Premature mortality in patients with rheumatoid arthritis: evolving concepts.
Explore the source record for details and available documents.
Antirheumatic Agents↗
Biomedical subjects
T Sokka
Publications and source records attributed to T Sokka.
A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.
OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. RESULTS: We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. CONCLUSION: Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.
Acetaminophen↗
How can the risk of long-term consequences of rheumatoid arthritis be reduced?
The long-term natural history of rheumatoid arthritis includes early radiographic damage and progression, severe functional declines, work disability and increased mortality rates. Emerging evidence suggests that this natural history may be favourably affected by disease-modifying anti-rheumatic drugs (DMARDs), which slow the radiographic progression and functional decline. It is necessary to document both the efficacy of these drugs in randomized controlled clinical trials and their long-term effectiveness in clinical observational studies. Although a 20% improvement in inflammatory measures in the American College of Rheumatology Core Data Set (ACR20) distinguishes DMARDs from placebo in clinical trials, it is not clear that a control of inflammation at this level, or even at 50%, is sufficient to prevent long-term damage. There is limited financial support for long-term observational studies, which depend on data from the clinical experience of rheumatologists. Quantitative databases from clinical care, can be developed to document long-term outcomes in patients with early rheumatoid arthritis to include additional physical, radiographic, laboratory and patient questionnaire quantitative data. Patient self-report questionnaires appear to provide the least expensive and most effective measures toward this goal.
Anti-Inflammatory Agents, Non-Steroidal↗
Markers for work disability in rheumatoid arthritis.
Work disability is common in rheumatoid arthritis (RA), and accounts for a large fraction of its costs. People with RA who are work disabled have more joint involvement, radiographic damage, and/or laboratory abnormalities than people who are working. However, analysis of predictive and associative markers in 15 studies of work disability indicate that the demographic variables, such as age, occupation, level of education, and duration of disease, as well as functional status in activities of daily living (ADL) identified on a patient questionnaire, appear to identify work status more than physiological variables. Work disability results from complex interactions of a medical disease, demographic variables, social conditions, and government policies. Some patients with RA are work disabled before they see a rheumatologist. Improved work disability outcomes in RA will require attention to social, economic, and political issues, and wider physician and public education concerning RA, in addition to improved medical management of disease.
Activities of Daily Living↗
Quantitative target values of predictors of mortality in rheumatoid arthritis as possible goals for therapeutic interventions: an alternative approach to remission or ACR20 responses?
Predictors of longterm mortality in rheumatoid arthritis (RA) include patient questionnaire measures, grip strength, walk time, physician and patient assessment of global status, joint examination abnormalities, erythrocyte sedimentation rate (ESR), and morning stiffness. In the rheumatology literature, these measures have been analyzed primarily according to mean values in groups or regression analyses, which are valuable to recognize that mortality in RA is predicted by more severe disease, but do not provide the clinician with specific goals of therapy. Goals for therapeutic intervention are often expressed either as complete remission or as statistically significant differences versus a placebo, as in a 20% or even 50% response of a measure such as the American College of Rheumatology Core Data Set. Remission may be too stringent, while statistically significant efficacy of a drug compared to placebo may not necessarily indicate effectiveness to control longterm damage. An alternative approach might be to identify possible target values for therapeutic efficacy that markers of a poor prognosis be "near normal" rather than necessarily at normal or remission levels, as has been explored in management of hypertension and diabetes. However, it remains uncertain whether the goal of therapy should be a "near normal" or entirely normal values for a clinical marker. Better control of quantitative markers that predict early mortality could provide a valuable approach to improving outcomes in RA.
Arthritis, Rheumatoid↗
Scores for functional disability in patients with rheumatoid arthritis are correlated at higher levels with pain scores than with radiographic scores.
