Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.

BACKGROUND: Tumour necrosis factor (TNF)-inhibiting therapy increases the risk of serious infections in rheumatoid arthritis (RA). However, it is not clear whether this risk differs between TNF inhibitors. OBJECTIVE: To analyse whether the risk of serious infections in patients with RA treated with an anti-TNF inhibitor is different for adalimumab, infliximab and etanercept. METHODS: Data from the Dutch RA monitoring registry were used. Incidence rates were calculated from the observed number of first serious infections and follow-up time up to 5 years. A Cox proportional hazards model with time-to-first-serious infection was used to estimate risk differences among the anti-TNF treatment groups, with correction for confounders. RESULTS: The unadjusted incidence rate of a first serious infection in patients with RA per 100 patient-years was 2.61 (95% CI 2.21 to 3.00) for adalimumab, 3.86 (95% CI 3.33 to 4.40) for infliximab and 1.66 (95% CI 1.09 to 2.23) for etanercept. Age, year of starting anti-TNF therapy, comorbidities at baseline and disease activity score 28 over time were included as confounders. No difference in risk for serious infections was found between adalimumab and infliximab with an adjusted HR (adjHR) of 0.90 (95% CI 0.55 to 1.48). The risk of serious infections was significantly lower in etanercept than in both infliximab (adjHR=0.49 (95% CI 0.29 to 0.83)) and adalimumab (adjHR=0.55 (95% CI 0.44 to 0.67)). CONCLUSIONS: The risk of serious infections in patients with RA treated with adalimumab or infliximab was similar, while the risk of serious infections in patients with RA treated with etanercept was lower than with both adalimumab and infliximab.

Fatigue in patients with systemic lupus erythematosus: the role of dehydroepiandrosterone sulphate.

Fatigue is a major problem in systemic lupus erythematosus (SLE), but the physiological substrate of this fatigue is largely unclear. To examine if low levels of dehydroepiandrosterone (DHEA) and its sulphate DHEAS play a role in SLE fatigue, we compared: 1) DHEAS levels and fatigue between 60 female patients with SLE with low disease activity (31 using, 29 not using prednisone) and 60 age-matched healthy women, and 2) fatigue between patients with SLE with low and normal DHEAS levels. Serum DHEAS levels were determined with an Advantage Chemiluminescense System. The Multidimensional Fatigue Inventory (MFI) was used to assess fatigue. Patients were more fatigued (p ≤ 0.001) than healthy women and more often had below-normal DHEAS levels (p < 0.001). Patients using prednisone with low and normal DHEAS levels reported a similar level of fatigue (p ≥ 0.39). Patients with low DHEAS levels not using prednisone reported less fatigue than those with normal DHEAS levels (p ≤ 0.03). Thus, our results indicate that low DHEAS levels in SLE are not - or even inversely - related to fatigue. After our previous finding that DHEA administration does not reduce fatigue, this result further indicates that low serum DHEA(S) levels alone do not offer an explanation for SLE fatigue.

Serum dehydroepiandrosterone sulphate levels and laboratory and clinical parameters indicating expression of disease are not associated with fatigue, well-being and functioning in patients with primary Sjögren's syndrome.

OBJECTIVES: The aim of this study was to compare serum dehydroepiandrosterone sulphate (DHEAS) levels and clinical and laboratory parameters reflecting expression of disease between female patients with primary Sjögren's syndrome (pSS) and age-matched healthy women and to examine in pSS patients the correlation of these variables with fatigue, well-being, and functioning. METHODS: Comparisons were made between 60 female pSS patients and 60 age-matched healthy women. We assessed questionnaire scores of general fatigue, depressed mood, mental wellbeing, and physical functioning, tear production (Schirmer I test), tender point counts, serum DHEAS level, haemoglobin concentration, erythrocyte sedimentation rate, and serum immunoglobulin G. RESULTS: As compared to healthy participants, patients had more fatigue and depressed mood, reduced well-being and functioning, more dryness and pain, lower serum DHEAS levels, and more expression of disease as reflected by laboratory assessments (p≤0.001). In pSS patients, fatigue, well-being, and functioning correlated with tender point counts, but not with the extent of dryness and also not with laboratory assessments including serum DHEAS levels. CONCLUSIONS: The high prevalence of fatigue and reduced functioning in pSS patients might suggest a mediating role of generalised autoimmune processes. In the present study, clinical observations and laboratory assessments are not correlated with persistent fatigue and reduced functioning. Our results suggest that treatment of fatigue, well-being, and functioning, should target other variables than those examined in this study, preferably psychological variables or perhaps specific immunologic parameters.

