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A. Screening

  1. Definition: application of a test to an asymtomatic group to estimate probability that members of group will have a disease
  2. Diseases for which screening is appropriate:
    1. Have serious consequences
    2. Are progressive
    3. Are treatable and early treatment produces better results than late treatment
    4. Prevalence of detectable preclinical phase is high in the population being screened.
  3. Characteristics of Good Screening Tests
    1. Inexpensive
    2. Comfortable enough to be acceptable to patients
    3. Convenient to perform
    4. Reliable (consistent, relatively insensitive to technique of performer)
    5. Valid (sensitivity - few false negatives, and specificity - few false positives, are high)
    6. High positive and negative predictive value, measures which combine test sensitivity and specificity with prevalence in the population being considered
  4. Results of an appropriate screening program
    1. For acute diseases, reduced morbidity and mortality
    2. For chronic diseases, reduced severity and/or prolonged remissions
    3. For infectious disease, screening and early treatment may reduce disease transmission, reducing disease incidence
  5. Results of inappropriate screening
    1. Exposes patient to risks associated with screening test (such as radiation exposure from mammography for low risk women under 40 years old)
    2. Exposes patient to risks associated with diagnostic test following positive screening test (for example, prostate biopsy following positive digital rectal exam)
    3. Exposes patient to anxiety associated with positive screening test (PSA, mammography)
    4. Creates unnecessary expense (CA-125 test for patient at low risk for ovarian cancer)
  6. Periodic Overall Health Evaluation [14]
    1. Some benefits in specific areas, but full physical examination in persons without specific complaints of questionable value
    2. Beneficial association with gynecologic examination and Pap smears
    3. Cholesterol (Chol) screening beneficial
    4. Fecal occult blood testing beneficial

