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Biomedical subjects

R F Laan

Publications and source records attributed to R F Laan.

At least 19 recordsLinked to original sources
PubMed2003

Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy.

OBJECTIVE: To evaluate predictors of vertebral fractures, including a threshold for bone mineral density (BMD), in patients receiving oral glucocorticoids (GCs). METHODS: Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but different inclusion criteria were applied with regard to prior exposure to GCs. Predictors of vertebral fracture in the placebo group were identified using Cox regression with forward selection. The BMD threshold analysis involved a comparison of the 1-year fracture risk in postmenopausal women receiving placebo in the GC trials with that in postmenopausal women not taking GCs in 3 other trials. RESULTS: The study population comprised 306 patients with baseline and 1-year followup data on vertebral fractures (111 receiving placebo and 195 receiving risedronate). In the placebo group, the statistically significant predictors of incident fracture were the baseline lumbar spine BMD (for each 1-point decrease in T score, relative risk [RR] 1.85, 95% confidence interval [95% CI] 1.06-3.21) and the daily GC dose (for each 10-mg dose increase, RR 1.62, 95% CI 1.11-2.36). In the BMD threshold analysis, compared with nonusers of GCs, patients receiving GCs were younger, had a higher BMD at baseline, and had fewer prevalent fractures; nevertheless, the risk of fracture was higher in the GC users compared with nonusers (adjusted RR 5.67, 95% CI 2.57-12.54). The increased risk of fracture was observed in GC users regardless of whether osteoporosis was present. CONCLUSION: The daily, but not cumulative, GC dose was found to be a strong predictor of vertebral fracture in patients receiving GCs. At similar levels of BMD, postmenopausal women taking GCs, as compared with nonusers of GCs, had considerably higher risks of fracture.

Absorptiometry, Photon↗
PubMed2001

Change in bone mineral density in patients with rheumatoid arthritis during the first decade of the disease.

OBJECTIVE: Rheumatoid arthritis (RA) has been reported to be associated with bone loss during the first years of the disease. The magnitude of this problem after the initial years has not yet been evaluated. In the present study, the change in bone mineral density (BMD) in patients with recent-onset RA as well as the effects of inflammation, mobility, and the use of prednisone on this change were studied in the first decade of the disease. METHODS: BMD was measured twice in 76 RA patients with mean disease durations of 2.35 years at the first BMD measurement and 8.90 years at the second BMD measurement. BMD was measured in both hips using dual x-ray absorptiometry. Results were expressed as mean +/- SEM Z scores (using age- and sex-matched reference values) and as mean +/- SEM percent change in BMD (in gm/cm2) per year. The effects of inflammation, mobility, and the use of prednisone on change in BMD were evaluated using multiple linear regression analyses. RESULTS: At the first BMD measurement, RA patients had lower BMD compared with the reference values (Z score -0.42+/-0.11, 95% confidence interval [95% CI] -0.64, -0.20). Between the 2 measurements, we observed a small decrease in BMD of -0.28+/-0.11%/year (95% CI -0.07 to -0.49). However, the rate of bone loss was smaller than expected. The Z score increased by 0.13+/-0.05 between the 2 BMD measurements (95% CI 0.02, 0.23). Only the use of prednisone was significantly associated with increased bone loss. In a separate analysis that included only postmenopausal women, increased physical activity and longer time since menopause were both associated with decreased bone loss. In this subgroup of patients, the use of prednisone was significantly associated with increased bone loss as well. A high erythrocyte sedimentation rate was associated with increased bone loss, but this did not reach statistical significance. CONCLUSION: After the initial years of the disease, bone loss in RA patients is lower than expected compared with age- and sex-matched reference values. Postmenopausal RA patients with low levels of physical activity are at increased risk of losing bone. Use of prednisone was the only variable consistently associated with reduction in BMD in RA patients.

