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Biomedical subjects

R B Landewé

Publications and source records attributed to R B Landewé.

At least 19 recordsLinked to original sources
PubMed2003

[The value of joint general practitioner and rheumatologist consultations in primary care patients].

OBJECTIVE: To compare the effects of regular referral by general practitioners to the Rheumatology outpatients' clinic with that of joint consultations by general practitioners (GPs) and rheumatologists, and to compare the subsequent treatment policy followed. DESIGN: Randomised. METHOD: In 1999 and 2000 all rheumatological patients who, according to the 17 participating GPs in the Maastricht region had an indication for referral, were referred to the outpatients' clinic or seen during a joint consultation where three GPs and one rheumatologist decided on a treatment policy in the presence of the patient. Agreement about diagnosis and diagnostic and therapeutic approaches between the rheumatologists and GPs was determined using questionnaires. The patient's state of health was assessed using the 'EuroQol health-related quality of life questionnaire' (EuroQol) and their satisfaction was determined by means of questionnaires. RESULTS: One hundred and sixty-six patients were included: 45 (27%) men and 121 (73%) women, with an average age of 53.7 years (SD: 14). The rheumatologists and the GPs differed in opinion on the diagnosis in 64% of the patients. Agreement on diagnosis resulted in greater agreement on the treatment policy than when there were discrepancies about the diagnosis. The rheumatologist used additional diagnostic tools and follow-up consultations at the outpatient clinic (78% and 65%) more frequently than during the joint consultation (44% and 15%). Patient satisfaction and general state of health were comparable in both groups.

Family Practice↗
PubMed2003

Joint consultation of general practitioner and rheumatologist: does it matter?

OBJECTIVE: To assess the effects of joint consultation on referral behaviour of general practitioners (GPs) in a prospective cohort study. METHODS: All patients with rheumatological complaints that 17 participating GPs, from the area of the University Hospital Maastricht, wanted to refer during a two year inclusion period (n=166) were eligible for inclusion. These patients were either referred to the outpatient clinic, or presented at a joint consultation held every six weeks at the practice of the GP, where groups of three GPs presented their patients to a visiting, consulting rheumatologist. The number of patients referred by each GP a year at the end of the trial, comparing participating and non-participating GPs, was the main outcome measure. RESULTS: During two years of inclusion, the 17 participating GPs presented 166 patients. The number of patients referred by each GP a year decreased for the participating GPs by 62% at the end of the whole study. By contrast, non-participating GPs maintained the same rate of referral. The range of diagnoses remained proportionally the same throughout the study, with the exception of fibromyalgia. The referral rate of this diagnosis decreased significantly (p=0.001). CONCLUSIONS: Joint consultation seems to be a good strategy in influencing the referral behaviour of GPs in the area of rheumatology. The decrease in referral is substantial and can subsequently lead to a reduction of waiting lists.

Adult↗
PubMed2001

High dose chemotherapy followed by autologous peripheral blood stem cell transplantation or conventional pharmacological treatment for refractory rheumatoid arthritis? A Markov decision analysis.

OBJECTIVE: To evaluate the effect of high dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (ASCT) in comparison to conventional pharmacological therapy in the treatment of patients with refractory, progressively erosive rheumatoid arthritis (RA). METHODS: Decision analysis using a Markov model with a 5.5 year time horizon. Probabilities of transition towards 5 different health states, ranging from 70% improvement to death, were derived from published case reports, patient series, and expert panels. Quality of life (QOL) estimates were obtained from 2 RA clinical trials. Patients were hypothetical cohorts of 50-year-old female patients with progressively erosive, active RA, who failed treatment with methotrexate, combination therapy, and tumor necrosis factor blocking agents. Interventions were HDC + ASCT versus conventional pharmacological treatment with a (combination) therapy of disease modifying antirheumatic drugs. As main outcome measures, we included the number of quality adjusted life years (QALY) after HDC + ASCT compared to conventional therapy. Sensitivity analysis was performed to investigate the influence of treatment related mortality (TRM) and the influence of QOL during HDC + ASCT, and to assess the minimal desired effectiveness of HDC + ASCT for a given TRM of 1% and 10%. RESULTS: HDC + ASCT and conventional pharmacological treatment were equally effective in the base-case analysis (3.48 vs 3.46 QALY). A TRM of less than 3.3% favored HDC + ASCT as the preferred treatment. The analysis showed that when TRM was set at 1%, a relatively short period of efficacy was sufficient to remain the preferred strategy, whereas a TRM of 10% would require a sustained response for several years. CONCLUSION: This model predicted equally favorable effects of HDC + ASCT and conventional therapy in the treatment of refractory RA in the base-case. The minor differences in terms of QALY seem to indicate that clinical decision making should be guided by patient preferences. However, better clinical efficacy might be achieved by adaptation of the treatment regimen of HDC + ASCT and patient selection. The model supports the need for randomized clinical trials and may contribute to an optimal study design.

