Showing papers by "James F. Fries published in 1996"

Gastrointestinal Tract Complications of Nonsteroidal Anti-inflammatory Drug Treatment in Rheumatoid Arthritis: A Prospective Observational Cohort Study

Abstract: Background: Gastrointestinal tract (GI) complications associated with nonsteroidal anti-inflammatory drug (NSAID) use are the most common serious adverse drug reactions in the United States. Nonsteroidal antiinflammatory drugs cause both minor GI side effects such as abdominal pain and vomiting and serious GI events such as ulcers and bleeding. This study evaluates the event rates for all NSAID-induced GI complications in patients with rheumatoid arthritis, describes the time course of these events, and evaluates the role of prophylactic therapy with antacids and H2receptor antagonists. Methods: We studied 1921 patients with rheumatoid arthritis from 8 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers. Patients were selected for the study if they were treated with NSAIDs and had at least 2.5 years of observation available. Information on GI complications attributed to NSAIDs was obtained from validated patient self-reports collected every 6 months and supplemented by review of hospital records for all hospitalizations. Results: Approximately 15% of the 1921 patients reported an NSAID-induced GI side effect during the 2.5-year observation period. Forty-two patients had a serious GI complication requiring hospitalization; 34 of these 42 patients did not have a preceding GI side effect. Patients who were taking antacids and H2receptor antagonists did not have a significantly lower risk for serious GI complications than did those not taking such medications. Asymptomatic patients taking these medications had a significantly higher risk for GI complications compared with those who did not take these medications (standardized odds ratio, 2.14; 95% confidence interval, 1.06-4.32). Conclusions: A large majority of patients with serious GI complications do not have preceding mild side effects. Prophylactic treatment with antacids and H2receptor antagonists is of questionable value and may increase the risk for subsequent serious GI complications. Arch Intern Med. 1996;156:1530-1536

Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug–based treatment strategies

Abstract: Objective. Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional “pyramid” approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs (DMARDs), in the hope of improving long-term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long-term functional outcomes. Methods. We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with ⩾1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D-penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ). Results. Increased DMARD use was strongly associated with better long-term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)–positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0–3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0–4, 5–9, 10–14, 15–19, and 20+ years). “Control” correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal antiinflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R2 of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDs more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30% reduction in longterm disability with consistent DMARD use, are most likely conservative. Conclusion. An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data.

Safety of Meloxicam: A Global Analysis of Clinical Trials

Abstract: Meloxicam is a new preferential cyclooxygenase-2 (COX-2) inhibitor for the treatment of rheumatic disease. This paper presents a global safety analysis of data from meloxicam clinical studies, focusing on gastrointestinal (GI) adverse events. Meloxicam 7.5 and 15 mg (n = 893 and 3282) were compared with piroxicam 20 mg (n = 906), diclofenac 100 mg slow release (n = 324) and naproxen 750-1000 mg (n = 243). With respect to all GI adverse events, meloxicam 7.5 and 15 mg were significantly better than all comparators in a pooled analysis of double-blind studies in rheumatoid arthritis (RA) and osteoarthritis (OA). When examining non-serious GI events, severe GI events, discontinuous due to GI events, dyspepsia, abdominal pain and upper GI events, both meloxicam doses were significantly better than comparator non-steroidal anti-inflammatory drugs (NSAIDs) in most cases. Where statistical significance was not demonstrated, there was generally a trend in favour of meloxicam. With respect to upper GI perforations, ulcerations and bleedings, the most serious of NSAID-associated side-effects, meloxicam was better tolerated than the comparators, reaching statistical significance for piroxicam and naproxen. Meloxicam's improved GI safety profile is likely to be due to its preferential inhibition of inducible COX-2 relative to constitutive COX-1.

Physical activity, the compression of morbidity, and the health of the elderly.

Abstract: The Compression of Morbidity hypothesis envisions a potential reduction of overall morbidity, and of health care costs, now heavily concentrated in the senior years, by compression of morbidity between an increasing age of onset of disability and the age of death, increasing perhaps more slowly. For this scenario to be able to be widely achieved, largely through prevention of disease and disability, we need to identify variables which predict future ill health, modify these variables, and document the improvements in health that result. Physical activity is perhaps the most obvious of the variables which might reduce overall lifetime morbidity.

