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1.  Physical Activity and Years of Healthy Life in Older Adults: Results From the Cardiovascular Health Study 
Little is known about how many years of life and disability-free years seniors can gain through exercise. Using data from the Cardiovascular Health Study, the authors estimated the extra years of life and self-reported healthy life (over 11 years) and years without impairment in activities of daily living (over 6 years) associated with quintiles of physical activity (PA) in older adults from different age groups. They estimated PA from the Minnesota Leisure Time Activities Questionnaire. Multivariable linear regression adjusted for health-related covariates. The relative gains in survival and years of healthy life (YHL) generally were proportionate to the amount of PA, greater among those 75+, and higher in men. Compared with being sedentary, the most active men 75+ had 1.49 more YHL (95% CI: 0.79, 2.19), and the most active women 75+ had 1.06 more YHL (95% CI: 0.44, 1.68). Seniors over age 74 experience the largest relative gains in survival and healthy life from physical activity.
PMCID: PMC3978479  PMID: 20651417
aging; exercise; mortality; health status; activities of daily living
2.  Effects of respiratory and non-respiratory factors on disability among older adults with airway obstruction: The Cardiovascular Health Study 
COPD  2013;10(5):588-596.
Background:
High rates of disability associated with chronic airway obstruction may be caused by impaired pulmonary function, pulmonary symptoms, other chronic diseases, or systemic inflammation.
Methods:
We analyzed data from the Cardiovascular Health Study, a longitudinal cohort of 5888 older adults. Categories of lung function (normal; restricted; borderline, mild-moderate, and severe obstruction) were delineated by baseline spirometry (without bronchodilator). Disability-free years were calculated as total years alive and without self-report of difficulty performing ≥1 Instrumental Activities of Daily Living over 6 years of follow-up. Using linear regression, we compared disability-free years by lung disease category, adjusting for demographic factors, body mass index, smoking, cognition, and other chronic comorbidities. Among participants with airflow obstruction, we examined the association of respiratory factors (FEV1 and dyspnea) and non-respiratory factors (ischemic heart disease, congestive heart failure, diabetes, muscle weakness, osteoporosis, depression and cognitive impairment) on disability-free years.
Results:
The average disability free years were 4.0 out of a possible 6 years. Severe obstruction was associated with 1 fewer disability-free year compared to normal spirometry in the adjusted model. For the 1,048 participants with airway obstruction, both respiratory factors (FEV1 and dyspnea) and non-respiratory factors (heart disease, coronary artery disease, diabetes, depression, osteoporosis, cognitive function, and weakness) were associated with decreased disability-free years.
Conclusions:
Severe obstruction is associated with greater disability compared to patients with normal spirometery. Both respiratory and non-respiratory factors contribute to disability in older adults with abnormal spirometry.
doi:10.3109/15412555.2013.781148
PMCID: PMC3903127  PMID: 23819728
Chronic airflow obstruction; instrumental activities of daily living; disability; disablement process
3.  Weight, mortality, years of healthy life and active life expectancy in older adults 
Journal of the American Geriatrics Society  2007;56(1):10.1111/j.1532-5415.2007.01500.x.
Objective
Two-thirds of older adults are currently classified as overweight or obese. Given that the importance of these weight categories was documented primarily in middle-aged persons, the survival and health status consequences for older adults are controversial. Here, we explore the issue of whether weight categories predict subsequent mortality and morbidity in older adults.
Design, Setting, and Participants
Data came from the Cardiovascular Health Study, a population-based cohort study of 5888 older adults.
Measurements
We estimated the age- and sex-specific probabilities of transition from one health state to another and from one weight category to another. From these probabilities we estimated future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65.
Results
Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese, and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than normal weight, while overweight and obesity were rarely worse than normal weight, and were sometimes associated with significantly better outcomes.
Conclusions
Similar to middle-aged populations, older adults are likely to be or to become overweight or obese. However, higher weight is not associated with worse health in this age group. Thus, the number of older adults at a “healthy” weight may be much higher than currently believed.
doi:10.1111/j.1532-5415.2007.01500.x
PMCID: PMC3865852  PMID: 18031486
self-rated health; equilibrium; activities of daily living; years of healthy life; active life expectancy; multi-state life tables; older adults
4.  Age-specific Prevalence and Years of Healthy Life in a System with 3 Health States 
Statistics in medicine  2008;27(9):10.1002/sim.3056.
