Health Maintenance

Presented by

John Zweifler, M.D., M.P.H.

Who and What do we screen?

• Significance of condition.– Severity– Frequency

• Detectable during asymptomatic period.

• Effective intervention available.

Targeting Health Maintenance Activities*

• Deaths/year attributable to various conditions.

– Cigarette smoking - 400,000

– Diet and exercise - 300,000

– Excess alcohol - 100,000

– Breast cancer - 40,000

– Cervical cancer - 4,000

– Colo-rectal cancer - 56,000

– Prostate - 30,000

– Lung -155,000

• *Ganiats T Prevenion Strategies in Family Practice. AAFP. 2003

Assessing screening interventions

• Quality of screening test.– Sensitivity, specificity– Accuracy

• Acceptability of screening.– Cost– Convenience– Availability

• Potential adverse effects of screening and treatment.

Sensitivity and Specificity

• Condition Present

Positive Test a

Negative Test c

Sensitivity=a/(a+c)

Positive Predictive Value=a/(a+b)

• Condition Absent

Positive Test b

Negative Test d

Specificity=d/(b+d)Legend:

a=true positive

b=false positive

c=false negative

d=true negative

Testing ConditionsSize of Population = 100,000

Sensitivity of Test = 90%Specificity of Test = 90%

• Cancer Prevalence = 1%

Cancer Cancer

Present Absent

Positive 900 9,900

Test

Negative 100 89,100

Test

Positive Predictive Value= 8.3%

• Cancer Prevalence = 0.1%

Cancer Cancer

Present Absent

Positive 90 9,990

Test

Negative 10 89,910

Test

Positive Predictive Value = 0.9%

Cost Effective Analysis

• Considerations in cost effective analysis:– Perspective - Patient, payor, society– Cost of intervention.– Cost of necessary additional tests or monitoring.– Cost of complications.– Opportunity cost - allocation of resources.

Cost effective analysis*Cost per year of life saved

• Mandating automatic seat-belts: $0-$25,000.• Influenza vaccination: $500.• Nicotine gum/smoking cessation: $6,000-$13,000.• Statin drugs for men 35-55 years with CHD and

chol >250mg/dl: $0-$9,000.• Statin drugs for women 35-45, no CHD,

cholesterol >300: $1,000,000.

– *Deyo R. JABFP JAN. - FEB. 2000. Vol. 13 #No. 1 47-54

Cost Effectiveness of Various Screenings

• Annual screening for cervical cancer, women 21 years or older - $50,000 per life year gained.

• Hypertension screening for asymptomatic men 20 years and older - $48,000.

• Hypertension screening for asymptomatic women 20 years and older - $87,000.

Types of Prevention

• Primary prevention: prevent or arrest the disease process in its earliest stages by promoting healthy lifestyles or immunizing against infectious disease.

• Secondary prevention: detecting and treating asymptomatic risk factors or early asymptomatic disease.

• Tertiary prevention: screening for complications of known disease.

United States Preventive Service Task Force (USPSTF)

Guide to Clinical Preventive Services

• www.preventiveservices.ahrq.gov• Released the first report in 1989.• Now supported by the Agency for Health Care

Research and Quality, and the United States Public Health Service.

• Relies on evidence based approaches.• Task force members represent health-care related

federal organizations and primary care and preventive medicine specialties.

Hierarchy of Research Design*

• I. At least one properly randomized control trial.

• II-1. Well designed control trials without randomization.

• II-2. Well designed cohort or case-control analytic studies.

• II-3. Multiple timed series with or without the intervention or dramatic results in uncontrolled experiments.

• III. Opinions of respected authorities, descriptive studies and case reports, or reports of expert committees.

– *USPSTF. 2001.

Pelvics and Rectals!?

Rectum 23 %

Rectosigmoid 9 %

Sigmoid 24 %

Descending 7 %

Transverse 11%

Ascending 9%

Cecum 11 %

Appendix 6 %

TOTAL 37 %

TOTAL63 %

Colorectal Screening Sigmoidoscopy

• Selby, NEJM, 1992 - Case control study showed 70% reduction in distal CRC in those exposed to sigmoidoscopy.