Toward an Understanding of NSAID-Related Adverse Events: The Contribution of Longitudinal Data

Abstract: The ARAMIS (Arthritis, Rheumatism and Ageing Medical Information System) databanks have been used to objectify and quantify drug toxicity. The relative risk of a gastrointestinal (Gl)-provoked hospitalization was more than five times greater in patients taking non-steroidal and-inflammatory drugs (NSAIDs) than in non-NSAID-treated patients, with an excess hospitalization rate of 1.3% per annum. Additionally, there was an excess Gl-related death rate of around 3% in rheumatoid arthritis (RA) patients compared with the normal population. Age, previous NSAID-related GI events, prednisone use, higher doses and greater disability predicted high-risk patients. A toxicity index showed clear differences between NSAIDs, with aspirin, salsalate and ibuprofen emerging as the least toxic, and meclofenamate and indomethacin as the most toxic. Disease modifying anti-rheumatic drugs (DMARDs) were, surprisingly, found to have similar toxicity scores to the NSAIDs. This supports the contemporary practice of employing DMAR...

Risk factors for adult Still's disease.

Abstract: Objective To assess risk factors for adult Still's disease (ASD). Methods A matched case-control study of 60 patients with ASD and 60 same sex siblings closest in age was conducted. Subjects were recruited from cohorts in Eastern Canada, Pittsburgh, and the Arthritis, Rheumatism, and Aging, Medical Information Systems (ARAMIS). A questionnaire was used to obtain data on demographic characteristics, education, income, occupation, exposure to toxic substances, stress, and medical history. Results 116 patients with ASD were identified, of which 104 participated. 86 identified same sex siblings, of which 60 replied. When compared to same sex siblings, ASD patients were similar with respect to education and occupation but had a trend to higher median income. There were no significant associations of ASD with smoking, alcohol consumption, individual toxic substances, vaccination, blood transfusion, minor or major surgery, pregnancy, or diet in the year preceding disease onset. There were no significant associations with tonsillectomy or adenoidectomy, appendectomy, asthma, hay fever, allergy shots, or pregnancy at any time preceding the onset of disease. There was a statistically nonsignificant increase in a history of exposure to coal dust [odds ratio (OR) 3.0; 95% confidence interval (CI) 0.30 to 28.84], in allergy preceding the onset of disease (OR 2.67; 95% CI 0.71 to 10.05), and in oral contraceptive use in the year preceding onset (OR 2.00; 95% CI 0.18 to 22.06). Stressful life events (OR 2.56; 95% CI 1.18 to 5.52) in the year preceding onset was significantly associated with increased risk for ASD. This positive association should be treated with caution unless confirmed by a separate study. Conclusion This exploratory study of risk factors for ASD draws attention to stress as a potentially important risk factor, while likely excluding a considerable number of others.

Why health care costs more in the US: comparing health care expenditures between systemic lupus erythematosus patients in Stanford and Montreal.

Abstract: Objective. Recent studies to identify the causes of higher health care expenditure in the US versus Canada have relied on population-based measures of health care utilization and have restricted their analysis to one sector, such as physician or hospital expenditures. We present a detailed comparative analysis of the direct costs (health services utilized) of treating systemic lupus erythematosus (SLE) patients in Stanford, CA and Montreal, Quebec. Methods. Using the self-report Stanford Health Assessment Questionnaire, we assessed 6-month direct costs incurred by 174 American and 164 Canadian SLE patients. We explored 3 potential reasons for the differential expenditure. These were 1) higher prices for health care inputs, 2) more severe disease in the patient case mix, and 3) greater resource utilization. Results. The direct health care costs for the American SLE patients exceeded those for the Canadian patients by almost 2-fold ($10,530 versus $5,271, expressed in 1991 US dollars). The higher direct costs were explained by the higher price of health services in the US and the more severe disease mix. In fact, for all health resource categories studied, Canadians utilized at least as many services as their American counterparts. Canadians had longer hospital stays, made more emergency room visits, and used more medications. Conclusion. Despite significantly greater per capita health care expenditure in the US, our data show that Canadian SLE patients actually receive more medical services.

Relationship of running to musculoskeletal pain with age. A six-year longitudinal study.

