Cardiovascular health in young and middle adulthood and medical care utilization and costs at older age - The Chicago Heart Association Detection Project Industry (CHA).

It is unclear how long-term medical utilization and costs from diverse care settings and their age-related patterns may differ by cardiovascular health (CVH) status earlier in adulthood. We followed 17,195 participants of the Chicago Heart Association Detection Project Industry (1967-1973) with linked Medicare claims (1992 to 2010). Baseline CVH is a composite measure of blood pressure, body mass index, diabetes, cholesterol, and smoking and includes four mutually exclusive strata: all factors were favorable (5.5%), one or more factors were elevated but none high (20.3%), one factor was high (40.9%), and two or more factors were high (33.2%). We assessed differences in the quantities (using negative binomial models) of and costs (using quantile regressions) for inpatient admissions, ambulatory care, home health care, and others between less favorable and all favorable CVH. All analyses adjusted for baseline age, race, sex, education, age at follow-up, year, state of residence, and death. We found that all favorable CVH in earlier adulthood was associated with lower long-term utilization and costs in all settings and the gap widened with age. Compared to all favorable CVH, the annual number of acute inpatient admissions per person was 79% greater (p-value < 0.001) for poor CVH, the median annual Medicare payment per person was $640 greater (41%, p-value < 0.001), and the mean was $4628 greater (67%, p-value < 0.001). The cost differences were greatest for acute inpatient, followed by ambulatory, post-acute inpatient, home health, and other. Early prevention efforts may potentially result in compressed all-cause morbidity in later years of age, along with reductions in resource use and health care costs for associated conditions.

Favorable Cardiovascular Health, Compression of Morbidity, and Healthcare Costs: Forty-Year Follow-Up of the CHA Study (Chicago Heart Association Detection Project in Industry).

BACKGROUND: We examined the association of cardiovascular health at younger ages with the proportion of life lived free of morbidity, the cumulative burden of morbidity, and average healthcare costs at older ages. METHODS: The CHA study (Chicago Heart Association Detection Project in Industry) is a longitudinal cohort of employed men and women 18 to 74 years of age at baseline examination in 1967 to 1973. Baseline measurements included blood pressure, cholesterol, diabetes mellitus, body mass index, and smoking. Individuals were classified into 1 of 4 strata of cardiovascular health: favorable levels of all factors, 0 factors high but ≥1 elevated risk factors, 1 high risk factor, and ≥2 high risk factors. Linked Medicare and National Death Index data from 1984 to 2010 were used to determine morbidity in older age. An individual's all-cause morbidity score and cardiovascular morbidity score were calculated from International Classification of Disease, Ninth Revision codes for each year of follow-up. RESULTS: We included 25 804 participants who became ≥65 years of age by 2010, representing 65% of all original CHA participants (43% female; 90% white; mean age, 44 years at baseline); 6% had favorable levels of all factors, 19% had ≥1 risk factors at elevated levels, 40% had 1 high risk factor, and 35% had ≥2 high risk factors. Favorable cardiovascular health at younger ages extended survival by almost 4 years and postponed the onset of all-cause and cardiovascular morbidity by 4.5 and 7 years, respectively, resulting in compression of morbidity in both absolute and relative terms. This translated to lower cumulative and annual healthcare costs for those in favorable cardiovascular health (P<0.001) during Medicare eligibility. CONCLUSIONS: Individuals in favorable cardiovascular health in early middle age live a longer, healthier life free of all types of morbidity. These findings provide strong support for prevention efforts earlier in life aimed at preserving cardiovascular health and reducing the burden of disease in older ages.

Responsiveness and minimally important difference for the patient-reported outcomes measurement information system (PROMIS) 20-item physical functioning short form in a prospective observational study of rheumatoid arthritis.