• Selby, Atkins & Sakamoto JFP, 1994 - Studies suggest sigmoidoscopic screening q 10 years may be effective.

• Atkins, NEJM, 1992 - Adenomatous polyps <1 cm no benefit to colonoscopic follow up.

Colorectal Cancer and Polyps

• ~30-50% of Americans 50-75 y.o. have polyps.

• 90% of polyps <one centimeter. • If polyp found in sigmoidoscopy -> biopsy• If adenomatous -> colonoscopy: • Risk of colorectal cancer S/P excision of

small polyp (<1 cm.) same as general population.

Colorectal Screening Colonoscopy

• Q3 year colonoscopic surveillance results in 88-90% reduction in colorectal cancer (Family Practice News. 8-1-94)

• Cost - 3 billion/year

Colorectal Screening Hemoccults

Allison, NEJM, 1996 - sens. spec. +PPV

Hemoccult 32 98 23

Hemoccult Sens 71 87 9

Hemeselect 67 95 20

Mandel, NEJM, 1993 - 1/3 reduction in colorectal cancer (CRC) with hemoccults and rehydration.

Colon cancer Fecal occult blood testing

• Newer tests (hemoccult Sensa, and Heme Select) are more sensitive.

• Newer tests less specific, resulting in high false positive rates.

: -.

Colonoscopy vs. Barium Enema

• BE safer, less costly.• Colonoscopy diagnostic & curative.• BE - 44% sensitive, 75% specific (Family Practice

News. Aug. 1,1994).

Colorectal Screening RecommendationsUSPSTF 2002

• Strongly recommends screen men and women 50 years of age or older: A

• Screening modalities;– FOBT, sigmoidoscopy, or FOBT + sigmoidoscopy– Colonoscopy– Double contrast barium enema

• Cost effective- <$30,000/year of life saved regardless which screening test used

• Interval and upper limits not specified

Prostate Cancer

• 50% of men >80 y.o. found to have prostate cancer at autopsy.

• Incidence increased from 90,000 in 1987 -> 317,000 in 1996.

• 2nd most common cause of death from cancer in men.

• 21st in years of life lost.

Prostate Cancer*

• Cost of screening and f/u of local disease in men 50-70 y.o. - $12-28 billion/year.

• Complications of treatment (impotence, incontinence, scarring).

• Screening results in marginal increase in life expectancy, decrease in quality of life, and high cost.

*Krahn M, et al., Screening for Prostate Cancer. JAMA Sept. 14,1994

Prostate Cancer Survival

• Rate of prostatectomy increased 600% from 1984-1990.

• Age adjusted mortality rates - no change.• 10 year survival with stage A cancer - 85%• 95% of men with prostate cancer die from other

causes.• 10 times more likely to die from cardiovascular

disease.

Prostate Specific Antigen (PSA)

• Approved by FDA, 1996 - 10% positive.• Large overlap between BPH & prostate cancer. • PSA 55-75% sensitive, 70% specific.• Follow-up with ultrasound, biopsy.

Prostate Cancer ScreeningUSPSTF 2002

• Insufficient evidence to recommend for or against routine screening with PSA or digital rectal exam: I– PSA can detect early stage prostate cancer.– Inconclusive evidence that early detection

improves health outcomes.– Screening associated with important harms

including false positives, biopsies, and complications of treatment.

– Uncertain if benefits exceed risk

Osteoporosis

• 1.3 million osteoporosis-related fractures in U.S. each year

• 15% of women have hip fractures• Strongly associated with low bone

mineral density(BMD)• Risk factors - female, age, anglo,

low body weight, & bilat. oophorectomy

Value of Screening

• Women >65 years old with low BMD are eight times more likely to have hip fracture

• No studies correlating perimenopausal BMD with long-term fracture risk

• Other risk factors-age, health,activity,vision

• ?impact on recommendations re calcium, hormone replacement therapy, or exercise

Screening Tests

• Plain films• C.T.• Absorptiometry-measures BMD

– Dual energy x-ray (DXA)– Femoral neck measure best predictor of hip

fx

• Experimental - Ultrasound and biochemical

Interventions

• Calcium, exercise, safety measures• Hormone replacement therapy• Selective estrogen receptor

modulators• Biphosphanates

Osteoporosis Treatment

• Meta analysis of Alendronate showed reductions in vertebral and forearm fractures

• Fracture Intervention Trial showed benefit of Alendronate in hip (50%) and total fx (30% less) in women with low BMD only.