Abstract: Objective To determine, by longitudinal study, whether long-distance running, maintained for many years, is associated with increased musculoskeletal pain with age Methods A 6-year prospective longitudinal study of 410 runners' club members and 289 community controls, age 53-75 years at study initiation, was conducted Subjects were also categorized as ever-runners (n = 488) and never-runners (n = 211) The primary dependent variable was pain score as indicated on a horizontal double-anchored analog scale; data for this variable were available beginning in 1987 Statistical adjustment for age, education level, smoking, alcohol consumption, history of arthritis, and presence of other major medical conditions was done by analysis of covariance Further analyses of previously reported associations of regular vigorous physical activity with decreased disability and mortality after 9 years were performed Results The degree of musculoskeletal pain was slightly lower in the exercise group compared with controls, and the difference was statistically significant for women but not for men Average adjusted pain scores for men were 183 (SEM 08) in runners' club members, 202 (12) in controls, 186 (08) in ever-runners, and 203 (16) in never-runners For women, these scores were 175 (18) in runners' club members versus 228 (14) in controls (P < 005), and 172 in ever runners versus 237 (15) in never-runners (P < 0002) Disability had continued to develop in runners' club members at a rate only one-third that in the controls after 9 years of observation Mortality over 9 years consisted of 51 deaths, of which 41 were in the control group and only 10 were among runners' club members Conclusion Vigorous running activity over many years is not associated with an increase in musculoskeletal pain with age, and there may be a moderate decrease in pain, particularly in women Vigorous physical activity is associated with greatly decreased levels of disability and with decreased mortality rates

Effectiveness and toxicity considerations in outcome directed therapy in rheumatoid arthritis.

Abstract: New paradigms of disease modifying antirheumatic drug based treatment strategies for rheumatoid arthritis (RA) raise new questions of sequencing of medications and employment of combination therapy. A broader view of chronic illness indicates that nonbiologic and self-management factors influence disease course and necessitate inclusion of patient oriented outcome measures such as disability and pain. I discuss these and related issues, present a broad model of disease progression in RA, introduce the concept of the "therapeutic segment," describe the dependence of clinical results on immediately prior therapy, and suggest a new research approach into the merits of combination therapy. Effectiveness is not necessarily increased by addition of a 2nd drug, nor is toxicity necessarily increased by combination therapy.

Lymphoma and luekemia in rheumatoid arthritis: are they associated with azathioprine, cyclophosphamide, or methotrexate?

Abstract: Incident cases of lymphoma and leukemia in a cohort of 3824 rheumatoid arthritis (RA) patients from the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) database were identified, and the use of azathioprine, cyclophosphamide, and methotrexate was compared in a matched case-control study. Controls were matched on age, sex, year of study entry, disease duration, center, and years of follow-up. Twenty-four cases of lymphoma and 10 cases of leukemia were identified: 21% of patients with cancer versus 9% of controls had taken azathioprine [McNemar statistic 1.50 (p = 0.22), odds ratio 5.0 (95% confidence interval 0.6,236.5)]. Equal numbers of cases and controls (6% each) had taken cyclophosphamide and 18% of cases and 12% of controls had taken methotrexate [McNemar statistic 0.13 (p = 0.72), odds ratio 1.7 (0.3, 10.7)]. Results suggest but do not prove that RA patients taking azathioprine and methotrexate may have an increased risk of developing lymphoma. However, even if this increased risk can be confirmed, it accounts for only a small proportion of the greatly increased incidence of these malignancies in RA.

Prevention of osteoporotic fractures: possibilities, the role of exercise, and limitations

Abstract: The Compression of Morbidity paradigm seeks to reduce lifetime illness and morbidity by compressing the dominant morbidity, that of the senior years, between an increasing age of onset of morbidity and a more slowly increasing average age at death. Fractures, often associated with osteoporosis, cause a substantial part of this morbidity. For morbidity resulting from fractures to be reduced, the age-specific incidence of fractures needs to decline, since treatment of fractures after they occur is not likely to prove a major benefit. Thus, the risk factors need to be identified and appropriate preventive interventions undertaken. The medical model seeks to diagnose, then to treat those with disease. In considering prevention, many apply the medical model. The disease is "osteoporosis", we must identify people with this disease and then treat them. The public health model, in contrast, seeks to prevent "disease" in all susceptibles. The disease is "morbidity resulting from fractures". The fatal flaws in the medical screening approach will be discussed, together with a lament that this conference was not entitled: "Recent Progress in the Prevention of Morbidity Associated with Fractures". Osteoporosis is only one of many factors associated with increased morbidity resulting from fractures. A fracture management model for reduction in this morbidity will be presented. Osteoporosis finds its genesis in many well-identified risk factors, including age, sex, estrogen levels, and exercise levels, together with positive (e.g. calcium, estrogen) and negative (corticosteroids) effects of medications. Falls, the other main branch of the model, find their genesis is such risk factor as slippery floors, medication side effects, and co-morbid conditions, often with their own antecedent risk factors. Together, over twenty preventable risk factors contribute to the major morbidity associated with fractures.