Variability of fatigue during the day in patients with primary Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis.

OBJECTIVES: Fatigue is a common complaint of patients with primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). The aim of this study was to examine and compare in patients with these diseases the course of fatigue within the first hour after awakening and during the day, and to examine sleep disturbance as a potential determinant of fatigue. METHODS: Eight repeated measurements at 5 fatigue dimensions were assessed on 2 consecutive days in the natural environment of female patients with pSS (n=29), SLE (n=23), RA (n=19), and healthy women (n=52). Sleep disturbance of the previous night was assessed. Fatigue levels and the change of fatigue after awakening and during the day were analysed with analyses of variance (adjusted for age). RESULTS: The patients showed significantly elevated levels at all fatigue dimensions as compared to healthy participants. Fatigue levels decreased in the first hour after awakening in patients with SLE and RA, but increased or did not change in patients with pSS. Fatigue progressively increased during the remainder of the day for all patient groups. Sleep disturbance correlated with overall fatigue levels, but hardly with the change of fatigue within the first hour after awakening. CONCLUSIONS: Our study confirms the presence of increased fatigue in patients with pSS, SLE, and RA. Patients with pSS failed to show a decrease in fatigue in the first hour after awakening. Future research should examine the causes of this difference in fatigue after awakening.

Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial.

OBJECTIVE: Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA administration on fatigue, well-being and functioning in women with inactive SLE. METHODS: In a double-blind, randomised, placebo-controlled study, 60 female patients with inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being and physical functioning. Assessments were made before treatment, after 3, 6 and 12 months on medication, and 6 months after cessation of treatment. RESULTS: Patients from the DHEA and placebo group improved on general fatigue (p<0.001) and mental well-being (p=0.04). There was no differential effect of DHEA. The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA (p=0.04). CONCLUSIONS: The trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE. Clinical Trials Registration Number NCT00391924.

Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjögren syndrome: a randomised controlled trial.

OBJECTIVE: Dehydroepiandrosterone (DHEA) administration has been reported to improve fatigue, psychological distress, and physical disability. These are common features of primary Sjögren syndrome (pSS). We investigated the effects of DHEA administration on fatigue, well-being, and functioning in women with pSS. METHODS: In a double-blind, randomised placebo-controlled clinical trial, 60 female patients with pSS received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being, and physical functioning. In addition, pain, sicca complaints and disease activity parameters were measured. Patients were assessed before treatment, after 3, 6, and 12 months on study medication, and 6 months after cessation of treatment. RESULTS: Patients from both the DHEA- and placebo-treated group improved on general fatigue (p<0.001), mental well-being (p = 0.04), and depressive mood (p = 0.008). Physical functioning did not change (p = 0.44). Of the secondary outcome variables, complaints of a dry mouth diminished during treatment in both groups (p = 0.006), the erythrocyte sedimentation rate showed a decrease for the DHEA group (p = 0.02), and complaints of dry eyes improved in the placebo group (p = 0.01). The belief to have used DHEA was a stronger predictor for improvement of fatigue and well-being than the actual use of DHEA. CONCLUSIONS: Our study does not support a superior effect of DHEA over placebo in female patients with pSS. Both DHEA and placebo induce improvement of fatigue and well-being. This may suggest possibilities for cognitive behavioural interventions.

The effect of dehydroepiandrosterone on lumbar spine bone mineral density in patients with quiescent systemic lupus erythematosus.

OBJECTIVE: Because dehydroepiandrosterone (DHEA) is an adrenal steroid hormone with weak intrinsic androgenic properties that can be converted in peripheral tissues into more potent sex hormones, one might expect a positive effect of DHEA on bone mineral density (BMD). We evaluated the effects on lumbar BMD of oral DHEA, 200 mg/day, for 1 year in female patients with quiescent systemic lupus erythematosus (SLE). METHODS: The study subjects were 60 women with SLE. All participants gave informed consent to participate in a double-blind, placebo-controlled study on the effects of DHEA on fatigue and general well-being. BMD was measured with dual-energy x-ray absorptiometry (DEXA) at baseline and after 12 months. RESULTS: Fifty-eight patients (mean age 42.6 years) could be evaluated; 2 patients (both in the DHEA group) refused to undergo DEXA a second time. In premenopausal women, DHEA did not influence BMD significantly. There was a significant increase in BMD with use of DHEA in postmenopausal women who were not receiving bisphosphonates or estrogen-containing medications. This increase was not observed in the group receiving placebo. CONCLUSION: In premenopausal women with quiescent SLE, use of DHEA does not have a significant effect on BMD. DHEA may increase BMD in postmenopausal SLE patients if they are not already protected from bone loss by use of estrogens or bisphosphonates. Small numbers, due to the absence of stratification for menopausal status, and the use of antiresorptive agents at randomization preclude firmer conclusions based on the results of this study.