Consider a 3-state system with one absorbing state, such as Healthy, Sick, and Dead. Over time, the prevalence of the Healthy state will approach an “equilibrium” value that is independent of the initial conditions. We derived this equilibrium prevalence (Prev:Equil) as a function of the local transition probabilities. We then used Prev:Equil to estimate the expected number of years spent in the healthy state over time. This estimate is similar to one calculated by multi-state life table methods, and has the advantage of having an associated standard error. In longitudinal data for older adults, the standard error was accurate when a valid survival table was known from other sources, or when the available data were sufficient to estimate survival accurately. Performance was better with fewer waves of data. If validated in other situations, these equilibrium estimates of prevalence and years of healthy life (YHL) and their standard errors may be useful when the goal is to compare YHL for different populations.
doi:10.1002/sim.3056
PMCID: PMC3865856  PMID: 17847058
self-rated health; years of healthy life; prevalence; multi-state lifetable; variance for area under the curve; Sullivan method
5.  Persistence and Remission of Musculoskeletal Pain in Community-Dwelling Older Adults: Results from the Cardiovascular Health Study 
OBJECTIVES
To characterize longitudinal patterns of musculoskeletal pain in a community sample of older adults over a 6-year period and to identify factors associated with persistence of pain.
DESIGN
Secondary analysis of the Cardiovascular Health Study.
SETTING
Community-based cohort drawn from four U.S. counties.
PARTICIPANTS
Five thousand ninety-three men and women aged 65 and older.
MEASUREMENTS
Over a 6-year period, pain was assessed each year using a single question about the presence of pain in any bones or joints during the last year. If affirmative, participants were queried about pain in seven locations (hands, shoulders, neck, back, hips, knees, feet). Participants were categorized according to the percentage of time that pain was present and according to the intermittent or chronic pattern of pain. Factors associated with persistent pain during five remaining years of the study were identified.
RESULTS
Over 6 years, 32% of participants reported pain for three or more consecutive years, and 32% reported pain intermittently. Of those who reported pain the first year, 54% were pain free at least once during the follow-up period. Most of the pain at specific body locations was intermittent. Factors associated with remission of pain over 5 years included older age, male sex, better self-rated health, not being obese, taking fewer medications, and having fewer depressive symptoms. Approximately half of those with pain reported fewer pain locations the following year.
CONCLUSION
Musculoskeletal pain in older adults, despite high prevalence, is often intermittent. The findings refute the notion that pain is an inevitable, unremitting, or progressive consequence of aging.
doi:10.1111/j.1532-5415.2012.04082.x
PMCID: PMC3633775  PMID: 22861385
pain; musculoskeletal; longitudinal analysis; remission; persistence; symptoms
6.  Prevalence, incidence, and persistence of major depressive symptoms in the cardiovascular health study 
Aging & mental health  2010;14(2):168-176.
Purpose
To explore the association of major depressive symptoms with advancing age, sex, and self-rated health among older adults.
Design and methods
We analyzed 10 years of annual assessments in a longitudinal cohort of 5888 Medicare recipients in the Cardiovascular Health Study. Self-rated health was assessed with a single question, and subjects categorized as healthy or sick. Major depressive symptoms were assessed using the Center for Epidemiologic Studies Short Depression Scale, with subjects categorized as nondepressed (score < 10) or depressed (≥ 10). Age-, sex-, and health-specific prevalence of depression and the probabilities of transition between depressed and nondepressed states were estimated.
Results
The prevalence of a major depressive state was higher in women, and increased with advancing age. The probability of becoming depressed increased with advancing age among the healthy but not the sick. Women showed a greater probability than men of becoming depressed, regardless of health status. Major depressive symptoms persisted over one-year intervals in about 60% of the healthy and 75% of the sick, with little difference between men and women.
Implications
Clinically significant depressive symptoms occur commonly in older adults, especially women, increase with advancing age, are associated with poor self-rated health, and are largely intransigent. In order to limit the deleterious consequences of depression among older adults, increased attention to prevention, screening, and treatment is warranted. A self-rated health item could be used in clinical settings to refine the prognosis of late-life depression.
doi:10.1080/13607860903046537
PMCID: PMC3622544  PMID: 20336548
self-rated health; mental health; epidemiology
7.  Mid- and Late-Life Obesity: Risk of Dementia in the Cardiovascular Health Cognition Study 
Archives of neurology  2009;66(3):336-342.