• Raloxifene study showed fewer vertebral fx.• USPSTF estimates need to screen 731

women over 64 years old, or 1,856 women 60-64 to prevent one hip fracture.

Raloxifene To Prevent Osteoporosis

• Estrogen-like effect on bones and lipid metabolism (decreases total LDL cholesterol without changing HDL).

• No estrogen-like effects on breast or uterine tissue.

• No post-menopausal bleeding or increase in breast CA.

• Patients may experience hot flashes• Decreases risk of osteoporosis, has not

been proven to decrease fracture risk.

USPSTF Osteoporosis Guidelines-2002

• Screen women aged 65 and older B • Begin at age 60 for women at increased risk for

osteoporotic fractures B • Benefits/harms of screening and treatment too close to

recommend for other age groups. C

– Risk for osteoporosis and fracture increases with age and other factors

– BMD measures accurately predict fracture risk– Treating asymptomatic women with osteoporosis

reduces fracture risk.

Hormone Replacement

• Can reduce risk of fractures by 25-50%

• Need to continue indefinitely• More likely to continue if have low

BMD• Decision re HRT hinges on factors

besides BMD

Proceed With Caution Estrogen Replacement Therapy • Risk of coronary heart disease exceeds risk of

breast cancer (230,000 deaths from CHD, 34,000 from breast cancer in women older than 55 years).

• Observational studies suggested 40-50% reduction in fatal coronary heart disease in post menopausal estrogen users. (Grady, et al., Ann Intern Med, 1992;117:1016-1037).

• Observational studies do not establish causal relationship.

Prevention of Coronary Heart Disease in Post-menopausal

Women*• Randomized trial of estrogen plus progesterone. -No differences in cardiovascular outcomes, cancer,

or total mortality despite lower LDL and higher HDL in HRT group.

-More thromboembolic events and gallbladder disease in HRT group.

-Trend toward more coronary heart disease in first year, and less in later years.

*Hulley, et al., JAMA, 1998;280:6055 & 613.

Hormone Replacement Therapy*

• Large RCT’s including women’s Health Initiative and the Heart and Estrogen/Progestin Replacement Study (HERS) have evaluated HRT.

• HRT beneficial in relieving vasomotor symptoms.• HRT has beneficial effects on colon cancer and hip fractures.• Benefits more than offset by increased risk of coronary events,

stroke, pulmonary embolism, and breast cancer.• Further analysis of WHI indicates HRT has no significant effects

on general health, vitality, mental health, depressive symptoms, or sexual satisfaction. (Hays et al. NEJM 2003; 348: 1839-54.)

– *Grady D NEJM 348; 19. May 8, 2003. 1835-1837.

Breast Cancer

• 192,000 cases of breast CA & 40,000 deaths in 2001

• Breast CA deaths decreased 8-9% in women 36-59 y/o & 3-5% in women 60-79 from 1989-92

• African-American women > 2 times more likely to die of breast CA

• More than 40% of years of life lost are from women diagnosed < 50 y/o

Mammography & Breast Cancer

• Seven randomized controlled trials in women ages 40-74

• The six trials involving women >50 years old demonstrate decrease in mortality from breast cancer of 20-30%

• No difference if screened every 12 months or every 18-33 months

Randomized Controlled Trials of Breast Screening for Women Age 40–49: Relative Risk (RR) of Mortality for

Screened Subjects Versus Control Subjects

# of subjectsTrial Year Screened Controls RR

HIP Study 1963–69 14,423 14,701 0.77Malmo 1976–86 3,658 3,679 0.51Kopparberg 1977–85 9,582 5,031 0.73Ostergotland 1977–85 10,262 10,573 1.02Edinburgh 1979–88 5,913 5,810 0.78Stockholm 1981–85 14,375 7,103 1.04Gothenburg 1982–88 10,600 12,800 0.73NBSS-1 1980–87 25,214 25,216 1.36HIP—Health Insurance Plan; NBSS—National Breast Screening Study.Modified from Smart R, 1995.

