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Biomedical subjects

Johannes W G Jacobs

Publications and source records attributed to Johannes W G Jacobs.

At least 19 recordsLinked to original sources
PubMed2006

Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis.

BACKGROUND: Treatment with glucocorticoids is associated with bone loss starting soon after therapy is initiated and an increased risk of fracture. METHODS: We performed a randomized, double-placebo, double-blind clinical trial of 18 months' duration among patients with a rheumatic disease who were starting glucocorticoids at a daily dose that was equivalent to at least 7.5 mg of prednisone. A total of 201 patients were assigned to receive either alendronate (10 mg) and a placebo capsule of alfacalcidol daily or alfacalcidol (1 microg) and a placebo tablet of alendronate daily. The primary outcome was the change in bone mineral density of the lumbar spine in 18 months; the secondary outcome was the incidence of morphometric vertebral deformities. RESULTS: A total of 100 patients received alendronate, and 101 received alfacalcidol; 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1 percent in the alendronate group (95 percent confidence interval, 1.1 to 3.1 percent) and decreased by 1.9 percent in the alfacalcidol group (95 percent confidence interval, -3.1 to -0.7 percent). At 18 months, the mean difference of change in bone mineral density between the two groups was 4.0 percent (95 percent confidence interval, 2.4 to 5.5 percent). Three patients in the alendronate group had a new vertebral deformity, as compared with eight patients in the alfacalcidol group (of whom three had symptomatic vertebral fractures) (hazard ratio, 0.4; 95 percent confidence interval, 0.1 to 1.4). CONCLUSIONS: During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced bone loss than was alfacalcidol. (ClinicalTrials.gov number, NCT00138983 [ClinicalTrials.gov].).

Aged↗
PubMed2006

Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo.

OBJECTIVE: In a previous clinical trial of patients with early rheumatoid arthritis (RA), it was determined that patients who received 10 mg of prednisone per day for 2 years had less radiographic joint damage compared with those who received placebo. Our goal was to investigate whether this beneficial effect persisted after the end of the trial. METHODS: A blinded assessment of radiographic joint damage was performed approximately 3 years after the end of the original 2-year study. Twenty-four patients from the original prednisone group (60%) and 28 patients from the original placebo group (68%) participated in this followup study. At the end of the original trial, prednisone dosages were tapered down in the prednisone group and stopped, if possible. Patients from the original prednisone group took prednisone during 35% of the followup period (approximately 1 year) at a mean daily dose of approximately 5 mg. Two patients from the original placebo group started taking prednisone during followup. Radiographs of the hands and feet were scored according to the van der Heijde modification of the Sharp method. RESULTS: During 3 additional years of followup, radiographic scores showed significantly less progression in the original prednisone group than in the original placebo group. Radiographic damage in the original prednisone group did not show an accelerated rate of progression during the followup period. CONCLUSION: The inhibition of radiographic joint damage in patients with early active RA treated with 10 mg of prednisone per day for 2 years seems to persist after the end of prednisone therapy.

Arthritis, Rheumatoid↗
PubMed2006

Are glucocorticoids DMARDs?

Disease modifying antirheumatic drugs (DMARDs) are drugs used in rheumatoid arthritis (RA) to control the disease and to limit joint damage and improve long-term outcome. The last decade evidence has accumulated that suggests that low dosages of glucocorticoids are indeed able to control the disease and limit the destruction. This role is especially present in early disease and in combination with other drugs. The evidence is carefully evaluated and discussed. The ultimate conclusion is that indeed glucocorticoids are DMARDs and are especially useful in early RA.

Antirheumatic Agents↗
PubMed2006

Revisiting the toxicity of low-dose glucocorticoids: risks and fears.