Objectives
To evaluate associations between mid- and late-life obesity and risk of dementia.
Design
Prospective cohort followed 5.4 years from 1992/4 through 1999.
Setting
Community-dwelling sample in four US sites recruited from Medicare eligibility files.
Participants
2,798 adults without dementia, mean age 74.7 years, 59.1% women, participating in the Cardiovascular Health Cognition Study completing a magnetic resonance image, measured for height and weight at baseline (late-life) and self-reporting weight at age 50 (mid-life). Body mass index (BMI) was calculated at both times.
Main Outcome Measures
Dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) classified by a multidisciplinary committee using standardized criteria.
Results
Classification resulted in 480 persons with incident dementia, 245 with AD (no VaD) and 213 with VaD (with or without AD). In evaluations of mid-life obesity, an increased risk of dementia was found for obese (BMI >30) compared to normal (BMI 20-25) persons adjusted for demographics (HR: 1.39, 95% CI: 1.03-1.87) and for caradiovascularl risk factors (HR: 1.36, 95% CI: 0.94-1.95). The risk estimates reversed in assessments of late-life BMI. Underweight persons (BMI < 20) had an increased risk of dementia (HR: 1.62, 95% CI: 1.02-2.64) while being overweight (BMI 25-30) was not associated (HR: 0.92, 95% CI: 0.72-1.18) and being obese reduced the risk of dementia (HR: 0.63, 95% CI: 0.44-0.91) compared to those with normal BMI.
Conclusions
These results help explain the “obesity paradox” as differences in dementia risk over time are consistent with physical changes in the trajectory toward disability.
doi:10.1001/archneurol.2008.582
PMCID: PMC3513375  PMID: 19273752
8.  Psychological Effects of Automated External Defibrillator Training A randomized trial 
Objectives
The objective of this study was to test if an Automated External Defibrillator (AED) training program would positively affect the mental health of family members of high risk patients.
Methods
305 ischemic heart disease patients and their family members were randomized to one of four AED training programs: two video-based training programs and two face-to-face training programs that emphasized self-efficacy and perceived control. Patients and family members were surveyed at baseline, 3 and 9 months post ischemic event on demographic characteristics, measures of quality of life (SF=36) , self-efficacy and perceived control. For this study, family members were the focus rather than the patients.
Results
Regression analyses showed that family members in the face-to-face training programs did not score better on any of the mental health status variables than family members who participated in the other training programs but for an increase in self-efficacy beliefs at 3 months post training.
Conclusion
The findings suggest that a specifically designed AED training program emphasizing self-efficacy and perceived control beliefs is not likely to enhance family member mental health.
doi:10.1016/j.hrtlng.2010.12.009
PMCID: PMC3158282  PMID: 21411144
9.  Transitions among Health States Using 12 Measures of Successful Aging in Men and Women: Results from the Cardiovascular Health Study 
Journal of Aging Research  2012;2012:243263.
Introduction. Successful aging has many dimensions, which may manifest differently in men and women at different ages. Methods. We characterized one-year transitions among health states in 12 measures of successful aging among adults in the Cardiovascular Health Study. The measures included self-rated health, ADLs, IADLs, depression, cognition, timed walk, number of days spent in bed, number of blocks walked, extremity strength, recent hospitalizations, feelings about life as a whole, and life satisfaction. We dichotomized variables into “healthy” or “sick,” states, and estimated the prevalence of the healthy state and the probability of transitioning from one state to another, or dying, during yearly intervals. We compared men and women and three age groups (65–74, 75–84, and 85–94). Findings. Measures of successful aging showed similar results by gender. Most participants remained healthy even into advanced ages, although health declined for all measures. Recuperation, although less common with age, still occurred frequently. Men had a higher death rate than women regardless of health status, and were also more likely to remain in the healthy state. Discussion. The results suggest a qualitatively different experience of successful aging between men and women. Men did not simply “age faster” than women.
doi:10.1155/2012/243263
PMCID: PMC3485538  PMID: 23193476
10.  Comparing Years of Healthy Life, Measured in 16 Ways, for Normal Weight and Overweight Older Adults 
Journal of Obesity  2012;2012:894894.
