Predictors and outcomes of sustained, intermittent or never achieving remission in patients with recent onset inflammatory polyarthritis:Results from the Norfolk Arthritis Register

Objectives: Early remission is the current treatment strategy for patients with inflammatory polyarthritis (IP) and RA. Our objective was to identify baseline factors associated with achieving remission: sustained (SR), intermittent (IR) or never (NR) over a 5-year period in patients with early IP.  Methods: Clinical and demographic data of patients with IP recruited to the Norfolk Arthritis Register (NOAR) were obtained at baseline and years 1, 2, 3 and 5. Remission was defined as no tender or swollen joints (out of 51). Patients were classified as NR or PR, respectively, if they were in remission at: no assessment or ⩾3 consecutive assessments after baseline, and IR otherwise. Ordinal regression and a random effects model, respectively, were used to examine the association between baseline factors, remission group and HAQ scores over time.  Results: A total of 868 patients (66% female) were included. Of these, 54%, 34% and 12% achieved NR, IR and SR, respectively. In multivariate analysis, female sex (odds ratio, OR 0.47, 95% CI: 0.35, 0.63), higher tender joint count (OR = 0.94, 95% CI: 0.93, 0.96), higher HAQ (OR = 0.59, 95% CI: 0.48, 0.74), being obese (OR = 0.70, 95% CI: 0.50, 0.99), hypertensive (OR = 0.67, 95% CI: 0.50, 0.90) or depressed (OR = 0.74, 95% CI: 0.55, 1.00) at baseline were independent predictors of being in a lower remission group. IR and SR were associated with lower HAQ scores over time and lower DAS28 at year 5.  Conclusion: Women with higher tender joint count and disability at baseline, depression, obesity and hypertension were less likely to achieve remission. This information could help when stratifying patients for more aggressive therapy

Self-reported pain severity is associated with a history of coronary heart disease

This study was funded by Arthritis Research UK (grant number: 17292).Peer reviewedPublisher PD

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis:Results from the Norfolk Arthritis Register

Objectives: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years’ follow-up in a cohort of patients with inflammatory polyarthritis (IP).  Methods: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.  Results: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.  Conclusions: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA

Mapping the <i>Shh</i> long-range regulatory domain

Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains

Investigating Variation in the Prevalence of Weathering in Faunal Assemblages in the UK: A Multivariate Statistical Approach

This article presents an exploratory multivariate statistical approach to gaining a more comprehensive understanding of variation in subaerial bone weathering in a British context. Weathering is among the most common taphonomic modifications and provides a crucial line of evidence for reconstructing the taphonomic trajectories of faunal assemblages and archaeological deposits. It provides clear evidence for prolonged subaerial exposure either before deposition in a context or because of later disturbance. In combination with other taphonomic indices such as gnawing, trampling, abrasion and fracture patterns, weathering can be used to reconstruct depositional histories and to investigate the structured treatment of different body parts or taxa in deposition. However, a broad range of factors affect the prevalence and severity of weathering, and therefore patterns can rarely be interpreted at face value. Many variables such as predepositional microenvironment cannot be traced archaeologically. Other contributory factors pertaining to the structural properties of elements and taxa can be discerned and must be taken into account in interpreting weathering signatures. However, disagreement exists regarding which variables are most important in mediating weathering. In addition for zooarchaeologists to interpret modification patterns, it is necessary for elements and taxa that are most likely to be affected by weathering to be defined. This is the case as deposits that are dominated by those classes of remains are likely to exhibit greater modification than those that are not, even if depositional histories were similar. Through a combination of classification tree and ordinal regression analysis, this article identifies which archaeologically recoverable variables explain the greatest variance in weathering and which anatomical elements and taxa are most likely to be affected in archaeological deposits in the UK

HLA-DRB1 amino acid positions 11/13, 71 and 74 are associated with inflammation level, disease activity and the Health Assessment Questionnaire disability index in patients with inflammatory polyarthritis

Objective: Rheumatoid arthritis (RA) susceptibility HLA–DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes. Methods: We tested the association of RA susceptibility HLA–DRB1 amino acids with the C-reactive protein (CRP) level, the tender joint count (TJC), the swollen joint count (SJC), the Disease Activity Score in 28 joints (DAS28), and the Health Assessment Questionnaire (HAQ) score in the Norfolk Arthritis Register (NOAR) and Early Rheumatoid Arthritis Study (ERAS) cohorts. Longitudinal modeling of disease activity/outcomes was performed using generalized linear latent and mixed models. Mediation analysis was performed using directed acyclic graphs to investigate the paths from genetic factors to outcome.  Results: A total of 2,158 patients were available for analysis in the NOAR cohort. Valine at position 11 showed the strongest association with the CRP level (P = 2.21 × 10−6), the SJC (P = 7.51 × 10−6), and the DAS28 (P = 0.002); it was marginally associated with the HAQ score (P = 0.044) but not with the TJC. The same amino acid and haplotype risk hierarchy observed for susceptibility and radiographic severity was observed for the CRP level and nonradiographic measures of disease activity/outcome, apart from the TJC. The results were replicated in the ERAS cohort. The effect of valine at position 11 on the SJC was mainly mediated by anti–citrullinated protein antibody status, the effect of which was mainly mediated by inflammation; however, the effect of valine at position 11 was also independent of the CRP level (P = 1.6 × 10−4).  Conclusion: Genetic markers of RA susceptibility located within HLA–DRB1 determine the levels of clinical and systemic inflammation independently, and also determine all objective measures of disease activity and outcome

