Showing papers by "James F. Fries published in 2002"

Lifestyle Habits and Compression of Morbidity

Abstract: Background There has been much debate regarding the degree to which healthy lifestyles can increase longevity and whether added years will be offset by increased morbidity at older ages. This study was designed to test the compression of morbidity hypothesis, proposing that healthy lifestyles can reduce and compress disability into a shorter period toward the end of life. Methods Functional status in 418 deceased members of an aging cohort was observed between 1986 and 1998 in relationship to lifestyle-related risk factors, including cigarette smoking, physical inactivity, and under- or overweight. Three risk groups were created based on the number of these factors at study entry. Disability scores prior to death were modeled for each risk group to compare levels and rates of change, as well as to determine if and when acceleration in functional decline occurred. Results The risk-factor-free group showed average disability scores near zero 10-12 years before death, rising slowly over time, without evidence of accelerated functional decline. In contrast, those with two or more factors maintained a greater level of disability throughout follow-up and experienced an increase in the rate of decline 1.5 years prior to death. For those at moderate risk, the rate of decline increased significantly only in the last 3 months of life. Other differences between groups provided no alternative explanations for the findings. Conclusions These results make a compelling argument for the reduction and postponement of disability with healthier lifestyles as proposed by the compression of morbidity hypothesis.

Reducing disability in older age.

Abstract: Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline up-date for the management of patients with unstable angina and non-ST-segmentelevation myocardial infarction—summary article: a report of the American Col-lege of Cardiology/American Heart Association task force on practice guidelines(Committee on the Management of Patients With Unstable Angina).

Postponed development of disability in elderly runners: a 13-year longitudinal study.

Abstract: Background The magnitude and duration of the benefit of running and other aerobic exercise on disability and mortality in elderly persons are not well understood. We sought to quantify the benefits of aerobic exercise, including running, on disability and mortality in elderly persons and to examine whether morbidity can be compressed into later years of life by regular exercise. Methods A 13-year prospective cohort study of 370 members of a runners' club for persons aged 50 and older and 249 control subjects initially aged 50 to 72 years (mean, 59 years), with annual ascertainment of the Health Assessment Questionnaire disability score, noting any deaths and their causes. Linear mixed models were used to compute postponement in disability, and survival analysis was conducted to determine the time to and causes of death. Results Significantly (P Conclusion Running and other aerobic exercise in elderly persons protect against disability and early mortality, and are associated with prolongation of a disability-free life.

Aging, natural death, and the compression of morbidity. 1980

Abstract: The average length of life has risen from 47 to 73 years in this century, but the maximum life span has not increased. Therefore, survival curves have assumed an ever more rectangular form. Eighty per cent of the years of life lost to nontraumatic, premature death have been eliminated, and most premature deaths are now due to the chronic diseases of the later years. Present data allow calculation of the ideal average life span, approximately 85 years. Chronic illness may presumably be postponed by changes in life style, and it has been shown that the physiologic and psychologic markers of aging may be modified. Thus, the average age at first infirmity can be raised, thereby making the morbidity curve more rectangular. Extension of adult vigor far into a fixed life span compresses the period of senescence near the end of life. Health-research strategies to improve the quality of life require careful study of the variability of the phenomena of aging and how they may be modified. (N Engl J Med. 198...

HLA-DRB1 genotype associations in 793 white patients from a rheumatoid arthritis inception cohort: frequency, severity, and treatment bias.

Abstract: Objective. The HLA–DRB1 “shared epitope” (SE) genotypes are associated with rheumatoid arthritis (RA), but it remains controversial whether the association is with incidence, severity, or both, whether there are associations in seronegative patients, and whether different DRB1 alleles that contain the SE have similar effects on RA susceptibility and/or severity. The present study was undertaken to study these issues in a large cohort of patients with RA. Methods. White patients with RA of <6 months’ duration (n 793) were enrolled in an inception cohort. HLA–DRB1 typing was performed, and patients were categorized into 21 DRB1 genotype groups. The disability index of the Health Assessment Questionnaire was the primary outcome measure. Results. DRB1 associations in seronegative RA patients closely resembled those in controls. Of seropositive patients, 21% had 2 copies of the epitope, 52% had 1 copy, and 27% had none. However, not all genotypes with 1 copy were associated with increased susceptibility; for example, frequencies of DRB1*0404/X and *01/X did not differ from those in controls. Absolute differences between seropositive RA patients and controls were greatest for DRB1*0401 homozygosity (3.8% versus 0.8%, respectively) and *0401/0404 heterozygosity (4.7% versus 1.0%). DRB1*0404 was increased in frequency in seropositive RA but, unlike *0401, an increased frequency was seen only with 2 epitope copies. The relatively rare DRB1*10 had an unexpected association with seropositive RA, being present in 1.7% of seropositive RA patients and 0.7% of controls, and also showed a trend toward association with greater disease severity. The presence of 2 epitope copies was associated with increased frequency of seropositivity and younger age at disease onset, not with disease severity. Treatment indication bias was substantial and may have accounted for some of these effects. HLA–DRB1*0401/ 0404 was found much more frequently in men and in patients with a lower age at disease onset, and there was a trend toward a higher frequency of *0404/0401 in women. Conclusion. This large inception cohort study confirms previously identified major associations and provides additional insights. Only one dominant association was found: *0401, which differs from other SE alleles in a single Lys-for-Arg substitution. The association of the rare DRB1*10 allele has not previously been postulated. Sex associations were confirmed. Associations with seronegative RA were not seen. Not all genotypes containing an SE copy showed increased susceptibility to RA. The association of SE genotypes found in this study related to disease susceptibility rather than severity.

