Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis.

OBJECTIVES: To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. METHODS: Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. RESULTS: This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. CONCLUSION: Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.

The reliability of radiographic measures of total ankle replacement position: an analysis from the OARS cohort.

OBJECTIVE: There is no validated radiographic measurement to diagnose prosthetic complication(s) following total ankle replacements (TARs) although a number of angular and linear measurements, used to define the TAR position on postoperative radiographs, have been recommended to detect prosthetic loosening. The aim of this study was to test the intra- and interobserver reliability of these measurements. MATERIALS AND METHODS: This is a prospective study embedded within a multicentre cohort study. Following sample size calculation, 62 patients were analysed. Six measurements were performed on the first postoperative anteroposterior and lateral ankle radiographs: angles α and ß, and length "a" defined the craniocaudal position of the tibial component, while angle γ, and lengths "b" and "c" defined the angular position of the talar component. Measurements were recorded by three independent observers. Inter- and intraobserver reliability was assessed with intraclass correlation coefficient (ICC), Bland-Altman plots, and within-subject coefficients of variation (CV). RESULTS: The intrarater ICC was "almost perfect" (ICC 0.83-0.97) for all six measurements. The interrater ICC was "substantial" to "almost perfect" (ICC 0.69-0.93). The mean difference in intrarater angular measurements was ≤ 0.6° and ≤ 0.8 mm for linear measurements, and ≤ 2.2° and ≤ 2.1 mm for interrater measurements. Maximum CV for the interrater linear measurements (≤ 17.7%) more than doubled that of the angular measurements (≤ 8.0%). The maximum width of the 95% limits of agreement was 6.5° and 8.4 mm for intrarater measures, and 8.9° and 10.6 mm for interrater measurements. CONCLUSION: Angular measures are more reliable than linear measures and have potential in routine clinical practice for TAR position assessment.

Cardiovascular risk factors associated with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Study.

OBJECTIVES: PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. METHODS: Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. RESULTS: In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. CONCLUSION: PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.

Trajectory of social isolation following hip fracture: an analysis of the English Longitudinal Study of Ageing (ELSA) cohort.

Background: social isolation is defined as a lack of meaningful and sustained communication or interactions with social networks. There is limited understanding on the prevalence of social isolation and loneliness in people following hip fracture and no previous understanding of how this changes over time. Objective: to determine the prevalence and trajectory of social isolation and loneliness before a hip fracture, during the recovery phase and a minimum of 2 years post-hip fracture in an English population. Methods: data were from the English Longitudinal Study of Ageing (ELSA) cohort (2004/5-2014/15). The sample comprised of 215 participants who had sustained a hip fracture. Measures of social isolation and loneliness were analysed through multilevel modelling to determine their trajectories during three-time intervals (pre-fracture; interval at hip fracture and recovery; minimum 2 years post-fracture). The prevalence of social isolation and loneliness were determined pre- and post-fracture. Results: prevalence of social isolation was 19% post-hip fracture and loneliness 13% post-hip fracture. There was no statistically significant change in social isolation pre-fracture compared to a minimum of 2 years post-fracture (P = 0.78). Similarly, there was no statistically significant change in loneliness pre-fracture compared to a minimum of 2 years post-fracture (P = 0.12). Conclusion: this analysis has determined that whilst social isolation and loneliness do not change over time following hip fracture, these remain a significant problem for this population. Interventions are required to address these physical and psychological health needs. This is important as they may have short and longer term health benefits for people post-hip fracture.

The association of vascular risk factors with visual loss in giant cell arteritis.