OBJECTIVE: To estimate responsiveness (sensitivity to change) and minimally important difference (MID) for the Patient-Reported Outcomes Measurement Information System (PROMIS) 20-item physical functioning scale (PROMIS PF-20). METHODS: The PROMIS PF-20, short form 36 (SF-36) physical functioning scale, and Health Assessment Questionnaire (HAQ) were administered at baseline, and 6 and 12 months later to a sample of 451 persons with rheumatoid arthritis. A retrospective change (anchor) item was administered at the 12-month follow-up. We estimated responsiveness between 12 months and baseline, and between 12 months and 6 months using one-way analysis of variance F-statistics. We estimated the MID for the PROMIS PF-20 using prospective change for people reporting getting 'a little better' or 'a little worse' on the anchor item. RESULTS: F-statistics for prospective change on the PROMIS PF-20, SF-36 and HAQ by the anchor item over 12 and 6 months (in parentheses) were 16.64 (14.98), 12.20 (7.92) and 10.36 (12.90), respectively. The MID for the PROMIS PF-20 was 2 points (about 0.20 of an SD). CONCLUSIONS: The PROMIS PF-20 is more responsive than two widely used ('legacy') measures. The MID is a small effect size. The measure can be useful for assessing physical functioning in clinical trials and observational studies.

Validation of the PROMIS physical function measures in a diverse US population-based cohort of cancer patients.

PURPOSE: To evaluate the validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function measures in a diverse, population-based cancer sample. METHODS: Cancer patients 6-13 months post-diagnosis (n = 4840) were recruited for the Measuring Your Health study. Participants were diagnosed between 2010 and 2013 with non-Hodgkin lymphoma or cancers of the colorectum, lung, breast, uterus, cervix, or prostate. Four PROMIS physical function short forms (4a, 6b, 10a, and 16) were evaluated for validity and reliability across age and race-ethnicity groups. Covariates included gender, marital status, education level, cancer site and stage, comorbidities, and functional status. RESULTS: PROMIS physical function short forms showed high internal consistency (Cronbach's α = 0.92-0.96), convergent validity (fatigue, pain interference, FACT physical well-being all r ≥ 0.68), and discriminant validity (unrelated domains all r ≤ 0.3) across survey short forms, age, and race-ethnicity. Known-group differences by demographic, clinical, and functional characteristics performed as hypothesized. Ceiling effects for higher-functioning individuals were identified on most forms. CONCLUSIONS: This study provides strong evidence that PROMIS physical function measures are valid and reliable in multiple race-ethnicity and age groups. Researchers selecting specific PROMIS short forms should consider the degree of functional disability in their patient population to ensure that length and content are tailored to limit response burden.

Propensity-adjusted association of methotrexate with overall survival in rheumatoid arthritis.

OBJECTIVE: While medications used to treat rheumatoid arthritis (RA) may affect survival in RA, few studies take into account the propensity for medication use, which may reflect selection bias in treatment allocation in survival models. We undertook this study to examine the relationship between methotrexate (MTX) use and mortality in RA, after controlling for individual propensity scores for MTX use. METHODS: We studied 5,626 RA patients prospectively for 25 years to determine the risk of death associated with MTX use, modeled in time-varying Cox regression models. We used the random forest method to generate individual propensity scores for MTX use at study entry and during followup in a time-varying manner; these scores were included in the multivariate model. We also investigated whether selective discontinuation of MTX immediately prior to death altered the risk of mortality, and we examined the association of duration of MTX use with survival. RESULTS: During followup, 666 patients (12%) died. MTX use was associated with reduced risk of death (adjusted hazard ratio 0.30 [95% confidence interval 0.09-1.03]). Selective MTX cessation immediately before death did not account for the protective association of MTX use with mortality. Only MTX use for >1 year was associated with lower risks of mortality, but associations were not stronger with longer durations of use. CONCLUSION: MTX use was associated with a 70% reduction in mortality in RA.

Upper-extremity and mobility subdomains from the Patient-Reported Outcomes Measurement Information System (PROMIS) adult physical functioning item bank.