Absorptiometry, Photon↗
PubMed2001

Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To study the effect of folates on discontinuation of methotrexate (MTX) as single-drug antirheumatic treatment due to toxicity, to determine which type of adverse events are reduced, to study the effects on the efficacy of MTX, and to compare folic with folinic acid supplementation in a 48-week, randomized, double-blind, placebo-controlled trial. METHODS: Patients with active RA (n = 434) were randomly assigned to receive MTX plus either placebo, folic acid (1 mg/day), or folinic acid (2.5 mg/week). The initial MTX dosage was 7.5 mg/week; dosage increases were allowed up to a maximum of 25 mg/week for insufficient responses. Folate dosages were doubled once the dosage of MTX reached 15 mg/week. The primary end point was MTX withdrawal because of adverse events. Secondary end points were the MTX dosage and parameters of efficacy and toxicity of MTX. RESULTS: Toxicity-related discontinuation of MTX occurred in 38% of the placebo group, 17% of the folic acid group, and 12% of the folinic acid group. These between-group differences were explained by a decreased incidence of elevated liver enzyme levels in the folate supplementation groups. No between-group differences were found in the frequency of other adverse events or in the duration of adverse events. Parameters of disease activity improved equally in all groups. Mean dosages of MTX at the end of the study were lower in the placebo group (14.5 mg/week) than in the folic and folinic acid groups (18.0 and 16.4 mg/week, respectively). CONCLUSION: Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX was discontinued less frequently in these patients. Folates seem to have no effect on the incidence, severity, and duration of other adverse events, including gastrointestinal and mucosal side effects. Slightly higher dosages of MTX were prescribed to obtain similar improvement in disease activity in the folate supplementation groups.

Adult↗
PubMed2001

The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients.

OBJECTIVE: To study the possible relationship between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the toxicity and efficacy of treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation. Outcomes were parameters of efficacy of MTX treatment, patient withdrawal due to adverse events, discontinuation of MTX treatment because of elevated liver enzyme levels, and the total occurrence of elevated liver enzyme levels during the study. Multivariate logistic regression analysis was used to study the relationship between the presence of the MTHFR C677T mutation and toxicity outcomes of MTX treatment. RESULTS: Forty-eight percent of the patients showed the homozygous (T/T) or heterozygous (T/C) mutation. The presence of the C677CT or C677TT genotypes was associated with an increased risk of discontinuing MTX treatment because of adverse events (relative risk 2.01; 95% confidence interval 1.09, 3.70), mainly due to an increased risk of elevated liver enzyme levels (relative risk 2.38; 95% confidence interval 1.06, 5.34). Efficacy parameters were not significantly different between the patients with and those without the mutation. CONCLUSION: The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.

Alanine Transaminase↗
PubMed2001

Modified sharp method: factors influencing reproducibility and variability.

BACKGROUND AND OBJECTIVES: In rheumatoid arthritis, joint radiography is still the most frequently used instrument to assess the progression of joint damage. Unfortunately, the poor quality of the radiographic scoring methods available has a negative impact on the power in clinical trials. This study focuses on the influence of the following 4 factors on radiographic scores according to van der Heijde's modification of the Sharp method: intraobserver variation, interobserver variation, follow-up time, and number of measurement occasions within a patient series. METHODS: One hundred and seventy-two patients in the early stages of rheumatoid arthritis were followed up. During the first 3 years, radiographs of the hands and feet were taken twice yearly and scored by 3 observers. The scoring process was repeated after an additional 3-year period. Correlation coefficients and differences between observers were calculated to define variability. The influence of the 4 factors on variability was studied. RESULTS: One observer assigned a significantly higher score than the other 2, who had been trained together. Interobserver variability decreased as follow-up time increased. Interobserver correlation coefficients became higher, with smaller differences between observers for progression scores than for absolute scores. Increasing the number of measurements within a patient series led to higher scores. Intraobserver correlation coefficients were high, and a training effect occurred when the time between measurements was 1 year, resulting in lower scores. CONCLUSIONS: This study demonstrates that, and shows how, the investigated factors influence the variability of the modified Sharp method. It is extremely important to take interobserver variation into account when designing protocols for multicenter clinical trials. A progression scoring method is recommended for studies assessing radiographic damage or clinical trials.