B. Cardiovascular (CV)

  1. Framingham Coronary Artery Disease (CAD) Prediction Scores [25]
    1. Consists of 6 parameters for predicting CAD events
    2. Age
    3. Blood Pressure
    4. Total Chol (see below)
    5. HDL Chol
    6. Diabetes
    7. Current Smoking
    8. These parameters are weighted and prediction scores calculated
    9. Framingham CAD Prediction has been validated in both sexes and many ethnic groups [25]
    10. Low risk CV profile associated with ~5-10 year increased lifespan
    11. Systemic inflammation level, assessed by C reactive protein (CRP) is a stronger predictor of first CV events than LDL Chol level [44]
    12. Strongly consider measuring CRP levels in all patients at risk for CAD
    13. Normal CRP <1mg/L; moderate risk 1-3mg/L; high risk >3mg/L [66]
  2. Uppsala Longitudinal Study of Adult Men (ULSAM) [18]
    1. Study of biomarkers to predict >10 year CV morbidity and mortality in adult men
    2. Combination of biomarkers more accurate than any one alone in predicting clinical outcomes
    3. Adult men with or without pre-existing cardiovascular disease
    4. Four independent markers were validated:
    5. Troponin I - myocardial damage
    6. N-terminal pro-brain ntatriuetic peptide (NT pro-BNP) - left ventricular dysfunction
    7. Cystatin C - renal dysfunction
    8. C-reactive protein (CRP) - inflammation
    9. These markers were all independent of known, existing CV risk factors
  3. Blood Pressure (BP) [78,79]
    1. All persons 18 years of age or older should be screened for hypertension (HTN)
    2. At least annual BP checks should be performed
    3. Diagnosis of HTN usually requires 3 separate determinations of high BP
    4. Use home monitoring to distinguish true from "white coat" hypertension
    5. Even high normal BP is associated with increased risk for CV disease [29]
    6. Persons with blood pressure >135/80 mm or being treated for HTN should be screened for type 2 diabetes (DM2) [84,85]
    7. Atorvastatin (Lipitor®) treatment in patients with HTN and average or low Chol levels reduces stroke and CV events ~30% [48]
  4. Pulse - all patients
  5. Chol levels (see below)
  6. US Preventive Task Force [3]
    1. Standard clinical history, vital signs, auscultation of heart are performed
    2. None of the following are recommended routinely for screening for cardiac disease
    3. Electrocardiography (ECG)
    4. Exercise Treadmill Test (ETT)
    5. Electron beam computerized tomography (EBCT)
    6. ECG is routinely done for patients with significant cardiac risks, preoperative evaluation
    7. ECG should be done in patients with new onset or worsening murmers
  7. Echocardiography [26]
    1. Not routinely included in health screening
    2. Left ventricular (LV) dysfunction prevalance 3-6% in community (similar to heart failure) [2]
    3. Physical exam and history are insensitive for early LV dysfunction
    4. Symptoms and signs of heart failure in only ~50% of those with clear LV dysfunction
    5. Low threshhold for echocardiography in patients with ANY cardiac risk factors
  8. Carotid Ultrasound
    1. All patients with evidence of CAD
    2. Patients with other vasculopathy
    3. Patients with carotid bruits
  9. Exercise Treadmill Test (ETT) [34]
    1. Usually first test for patients with clinical suspicion of angina, coronary diseaes
    2. ETT leads to increased myocardial workload to identify potentially ischemic regions
    3. Workload includes increased heart rate, blood pressure, and myocardial vessel dilation
    4. Workload is the most important parameter derived from ETT in any age patient [28]
    5. In general, attempt to achieve >90% of maximal heart rate: maximal HR ~ 220 - Age
    6. Monitor symptoms and ECG for specific changes
    7. Overall sensitivity ~45-66% and specificity ~85% for ETT in a moderate probability cohort which had undergone minimal previous testing
    8. Peak exercise capacity on ETT was best overall best predictor mortality in men [34]
  10. Chest Radiography
    1. Symptomatic evaluation of chest pain
    2. Not useful for routine pre-operative evaluations
  11. Abdominal Aortic Aneurysms (AAA) [15,16,43]
    1. All men age 65-74 should have ultrasound screening for AAA [20,43]
    2. High suspicion in patients with other CV disease, particularly HTN
    3. ~75% of AAA occur in men
    4. Prevalance in men >64 years old is ~5% (aorta >3cm diameter)
    5. Physical examination is unreliable; ultrasound is screening method of choice
    6. Repeat ultrasound for aneurysms >3-4cm
    7. AAA repair considered only for aneurysms >5.5cm or expansion >1cm/year, symptoms
  12. Peripheral Vascular (Arterial) Disease (PVD) [12,27]
    1. Increasing prevalance with age
    2. Low index of suspicion by most primary care physicians
    3. Prevalance ~30% in patients at least 70 years of age
    4. Strongly recommend ankle-brachial index screening in patients with risk factors
    5. Over 40% of patients >70 years with PVD do not have CAD
    6. CV risks are associated with development of new onset kidney disease [4]
    7. Lifestyle modifications and initiation of walking exercises in all PAD patients [12]
  13. Attention to all aspects of therapy for patients with CV disease
    1. Patients should NOT smoke
    2. Alcohol - 1-2 servings of alcohol per day is associated with improved CV outcomes
    3. Weight should be maintained in normal range
    4. Exercise should be strongly encouraged
    5. Reduce exposure to fine particulate air pollution [32]
    6. Mortality reduction 36% in patients with CAD who quit smoking [51]
  14. Hemoglobin A1c (HbA1c) [6,7]
    1. Measure levels of glycosylated hemoglobin
    2. Marker for risk of insulin resistance and diabetes mellitus (DM)
    3. Levels correlate with CV mortality with or without DM
    4. Improvement in markers for insulin resistance reduce HbA1c (see below)
  15. B type natriuretic peptide (BNP, BNF)
    1. Elevated BNP levels are associated with LV dysfunction
    2. Elevated N-terminal pro-Brain (B) natriuretic peptide (BNP) associated with CV death
    3. Elevated baseline BNP levels associated with increased CV events, death [60]

C. Cholesterol (Chol)

  1. NCEP recommends screening in all patients >25 years of age
  2. Possibly in younger patients with multiple CV risk factors
  3. Normal Chol level (<200mg/dL) should be followed q5 years
  4. Total Chol, HDL and triglycerides should be measured directly in screening tests
    1. Adding direct LDL, lipoprotein(a), or IDL measurements does not improve prognostic accuracy in young persons without vascular disease [68]
    2. In a direct comparison study, ratio of apolipoprotein B100 (ApoB) to apolipoprotein A (Apo A) was a better predictor of myocardial infarction (MI) than any Chol ratio [88]
    3. Therefore, consider obtaining ApoB and ApoA levels
  5. Abnormal level should be repeated with complete Chol profile
  6. Chol Level and Mortality [77]
    1. Linear relationship between Chol level and mortality across cultures
    2. Total Chol and total/HDL Chol strongly associated with CAD mortality
    3. Ratio of Total/HDL (or LDL/HDL) Chol is the best overall predictor of CAD mortality
    4. Much weaker association of Chol with stroke
    5. Chol effects on CAD mortality independent of age and blood pressure
    6. Chol effects on CAD mortality are more pronounced in age 40-49 than in 70-89 years
  7. Nonfasting trigylcerides are a useful risk marker for CAD in both men and women [75,76]
  8. CRP level should probably be measured in any patient at risk for CAD [44]
  9. Very Low Total Chol
    1. Has been associated with increased risk of cancer, hemorrhagic stroke, trauma
    2. Part of the cancer risk is due to confounding variables: smoking, gastrointestinal disease, alcohol
  10. Chol Reduction with Statins
    1. Marked reduction in mortality and CV morbidity with statin treatment [5]
    2. Consider atorvastatin 80mg (high dose) in secondary stroke/TIA prevention [12]