OBJECTIVE: To create upper-extremity and mobility subdomain scores from the Patient-Reported Outcomes Measurement Information System (PROMIS) physical functioning adult item bank. DESIGN: Expert reviews were used to identify upper-extremity and mobility items from the PROMIS item bank. Psychometric analyses were conducted to assess empirical support for scoring upper-extremity and mobility subdomains. SETTING: Data were collected from the U.S. general population and multiple disease groups via self-administered surveys. PARTICIPANTS: The sample (N=21,773) included 21,133 English-speaking adults who participated in the PROMIS wave 1 data collection and 640 Spanish-speaking Latino adults recruited separately. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We used English- and Spanish-language data and existing PROMIS item parameters for the physical functioning item bank to estimate upper-extremity and mobility scores. In addition, we fit graded response models to calibrate the upper-extremity items and mobility items separately, compare separate to combined calibrations, and produce subdomain scores. RESULTS: After eliminating items because of local dependency, 16 items remained to assess upper extremity and 17 items to assess mobility. The estimated correlation between upper extremity and mobility was .59 using existing PROMIS physical functioning item parameters (r=.60 using parameters calibrated separately for upper-extremity and mobility items). CONCLUSIONS: Upper-extremity and mobility subdomains shared about 35% of the variance in common, and produced comparable scores whether calibrated separately or together. The identification of the subset of items tapping these 2 aspects of physical functioning and scored using the existing PROMIS parameters provides the option of scoring these subdomains in addition to the overall physical functioning score.

Disability in rheumatoid arthritis in the era of biological treatments.

OBJECTIVE: Rheumatoid arthritis (RA) is a disabling disease. The authors studied the impact of new, expensive and occasionally toxic biological treatments on disability outcomes in real-world populations of patients with RA. METHODS: The authors analysed Health Assessment Questionnaire Disability Index data on 4651 adult patients with RA collected prospectively from 1983 to 2006. They studied trends in disability using multilevel mixed-effects multivariable linear regression (mixed) models that adjusted for the effects of time trends in gender, ethnicity, age, smoking behaviour and disease duration. RESULTS: Overall, the patients were predominantly female (76%), were predominantly white (88%), had 13 years of education and have had RA for 13 years, on average. The time period from 1983 to 2006 saw major increases in the use of disease-modifying agents and biological agents, and a decrease in smoking. After adjustments, the disability rates declined at annual rates of 1.7% (1.5-1.8%) overall and 2.7% (2.4-3.1%) among men. The annual rate of disability declines in the biological era was greater than that in the preceding period, suggesting accelerated improvement. These declines were documented in all patient subgroups such as men, women, African-Americans, obese, older age groups and early disease (p<0.001), but not among the 1401 patients (where disability remained stable) who died on follow-up. CONCLUSION: Aggressive use of traditional disease-modifying agents and introduction of biological agents were associated with substantial gains in disability outcomes. Our finding supports the prevailing notion that 'tight inflammation control' is a desirable therapeutic strategy.

Favorable Cardiovascular Health at Young and Middle Ages and Dementia in Older Age-The CHA Study.

Background Data are sparse on the association of cardiovascular health ( CVH ) in younger/middle age with the incidence of dementia later in life. Methods and Results We linked the CHA (Chicago Heart Association Detection Project in Industry) study data, assessed in 1967 to 1973, with 1991 to 2010 Medicare and National Death Index data. Favorable CVH was defined as untreated systolic blood pressure/diastolic blood pressure ≤120/≤80 mm Hg, untreated serum total cholesterol <5.18 mmol/L, not smoking, bone mass index <25 kg/m2, and no diabetes mellitus. International Classification of Diseases, Ninth Revision (ICD-9) codes and claims dates were used to identify the first dementia diagnosis. Cox models were used to estimate hazard ratios of incident dementia after age 65 years by baseline CVH status. Among 10 119 participants baseline aged 23 to 47 years, 32.4% were women, 9.2% were black, and 7.3% had favorable baseline CVH . The incidence rate of dementia during follow-up after age 65 was 13.9%. After adjustment, the hazard ratio for incident dementia was lowest in those with favorable baseline CVH and increased with higher risk factor burden ( P-trend<0.001). The hazards of dementia in those with baseline favorable, moderate, and 1-only high-risk factor were lower by 31%, 26%, and 20%, respectively, compared with those with ≥2 high-risk factors. The association was attenuated but remained significant ( P-trend<0.01) when the model was further adjusted for competing risk of death. Patterns of associations were similar for men and women, and for those with a higher and lower baseline education level. Conclusions In this large population-based study, a favorable CVH profile at younger age is associated with a lower risk of dementia in older age.