Arthritis, Rheumatoid↗
PubMed2001

Patient satisfaction after total knee arthroplasty: a comparison between subjective and objective outcome assessments.

We used a visual analog scale (VAS) to assess the satisfaction after total knee arthroplasty (TKA) in a group of 108 patients (126 TKAs) with short-term to medium-term follow-up. We also used the Knee Society scoring system, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), pain VAS, and survival analysis. A comparison between the subjective and objective outcome systems revealed only poor correlations. This comparison suggests that the concerns and priorities of patients and surgeons differ. The outcome assessed with the satisfaction VAS revealed a significantly better subjective outcome in rheumatoid arthritis patients compared with osteoarthritis patients, whereas Knee Society scores were not different. The satisfaction VAS provides additional information about subjective outcome after TKA.

Aged↗
PubMed2001

Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis.

OBJECTIVE: This study was designed to determine whether the prevalence of vertebral deformities in patients with rheumatoid arthritis (RA) treated with corticosteroids (Cs) is higher than in RA patients not receiving Cs therapy. PATIENTS AND METHODS: This multicentre cross-sectional study included 205 patients with RA who were receiving Cs orally on a daily basis and 205 patients with RA who did not receive Cs, matched for sex and age. Vertebral deformities were scored according to the Kleerekoper method. RESULTS: Vertebral deformities were found in 52 (25%) patients on Cs and in 26 (13%) patients not on Cs. Sixteen (8%) patients in the group on Cs had experienced clinical manifestations of an acute vertebral fracture in the past vs only three patients (1.5%) among those not on Cs. The use of Cs tended to increase the risk of developing a vertebral deformity [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81-2.99] and symptomatic vertebral fracture (adjusted OR 1.42, 95% CI 0.24-8.32). Each 1-mg increase in the current daily Cs dose increased the risk of a vertebral deformity (adjusted OR 1.05, 95% CI 0.98-1.13) and of a symptomatic vertebral fracture (adjusted OR 1.05, 95% CI 0.89-1.24). CONCLUSION: There is a higher prevalence of vertebral deformities and clinical manifestations of vertebral fractures in patients on Cs than in those not on Cs. Our data indicate that the use of Cs and each 1-mg increase in the current daily Cs dose may increase the risk of development of a vertebral deformity and symptomatic vertebral fracture in patients with RA.

Aged↗
PubMed2001

Leflunomide and methotrexate.

Methotrexate and leflunomide are both effective drugs in the treatment of patients with rheumatoid arthritis. Methotrexate has been available for many years, whereas leflunomide is a relatively new drug. Several large trials describing its efficacy and safety in comparison with both sulfasalazine and methotrexate and with placebo have been published recently. It appears that leflunomide is approximately equally effective as sulfasalazine and methotrexate. New data are also available on the mechanism of action of leflunomide especially. This drug probably acts as an immunomodulatory agent by interfering with the de novo synthesis of pyrimidines.

Arthritis, Rheumatoid↗
PubMed2001

Prevention of symptomatic thrombosis with short term (low molecular weight) heparin in patients with rheumatoid arthritis after hip or knee replacement.

The need for prevention of venous thromboembolism (VTE) after total hip or knee replacement is obvious. However, the optimal regimen to achieve this remains to be defined. In patients with rheumatoid arthritis (RA) long term coumarins may not be necessary owing to the use of non-steroidal anti-inflammatory drugs (NSAIDs). 103 patients in whom 151 surgical procedures were performed (55 hip and 96 knee prostheses) were treated only with short term subcutaneous heparin. NSAIDs were used daily in 85% of the patients, and they were continued after hospital discharge. Only one patient developed symptomatic deep venous thrombosis during one year follow up. Bleeding complications were seen in 20/151 (13%) of the surgical procedures, all clinically judged as minor, and recovery was not delayed except in one case. Short term (low molecular weight) heparin appears to be an adequate, simple, and safe method for prevention of symptomatic VTE in patients with RA after knee or hip replacement, though further studies are necessary to confirm these preliminary findings.

