OBJECTIVE:The objectives of this study were to explore the needs of patients with rheumatoid arthritis (RA) regarding support for medication use and to gain insight into their perspective on the suitability of eHealth technologies to address these needs.METHODS:Three focus groups were conducted with 28 patients with RA. Audio recordings made during the focus groups were transcribed verbatim. Two researchers independently performed an inductive, thematic analysis on the data (ie, the transcripts and field notes).RESULTS:The following three themes that described support needs of patients with RA for medication use were identified in the data: 1) informational support; 2) practical support; and 3) emotional support. Informational support reflected the provision of information and facts, including advice, suggestions, and feedback from health care providers. Practical support included the reinforcement of practical skills as well as the provision of medication aids and pharmacy services. Emotional support reflected a trusted patient-health care provider relationship, characterized by good communication. Although potential advantages of eHealth technologies to address the patients' support needs were recognized, concerns over matters such as personal interaction with health care providers, privacy and data security, and the quality and reliability of online information were prevalent.CONCLUSION:Patients with RA have informational, practical, and emotional support needs for medication use. Informational support seems to be most important. From the patients' perspective, eHealth technologies may have the potential to address these needs. However, these technologies are regarded as a complement to, rather than a replacement of, current practices.

Objective. Stress is one of the factors that may exacerbate the progression of chronic inflammatory diseases such as RA and psoriasis. We exploratively compared the effects of acute stress on levels of circulating cytokines involved in disease progression and/or the stress response in patients with RA, patients with psoriasis and healthy subjects. Methods. Patients with RA, patients with psoriasis and healthy controls underwent a standardized psychosocial stress test (Trier Social Stress Test). Levels of circulating cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IFN-γ and TNF-α) were measured before and after the stress test. Results. The baseline levels of all cytokines, except IL-8, were significantly higher in patients with RA. After correction for baseline levels, patients with RA showed higher stress-induced levels of IL-1β and IL-2 than patients with psoriasis and healthy controls. Conclusion. The results suggest that patients with RA have a different immune response to stress than patients with psoriasis or healthy controls. More needs to be learned about the complex interaction between stress, immune parameters and chronic inflammation.

INTRODUCTION:Psychological stress may alter immune function by activating physiological stress pathways. Building on our previous study, in which we report that stress management training led to an altered self-reported and cortisol response to psychological stress in patients with rheumatoid arthritis (RA), we explored the effects of this stress management intervention on the immune response to a psychological stress task in patients with RA.METHODS:In this study, 74 patients with RA, who were randomly assigned to either a control group or a group that received short stress management training, performed the Trier Social Stress Test (TSST) 1 week after the intervention and at a 9-week follow-up. Stress-induced changes in levels of key cytokines involved in stress and inflammatory processes (for example, interleukin (IL)-6 and IL-8) were assessed.RESULTS:Basal and stress-induced cytokine levels were not significantly different in patients in the intervention and control groups one week after treatment, but stress-induced IL-8 levels were lower in patients in the intervention group than in the control group at the follow-up assessment.CONCLUSIONS:In line with our previous findings of lower stress-induced cortisol levels at the follow-up of stress management intervention, this is the first study to show that relatively short stress management training might also alter stress-induced IL-8 levels in patients with RA. These results might help to determine the role of immunological mediators in stress and disease.TRIAL REGISTRATION:The Netherlands National Trial Register (NTR1193)

Objective: To examine the potential effectiveness of a multimodal rehabilitation program including an acceptance-oriented cognitive-behavioral therapy for highly distressed patients with rheumatic diseases.Methods: An observational study employing a one-group pre-post test design (N = 25). The primary outcome was psychological distress. Secondary outcomes were quality of life, illness acceptance, and coping flexibility. Group pre-to-post and pre-to-12 months follow-up treatment changes were evaluated by paired-samples t-tests and Cohen's effect sizes (d). Individual changes were evaluated by the reliable change index (RCI) and clinically significant change (CSC) parameters.Results: Significant effects were found post-treatment and maintained at 12 months in psychological distress (d > 0.80), illness acceptance (d = 1.48) and the SF-36 subscales role physical, vitality, and mental health (d >= 0.65). No significant effects were found for coping flexibility and the SF-36 subscales physical functioning, bodily pain, social functioning, and role emotional. Both a reliable (RCI) and clinically significant (CSC) improvement was observed for almost half of the highly distressed patients.Conclusion: The patients enrolled in the multimodal rehabilitation program showed improved psychological health status from pre to post-treatment.Practice implications: A randomized clinical trial is needed to confirm or refute the added value of an acceptance-oriented cognitive-behavioral therapy for highly distressed patients in rehabilitation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

