Preventive Medicine: Preventive Medicine 2

Passive Immunization

• Medical indications for passive immunization are limited compared to active immunization.
• Table 15-3 provides information on biologic agents available in the United States and their indications for use in immunocompetent and immunocompromised individuals.

Indications for Passive Immunization

• Hepatitis A vaccine or immune globulin can be administered to immunocompetent individuals at high risk for exposure to hepatitis A, such as travel to a country where it is common.
• Specific immune globulin can be used for post-exposure prophylaxis for individuals recently exposed to hepatitis B or rabies and not known to have a protective antibody titer.
• Antitoxin injection is recommended for individuals who lack active immunity to exotoxin-producing bacteria, such as Clostridium botulinum, after tests are performed to rule out hypersensitivity to the antitoxin.
• Immune globulin can be lifesaving for immunocompromised individuals who have been exposed to a common but potentially life-threatening infection, such as chickenpox, if given intravenously soon after exposure.

Vaccine Surveillance and Testing

• The rates and patterns of reportable diseases are monitored, and any cases thought to be vaccine-associated are investigated.
• Goals of vaccine surveillance and testing include monitoring the effectiveness of vaccines and detecting vaccine failures or adverse effects.

Randomized Field Trials

• Randomized field trials are used to measure the effectiveness of a new vaccine.
• In this type of trial, susceptible persons are randomized into two groups and are given the vaccine or a placebo.
• The vaccinated subjects and unvaccinated controls are followed through the high-risk season to determine the attack rate (AR) in each group.
• Vaccine effectiveness (VE) is calculated using the formula: VE = (AR(unvaccinated) - AR(vaccinated)) x 100 / AR(unvaccinated).

Retrospective Cohort Studies

• These studies are used to evaluate the protective efficacy of vaccines when randomized field trials are not feasible.
• Retrospective cohort studies have limitations, such as potential selection bias, and may not be able to ensure that the participants who were immunized are comparable to those who were not immunized.

Case-Control Studies

• Case-control studies are used to evaluate the effectiveness of vaccines when the disease is uncommon.
• The vaccine effectiveness formula can be rewritten as VE = 1 - [AR(vaccinated) / AR(unvaccinated)] = (1 - RR) ≈ (1 - OR) when the disease is rare.

Incidence Density Measures

• Incidence density measures are used to determine the rate of disease incidence in a population over time.
• The formula for incidence density is: ID = Number of new cases of a disease / Person-time of exposure.

Immunization Goals

• The strategy of developing disease control programs through the use of vaccines depends on the objectives of the vaccine campaign.
• Goals may include eradication of disease, regional elimination of disease, or control of disease to reduce morbidity and mortality.

Vaccine-Related Supplies and Lawsuits

• Recent shortages of some vaccines have caused concern about vaccine supplies.
• Fewer companies are making vaccines for the United States, citing the cost and risk of developing and making vaccines, tighter regulation of production, and the risk of liability for the companies.
• The National Vaccine Injury Compensation Program was established to cover diphtheria, tetanus, pertussis, measles, mumps, rubella, and oral and inactivated polio vaccines.
• The program essentially protects vaccine manufacturers from liability lawsuits, unless it can be shown that their vaccines differed from the federal requirements.

Secondary Prevention

• Based on early detection of disease through screening or case finding, followed by treatment
• Screening involves evaluating a group of people for asymptomatic disease or risk factors in a community setting
• Case finding is the process of searching for asymptomatic diseases and risk factors among people in a clinical setting

Objectives of Screening

• Test large numbers of individuals for one or more diseases or risk factors in a community setting
• Minimum requirements for establishing a safe, ethical, and cost-effective screening program:
  • Disease requirements:
    • Disease must be serious and have effective therapy
    • Natural history of disease must be understood
    • Disease must not be too rare or too common
  • Screening test requirements:
    • Test must be reasonably quick, easy, and inexpensive
    • Test must be safe and acceptable to individuals and clinicians
    • Operating characteristics of the test must be known and acceptable
  • Health care system requirements:
    • People with positive test results must have access to follow-up
    • Treatment already available for people with the disease
    • Individuals with positive results must have access to treatment
    • Population to be screened must be clearly defined
    • Responsibility for screening, cutoff points, and how findings will be part of participants' medical records

Minimum Requirements for Community Screening Programs

• Disease requirements:
  • Hypertension: fulfills requirements
  • Hypercholesterolemia: fulfills requirements
  • Cervical cancer: fulfills requirements
  • Ovarian cancer: fails to fulfill requirements (low yield of detection, and few cancers can be cured by detection)
• Screening test requirements:
  • Hypertension: blood pressure measurement
  • Hypercholesterolemia: blood screening
  • Cervical cancer: Papanicolaou smear
  • Ovarian cancer: CT scan (not recommended)
• Health care system requirements:
  • Access to follow-up and treatment
  • Clear definition of the population to be screened