Introduction. The traditional definitions of overweight and obesity are not age specific, even though the relationship of weight to mortality is different for older adults. Effects of adiposity on aspects of health beside mortality have not been well investigated. Methods. We calculated the number of years of healthy life (YHL) in the 10 years after baseline, for 5,747 older adults. YHL was defined in 16 different ways. We compared Normal and Overweight persons, classified either by body mass index (BMI) or by waist circumference (WC). Findings. YHL for Normal and Overweight persons differed significantly in 25% of the comparisons, of which half favored the Overweight. Measures of physical health favored Normal weight, while measures of mental health and quality of life favored Overweight. Overweight was less favorable when defined by WC than by BMI. Obese persons usually had worse outcomes. Discussion. Overweight older adults averaged as many years of life and years of healthy life as those of Normal weight. There may be no outcome based reason to distinguish Normal from Overweight for older adults. Conclusion. The “Overweight paradox” appears to hold for nonmortality outcomes. New adiposity standards are needed for older adults, possibly different by race and sex.
doi:10.1155/2012/894894
PMCID: PMC3388309  PMID: 22778920
11.  Patterns and Predictors of Recovery from Exhaustion in Older Adults: The Cardiovascular Health Study 
Objectives
To estimate the likelihood of, and factors associated with, recovery from exhaustion in older adults
Design and Setting
Retrospective analysis of data from six annual examinations of a community-based cohort study
Participants
4584 men and women aged 69 years or older
Measurements
Exhaustion was considered present when a participant responded “a moderate amount” or “most of the time” to either of two questions: “How often have you had a hard time getting going?” and “How often does everything seem an effort?”
Results
Of the 964 participants who originally reported exhaustion, 634 (65.8%) were exhaustion-free at least once during follow up. When data from all time points were considered, 48% of exhaustion-reporters were exhaustion-free the following year. After adjustment for age, sex, race, education, and marital status, one-year recovery was less likely among individuals with worse self-rated health, ≥ six medications, obesity, depression, musculoskeletal pain, and history of stroke. In proportional hazards models, the following risk factors were associated with more persistent exhaustion over five years: poor self-rated health, ≥ six medications, obesity, and depression. Recovery was not less likely among participants with a history of cancer or heart disease.
Conclusion
Exhaustion is common in old age but is quite dynamic, even among those with a history of cancer and congestive heart failure. Recovery is especially likely among seniors who have a positive perception of their overall health, take few medications, and are not obese or depressed. These findings support the notion that resiliency is associated with physical and psychological well-being.
doi:10.1111/j.1532-5415.2010.03238.x
PMCID: PMC3059104  PMID: 21288229
symptoms; frailty; fatigue; transition analysis
12.  Health Benefits of Increased Walking for Sedentary, Generally Healthy Older Adults: Using Longitudinal Data to Approximate an Intervention Trial 
Background.
Older adults are often advised to walk more, but randomized trials have not conclusively established the benefits of walking in this age group. Typical analyses based on observational data may have biased results. Here, we propose a “limited-bias,” more interpretable estimate of the health benefits to sedentary healthy older adults of walking more, using longitudinal data from the Cardiovascular Health Study.
Methods.
The number of city blocks walked per week, collected annually, was classified as sedentary (<7 blocks per week), somewhat active, or active (≥28). Analysis was restricted to persons sedentary and healthy in the first 2 years. In Year 3, some became more active (the treatment groups). Self-rated health at Year 5 (follow-up) was regressed on walking at Year 3, with additional covariates from Year 2, when all were sedentary.
Results.
At follow-up, 83.5% of those active at baseline had excellent, very good, or good self-rated health, as compared with 63.9% of the sedentary, an apparent benefit of 19.6 percentage points. After covariate adjustment, the limited-bias estimate of the benefit was 11.2 percentage points (95% confidence interval 3.7–18.6). Ten different outcome measures showed a benefit, ranging from 5 to 11 percentage points. Estimates from other study designs were smaller, less interpretable, and potentially more biased.
Conclusions.
In longitudinal studies where walking and health are ascertained at every wave, limited-bias estimates can provide better estimates of the benefits of walking. A surprisingly small increase in walking was associated with meaningful health benefits.
doi:10.1093/gerona/glq070
PMCID: PMC2920578  PMID: 20484337
Exercise; Walking; Selection bias; Self-rated health; ADL
13.  Comparison of Health Care Expenditures Among Insured Users and Nonusers of Complementary and Alternative Medicine in Washington State: A Cost Minimization Analysis 
Abstract
Objectives
The purpose of this analysis was to compare health care expenditures between insured patients with back pain, fibromyalgia syndrome, or menopause symptoms who used complementary and alternative medical (CAM) providers for some of their care to a matched group of patients who did not use any CAM care. Insurance coverage was equivalent for both conventional and CAM providers.