We have recently participated in a careful literature search and critical evaluation of glucocorticoids, and we have revised the side-effects data of four recent controlled trials of low-dose glucocorticoids (GCs) in rheumatoid arthritis. The toxicity profile stands out as remarkably more benign than expected from most textbook recommendations. Data regarding low-dose therapy are scarce and of low quality, as no controlled trials have been designed to specifically address toxicity. Common fears of GC toxicity seem to originate from an excessive weight on anecdotal data and observations with high doses, as in organ transplantation. There is now evidence that mechanisms of action of GCs vary considerably according to the dose, thus allowing the possibility of a different toxicity profile. Data from recent controlled trials are quite reassuring, overall. Certainly, risks and benefits of GCs need to be carefully weighed in every patient. But we need to make a clear distinction between established risks and unchecked fears while trying to get the best result for our patient. Clearly, there is a need for studies that are appropriately designed to address the toxicity of GCs and to avoid the risk of "throwing out the baby with the bath water."

Arthritis, Rheumatoid↗
PubMed2005

Is radiation synovectomy for arthritis of the knee more effective than intraarticular treatment with glucocorticoids? Results of an eighteen-month, randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: To compare the clinical efficacy and safety of radiation synovectomy (RSO) with intraarticular (IA) yttrium-90 plus glucocorticoids (GCs) with the efficacy and safety of IA placebo yttrium plus GCs and to identify parameters that predict efficacy. METHODS: The knees of 97 patients with persistent arthritis despite outpatient treatment with IA GCs (n = 113 knees), were treated with either IA (90)Y plus GCs (50%) or IA placebo yttrium plus GCs (50%), followed by 3 days of bed rest in the hospital clinic, with splinting of the treated knee. Predominant diagnoses were undifferentiated arthritis (39%) and rheumatoid arthritis (32%). The clinical effect of therapy was assessed at 6 months using a composite change index (CCI; range 0-12). The primary outcome measure was the response rate (i.e., the percentage of joints with a CCI > or =6). Knees with persistent arthritis after 6 months underwent crossover therapy (51% of the (90)Y plus GCs group versus 45% of the placebo plus GCs group). Adverse effects and radiologic damage during followup were documented. RESULTS: Neither the response rate (48% in both groups), the mean CCI, nor the duration of remission was significantly different between groups. No clinically relevant short-term adverse effects were observed, except for progression of radiologic damage in 34% of the (90)Y plus GCs group versus 28% of the placebo plus GCs group (knee prosthesis placement in 8% versus 1%). The functional and radiologic status at study entry predicted the clinical effect. CONCLUSION: Treatment with (90)Y plus GCs with bed rest and splinting is not superior to IA GCs with bed rest and splinting. Over the short term, both treatments appeared to be safe, although a negative effect of (90)Y on cartilage and bone cannot be ruled out. Thus, it appears that RSO with (90)Y should no longer be considered the treatment of first choice for persistent arthritis of the knee.

Adult↗
PubMed2005

Rheumatoid arthritis: neuroendocrine immune integrated physiopathogenetic perspectives and therapy.

Current concepts of neuroendocrine immune (NEI) aspects of rheumatoid arthritis (RA) are reviewed and recent clinical trials of glucocorticoids and sex steroids are summarized. A novel physiopathogenetic perspective is presented. Data are provided of amplified NEI interactions and dysregulation, many years before symptomatic onset of RA. Chronic imbalances between the NEI, vascular endothelial, neural, and other vital counterregulatory intertwined networks are proposed to cause RA and influence its disease activity. Future research may reveal means of diminishing the onset risk as well as disease activity of RA by controlling these imbalances of NEI and other vital networks.

Adrenal Cortex Hormones↗
PubMed2005

Measurement of joint space width and erosion size.

Measurement of radiographic abnormalities in metric units has been reported by several investigators during the last 15 years. Measurement of joint space in large joints has been employed in a few trials to evaluate therapy in osteoarthritis. Measurement of joint space width in small joints has been reported by several investigators but has not yet found a place in clinical trials in rheumatoid arthritis or osteoarthritis. We review methods for measuring joint space width in finger, toe, and wrist joints; special attention is given to how the joint edges are found, the method used to measure distance between joint margins, size of an area of the sampled joint, and reproducibility of measurements. Methods for measurement of erosion size, which have had less attention, are briefly discussed.

