely overweight individuals can be identified easily in the clinical setting by their physical appearance. More precise methods are often necessary, however, to evaluate persons who are mildly or moderately overweight. The complications of obesity occur among those with elevated body fat composition, which is most accurately measured by underwater (hydrostatic) weighing, isotopic dilution measures, and other sophisticated techniques that are not suited to clinical practice.Body fat distribution, which may be an independent predictor of the complications of obesity, can be measured in the clinical setting by comparing the circumference or skinfold thickness of the trunk and limbs. For example, a waist/hip circumference ratio greater than 1.0 in men and 0.8 in women may be a reliable predictor of complications from obesity, and studies have shown that such anthropometric measurements compare favorably with estimates obtained from hydrostatic weighing.(15) Further research is needed, however, to develop standardized diagnostic criteria for these tests and to minimize interobserver variation due to differences in anthropometric measurement techniques among clinicians.(16,17)
The most common clinical method for detecting obesity, the evaluation of body weight and height based on tables of average weights, only approximates the extent of overweight. The criteria for desirable body weight are a matter of controversy among experts and vary considerably as presented in different weight-for-height tables.(18)
Effectiveness of Early Detection
The purpose of screening for obesity is to convince the individual to lose weight and thereby prevent the complications of obesity. Interventions reserved for persons at high risk for coronary artery disease may also be implemented as a result of the diagnosis. The identification of individuals at increased risk of becoming obese (e.g., children) because of family history or other risk factors may also help in the primary prevention of obesity. Although there is little evidence from prospective studies that losing weight improves longevity,(19) there is evidence that obesity increases mortality(12) and that weight loss reduces important risk factors such as hypertension, elevated serum cholesterol, and impaired glucose tolerance.1 To benefit from the detection of obesity, however, patients must be motivated by nutritional and exercise counseling to lose weight, must have access to an efficacious method of reducing body weight, and must maintain the resulting weight loss.Although a variety of weight-reducing regimens are available, many have only short-term efficacy and fail to achieve long-term weight loss.(3,6,20-23) The lowest failure rates have been reported for conservative weight-loss regimens such as behavior therapy, nutrition education, and exercise programs, primarily involving persons with mild to moderate obesity.(23) One study reported that only 27% of patients on behavior therapy had regained their weight one year after treatment had ended.(23) More intensive approaches, such as very-low-calorie diets, are appropriate only for highly selected individuals.(22,24) Surgery is indicated for an even smaller group of patients,(25) and pharmacotherapy is effective only when used for an indefinite period of time.(26) Recent evidence suggests that some intensive weight-loss measures, such as the insertion of a gastric balloon,(27) may not be effective. Weight loss during childhood and adolescence may reduce growth velocity and produce other complications.(28,29)
Recommendations of Others
The Institute of Medicine recommends height and weight measurement at five age intervals during adulthood (18-24, 25-39, 40-59, 60-74, over 75).(30) The American Heart Association recommends a body weight measurement every five years.(31) Others have suggested a periodicity of four years(20) and two to three years.(32) The American Academy of Pediatrics recommends height and weight measurements for children throughout infancy, annually from ages 1-6, and every two years thereafter.(33) The Canadian Task Force recommends measurement of height, weight, and head circumference throughout infancy, at ages 18 months, 2-3 years, 4 years, 5-6 years, 10-11 years, and at the clinician's discretion during adolescence and adulthood.(34)Discussion
Evidence that screening for obesity and weight-reducing strategies are effective in reducing long-term morbidity and mortality is unlikely to improve in the near future due to the difficulty of conducting controlled trials of weight loss with these outcome measures and of separating the effect of obesity from that of other risk factors. It is clear, however, that weight loss reduces an individual's risk for major chronic diseases such as diabetes, hypertension, and coronary artery disease. Periodic height and weight measurements, although not proven to be effective, are inexpensive, rapid, and acceptable to patients. They may also be useful for the detection of medical conditions causing unintended weight loss and weight gain, such as cancer or thyroid disorders. The intervention is especially prudent in children to detect growth abnormalities and obesity in early childhood.(35) The reliability of other methods of detecting obesity, such as the measurement of skinfold thickness and limb circumference, requires further study before these techniques are deemed suitable for widespread implementation in the clinical setting. There are inadequate data to determine the optimal frequency of obesity screening, and this is best left to clinical discretion.Clinical Intervention
The height and weight of all adults should be routinely measured and evaluated, using a table of desirable weights (e.g., Metropolitan Life Insurance Company Table)(36)or a body mass index (body weight in kilograms divided by the square of height in meters) above 27.8 in men or 27.3 in women as a basis for further intervention.(1) The height and weight of children should be measured regularly and plotted on a growth chart throughout infancy and childhood. The optimal frequency for measuring height and weight in adults is a matter of clinical discretion. Those individuals who are 20% or more above desirable weight should receive appropriate nutritional and exercise counseling.References
1. Foster WR, Burton BT, eds. National Institutes of Health consensus conference: health implications of obesity. Ann Intern Med 1985; 103:977-1077.
