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Aging Outside the Box

Aging Outside the Box. Stanford Continuing Studies James F. Fries, MD October 31, 2007 Slides Available at ARAMIS.Stanford.edu. Class Schedule. General Themes October 17 – Longevity October 24 – Compression of Morbidity

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Aging Outside the Box

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  1. Aging Outside the Box Stanford Continuing Studies James F. Fries, MD October 31, 2007 Slides Available at ARAMIS.Stanford.edu

  2. Class Schedule General Themes • October 17 – Longevity • October 24 – Compression of Morbidity • October 31 – Declining Disability • November 7 – Aging and Health Policy • December 5 – Synthesis and Application

  3. Evidence for Compression of Morbidity • Longitudinal studies documenting morbidity compression by risk factor levels • National surveys of disability since 1982 • Randomized trials showing disability and cost reductions with ‘healthy aging’ interventions

  4. THE HIERARCHY OF SCIENTIFIC EVIDENCE • Randomized Controlled Trial (RCT)-triple blinded, double-blinded, single-blinded, open • Prospective Observational Study-longitudinal, controlled, blinded endpoints, protocol-driven • Population Surveys-repeated cross-sectional waves • Retrospective Case-Control Studies-easiest • Uncontrolled Case Series, Case Reports, Anecdotes-nearly worthless

  5. Long in Duration Mortality Endpoints Rigorous Entry Criteria Longitudinal Not Grouped at End (Retrospective) Grouped at Baseline (Prospective) Non-Randomized Morbidity (Disability) Endpoints Protocol-Driven Population Surveys Involve Different People Over Time DIFFICULTIES OF STUDIES OF HUMAN AGING

  6. Strict Entry Criteria Internal Validity Lacks External Validity Selection Bias Short-Term Accepts All Comers External Validity Lacks Internal Validity Selection Bias Multiple Other Biases Long-Term EXPERIMENTAL VERSUS OBSERVATIONAL STUDIES

  7. THE UNIVERSITY OF PENNSYLVANIA STUDY • All 2500 attendees 1939-1940, aged 68 in 1986, risk factor data available from student days and at age 40, followed yearly from 1986 through 2006 • Question: Do healthy lifestyle behaviors (exercise, non-smoking, not obese) in mid-life and later affect cumulative mortality and morbidity over the life span? • Male (80 %), educated, affluent, good access to medical care-biases or strengths?

  8. University of Pennsylvania Study, 2007 Three lifestyle risk factors (1986) • Body mass index 25 or greater • Cigarette smoking • No regular vigorous activity Three risk groups - LOW = zero risk factors - MOD = one risk factor - HIGH = two or three risk factors

  9. University of Pennsylvania Study, 2007Death Rates (per 10,000 Person-Years)

  10. University of Pennsylvania Study, 2007 Mortality Rates by Risk Group (per 10,000 person-years) CI=95% confidence interval around the rate

  11. University of Pennsylvania Study, 2007 Hubert et al, A&R, 2006

  12. University of Pennsylvania Study, 2007

  13. University of Pennsylvania Attendees 1939-40Disability Index by Age and Risk Factor Category Disability Index Age Vita et al, NEJM, 1998

  14. University of Pennsylvania Study, 2007 • Conclusions: • Mortality reduction from low risk to high risk groups is about 4 years • Disability postponement from high to low risk groups is about 8 years • Healthy lifestyle-related risk factors in seniors, including normal weight, regular physical activity and smoking abstinence offer protection against disability despite the associated survival advantages over time

  15. Exercise and Disability: A 21-Year StudyWang et al, Archives Internal Medicine, 2002: Chakravarty et al, Arch Int Med 2007 (In Press) 538 Runners423 Controls Average Age 58 in 1984 Average Age 79 in 2005 Followed Annually for: • Disability • Pain • Osteoporosis • X-rays of Hip and Knee each five years

  16. EXERCISE AND DISABILITY • Runner’s Club – Pro-exercise, near fanatic runners, 12,000 miles run by baseline in 1984, lean, non-smoking (2 %) • Community Controls – Stanford community, LRC controls, one-third runners but only 10 % the mileage, generally lean but not as lean, few smokers (6 %), more women • Can selection bias favoring runners be overcome?