OBJECTIVE: To analyze correlations of functional disability scores with other measures of clinical status, in particular, Larsen radiographic scores and pain scores, in patients with rheumatoid arthritis (RA). METHODS: The functional capacity of 141 patients with RA (102 women, 39 men; median age 57 years; median disease duration 11.8 years; 83% rheumatoid factor positive) was assessed according to the Stanford Health Assessment Questionnaire (HAQ). Other variables studied included Larsen scores for radiographic damage of the small joints of the hands, wrists, and feet, pain scores by visual analog scale (VAS), Disease Activity Scores, general health scores by VAS, and Beck Depression Inventory (BDI) scores. RESULTS: The Spearman correlation coefficient comparing HAQ and Larsen scores was 0.277 (P = 0.001) and between HAQ and pain scores 0.652 (P < 0.001). In regression analysis, pain scores explained 41.4% of the variation in HAQ scores, normalized Larsen scores explained 7.3%, and BDI scores explained 5.5%; other variables were not significant in the model. CONCLUSION: Functional capacity scores of patients with RA are correlated at higher levels with pain scores than with radiographic scores of small joints.
Aged↗
Disease-modifying anti-rheumatic drug use according to the 'sawtooth' treatment strategy improves the functional outcome in rheumatoid arthritis: results of a long-term follow-up study with review of the literature.
OBJECTIVES: To investigate long-term functional outcomes of early rheumatoid arthritis (RA) patients treated actively with disease-modifying anti-rheumatic drugs (DMARDs) from diagnosis, according to the 'sawtooth' principle, and to compare the results to historical data. METHODS: The surviving 46 and 65 patients from two early RA cohorts were examined on average 13.0 (cohort 1) and 8.5 (cohort 2) yr, respectively, after onset of disease. Functional outcome was measured by the Health Assessment Questionnaire (HAQ) and compared with the HAQ scores of 57 RA patient cohorts found through a Medline computer search. RESULTS: The respective cross-sectional mean HAQ scores of cohorts 1 and 2 were 0.75 and 0. 55, and were more favourable than the mean HAQ scores of 1.27 (27 cohorts, disease duration >10 yr) and 1.13 (13 cohorts, disease duration 5-10 yr) of the comparator cohorts. The median time that our patients were treated with DMARDs out of the total follow-up period was 88%, while in the majority of comparator cohorts the use of DMARDs was less extensive or poorly described. CONCLUSIONS: The observation of better preserved function in patients with RA over 13 and 8.5 yr, compared to earlier reports which indicated more severe declines, is a hopeful sign for the rheumatology community.
Adolescent↗
Healing of erosions in rheumatoid arthritis.
Reports on healing of erosions in rheumatoid arthritis are rare. However, it is expected that repair of erosions should be seen more often during the period of extensive use of disease modifying antirheumatic drugs, especially in patients who experience sustained remission. Two such cases are described.
Adult↗
Muscle strength characteristics and central bone mineral density in women with recent onset rheumatoid arthritis compared with healthy controls.
Muscle strength and bone mineral density (BMD) at the lumbar spine (BMDspine) and femoral neck (BMDfem) were determined in 20 healthy women and in 20 women with recent onset rheumatoid arthritis (RA). The mean duration of articular symptoms of the patients was eleven months and none of them had used glucocorticoids or disease modifying antirheumatic drugs. BMDs were measured by dual x-ray absorptiometry (DXA). Knee extension, trunk extension, and flexion as well as grip strength were measured with David 200 and Digitest dynamometers. BMDspine (1.17 g/cm2 and 1.20 g/cm2) and BMDfem (0.98 g/cm2 and 0.96 g/cm2) between the women with early RA and healthy women did not differ. However, knee extension strength was 46%, grip strength 31%, trunk extension strength 14% and overall muscle strength index 29% lower in RA women (p < 0.020-0.001) than in healthy subjects. Femoral neck BMD correlated statistically significantly with knee extension strength and muscle strength index in both groups and with trunk extension and flexion strength as well as rapid force development in RA women. The data indicates that the loss of muscle strength is clearly visible during the first months of disease but the significant bone loss at central bone regions develops later.
