James F. Fries

Bio: James F. Fries is an academic researcher from Stanford University. The author has contributed to research in topics: Rheumatoid arthritis & Arthritis. The author has an hindex of 100, co-authored 369 publications receiving 83589 citations. Previous affiliations of James F. Fries include University of Saskatchewan & National Institutes of Health.

How to ascertain drug safety in the context of benefit. Controversies and concerns.

Abstract: There is great concern about clearly defining benefit and risk in the context of both drug development and clinical practice. In view of this pressure, the OMERACT Executive identified the need to bring together clinical trialists, pharmacoepidemiologists, clinicians, clinical epidemiologists, statistical experts, and regulatory representatives to discuss different approaches to define risk and perhaps improved ways to express it. Each attendee spoke on a given topic and the group was charged to consider the issue of risk in the context of formally posed questions. This article provides a summary of the presentations and outlines the discussions that followed.

Reducing cumulative lifetime disability: the compression of morbidity.

Abstract: The compression of morbidity hypothesis envisages a potential reduction of overall morbidity and of health care costs, now heavily concentrated in the senior years, by compression of the period of morbidity between an increasing average age of onset of disability and the age of death, increasing perhaps more slowly. The healthy life is seen as a one that is vigorous and vital until shortly before its natural close. Intuitively, the concept of delaying the onset of disability through prevention of disease and maintenance of good function seems natural enough. However, in the early and middle years of this century most observers believed that there was movement away from this ideal, with a steady increase in the proportion of a typical life spent ill or infirm. 3 The previously prevalent acute illnesses had given way to chronic diseases with longer periods of morbidity. As people took better care of themselves and lived longer, the contrarians suggested that they would live into those later years in which disability is greatest and would experience an increase in overall lifetime disability. Such critics feared that good behavioral health habits would lead to an epidemic of Alzheimer’s disease and a huge population of enfeebled demented elders who would pose an immense strain upon medical care resources. Fortunately for the healthy life, these fears are unfounded. Firstly, life expectancy from advanced ages has plateaued rather than having increased markedly as predicted. In the United States, the life expectancy of women from age 65 has increased only 0.3 years over a 15 year period. From age 85, female life expectancy in the United States has been constant at 6.0 years since 1980. Secondly, recent longitudinal data document the ability to greatly postpone the onset of disability with age. For the past 13 years our research group at Stanford has studied the eVects of long distance running on patient outcomes in 537 members of a runners club, with participants at least 50 years old, compared with 423 age matched community controls. The study was designed as a test of the compression of morbidity hypothesis. Appropriate controls of self selection bias were included and disability levels were assessed yearly, allowing the area under the disability curve to be assessed. Runners who exercised vigorously for an average of 280 minutes a week delayed the onset of disability by about 10 years compared with controls. Both male and female runners increased disability at a rate only one third of that of the controls, after adjustment for age, initial disability, educational level, smoking behaviour, body mass index, history of arthritis, and the presence of co-morbid disease. As these subjects moved from age 58 toward age 70, the diVerences in physical function between the exercising and the control population increased, rather than decreased. Lifetime disability in exercisers is only one third to one half of that in sedentary individuals. 7 In the University of Pennsylvania study, we looked at 1741 university attendees, surveyed in 1962 at an average age of 43, and then annually since 1986. This unique data set contains over 50 years of longitudinal follow up since the participants’ days at university. Health risk strata were developed for persons at high, moderate, and low risk, based on the three risk factors of smoking, body mass index, and lack of exercise. Cumulative disability from 1986 (at an average age of 67) to 1994 (at an average age of 75) or until death served as a surrogate for lifetime disability. Persons with high health risks in 1962 or in 1986 have about twice the cumulative disability of those with low health risks. Results were consistent across survivors, deceased,men, women, and over the last one and two years of observation. Deceased low risk subjects had had only one half of the disability of high risk subjects in their last one and two years of life. High risk subjects, despite having increased mortality, had greatly increased lifetime disability. Onset of disability was postponed by about 7.75 years in the low risk stratum as compared with the high risk stratum. The 100% reduction in disability rates was balanced against only a 50% reduction in mortality rates, yielding compression of morbidity. The compression of morbidity is readily demonstrable in those who exercise vigorously compared with those who do not, and those with low behavioral health risks versus those with high, and those with high educational attainment as compared with low. 10 Health risk behaviours as determined in mid life and late adulthood strongly predict subsequent lifetime disability. Both cumulative morbidity and morbidity at the end of life are decreased in those with good health habits. Morbidity is postponed and compressed into fewer years in those with fewer health risks. The paradigm of a long healthy life with a relatively rapid terminal decline represents an attainable ideal. Health policies must be directed at modifying those health risks that precede and cause morbidity if this ideal is to be approached for a population. 13

The promise of the future, updated: better outcome tools, greater relevance, more efficient study, lower research costs

Abstract: Better tools are needed to evaluate our treatments for rheumatic diseases. The long-overdue patient-reported outcome measurement information system project is a NIH roadmap initiative to build better instruments for measuring patient-reported outcomes through use of item banking, item response theory and computerized adaptive testing. The resulting tools are intended to supplant current standards, such as the health assessment questionnaire and the SF-36, and will enable greater study power with reduced sample sizes, as well as integrating greater relevance to the patient into the measures. In some part of early prehistory, it was noticed that clinical studies required ‘dependent variables’ by which to judge the study results. In complex chronic illnesses, such as rheumatoid arthritis (RA), such dependent variables need to provide summary end points and to reflect the values of patients as well as health professionals. Under the medical model, dependent variables were traditionally typified by the erythrocyte sedimentation rate (ESR) and the number of swollen or tender joints as counted by a physician. Curiously, these dependent variables were accepted as a matter of faith and were very rarely an object of study. Had they been studied, it would have been easily observed that there was an extraordinary amount of noise in these variables, with great variability in repeated measurements, between observers, between the same observer on different days, and across laboratories. The ESR and the joint counts are simply not very reproducible. It would have been observed just as easily that the ESR or joint counts did not correlate

Unilateral ptosis as an initial manifestation of D-penicillamine induced myasthenia gravis.

Abstract: We describe 2 patients presenting with isolated unilateral ptosis without other signs of cranial or peripheral nerve involvement or sympathetic denervation Both patients (one case of progressive systemic sclerosis and one of rheumatoid arthritis) were currently taking D-penicillamine In these cases, the ptosis was reversed a few minutes after a Tensilon test, hallmark of myasthenia gravis Antibodies to acetylcholine receptors were present Myasthenia gravis should be suspected with ptosis without other cranial nerve involvement or miosis, even if the ptosis is unilateral Thus, unilateral ptosis can be the first manifestation of a toxic side reaction to D-penicillamine

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

Abstract: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

The 1982 revised criteria for the classification of systemic lupus erythematosus

Abstract: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.

Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.

Abstract: In 1982, the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology (ACR)published revised criteria for the classification of systemiclupus erythematosus (SLE) (1). During the ensuing decade several investigators, including Drs. Graham Hughes and Donato Alarcon-Segovia, among others, have described the presence and clinical associations or antiphospholipid antibodies in patients with SLE, as well as the occurrence of theprimary antiphospholipid syndrome (2-5). In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries (6).

The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee.

Abstract: To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.