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Background: Although the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of constituents of plant-based foods.Methods: We aimed to determine whether higher habitual intake of dietary flavonoids, key components of plant-based diets, were associated with improved cognition and medial temporal lobe volumes using three complementary approaches (longitudinal, cross-sectional and co-twin analyses). In 1126 female twins (n=224 with a 10-year follow-up of diet and cognition data) aged 18-89 years, habitual intakes of total flavonoids and seven subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymeric flavonoids (and proanthocyanidins separately)) were calculated using validated food frequency questionnaires. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery test. Hippocampal volumes were measured in a subset using magnetic resonance imaging (16 monozygotic-twin pairs). Statistical models were adjusted for a range of diet and lifestyle factors.Results: Higher intakes of flavanones (tertile (T)3-T1=0.45, 95%CI 0.13,0.77; p=0.01) and anthocyanins (T3-T1=0.45, 95%CI 0.08,0.81; p=0.02) were associated with improvements in age-related cognition score over 10 years. In cross-sectional analysis higher intake of flavanones (T3-T1= 0.12, 95% CI 0.02, 0.21; p=0.02) and proanthocyanidins (T3-T1= 0.13, 95% CI 0.02, 0.24; p=0.02) were associated with improved paired-associates learning. Higher intake of anthocyanins was significantly associated with improved executive function (T3-T1= -0.52, 95% CI 0.19, 0.84; p=0.001) and with faster simple reaction times (T3-T1= -18.1, 95% CI -35.4, -0.7; p=0.04). In co-twin analysis, those with higher anthocyanin (2.0%, p=0.01) and proanthocyanidin (2.0%, p=0.02) intakes at baseline had the largest left hippocampal volumes after 12 years.Conclusion: Small increases in habitual intake of flavonoid-rich foods (containing anthocyanins, flavanones and proanthocyanidins; equivalent to approximately two servings of oranges and blueberries per day) over long time periods have the potential to attenuate cognitive ageing. [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G‐PROB) has been developed to aid diagnosis has not yet been tested in a real‐world setting. Our aim was to assess whether G‐PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. Methods: Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G‐probabilities (0%–100%) were created for each patient based on known disease‐associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or "other diseases." Performance of the G‐probabilities compared with clinician diagnosis was assessed. Results: We tested G‐PROB on 1,047 patients. Calibration of G‐probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G‐probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84–0.86). G‐probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G‐probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G‐probability corresponded to clinician diagnosis. Conclusion: G‐PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) leads to biomechanical joint changes, which increases the risk of falling. The consequence of falling may be physical injury. However, the psychological consequences, including the fear of falling, can be equally important. Methods: Participants were recruited from a larger prospective study which explored the incidence of falls in people with RA. Purposive sampling considered age, sex, time since diagnosis and fall history. The recruitment site was a regional hospital. Data were collected from semi‐structured qualitative interviews and, after each fall, brief telephone interviews. Thematic analysis methods were used to investigate the psychological and social impact of falling in people with RA. Results: Twelve participants were interviewed (aged 64–85, mean 74 years; six had fallen between one and 23 times, and six had no reported falls in last 12 months). Data were supplemented with telephone notes from 287 post‐fall telephone calls. Three themes were developed: (i) the falls imaginary illustrates that the fear of falling is not dependent on experience; (ii) agentic risk management reports on the ways people self‐manage and display resilience when at risk of falling; (iii) the absence of the health professional explores the ways in which people reported being unsupported by healthcare services. Conclusion: Fear of falling when living with RA is tangible in those who have and have not fallen. This fear may limit opportunities for full participation in life. However, some people display personal resourcefulness, continuing to live purposeful lives. Understanding personal responses to falling will support the development of community interventions specific to this high‐risk group. [ABSTRACT FROM AUTHOR]