Long distance running and knee osteoarthritis. A prospective study.

BACKGROUND: Prior studies of the relationship of physical activity to osteoarthritis (OA) of the knee have shown mixed results. The objective of this study was to determine if differences in the progression of knee OA in middle- to older-aged runners exist when compared with healthy nonrunners over nearly 2 decades of serial radiographic observation. METHODS: Forty-five long-distance runners and 53 controls with a mean age of 58 (range 50-72) years in 1984 were studied through 2002 with serial knee radiographs. Radiographic scores were two-reader averages for Total Knee Score (TKS) by modified Kellgren & Lawrence methods. TKS progression and the number of knees with severe OA were compared between runners and controls. Multivariate regression analyses were performed to assess the relationship between runner versus control status and radiographic outcomes using age, gender, BMI, education, and initial radiographic and disability scores among covariates. RESULTS: Most subjects showed little initial radiographic OA (6.7% of runners and 0 controls); however, by the end of the study runners did not have more prevalent OA (20 vs 32%, p =0.25) nor more cases of severe OA (2.2% vs 9.4%, p=0.21) than did controls. Regression models found higher initial BMI, initial radiographic damage, and greater time from initial radiograph to be associated with worse radiographic OA at the final assessment; no significant associations were seen with gender, education, previous knee injury, or mean exercise time. CONCLUSIONS: Long-distance running among healthy older individuals was not associated with accelerated radiographic OA. These data raise the possibility that severe OA may not be more common among runners.

Regular vigorous physical activity and disability development in healthy overweight and normal-weight seniors: a 13-year study.

OBJECTIVES: We examined the relationship of regular exercise and body weight to disability among healthy seniors. METHODS: We assessed body mass index (BMI) and vigorous exercise yearly (1989-2002) in 805 participants aged 50 to 72 years at enrollment. We studied 4 groups: normal-weight active (BMI< 25 kg/m(2); exercise> 60 min/wk); normal-weight inactive (exerciseor= 25 kg/m(2)); and overweight inactive. Disability was measured with the Health Assessment Questionnaire (0-3; 0= no difficulty, 3= unable to do). We used multivariable analysis of covariance to determine group differences in disability scores after adjustment for determinants of disability. RESULTS: The cohort was 72% men and 96% White, with a mean age of 65.2 years. After 13 years, overweight active participants had significantly less disability than did overweight inactive (0.14 vs 0.19; P= .001) and normal-weight inactive (0.22; P= .03) participants. Similar differences were found between normal-weight active (0.11) and normal-weight inactive participants (P< .001). CONCLUSIONS: Being physically active mitigated development of disability in these seniors, largely independent of BMI. Public health efforts that promote physically active lifestyles among seniors may be more successful than those that emphasize body weight in the prevention of functional decline.

Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis.