D. Type 2 Diabetes Mellitus (DM2) [46,47]

  1. Increasing incidence of DM2 suggests routine screening may be warranted
  2. Lifetime probability of DM2 for person born in 2000 ~33% for men, 39% for women [1]
  3. Screening any adult at elevated risk for DM2 is recommended
    1. All obese and overweight persons
    2. Strong family history
    3. HTN
    4. Hyperlipidemia
    5. Chronic glucocorticoid use (>14 days)
  4. Random plasma glucose >200mg/dL (>11.1mmol/L) + HbA1c at least 2 standard deviations (SD) above mean for laboratory should be diagnostic for DM [38]
  5. Abnormal tests may be followed up with glucose tolerance test
  6. Consider fructosamine and/or HBaA1c levels added to glucose level
  7. Incidence of DM2 higher in African versus Caucasian Americans [22]
    1. 1.5X higher incidence in men
    2. 2.4X higher incidence in women
  8. Prevention of DM2
    1. Behavioral and lifestyle modification very effective in reducing DM2 risk
    2. Diet, exercise, nonsmoking all critical to reduce risk of DM2
    3. Alcohol [62] and coffee [63] intake associated with reduced risk of DM2
    4. Ramipril reduced risk of developing DM2 in vascular disease patients >55 by >30% [28]
    5. Metformin reduced risk of developing DM2 by 31 % in patients with impaired glucose tolerance [36]
    6. Acarbose 100mg tid reduces risk of developing frank DM2 ~25% in patients with impaired glucose tolerance [37]

E. Urinalysis and Renal Function

  1. Urinalysis (Urine Analysis)
    1. Dipstick analysis includes pH, glucose, protein levels, leukocytes, nitrites
    2. All pregnant women; renal patients; symptomatic patients
  2. Bactiuria Screen with Urine cultures [87]
    1. All pregnant women at 12-16 weeks gestation oir first prenatal visit
    2. Do not screen asympatomic men or non-pregnant women
  3. Serum Electrolytes - baseline may be recommended q1-5 yrs
  4. Renal Dysfunction - screening BUN, creatinine; urinalysis for hematuria, proteinuria
  5. Hematuria - malignancy evaluation is required

F. Osteoporosis [30,39,40]

  1. Highly prevalent condition in postmenopausal women:
    1. Osteopenia prevalence in is ~40%
    2. Osteoporosis prevalence is 7.2%
  2. Screening should be considered in any woman (or man) with increased risk
    1. Consider in post-menopausal women age >49 years with other risk factors
    2. General screening in postmenopausal women >60 years is not clearly beneficial [40]
    3. Screening in white women >65 years is recommended if they will initiate treatment [41,42]
    4. Screening recommended in men age >60-65 years with other osteoporosis risk factors [83]
  3. Screening by bone mineral density (BMD)
    1. BMD by dual-energy X-ray absorption (DEXA) in white women >65 recommended [41,42]
    2. Femoral neck BMD is best predictor for hip fracture risk
    3. In older persons, osteoarthritis may interfere with accurate vertebral measurements
    4. Persons with BMD >2.5 SD below mean have very high risk of osteoporotic fractures
    5. BMD in non-white women and in other women at high risk may be beneficial [41,42]
  4. Screening for osteoporosis associated with 35% reduction in fractures [67]