Arthrography↗
PubMed2004

The clinical effect of glucocorticoids in patients with rheumatoid arthritis may be masked by decreased use of additional therapies.

OBJECTIVE: Our previous analysis of patients with early active rheumatoid arthritis (RA) treated with prednisone or placebo revealed the following discrepancy: although a significant retardation of joint damage was observed in the prednisone group compared with the placebo group, no differences in clinical variables between the 2 groups were observed, due to greater use of additional therapy in the placebo group. We sought to investigate whether this discrepancy would extend to variables of well-being. METHODS: We conducted a double-blind, randomized, placebo-controlled clinical trial of prednisone (10 mg) in patients with RA; the duration of the study was 2 years. Following the placebo-controlled trial, a 1-year open-label followup study was conducted in 81 patients with early (</=1 year) active, previously untreated RA. Forty-one patients were allocated to receive oral prednisone, 10 mg/day, and 40 patients were assigned to the placebo group. Analgesics, nonsteroidal antiinflammatory drugs (NSAIDs), local injections of a glucocorticoid (only when absolutely necessary), and use of physiotherapy were allowed in both groups. After 6 months, sulfasalazine (2 gm/day) could be prescribed as rescue therapy in both groups. At the beginning of the study and every 6 months thereafter, 2 questionnaires (the VDF [Dutch version of the Health Assessment Questionnaire] and the IRGL [Dutch version of the Arthritis Impact Measurement Scales]) were administered. A visual analog scale (VAS) for morning pain was administered every 3 months. Disease activity and radiologic scores were assessed. RESULTS: VDF scores in the 2 groups were not statistically significantly different. No statistically significant differences between groups were observed in almost all parameters of the IRGL. In the prednisone group (and only at 6 months), the VAS scores for morning pain and general well-being showed improvement comparable with the transient improvement in some of the disease activity variables. In the prednisone group, use of NSAIDs, analgesics, local injections of glucocorticoids, and physiotherapy sessions was approximately 50% that in the placebo group. CONCLUSION: Although significant retardation of joint damage in the prednisone group indicates better disease control, no differences between the groups for variables of well-being were found. This discrepancy may be attributed to greater use of additional therapy in the placebo group. In future clinical trials, the use of additional therapies should be taken into account when analyzing the differences in effect between drugs.

Activities of Daily Living↗
PubMed2004

Radiation synovectomy of the ankle with 75 MBq colloidal 186rhenium-sulfide: effect, leakage, and radiation considerations.

OBJECTIVE: In a retrospective study we evaluated the effect, duration of effect, and safety of radiosynoviorthesis of the ankle in patients with persistent synovitis, refractory to disease modifying antirheumatic drugs (DMARD) and intraarticular glucocorticoid injections. We estimated leakage and dose to target and non-target organs. METHODS: Radiation synovectomy was performed by injection of 75 MBq 186rhenium colloid and 20 mg triamcinolone-hexacetonide mixed in a volume of about 1.5 ml. About 24 hours after injection, leakage of the radionuclide was measured with a single-head gamma camera, with views of the ankle joint, regional (inguinal) lymph nodes, and liver. Leakage was expressed as counts in the target region of interest corrected for background relative to total counts corresponding with percentage of injected dose. The effect of radiosynoviorthesis was scored into 3 categories: (1) No effect, i.e., persistent synovitis or only minimal reduction of swelling and/or pain, or the need of intraarticular glucocorticoid injection within 3 months or arthrodesis of the treated joint within 6 months. (2) Moderate effect, i.e., significant reduction of swelling, pain, and improvement of function. (3) Good effect, i.e., complete or almost complete remission of synovitis. RESULTS: The mean age of patients (28 women, 12 men) at the time of treatment was 58 years (range 33-76); 54 consecutive procedures in ankles of the 40 patients were evaluated. No effect was found in 12 of 54 (22%) treated joints; moderate effect in 12 (22%), with a mean duration of effect of 34 months (range 12-49); and good effect in 30 (56%), with a mean duration of effect of 41 months (range 21-75). Mean effect-duration did not differ significantly between the moderate and good effect groups. Mean leakage did not differ significantly between the effect groups. CONCLUSION: Radiation synovectomy of the ankle is a safe and effective treatment in persistent synovitis, although all patients eventually experienced recurrence of arthritis.