CONTEXT: Hydroxychloroquine, a commonly used antirheumatic medication, has hypoglycemic effects and may reduce the risk of diabetes mellitus. OBJECTIVE: To determine the association between hydroxychloroquine use and the incidence of self-reported diabetes in a cohort of patients with rheumatoid arthritis. DESIGN, SETTING, AND PATIENTS: A prospective, multicenter observational study of 4905 adults with rheumatoid arthritis (1808 had taken hydroxychloroquine and 3097 had never taken hydroxychloroquine) and no diagnosis or treatment for diabetes in outpatient university-based and community-based rheumatology practices with 21.5 years of follow-up (January 1983 through July 2004). MAIN OUTCOME MEASURES: Diabetes by self-report of diagnosis or hypoglycemic medication use. RESULTS: During the observation period, incident diabetes was reported by 54 patients who had taken hydroxychloroquine and by 171 patients who had never taken hydroxychloroquine, with incidence rates of 5.2 per 1000 patient-years of observation compared with 8.9 per 1000 patient-years of observation, respectively (P < .001). In time-varying multivariable analysis with adjustments for possible confounding factors, the hazard ratio for incident diabetes among patients who had taken hydroxychloroquine was 0.62 (95% confidence interval, 0.42-0.92) compared with those who had not taken hydroxychloroquine. In Poisson regression, the risk of incident diabetes was significantly reduced with increased duration of hydroxychloroquine use (P < .001 for trend); among those taking hydroxychloroquine for more than 4 years (n = 384), the adjusted relative risk of developing diabetes was 0.23 (95% confidence interval, 0.11-0.50; P < .001), compared with those who had not taken hydroxychloroquine. CONCLUSION: Among patients with rheumatoid arthritis, use of hydroxychloroquine is associated with a reduced risk of diabetes.

Varying the item format improved the range of measurement in patient-reported outcome measures assessing physical function.

BACKGROUND: Physical function (PF) is a core patient-reported outcome domain in clinical trials in rheumatic diseases. Frequently used PF measures have ceiling effects, leading to large sample size requirements and low sensitivity to change. In most of these instruments, the response category that indicates the highest PF level is the statement that one is able to perform a given physical activity without any limitations or difficulty. This study investigates whether using an item format with an extended response scale, allowing respondents to state that the performance of an activity is easy or very easy, increases the range of precise measurement of self-reported PF. METHODS: Three five-item PF short forms were constructed from the Patient-Reported Outcomes Measurement Information System (PROMIS®) wave 1 data. All forms included the same physical activities but varied in item stem and response scale: format A ("Are you able to …"; "without any difficulty"/"unable to do"); format B ("Does your health now limit you …"; "not at all"/"cannot do"); format C ("How difficult is it for you to …"; "very easy"/"impossible"). Each short-form item was answered by 2217-2835 subjects. We evaluated unidimensionality and estimated a graded response model for the 15 short-form items and remaining 119 items of the PROMIS PF bank to compare item and test information for the short forms along the PF continuum. We then used simulated data for five groups with different PF levels to illustrate differences in scoring precision between the short forms using different item formats. RESULTS: Sufficient unidimensionality of all short-form items and the original PF item bank was supported. Compared to formats A and B, format C increased the range of reliable measurement by about 0.5 standard deviations on the positive side of the PF continuum of the sample, provided more item information, and was more useful in distinguishing known groups with above-average functioning. CONCLUSIONS: Using an item format with an extended response scale is an efficient option to increase the measurement range of self-reported physical function without changing the content of the measure or affecting the latent construct of the instrument.

A low tension between individual and societal time aspects in health improved outcomes.

OBJECTIVES: To review intertemporal choices, involving decisions with a trade-off between something now and something later. These choices are common in health both at an individual and societal level. METHODS: The present value of an outcome, for example, the amount of money or the health outcomes in various aspects, is equivalent to the value of a future outcome discounted with the delay of time. The concept of diminishing value over time is positive discounting. Economic forecasts generally use discount rates in which the value of a future dollar is less than the value of a present dollar, and where the discount rates are similar for the individual investor and society. The value of future health is commonly thought of as similar to the value of future money. Yet, the individual may rationally choose a discount rate that is exceedingly low or even negative. This paradox is particularly relevant when considering primary and secondary prevention, where initial and continuing costs may precede beneficent outcomes by decades, making discount rate selections the dominant factor in determining decisions. CONCLUSION: We suggest that the societal perspective should also recognize that discount rates for health outcomes are largely irrelevant and that even negative discount rates have crucial relevance.