Adult↗
Mortality in early "sawtooth" treated rheumatoid arthritis patients during the first 8-14 years.
OBJECTIVE: To describe mortality in a cohort of early RA patients treated from the onset with disease-modifying antirheumatic drugs (DMARDs) according to the 'sawtooth' strategy. PATIENTS AND METHODS: A total of 135 early RA patients were followed up for 8-14 years or until death. Causes of death were checked on the death certificates and in patient files. Standardized mortality ratio (SMR) was calculated. Results. A total of 25 (14F, 11M) patients died during the 1422 person-years of follow-up. The SMR (95%CI) was 1.28 (0.83-1.89); 1.69 (0.92-2.82) for women and 0.98 (0.49-1.74) for men. In five cases death was closely related to RA. No one died from amyloidosis. Not a single death was caused by DMARDs in spite of extensive use of these drugs. Patient's age at the start was the only statistically significant predictor for death. CONCLUSION: Despite active treatment with available DMARDs, RA seems still to be a fatal disease in a proportion of cases.
Adolescent↗
Utility of disease modifying antirheumatic drugs in "sawtooth" strategy. A prospective study of early rheumatoid arthritis patients up to 15 years.
OBJECTIVES: To study long term utility of early, continual, and serial use of disease modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA) in clinical setting. METHODS: A total of 135 patients with early RA were treated according to the "sawtooth" strategy and prospectively followed up to 15 years. DMARD survivals as well as reasons for drug terminations were documented and are reported here. RESULTS: During 1401 person years of follow up, a DMARD or a combination of two or several DMARDs (COMBOs) was started 606 times. A total of 528 drug periods were terminated because of inefficacy, adverse effects, remission, and other reasons in respective 270 (51.1%), 149 (28.2%), 32 (6.1%), and 77 (14.6%) cases. Severe drug related adverse events were rare. The median duration of DMARD periods of individual DMARDs or COMBOs was 10 months ranging from six to 18 months. Not a single DMARD/COMBO stood out favourably from the others with respect to ineffecacy, toxicity or drug survival. CONCLUSION: The use of serial DMARDs/COMBOs was safe even in the long run. Inefficacy rather than toxicity was the leading reason for drug terminations. More powerful drug therapies are needed.
Antirheumatic Agents↗
Dynamic strength training in patients with early rheumatoid arthritis increases muscle strength but not bone mineral density.
OBJECTIVE: To assess the effects of 12 months' dynamic strength training on muscle strength and bone mineral density (BMD) at the lumbar spine and femoral neck in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two subjects in the training group (EG) and 33 in the control group (CG) completed the study. EG carried out strength training 2 times a week with moderate loads of 50-70% of repetition maximum. They were also encouraged to do recreational physical activities. CG performed recreational physical activities and range of motion exercises. Maximal strength of the knee extensors, trunk extensors and flexors, and grip strength were recorded with dynamometers. BMD was measured using dual x-ray absorptiometry. Modified Disease Activity Score, erythrocyte sedimentation rate, and pain were used for the estimation of disease activity, and Stanford Health Assessment Questionnaire to measure functional disability. RESULTS: The 12 month resistance training in EG led to statistically significant mean increases of 22-35% in all muscle groups examined. CG patients were also able to increase their strength to some degree (3-24%), but at the end of the study strengths in CG were significantly lower than in EG. By the end of the study lumbar spine BMD had changed by +0.19% (4.24) in EG and by -1.14% (4.36) in CG. The corresponding changes of femoral BMD were +1.10% (3.71) and -0.03% (3.58). The changes in BMD were minor and statistically not significant in both groups. However, femoral BMD was found to be decreased among those patients treated periodically with oral glucocorticoids (n = 15, 3 subjects from EG and 12 from CG) compared with changes in BMD among those not treated with systemic glucocorticoids (n = 50). CONCLUSION: Minimally supervised strength training resulted in significant improvements in muscle strength without detrimental effects on disease activity. The detected annual changes in central BMD were minor and statistically insignificant in both groups. Special attention should be focused on those patients with RA with high disease activity and concomitant glucocorticoid treatment.