So far, there are no means of identifying rheumatoid arthritis (RA) patients who will fail to respond to tumour necrosis factor blocking agents (anti-TNF), prior to treatment. We set out to validate eight previously reported gene expression signatures predicting therapy outcome. Genome-wide expression profiling using Affymetrix GeneChip Exon 1.0 ST arrays was performed on RNA isolated from whole blood of 42 RA patients starting treatment with infliximab or adalimumab. Clinical response according to EULAR criteria was determined at week 14 of therapy. Genes that have been reported to be associated with anti-TNF treatment were extracted from our dataset. K-means partition clustering was performed to assess the predictive value of the gene-sets. We performed a hypothesis-driven analysis of the dataset using eight existing gene sets predictive of anti-TNF treatment outcome. The set that performed best reached a sensitivity of 71% and a specificity of 61%, for classifying the patients in the current study. We successfully validated one of eight previously reported predictive expression profile. This replicated expression signature is a good starting point for developing a prediction model for anti-TNF treatment outcome that can be used in a daily clinical setting. Our results confirm that gene expression profiling prior to treatment is a useful tool to predict anti-TNF (non) response.

INTRODUCTION:The goal of this study is to investigate whether the -308G > A promoter polymorphism in the tumor necrosis factor alpha (TNFA) gene is associated with disease severity and radiologic joint damage in a large cohort of patients with rheumatoid arthritis (RA).METHODS:A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629). A longitudinal regression analysis was performed to assess the effect of genotype on RA disease severity and joint damage. Subsequently, a meta-analysis, including all publically available data, was performed to further test the association between joint erosions and the TNFA polymorphism. To learn more about the mechanism behind the effect of the polymorphism, RNA isolated from peripheral blood from RA patients (n = 66) was used for TNFA gene expression analysis by quantitative PCR.RESULTS:Longitudinal regression analysis with correction for gender and disease activity showed a significant difference in total joint damage between GG and GA+AA genotype groups (P = 0.002), which was stable over time. The meta-analysis, which included 2,053 patients, confirmed an association of the genetic variant with the development of erosions (odds ratio 0.78, 95% CI 0.62, 0.98). No significant differences in TNFA gene expression were observed for the different genotypes, confirming earlier findings in healthy individuals.CONCLUSIONS:Our data confirm that the TNFA -308G > A promoter polymorphism is associated with joint damage in patients with RA. This is not mediated by differences in TNFA gene expression between genotypes.

Coping flexibility may be beneficial for the adjustment in the context of a progressive and unpredictable course of chronic rheumatic diseases. The aim of this study was to develop and initially validate a self-report measure that assesses coping flexibility. Study participants were 147 outpatients with chronic rheumatic diseases (73% women, mean age 59 (range 20–79) years). Principal axis factoring analysis with oblique rotation was applied and internal consistency was determined. To investigate the initial validity of the coping flexibility questionnaire (COFLEX), hypothesised correlations with psychological and physical adjustment outcomes, pain, and coping strategies were examined. Factor analysis yielded a two-factor model of coping flexibility with acceptable internal consistency: versatility, the capability of switching between assimilative and accommodative coping strategies according to personal goals and situational demands (α = .88) and reflective coping, the capability of generating and considering coping options, and appraising the suitability of a coping strategy in a given situation (α = .70). Versatility was correlated with adaptive ways of coping and psychological adjustment, but not with physical adjustment and pain. Reflective coping was correlated with both adaptive and maladaptive ways of coping, but it was not correlated with adjustment outcomes. In conclusion, the current study suggests acceptable internal consistency of the COFLEX. Preliminary evidence of the validity of the versatility dimension is indicated, while the validity of reflective coping could not be firmly established. The associations of versatility with favourable adjustment to the disease warrant future confirmatory and validity research in larger samples of patients with chronic rheumatic diseases.