Associations of changes in exercise level with subsequent disability among seniors: a 16-year longitudinal study.

BACKGROUND: The effect of changes in physical exercise on progression of musculoskeletal disability in seniors has rarely been studied. METHODS: We studied a prospective cohort annually from 1984 to 2000 using the Health Assessment Questionnaire Disability Index (HAQ-DI). The cohort included 549 participants, 73% men, with average end-of-study age of 74 years. At baseline and at the end of the study, participants were classified as "High" or "Low" vigorous exercisers using a cut-point of 60 min/wk. Four groups were formed: "Sedentary" (Low-->Low; N = 71), "Exercise Increasers" (Low-->High; N = 27), "Exercise Decreasers" (High-->Low; N = 73), and "Exercisers" (High-->High; N = 378). The primary dependent variable was change in HAQ-DI score (scored 0-3) from 1984 to 2000. Multivariate statistical adjustments using analysis of covariance included age, gender, and changes in three risk factors, body mass index, smoking status, and number of comorbid conditions. Participants also prospectively provided reasons for exercise changes. RESULTS: At baseline, Sedentary and Increasers averaged little exercise (16 and 22 exercise min/wk), whereas Exercisers and Decreasers averaged over 10 times more (285 and 212 exercise min/wk; p <.001). All groups had low initial HAQ-DI scores, ranging from 0.03 to 0.08. Increasers and Exercisers achieved the smallest increments in HAQ-DI score (0.17 and 0.11) over 16 years, whereas Decreasers and Sedentary fared more poorly (increments 0.27 and 0.37). Changes in HAQ-DI score for Increasers compared to Sedentary were significantly more favorable (p <.05) even after multivariate statistical adjustment. CONCLUSIONS: Inactive participants who increased exercise achieved excellent end-of-study values with increments in disability similar to those participants who were more active throughout. These results suggest a beneficial effect of exercise, even when begun later in life, on postponement of disability.

Cardiovascular risk profile earlier in life and Medicare costs in the last year of life.

BACKGROUND: Health care costs are generally highest in the year before death, and much attention has been directed toward reducing costs for end-of-life care. However, it is unknown whether cardiovascular risk profile earlier in life influences health care costs in the last year of life. This study addresses this question. METHODS: Prospective cohort of adults from the Chicago Heart Association Detection Project in Industry included 6582 participants (40% women), aged 33 to 64 years at baseline examination (1967-1973), who died at ages 66 to 99 years. Medicare billing records (1984-2002) were used to obtain cardiovascular disease-related and total charges (adjusted to year 2002 dollars) for inpatient and outpatient services during the last year of life. Participants were classified as having favorable levels of all major cardiovascular risk factors (low risk), that is, serum cholesterol level lower than 200 mg/dL (<5.2 mmol/L), blood pressure 120/80 mm Hg or lower and no antihypertensive medication, body mass index (calculated as weight in kilograms divided by the square of height in meters) lower than 25, no current smoking, no diabetes, and no electrocardiographic abnormalities, or unfavorable levels of any 1 only, any 2 only, any 3 only, or 4 or more of these risk factors. RESULTS: In the last year of life, average Medicare charges were lowest for low-risk persons. For example, cardiovascular disease-related and total charges were lower by 10,367 dollars and 15,318 dollars compared with those with 4 or more unfavorable risk factors; the fewer the unfavorable risk factors, the lower the Medicare charges (P for trends <.001). Analyses by sex showed similar patterns. CONCLUSION: Favorable cardiovascular risk profile earlier in life is associated with lower Medicare charges at the end of life.

Midlife body mass index and hospitalization and mortality in older age.