Arthritis, Rheumatoid↗
Work disability in rheumatoid arthritis 10 years after the diagnosis.
OBJECTIVE: To describe employment status of patients with early rheumatoid arthritis (RA) 10 years after diagnosis; and to identify predictive and associative factors related to permanent work disability. METHODS: The study population consisted of 82 patients with early RA who were gainfully employed at onset of RA. Patients were prospectively followed for an average of 10 years and were treated according to the "sawtooth" strategy. RESULTS: After a time since diagnosis of 2 and an average of 9.9 years, respectively, 19/82 (19%) and 36/82 (44%) cases have been retired merely or partly due to RA. Further, at the latest checkup 42/82 (51%) patients were still gainfully employed, while the prevalence of patients working full time under the common retirement age of 65 yrs was 58% (42/72). Cox regression analysis revealed that physically heavy work at baseline was the strongest independent predictive factor for permanent work disability. Ten years after disease onset, however, work disabled patients had more severe disease than those who continued in work. CONCLUSION: Our study confirms that the working capacity of patients with RA is in danger from the very start. Despite early and active therapy with disease modifying antirheumatic drugs, at 10 years the cumulative work disability prevalence was 44%.
Adolescent↗
Nonsteroidal anti-inflammatory drug-associated upper gastrointestinal lesions in rheumatoid arthritis patients. Relationships to gastric histology, Helicobacter pylori infection, and other risk factors for peptic ulcer.
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are risk factors for peptic ulcer in rheumatoid arthritis (RA) patients, but the contribution of reactive gastritis, concomitant Helicobacter pylori infection, or RA activity to NSAID ulcer pathogenesis is unknown. METHODS: Ninety-six RA patients taking NSAIDs and dyspeptic sex- and age-matched control patients without NSAID use or an RA diagnosis were enrolled in the study. RESULTS: Gastric ulcer (GU) was detected in 29 (30%) RA patients and 3 control patients (P < 0.001). Sixteen RA patients and no control patient had an H. pylori-negative GU. The GUs of the RA patients were mainly located in the prepyloric region (28%) and antrum (62%). Nine of the 29 RA patients (31%) with GU had more than 1 ulcer. Erosive gastropathy was detected in 34 (71% H. pylori-negative) RA patients and in 13 (62% H. pylori-negative) control subjects (P < 0.001). Chronic gastritis was observed in 65 RA patients (48% H. pylori-negative) and in 58 control subjects (43% H. pylori-negative) (NS). whereas reactive gastritis was found in only 2 RA patients and in none of the controls. Corticosteroid use was the only independent risk factor for GU: odds ratio was 6.8 (95% confidence interval, 1.3-36.0). The prevalences of duodenal ulcer or esophagitis were not increased in RA patients. CONCLUSIONS: RA patients using NSAIDs continuously are at a greatly increased risk of developing both H. pylori-negative and -positive GUs, and corticosteroid use is an independent risk factor for ulcer development. Most RA patients have chronic gastritis, whereas reactive gastritis is rarely associated with continuous NSAID use in RA patients.
Aged↗
Functional LH receptor appears in the neonatal rat ovary after changes in the alternative splicing pattern of the LH receptor mRNA.