G. Endocrinopathies

  1. Thyroid Dysfunction
    1. Routine screening of all persons is neither recommended or oppposed [55,56]
    2. Thyroid stimulating hormone (TSH) should be obtained in any patient with possible thyroid disease
    3. Includes patients with hypertension or tachycardias or other suggestive symptoms
    4. Screening women over 35 yrs every 5 years with TSH appears to be cost effective
    5. Whether men should be screened with TSH is less clear
    6. Screening all women >50 with a TSH test is recommended (1 in 71 will be positive)
    7. Persons with TSH <0.5 mU/L have subclinical hyperthyroidism
    8. These persons are at increased risk for atrial fibrillation, osteoporosis, and frank hyperthyroidism
    9. Persons with TSH 5-10 mU/L (>10% of women >60 years) have subclinical hypothyroidism
    10. These persons are at risk for hypercholesterolemia and frank hypothyroidism
    11. It is currently unclear whether patients with asymptomatic subclinical thyroid disease will benefit from any treatment; treatment usually reserved for symptoms [55,56,57,58]
  2. Hemochromatosis [71,72]
    1. Screening is neither advocated nor discouraged; evidence is insufficient
    2. However, population based screening is practical and can lead to preventative therapy [69]
    3. Current genetic tests have ~85% sensitivity and very high specificity
    4. Hemochromatosis is a common and very treatable disease in early stages
    5. Functional screen consists of ferritin level, transferrin saturation, iron levels
    6. Transferrin saturation >60% and/or ferritin >500ng/mL are strongly suggestive
    7. Such patients should be evaluated liver function testing, possible liver biopsy
    8. Women at much reduced risk than men (usually develop disease at later age)
    9. Elevated iron stores also linked to increased risk of DM2 in healthy women [59]

H. Pulmonary Function

  1. Pulmonary Function Tests (PFTs) - Perform Tests In:
    1. Active pulmonary disease
    2. Smokers with symptoms
    3. PFTs for pre-op evaluation only in symptomatic patients
    4. PFTs should not be done (for COPD screening) in healthy adults without symptoms [81,82]
    5. PFTs should not be performed in smokers who do not have symptoms [81]
  2. PFTs to detect early COPD prior to symptoms even in smokers is not recommended [81,82]
  3. Chest radiograph - symptomatic screening only, asbestos exposure

I. Colon Cancer Screening

  1. Stool (fecal) occult blood (FOBT) tests are mainstay of colorectal cancer screening
  2. Usually 1 survey per year in all patients >49 years (or >45 years) old
  3. At least 3 stool specimens should be surveyed
  4. Biennial occult blood screening reduces death due to colorectal cancer ~20%
  5. For any history of rectal bleeding, full evaluation of colon is recommended
    1. Sigmoidoscopy + double contrast (barium/air) enema OR
    2. Full Colonoscopy
  6. Majority (~60%) of patients with positive occult blood have uper GI lesions
    1. Many patients with upper GI lesions take aspirin, ethanol, or other NSAIDs chronically
    2. Esophagitis, gastric ulcer, gastritis and duodenal ulcer all found
  7. Flexible sigmoidoscopy in asymptomatic persons over age 50 is recommended regardless of stool occult blood results
  8. Finding of even small adenomas (<6mm) should lead to further evaluation
  9. Positive Occult Blood and Negative Colonoscopy
    1. Upper GI endoscopy should be considered in FOBT+ patients negative for colonoscopy
    2. About 13% of patients will have had upper gastrointestinal (GI) lesions
    3. About 55 of these had peptic ulcer disease (PUD)
    4. Cancer (gastric > esophageal) in >1% of the patients
    5. In patients with anemia (Hb <12-14gm/dL) and positive occult blood, >25% had significant upper GI lesions
  10. For individuals with high risk (at least 3 adenomas or any advanced adenoma) on initial testing, repeat colonoscopy at 3 years is recommended (6.6% risk of advanced adenoma on repeat) [80]

J. Depression and Anxiety Screening [11,33]

  1. These are critical and often overlooked parts of primary care medicine
    1. Depression is a major problem in primary care (~30% of typical practice) [35]
    2. Anxiety disorders are common in primary care (~20% of screened patients) [73]
  2. Screening for Depression and Anxiety
    1. Screening is considered a standard and essential component of primary care
    2. Failure to detect depression may result in unnecessary diagnostics, treatments, suffering, and even suicide
    3. Majority of managed care organizations require depression screening in primary care
    4. Failure to detect and/or treat depression may have negative medicolegal ramifications
  3. Two questions can cover depression screening about as well as more complex screens
    1. "During the past month, have you often been bothered by feeling down, depressed, or hopeless ?"
    2. During the past month, have you been bothered by little interest or pleasure in doing things ?"
    3. This test has a fairly high false positive rate (specificity 57%)
  4. Two questions can cover anxiety screening as well as more complex screens (GAD-2) [73]
    1. Generalized anxiety disorder (GAD): 6.8% prevalence in primary care
    2. Post-traumatic stress disorder (PTSD): 7.6% prevalence
    3. Panic disorder 6.8% prevalence
    4. Social anxiety disorder: 6.2% prevalence
  5. Positive answers to above questions should prompt further assessment [33]
    1. Frequency and duration of symptoms in nine specific areas should be assessed:
    2. Depressed mood
    3. Anhedonia (markedly diminished interest or pleasure)
    4. Sleep disturbance
    5. Appetite or weight change
    6. Decreased energy
    7. Increased or decreased psychomotor activity
    8. Decreased concentration
    9. Guilt or feelings of worthlessness
    10. Suicidal ideation