Background: Plant-based diets may provide protection against cognitive decline and Alzheimer's disease, but observational data have not been consistent. Previous studies include early life confounding from socioeconomic conditions and genetics that are known to influence both cognitive performance and diet behaviour. This study investigated associations between Mediterranean (MED) diet and MIND diets and cognitive performance accounting for shared genotype and early-life environmental exposures in female twins. Methods: Diet scores were examined in 509 female twins enrolled in TwinsUK study. The Cambridge Neuropsychological Test Automated Battery was used to assess cognition at baseline and 10 years later (in n = 275). A co-twin case–control study for discordant monozygotic (MZ) twins examined effects of diet on cognitive performance independent of genetic factors. Differences in relative abundance of taxa at 10-year follow-up were explored in subsamples. Results: Each 1-point increase in MIND or MED diet score was associated with 1.75 (95% CI: − 2.96, − 0.54, p = 0.005 and q = 0.11) and 1.67 (95% CI: − 2.71, − 0.65, p = 0.002 and q = 0.02) fewer respective errors in paired-associates learning. Within each MZ pair, the twin with the high diet score had better preservation in spatial span especially for MED diet (p = 0.02). There were no differences between diet scores and 10-year change in the other cognitive tests. MIND diet adherence was associated with higher relative abundance of Ruminococcaceae UCG-010 (0.30% (95% CI 0.17, 0.62), q = 0.05) which was also associated with less decline in global cognition over 10 years (0.22 (95% CI 0.06, 0.39), p = 0.01). Conclusions: MIND or MED diets could help to preserve some cognitive abilities in midlife, particularly episodic and visuospatial working memory. Effects may be mediated by high dietary fibre content and increased abundance of short-chain fatty acid producing gut bacteria. Longer follow-up with repeated measures of cognition will determine whether diet can influence changes in cognition occurring in older age. [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.

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]

A letter to the editor is presented in response to the article "Mortality and implant revision rates of hip arthroplasty in patients with osteoarthritis: registry based cohort study," by D.J.W. McMinn, published in the 14 June 2012 issue.

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]

Fibromyalgia Syndrome (FMS) is highly prevalent with a significant associated morbidity and socioeconomic burden. Effective treatments for FMS remain elusive with pharmacological management (including use of opioids) often proving ineffective. There is a need to develop accessible, innovative management approaches to improve patient care.Virtual reality (VR) interventions have shown evidence of efficacy in the management of acute pain and chronic low back pain, but their feasibility in FMS has not hitherto been explored.This feasibility study investigates the use of four different VR systems, four interactive VR activities and two virtual environments in patients with FMS. Acceptability (including adverse effects) and study engagement were the main outcomes investigated. Clinical outcome data on pain and mood were also collected to gather preliminary information for future studies.The results demonstrated good feasibility across VR systems, activities and virtual environments with high levels of acceptability, low frequency of adverse effects, and positive perceptions of VR in patients with FMS. Reporting of adverse effects (including fatigue) varied across different VR components, with system comfort and virtual environmental design being particularly important.The findings increase our confidence with respect to the feasibility of using VR in people with FMS, help to inform future randomised controlled trials and emphasise the importance of tailored interventional design for future VR therapeutics. [ABSTRACT FROM AUTHOR]