Design
Insurance claims data for 2000–2003 from Washington State, which mandates coverage of CAM providers, were analyzed. CAM-using patients were matched to CAM-nonusing patients based on age group, gender, index medical condition, overall disease burden, and prior-year expenditures.
Results
Both unadjusted tests and linear regression models indicated that CAM users had lower average expenditures than nonusers. (Unadjusted: $3,797 versus $4,153, p = 0.0001; β from linear regression -$367 for CAM users.) CAM users had higher outpatient expenditures that which were offset by lower inpatient and imaging expenditures. The largest difference was seen in the patients with the heaviest disease burdens among whom CAM users averaged $1,420 less than nonusers, p < 0.0001, which more than offset slightly higher average expenditures of $158 among CAM users with lower disease burdens.
Conclusions
This analysis indicates that among insured patients with back pain, fibromyalgia, and menopause symptoms, after minimizing selection bias by matching patients who use CAM providers to those who do not, those who use CAM will have lower insurance expenditures than those who do not use CAM.
doi:10.1089/acm.2009.0261
PMCID: PMC3110809  PMID: 20423210
14.  Identification of Ovarian Cancer Symptoms in Health Insurance Claims Data 
Journal of Women's Health  2010;19(3):381-389.
Abstract
Background
Women with ovarian cancer have reported abdominal/pelvic pain, bloating, difficulty eating or feeling full quickly, and urinary frequency/urgency prior to diagnosis. We explored these findings in a general population using a dataset of insured women aged 40–64 and investigated the potential effectiveness of a routine review of claims data as a prescreen to identify women at high risk for ovarian cancer.
Methods
Data from a large Washington State health insurer were merged with the Seattle-Puget Sound Surveillance, Epidemiology and End Results (SEER) cancer registry for 2000–2004. We estimated the prevalence of symptoms in the 36 months prior to diagnosis for early and late-stage ovarian cancer cases and for two comparison groups. The potential performance of a passive screener that would flag women with two or more visits for any of the symptoms in the previous 2-month period was examined.
Results
Of the 223,903 insured women, 161 had incident cases of ovarian cancer. Both early and late-stage patients had a higher prevalence of abdominal/pelvic pain and bloating than the comparison groups, primarily in the 3 months before diagnosis. The passive screener had a sensitivity of 0.31 and specificity of 0.83 and usually identified women right before diagnosis. Assuming an average cost of $500 per false positive, the screener would be considered cost-effective if the true positives had an average increase of 8.5 years of life expectancy.
Conclusions
These results support previous findings that ovarian cancer symptoms were reported in health insurance claims and were more prevalent before diagnosis, but the symptoms may occur too close to the diagnosis date to provide useful diagnostic information. The passive screening approach should be reevaluated in the future using electronic medical records; if found to be effective, the method may be potentially useful for other incident diseases.
doi:10.1089/jwh.2009.1550
PMCID: PMC2867625  PMID: 20156131
15.  Evaluating a Preventive Services Index to Adjust for Healthy Behaviors in Observational Studies of Older Adults 
Preventing Chronic Disease  2010;7(5):A110.
Introduction
Analysis of outcome measures from nonrandomized, observational studies of people participating or not participating in health programs may be suspect because of selection bias. For example, fitness programs may preferentially enroll people who are already committed to healthy lifestyles, including use of preventive services. Some of our earlier studies have attempted to account for this potential bias by including an ad hoc preventive services index created from the patient's number of earlier clinical preventive services, to adjust for health-seeking behaviors. However, this index has not been validated. We formally evaluated the performance of this preventive services index by comparing it with its component parts and with an alternative index derived from principal component analysis by using the weighted sums of the principal components.
Methods
We used data from a cohort of 38,046 older adults. We used the following variables from the administrative database of a health maintenance organization to create this index: fecal occult blood test, flexible sigmoidoscopy, screening mammogram, prostate cancer screening, influenza vaccination, pneumococcal vaccination, and preventive care office visits.
