Thomas M. Gill, MD; Jack M. Guralnik, MD, PhD; Marco Pahor, MD; Timothy Church, MD, PhD; Roger A. Fielding, PhD; Abby C. King, PhD; Anthony P. Marsh, PhD; Anne B. Newman, MD; Christine A. Pellegrini, PhD; Shyh-Huei Chen, PhD; Heather G. Allore, PhD; Michael E. Miller, PhD; for the LIFE Study Investigators (*)
Note: Dr. Miller had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Disclaimer: Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture.
Acknowledgment: The authors thank Evan C. Hadley, MD, and Sergei Romashkan, MD, PhD, from the National Institute on Aging (Bethesda, Maryland), for their substantial intellectual contribution to the development and implementation of the LIFE study. Dr. Hadley and Dr. Romashkan are federal employees fully paid by the NIH. They did not receive any additional compensation from the study.
Grant Support: The LIFE study is funded by cooperative agreement U01AG22376 from the NIH and National Institute on Aging and supplement U01AG022376 from the National Heart, Lung, and Blood Institute, and was sponsored in part by the Intramural Research Program. The research is partially supported by the Claude D. Pepper Older Americans Independence Centers at the University of Florida (P30AG028740), Wake Forest University (P30AG21332), Tufts University (P30AG031679), the University of Pittsburgh (P30AG024827), and Yale University (P30AG021342) and by the NIH/National Center for Advancing Translational Sciences Clinical and Translational Science Awards program at Stanford University (UL1RR025744), the University of Florida (U54RR025208), and Yale University (UL1TR000142). Tufts University is also supported by the Boston Rehabilitation Outcomes Center (R24HD065688) and the U.S. Department of Agriculture under agreement 58-1950-4-003. Dr. Gill has received an Academic Leadership Award (K07AG043587) from the National Institute on Aging. Dr. Fielding is partially supported by the U.S. Department of Agriculture, under agreement 58-1950-0-014.
Disclosures: Drs. King, Marsh, and Miller report grants from the NIH during the conduct of the study. Dr. Fielding reports grants from the NIH and U.S. Department of Agriculture during the conduct of the study; personal fees from Biophytis and Cytokinetics outside the submitted work; and grants and personal fees from Nestle, Astellas, and Pronutria outside the submitted work. Dr. Pellegrini reports a grant (K12HS023011) from the Agency for Healthcare Research and Quality during the conduct of the study. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0529.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at www.thelifestudy.org/public/index.cfm. Statistical code and data set: Available from Dr. Miller (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Thomas M. Gill, MD, Yale School of Medicine, Adler Geriatric Center, 874 Howard Avenue, New Haven, CT 06519; e-mail, email@example.com.
Current Author Addresses: Dr. Gill: Yale School of Medicine, Adler Geriatric Center, 874 Howard Avenue, New Haven, CT 06519.
Dr. Guralnik: University of Maryland School of Medicine, Department of Epidemiology and Public Health, Division of Gerontology, 660 West Redwood Street, Room 204, Baltimore, MD 21201.
Dr. Pahor: Department of Aging and Geriatric Research, College of Medicine, University of Florida, 2004 Mowry Road, Gainesville, FL 32611.
Dr. Church: 6400 Perkins Road, Baton Rouge, LA 75080.
Dr. Fielding: Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111.
Dr. King: Stanford University School of Medicine, 259 Campus Drive, HRP Redwood Building, Room T221, Stanford, CA 94305.
Dr. Marsh: Wake Forest University, Department of Health and Exercise Science, PO Box 7868, Winston-Salem, NC 27109.
Dr. Newman: Graduate School of Public Health, University of Pittsburgh, A527 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261.
Dr. Pellegrini: Department of Preventive Medicine, Northwestern University, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611.
Drs. Chen and Miller: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.
Dr. Allore: Yale School of Medicine, Program on Aging, 300 George Street, New Haven, CT 06511.
Author Contributions: Conception and design: T.M. Gill, J.M. Guralnik, M. Pahor, T. Church, R.A. Fielding, A.P. Marsh, H.G. Allore, M.E. Miller.
Analysis and interpretation of the data: T.M. Gill, J.M. Guralnik, R.A. Fielding, A.C. King, C.A. Pellegrini, S.H. Chen, H.G. Allore, M.E. Miller.
Drafting of the article: T.M. Gill, R.A. Fielding, A.C. King, A.P. Marsh, H.G. Allore, M.E. Miller.
Critical revision for important intellectual content: T.M. Gill, J.M. Guralnik, M. Pahor, R.A. Fielding, A.C. King, C.A. Pellegrini, H.G. Allore, M.E. Miller.