Objective Joint hypermobility can lead to pain and motor developmental problems in children and young people (CYP). Exercise programmes may help CYP with joint hypermobility strengthen core muscle groups. Non- adherence to home physiotherapy is common. The present study aimed to understand how families experienced an intensive multidisciplinary intervention. Method This was a qualitative study nested within a randomized controlled trial of a multidisciplinary treatment intervention, including physiotherapy, for children aged five to 17 years. Twenty-eight families were recruited following the intervention. Semi-structured interviews were used to examine the views and expectations of parents and CYP, and examine adherence to the exercise programme. Thematic analysis of data was used to develop findings. Results Parents and CYP reported that exercise reduced the symptoms of hypermobility. Parental motivation, adapting family routines, making exercise a family activity and seeing benefit increased adherence to exercise. Non-adherence to exercise was linked to lower levels of parental supervision, not understanding the treatment, not seeing benefit and not having specific time to dedicate to doing the exercises. Conclusion Even when exercise is seen to benefit a child's well-being, families experience challenges in adhering to a physiotherapy programme for hypermobility. Therapists can utilize findings on what enhances adherence to help CYP effectively exercise in the home setting. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Nutrition plays an important role in human metabolism and health. Metabolomics is a promising tool for clinical, genetic and nutritional studies. A key question is to what extent metabolomic profiles reflect nutritional patterns in an epidemiological setting. We assessed the relationship between metabolomic profiles and nutritional intake in women from a large cross-sectional community study. Food frequency questionnaires (FFQs) were applied to 1,003 women from the TwinsUK cohort with targeted metabolomic analyses of serum samples using the Biocrates Absolute-IDQ™ Kit p150 (163 metabolites). We analyzed seven nutritional parameters: coffee intake, garlic intake and nutritional scores derived from the FFQs summarizing fruit and vegetable intake, alcohol intake, meat intake, hypo-caloric dieting and a 'traditional English' diet. We studied the correlation between metabolite levels and dietary intake patterns in the larger population and identified for each trait between 14 and 20 independent monozygotic twins pairs discordant for nutritional intake and replicated results in this set. Results from both analyses were then meta-analyzed. For the metabolites associated with nutritional patterns, we calculated heritability using structural equation modelling. 42 metabolite nutrient intake associations were statistically significant in the discovery samples (Bonferroni P < 4 × 10) and 11 metabolite nutrient intake associations remained significant after validation. We found the strongest associations for fruit and vegetables intake and a glycerophospholipid (Phosphatidylcholine diacyl C38:6, P = 1.39 × 10) and a sphingolipid (Sphingomyeline C26:1, P = 6.95 × 10). We also found significant associations for coffee (confirming a previous association with C10 reported in an independent study), garlic intake and hypo-caloric dieting. Using the twin study design we find that two thirds the metabolites associated with nutritional patterns have a significant genetic contribution, and the remaining third are solely environmentally determined. Our data confirm the value of metabolomic studies for nutritional epidemiologic research. [ABSTRACT FROM AUTHOR]

Abstract: A UV method for the analysis of ascorbic acid with methanol as solvent to prepare a sample has been developed and applied. The effect of copper(II) concentrations on the oxidation of ascorbic acid in aqueous solution has been studied in detail, and the regularities of ascorbic acid oxidation in methanol, USP phosphate buffer (pH 2.50) and de-ionized water have been found. Upon experiments ascorbic acid has been found to dissolve in methanol, and its solubility in it has been measured to be 81.0mg/ml at room temperature (22°C). The ascorbic acid bulk material from a manufacturer has been assayed to be 89.34% with this method, in good agreement with the assay value (89.58%) from the titration method. The ascorbic acid granule and tablet content uniformity also has been tested using this method. This method is simple, rapid, accurate and reliable, and can be adopted for the routine determination of ascorbic acid in its granule and tablet formulations. [Copyright &y& Elsevier]

Aim: To assess revision rates and postoperative mortality in patients undergoing hip arthroplasty (HA) for inflammatory arthritis compared to hip osteoarthritis (OA). Methods: The analysis was conducted among cases of HA that were recorded in the National Joint Registry for England and Wales (NJR) between April 2003 and December 2012 and linked to Office for National Statistics mortality records. Procedures were identified where the indication for surgery was listed as seropositive rheumatoid arthritis (RA), ankylosing spondylitis (AS), other inflammatory arthritis (otherIA), or OA. 5-year revision risk and 90-day postoperative mortality according to indication were compared using Cox regression models adjusted for age, sex, American Society of Anaesthesiologists (ASA) grade, year of operation, implant type, and surgical approach. Results: The cohort included 1457 HA procedures conducted for RA, 615 for AS, 1000 for otherIA, and 183,108 for OA. When compared with OA, there was no increased revision risk for any form of inflammatory arthritis (adjusted HRs: RA: 0.93 (0.64–1.35); AS: 1.14 (0.73–1.79); otherIA: 1.08 (0.73–1.59)). Postoperative 90-day mortality was increased for RA when compared with OA (adjusted HR: 2.86 (1.68–4.88)), but not for AS (adjusted HR: 1.56 (0.59–4.18)) or otherIA (adjusted HR: 0.64 (0.16–2.55)). Conclusions: The revision risk in HA performed for all types of inflammatory arthritis is similar to that for HA performed for OA. The 3-fold increased risk of 90-day mortality in patients with RA compared with OA highlights the need for active management of associated comorbidities in RA patients during the perioperative period. [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]