Background Stress management interventions may prove useful in preventing the detrimental effects of stress on health. This study assessed the effects of a stress management intervention on the psychophysiological response to stress in patients with rheumatoid arthritis (RA). Methods Seventy-four patients with RA, who were randomly assigned to either a control group or a group that received short-term stress management training, performed a standardized psychosocial stress task (Trier Social Stress Test; TSST) 1 week after the stress management training and at a 9-week follow-up. Psychological and physical functioning, and the acute psychophysiological response to the stress test were assessed. Results Patients in the intervention group showed significantly lower psychological distress levels of anxiety after the training than did the controls. While there were no between-group differences in stress-induced tension levels, and autonomic (α-amylase) or endocrine (cortisol) responses to the stress test 1 week after the intervention, levels of stress-induced tension and cortisol were significantly lower in the intervention group at the 9-week follow-up. Overall, the response to the intervention was particularly evident in a subgroup of patients with a psychological risk profile. Conclusion A relatively short stress management intervention can improve psychological functioning and influences the psychophysiological response to stress in patients with RA, particularly those psychologically at risk. These findings might help understand how stress can affect health and the role of individual differences in stress responsiveness. Trial Registration TrialRegister.nl NTR1193

Objective: To evaluate the efficacy of the Nijmegen Falls Prevention Program (NFPP) for persons with osteoporosis and a fall history in a randomized controlled trial. Persons with osteoporosis are at risk for fall-related fractures because of decreased bone strength. A decrease in the number of falls therefore is expected to be particularly beneficial for these persons.Design: Randomized controlled trial.Setting: Hospital.Participants: Persons with osteoporosis and a fall history (N=96; mean +/- SD age, 71.0+/-4.7y; 90 women).Intervention: After baseline assessment, participants were randomly assigned to the exercise (n=50; participated in the NFPP for persons with osteoporosis [5.5wk]) or control group (n=46; usual care).Main Outcome Measures: Primary outcome measure was fall rate, measured by using monthly fall calendars for 1 year. Secondary outcomes were balance confidence (Activity-specific Balance Confidence Scale), quality of life (QOL; Quality of Life Questionnaire of the European Foundation for Osteoporosis), and activity level (LASA Physical Activity Questionnaire, pedometer), assessed posttreatment subsequent to the program and after 1 year of follow-up.Results: The fall rate in the exercise group was 39% lower than for the control group (.72 vs 1.18 falls/person-year; risk ratio, .61; 95% confidence interval, .40.94). Balance confidence in the exercise group increased by 13.9% (P=.001). No group differences were observed in QOL and activity levels.Conclusion: The NFPP for persons with osteoporosis was effective in decreasing the number of falls and improving balance confidence. Therefore, it is a valuable new tool to improve mobility and independence of persons with osteoporosis.

PURPOSE:To examine psychological health status among patients with inflammatory rheumatic diseases (i.e. rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) and osteoarthritis in multidisciplinary rehabilitation, and to describe changes in psychological distress, illness cognitions, and pain coping from pre- to post-treatment.METHOD:Eighty-nine patients referred to multidisciplinary rehabilitation completed a set of questionnaires to assess pain (AIMS2-SF), physical functioning (AIMS2-SF), psychological distress (IRGL), illness cognitions (ICQ) and pain coping (PCI) at pre- and post-treatment. Changes in physical functioning, pain, and psychological health status were determined. On the basis of the cut-off scores of psychological distress, distressed, and non-distressed patients were compared on physical and psychological outcomes.RESULTS:Psychological distress was found in 64% of the study sample. In addition, high levels of helplessness and worrying, low levels of acceptance, and moderate levels of physical functioning were found. After treatment, positive changes in pain, psychological distress, and illness cognitions were observed. However, 69% (29/42) of the distressed patients at baseline still experienced elevated levels of psychological distress and maladaptive cognitions.CONCLUSIONS:Psychological distress and maladaptive illness cognitions are important characteristics of this study sample, and psychological distress remains high after rehabilitation. More attention should be given to the appropriate assessment and treatment of psychological distress within multidisciplinary rehabilitation.