2. Department of Health and Human Services, Department of Agriculture. Nutrition monitoring in the United States. Washington, D.C.: Government Printing Office, 1986:2,54, 59-62.
3. Dietz WH. Childhood obesity: susceptibility, cause, and management. J Pediatr 1983; 103:676-86.
4. Gortmaker SL, Dietz WH, Sobol AM, et al. Increasing pediatric obesity in the United States. Am J Dis Child 1987; 141:535-40.
5. Epstein LH, Wing RR, Valoski A, et al. Childhood obesity. Pediatr Clin North Am 1985; 32:363-79.
6. Van Itallie TB, Kral JG. The dilemma of morbid obesity. JAMA 1981; 246:999-1003.
7. Manson JE, Stampfer MJ, Hennekens CH, et al. Body weight and longevity: a reassessment. JAMA 1987; 257:353-8.
8. Ernsberger P. Body weight and longevity (letter). JAMA 1987; 257:1895-6. 9. Keys A. Overweight, obesity, coronary heart disease and mortality. Nutr Rev 1980; 38:297-307.
10. Simopoulos AP, Van Itallie TB. Body weight, health, longevity. Ann Intern Med 1984; 100:285-95.
11. Stallones RA. Epidemiologic studies of obesity. Ann Intern Med 1985; 103:1003-5.
12. Harris T, Cook EF, Garrison R, et al. Body mass index and mortality among nonsmoking older persons: the Framingham Heart Study. JAMA 1988; 259:1520-4.
13. Van Itallie TB. Health implications of overweight and obesity in the United States. Ann Intern Med 1985; 103:983-8.
14. Hubert HB, Feinleib M, McNamara PM, et al. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983; 67:968-77.
15. Latin RW, Johnson SC, Ruhling RO. An anthropometric estimation of body composition of older men. J Gerontol 1987; 42:24-8.
16. Kispert CP, Merrifield HH. Interrater reliability of skinfold fat measurements. Phys Ther 1987; 67:917-20.
17. Jung E, Kaufman JJM, Narins DC, et al. Skinfold measurements in children: a comparison of Lange and McGaw calipers. Clin Pediatr 1984; 23:25-8.
18. Schulz LO. Obese, overweight, desirable, ideal: where to draw the line in 1986? J Am Diet Assoc 1986; 86:1702-4.
19. Kannel WB. Weight loss as a homeostatic stress (letter). JAMA 1986; 256:2881.
20. Frame PS. A critical review of adult health maintenance. Part 4. Prevention of metabolic, behavioral, and miscellaneous conditions. J Fam Pract 1986; 23:29-39.
21. Currey H, Malcolm R, Riddle E, et al. Behavioral treatment of obesity: limitations and results with the chronically obese. JAMA 1977; 237:2829-31.
22. Wadden TA, Stunkard AJ, Brownell KD. Very low calorie diets: their efficacy, safety, and future. Ann Intern Med 1983; 99:675-84. 23. Stunkard AJ. Conservative treatments for obesity. Am J Clin Nutr 1987; 45:1142-54.
24. Wadden TA, Stunkard AJ. Controlled trial of very-low-calorie diet, behavior therapy and their combination in the treatment of obesity. J Consult Clin Psychol 1986; 54:482-8.
25. Mason EE. Surgical treatment of obesity. Philadelphia: WB Saunders, 1981.
26. Stunkard AJ. Anorectic agents lower a body weight set point. Life Sciences 1982; 30:2043-55.
27. Kramer FM, Stunkard AJ, Spiegel TA, et al. Limited weight losses with a gastric balloon. Arch Intern Med 1989; 149:411-3.
28. Dietz WH, Hartung R. Changes in height velocity of obese preadolescents during weight reduction. Am J Dis Child 1985; 139:705-7.
29. Mallick MJ. Health hazards of obesity and weight control in children: a review of the literature. Am J Public Health 1983; 73:78-82.
30. National Academy of Sciences, Institute of Medicine. Ad Hoc Advisory Group on Preventive Services. Preventive services for the well population. Washington, D.C.: National Academy of Sciences, 1978.
31. Grundy SM, Greenland P, Herd A, et al. Cardiovascular and risk factor evaluation of healthy American adults. Circulation 1987; 75:1340A-62A.