Study Design Controversy

• Non-compliance and Contamination• Study size & statistical significance• Follow-up period• Lead-time & length-time bias• Inclusion of women with breast Ca.• False positives

Screening for Breast Cancer in Women 40-49 Years Old

• Canadian national breast screening study designed to answer this question

• No benefit shown -study has been criticized (Miles A. Can Med Assoc J 1992;147:1459-1476)

• 3 trials - no benefit, 4 trials - nonsignificant benefit of 22% or more

• Meta-analysis of 40-49 y.o.subgroup showed no reduction in breast cancer mortality (Elwood J, Online Curr. Clin. Trials 1993, Doc. #32)

Benefits of Screening

40-49 y/o• 10% shift from Stage

II Ca. to Stage I• No benefit first 9 years• 16% decrease in breast

CA mortality 10-14 years

50-69 y/o• 40% shift from Stage

II Ca. to Stage I• No benefit first 5 years• 27% decrease in breast

CA mortality after 5 years

Peer, et al. Age Specific Effectiveness … J Nat’l Cancer Inst. 994;86:436-41

Kerlikowske, Efficacy of Screening Mammography. Monogr. Nat’l Cancer Inst. 1997;22:79-86

Cost Effectiveness of Mammography

• Breast CA incidence 2-3 x greater in 50-69 y/o than 40-49 age group (Saltzmann et al. Ann Intern Med 1997;127:955-965)

• Previous studies showing equal cost effectiveness did not account for 10 year lag in benefits (Lindfors JAMA 1995;274:881-4 Feig. Cancer 1995;76:97-106)

Cost Effectiveness of Mammography (cont.)

• 40-49 y/o (screen q 18 mo)• Increase life exectancy 2.5 d.• 4 deaths prevented/10,000 at

80 y/o• $105,000 per year of life

saved

• 50-69 y/o (screen q 2 years)• Increase life expectancy 12 d.• 37 deaths prevented/10,000

at 80 y/o• $21.400 per year of life saved

Genetic Testing for Breast Cancer*

• 5-6% of breast cancers associated with inherited genetic mutation.

• BRCA1 and BRCA2 among hundreds of mutations associated with breast cancer.

• Found in .1% of general population.• Account for less than 1/5 of familial risk

of breast cancer.• Also linked with ovarian cancer.

*Isaacs C, Fletcher SW, Peshkin BN, Up To Date, last updated December 4, 2002

BRCA 1 and 2 and Cancer*

• Ashkenazi Jews with high incidence of BRCA mutations studied.

• 10% of breast cancer associated with BRCA 1 or 2.

• Associated with 82% lifetime risk of breast cancer.

• Associated with 20-40% lifetime risk of ovarian cancer.

*King M. Science October 2003

Treatment Options for Breast Cancer Genetic Pre-disposition *

Increased Surveillance

• Cancer Genetic Study Consortium recommends: – monthly BSE at age 21,– annual CBE beginning at age 25-35, – annual mammography beginning at age 25-35, – annual or semi-annual ovarian cancer screening

with ultrasound and CA-125 beginning at ages 25 or 35.

• Efficacy of early and increased surveillance not known.

*Isaacs C, Fletcher SW, Peshkin BN, UpToDate, last updated April 28, 2003

Treatment Options for Breast Cancer Genetic Pre-disposition *

Surgery

• Prophylactic bilateral mastectomies and oophorectomies.- No recurrence after three years in 76 healthy women with prophylactic mastectomies, compared to eight cases amongst 63 new patient carriers who did not undergo surgery.- 70% satisfied re decision 14 years later, 25% less feminine.

• In one study, bilateral salpingo – oophorectomy reduced risk of breast cancer by over 50%.