Background: Continuous monitoring of surgical outcomes after joint replacement is needed to detect which brands' components have a higher than expected failure rate and are therefore no longer recommended to be used in surgical practice. We developed a monitoring method based on cumulative sum (CUSUM) chart specifically for this application.Methods: Our method entails the use of the competing risks model with the Weibull and the Gompertz hazard functions adjusted for observed covariates to approximate the baseline time-to-revision and time-to-death distributions, respectively. The correlated shared frailty terms for competing risks, corresponding to the operating unit, are also included in the model. A bootstrap-based boundary adjustment is then required for risk-adjusted CUSUM charts to guarantee a given probability of the false alarm rates. We propose a method to evaluate the CUSUM scores and the adjusted boundary for a survival model with the shared frailty terms. We also introduce a unit performance quality score based on the posterior frailty distribution. This method is illustrated using the 2003-2012 hip replacement data from the UK National Joint Registry (NJR).Results: We found that the best model included the shared frailty for revision but not for death. This means that the competing risks of revision and death are independent in NJR data. Our method was superior to the standard NJR methodology. For one of the two monitored components, it produced alarms four years before the increased failure rate came to the attention of the UK regulatory authorities. The hazard ratios of revision across the units varied from 0.38 to 2.28.Conclusions: An earlier detection of failure signal by our method in comparison to the standard method used by the NJR may be explained by proper risk-adjustment and the ability to accommodate time-dependent hazards. The continuous monitoring of hip replacement outcomes should include risk adjustment at both the individual and unit level. [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]

Background: The influence of obesity on outcomes following total hip replacement is unclear. Restriction of total hip replacement on the basis of body mass index (BMI) has been suggested. The purpose of this study was to assess the influence of BMI on the risk of revision and 90-day mortality.Methods: This was a population-based, longitudinal cohort study of the National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man. Using data recorded from April 2003 to December 2015, linked to Office for National Statistics data, we ascertained revision and 90-day mortality rates following primary total hip replacement by BMI category. The probability of revision was estimated using Kaplan-Meier methods. Associations of BMI with revision and mortality were explored using adjusted Cox proportional hazards regression models.Results: We investigated revision and 90-day mortality among 415,598 and 413,741 primary total hip replacements, respectively. Each data set accounts for approximately 52% of the total number of recorded operations in the NJR. Thirty-eight percent of the patients were classified as obese. At 10 years, class-III obese patients had the highest cumulative probability of revision (6.7% [95% confidence interval (CI), 5.5% to 8.2%]), twice that of the underweight group (3.3% [95% CI, 2.2% to 4.9%]). When the analysis was adjusted for age, sex, American Society of Anesthesiologists [ASA] grade, year of operation, indication, and fixation type, compared with patients with normal BMI, significantly elevated hazard ratios (HRs) for revision were observed for patients in the BMI categories of class-I obese (≥30 to <35 kg/m) (HR, 1.14 [95% CI, 1.07 to 1.22]), class-II obese (≥35 to <40 kg/m) (HR, 1.30 [95% CI, 1.19 to 1.40]), and class-III obese (≥40 to ≤60 kg/m) (HR, 1.43 [95% CI, 1.27 to 1.61]) (p < 0.0005 for all). Underweight patients had a substantially higher cumulative probability of 90-day mortality (1.17%; 95% CI, 0.86% to 1.58%) compared with patients with normal BMI (0.43%; 95% CI, 0.39% to 0.48%). The risk of 90-day mortality was significantly higher for the underweight group (HR, 2.09 [95% CI, 1.51 to 2.89]; p < 0.0005) and significantly lower for patients who were categorized as overweight (HR, 0.70; 95% CI, 0.61 to 0.81; p < 0.0005), class-I obese (HR, 0.69 [95% CI, 0.59 to 0.81]; p < 0.0005), and class-II obese (HR, 0.79 [95% CI, 0.63 to 0.98]; p = 0.049) compared with patients with normal BMI.Conclusions: Although long-term revision rates following total hip replacement were higher among obese patients, we believe that the rates remained acceptable by contemporary standards and were balanced by a lower risk of 90-day mortality.Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Purpose: Milk provides a significant source of calcium, protein, vitamins and other minerals to Western populations throughout life. Due to its widespread use, the metabolic and health impact of milk consumption warrants further investigation and biomarkers would aid epidemiological studies. Methods: Milk intake assessed by a validated food frequency questionnaire was analyzed against fasting blood metabolomic profiles from two metabolomic platforms in females from the TwinsUK cohort ( n = 3559). The top metabolites were then replicated in two independent populations (EGCUT, n = 1109 and KORA, n = 1593), and the results from all cohorts were meta-analyzed. Results: Four metabolites were significantly associated with milk intake in the TwinsUK cohort after adjustment for multiple testing ( P < 8.08 × 10) and covariates (BMI, age, batch effects, family relatedness and dietary covariates) and replicated in the independent cohorts. Among the metabolites identified, the carnitine metabolite trimethyl-N-aminovalerate ( β = 0.012, SE = 0.002, P = 2.98 × 10) and the nucleotide uridine ( β = 0.004, SE = 0.001, P = 9.86 × 10) were the strongest novel predictive biomarkers from the non-targeted platform. Notably, the association between trimethyl-N-aminovalerate and milk intake was significant in a group of MZ twins discordant for milk intake ( β = 0.050, SE = 0.015, P = 7.53 × 10) and validated in the urine of 236 UK twins ( β = 0.091, SE = 0.032, P = 0.004). Two metabolites from the targeted platform, hydroxysphingomyelin C14:1 ( β = 0.034, SE = 0.005, P = 9.75 × 10) and diacylphosphatidylcholine C28:1 ( β = 0.034, SE = 0.004, P = 4.53 × 10), were also replicated. Conclusions: We identified and replicated in independent populations four novel biomarkers of milk intake: trimethyl-N-aminovalerate, uridine, hydroxysphingomyelin C14:1 and diacylphosphatidylcholine C28:1. Together, these metabolites have potential to objectively examine and refine milk-disease associations. [ABSTRACT FROM AUTHOR]