32. Breslow L, Somers AR. The lifetime health-monitoring program. N Engl J Med 1977; 296:601-8.
33. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine. Guidelines for health supervision. Elk Grove, Ill.: American Academy of Pediatrics, 1987.
34. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979; 121:1194-254.
35. Peckham C, Stark O, Moynihan C. Obesity in school children: is there a case for screening? Public Health (London) 1985; 99:3-9.
36. 1983 Metropolitan height and weight tables. Stat Bull Metrop Insur Co 1983; 64:3.
Screening for Phenylketonuria
Recommendation
Screening for phenylketonuria (PKU) is recommended for all newborns prior to discharge from the nursery. Infants who are tested before 24 hours of age should receive a repeat screening test before the third week of life. Routine prenatal screening for maternal PKU is not recommended.Burden of Suffering
Phenylketonuria occurs once in every 15,000 births.(1-3) In the absence of treatment during infancy, most persons with this disorder develop severe, irreversible mental retardation. Many experience neurobehavioral symptoms such as seizures, tremors, gait disorders, athetoid movements, and psychotic episodes with autism.(4) These clinical manifestations of PKU have rarely developed in children born after the mid-1960s, when routine screening was legislated and early treatment for PKU became common. A cohort of healthy phenylketonuric females have now entered childbearing age, however, thus increasing the incidence of maternal PKU (estimated at 1 per 30,000-40,000 pregnancies).(5) These women are at increased risk of giving birth to a child with mental retardation, microcephaly, congenital heart disease, and low birthweight.(6) It has been estimated that, if treatment is not made available to protect offspring from the teratogenic effects of maternal phenylalanine, the incidence of PKU-related mental retardation could return to previous levels after only one generation.(7)Efficacy of Screening Tests
Automated blood phenylalanine determinations, such as the Guthrie test, have been the principal screening tests for phenylketonuria for over two decades.(8) Although well-designed evaluations of the sensitivity and specificity of the Guthrie test have never been performed,(1) international experience with its use in millions of newborns suggests that missed cases are very uncommon; most appear to be due to administrative or laboratory errors. Fluorometric assays are an alternative form of testing that offers excellent sensitivity.(1) False-positive results can occur in PKU screening. In certain situations and population conditions, the ratio of false positives to true positives could be as high as 32 to 1.(1) Although false positives have been viewed for many years as less important than false-negative results because they can be corrected easily by repeating the test, it should be noted that recalling patients for a second PKU test does generate significant parental anxiety.(9,10)The sensitivity of the Guthrie test is influenced by the age of the newborn when the sample is obtained. The current trend toward early discharge from the nursery (resulting in PKU screening being performed as early as 1 to 2 days of age) has raised concerns that test results obtained during this early period may be inaccurate. This is because the blood level of phenylalanine is typically normal in affected neonates immediately after birth and increases progressively during the first days of life. Using the conventional cutoff of 4 mg/dL, diagnostic levels of phenylalanine may not be present in some phenylketonuric newborns for several days. Early data on the frequency of this problem were inconsistent: one group found that all cases could be detected within the first 48 hours of life,(11) but others reported that the false-negative rate during the first 24 hours might be 2-6%(1) or as high as 15-16%.(12,13) The error rate in these studies decreased to 0.6-2% on the second day and to 0.3% by the third day.(1,12,13) Current rates may be lower as a result of recent improvements in laboratory standardization. Moreover, fluorometric assays have been reported to have higher sensitivity than the Guthrie test.(1) Two additional solutions to improve sensitivity, repeat testing of all newborns after early discharge and lowering the cutoff value to reduce the false-negative rate, have encountered criticism for several reasons. Repeat testing would have low yield and cost-effectiveness;(13,14) it has been estimated that detecting even one case of PKU in this manner would require performing from 600,000 to perhaps 6 million tests.(1,14) Lowering the cutoff value, on the other hand, would improve sensitivity at the expense of specificity, thereby increasing the ratio of false positives to true positives.(1) Nonetheless, many screening programs now use a cutoff level of 2 mg/dL.