  17. AVOIDING SELECTION BIAS • Age, education, geography, leg injuries, leg length, arthritis, FH arthritis already similar • Gender: Analyze genders separately • Baseline disability: Similar, but analyze separately all without baseline disability • Adjust for weight (BMI), age, smoking, and other variables with differences between groups (other than exercise) • Deliberately select populations so that the variable of interest (vigorous exercise activity) is extremely different between groups. • Study longitudinally!

  18. Disability by Age in Runners and Controls Mean Disability Score Community Control (n=249) Runners Club (n=369) Age Category Wang et al, Arch Int Med, 2002

  19. Exercise and Disability

  20. Exercise and DisabilityConclusions • Regular vigorous physical activity, including running and jogging, may postpone disability by 12 to 16 years, far more than more casual exercise. • Bone mineral density is increased by exercise; osteoporosis is decreased. • X-rays of knees are better in exercising subjects, even regular long-distance runners, than controls.

  21. Total Joint Replacement Contributes to Declining Disability Rates in Seniors James F. Fries, M.D. Eliza F. Chakravarty, M.D. Bharathi Lingala, Ph.D. Helen H. Hubert, Ph.D. Stanford University, Stanford CA

  22. Objective • The National Long-Term Care Survey documented a nearly 2% annual decline in disability rates among seniors (age ≥ 65 years) from 1982 to 2004* • Objective: To estimate how much of the national decline may be attributed to knee and hip joint replacement (TJR) Manton KG, et al. PNAS 2006;103:18374.

  23. Assumptions • Observed decrease in disability is linear • TJR has no significant effect on mortality • Impact of TJR on disability remains constant over time • Duration of effect of TJR is ~ 10 years • Benefit from individual TJR procedures is constant from 1982 to 2004

  24. Sources of Data • U.S. population ≥ 65 years: US. Census • # TJR’s performed: National Hospital Discharge Survey (CDC) • Baseline disability (Health Assessment Questionnaire-Disability Index): ARAMIS dataset • Disability improvement at 7-12 months following TJR (HAQ-DI): ARAMIS dataset

  25. Statistics • Cohort study: All ARAMIS participants who underwent TJR with HAQ-DI scores before and after compared with 12-month change data in participants without TJR. • Case-Control study: ARAMIS participants with TJR compared to controls matched on age (same year), gender, and baseline HAQ-DI (exact). Pair-wise t-tests • Extrapolation: Change in HAQ-DI prior to TJR extrapolated out 12 months and compared to observed HAQ-DI 12 months post TJR

  26. TJR rates by Year

  27. Change in disability/pain over one year for subjects with TJR * p < 0.05 ** p < 0.01 *** p < 0.001

  28. Change in disability/Pain over one year without TJR ** p < 0.01 *** p < 0.001

  29. Case/Control Analysis Matched for age (year), gender, and HAQ-DI (exact)

  30. 12-month disability = 1.74 expected HAQ-DI -1.46 observed HAQ-DI = 0.28 HAQ-DI Units

  31. Figure 2 12-month pain = 2.20 expected score -1.32 observed score = 0.88 units

  32. Summary * Four-fold increase in TJR in seniors from 1982-2004

  33. Master Equation Change in Nationwide disability = (Δ HAQ/ Baseline HAQ) x proportion with TJR x duration of response = (0.10/1.5) x 0.016 x 10 years = 0.011 % reduction in disability attributable to TJR ~ 5.5% of the 2% decline in nationwide disability

  34. Sensitivity Analyses

  35. Conclusions • TJR has made a small but detectable impact on national disability rates • The benefits of TJR are greater in the pain domain than in disability • Different approaches to estimating the disability reduction yield similar estimates • Approximately 5 -10% of the national disability decline is attributable to knee and hip replacement

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