Antirheumatic Agents↗
PubMed1999

Chloroquine therapy in patients with recent-onset rheumatoid arthritis: the clinical response can be predicted by the low level of acute-phase reaction at baseline.

If rheumatoid arthritis (RA) patients with a mild disease course could be identified early in the phase of the disease, therapy with less aggressive and probably less toxic antirheumatic drugs seems to be rational. The aim of this study was to investigate which factors at baseline could predict a clinical response (American College of Rheumatology preliminary response criteria) after treatment with chloroquine for 16 weeks. Two hundred and three early RA patients with active disease were treated with oral chloroquine sulphate (Nivaquine) at a daily dose of 300 mg during the first 4 weeks, 200 mg during the second 4 weeks and 100 mg thereafter. One hundred and eighty-three patients (90%) completed the study and 20 patients prematurely discontinued treatment. Of all the patients, 43 patients (21%) met the response criteria. A low level of C-reactive protein (CRP) was the only independent predictor for clinical response [relative risk: 0.97 (95% confidence interval: 0.95-0.98)]. It was concluded that a clinical response to chloroquine therapy in early RA patients can be predicted by a low CRP level at baseline.

Acute-Phase Reaction↗
PubMed1999

Cyclosporin A therapy in rheumatoid arthritis: only strict application of the guidelines for safe use can prevent irreversible renal function loss.

OBJECTIVES: To investigate (1) whether the increase in serum creatinine observed during cyclosporin A (CsA) therapy was reversible in a group of patients with rheumatoid arthritis (RA) treated before the current guidelines for safe use in RA were developed and (2) whether the application of these guidelines prevents serum creatinine increases in the long term. PATIENTS AND METHODS: Eighty-three RA patients who had started low-dose CsA therapy between September 1990 and October 1992, and who were treated according to guidelines that allowed a 50% rise in serum creatinine, were tested for serum creatinine levels in December 1995 if they had discontinued CsA for at least 3 months. Predictors for irreversibility of renal function were determined by using multiple regression analysis. RESULTS: The mean level of serum creatinine gradually increased from 69+/-14 (mean+/-S.D.) micromol/l when starting CsA therapy to 88+/-23 micromol/l (28% above baseline) at the moment of CsA discontinuation, and had decreased to 80+/-17 micromol/l (16% above baseline) at follow-up, 35+/-14 months after drug discontinuation. During CsA therapy, the mean level of serum creatinine had increased to 82+/-19 micromol/l (26% above baseline) at 6 months and to 87+/-22 micromol/1 (39% above baseline) at 42 months. The mean CsA dose had decreased from 3.1+/-0.9 mg/kg/day at 6 months to 1.9+/-0.8 mg/kg/day at 42 months. The absolute number of months that serum creatinine levels were > 30% above baseline was an independent predictor for a persistent increase of the serum creatinine after CsA discontinuation. More than 2 months with a serum creatinine increase of > or = 30% resulted in a higher percentage irreversible increase than for less than 2 months with a > or = 30% increase: 27 and 6%, respectively (P < 0.0001). CONCLUSION: Long-term low-dose CsA administration in RA patients was associated with an increase in serum creatinine which was partially irreversible after drug discontinuation. The increase in serum creatinine was completely reversible in the patient group that was treated according to the current guidelines for safe use of CsA.