Fallow deer (Dama dama dama) management in Roman South-East Britain

This paper presents new carbon, nitrogen and sulphur isotope data for European fallow deer (Dama dama dama) in Roman Britain and discusses results in light of evidence from classical texts, landscape archaeology, zooarchaeology and the limited available samples of metric data. The new isotope data presented here are from Fishbourne Roman Palace (Sussex), two sites on the Isle of Thanet (Kent) and a further two sites in London. In spite of small sample sizes the data make an important contribution to the very limited corpus of scientific research on the species and provide new resolution to the nature of fallow deer movement and management in Roman Britain

Long-term stability of anti-cyclic citrullinated peptide antibody status in patients with early inflammatory polyarthritis.

INTRODUCTION: The utility of reassessing anti-cyclic citrullinated peptide (anti-CCP) antibody status later in disease in patients presenting with early undifferentiated inflammatory polyarthritis, particularly in those who test negative for both anti-CCP and rheumatoid factor (RF) at baseline, remains unclear. We aimed therefore to determine the stability of CCP antibody status over time and the prognostic utility of repeated testing in subjects with early inflammatory polyarthritis (IP). METHODS: Anti-CCP and RF were measured at baseline and 5 years in 640 IP patients from the Norfolk Arthritis Register, a primary care-based inception cohort. The relation between change in anti-CCP status/titer and the presence of radiologic erosions, the extent of the Larsen score, and Health Assessment Questionnaire (HAQ) score by 5 years was investigated. RESULTS: With a cut-off of 5 U/ml, 28% subjects tested positive for anti-CCP antibodies, 29% for RF, and 21% for both at baseline. Nine (2%) anti-CCP-negative patients seroconverted to positive, and nine (4.6%) anti-CCP-positive individuals became negative between baseline and 5 years. In contrast, RF status changed in 17% of subjects. However, change in RF status was strongly linked to baseline anti-CCP status and was not independently associated with outcome. Ever positivity for anti-CCP antibodies by 5 years did not improve prediction of radiographic damage compared with baseline status alone (accuracy, 75% versus 74%). A higher baseline anti-CCP titer (but not change in anti-CCP titer) predicted worse radiologic damage at 5 years (P < 0.0001), even at levels below the cut-off for anti-CCP positivity. Thus, a titer of 2 to 5 U/ml was strongly associated with erosions by 5 years (odds ratio, 3.6 (1.5 to 8.3); P = 0.003). CONCLUSIONS: Repeated testing of anti-CCP antibodies or RF in patients with IP does not improve prognostic value and should not be recommended in routine clinical practice.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

The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis

Objective. To explore the influence of TNF inhibitor (TNFi) therapy and rituximab (RTX) upon the incidence of cancer in patients with RA and prior malignancy. Methods. The study population comprised RA subjects with a prior malignancy reported to the UK national cancer registers, recruited to the British Society for Rheumatology Biologics Register from 2001 to 2013. We compared rates of first incident malignancy in a TNFi cohort, RTX cohort and synthetic DMARDs (sDMARD) cohort. Results. We identified 425 patients with a prior malignancy from 18 000 RA patients in the study. Of these, 101 patients developed a new malignancy. The rates of incident malignancy were 33.3 events/1000 person-years (py) in the TNFi cohort, 24.7 events/1000 py in the RTX cohort and 53.8 events/1000 py in the sDMARD cohort. The age- and gender-adjusted hazard ratio was 0.55 (95% CI: 0.35, 0.86) for the TNFi cohort and 0.43 (95% CI: 0.10, 1.80) for the RTX cohort in comparison with the sDMARDs cohort. The 17.0% of patients in the sDMARDs cohort had a recurrence of the same cancer in comparison with the 12.8% and the 4.3% in the TNFi and RTX cohorts, respectively. Conclusions. Although numbers are still low, it seems that patients with RA and prior malignancy selected to receive either a TNFi or RTX in the UK do not have an increased risk of future incident malignancy

Concealed concern: Fathers' experience of having a child with Juvenile Idiopathic Arthritis

Despite increased research into families of chronically ill children, more needs to be known about the father’s experience. We address this issue through asking: ‘What is it like to be the father of a child with juvenile idiopathic arthritis?’ (JIA). Four members of eight families with an adolescent diagnosed with JIA, including seven fathers, were interviewed and transcripts analyzed using grounded theory. This study suggests that fathers of children with JIA experience several severe losses which are exacerbated through comparisons they make between their own situation and that of fathers of healthy children. In addition, the fathers faced several constraints which reduced their opportunities to communicate with their ill child through shared activities. Fathers appeared to conceal their distress by adopting strategies of denial and distraction however their adjustment was facilitated, to some extent, by social support. They could also develop greater acceptance of their situation over time as the care of their ill child became assimilated into family life and constraints upon their life gradually reduced through the increased maturity of their son or daughter with JIA. These findings have implications for healthcare professionals and voluntary organizations