Aged↗
PubMed2000

Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy.

Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500-1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall population, the mean (SE) lumbar spine BMD increased 1.9 +/- 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 +/- 0.4% in the placebo group (P = 0. 005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A significant reduction of 70% in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group (P = 0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy.

Absorptiometry, Photon↗
PubMed2000

Postural control in rheumatoid arthritis patients scheduled for total knee arthroplasty.

OBJECTIVE: To investigate the use of compensatory visual and attentional control strategies for standing balance in patients with rheumatoid arthritis (RA) with severe knee joint impairment. DESIGN: Experimental 2-group design. SETTING: Specialized clinic for orthopedics, rheumatology, and rehabilitation in The Netherlands. PARTICIPANTS: Eighteen patients without comorbidity (age range, 65 +/- 7.7 yr; 16 women, 2 men) from a consecutive sample of patients with RA scheduled for total knee arthroplasty; 23 controls of the same age group also were tested (13 women, 10 men). MAIN OUTCOME MEASURES: By means of a dual-plate force platform, the velocity of center of pressure (COP) fluctuations were analyzed in the anteroposterior and lateral sway directions during quiet standing with eyes open, eyes closed, and while performing a secondary attention-demanding arithmetic task. RESULTS: Patients showed an average 80% greater COP velocity in both directions of sway compared with controls. In addition, stability deteriorated substantially more in patients than controls when deprived of visual information, which was associated with the degree of knee destruction. The effect of the arithmetic task was small and similar in patients and controls. CONCLUSION: RA patients with severe knee joint impairment can have a substantial basic postural instability; their relatively high reliance on visual information suggests impaired sensory feedback from the lower limbs. Current research is aimed at determining whether these postural deficits can be improved by total knee replacement.

Activities of Daily Living↗
PubMed2000

Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study.

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.

Adolescent↗
PubMed2000

A pooled data analysis on the use of intermittent cyclical etidronate therapy for the prevention and treatment of corticosteroid induced bone loss.

OBJECTIVE: To conduct a pooled data analysis in a group of patients defined by sex, menopausal status, and underlying disease in order to examine the effect of intermittent cyclical etidronate in the prevention and treatment of corticosteroid induced osteoporosis. METHODS: We selected 5 randomized, placebo controlled studies that examined the efficacy of intermittent cyclical etidronate therapy in which the raw data were available for analysis. Three were prevention studies and 2 treatment studies. The primary outcome was the difference between treatment groups in the percentage change from baseline in lumbar spine bone density. Secondary outcomes included the difference between treatment groups in the percentage change from baseline in femoral neck and trochanter bone density, and vertebral fracture rates. RESULTS: Results are separately pooled for the prevention and treatment studies. The prevention studies had significant mean differences (95% CI) between groups in mean percentage change from baseline in lumbar spine, femoral neck, and trochanter bone density of 3.7 (2.6 to 4.7), 1.7 (0.4 to 2.9), and 2.8% (1.3 to 4.2) after one year of treatment, in favor of the etidronate group. The treatment studies displayed a mean difference between groups in mean percentage change from baseline in lumbar spine bone density of 4.8 (2.7 to 6.9) and 5.4% (2.5 to 8.4) after one and 2 years of therapy. In the prevention studies, a reduced fracture incidence was observed in the etidronate group compared with the placebo group (relative risk 0.50; CI 0.21 to 1.19). CONCLUSION: Etidronate therapy was effective in preventing bone loss in the prevention studies and in preventing or slightly increasing bone mass in the treatment studies. A fracture benefit was observed in postmenopausal women treated with etidronate in the prevention studies.

Adult↗
PubMed1999

Glucocorticosteroids in the management of rheumatoid arthritis.