Objectives: Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results 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-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve 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-naïve 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Aims: The aim of this study was to capture 12-month outcomes from a representative multicentre cohort of patients undergoing total ankle arthroplasty (TAA), describe the pattern of patient-reported outcome measures (PROMs) at 12 months, and identify predictors of these outcome measures., Methods: Patients listed for a primary TAA at 19 NHS hospitals between February 2016 and October 2017 were eligible. PROMs data were collected preoperatively and at six and 12 months including: Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ (foot and ankle)) and the EuroQol five-dimension five-level questionnaire (EQ-5D-5L). Radiological pre- and postoperative data included Kellgren-Lawrence score and implant position measurement. This was supplemented by data from the National Joint Registry through record linkage to determine: American Society of Anesthesiologists (ASA) grade at index procedure; indication for surgery, index ankle previous fracture; tibial hind foot alignment; additional surgery at the time of TAA; and implant type. Multivariate regression models assessed outcomes, and the relationship between MOXFQ and EQ-5D-5L outcomes, with patient characteristics., Results: Data from 238 patients were analyzed. There were significant improvements in MOXFQ and EQ-5D-5L among people who underwent TAA at six- and 12-month assessments compared with preoperative scores (p < 0.001). Most improvement occurred between preoperative and six months, with little further improvement at 12 months. A greater improvement in MOXFQ outcome postoperatively was associated with older age and more advanced radiological signs of ankle osteoarthritis at baseline., Conclusion: TAA significantly benefits patients with end-stage ankle disease. The lack of substantial further overall change between six and 12 months suggests that capturing PROMs at six months is sufficient to assess the success of the procedure. Older patients and those with advanced radiological disease had the greater gains. These outcome predictors can be used to counsel younger patients and those with earlier ankle disease on the expectations of TAA., Competing Interests: None declared., (© 2023 The British Editorial Society of Bone & Joint Surgery.)