Serum cytokine levels related to multiple dimensions of fatigue in patients with primary Sjogren's syndrome.

OBJECTIVE: To test whether serum levels of selected cytokines relate to different dimensions of fatigue in patients with primary Sjögren's syndrome (pSS). METHODS: Sixty female patients with pSS filled out a questionnaire to assess multiple dimensions of fatigue. Scores were compared with values in a population based control group (n = 139). Levels of interleukin (IL)1beta, IL2, IL6, IL10, and tumour necrosis factor alpha were measured in serum with commercial sandwich ELISAs. The relationship between self reported dimensions of fatigue and these serum cytokine levels was determined. RESULTS: Patients with pSS had high scores at all dimensions of fatigue (p<0.001): general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Fatigue levels were not related to serum cytokine levels. The incidental finding that reduced motivation was higher in patients with detectable serum levels of IL10 (p = 0.04) disappeared after correction for multiple testing. CONCLUSION: Fatigue is prominent in patients with pSS and involves all dimensions of fatigue. The findings do not suggest a widespread effect of circulating cytokines on multiple aspects of fatigue.

PTU-associated cutaneous vasculitis with ANCA anti-MPO and anti-PR3 antibodies.

A 36-year-old woman presented at our clinic with symmetrical, tender, palpable purpuric lesions on her lower legs and buttocks after restarting PTU therapy for relapsing Graves' disease. PTU-induced vasculitis was diagnosed with remarkable ANCA anti-MPO and anti-PR3 antibody positivity. The purpuric skin lesions resolved immediately after discontinuation of the drug and the ANCA titres lowered. In the presence of activated neutrophils, PTU could induce a high cytotoxity and injure the vessel walls. Treatment of choice is discontinuation of the drug. Sometimes more aggressive therapy as cyclophosphamide or plasmapheresis is warranted.

Fatigue in daily life in patients with primary Sjögren's syndrome and systemic lupus erythematosus.

Fatigue is a well-recognized complaint with major impact on daily life in primary Sjögren's syndrome (PSS) and systemic lupus erythematosus (SLE). Previous research has not taken into account several crucial aspects of fatigue. This study examined various aspects of fatigue in the daily life of patients with PSS and SLE and in healthy controls. We compared age-adjusted, repeated measurements of fatigue across the day of female patients with SLE (n = 20, mean age 43.4 +/- 11.3), with PSS (n = 28, mean age 53.7 +/- 13.9) and healthy participants (n = 30, mean age 50.5 +/- 13.4). General and physical fatigue was significantly higher in patients than in healthy participants. Groups did not differ with respect to average levels of reduced motivation or mental fatigue. Both general and physical fatigue and reduced activity varied significantly during the day. Adjusting for depressive symptoms, groups showed significantly different time courses during the day. In healthy participants and patients with SLE, fatigue first decreased and then increased, whereas a rather opposite course-at least for the first part of the day-was observed in patients with PSS. Using an ecologically valid assessment method, we demonstrated substantially higher levels of daily fatigue in SLE and PSS patients as compared to healthy participants, thereby jeopardizing these patients' quality of life. The effect of disease on variations in fatigue over the day should be the subject of further inquiry, especially as it might clarify underlying mechanisms.

Influenza virus vaccination and booster in B-cell chronic lymphocytic leukaemia patients.