Routine screening of pregnant women for maternal PKU has been recommended as a means of preventing fetal complications.(5,15,16) This disorder is rare in the general population, however, and many women with PKU are already aware of the diagnosis. Thus, the yield from screening all pregnant women would be very low. One program that has provided this form of prenatal screening reports performing 260,000 tests to detect 9 cases of previously unknown hyperphenylalaninemia.(17) Of the 11 resulting pregnancies, 5 were in women with benign hyperphenylalaninemia and 4 of their offspring were normal (the fifth pregnancy was terminated by abortion). In Massachusetts, routine screening of cord blood for 10 years detected only 22 mothers with previously undiagnosed hyperphenylalaninemia.(16,18)
Effectiveness of Early Detection
Before treatment with dietary phenylalanine restriction became common in the early 1960s, severe mental retardation was a common outcome in children with PKU. A review in 1953 reported that 85% of patients had an intelligence quotient (IQ) less than 40, and 37% had IQ scores below 10; less than 1% had scores above 70.(4) The majority of proven cases of the disease resided in mental institutions.(4) Since dietary phenylalanine restriction was introduced, however, over 95% of children with PKU have developed normal or near-normal intelligence(19-22) A large longitudinal study reports a mean IQ of 100 in children who have been followed to age 8,(230 and other reports show adolescent and young adult patients are functioning well in society.(24) The efficacy of dietary treatment has never been proved in a properly designed controlled trial,(25) and the performance of such a study in the future is unlikely for ethical reasons. Nonetheless, the compelling contrast in outcome between children receiving treatment and historical controls prompted most Western governments to require routine neonatal screening as early as the late 1960s.Nevertheless, there are limitations to the effectiveness of dietary treatment. It is essential that phenylalanine restrictions be instituted in early infancy to prevent the irreversible effects of PKU.(19,21,23,26) Adherence to the diet must continue for at least four to eight years,(19,21,23,26,27) and there are now data suggesting that continuation of the diet through adolescence and perhaps into the adult years may be advisable.(23,26) Finally, even if these precautions are taken, dietary treatment may not offer full protection from subtle effects of PKU. Intelligence scores in treated persons with PKU, although often in the normal range for the general population, may be significantly lower than those of siblings and parents,(19) and mild psychological deficits, such as perceptual motor dysfunction and academic difficulties, have also been reported.(28-30) Early detection of maternal PKU in pregnant women may also be beneficial. The incidence of maternal PKU is increasing with the growing number of healthy phenylketonuric females now entering childbearing age. Maternal hyperphenylalaninemia can produce teratogenic effects, even on normal fetuses who have not inherited PKU. If the mother does not follow a low phenylalanine diet during pregnancy, there is an overwhelming risk of birth of an abnormal child: over 90% of these children will have mental retardation, 75% microcephaly, 40-50% intrauterine growth retardation, and 10-25% other birth defects.(5,6) Uncertainties exist, however, as to whether these outcomes can be prevented by instituting treatment with dietary phenylalanine restriction.(6,31) Although some pregnant women under treatment have given birth to normal children, a number of investigators(6,31-33) have found that dietary intervention fails to prevent fetal damage. Many believe restrictions must be instituted prior to conception to achieve efficacy.(6,16,17,33,34) There are also concerns that the low-phenylalanine diet may produce deficiencies in calories, protein, and other nutrients that are needed for proper fetal growth.(5,31) A number of studies examining the health effects of such diets during pregnancy are currently under way.(35)
Recommendations of Others
Routine screening of all newborns for PKU is required in every state.(36) The American Academy of Pediatrics recommends that a heel blood specimen be obtained before leaving the nursery and as close as possible to discharge.(37) Premature infants and those being treated for illness should be tested on or near the seventh day. The Academy recommends that infants who are tested before 24 hours of age receive a repeat screening test before the third week of life. Routine prenatal screening for maternal PKU has been advocated by some authors,(15) but most groups have not recommended this approach due to concerns about cost-effectiveness.(5)Clinical Intervention
A heel-prick test for blood phenylalanine level is recommended for all newborns before discharge from the nursery, preferably after 3 days of age. Infants who are tested in the first 24 hours of age should receive a repeat screening test before the third week of life. Premature infants and those with illnesses should be tested at or near 7 days of age. All parents should receive adequate information regarding the proper interpretation of PKU test results, including the probability of false positives. Routine prenatal screening for maternal PKU is not recommended.References
1. Kirkman HN, Carroll CL, Moore EG, et al. Fifteen-year experience with screening for phenylketonuria with an automated fluorometric method. Am J Hum Genet 1982; 34:743-52.
2. Walker V, Clayton BE, Ersser RS, et al. Hyperphenylalaninaemia of various types among three-quarters of a million neonates tested in a screening programme. Arch Dis Child 1981; 56:759-64.
3. Somens DG, Favreau L. Newborn screening for phenylketonuria: incidence and screening procedures in North America. Can J Public Health 1982; 73:206-7.
4. Jervis GA. Phenylpyruvic oligophrenia (phenylketonuria). Res Publ Assoc Res Nerv Ment Dis 1953; 33:259-82.
5. Hanley WB, Clarke JTR, Schoonheyt W. Maternal phenylketonuria (PKU): a review. Clin Biochem 1987; 20:149-56.
6. Lenke RR, Levy HL. Maternal phenylketonuria and hyperphenylalaninemia: an international survey of the outcome of untreated and treated pregnancies. N Engl J Med 1980; 303:1202-8.
