Is there an association between anti-TNF monoclonal antibody therapy in rheumatoid arthritis and risk of malignancy and serious infection? Commentary on the meta-analysis by Bongartz et al

A recent meta-analysis of randomized clinical trials reported by Bongartz and coworkers raised concerns about an increased rate of malignancy and serious infection in rheumatoid arthritis patients treated with anti-tumour necrosis factor monoclonal antibodies. This commentary discusses some of the methodological issues in their analysis and urges caution in interpreting the results

What epidemiology has told us about risk factors and aetiopathogenesis in rheumatic diseases

This article will review how epidemiological studies have advanced our knowledge of both genetic and environmental risk factors for rheumatic diseases over the past decade. The major rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, osteoarthritis, gout, and fibromyalgia, and chronic widespread pain, will be covered. Advances discussed will include how a number of large prospective studies have improved our knowledge of risk factors, including diet, obesity, hormones, and smoking. The change from small-scale association studies to genome-wide association studies using gene chips to reveal new genetic risk factors will also be reviewed

Why are women predisposed to autoimmune rheumatic diseases?

The majority of autoimmune diseases predominate in females. In searching for an explanation for this female excess, most attention has focused on hormonal changes - both exogenous changes (for example, oral contraceptive pill) and fluctuations in endogenous hormone levels particularly related to menstruation and pregnancy history. Other reasons include genetic differences, both direct (influence of genes on sex chromosomes) and indirect (such as microchimerism), as well as gender differences in lifestyle factors. These will all be reviewed, focusing on the major autoimmune connective tissue disorders: rheumatoid arthritis, systemic lupus erythematosus and scleroderma

Aspects of early arthritis. What determines the evolution of early undifferentiated arthritis and rheumatoid arthritis? An update from the Norfolk Arthritis Register

Over 3500 patients with recent onset inflammatory polyarthritis (IP) have been recruited by the Norfolk Arthritis Register (NOAR) since 1990. Longitudinal data from this cohort have been used to examine the prevalence and predictors of remission, functional disability, radiological outcome, cardiovascular mortality and co-morbidity and the development of non-Hodgkin's lymphoma. Rheumatoid factor titre, high baseline C-reactive protein and high baseline HAQ score are all predictors of a poor outcome. There is a strong association between possession of the shared epitope and the development of erosions. Patients who satisfy the American College of Rheumatology criteria for rheumatoid arthritis (RA) have a worse prognosis than those who do not. However, it appears that these patients are a poorly defined subset of all those with IP rather than having an entirely separate disease entity. New statistical techniques offer exciting possibilities for using longitudinal datasets such as NOAR to explore the long-term effects of treatment in IP and RA

Longitudinal trajectories of frailty are associated with short-term mortality in older people: a joint latent class models analysis using two UK primary care databases

Objective: Frailty is a dynamic health state that changes over time. Our hypothesis was that there are identifiable subgroups of the older population that have specific patterns of deterioration. The objective of this study was to evaluate the application of joint latent class model (JLCM) in identifying trajectories of frailty progression over time and their group-specific risk of death in older people. Study design and setting: The primary care records of UK patients, aged over 65 as of January 1st 2010, included in the CPRD: GOLD and AURUM databases, were analysed and linked to mortality data. Electronic frailty index (eFI) scores were calculated at baseline and annually in subsequent years (2010-2013). JLCM was used to divide the population into clusters with different trajectories and associated mortality hazard ratios (HR). The model was built in GOLD and validated in AURUM. Results: Five trajectory clusters were identified and characterised based on baseline and speed of progression: low-slow, low-moderate, low-rapid, high-slow and high-rapid. The high-rapid cluster had the highest average starting eFI score; 7.9, while low-rapid cluster had the steepest rate of eFI progression; 1.7. Taking the low-slow cluster as reference, low-rapid and high-rapid had the highest HRs: 3.73 (95%CI 3.71 to 3.76) and 3.63 (3.57 to 3.69), respectively. Good validation was found in the AURUM population. Conclusion: Our research found that there are vulnerable subgroups of the older population who are currently frail or have rapid frailty progression. Such groups may be targeted for greater healthcare monitoring

Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents

In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. A population study ascertained pain and psychological status in subjects aged 25 to 65 years. Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group. HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 0.25 mg dexamethasone suppression test) stressors. The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender. In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied. Those in the chronic widespread pain and 'at risk' groups were, respectively, 3.1 (95% CI (1.3, 7.3)) and 1.8 (0.8, 4.0) times more likely to have a saliva cortisol score in the lowest third. None of the psychosocial factors measured were, however, associated with saliva cortisol scores. Further, those in the chronic widespread pain (1.9 (0.8, 4.7)) and 'at risk' (1.6 (0.7, 3.6)) groups were also more likely to have the highest serum cortisol scores. High post-stress serum cortisol was related to high levels of psychological distress (p = 0.05, 95% CI (0.02, 0.08)). After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress

Influence of inflammatory polyarthritis on quantitative heel ultrasound measurements.

BACKGROUND: There are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements. METHODS: Men and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors. RESULTS: 139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = -10.0; 95% confidence interval (CI) -17.4, -2.6) though BUA was similar (difference = -1.2; 95% CI -4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS. CONCLUSIONS: In this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Patients' experience on pain outcomes after hip arthroplasty: insights from an information tool based on registry data

Background Arthroplasty registries are rarely used to inform encounters between clinician and patient. This study is part of a larger one which aimed to develop an information tool allowing both to benefit from previous patients’ experience after total hip arthroplasty (THA). This study focuses on generating the information tool specifically for pain outcomes. Methods Data from the Geneva Arthroplasty Registry (GAR) about patients receiving a primary elective THA between 1996 and 2019 was used. Selected outcomes were identified from patient and surgeon surveys: pain walking, climbing stairs, night pain, pain interference, and pain medication. Clusters of patients with homogeneous outcomes at 1, 5, and 10 years postoperatively were generated based on selected predictors evaluated preoperatively using conditional inference trees (CITs). Results Data from 6,836 THAs were analysed and 14 CITs generated with 17 predictors found significant (p  Conclusions The information tool generated under this study can provide prospective patients and clinicians with valuable and understandable information about the experiences of “patients like them” regarding their pain outcomes