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Objectives Disease-modifying antirheumatic drugs (DMARDs) are a first-line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results are variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy) and potentially improve patient outcome. Methods A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naive, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n  = 144) in DMARD-naive patients and at six weeks (n  = 117) and 12 weeks (n  = 95) into DMARD therapy. Samples collected (n  = 365 stool, n  = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined. Results In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naive patients were indicative of future response. Conclusion DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD. [ABSTRACT FROM AUTHOR]

Objective To elucidate the prevalence of undiagnosed rheumatology-verified diagnosis of axial spondyloarthritis (RVD-axSpA) in patients attending routine secondary care IBD clinics with chronic back pain. Methods Screening questionnaires were sent to consecutive patients attending IBD clinics in a university teaching hospital. Patients fulling the eligibility criteria (gastroenterologist-verified diagnosis, 18–80 years old, biologic therapy naive, no previous diagnosis of axSpA); and a moderate diagnostic probability of axSpA [self-reported chronic back pain (CBP) >3 months, onset <45 years] were invited for rheumatology assessment. This included medical review, physical examination, patient reported outcome measures, human leucocyte antigen B27, C-reactive protein, pelvic radiograph and axSpA protocol magnetic resonance imaging. A diagnosis of RVD-axSpA was made by a panel of rheumatologists. Results Of the 470 patients approached, 91 had self-reported CBP >3 months, onset <45 years, of whom 82 were eligible for clinical assessment. The prevalence of undiagnosed RVD-axSpA in patients attending IBD clinics in a secondary care setting, with self-reported CBP, onset <45 years is estimated at 5% (95% CI 1.3, 12.0) with a mean symptom duration of 12 (s. d. 12.4) years. Conclusion There is a significant hidden disease burden of axSpA among IBD patients. Appropriate identification and referral from gastroenterology is needed to potentially shorten the delay to diagnosis and allow access to appropriate therapy. [ABSTRACT FROM AUTHOR]

Objective To identify the clinical and biomechanical characteristics associated with falls in people with RA. Methods A total of 436 people ≥60 years of age with RA completed a 1 year prospective survey of falls in the UK. At baseline, questionnaires recorded data including personal and medical history, pain and fatigue scores, health-related quality of life (HRQoL), physical activity and medication history. The occurrence of falls wasmonitored prospectively over 12 months by monthly self-reporting. A nested sample of 30 fallers (defined as the report of one or more falls in 12 months) and 30 non-fallers was evaluated to assess joint range of motion (ROM), muscle strength and gait parameters. Multivariate regression analyses were undertaken to determine variables associated with falling. Results Compared with non-fallers (n  = 236), fallers (n  = 200) were older (P  = 0.05), less likely to be married (P  = 0.03), had higher pain scores (P  < 0.01), experienced more frequent dizziness (P  < 0.01), were frequently taking psychotropic medications (P  = 0.02) and reported lower HRQoL (P  = 0.02). Among those who underwent gait laboratory assessments, compared with non-fallers, fallers showed a greater anteroposterior (AP; P  = 0.03) and medial-lateral (ML) sway range (P  = 0.02) and reduced isokinetic peak torque and isometric strength at 60° knee flexion (P  = 0.03). Fallers also showed shorter stride length (P  = 0.04), shorter double support time (P  = 0.04) and reduced percentage time in swing phase (P  = 0.02) and in knee range of motion through the gait cycle (P  < 0.01). Conclusion People with RA have distinct clinical and biomechanical characteristics that place them at increased risk of falling. Assessment for these factors may be important to offer more targeted rehabilitation interventions. [ABSTRACT FROM AUTHOR]

Objectives Trial data have provided an evidence base to guide early treatment in RA. Few studies have investigated rheumatologists' adherence to guidelines, and subsequent impact on outcomes. The objectives of this study are to characterize baseline prescribing for patients with RA across the National Health Service, identifying treatment decisions that associate with patient outcomes. Methods A nationwide audit of RA collected information on treatment choices, DAS and sociodemographic factors at baseline. Treatment response was assessed at 3 months. Multilevel regression models were used to characterize departmental variations in prescribing. Heat maps were used to visualize geographical variation. Mixed effects regression models were constructed to assess the relationship between treatment decisions and disease outcomes, adjusting for patient and department level covariates. Results A total of 7154 patients with a diagnosis of RA were recruited from 136 departments. There was broad variation in prescribing choices, even between departments close to one another, with evidence of substantial deviation from guidelines. Over 75% of patients received glucocorticoids, fewer than half received combination conventional DMARDs. Early glucocorticoid therapy associated with achieving a good treatment response [odds ratio 1.93 (95% CI 1.31, 2.84), P -value = 0.001]. The association was maintained following propensity modelling and imputation. Conclusion Guideline adherence varies between departments and cannot be explained by case-mix alone. Departments that prescribe early adjunctive steroid achieve better short-term outcomes. Further research should work to ensure that the early arthritis evidence base translates into better outcomes for patients. [ABSTRACT FROM AUTHOR]