7. Kirkman HN. Projections of mental retardation from PKU. Pediatr Res 1979; 13:414.
8. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963; 32:338-43.
9. Rothenberg MB, Sills EM. Iatrogenesis: the PKU anxiety syndrome. J Am Acad Child Psychiatry 1968; 7:689-92.
10. Sorenson JR, Levy HL, Mangione TW, et al. Parental response to repeat testing of infants with "false-positive" results in a newborn screening program. Pediatrics 1984; 73:183-7.
11. Meryash DL, Levy HL, Guthrie R, et al. Prospective study of early neonatal screening for phenylketonuria. N Engl J Med 1981; 304:294-6. 12. Holtzman NA, McCabe ERB, Cunningham GC, et al. Screening for phenylketonuria. N Engl J Med 1981; 304:1300.
13. Schneider AJ. Newborn phenylalanine/tyrosine metabolism: implications for screening for phenylketonuria. Am J Dis Child 1983; 137:427-32.
14. Sepe SJ, Levy HL, Mount FW. An evaluation of routine follow-up blood screening of infants for phenylketonuria. N Engl J Med 1979; 300:606.
15. MacCready RA, Levy HL. The problem of maternal phenylketonuria. Am J Obstet Gynecol 1972; 123:121-8.
16. Waisbren SE, Doherty LB, Bailey IV, et al. The New England Maternal PKU Project: identification of at-risk women. Am J Public Health 1988; 78:789-92.
17. Buist NRM, Lis EW, Tuerck JM, et al. Maternal phenylketonuria. Lancet 1979; 2:589.
18. Levy HL, Waisbren SE. Effects of untreated maternal phenylketonuria and hyperphenylalaninemia in the fetus. N Engl J Med 1983; 309:1269-74.
19. Berman PW, Waisman HA, Graham FK. Intelligence in treated phenylketonuric children: a developmental study. Child Develop 1966; 37:731-47.
20. Hudson FP, Mordaunt VL, Leahy I. Evaluation of treatment begun in first three months of life in 184 cases of phenylketonuria. Arch Dis Child 1970; 45:5-12.
21. Williamson ML, Koch R, Azen C, et al. Correlates of intelligence test results in treated phenylketonuric children. Pediatrics 1981; 68:161-7.
22. Hsia DY. Phenylketonuria 1967. Dev Med Child Neurol 1967; 9:531-40.
23. Holtzman NA, Kronmal RA, van Doorninck W, et al. Effect of age at loss of dietary control on intellectual performance and behavior of children with phenylketonuria. N Engl J Med 1986; 314:593-8.
24. Koch R, Yusin M, Fishler K. Successful adjustment to society by adults with phenylketonuria. J Inherited Metab Dis 1985; 8:209-11.
25. Birch HG, Tizard J. The dietary treatment of phenylketonuria: not proven? Dev Med Child Neurol 1967;9:9-12.
26. Waisbren SE, Mahon BE, Schnell RR, et al. Predictors of intelligence quotient and intelligence quotient change in persons treated for phenylketonuria early in life. Pediatrics 1987; 79:351-5.
27. Hackney IM, Hanley WB, Davidson W, et al. Phenylketonuria: mental development behavior and termination of low phenylalanine diet. J Pediatr 1968; 72:646-55.
28. Pennington BF, van Doorninck WJ, McCabe LL, et al. Neuropsychological deficits in early treated phenylketonuric children. Am J Ment Defic 1985; 5:467-74.
29. Smith I, Beasley MG, Wolff OH, et al. Behavior disturbance in 8-year- old children with early treated phenylketonuria. Report from the MRC/DHHS Phenylketonuria Register. J Pediatr 1988; 112:403-8.
30. Faust D, Libon D, Pueschel S. Neuropsychological functioning in treated phenylketonuria. Int J Psych Med 1986-87; 16:169-77.
31. Lenke RR, Levy HL. Maternal phenylketonuria: results of dietary therapy. Am J Obstet Gynecol 1982; 142:548-53.
32. Murphy D, Saul I, Kirby M. Maternal PKU and phenylalanine-restricted diet: studies of seven pregnancies and of offspring produced. Ir J Med Sci 1985; 154:66-70.
33. Scott TM, Fyfe WM, Hart DM. Maternal phenylketonuria: abnormal baby despite low phenylalanine diet during pregnancy. Arch Dis Child 1980; 55:634-7.
34. Rohn FJ, Doherty LB, Waisborn SE, et al. The New England Maternal PKU Project: prospective study of untreated and treated pregnancies and their outcomes. J Pediatr 1987; 110:391-8.