CONTEXT: Abundant evidence links overweight and obesity with impaired health. However, controversies persist as to whether overweight and obesity have additional impact on cardiovascular outcomes independent of their strong associations with established coronary risk factors, eg, high blood pressure and high cholesterol level. OBJECTIVE: To assess the relation of midlife body mass index with morbidity and mortality outcomes in older age among individuals without and with other major risk factors at baseline. DESIGN: Chicago Heart Association Detection Project in Industry study, a prospective study with baseline (1967-1973) cardiovascular risk classified as low risk (blood pressure < or =120/< or =80 mm Hg, serum total cholesterol level <200 mg/dL [5.2 mmol/L], and not currently smoking); moderate risk (nonsmoking and systolic blood pressure 121-139 mm Hg, diastolic blood pressure 81-89 mm Hg, and/or total cholesterol level 200-239 mg/dL [5.2-6.2 mmol/L]); or having any 1, any 2, or all 3 of the following risk factors: blood pressure > or =140/90 mm Hg, total cholesterol level > or =240 mg/dL (6.2 mmol/L), and current cigarette smoking. Body mass index was classified as normal weight (18.5-24.9), overweight (25.0-29.9), or obese (> or =30). Mean follow-up was 32 years. SETTING AND PARTICIPANTS: Participants were 17,643 men and women aged 31 through 64 years, recruited from Chicago-area companies or organizations and free of coronary heart disease (CHD), diabetes, or major electrocardiographic abnormalities at baseline. MAIN OUTCOME MEASURES: Hospitalization and mortality from CHD, cardiovascular disease, or diabetes, beginning at age 65 years. RESULTS: In multivariable analyses that included adjustment for systolic blood pressure and total cholesterol level, the odds ratio (95% confidence interval) for CHD death for obese participants compared with those of normal weight in the same risk category was 1.43 (0.33-6.25) for low risk and 2.07 (1.29-3.31) for moderate risk; for CHD hospitalization, the corresponding results were 4.25 (1.57-11.5) for low risk and 2.04 (1.29-3.24) for moderate risk. Results were similar for other risk groups and for cardiovascular disease, but stronger for diabetes (eg, low risk: 11.0 [2.21-54.5] for mortality and 7.84 [3.95-15.6] for hospitalization). CONCLUSION: For individuals with no cardiovascular risk factors as well as for those with 1 or more risk factors, those who are obese in middle age have a higher risk of hospitalization and mortality from CHD, cardiovascular disease, and diabetes in older age than those who are normal weight.

Validity of PROMIS physical function measured in diverse clinical samples.

OBJECTIVES: To evaluate the validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function measures using longitudinal data collected in six chronic health conditions. STUDY DESIGN AND SETTING: Individuals with rheumatoid arthritis (RA), major depressive disorder (MDD), back pain, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and cancer completed the PROMIS Physical Function computerized adaptive test or fixed-length short form at baseline and at the end of clinically relevant follow-up intervals. Anchor items were also administered to assess change in physical function and general health. Linear mixed-effects models and standardized response means were estimated at baseline and follow-up. RESULTS: A total of 1,415 individuals participated (COPD n = 121; CHF n = 57; back pain n = 218; MDD n = 196; RA n = 521; cancer n = 302). The PROMIS Physical Function scores improved significantly for treatment of CHF and back pain patients but not for patients with MDD or COPD. Most of the patient subsamples that reported improvement or worsening on the anchors showed a corresponding positive or negative change in PROMIS Physical Function. CONCLUSION: This study provides evidence that the PROMIS Physical Function measures are sensitive to change in intervention studies where physical function is expected to change and able to distinguish among different clinical samples. The results inform the estimation of meaningful change, enabling comparative effectiveness research.