Objective: The diagnosis of axial spondyloarthritis (axSpA) is hampered by diagnostic delay. Computed tomography (CT) undertaken for nonmusculoskeletal (non-MSK) indications in patients with inflammatory bowel disease (IBD) offers an opportunity to identify sacroiliitis for prompt rheumatology referral. This study aims to identify what proportion of patients with IBD who underwent abdominopelvic CT for non-MSK indications have axSpA and to explore the role of a standardized screening tool to prospectively identify axSpA on imaging., Methods: Abdominopelvic CT scans of patients with verified IBD, aged 18 to 55 years, performed for non-MSK indications were reviewed by radiologists for the presence of CT-defined sacroiliitis (CTSI), using criteria from a validated CT screening tool. All patients identified were sent a screening questionnaire, and those with self-reported chronic back pain (CBP), CBP duration of greater than 3 months, and age of onset of less than 45 years were invited for rheumatology review., Results: CTSI was identified in 60 out of 301 (19.9%) patients. Out of these 60 patients, 32 (53%) responded to an invitation to participate, and 27 out of 32 (84.3%) were enrolled. Of these, 8 had a preexisting axSpA diagnosis and 5 did not report CBP. In total, 14 patients underwent rheumatology assessment, and 3 out of 14 (21.4%, 95% CI 4.7-50.8) had undiagnosed axSpA. In total, 11 out of 27 (40.7%, 95% CI 22.4-61.2) patients had a rheumatologist-verified diagnosis of axSpA., Conclusion: In this study, 5% (3/60) of patients with IBD undergoing abdominopelvic CT for non-MSK indications with CTSI were found to have undiagnosed axSpA and, overall, 18.3% (11/60) were found to have axSpA. This reveals a significant hidden population of axSpA and highlights the need for a streamlined pathway from sacroiliitis detection to rheumatology referral., (Copyright © 2023 by the Journal of Rheumatology.)

Background: Several long-term chronic illnesses are known to be associated with an increased risk of dementia independently, but little is known how combinations or clusters of potentially interacting chronic conditions may influence the risk of developing dementia., Methods: 447 888 dementia-free participants of the UK Biobank cohort at baseline (2006-2010) were followed-up until 31 May 2020 with a median follow-up duration of 11.3 years to identify incident cases of dementia. Latent class analysis (LCA) was used to identify multimorbidity patterns at baseline and covariate adjusted Cox regression was used to investigate their predictive effects on the risk of developing dementia. Potential effect moderations by C reactive protein (CRP) and Apolipoprotein E (APOE) genotype were assessed via statistical interaction., Results: LCA identified four multimorbidity clusters representing Mental health , Cardiometabolic , Inflammatory/autoimmune and Cancer -related pathophysiology, respectively. Estimated HRs suggest that multimorbidity clusters dominated by Mental health (HR=2.12, p<0.001, 95% CI 1.88 to 2.39) and Cardiometabolic conditions (2.02, p<0.001, 1.87 to 2.19) have the highest risk of developing dementia. Risk level for the Inflammatory/autoimmune cluster was intermediate (1.56, p<0.001, 1.37 to 1.78) and that for the Cancer cluster was least pronounced (1.36, p<0.001, 1.17 to 1.57). Contrary to expectation, neither CRP nor APOE genotype was found to moderate the effects of multimorbidity clusters on the risk of dementia., Conclusions: Early identification of older adults at higher risk of accumulating multimorbidity of specific pathophysiology and tailored interventions to prevent or delay the onset of such multimorbidity may help prevention of dementia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10 -8 ), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aims: To determine the trajectories of patient reported pain and functional disability over five years following total hip arthroplasty (THA) or total knee arthroplasty (TKA)., Methods: A prospective, longitudinal cohort sub-study within the National Joint Registry (NJR) was undertaken. In all, 20,089 patients who underwent primary THA and 22,489 who underwent primary TKA between 2009 and 2010 were sent Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires at six months, and one, three, and five years postoperatively. OHS and OKS were disaggregated into pain and function subscales. A k-means clustering procedure assigned each patient to a longitudinal trajectory group for pain and function. Ordinal regression was used to predict trajectory group membership using baseline OHS and OKS score, age, BMI, index of multiple deprivation, sex, ethnicity, geographical location, and American Society of Anesthesiologists grade., Results: Data described two discrete trajectories for pain and function: 'level 1' responders (around 70% of cases) in whom a high level of improvement is sustained over five years, and 'level 2' responders who had sustained improvement, but at a lower level. Baseline patient variables were only weak predictors of pain trajectory and modest predictors of function trajectory. Those with worse baseline pain and function tended to show a greater likelihood of following a 'level 2' trajectory. Six-month patient-reported outcome measures data reliably predicted the class of five-year outcome trajectory for both pain and function., Conclusion: The available preoperative patient variables were not reliable predictors of postoperative pain and function after THA and TKA. Reviewing patient outcomes at six months postoperatively is a reliable indicator of outcome at five years. Cite this article: Bone Joint J  2021;103-B(6):1111-1118.