The LH receptor (R) function, as assessed by ligand binding and stimulation of cAMP production, is initiated in the neonatal rat ovary around day 7 of life. To correlate this with the onset of expression of the LHR gene, we assessed the presence of the cognate mRNA in the developing rat ovary from day 17 of fetal life onwards using PCR multiplication of reverse transcribed LHR mRNA, followed by southern hybridization and sequencing of the PCR products. Our findings indicate that only truncated versions of LHR mRNA are present in the developing rat ovary as early as day 17 fetal life and up to day 7 post partum. Concomitant with the appearance of a functional LH receptor (after day 7 post partum), two larger LHR mRNA species (2.6 and 6.7 kb) appear, which are also present in the adult ovary. These findings indicate that the LHR gene is probably constitutively expressed in the developing rat ovary, and that the onset of translation of functional LH receptor occurs through a change in the alternative splicing pattern of LHR mRNA.
Animals↗
Molecular aspects of the ontogeny of pituitary and gonadal function.
Explore the source record for details and available documents.
Aging↗
Ontogeny of gonadotrophin receptors and gonadotrophin-stimulated cyclic AMP production in the neonatal rat ovary.
The sequence of appearance of FSH and LH receptors, and response of cyclic AMP (cAMP) production to these hormones and cholera toxin, were studied in the fetal and neonatal rat ovary. Specific binding of radiolabelled human (h)FSH and chorionic gonadotrophin (CG) to ovarian homogenates was first detectable on day 7 of life. The content of FSH receptors per ovary increased tenfold between days 7 and 16, and that of LH receptors 27-fold. A significant response of cAMP production in vitro to FSH appeared on day 4 of life, but no significant effect of hCG on cAMP was achieved until day 7. In contrast, cholera toxin had a marked effect on cAMP production by day 17 of fetal life. Although both FSH and LH receptors were detectable in the neonatal rat ovary by day 7, the present findings indicate that the FSH responsiveness of the ovary appears earlier than that of LH. The post-receptor machinery of cAMP production is already functional in the fetal ovary as shown by the experiments with cholera toxin. The appearance of the receptor may therefore be the last link in the ontogeny of the gonadotrophin signal transduction system in the ovary. To study the hormone dependence of the appearance of gonadotrophin responsiveness, neonatal female rats were treated on days 1-6 or 1-9 of life with a potent gonadotrophin-releasing hormone antagonist, and killed on the following day. In both treatment groups, the pituitary LH and FSH contents were suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A historical perspective concerning population-based and clinical studies of early arthritis and early rheumatoid arthritis.
Research concerning early arthritis and early rheumatoid arthritis (RA) may be considered to have begun with population-based studies in the United Kingdom, the United States and Scandinavia, from the late 1950s to the late 1960s. These studies indicated that the majority of people with clinical findings of RA had no evidence of disease 3-5 years later, and that only about 25% to 30% of people in a population who met the criteria for RA had rheumatoid factor. These findings may have contributed to an underestimation of RA until the severity of long-term outcomes of clinical RA were recognized in the 1980s on the basis of clinical cohorts. The first major early RA clinical cohort was established in 1957-1963 in Bath, England. Although results at 3 and even 11 years were not overly unfavorable, by 15 and 20 years most patients had severe outcomes of functional declines and premature mortality. The Middle-sex (UK) early RA cohort established in 1966-1971 indicated that radiographic abnormalities were observed in about 70% of patients by 2 years of disease, and were seen in most patients initially in the feet. The Memphis (Tennessee, USA) early RA cohort established in 1967-1971 suggested that a progressive course of RA is predicted by a higher number of involved joints at baseline. The Lund (Sweden) early RA cohort established in 1985-1989 indicated rather severe long-term outcomes in patients treated according to traditional conservative approaches to use of disease modifying anti-rheumatic drugs (DMARDs). The early RA study (ERAS) involving nine National Health Service trusts in the UK was established in 1987-93, and showed associations of education level and socioeconomic status with clinical status. The movement towards early arthritis clinics was given great impetus following the work by Emery in the early 1990s. These studies and others described elsewhere in this supplement have contributed to the foundations for the clinical approach to early arthritis in the 21st century.
Adult↗