Adolescent↗
PubMed1998

No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the cyclosporin A (CSA)-attributed risk of developing malignancies in general and malignant lymphoproliferative diseases (LPDs) and skin cancers in particular, as well as the CSA-attributed incidence of mortality in patients with rheumatoid arthritis (RA). METHODS: In a retrospective, controlled cohort study, the incidence of malignancies and mortality was evaluated in 208 CSA-treated patients with RA compared with 415 matched control patients with RA between 1984 and 1995. Patients were followed up for a median of 5.0 years (range 1.4-12.0). RESULTS: Forty-eight cases of malignancy (8 in the CSA group and 40 in the control group; relative risk [RR] 0.40, 95% confidence interval [95% CI] 0.19-0.84) were identified, of which 8 were malignant LPDs (2 CSA versus 6 control; RR 0.67, 95% CI 0.14-3.27) and 14 were skin cancers (2 CSA versus 12 control; RR 0.33, 95% CI 0.08-1.47). Seventy-three patients died (16 CSA versus 57 control; RR 0.56, 95% CI 0.33-0.95) due primarily to cardiovascular diseases (4 CSA versus 22 control; RR 0.36, 95% CI 0.13-1.04) or a malignancy (3 CSA versus 8 control; RR 0.67, 95% CI 0.18-2.43). Proportional hazards regression analysis with correction for potential confounding factors did not significantly change the results. CONCLUSION: The study findings suggest that CSA treatment in RA patients does not increase the risk of malignancies in general or the risk of malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable to that in matched control RA patients.

Adult↗
PubMed1998

Chylothorax or leakage of total parenteral nutrition?

The diagnosis chylothorax is based on a chemical analysis of the pleural effusion. According to the literature, this analysis can be rather straightforward, comprising measurements of triglycerides, chylomicrons, and cholesterol. In this report we present an autopsy case that alerted us to interpret these results critically. Although the laboratory tests of the pleural effusion in this patient with parenteral nutrition suggested chylothorax, additional tests (potassium (11.3 mmol.L(-1)) and glucose (128 mmol.L(-1)) proved otherwise. Comparison of the pleural effusion analysis and the content of the parenteral nutrition led to the final conclusion that the effusion was due to a leakage of parenteral nutrition instead of chylothorax. We therefore suggest adding glucose and potassium measurements to the biochemical work-up of a patient under suspicion of chylothorax.

Aged↗
PubMed1998

Combination therapy in recent onset rheumatoid arthritis: a randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine.

OBJECTIVE: To investigate whether there is interaction between chloroquine and cyclosporine (CyA) at the level of efficacy and toxicity in patients with recent onset rheumatoid arthritis (RA). METHODS: Eighty-eight patients with recent onset RA, who had shown a suboptimal clinical response on low dose chloroquine monotherapy, were randomly assigned to additional treatment with placebo, CyA 1.25 mg/kg/day, or CyA 2.50 mg/kg/day (fixed doses) for another 24 weeks. The tender joint count was the primary outcome assessment of efficacy and the serum creatinine of toxicity. The 1995 preliminary ACR response criteria for improvement were applied to evaluate individual clinical responses. RESULTS: Two patients in the placebo group (n = 29), 7 patients in the CyA 1.25 mg group (n = 29), and 8 patients in the CyA 2.50 mg group (n = 30) (p = 0.06) discontinued study medication prematurely for inefficacy or adverse events. The intention-to-treat analysis revealed that the tender joint count decreased 2.2 +/- 6.1 (mean +/- SD) joints in the placebo group, 2.2 +/- 6.6 joints in the CyA 1.25 mg group, and 5.0 +/- 5.8 joints in the CyA 2.50 mg group (p = 0.04). The 1995 preliminary ACR response criteria for clinical improvement were met by 8 (28%) patients in the placebo group, 10 (34%) patients in the CyA 1.25 mg group, and 15 (50%) patients in the CyA 2.50 mg group (p = 0.07). The serum creatinine increased 2 +/- 7 micromol/l in the placebo group, decreased 1 +/- 8 micromol/l in the CyA 1.25 mg group, and increased 10 +/- 15 micromol/l in the CyA 2.50 mg group (p < 0.001). CONCLUSION: The addition of low dose CyA is moderately effective in patients with early RA already treated with low dose chloroquine, but results in statistically significant renal function loss.

Adolescent↗
PubMed1996

Persistent CD3-crosslinking down-regulates interleukin-2 responsiveness in interleukin-2-competent cloned T cells: the possible involvement of protein kinase C.