OBJECTIVE To investigate whether there is a difference in waiting time between indication and start of anti-TNF-alpha therapy in younger and older RA patients. METHODS The study was carried out in the Nijmegen inception cohort of early RA. All patients meeting indications for anti-TNF-alpha therapy according to the Dutch reimbursement criteria were included in the analysis. Time from indication to start of anti-TNF-alpha therapy or censoring was calculated in all patients. Multivariable Cox regression analysis was used to investigate the influence of age at indication on the time to commencement of anti-TNF-alpha treatment. Hazard ratios were calculated for groups in age quartiles. The model was corrected for 28-joint disease activity score (DAS28), disease duration, gender, the Charlson comorbidity index and episodes of serious illnesses between indication and anti-TNF-alpha therapy or censoring. RESULTS From the 487 eligible patients, 215 patients started anti-TNF-alpha treatment during their follow-up (44%). Age significantly influenced the time to receiving anti-TNF-alpha after first indication, adjusting for confounders (HR = 0.975/year, P < 0.001). The same analysis using age quartiles showed that the younger age groups had a higher chance of receiving anti-TNF-alpha treatment within an equal period of time than older patients [HR 2.67 (95% CI 1.64, 4.35); 2.30 (1.43, 3.71); 1.79 (1.14, 2.81) with increasing age; the eldest group as reference]. The eldest patients had significantly higher DAS28 values prior to anti-TNF-alpha treatment than younger patients. CONCLUSION Elderly RA patients were less likely to receive anti-TNF-alpha treatment within an equal period of time compared with younger patients, taking disease activity, disease duration and comorbidities into account.

AIM:To study the effect of the nonsteroidal anti-inflammatory drug naproxen on the activity of the hypothalamic-pituitary-adrenal (HPA) axis in healthy volunteers.METHODS:A double-blind, randomized study in two groups of 20 healthy volunteers was performed. The activity of the HPA axis was measured before and after the use of naproxen or placebo during a period of 2 weeks. Basal plasma adrenocorticotropic hormone (ACTH) and cortisol, 24-h urinary cortisol, and circadian cortisol rhythm in saliva were determined. Plasma ACTH and cortisol were also measured during submaximal physical exercise.RESULTS:There were no significant differences between the placebo and naproxen groups in basal plasma ACTH [09.00 h 3.1 pmol l(-1), 95% confidence interval (CI) 2.0, 4.2, and 2.8 pmol l(-1), 95% CI 1.9, 3.7, respectively], cortisol levels (09.00 h 0.45 micromol l(-1), 95% CI 0.39, 0.51, and 0.40 micromol l(-1), 95% CI 0.35, 0.44, respectively), 24 h urinary cortisol excretion (67.5 nmol 24 h(-1), 95% CI 54.3, 80.7, and 86.8 nmol 24 h(-1), 95% CI 54.4, 119.2, respectively), circadian cortisol rhythm measured in salivary samples, or ACTH and cortisol concentrations after physical exercise. After the use of placebo or naproxen for 2 weeks, no significant change in any of the parameters occurred (ACTH 09.00 h 3.0 pmol l(-1), 95% CI 2.0, 3.9, and 3.0 pmol l(-1), 95% CI 2.2, 3.8, respectively; cortisol 09.00 h 0.45 micromol l(-1), 95% CI 0.37, 0.52, and 0.39 micromol l(-1), 95% CI 0.34, 0.44, respectively; cortisol urine 79.5 nmol 24 h(-1), 95% CI 59.5, 99.4, and 81.7 nmol 24 h(-1), 95% CI 64.0, 99.4, respectively), and no significant differences were found in these parameters between the placebo and naproxen groups.CONCLUSIONS:The use of naproxen does not influence the activity of the HPA axis in healthy volunteers under basal circumstances or in response to physical stress.

Background: Antigen-presenting cells (APC) and T cells are considered to play a significant role in the pathogenesis of rheumatoid arthritis ( RA). CCL18 and CXCL16 are two chemokines that facilitate T cell attraction by APC, of which a role in the pathogenesis of RA has been suggested.Objective: To compare the circulating levels of CXCL16 and CCL18 in RA with controls and to investigate the relation of CXCL16 and CCL18 with RA disease activity and joint damage.Methods: Circulating CCL18 and CXCL16 levels were determined in 61 RA patients with a follow-up of 6 years and a group of 41 healthy controls with ELISA. Chemokine levels were correlated with demographic data, disease activity (DAS28) and joint damage ( modified Sharp score). In addition, serum CCL18 and CXCL16 levels from a cohort of 44 RA patients treated with anti-TNF-alpha were correlated with disease activity.Results: CCL18 levels in serum were significantly elevated in RA patients compared with controls, while serum CXCL16 levels were not. In contrast to CXCL16, serum CCL18 was positively correlated with disease activity. Both CCL18 and CXCL16 levels decreased upon treatment with anti-TNF-alpha. Neither CCL18 nor CXCL16 correlated with joint damage and progression.Conclusion: Here, we show, for the first time, that circulating CCL18 and not CXCL16 levels are elevated in RA patients as compared with controls and correlate with disease activity in RA. More knowledge regarding the regulation and function of both CCL18 and CXCL16 is essential to value their role in RA.