*Isaacs C, Fletcher SW, Peshkin BN, UpToDate, last updated April 28, 2003

Prognosis of BRCA Associated Breast Cancer*• Treatment of BRCA initial breast cancer as

effective as women with sporadic breast CA.• BRCA women at higher risk for new primary

breast cancer.- 30-40% ten year risk.

• Several hundred possible BRCA related mutations, most concerning if specific mutations identified in a family member with CA.

*Isaacs C, Fletcher SW, Peshkin BN, Up To Date, last updated December 4

Treatment Options for Breast Cancer Genetic Pre-disposition *

Chemo prevention

• Selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene

• Tamoxifen approved for use in women at high risk for breast CA by the FDA.

• No prospective studies demonstrating benefits from chemo prevention in BRCA carriers.

• Oral contraceptives: May increase risk of breast CA but decrease risk of ovarian cancer.

*Isaacs C, Fletcher SW, Peshkin BN, UpToDate, last updated April 28, 2003

USPSTF 2002 Breast Cancer Screening Recommendations

• Screening mammography with or without clinical breast exam every one to two years for women aged 40 years and older. B– Evidence strongest for women aged 50-69.– For ages 40-49; evidence weaker, benefit smaller, and

optimal interval uncertain. • Delay in observed benefit makes it difficult to determine

incremental benefit of beginning screening at 40 rather than 50.

• Screening recommendations generalizable to age 70 and older if life expectancy not compromised by co-morbid disease.

• Evidence insufficient to recommend for or against clinical breast exam or breast self examination. I

• Has not assessed efficacy of screening for BRCA mutations.

Lung Cancer ScreeningWhy?*

• 155,000 deaths per year - most related to smoking.

• Screening methods include chest X-ray, spiral CT, sputum analysis, and bronchoscopy.

• Five year survival 15%, 60% if tumor stage 1a.

• Spiral CT screening in Japan increased five year survivals from 15% to 34%.

*Patty JAMA 10-18-2002, 284: 15. 1977-1980

Lung Cancer Screening-Why not?• Despite improvements in five year lung ca. survival rates, overall

mortality in screened populations unchanged even after 25 years of follow-up. (Marcus P. et. al. J Natl Cancer Inst. 2000; 92 (16): 1308-16.)

• Screening programs pick up more indolent cancers, adeno- carcinoma versus squamous cell.

• Spiral CT screening picked up equal numbers of cancers in smokers and nonsmokers, despite lethal lung cancer being 10 times more common in smokers. (Sones Lancet 1998; 351: 1242-45.)

• Lung CA can be asymptomatic - almost half of patients assessed for lung reduction surgery have lung CA. (Pigula F. Ann Thorac Surg. 1996; 61: 174-76.)

• Lead time and length time bias. (Woloshins Lancet 2002; 359: 2108-11.)

Comparison of Cancer Screening Tests*

TEST RELATIVE RISKREDUCTION

NUMBER NEEDEDTO SCREEN

Pap smear forcervical cancer

>0.80 1,140

Mammographyage >50 years

0.23 543

Mammographyage 40-49

0.08 3,125

Fecal-occultblood Colon Ca.

0.15 - 0.20 588 - 1,000

*Gates TJ Am Fam Physician. 2001; 63: 513-22

Screening for Lipid DisordersUSPSTF 2001

• Important risk factor for coronary heart disease.

• Coronary heart disease leading cause of mortality in U.S. - 500,000 deaths/year.

• 1/2 of men, and 1/3 of women will have coronary heart disease event in their lifetime.

• 17% of men, and 20% of women in U.S. have total cholesterol >240.

• 27% of coronary heart disease events in men, and 34% in women attributable to total cholesterol >200mg/dl.

Screening for Lipid Disorders

• USPSTF recommendations based on four RCTs showing decreases in CHD events of 19%-37% and CHD mortality of 20%-28%.– Inconclusive regarding total mortality.