Methotrexate, hydroxychloroquine, and intramuscular gold in rheumatoid arthritis: relative area under the curve effectiveness and sequence effects.

Abstract: OBJECTIVE: The use of disease modifying antirheumatic drugs (DMARD) for rheumatoid arthritis (RA) is predicated on the expected value of the treatment course. Most clinical data are generalized from randomized controlled trials (RCT), which may result in estimates that are discordant with clinical experience and cannot address the effects of sequence of drugs. We computed estimates of relative DMARD effectiveness from a large observational database using area under the curve (AUC) data. METHODS: We examined data collected over a 20 year period on 1160 patients who were followed at the Wichita Arthritis Center. We utilized Health Assessment Questionnaire (HAQ) disability index data to quantify the effect of methotrexate (MTX), hydroxychloroquine (HCQ), and injectable gold (gold) on subsequent patient outcome. Using an AUC analysis, we compared length of treatment course, total disability averted, annual disability averted, and percentage of possible disability averted across drugs, and examined differences between first courses of therapy in DMARD naive patients and subsequent courses of the same and different DMARD in patients. RESULTS: Patients treated with MTX, HCQ, and gold improved at a rate of -0.33, -0.18 and -0.38 annualized HAQ area units, respectively. Since duration taking drug was greatest for MTX, then HCQ, then gold, the cumulative improvement was greatest with MTX (-1.07) versus gold (-0.74) versus HCQ (-0.47) in disability unit years. All 3 drugs were better cumulatively with earlier disease (MTX-1.74 for 1 yr; HCQ -0.68 vs -0.43; gold -1.71 vs -0.49). A second trial of the same drug was far less effective than the first course. On a percentage of possible improvement basis, these drugs were nearly equal since HCQ is given to less severely affected patients. CONCLUSION: MTX is the most effective DMARD of these 3 because of the length the therapeutic segment. In terms of disability averted, none of the agents decrease disability by more than 25% of the theoretically possible improvement. We documented that effectiveness of RA treatment is a function of drug sequence, duration of disease, whether it is a first or second course, and severity of disease. None of these clinically relevant observations have emerged from clinical trials. These methodologic approaches provide important quantitative comparative data and will be useful in further assessment of the relative effectiveness of present and future DMARD.

The methotrexate therapeutic response in rheumatoid arthritis.

Abstract: OBJECTIVE: Methotrexate (MTX) is used frequently as a disease modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), and patients tend to continue taking this drug for longer periods than alternative single agents. The shape of the therapeutic response beyond one or 2 years, however, has not been fully studied. We examined the properties of the pure MTX "therapeutic segment," that period that begins with start of MTX and terminates when MTX is discontinued or another DMARD is added, by observational study. METHODS: We studied new MTX starts for the period 1988 through 1996 for 437 patients from a parent cohort of 4253 patients. Patients were drawn from 8 Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) data centers: 2 community based populations; 2 private rheumatological practices; 2 university referral practices; and 2 university clinics for underserved minority urban populations. Health Assessment Questionnaire (HAQ) Disability Index scores (0-3) were obtained prospectively each 6 months. RESULTS: At MTX start, patients had relatively long average disease duration of 16.7 years, and had moderately severe disability, with an initial HAQ mean disability score of 1.48. Over the 10 year period examined in the parent cohort of 4253 patients (and thus irrespective of therapy), the prevalence of MTX use rose from 19% to 45%, while mean HAQ disability declined from 1.34 to 1.11. This correspondence is consistent with an accrual of benefits from more frequent use of MTX and other DMARD over this period. The MTX therapeutic segment revealed a distinct shape. HAQ-Disability Index values began at 1.48 at baseline and declined to a maximal improvement of 1.23 at 30 months. This long period to maximum benefit may have been partly driven by a slow titration upward to an optimal dosage. After 42 months, disability for this population began to re-progress and reached 1.39 at 84 months, still below the pretreatment baseline. Re-progression to baseline was about 8 or more years. Cumulative disability averted with MTX treatment for this population was roughly 1.30 disability-unit-years. CONCLUSION: MTX treatment of RA in practice differs substantially from common perception and appears suboptimal by being too little, too late, and too long to treatment change. A modification of the "sawtooth strategy" in which the disease is "ratcheted down" by change of MTX therapy at 3 years or when re-progression has proceeded halfway to baseline, rather than waiting for return to baseline, is suggested by these data. Also suggested is the need for more rapid upward dosage titration and longer maintenance of an optimal or highest tolerated dosage. "Therapeutic segment" data provide insights into strategic approaches to management of RA since they allow estimation of population aggregate properties such as time to maximum benefit and the time to return to baseline.

Frailty and Education in the Hispanic Health and Nutrition Examination Survey

Abstract: This study tests for the presence of education-frailty correla- tions among 1,176 Mexican Americans, 522 Cuban Americans, and 560 Puerto Ricans, 50 years and older, in the Hispanic Health and Nutrition Examination Survey. Hispanics with the least schooling (less than 7 years) were found to have the highest frailty rates, and those with the most (more than 12 years of schooling) were found to have the lowest frailty rates. Similar, but somewhat weaker, correlations were discovered after a measure of self-efficacy was accounted for.