Glucocorticosteroids are used frequently in the management of patients with rheumatoid arthritis. Data supporting their efficacy and safety are still meagre. Glucocorticosteroids may be used systemically with different routes of administration (oral, i.m. and i.v.), in different doses and for different periods of time. The effectiveness of glucocorticosteroids in reducing inflammation in the short term has been shown for oral treatment in a dose of 7.5 mg prednisolone daily or more, for i.m. pulses (120 mg methylprednisolone every 4 weeks) and for i.v. methylprednisolone pulses. For longer periods of treatment, the evidence suggesting effectiveness of low-dose oral glucocorticosteroids is more limited. Some data suggest that different regimens of glucocorticosteroids may retard the development of erosions in patients with rheumatoid arthritis. The toxicity of short-term treatment is relatively low. For long-term treatment, the development of osteoporosis is a serious problem. Concomitant therapy with either calcitriol or bisphosphonates may reduce this risk.

Arthritis, Rheumatoid↗
PubMed1998

Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity.

OBJECTIVES: To provide an update of the current knowledge of the mechanism of action of low-dose methotrexate (MTX) in the treatment of patients with rheumatoid arthritis (RA), with an emphasis on the mechanisms involved in toxicity. We also considered strategies currently used to prevent or decrease toxicity of MTX. METHODS: We reviewed the literature dealing with the subjects of MTX treatment of RA, the mechanisms of action of low-dose MTX regarding efficacy and toxicity, and strategies used to prevent or decrease MTX toxicity. RESULTS: MTX is a fast working and effective second-line antirheumatic agent (SLA). Its use is limited mainly because of side effects. The mechanisms of action regarding efficacy and toxicity are probably determined by different metabolic pathways. Recent data indicate that the antiinflammatory effect of MTX is mediated by adenosine. However, MTX side effects can only partly be explained by folate antagonism and may also depend on its action on other related metabolic pathways. The latter include the homocysteine-methionine-polyamine pathway and purine metabolism. Variants in these metabolic routes (ie, the C677T mutation in the methylene-tetrahydrofolate reductase [MTHFR] gene), may predispose to the development of side effects. Currently the most promising strategy to decrease or prevent toxicity of MTX is concomitant prescription of folic acid or folinic acid. Other strategies are currently under investigation. CONCLUSIONS: MTX benefits a majority of RA patients. Approximately 30% of patients, however, abandon treatment because of drug-related side effects. Folic acid or folinic acid likely reduces MTX toxicity. More data, however, are needed to evaluate a potential detrimental effect on the antirheumatic efficacy of MTX.

Antirheumatic Agents↗
PubMed1998

Septic arthritis with Listeria monocytogenes during low-dose methotrexate.

We describe a 22-year-old female with systemic lupus erythematosus and lymphopenia, who developed septic arthritis of the right knee with Listeria monocytogenes type 1/2 A, whilst on low-dose methotrexate (MTX). So far, septic arthritis due to this microorganism has been reported in two other patients treated with low-dose MTX, one having rheumatoid arthritis and the other psoriatic arthritis. No reports exist on patients treated with other cytotoxic antirheumatic therapies.

Adult↗
PubMed1995

Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial.

The efficacy of oral prednisone as bridge therapy in rheumatoid arthritis (RA) was studied. Forty patients starting aurothioglucose were randomized to receive either prednisone or placebo for 18 weeks. The dose was 10 mg/day in the first 12 weeks, 7.5 mg/day in weeks 13 and 14, 5 mg/day in weeks 15 and 16, and 2.5 mg/day in weeks 17 and 18. Patients were followed for 44 weeks. We found that disease activity was significantly lower in the prednisone group as early as week 1 and continued up to week 12. Response to prednisone was noticed in 60% of the patients. After tapering prednisone, a rebound deterioration was noticed at weeks 20 and 24 in 58% of the responders. No significant differences in X-ray progression were found between the two groups. We concluded that oral prednisone (10 mg/day) significantly reduces short-term disease activity in 60% of patients with active RA. The rebound deterioration after tapering the dose means that bridge therapy with prednisone using this dose-reduction scheme is not recommended.

Administration, Oral↗