To investigate the regulation of interleukin-2 (IL-2) responsiveness of T cells, a human CD4+ T-cell clone with constitutive expression of IL-2 receptors was stimulated with recombinant IL-2 (rIL-2) in the presence or absence of immobilized anti-CD3 monoclonal antibodies (alpha CD3imm MoAb). Incubation of T cells with alpha CD3imm MoAb decreased IL-2-induced proliferation which could not be ascribed to the modulation of IL-2 receptor expression nor to cell death. Phorbol-myristate-acetate (PMA), an activator of protein kinase C (PKC), also induced down-regulation of IL-2 responsiveness. The alpha CD3sol MoAb, inducing Ca(2+)-mobilization without activating PKC, did not inhibit IL-2 responsiveness whereas cyclosporine A (CsA), a drug that inhibits the Ca(2+)-dependent activation pathway, did not prevent the induction of IL-2 hyporesponsiveness induced by alpha CD3imm MoAb. It is concluded that modulation of IL-2 responsiveness of T cells via the T-cell receptor/CD3 complex (TCR/CD3) may be mediated by a PKC-activating signal.

Antibodies, Monoclonal↗
PubMed1996

Low dose cyclosporine in early rheumatoid arthritis: effective and safe after two years of therapy when compared with chloroquine.

Forty-four patients with early RA who had participated in a six months double-blind trial, comparing cyclosporine A (CsA) (n = 22) with chloroquine (Chl) (n = 22), were followed for a further 18 months irrespective of their treatment status. At two years follow up, the mean CsA dose was 2.7 +/- 1.1 mg/kg/day (n = 15) and the dose of Chl (n = 11) was 100 mg/day in every patient. Maximal difference in efficacy (represented by the percentage of patients who fulfilled the Paulus 50% response) was reached at one year (CsA group: 68% and Chl group: 36%; p = 0.07). At two years, the differences in efficacy and toxicity between the two groups had diminished. The conclusions of this follow-up study are: 1. maximal efficacy of low dose CsA in early RA patients is reached after one year of therapy. 2. CsA can maintain clinical efficacy and safety comparable to Chl for a period of at least two years.

Adolescent↗
PubMed1996

Longterm low dose cyclosporine in patients with rheumatoid arthritis: renal function loss without structural nephropathy.

OBJECTIVE: To investigate whether administration of low dose cyclosporine for 2 years induces structural changes in the kidneys of patients with rheumatoid arthritis (RA). METHODS: Renal biopsies were performed in 11 patients with RA who had been treated with cyclosporine [mean dose 3.3 mg/kg/day; mean maximum dose 4.4 (3.5-5.1) mg/kg/day; mean cumulative dose 2.8 (1.6-3.9) g/kg] [mean (range)] for a mean period of 26 (15-30) months. The renal biopsy specimens and specimens of autopsy material of 22 control patients with RA matched for age, disease duration, sex, and previous use of gold and/or D-penicillamine were scored by 2 renal pathologists according to a semiquantitative scoring system (absence of lesions to severe lesions). RESULTS: In the patients taking cyclosporine, creatinine clearance decreased from 111 ml/min before cyclosporine to 82 ml/min (-26%) after 24 months. Seven percent of the glomeruli in the renal biopsy specimens compared to 13% of glomeruli in the autopsy specimens showed obsolescence. Minimal arteriolopathy (one hyaline deposition in one arteriole) was detected in 3 biopsy specimens and in one autopsy specimen. Moderate and severe lesions were not seen. Tubular atrophy was common but mild in both the biopsy specimens (10/11 patients) and the autopsy specimens (16/22 patients). Five of 11 renal biopsy specimens and 13 of 22 autopsy specimens showed minimal to slight interstitial fibrosis. All biopsy specimens were classified as Group I (minimal lesions) according to the advisory board of nephropathologists. CONCLUSION: Longterm continuous treatment of RA with low dose cyclosporine does not result in more structural nephropathy than the disease process itself, in spite of substantial and persistent deterioration of the renal function.

Adult↗
PubMed1995

Relative bioavailability of a new oral form of cyclosporin A in patients with rheumatoid arthritis.

The relative bioavailability of cyclosporin A (CsA) from a new microemulsion oral formulation (NEO) and the currently used soft gelatine capsule (SGC) was determined at steady state in 12 patients with rheumatoid arthritis. The AUC(0,12 h) values of cyclosporin A were significantly greater after NEO than SGC (2873 +/- 848 ng ml-1 h (mean +/- s.d.) vs 2355 +/- 1128 ng ml-1 h; P = 0.02, 95% CI (confidence interval of the difference: 81 to 955 ng ml-1 h). Cmax values were significantly higher after NEO than after SGC (811 +/- 244 ng ml-1 vs 495 +/- 291 ng ml-1, P < 0.0001, 95% CI of the difference: 209 to 422 ng ml-1).