Ethical Concerns about Community Screening

• Professionals involved have an obligation to show that benefits of screening outweigh costs and potential risks
• Methods used in performing public screening programs should be safe, with minimal side effects
• Potential benefits of screening include reduced mortality, reduced morbidity, and reassurance
• Potential adverse effects of screening include anxiety from false-positive results, false reassurance, and costs

Controversies in Screening Programs

• Breast cancer screening:
  • Debate about age to start screening, when to stop, and how often to repeat
  • False-positive results and anxiety
  • Potential harm of overdiagnosis and overtreatment
• Prostate cancer screening:
  • Debate about effectiveness in reducing mortality
  • False-positive results and anxiety
  • Potential harm of overdiagnosis and overtreatment
• Need for personalized screening decisions based on individual risk preferences and values### Screening Biases
• Selection bias occurs when individuals with a family history of disease or higher risk participate in screening programs, leading to overestimation of screening effectiveness
• Lead-time bias occurs when screening detects disease earlier in its natural history, increasing the period from diagnosis to death, but not changing the natural history of the disease
• Length bias occurs when screening detects slower-growing tumors, leading to longer survival times regardless of treatment given

Repetition of Screening Programs

• Repeating screening programs too soon can lead to disappointing results due to detecting incident cases rather than prevalent cases
• The more screening tests done, the more likely positive findings will occur, including false positives

Multiphasic Screening

• Multiphasic screening involves screening for multiple diseases at once, but has doubtful yield and high frequency of false-positive results
• The probability of false-positive results increases with the number of screening tests done
• One study found no major differences in health outcomes between multiphasic screening and regular care, but higher hospitalization rates in the screened group

Genetic Screening

• Genetic testing can be used for presymptomatic testing or susceptibility testing for diseases like Huntington's disease and coronary artery disease
• Genetic testing has significant implications for population health, particularly for prenatal screening for certain genetic disorders
• Quality requirements for genetic screening tests include clinical validity, clinical utility, and consideration of environmental influences on gene expression

Periodic Health Examination

• Historically, the most common method of prevention in clinical medicine, especially for adults, was the annual physical examination (checkup), now known as the periodic health examination.
• After World War II, the number of available treatments for chronic illnesses increased, and more people began to have an annual checkup.
• Research on the periodic health examination before the 1960s concerned examinations sponsored by businesses or industries or conducted by the few large health plans existing at the time.
• Most investigators agreed that examinations in children were beneficial, but studies began to cast doubts about the cost-effectiveness of periodic health examinations in adults.
• In the 1970s, investigators began moving toward the idea of modifying the periodic examination to focus only on the conditions and diseases that would be most likely to be found in a person of a given age, gender, and family history, termed “lifetime health monitoring.”
• The Canadian Task Force on the Periodic Physical Examination recommended that the traditional form of periodic checkup be replaced by the use of health protection packages that included gender-appropriate and age-appropriate immunizations, screening, and counseling of patients on a periodic basis.

Health Risk Assessments

• Health risk assessments (HRAs) use questionnaires or computer programs to elicit and evaluate information concerning individuals in a clinical or industrial medical practice.
• Each assessed person receives information concerning his or her estimated life expectancy and the types of interventions that are likely to have a positive impact on health and longevity.
• HRAs assess the needs of individual patients as they enter a medical care system or of employees in an industrial setting, develop health education information tailored to the needs of the individuals, and develop cost-containment strategies based on better acquisition of health risk information from individuals.
• Most HRAs use questionnaires or interactive computer programs to gather data concerning each person being assessed, including height, weight, blood pressure, cholesterol level, and previous and present diseases, as well as lifestyle and family history.
• An algorithm calculates the person’s “risk age” on the basis of the data, usually based on findings of the Framingham Heart Study.

Screening Guidelines and Recommendations

• Many organizations issue screening guidelines and recommendations, including specialty organizations, primary care specialties, foundations for the treatment and prevention of particular diseases, and organizations dedicated to evaluating screening recommendations.
• The U.S. Department of Health and Human Services created the U.S. Preventive Services Task Force (USPSTF) to clarify issues concerning screening and case finding and to make evidence-based recommendations.
• The USPSTF reviews data concerning the efficacy of three broad categories of interventions: screening for disease in asymptomatic clinical populations and in certain high-risk groups, counseling to promote good health habits and prevent disease, and immunizations and chemoprophylaxis to prevent specific diseases.

Lung Cancer Screening

• Development of new diagnostic methods offers new screening possibilities, and conducting a randomized controlled trial (RCT) of a new screening intervention is arduous and time-consuming.
• The history of lung cancer screening illustrates the pitfalls of relying on single-arm studies or mathematical modeling of screening interventions through cost-utility analysis.
• The National Lung Screening Trial was launched in 2002, randomizing over 53,000 participants to either three annual helical CT scans or chest x-ray films, and published results in 2011 showing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0%.
• The trial also likely showed evidence of overdiagnosis; even after the gap in detection time between the two screening modalities closed, the screened group had more cancer than the control arm.