35. de la Cruz F, National Institute of Child Health and Human Development. Personal communication, September 1988.
36. Stevens MB, Rigilano JC, Wilson CC. State screening for metabolic disorders in newborns. Am Fam Physicisn 1988; 37:223-8.
37. Committee on Genetics. New issues in newborn screening for phenylketonuria and congenital hypothyroidism. Pediatrics 1982; 69:104-6.
Screening for Hepatitis B
Recommendation
All pregnant women should be tested for hepatitis B surface antigen at their first prenatal visit. The test may be repeated in the third trimester in women at increased risk of exposure during pregnancy (see Clinical Intervention). See Adult Immunizations for recommendations on vaccination against hepatitis B in high risk groups and Postexposure Prophylaxis for information about immunization of persons with possible exposure to infected individuals or blood products.Burden of Suffering
Each year in the United States, over 300,000 persons become infected with hepatitis B virus (HBV) and more than 10,000 require hospitalization.(1) Although most infections resolve with time, 6-10% of patients develop an asymptomatic chronic carrier state that places them at risk for developing chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma.(2) The United States has an estimated pool of 500,000 to 1 million chronic carriers of HBV.(2) An estimated 4000 hepatitis B-related deaths occur each year as a result of cirrhosis, and more than 1000 occur as a result of liver cancer.(2) An estimated 16,500 births occur to HBV-infected women each year in the United States.(3) Infants whose mothers are positive for hepatitis B "e" antigen have a 70-90% chance of becoming infected perinatally, and virtually all (85-90%) infants who do become infected develop chronic HBV carrier status.(4,5) It has been estimated that more than 25% of chronic HBV carriers die from primary hepatocellular carcinoma or cirrhosis of the liver, with the median age of death in the fifth decade of life.(6-8) The principal risk factors for HBV infection in the United States are intravenous drug abuse; heterosexual contact with HBV-infected persons, HBV chronic carriers, or multiple partners; and male homosexual activity.(9) Certain population groups, such as immigrants from Asia and Africa, may also be at increased risk.(2) In recent years, a growing number of intravenous drug abusers have become infected; currently, between 60% and 80% of persons who use illicit parenteral drugs have serologic evidence of HBV infection.(2) This population now accounts for the largest proportion of HBV cases in the United States.(9)Efficacy of Screening Tests
The principal screening test for detecting current HBV infection or carrier state in asymptomatic persons is the identification of hepatitis B surface antigen (HBsAg). The immunoassay for detecting HBsAg has a reported sensitivity of 97.5% and a specificity of 98%.(10) Spontaneous clearance of HBsAg occurs each year in 1-2% of carriers.Effectiveness of Early Detection
The most important benefit of detecting HBV infection or carrier state in asymptomatic persons is the prevention of transmission of the virus to others. There is little evidence that early detection reduces the risk of developing chronic liver disease or its complications. Theoretically, the results of screening tests coupled with counseling have the potential to influence high-risk behaviors (e.g., sexual intercourse, sharing needles among drug abusers, donating blood products) in infected persons, and thereby prevent transmission. Sexual contacts and persons with possible percutaneous exposure may be identified in the process and offered vaccination. However, the effectiveness of routine screening of asymptomatic persons in the clinical setting as a means of reducing HBV transmission requires further study. Counseling on preventive behaviors to reduce the risk of infection and transmission currently appears to be a more effective strategy.There is evidence that early detection of HBsAg in pregnant women can help prevent infection in the newborn. Studies have shown that treatment beginning 2-12 hours after birth with hepatitis B immune globulin and hepatitis B vaccine is 85-95% effective in preventing the development of the HBV chronic carrier state during childhood.(5,11-13) Based on this evidence, prenatal testing for HBsAg has been recommended for pregnant women at high risk of having acquired hepatitis B.(14) Recent studies have shown, however, that only 35-65% of HBsAg-positive mothers are identified when testing is restricted to high-risk groups.(15-19) It is thought that many women at risk are not tested because their sexual and drug-related histories are not discussed with clinicians or because their clinicians are unfamiliar with perinatal transmission of HBV and recommended preventive measures.(3) In addition, many women who are carriers may not have known risk factors even after a careful history is taken.
