A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

BackgroundThe Internet increases the availability of health information, which consequently expands the amount of skills that health care consumers must have to obtain and evaluate health information. Norman and Skinner in 2006 developed an 8-item self-report eHealth literacy scale to measure these skills: the eHealth Literacy Scale (eHEALS). This instrument has been available only in English and there are no data on its validity.ObjectivesThe objective of our study was to assess the internal consistency and the construct and predictive validity of a Dutch translation of the eHEALS in two populations.MethodsWe examined the translated scale in a sample of patients with rheumatic diseases (n = 189; study 1) and in a stratified sample of the Dutch population (n = 88; study 2). We determined Cronbach alpha coefficients and analyzed the principal components. Convergent validity was determined by studying correlations with age, education, and current (health-related) Internet use. Furthermore, in study 2 we assessed the predictive validity of the instrument by comparing scores on the eHEALS with an actual performance test.ResultsThe internal consistency of the scale was sufficient: alpha = .93 in study 1 and alpha = .92 in study 2. In both studies the 8 items loaded on 1 single component (respectively 67% and 63% of variance). Correlations between eHEALS and age and education were not found. Significant, though weak, correlations were found between the eHEALS and quantity of Internet use (r = .24, P = .001 and r = .24, P = .02, respectively). Contrary to expectations, correlations between the eHEALS and successfully completed tasks on a performance test were weak and nonsignificant: r = .18 (P = .09). The t tests showed no significant differences in scores on the eHEALS between participants who scored below and above median scores of the performance test.ConclusionsThe eHEALS was assessed as unidimensional in a principal component analysis and the internal consistency of the scale was high, which makes the reliability adequate. However, findings suggest that the validity of the eHEALS instrument requires further study, since the relationship with Internet use was weak and expected relationships with age, education, and actual performance were not significant. Further research to develop a self-report instrument with high correlations with people’s actual eHealth literacy skills is warranted.

Ever since the rise of online support groups it has been presumed that there is an empowering effect from patients' participating in these groups, despite a lack of evidence to back up this assumption. In this study we explored if, and in which ways, patients feel empowered by participation. Additionally, we studied which empowering and disempowering processes occur as a result of taking part in these groups. To accomplish this aim, we interviewed 32 participants of online support groups. This analysis revealed the following empowering processes: exchanging information, encountering emotional support, finding recognition, sharing experiences, helping others, and amusement. Disempowering processes were mentioned far less often. Empowering outcomes mentioned were being better informed; feeling confident in the relationship with their physician, their treatment, and their social environment; improved acceptance of the disease; increased optimism and control; enhanced self-esteem and social well-being; and collective action. This article demonstrates that participation in online support groups can make a valuable contribution to the emergence of empowered patients.

Objective. The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that stepdown combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome.Methods. All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline).Results. At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the timeaveraged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28.Conclusion. An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.Rheumatoid arthritis (RA) is a chronic, potentially disabling disease characterized by inflammation of the joints, periarticular bone resorption and cartilage

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Objective. Although patients with rheumatoid arthritis (RA) experience fatigue, little is known about its causes and consequences, and a fully developed theoretical model explaining the experience of fatigue in RA is lacking. Our goal was to systematically review studies in RA that examined factors related to fatigue to gain more insight into its possible causes and consequences. Methods. Medline, Web of Science, Scopus, and PsycINFO were searched for relevant studies. All studies with RA samples about the relationship between fatigue and other variables that defined dependent and independent variables and used multivariate statistical methods were preliminarily included. After reviewing 129 full texts, we identified 25 studies on possible causes of fatigue and 17 studies on possible consequences of fatigue. Results. The studies found possible causes of fatigue in illness-related aspects, physical functioning, cognitive/emotional functioning, and social aspects. Additionally, being a woman was related to higher levels of fatigue. Inflammatory activity showed an unclear relationship with fatigue in RA. Possible consequences of fatigue were also found among illnessrelated aspects, physical functioning, cognitive/emotional functioning, and social aspects. The strongest evidence for a relationship between fatigue and other variables was found regarding pain, physical functioning, and depression. Conclusion. This review summarizes the current knowledge in the field in order to inform future research on causes and consequences of fatigue in RA. However, the results are based on cross-sectional and longitudinal studies with different designs and different fatigue scales. For a better identification of causal associations between fatigue in RA and related factors, longitudinal prospective designs with adequate fatigue measurements are suggested.

Objective. To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention.Methods. The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-month intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis.Results. There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age 280 years (odds ratio [OR] Conclusion. These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection.

Background Patients who visit online support groups benefit in various ways. Results of our earlier study indicated that participation in online support groups had a profound effect on the participants’ feelings of “being empowered.” However, most studies of online patient support groups have focused on the members of these groups who actively contribute by sending postings (posters). Thus far, little is known about the impact for “lurkers” (ie, those who do not actively participate by sending postings).Objective In the present study, we explored if lurkers in online patient support groups profit to the same extent as posters do.MethodsWe searched the Internet with the search engine Google to identify all Dutch online support groups for patients with breast cancer, fibromyalgia, and arthritis. Invitations to complete an online survey were sent out by the owners of 19 groups. In the online questionnaire, we asked questions about demographic and health characteristics, use of and satisfaction with the online support group, empowering processes, and empowering outcomes. The online questionnaire was completed by 528 individuals, of which 109 (21%) identified themselves as lurkers.Results Lurkers (mean age 47 years) were slightly older than active participants (mean age 43 years, P = .002), had a shorter disease history (time since diagnosis 3.7 years vs 5.4 years, P = .001), and reported lower mental well-being (SF 12 subscore 37.7 vs 40.5, P = .004). No significant differences were found in other demographic variables. Posters indicated visiting the online support groups significantly more often for social reasons, such as curiosity about how other members were doing, to enjoy themselves, as a part of their daily routine (all P < .001), and because other members expected them to be there (P = .003). Lurkers and posters did not differ in their information-related reasons for visiting the online support group. Lurkers were significantly less satisfied with the online support group compared to posters (P < .001). With regard to empowering processes such as “exchanging information” and “finding recognition,” lurkers scored significantly lower than posters. However, lurkers did not differ significantly from posters with regard to most empowering outcomes, such as “being better informed,” “feeling more confident in the relationship with their physician,” “improved acceptance of the disease,” “feeling more confident about the treatment,” “enhanced self-esteem,” and “increased optimism and control.” The exception was “enhanced social well-being,” which scored significantly lower for lurkers compared to posters (P < .001).Conclusion Our study revealed that participation in an online support group had the same profound effect on lurkers’ self-reported feelings of being empowered in several areas as it had on posters. Apparently, reading in itself is sufficient to profit from participation in an online patient support group.