Adult↗
PubMed2003

Five-year followup of rheumatoid arthritis patients after early treatment with disease-modifying antirheumatic drugs versus treatment according to the pyramid approach in the first year.

OBJECTIVE: To evaluate whether the clinical advantages observed after 1 year in a randomized controlled clinical trial, in which 2 treatment strategies were compared (the early disease-modifying antirheumatic drug [DMARD] approach versus the pyramid approach), persist after 5 years. METHODS: In this study, 238 patients with recently diagnosed rheumatoid arthritis (RA) were randomized to either the pyramid group (n = 56) or the early DMARD group (n = 182). Patients assigned to the pyramid group received nonsteroidal antiinflammatory drugs for at least 1 year after inclusion (the mean +/- SD lag time until first prescription of a DMARD was 14 +/- 9 months). Patients in the early DMARD group were treated with a DMARD immediately after inclusion. RESULTS: After 5 years, data were available for 44 patients in the pyramid group (79%) and 145 patients in the early DMARD group (80%). No prolongation of the clinical advantages in favor of the early DMARD group, as observed after the first year, was demonstrated. Nevertheless, a significantly shorter delay time until complete response and a higher number of patients with overall clinically relevant improvement at several assessment points were observed in the early DMARD group compared with the pyramid group. CONCLUSION: The clinical results in favor of the early DMARD group, as observed after the first year, were not as evident after 5 years. This indicates that a more aggressive treatment approach in early RA is required, and that treatment should be continued for a prolonged period of time, in order to maintain the advantages obtained in the first year.

Adult↗
PubMed2003

Pain coping and social support as predictors of long-term functional disability and pain in early rheumatoid arthritis.

Pain-related avoidance factors and social resources, as assessed by pain coping and social support, are supposed to have lasting effects on functional disability and pain in chronic pain disorders. As a follow-up to a prospective study demonstrating short-term effects after one year (Behaviour Research and Therapy, 36, 179-193, 1998), the role of pain coping and social support at the time of diagnosis was investigated in relationship to the long-term course of functional disability and pain after three and five years in 78 patients with rheumatoid arthritis (RA), taking into account personality characteristics of neuroticism and extraversion, clinical status and use of medication. In line with findings at the one-year follow-up, results showed that more passive pain coping predicted functional disability at the three-year, but not the five-year follow-up. In addition, low levels of social support at the time of diagnosis consistently predicted both functional disability and pain at the three and five-year follow-ups. Results indicate that pain coping and social support, assessed very early in the disease process, can affect long-term functional disability and pain in RA, and suggest that early interventions focusing on pain-related avoidance factors and social resources for patients at risk may beneficially influence long-term outcomes in RA.

Adaptation, Psychological↗
PubMed2003

Stress-vulnerability factors as long-term predictors of disease activity in early rheumatoid arthritis.

OBJECTIVE: Stress-vulnerability factors were studied for their ability to predict long-term disease activity in early rheumatoid arthritis. METHODS: In a prospective study involving 78 recently diagnosed rheumatoid arthritis (RA) patients, the role of personality characteristics (neuroticism, extraversion), physical and psychological stressors (chronic, disease-related stressors of functional disability, pain, disease impact on daily life, as well as major life events), coping and social support at the time of diagnosis was examined to predict changes in clinical indicators of disease activity 1, 3 and 5 years later. RESULTS: While stress-vulnerability factors failed to predict disease activity at the 1-year follow-up, disease activity at the 3- and 5-year follow-ups was predicted by coping and social support at the time of diagnosis, after adjusting for disease activity at first assessment, other biomedical and psychosocial factors and use of medication. Low levels of social support predicted increased disease activity at the 3-year follow-up, and high avoidance coping predicted increased disease activity at the 3- and 5-year follow-ups. CONCLUSION: Findings indicate the potential prognostic value of avoidance coping and social support for the long-term course of disease activity in early RA and suggest that the effects of these vulnerability factors predominantly operate in the long term.