• ALLHAT study “no significant impact on mortality*”– Treated with pravastatin 40mg daily.– Total cholesterol level 17% lower, and LDL cholesterol levels 28%

lower in pravastatin group.– Usual care group had 8% decrease in total cholesterol and 11%

drop in LDL cholesterol.– All cause mortality no different after 4.8 years.

– *JAMA 288 [23]: 2998-3007, 2002.

Screening for Lipid DisordersUSPSTF Recommendations

• Routinely screen men 35 and women 45 y.o. for lipid disorders and treat if at increased risk for CHD: A

• Routinely screen men age 20-35 and women age 20-45 if other risk factors present: B

• Screen with total cholesterol and high density lipoprotein levels: B– Can be measured with non-fasting sample.

• Insufficient evidence for or against triglyceride screening: I

• Interval (5 years?) and upper age limit (65?) not specified.

Type II Diabetes• Screening recommended by ADA after age 45.• Cost of screening on all persons aged 25 or older

estimated at $236,000 per life year gained ($57,000 per quality adjusted life year gained).*

• Based on single screening only.• Reduces lifetime cumulative incidence of end stage

renal disease, blindness, and lower extremity amputation by 26%, 35%, and 22% respectively.

• More cost effective in younger individuals and African-Americans.

*CDC diabetes cost effectiveness study group, JAMA, November 25, 1998:280, No. 20, 1757-1763.

Screening for Microalbuminuria

• 3-8% of diabetics have macroalbuminuria• 20-30% of diabetics develop nephropathy.• Over half of all dialysis patients are diabetic.• Diabetes Control and Complications Trial (DCCT) with

Type 1 diabetics demonstrated benefit of enalapril on blood pressure, serum creatinine, and albumin excretion (N Engl J Med, 1993;9:977-86).

• Screening for microalbuminuria recommended by ADA, NIH,and WHO, all consensus-based.

• No RCTs have evaluated efficacy of screening diabetics for microalbuminuria in reducing renal failure.

• Control of BP and lipids more important in reducing microvascular complications than tight glucose control.

USPSTF Diabetes Screening

2003• Insufficient evidence to recommend routine

screening in asymptomatic adults: I-Tight control of glucose does not significantly

affect macrovascular complications -Tight control benefits microvascular complications

but takes years to manifest, uncertain benefit of early detection

• Screen adults with HTN or hyperlipidemia for diabetes : B

• Tight glycemic and BP control reduce albuminuria but uncertain if important impact on renal failure.

Serum Tumor Markers*• Prostate Specific Antigen (PSA)• Cancer antigen (CA) 27.29-monitor response in metastatic

breast CA patients.• Carcinoembryonic antigen (CEA) – detect colorectal relapse.• CA 125 – used to evaluate pelvic masses in post-menopausal

women, therapy for ovarian CA, and detect recurrence.• Alphafetoprotein (AFP) – marker for hepatocellular CA.• With the exception of PSA, not sensitive or specific enough to

be used in screening.• “No tumor marker has demonstrated survival benefit in

randomized control trials of screening in the general population.”

*Perkins GL, 2003;68:1075-82, AFP

Proceed With Caution Cerebral aneurysms*

• 15,000,000 Americans may develop aneurysms. • Ruptured aneurysms account for 20% of the

3,000,000 strokes annually in the USA, and 80% of stroke deaths.

• More and more detected as incidental findings on MRI. • Cerebral bleeding or stroke in asymptomatic

individuals with aneurysms less than 10 mm in diameter-.05% per year.*

• Complications or deaths from corrective surgery-13% in first year.

*Wiebers, et al., N Engl J Med 1998;339:1725-33.

Medicare Coverage of Preventive Services

• Expanded with Budget Reconciliation Act, August 1997.

• Estimated cost - 2 billion/year. • Annual mammos - 40 y.o. and older. • Pelvic exam & pap smear - q 3 years. • Annual prostate screening in men >50 y.o. with

Digital Rectal Exam and PSA beginning in year 2000.• Colorectal screening >50 y.o. with Fecal Occult

Blood q year, Flexible sigmoidoscopy q4 years, Colonoscopy and barium enemas q 2 years in high risk groups.

• Bone mass measurements in high risk groups.