Results
The preventive services index was positively correlated with each of the following components: colon cancer screening (r = .752), screening mammogram (r = .559), prostate cancer screening (r = .592), influenza vaccination (r = .844), pneumococcal vaccination (r = .487), and preventive care office visits (r = .737). An alternative preventive services index, created by using principal component analysis, had similar performance.
Conclusion
A preventive services index created by using administrative data has good face validity and construct validity and can be used to partially adjust for selection bias in observational studies of cost and use outcomes.
PMCID: PMC2938404  PMID: 20712937
16.  Might Massage or Guided Meditation Provide “Means to a Better End”? Primary Outcomes from an Efficacy Trial with Patients at the End of Life 
Journal of palliative care  2009;25(2):100-108.
This article reports findings from a randomized controlled trial of massage and guided meditation with patients at the end of life. Using data from 167 randomized patients, the authors consider patient outcomes through 10 weeks post-enrollment, as well as next-of-kin ratings of the quality of the final week of life for 106 patients who died during study participation. Multiple regression models demonstrated no significant treatment effects of either massage or guided meditation, delivered up to twice a week, when compared with outcomes of an active control group that received visits from hospice-trained volunteers on a schedule similar to that of the active treatment arms. The authors discuss the implications of their findings for integration of these complementary and alternative medicine therapies into standard hospice care.
PMCID: PMC2858762  PMID: 19678461
17.  Evaluation of a method for fitting a semi-Markov process model in the presence of left-censored spells using the Cardiovascular Health Study‡ 
Statistics in medicine  2008;27(26):5509-5524.
SUMMARY
We used a longitudinal data set covering 13 years from the Cardiovascular Health Study to evaluate the properties of a recently developed approach to deal with left censoring that fits a semi-Markov process (SMP) model by using an analog to the stochastic EM algorithm—the SMP-EM approach. It appears that the SMP-EM approach gives estimates of duration-dependent probabilities of health changes similar to those obtained by using SMP models that have the advantage of actual duration data. SMP-EM estimates of duration-dependent transition probabilities also appear more accurate and less variable than multi-state life table estimates.
doi:10.1002/sim.3382
PMCID: PMC2878178  PMID: 18712777
multi-state life table; semi-Markov process model; functional disability; healthy aging; event history analysis; left censoring
18.  Joint modeling of self-rated health and changes in physical functioning 
Self-rated health is an important indicator of future morbidity and mortality. Past research has indicated that self-rated health is related to both levels of and changes in physical functioning. However, no previous study has jointly modeled longitudinal functional status and self-rated health trajectories. We propose a joint model for self-rated health and physical functioning that describes the relationship between perceptions of health and the rate of change of physical functioning or disability. Our joint model uses a non-homogeneous Markov process for discrete physical functioning states and connects this to a logistic regression model for “healthy” versus “unhealthy” self-rated health through parameters of the physical functioning model. We use simulation studies to establish finite sample properties of our estimators and show that this model is robust to misspecification of the functional form of the relationship between self-rated health and rate of change of physical functioning. We also show that our joint model performs better than an empirical model based on observed changes in functional status. We apply our joint model to data from the Cardiovascular Health Study (CHS), a large, multi-center, longitudinal study of older adults. Our analysis indicates that self-rated health is associated both with level of functioning as indicated by difficulty with activities of daily living (ADL) and instrumental activities of daily living (IADL), and the risk of increasing difficulty with ADLs and IADLs.
doi:10.1198/jasa.2009.ap08423
PMCID: PMC2819480  PMID: 20151036
Disability; functional status; joint modeling; Markov process; non–homogeneous; self–rated health
20.  Longitudinal Data with Follow-up Truncated by Death: Match the Analysis Method to Research Aims 
Diverse analysis approaches have been proposed to distinguish data missing due to death from nonresponse, and to summarize trajectories of longitudinal data truncated by death. We demonstrate how these analysis approaches arise from factorizations of the distribution of longitudinal data and survival information. Models are illustrated using cognitive functioning data for older adults. For unconditional models, deaths do not occur, deaths are independent of the longitudinal response, or the unconditional longitudinal response is averaged over the survival distribution. Unconditional models, such as random effects models fit to unbalanced data, may implicitly impute data beyond the time of death. Fully conditional models stratify the longitudinal response trajectory by time of death. Fully conditional models are effective for describing individual trajectories, in terms of either aging (age, or years from baseline) or dying (years from death). Causal models (principal stratification) as currently applied are fully conditional models, since group differences at one timepoint are described for a cohort that will survive past a later timepoint. Partly conditional models summarize the longitudinal response in the dynamic cohort of survivors. Partly conditional models are serial cross-sectional snapshots of the response, reflecting the average response in survivors at a given timepoint rather than individual trajectories. Joint models of survival and longitudinal response describe the evolving health status of the entire cohort. Researchers using longitudinal data should consider which method of accommodating deaths is consistent with research aims, and use analysis methods accordingly.