Aged↗
PubMed1995

Chloroquine inhibits T cell proliferation by interfering with IL-2 production and responsiveness.

Chloroquine (Chl) is an anti-rheumatic drug that is widely used in the treatment of rheumatoid arthritis (RA). It seems that T cells are important in the pathogenesis of RA, but it is not known whether Chl acts via inhibition of T cell function. We here present evidence that Chl, just like cyclosporine A (CsA), inhibits T cell proliferation as induced with immobilized alpha CD3 MoAb in a concentration-dependent manner, at least partly through interfering with the production of IL-2 protein and the induction of IL-2 mRNA. Furthermore, Chl impedes the responsiveness of T cell clones to IL-2 since (1) the inhibition of alpha CD3 MoAb-induced proliferation by Chl could not be reversed by rIL-2 and (2) Chl directly blocks IL-2-driven proliferation of cloned T cells. Chl appeared to interfere with the internalization (50% inhibition) and degradation (total blockade) of rIL-2. Finally, the combination of Chl and CsA synergistically inhibited T cell proliferation. We conclude that Chl may inhibit functional properties of human T cells, although the drug is 100- to 1000-fold less potent than CsA in inhibiting T cell proliferation and IL-2 production, respectively. It is speculated that the in vitro effects of Chl might be relevant in explaining the anti-rheumatic effect of this drug in patients with RA.

Antibodies, Monoclonal↗
PubMed1995

Antimalarial drug induced decrease in creatinine clearance.

OBJECTIVE: To confirm the antimalarial drug induced increase of creatinine to determine the factors contributing to this effect. METHODS: Patients with rheumatoid arthritis (RA) (n = 118) who have used or still use antimalarials (chloroquine or hydroxychloroquine). Serum creatinines prior to antimalarials and serum creatinines during antimalarials were recorded and the creatinine clearance was estimated. RESULTS: The mean creatinine clearance decreased from 99 ml/min to 92 ml/min (p < 0.001) after the start of antimalarial drugs. Fifty-five percent of the patients with chloroquine compared to 15% of the patients with hydroxychloroquine (chi 2 = 17.8; p < 0.001) had more than 10% decrease of the creatinine clearance. Age (beta = 0.004; p = 0.0002) and the kind of antimalarial (beta = 0.095; p = 0.0002) were strong independent predictors of the decrease of the creatinine clearance in the multiple regression analysis. For patients using chloroquine the mean age adjusted decrease of creatinine clearance was 11.2%. CONCLUSION: Antimalarials cause a significant reduction of the creatinine clearance. The use of chloroquine and older age were associated with decreased creatinine clearance. Whether antimalarials affect glomerular filtration or tubular excretion of creatinine remains to be investigated.

Adult↗
PubMed1994

A randomized, double-blind, 24-week controlled study of low-dose cyclosporine versus chloroquine for early rheumatoid arthritis.

OBJECTIVE: To investigate whether low-dose cyclosporin A (CSA) is safe and effective in comparison with chloroquine (CQ) in patients with early rheumatoid arthritis (RA). METHODS: We performed a randomized, double-blind study comparing CSA with CQ in patients with early RA (duration < 2 years) who had had active disease for at least 3 months. Forty-four RA patients with a mean disease duration of 6 months were randomly allocated to receive CSA (initial dosage 2.5 mg/kg/day, maintenance dosage 3.6 mg/kg/day) or CQ (initial dosage 300 mg/day, maintenance dosage 100 mg/day) for 24 weeks. RESULTS: Five patients (2 taking CSA and 3 taking CQ) discontinued the study prematurely. Intention-to-treat analysis disclosed a decrease in the swollen joint count by 7 in both groups. The erythrocyte sedimentation rate and C-reactive protein level did not change significantly. CSA and CQ were tolerated equally well, although mild paraesthesia occurred more frequently in the CSA-treated group. The serum creatinine level increased by 13 mumoles/liter (95% confidence interval [95% CI] 4, 22) in the CSA group and by 6 mumoles/liter (95% CI 1, 11) in the CQ group (difference not statistically significant). CONCLUSION: Both CSA and CQ are effective in alleviating the symptoms of active early RA. There is only slightly impaired renal function after 24 weeks of drug administration of either drug in patients with early RA.

Adult↗