K. Substance Abuse

  1. Smoking [31]
    1. "Quitting smoking is the MOST important action you can take to stay healthy"
    2. Physicians must play an aggressive role in getting patients to quit smoking
    3. Mortality reduction 36% in patients with CAD who quit smoking [51]
  2. Alcohol
    1. Recreational (mild to moderate) alcohol use is beneficial
    2. Men >2 drinks per day and women >1 drink per day associated with increased risks [74]
  3. Recreational Drug Abuse
    1. Cocaine
    2. Opiates
  4. Anabolic Steroids
    1. Particularly in young athletes
    2. Androstenedione available over the counter 300mg/d increases serum testosterone [21]

L. Miscellaneous Screening

  1. Obesity [52,53]
    1. Major increasing problem in all developed countries
    2. All persons should be screened for obesity and counseling initiated as appropriate [57,58]
    3. In 2003-4, 32% of adults in US were obese [13]
    4. In 2003-4, 17% of US children and adolescents were overweight; increased since 1999 [13]
  2. Sexually Transmitted Diseases
    1. Chlamydia - often asymptomatic; screening can prevent spread and complications [45]
    2. Chlamydia screening in any sexually active woman <24 years old, in age >24 at increased risk (multiple partners, others), and in pregnant women [74]
    3. Pap smear should be performed in all sexually active women
    4. Pap smear is not beneficial and should not be done after hysterectomy for benign disease [64]
    5. Human Papilloma Virus (HPV) - may be alternative to Pap smear screening [54]
  3. HIV Infection [8,9,10]
    1. Screening recommended in all persons regardless of risk unless they decline [12]
    2. Includes adolescents, adults, and particularly pregnant women
    3. FDA approved rapid screening tests are highly accurate and effective
    4. Early institution of antiretroviral therapy improves mortality and quality of life
    5. Use of antiretoviral therapy in pregnant women reduces mother-to-child transmission
  4. Hepatitis C Virus (HCV)
    1. General screening for HCV is not recommended [61]
    2. Test ANY patient at high risk for HCV [65]
    3. Test ANY patient with abnormal liver function tests (LFTs)
  5. Glaucoma - tonometry for intraocular pressure
  6. Melanoma
    1. Monthly to bimonthly self screening
    2. Help from spouse / significant other
    3. Yearly or semi-annual screening by dermatologist
    4. Special attention to screening in high risk groups
  7. Proteinuria - weak risk factor for all cause mortality and for CV disease [24]
  8. Hemochromatosis
    1. Overall incidence is 0.5-1% in Caucasian populations
    2. Screening with iron levels ± transferrin is generally considered cost-effective
    3. Persons with (mild) chronic elevations of transaminases should be evaluated
    4. Relatives of hemochromatosis patients are at high risk for this and related diseases [23]
  9. Dementia [19,49,50]
    1. Unclear if dementia screening is warranted given modest benefits of potential therapy
    2. Screening tests have good sensitivity but only fair specificity
    3. Mini-Mental State Exam (MMSE) or Memory Impairment Screen (MIS) are recommended [19]
    4. Cholinesterase inhibitors are somewhat effective in slowing cognitive decline in Alzheimer's disease (AD) by 2-7 months
  10. Breast Implants
    1. No increased risk of breast cancer
    2. Increased risk of local reactions
    3. Systemic lupus incidence was NOT increased
    4. Main risk was "any connective tissue disease", not any specific disease
  11. Hearing in Elderly [70]
    1. Hearing loss normally occurs with aging
    2. Hearing loss can contribute to isolateion, depression, possibly dementia
    3. Primary care physicians should screen all elderly for hearing loss, refer their patients
  12. Domestic Violence - clinical assessment, cautious questioning
  13. Coffee consumption does not increase mortality, but may reduce mortality [86]

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