Final approval of the article: T.M. Gill, J.M. Guralnik, M. Pahor, T. Church, R.A. Fielding, A.C. King, A.P. Marsh, A.B. Newman, C.A. Pellegrini, S.H. Chen, H.G. Allore, M.E. Miller.
Provision of study materials or patients: T.M. Gill, M. Pahor, A.C. King, A.P. Marsh.
Statistical expertise: H.G. Allore, M.E. Miller.
Obtaining of funding: T.M. Gill, M. Pahor, H.G. Allore, M.E. Miller.
Administrative, technical, or logistic support: M. Pahor, A.P. Marsh, M.E. Miller.
Collection and assembly of data: T.M. Gill, J.M. Guralnik, M. Pahor, T. Church, R.A. Fielding, A.P. Marsh, M.E. Miller.
Gill TM, Guralnik JM, Pahor M, Church T, Fielding RA, King AC, et al. Effect of Structured Physical Activity on Overall Burden and Transitions Between States of Major Mobility Disability in Older Persons: Secondary Analysis of a Randomized Trial. Ann Intern Med. 2016;165:833-840. doi: 10.7326/M16-0529
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Published: Ann Intern Med. 2016;165(12):833-840.
Published at www.annals.org on 27 September 2016
The total time a patient is disabled likely has a greater influence on his or her quality of life than the initial occurrence of disability alone.
To compare the effect of a long-term, structured physical activity program with that of a health education intervention on the proportion of patient assessments indicating major mobility disability (MMD) (that is, MMD burden) and on the risk for transitions into and out of MMD.
Single-blinded, parallel-group, randomized trial. (ClinicalTrials.gov: NCT01072500)
8 U.S. centers between February 2010 and December 2013.
1635 sedentary persons, aged 70 to 89 years, who had functional limitations but could walk 400 m.
Physical activity (n = 818) and health education (n = 817).
MMD, defined as the inability to walk 400 m, was assessed every 6 months for up to 3.5 years.
During a median follow-up of 2.7 years, the proportion of assessments showing MMD was substantially lower in the physical activity (0.13 [95% CI, 0.11 to 0.15]) than the health education (0.17 [CI, 0.15 to 0.19]) group, yielding a risk ratio of 0.75 (CI, 0.64 to 0.89). In a multistate model, the hazard ratios for comparisons of physical activity with health education were 0.87 (CI, 0.73 to 1.03) for the transition from no MMD to MMD; 0.52 (CI, 0.10 to 2.67) for no MMD to death; 1.33 (CI, 0.99 to 1.77) for MMD to no MMD; and 1.92 (CI, 1.15 to 3.20) for MMD to death.
The intention-to-treat principle was maintained for MMD burden and first transition out of no MMD, but not for subsequent transitions.
A structured physical activity program reduced the MMD burden for an extended period, in part through enhanced recovery after the onset of disability and diminished risk for subsequent disability episodes.
National Institute on Aging, National Institutes of Health.
Flow of participants through the study.
GEE = generalized estimating equation; MMD = major mobility disability; SPPB = Short Physical Performance Battery.
* Participants who did not receive the allocated intervention (that is, attended no intervention sessions).
† Partial follow-up indicates participants who had censoring times before the last planned follow-up visit.
‡ Discontinuation of the intervention was operationalized as participants who did not attend at least 1 intervention session during their last 6 mo of follow-up before the last planned follow-up visit date. Deaths and intervention withdrawals are included in these numbers.
Table 1. Number and Percentage of Transitions Between Each State Across All Follow-up Visits*
Risk ratios denoting the burden of major mobility disability over time for physical activity versus health education according to subgroups.
MMSE = Mini-Mental State Examination; SPPB = Short Physical Performance Battery.
Table 2. Effect of Physical Activity on MMD Burden Under Different Imputation Assumptions for Missing Observations*
Appendix Table 1. Number and Percentage of Transitions Between Each State Across All Follow-up Visits: Indeterminate and Censored Data Reported Separately*
Six-month probability of transitions between no MMD, MMD, and death, by group, for all follow-up, year 1, and after year 1.
Values were estimated from the multistate model as described in the Multistate Survival Models section in the Appendix. Bars represent 95% CIs. MMD = major mobility disability.
Appendix Table 2. Results From Likelihood Ratio Tests Evaluating 3-State Models
MMD = major mobility disability.
Appendix Table 3. Hazard Ratios for the Intervention From the 4-State Models
Appendix Table 4. Description of 3-State Models
Appendix Table 5. Observed and Expected Prevalence at Selected Follow-up Times
Observed versus expected prevalence of each state as a function of follow-up time.
Appendix Table 6. Intervention Hazard Ratios From 3-State Multistate Model
Appendix Table 7. Transition Probabilities From Model M2_F
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