Prednisone Use and Risk of Mortality in Patients With Rheumatoid Arthritis: Moderation by Use of Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: Medications for rheumatoid arthritis (RA) may affect survival. However, studies often include limited followup and do not account for selection bias in treatment allocation. Using a large longitudinal database, we examined the association between prednisone use and mortality in RA, and whether this risk was modified with concomitant disease-modifying antirheumatic drug (DMARD) use, after controlling for propensity for treatment with prednisone and individual DMARDs. METHODS: In a prospective study of 5,626 patients with RA followed for up to 25 years, we determined the risk of death associated with prednisone use alone and combined treatment of prednisone with methotrexate (MTX) or sulfasalazine. We used the random forests method to generate propensity scores for prednisone use and each DMARD at study entry and during followup. Mortality risks were estimated using multivariate Cox models that included propensity scores. RESULTS: During followup (median 4.97 years), 666 patients (11.8%) died. In a multivariate, propensity-adjusted model, prednisone use was associated with an increased risk of death (hazard ratio [HR] 2.83 [95% confidence interval (95% CI) 1.03-7.76]). However, there was a significant interaction between prednisone use and MTX use (P = 0.03), so that risk was attenuated when patients were treated with both medications (HR 0.99 [95% CI 0.18-5.36]). However, combination treatment also weakened the protective association of MTX with mortality. Results were similar for sulfasalazine. CONCLUSION: Prednisone use was associated with a significantly increased risk of mortality in patients with RA. This association was mitigated by concomitant DMARD use, but combined treatment also negated the previously reported beneficial association of MTX with survival in RA.

PROMIS measures of pain, fatigue, negative affect, physical function, and social function demonstrated clinical validity across a range of chronic conditions.

OBJECTIVE: To present an overview of a series of studies in which the clinical validity of the National Institutes of Health's Patient Reported Outcome Measurement Information System (NIH; PROMIS) measures was evaluated, by domain, across six clinical populations. STUDY DESIGN AND SETTING: Approximately 1,500 individuals at baseline and 1,300 at follow-up completed PROMIS measures. The analyses reported in this issue were conducted post hoc, pooling data across six previous studies, and accommodating the different designs of the six, within-condition, parent studies. Changes in T-scores, standardized response means, and effect sizes were calculated in each study. When a parent study design allowed, known groups validity was calculated using a linear mixed model. RESULTS: The results provide substantial support for the clinical validity of nine PROMIS measures in a range of chronic conditions. CONCLUSION: The cross-condition focus of the analyses provided a unique and multifaceted perspective on how PROMIS measures function in "real-world" clinical settings and provides external anchors that can support comparative effectiveness research. The current body of clinical validity evidence for the nine PROMIS measures indicates the success of NIH PROMIS in developing measures that are effective across a range of chronic conditions.

Frailty, heart disease, and stroke: the Compression of Morbidity paradigm.

Frailty, the loss of physiologic organ reserve with age, and chronic illness, such as heart disease and stroke, which may accelerate the development of frailty, become the dominant determinants of ill-health in those who escape the hazards of early and mid-life. The Compression of Morbidity paradigm holds that if the average age at first chronic infirmity is postponed, and if this postponement is greater than increases in life expectancy, then average cumulative lifetime morbidity will decrease, squeezed between a later onset and the time of death. The National Long-Term Care Survey, National Health Interview Survey, and other data document declining U.S. disability trends since 1982; accelerating recently, at about 2% per year. The decline in mortality is only 1% a year, documenting Compression of Morbidity in the U.S. population. Frailty, increasing exponentially because of linear declines in multiple organ systems, mandates converging morbidity and mortality rates as longevity increases. Longitudinal studies now link good health risk status with reduced lifetime disability; those with few health risks have only one-fourth the disability of those who have more risks, and the onset of disability is postponed from 7 to 12 years. Randomized controlled trials of senior health enhancement programs have shown reduction in health risks, improved health status, and decreased medical costs. Current health enhancement opportunities can increase health gains for seniors under the umbrella paradigm of the Compression of Morbidity. Effective interventions to prevent or postpone heart disease and stroke will decrease lifetime morbidity.