doi:10.1214/09-STS293
PMCID: PMC2812934  PMID: 20119502
Censoring; Generalized estimating equations; Longitudinal data; Missing data; Quality of life; Random effects models; Truncation by death
21.  Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study 
Atherosclerosis  2007;197(2):922-930.
Common polymorphisms in the CRP gene are associated with plasma CRP levels in population-based studies, but associations with age-related events are uncertain. A previous study of CRP haplotypes in older adults was broadened to include longevity and cause-specific mortality (all-cause, non-cardiovascular (nonCV), and cardiovascular (CV)). Common haplotypes were inferred from four tagSNPs in 4512 whites and five tagSNPs in 812 blacks from the Cardiovascular Health Study, a longitudinal cohort of adults over age 65. Exploratory analyses addressed early versus late mortality. CRP haplotypes were not associated with all-cause mortality or longevity overall in either population, but associations with all-cause mortality differed during early and late periods. In blacks, the haplotype tagged by 3872A (rs1205) was associated with increased risk of nonCV mortality, relative to other haplotypes (adjusted hazard ratio for each additional copy: 1.42, 95% CI: 1.07, 1.87). Relative to other haplotypes, this haplotype was associated with decreased risk of early but not decreased risk of late CV mortality in blacks; among whites, a haplotype tagged by 2667C (rs1800947) gave similar but nonsignificant findings. If confirmed, CRP genetic variants may be weakly associated with CV and nonCV mortality in older adults, particularly in self-identified blacks.
doi:10.1016/j.atherosclerosis.2007.08.012
PMCID: PMC2362133  PMID: 17888441
22.  CAM Provider Use and Expenditures by Cancer Treatment Phase 
Objective
To assess cancer patients’ utilization of complementary and alternative medical providers and the associated expenditures by specific treatment phases.
Study Design
Cross-sectional analysis of medical services utilization and expenditures during three therapeutic intervals: an initial treatment phase, continuing care, and end-of-life.
Methods
Analysis of an insurance claims database that had been matched to the Washington State SEER cancer registry.
Results
Of 2,900 registry-matched cancer patients 63.2% were female, the median age was 54 years, and 92.7% were white. Breast cancer was the most frequent diagnosis (52.7%), followed by prostate cancer (24.7%), lung cancer (10.1%), colon cancer (7.0%), and hematologic malignancies (5.6%). CAM provider using patients were 26.5% of the overall cohort (18.5% used chiropractors, 7.7% naturopathic physicians, 5.3% massage therapists, and 4.2% saw acupuncturists). The proportion of CAM using patients was similar during each treatment phase. All patients used some conventional care. Female gender, a breast cancer diagnosis, age, and white race were significant predictors of CAM use. Diagnosis of a musculoskeletal problem occurred at sometime during the study for 72.1% of cancer patients. CAM provider visits were 7.2% of total outpatient medical visits and 85.1% of CAM visits resulted in a musculoskeletal diagnosis. Expenditures for CAM providers were 0.3%, 1.0%, and 0.1% of all expenditures during the initial, continuing, and end-of-life phases respectively.
Conclusion
For cancer patients, musculoskeletal issues were the most commonly listed diagnosis made by a CAM provider. Although expenditures associated with CAM are a small proportion of the total, additional studies are necessary to determine the importance patients place on access to these services.
PMCID: PMC2587209  PMID: 18471036
Alternative Medicine; Oncology; Healthcare Expenditures; Treatment Phase
23.  Use of Complementary and Alternative Medicine Providers by Fibromyalgia Patients Under Insurance Coverage 
Arthritis and rheumatism  2007;57(1):71-76.
Objective
To quantify how visits and expenditures differ between insured patients with fibromyalgia syndrome (FMS) who use complementary and alternative medicine (CAM) providers compared to FMS patients who do not. FMS patients were also compared to an age and gender matched comparison group without FMS.
