Transcript Health Maintenance

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
• Condition Absent
Positive Test
a
Negative Test
c
Sensitivity=a/(a+c)
Positive Test
b
Negative Test
d
Specificity=d/(b+d)
Positive Predictive
Value=a/(a+b)
Legend:
a=true positive
b=false positive
c=false negative
d=true negative
Testing Conditions
Size of Population = 100,000
Sensitivity of Test = 90%
Specificity of Test = 90%
• Cancer Prevalence = 1%
Cancer
Cancer
Present
Absent
• Cancer Prevalence = 0.1%
Cancer
Cancer
Present
Absent
Positive
Test
900
9,900
Positive
Test
90
9,990
Negative
Test
100
89,100
Negative
Test
10
89,910
Positive Predictive Value= 8.3%
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!?
TOTAL
37 %
TOTAL
63 %
Transverse 11%
Descending 7 %
Ascending 9%
Sigmoid 24 %
Cecum 11 %
Appendix 6 %
Rectosigmoid 9 %
Rectum 23 %
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 Recommendations
USPSTF 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 19841990.
• 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 Screening
USPSTF 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 198992
• 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
Trial
Year
HIP Study
Malmo
Kopparberg
Ostergotland
Edinburgh
Stockholm
Gothenburg
NBSS-1
1963–69
1976–86
1977–85
1977–85
1979–88
1981–85
1982–88
1980–87
# of subjects
Screened Controls
14,423
3,658
9,582
10,262
5,913
14,375
10,600
25,214
14,701
3,679
5,031
10,573
5,810
7,103
12,800
25,216
HIP—Health Insurance Plan; NBSS—National Breast Screening Study.
Modified from Smart R, 1995.
RR
0.77
0.51
0.73
1.02
0.78
1.04
0.73
1.36
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
50-69 y/o
• 10% shift from Stage
• 40% shift from Stage
II Ca. to Stage I
II Ca. to Stage I
• No benefit first 9 years • No benefit first 5 years
• 16% decrease in breast • 27% decrease in breast
CA mortality 10-14
CA mortality after 5
years
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 Screening
Why?*
• 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
Pap smear for
cervical cancer
RELATIVE RISK NUMBER NEEDED
REDUCTION
TO SCREEN
>0.80
1,140
Mammography
age >50 years
0.23
543
Mammography
age 40-49
0.08
3,125
Fecal-occult
blood Colon Ca.
0.15 - 0.20
588 - 1,000
*Gates TJ Am Fam Physician. 2001; 63: 513-22
Screening for Lipid Disorders
USPSTF 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 Disorders
USPSTF 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 2045 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 postmenopausal 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.