Activities of Daily Living↗
PubMed2002

Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis. OBJECTIVE: To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis. DESIGN: 2-year randomized, double-blind, placebo-controlled clinical trial. SETTING: 2 outpatient rheumatology clinics. PATIENTS: 81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs. INTERVENTION: 41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti-inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication. MEASUREMENTS: Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months. RESULTS: In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group. CONCLUSIONS: Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

Administration, Oral↗
PubMed2002

Evaluation and management of endocrine dysfunction in fibromyalgia.

Fibromyalgia-like symptoms such as muscle pain and tenderness, exhaustion, reduced exercise capacity, and cold intolerance, resemble symptoms associated with endocrine dysfunction like hypothyroidism, and adrenal or growth hormone insufficiency. To investigate the potential of management of endocrine abnormalities for relieve of symptoms of patients with fibromyalgia, we reviewed experimental and clinical studies of endocrine functioning and endocrine treatment. Serum GH, androgen, and 24-hour urinary cortisol levels of patients with fibromyalgia tend to be in the lower part of the normal range, while serum levels of thyroid hormone, female sex hormones, prolactin, and melatonin are normal. With exception of GH, these conclusions are based on studies in small samples. With respect to dynamic responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis, the dexamethasone suppression test and stimulation with ACTH show normal results, while patients show marked ACTH hypersecretion in response to severe acute stressors, perhaps indicative of chronic CRH hyposecretion. This finding and slightly altered responsiveness of growth hormone, thyroid hormone, and prolactin in pharmacologic stimulation tests suggest a central rather than peripheral origin of endocrine deviations. Because hormone level deviations were not severe, occurred in subgroups of patients only, and few controlled clinical trials were performed, there is--unless future research shows otherwise--little support for hormone supplementation as a general therapy in the common patient with fibromyalgia. In patients with clinically overt hormone deficiency, hormonal supplementation is an option. In patients with hormone levels that are in the lower part of the normal range, interventions aimed at pain, fatigue, sleep or mood disturbance, and physical deconditioning may indirectly improve endocrine functioning.

Endocrine System Diseases↗
PubMed2002

Glucocorticoid receptor downregulation in early diagnosed rheumatoid arthritis.

In patients with rheumatoid arthritis (RA) with a mean duration of six years, glucocorticoid receptor (GR) downregulation has been reported without change in cortisol levels. This phenomenon might play a role in the etiopathogenesis of RA. If this is the case, GR downregulation should also be found in early-diagnosed RA. We compared GR expression and cortisol levels of early RA patients with those of sex and age matched healthy controls. In early (disease duration less than one year) RA patients (52F/29M; mean [SE] age 63 +/- 2 years) and in 39 controls (23F/16M; mean age 63 +/- 2 years) blood samples were taken between 8:00 and 10:00 a.m. GR expression (GR number), cortisol levels (fluorescence polarization immunoassay, FPIA), ESR, CRP, and the presence of swollen and painful knees were determined. RA was diagnosed according to the ACR classification criteria. In early RA a significantly lower GR expression was found compared to controls. Interestingly, cortisol levels were also significantly lower. Both findings were due to the observed differences in the female population. In the male population no differences were found. No correlations were found among parameters of disease activity, nor was there a relation between GR expression and serum cortisol levels. In female patients with early-diagnosed RA a decrease in glucocorticoid receptor expression was found as well as a decrease in cortisol levels. Since normal glucocorticoid receptor expression was found in the male population with early-diagnosed RA, it remains questionable if glucocorticoid receptor expression is causally involved in pathogenesis of RA.

Arthritis, Rheumatoid↗