No abstract

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. MethodsWe did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. FindingsIn the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.

No abstract

Objectives. The self-regulatory model proposes that an individual"s cognitive representations of illness threat (illness representations) influence the selection and performance of strategies to cope with that illness (Leventhal, Meyer & Nerenz, 1980). Also implicit in the model is the proposal that such coping strategies influence illness outcomes. These relationships represent a mediational model (Baron & Kenny, 1986). The aim of the present study was to test the hypothesis that coping strategies partially mediate the relationship between illness representations and illness outcome in women with rheumatoid arthritis.Design and Methods. The study was an observational cross-sectional design. Self-report measures of illness representations, coping strategies, and illness outcome were collected from 125 women with rheumatoid arthritis attending rheumatology outpatient clinics. Clinical measures of disease activity and severity were obtained from hospital records.Results. Avoidant and resigned coping was found to partially mediate the relationship between symptom identity and the illness outcome measures of disability and psychiatric morbidity. As in other studies, strong relationships were found between illness representations and illness outcome.Conclusions. The finding that avoidant and resigned coping partially mediated the relationships between the illness representation dimension of symptom identity and two of the illness outcome measures (disability and psychiatric morbidity) provided some support for the hypothesis.However, the hypothesis was not fully supported, as coping did not partially mediate the relationship between any of the other illness representations and illness outcomes. (1977). Such social-cognition models have been used to help identify the complex processes involved in mediating between disease, pain, disability & adjustment.However this research has been inconclusive, as none of the individual factors studied have consistently predicted health and illness behaviours (Turk, Rudy & Salovey, 1986). Marteau (1993) suggests that this may either be due to inadequacies in the research, or may indicate that the above theories do not contain the cognitions that predict health behaviour and outcomes. In the last decade much attention has been directed towards Leventhal"s self-regulatory model (Leventhal et al. 1980) in the hope that this will provide a more complete model of health behaviour.An advantage of utilising the self-regulatory model with individuals who are diagnosed with a chronic illness is the potential to explore sophisticated responses to an illness from a number of domains. The self-regulatory model proposes that an individual"s cognitive representations of illness threat (illness representations) influence the selection and performance of strategies to cope with that illness, which in turn influence outcome appraisals (Leventhal et al., 1980). Also implicit in the model is the proposal that such coping strategies influence illness outcomes (Leventhal et al., 1980). The mode...

Objective-To assess the association between serum insulin-like growth factor-I (IGF-1) concentrations and osteoarthritis, and bone mineral density, and fractures in a large group of middle aged women from the general population. Methods-761 women aged 44-64 years from the Chingford study had serum IGF-I concentrations measured; hand, hip, spine, and anteroposterior weight bearing knee radiographs taken; and dual energy x ray absorptiometry (DEXA) scans of the hip and spine. X rays were scored using the Kellgren and Lawrence system. In addition knee x rays were scored using a standard atlas for individual features of osteophytes and joint space narrowing (both graded 0-3). IGF-I concentrations were adjusted for the effects of age.