Objectives Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. Methods Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). Results Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R 2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <−2.6, P < 0.01), Larsen score and presence of erosions. Conclusion A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established. [ABSTRACT FROM AUTHOR]

Objectives. To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years. Methods. Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression. Results. Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient's risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [β = 0.17 (95% CI 0.03, 0.32)]. Conclusion. HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment. [ABSTRACT FROM AUTHOR]

The author discusses the role of therapeutic virtual reality (VR) in the future management of chronic pain as indicated in several studies. Topics covered include the importance of attention in modulating pain, how modulation of neural activity during acute painful stimuli has been shown to occur during VR experiences and the evidence from clinical trials that VR significantly reduces subjective experiences of acute pain. It tackles VR as a tool for traditional non-pharmacological treatments.

Although a higher protein intake, particularly from vegetable sources, has been shown to be associated with higher bone mineral density (BMD) the relative impact of specific amino acids on BMD and risk of osteoporosis remains to be determined. Mechanistic research suggests that a number of specific amino acids, including five nonessential amino acids-alanine, arginine, glutamic acid, glycine, and proline-may play a role in bone health, principally through improved production of insulin and insulin-like growth factor 1 and the synthesis of collagen and muscle protein. However to date, no previous studies have examined the associations between habitual intake of amino acids and direct measures of BMD and prevalence of osteoporosis or osteopenia, and no studies have examined this relationship in discordant identical twin-pairs. In these analyses of female monozygotic twin-pairs discordant for amino acid intake ( n = 135), twins with higher intakes of alanine and glycine had significantly higher BMD at the spine than their co-twins with within-pair differences in spine-BMD of 0.012 g/cm2 (SE 0.01; p = 0.039) and 0.014 g/cm2 (SE 0.01; p = 0.026), respectively. Furthermore, in cross-sectional multivariable analyses of 3160 females aged 18 to 79 years, a higher intake of total protein was significantly associated with higher DXA-measured BMD at the spine (quartile Q4 to quartile Q1: 0.017 g/cm2, SE 0.01, p = 0.035) and forearm (Q4 to Q1: 0.010 g/cm2, SE 0.003, p = 0.002). Intake of six amino acids (alanine, arginine, glutamic acid, leucine, lysine, and proline) were associated with higher BMD at the spine and forearm with the strongest association observed for leucine (Q4 to Q1: 0.024 g/cm2, SE 0.01, p = 0.007). When intakes were stratified by protein source, vegetable or animal, prevalence of osteoporosis or osteopenia was 13% to 19% lower comparing extreme quartiles of vegetable intake for five amino acids (not glutamic acid or proline). These data provide evidence to suggest that intake of protein and several amino acids, including alanine and glycine, may be beneficial for bone health, independent of genetic background. © 2015 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Age-related loss of skeletal muscle mass and strength are risk factors for sarcopenia, osteoporosis, falls, fractures, frailty, and mortality. Dietary magnesium (Mg) could play a role in prevention of age-related loss of skeletal muscle mass, power, and strength directly through physiological mechanisms or indirectly through an impact on chronic low-grade inflammation, itself a risk factor for loss of skeletal muscle mass and strength. In a cross-sectional study of 2570 women aged 18 to 79 years, we examined associations between intakes of Mg, estimated using a food-frequency questionnaire (FFQ), dual-energy X-ray absorptiometry (DXA)-derived measures of muscle mass (fat-free mass as a percentage of body weight [FFM%], fat-free mass index [FFMI, kg/m2]), leg explosive power (LEP), and grip strength ( n = 949 only). We also examined associations between circulating hs-CRP (C-reactive protein) and muscle mass and LEP, and explored the potential attenuation of these relationships by Mg. We compared our findings with those of age and protein intake. Endpoints were calculated by quintile of Mg and adjusted for relevant confounders. Significant positive associations were found between a higher Mg and indices of skeletal muscle mass and LEP, and also with hs-CRP, after adjustment for covariates. Contrasting extreme quintiles of Mg intake showed differences of 2.6% for FFM% ( p trend < 0.001), 0.4 kg/m2 for FFMI ( p trend = 0.005), and 19.6 watts/kg for LEP ( p trend < 0.001). Compared with protein, these positive associations were 7 times greater for FFM% and 2.5 times greater for LEP. We also found that higher hs-CRP was negatively associated with skeletal muscle mass and, in statistical modeling, that a higher dietary Mg attenuated this negative relationship by 6.5%, with greater attenuation in women older than 50 years. No association was found between Mg and grip strength. Our results suggest that dietary magnesium may aid conservation of age-related loss of skeletal muscle mass and power in women of all ages. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the occurrence of giant cell arteritis (GCA) in Great Britain as of May 2014, particularly in individuals 55 years old and above.