For these reasons, routine HBsAg testing of all pregnant women may be a more effective strategy. It has been calculated that screening all of the 3.5 million pregnant women per year in the United States would detect about 16,500 HBsAg-positive mothers. Treatment of their newborns would prevent the development of HBV carrier status in an estimated 3500 neonates each year.(3) At $12-$20 per test,(20) the HBsAg assay is an expensive screening test to be performed on large numbers of women. Several studies have demonstrated, however, that the long-term benefits of preventing chronic liver disease make routine prenatal HBsAg testing as cost-effective as other widely implemented prenatal and blood-donor screening practices.(19-21) In certain populations in the United States in which HBV infection is endemic (e.g., Alaskan Natives, Pacific Islanders), universal vaccination of newborns with HBV vaccine may be a more practical strategy than prenatal screening.(3)
Recommendations of Others
Routine testing of asymptomatic persons for HBV infection is recommended primarily as a means of identifying persons in high-risk groups who require vaccination. Screening of pregnant women is, however, widely recommended. The Immunization Practices Advisory Committee of the Centers for Disease Control, in consultation with the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, has recently recommended that all pregnant women be tested for HBsAg during an early prenatal visit.(3) The test may be repeated in the third trimester if acute hepatitis is suspected, an exposure to hepatitis has occurred, or the woman practices a high-risk behavior such as intravenous drug abuse.Clinical Intervention
All pregnant women should be tested for HBsAg at their first prenatal visit. The test may be repeated in the third trimester if the mother engages in high-risk behavior such as intravenous drug abuse or if exposure to hepatitis B during pregnancy is suspected. Infants born to HBsAg- positive mothers should receive hepatitis B immune globulin (0.5 mL) intramuscularly within 12 hours of birth. Hepatitis B vaccine, either plasma-derived (10 mcg per dose) or recombinant (5 mcg per dose), should be administered intramuscularly concurrently with immune globulin (at a different injection site) or within seven days. The second and third doses should be given one and six months after the first dose. Persons with sexual or percutaneous exposure to the mother should be tested to determine susceptibility to HBV and vaccinated if susceptible.Note
See Appendix A for the U.S. Preventive Services Task Force Table of Ratings for this topic. See also the relevant Task Force background paper: LaForce FM. Immunizations, immunoprophylaxis, and chemoprophylaxis to prevent selected infections. JAMA 1987; 257:2464-70.References
1. Immunization Practices Advisory Committee. Update on hepatitis B prevention. MMWR 1987; 36:353-60,366.
2. Idem. Recommendations for protection against viral hepatitis. MMWR 1985; 34:313-24, 329-35.
3. Idem. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR 1988; 37:341-6,351.
4. Stevens CE, Beasley RP, Tsui J, et al. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975; 292:771-4.
5. Stevens CE, Toy PT, Tong MJ, et al. Perinatal hepatitis B virus transmission in the United States: prevention by passive-active immunization. JAMA 1985; 253:1740-5.
6. Beasley RP, Hwang LY. Epidemiology of hepatocellular carcinoma. In: Vyas GN, Dienstag JL, Hoofnagle JH, eds. Viral hepatitis and liver disease. Orlando, Fla.: Grune and Stratton, 1984:209-24.
7. Beasley RP. Hepatitis B virus as the etiologic agent in hepatocellular carcinoma: epidemiologic considerations. Hepatology 1982; 2:21S-6S.
8. Beasley RP, Hwang LY, Lin CC, et al. Hepatocellular carcinoma and HBV: a prospective study of 22,707 men in Taiwan. Lancet 1981; 2:1129-33.
9. Centers for Disease Control. Changing patterns of groups at high risk for hepatitis B in the United States. MMWR 1988; 37:429-32,437.
10.Holland P. Hepatitis B surface antigen and antibody (HBsAg/anti HBs). In: Gerety RJ, ed. Hepatitis B. Orlando, Fla.: Academy Press, 1985.
11.Beasley RP, Hwang LY, Lee GCY, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet 1983; 2:1099-102.
12.Wong VCW, Ip HMH, Reesink HW, et al. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin: double-blind randomised placebo controlled study. Lancet 1984; 1:921-6.
13.Stevens CE, Taylor PE, Tong MJ, et al. Yeast-recombinant hepatitis B vaccine: efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission. JAMA 1987; 257:2612-6.
14.Immunization Practices Advisory Committee. Postexposure prophylaxis of hepatitis B. MMWR 1984; 33:285-90.
15.Kumar ML, Dawson NV, McCullough AJ, et al. Should all pregnant women be screened for hepatitis B? Ann Intern Med 1987; 107:273-7.
16.Jonas MM, Schiff ER, O'Sullivan MJ, et al. Failure of Centers for Disease Control criteria to identify hepatitis B infection in a large municipal obstetrical population. Ann Intern Med 1987; 107:335-7.
17.Summers PR, Biswas MK, Pastorek JG II, et al. The pregnant hepatitis B carrier: evidence favoring comprehensive antepartum screening. Obstet Gynecol 1987; 69:701-4.
18.Wetzel AM, Kirz DS. Routine hepatitis screening in adolescent pregnancies: is it cost effective? Am J Obstet Gynecol 1987; 156:166-9.