Background: Influenza vaccination is recommended for patients with B-cell chronic lymphocytic leukaemia (CLL). Because response rates are often low, we decided to evaluate antibody response to single and booster vaccinations with influenza A and B virus vaccine in these patients. Methods: Twenty patients with B-CLL received two subunit virus vaccine injections 21 days apart. Antibody titres were determined before and 21 days after the single and booster vaccinations. The serological response was expressed using the following criteria: (1) response rate, i.e. the proportion of subjects with at least a 4-fold titre increase; (2) the protection rate, i.e. the proportion of subjects exceeding the threshold of 100 (influenza A) or 200 (influenza B); and (3) the mean fold increase (MFI), i.e. the difference between the log-adjusted geometric mean titres of pre- and post-vaccination sera. Results: Response rates were 5% for influenza A and 15% for B after the single vaccination and 15% for A and 30% for B after the booster vaccination. Protection rates were 0% for influenza A and 25% for B after the single vaccination; they were 5% (H1N1) and 10% (H3N2) for influenza A and 30% for B after the booster. The MFI+/-S.D. (range) after the booster vaccination was 0.26+/-0.33 (0-1.00), 0.17+/-0.34 (0-1.00) and 0.35+/-0.34 (0-1.20) for H1N1, H3N2 and influenza B, respectively. Conclusion: In this study with B-CLL patients, immune response to influenza vaccination was poor. Thus, single and booster vaccinations with influenza virus vaccine do not appear to be of great value to patients with B-cell CLL.

Antibody responses to pneumococcal and haemophilus vaccinations in patients with B-cell chronic lymphocytic leukaemia.

Although vaccination against Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae type b (Hib) is recommended for immunocompromised patients, such as patients with B-cell chronic lymphocytic leukaemia (B-CLL), its protective effect is questionable. We studied antibody responses to pneumococcal polysaccharide vaccine (Pneumovax-23) and to conjugated H. influenzae type b-vaccine (Act-Hib) in 25 patients with B-CLL. After vaccination, the number of patients with antibody levels in the protective range against pneumococcal serotypes and H. influenzae b increased from 9 (38%) to 12 (50%) of 24 patients and from 8 (35%) to 11 (48%) of 23 patients, respectively. The patients with adequate antibody response to Pneumovax-23 and Act-Hib had significantly less advanced stages of B-CLL, higher gammaglobulin levels, total IgG-levels and IgG-subclasses 2 and 4 levels, and lower levels of soluble CD23. Consequently, vaccination with these vaccines should be given as soon as the diagnosis of B-CLL is made, early in the course of the disease with determination of post-vaccination antibody levels.

Totally implantable venous access devices: evaluation of complications and a prospective comparative study of two different port systems.

BACKGROUND: Totally implantable venous access devices (TIVADs) are valuable instruments in case prolonged intravenous therapy is required, but implantation and use of these devices are associated with complications. The purpose of this study was to evaluate perioperative and long-term complications associated with TIVADs. In addition, we compared two different types of TIVADs with respect to implantation, care protocol and patients' comfort. METHODS: In a retrospective study perioperative and long-term complications in a general oncology population were analysed. In a prospective randomized study comparison of two types of TIVADs was carried out. RESULTS: Perioperative complications occurred in 27 (21.4%) of 126 implanted TIVADs: catheter malposition (16.7%) in 21 patients, pneumothorax (0.8%) in one and haemorrhage (4.0%) in five. Long-term complications appeared in 31 (25.2%) out of 123 TIVADs: thrombosis in 9 (7.3%), especially associated with malposition of the tip of the catheter; infection in 10 (8.1%); extravasation in 2 (1.6%); migration of the catheter tip in 6 (4.8%); pain at reservoir in 3 (2.4%) and inaccessibility of the port in 1 (0.8%). No significant differences were found with respect to implantation, care accessibility and patients' comfort between the two TIVADs. CONCLUSIONS: The use of TIVADs is associated with some risk of serious perioperative and long-term complications. In case of thrombotic complications these systems can be saved with appropriate treatment. Correct positioning of the catheter tip is essential to prevent thrombotic complications. In case of TIVAD-related infectious complications, the possibility of saving the TIVAD depends on the causative microorganism and type of infection. Furthermore, to increase patients' satisfaction with TIVADs they should be well informed about the surgical procedure and possible disadvantages of these devices.

[Scoliosis studies with low-dose X-rays]. / Skoliosestudies met lae X-straaldosis.

A modification of the Oxford technique for the radiological examination of scoliotic curvatures in school-children has been devised. Satisfactory image quality is achieved in this way and the radiation dose to patients, despite examinations every 3 months, is only a fraction of the maximum permissible level for radiation workers. The method is simple. Conventional X-ray equipment can be employed.