Objective: Blindness is a recognized complication of GCA; however, the frequency of and risk factors for this complication have not been firmly established. The aim of this study was to examine the incidence and determinants of blindness in patients with GCA, using a large international cohort. Methods: The analysis was conducted among subjects recruited into the Diagnosis and Classification Criteria in Vasculitis Study. The study captures consecutive patients presenting to clinic-based physicians. New-onset blindness was assessed 6 months after diagnosis by completion of the Vasculitis Damage Index. Logistic regression analysis was used to assess the association between blindness and clinical variables. Results: Of 433 patients with GCA from 26 countries, 7.9% presented with blindness in at least one eye at 6 months. Risk factors identified at baseline for blindness at 6 months were identified and included prevalent stroke [odds ratio (OR) = 4.47, 95% CI: 1.30, 15.41] and peripheral vascular disease (OR = 10.44, 95% CI: 2.94, 37.03). Conclusion: This is the largest study to date of subjects with incident GCA and confirms that blindness remains a common complication of disease and is associated with established vascular disease.Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov , NCT01066208.

Can Rheumatologists Predict Eventual Need for Orthopaedic Intervention in Patients with Rheumatoid Arthritis? Results of a Systematic Review and Analysis of Two UK Inception Cohorts.

PURPOSE OF REVIEW: The structural damage caused by rheumatoid arthritis (RA) can often be mitigated by orthopaedic surgery in late disease. This study evaluates the value of predictive factors for orthopaedic intervention. METHODS: A systematic review of literature was undertaken to identify papers describing predictive factors for orthopaedic surgery in RA. Manuscripts were selected if they met inclusion criteria of cohort study design, diagnosis of RA, follow-up duration/disease duration ≥3 years, any orthopaedic surgical interventions recorded, and then summarised for predictive factors. A separate predictive analysis was performed on two consecutive UK Early RA cohorts, linked to national datasets. RECENT FINDINGS: The literature search identified 15 reports examining predictive factors for orthopaedic intervention, 4 inception, 5 prospective and 6 retrospective. Despite considerable variation, acute phase, x-ray scores, women and genotyping were the most commonly reported prognostic markers. The current predictive analysis included 1602 procedures performed in 711 patients (25-year cumulative incidence 26%). Earlier recruitment year, erosions and lower haemoglobin predicted both intermediate and major surgery (P<0.05). Studies report variations in type of and predictive power of clinical and laboratory parameters for different surgical interventions suggesting specific contributions from different pathological and/or patient-level factors. Our current analysis suggests that attention to non-inflammatory factors in addition to suppression of inflammation is needed to minimise the burden of orthopaedic surgery.

Changes in physical activity following total hip or knee arthroplasty: a matched case-control study from the EPIC-Norfolk cohort.

OBJECTIVE: To assess self-reported physical activity changes pre- compared to post-operatively in patients undergoing total hip or knee arthroplasty, and to compare this to an age- and gender-matched cohort of people who have not undergone arthroplasty. DESIGN: Population-based prospective cohort study. SETTING: Norfolk, United Kingdom. SUBJECTS: People who had undergone hip or knee arthroplasty, compared to an age- and gender-matched non-arthroplasty cohort. INTERVENTION: Primary total hip or knee arthroplasty. MAIN MEASURES: Physical activity, measured using the EPIC Physical Activity Questionnaire (EPAQ2). RESULTS: A total of 400 people from the EPIC-Norfolk community cohort were identified who had undergone hip or knee arthroplasty. In all, 767 people were identified to form an age- and gender-matched non-arthroplasty cohort. Mean post-operative follow-up was 43 months post-total hip and 41 months post-total knee arthroplasty. There was a statistically significant reduction from pre- to post-arthroplasty in the number of flights of stairs climbed weekly (hip: mean difference (MD): 6.8; P < 0.01; knee: MD: 10.2; P < 0.01), duration of walking (hip: MD: 1.4 hours/week; P = .02; knee: MD: 2.2 hours/week; P < 0.01) and duration of total recreational activity (hip: MD: 1.1 hours/week; P = 0.02). Compared to the non-arthroplasty cohort, duration of physical activity was lower post-total hip arthroplasty (MD: 1.8 hours/week; P = 0.01). The number of flights of stairs climbed weekly (MD: 12.0; P < 0.01), total recreational activity (MD: 1.7 hours/week; P = 0.04) and physical activity energy expenditure (MD: 5.7 Mets-hours/week; P = 0.05) were lower for people post-total knee arthroplasty compared to the matched controls. CONCLUSIONS: Physical activity did not increase, and in some instances decreased, following total hip or knee arthroplasty.