19.Delage G, Montplaisir S, Remy-Prince S, et al. Hepatitis B Virus Transmission Study Group. Prevalence of hepatitis B virus infection in pregnant women in the Montreal area. Can Med Assoc J 1986; 134:897-901.
20.Arevalo JA, Washington AE. Cost-effectiveness of prenatal screening and immunization for hepatitis B virus (Published erratum appears in JAMA 1988; 260:478). JAMA 1988; 259:365-9.
21.Kane MA, Hadler SC, Margolis HS, et al. Routine prenatal screening for hepatitis B surface antigen. JAMA 1988; 259:408-9.
Screening for Tuberculosis
Recommendation
Tuberculin skin testing of asymptomatic persons should be performed on those at high risk of acquiring tuberculosis (see Clinical Intervention).Burden of Suffering
Over 22,000 reported cases of tuberculosis (TB) occurred in the United States in 1987.(1) This disease is associated with considerable morbidity from pulmonary and extrapulmonary symptoms. Pulmonary symptoms are progressive and include cough, hemoptysis, dyspnea, and pleuritis. Extrapulmonary TB can involve the bones, joints, pericardium, and lymphatics, and it can cause spinal cord compression from Pott's disease. Death is more common in older patients, with estimated case-fatality rates ranging from 0.8-2.1% in adolescents to 16.5% in the elderly.(2) The incidence of TB is greatest in Asians, Pacific Islanders, blacks, American Indians, Alaska Natives, and Hispanics.(3) About one-third of all reported cases in the United States occur in blacks,(4) 14% occur in Hispanics,(5) 11% occur in Asians and Pacific Islanders,(6) and 2% occur in American Indians and Alaska Natives.(7) TB is 150-300 times as common in the homeless as in the general population; the prevalence in homeless persons is 2-7% for clinically active TB and 22-50% for asymptomatic infection.(8) The incidence of TB has recently increased after experiencing a steady decline from 1963 to 1985.(3) A disproportionately large number of new cases are occurring among black and Hispanic persons.(3) There is also evidence that compromised immunity due to infection withhuman immunodeficiency virus (HIV) is contributing to the rise in incidence.(9)
Efficacy of Screening Tests
Tuberculin skin testing is the principal means of detecting TB infection in asymptomatic persons. Although some authors continue to recommend chest radiography as a first-line test in high-risk populations,(10) roentgenography is generally considered to be inappropriate as the initial screening test for detecting TB in asymptomatic persons. It is important, however, as a follow-up test to identify active pulmonary TB in infected persons identified through tuberculin testing. The most accurate tuberculin skin test is the Mantoux test, in which 5 units (5 TU) of tuberculin purified protein derivative (PPD) are injected intradermally to detect delayed hypersensitivity; induration of 10 mm or more in diameter is generally considered a positive test.The frequency of false-positive and false-negative tuberculin skin tests depends on a number of variables, including immunologic status, the size of the hypersensitivity reaction and the prevalence of a typical mycobacteria.(11,12) In certain geographic areas, cross-reacting atypical mycobacteria (as well as previous BCG vaccination) can produce intermediate size reactions, thereby limiting the specificity of the test.(11-14) False- positive results can also be produced by improper technique (e.g., measuring erythema rather than induration), hypersensitivity to PPD constituents, an Arthus reaction, and cellulitis.(11-14) False-negative reactions, which are estimated to occur in about 5-10% of patients, can be observed early in infection before hypersensitivity develops, in anergic individuals and those with severe illnesses (including active TB), and as a result of improper technique in handling the PPD solution, administering the intradermal injection, and interpreting the results.(11-15) Other limitations of the Mantoux test include the time and skill required for proper administration and variability among clinicians in interpreting results.(16) In recent years, multiple puncture tests (e.g., tine, Heaf, Mono-Vacc) have become available that are less expensive and easier to administer than the Mantoux test. Studies evaluating the accuracy of these devices, however, have produced inconsistent results. In general, the evidence suggests that multiple puncture tests have poor specificity and may have inadequate sensitivity when compared with the Mantoux test.(11,15,17,18) Patient compliance can also affect the effectiveness of tuberculin skin testing because patients must either return to the clinician or telephone results 48-72 hours after the injection. Studies in pediatric patients report noncompliance rates of 28-82%.(19-21)
Persons who are tuberculin test negative may need repeat testing, but there are inadequate data from which to determine the optimal frequency of PPD screening. In the absence of such data, clinical decisions regarding the need for repeat testing and its frequency should be based on the likelihood of further exposure to TB and the clinician's level of confidence in the accuracy of the test results.
Effectiveness of Early Detection
The early detection of tuberculin reactivity is of p