Methods
Calendar year 2002 claims data from two large insurers in Washington State were analyzed for provider type (CAM vs. conventional), patient comorbid medical conditions, number of visits, and expenditures.
Results
Use of CAM providers by FMS patients was two and a half times higher than in a comparison group without FMS. (56% vs. 21%) FMS patients who used CAM had more health care visits than FMS patients not using CAM (34 vs. 23, p < .001); however, CAM users had similar expenditures to non-users among FMS patients ($4638 vs. $4728, n.s.), because expenditure per CAM visit is lower than expenditure per conventional visit. FMS patients who used CAM also had heavier overall disease burdens than those not using CAM.
Conclusion
With insurance coverage, a majority of FMS patients will use CAM providers. The sickest patients use more CAM and this leads to an increased number of health care visits. However, CAM use is not associated with higher overall expenditures. Until a cure for FMS is found, CAM providers may offer an economical alternative for FMS patients seeking symptomatic relief.
doi:10.1002/art.22471
PMCID: PMC1853385  PMID: 17266066
Fibromyalgia; Complementary and alternative medicine; Health services research
24.  Quality of life at the end of life 
Background
Little is known about self-perceived quality of life (QOL) near the end of life, because such information is difficult to collect and to interpret. Here, we describe QOL in the weeks near death and determine correlates of QOL over time, with emphasis on accounting for death and missing data.
Methods
Data on QOL were collected approximately every week in an ongoing randomized trial involving persons at the end of life. We used these data to describe QOL in the 52 weeks after enrollment in the trial (prospective analysis, N = 115), and also in the 10 weeks just prior to death (retrospective analysis, N = 83). The analysis consisted of graphs and regressions that accounted explicitly for death and imputed missing data.
Results
QOL was better than expected until the final 3 weeks of life, when a terminal drop was observed. Gender, race, education, cancer, and baseline health status were not significantly related to the number of “weeks of good-quality life” (WQL) during the study period. Persons younger than 60 had significantly higher WQL than older persons in the prospective analysis, but significantly lower WQL in the retrospective analysis. The retrospective results were somewhat sensitive to the imputation model.
Conclusion
In this exploratory study, QOL was better than expected in persons at the end of life, but special interventions may be needed for persons approaching a premature death, and also for the last 3 weeks of life. Our descriptions of the trajectory of QOL at the end of life may help other investigators to plan and analyze future studies of QOL. Methodology for dealing with death and the high amount of missing data in longitudinal studies at the end of life needs further investigation.
doi:10.1186/1477-7525-5-51
PMCID: PMC2077331  PMID: 17683554
25.  The effect of different public health interventions on longevity, morbidity, and years of healthy life 
BMC Public Health  2007;7:52.
Background
Choosing cost-effective strategies for improving the health of the public is difficult because the relative effects of different types of interventions are not well understood. The benefits of one-shot interventions may be different from the benefits of interventions that permanently change the probability of getting sick, recovering, or dying. Here, we compare the benefits of such types of public health interventions.
Methods
We used multi-state life table methods to estimate the impact of five types of interventions on mortality, morbidity (years of life in fair or poor health), and years of healthy life (years in excellent, very good, or good health).
Results
A one-shot intervention that makes all the sick persons healthy at baseline would increase life expectancy by 3 months and increase years of healthy life by 6 months, in a cohort beginning at age 65. An equivalent amount of improvement can be obtained from an intervention that either decreases the probability of getting sick each year by 12%, increases the probability of a sick person recovering by 16%, decreases the probability that a sick person dies by 15%, or decreases the probability that a healthy person dies by 14%. Interventions aimed at keeping persons healthy increased longevity and years of healthy life, while decreasing morbidity and medical expenditures. Interventions focused on preventing mortality had a greater effect on longevity, but had higher future morbidity and medical expenditures. Results differed for older and younger cohorts and depended on the value to society of an additional year of sick life.
Conclusion
Interventions that promote health and prevent disease performed well, but other types of intervention were sometimes better. The value to society of interventions that increase longevity but also increase morbidity needs further research. More comprehensive screening and treatment of new Medicare enrollees might improve their health and longevity without increasing future medical expenditures.
doi:10.1186/1471-2458-7-52
PMCID: PMC1853080  PMID: 17411436

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