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.

The relationship between Modic changes and intervertebral disc degeneration.

BACKGROUND: Recent reported results have added to the weight of evidence supporting association between disc degeneration and Modic changes. Endplate or Modic changes are also associated with increased body mass index. The most recent study from Teichtahl et al. titled 'Modic changes in the lumbar spine and their association with body composition, fat distribution and intervertebral disc height - a 3.0 T-MRI study' showed associations of Modic changes with quantitatively measured reduced disc height and fat mass index. However, there were some facts, which we would like to address in this Correspondence to their article. DISCUSSION: The different components of intervertebral disc degeneration such as loss of disc height and disc signal intensity have already been shown associated with endplate changes - but not disc height if it is assessed using newer more precise methods of quantitation of disc height. A possible protective effect of different adiposity distribution in the body to Modic change development would be of interest if observed in a longitudinal study in the future. Modic changes have been associated with different components of intervertebral disc degeneration such as loss of disc height and disc signal intensity previously. The influence of body fat distribution on endplate changes would be interesting to study longitudinally.

45-day mortality after 467,779 knee replacements for osteoarthritis from the National Joint Registry for England and Wales: an observational study.

BACKGROUND: Understanding the risk factors for early death after knee replacement could help to reduce the risk of mortality after this procedure. We assessed secular trends in death within 45 days of knee replacement for osteoarthritis in England and Wales, with the aim of investigating whether any change that we recorded could be explained by alterations in modifiable perioperative factors. METHODS: We took data for knee replacements done for osteoarthritis in England and Wales between April 1, 2003, and Dec 31, 2011, from the National Joint Registry for England and Wales. Patient identifiers were used to link these data to the national mortality database and the Hospital Episode Statistics database to obtain details of death, sociodemographics, and comorbidity. We assessed mortality within 45 days by Kaplan-Meier analysis and assessed the role of patient and treatment factors by Cox proportional hazards models. FINDINGS: 467,779 primary knee replacements were done to treat osteoarthritis during 9 years. 1183 patients died within 45 days of surgery, with a substantial secular decrease in mortality from 0·37% in 2003 to 0·20% in 2011, even after adjustment for age, sex, and comorbidity. The use of unicompartmental knee replacement was associated with substantially lower mortality than was total knee replacement (hazard ratio [HR] 0·32, 95% CI 0·19­0·54, p<0·0005). Several comorbidities were associated with increased mortality: myocardial infarction (HR 3·46, 95% CI 2·81­4·14, p<0·0005), cerebrovascular disease (3·35, 2·7­4·14, p<0·0005), moderate/severe liver disease (7·2, 3·93­13·21, p<0·0005), and renal disease (2·18, 1·76­2·69, p<0·0005). Modifiable perioperative risk factors, including surgical approach and thromboprophylaxis were not associated with mortality. INTERPRETATION: Postoperative mortality after knee replacement has fallen substantially between 2003 and 2011. Efforts to further reduce mortality should concentrate more on older patients, those who are male and those with specific comorbidities, such as myocardial infarction, cerebrovascular disease, liver disease, and renal disease. FUNDING: National Joint Registry for England and Wales.

HLA allele variation as a potential explanation for the geographical distribution of granulomatosis with polyangiitis.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare autoimmune systemic vasculitis considered to result from the interaction of environmental factors with a genetically predisposed host. The HLA-DPB1*0401 allele, the PI*Z allele of the gene encoding α1-antitrypsin (SERPINA1) and the proteinase 3 (PRTN3) gene have been associated with GPA. The incidence of GPA is lower in non-Caucasian populations and has been associated with higher latitude. Our aim was to determine whether variation in population carrier frequency of the HLA-DPB1*0401 and PI*Z alleles could explain in part the variation in GPA incidence between countries. METHODS: We systematically identified published reports on the incidence of GPA and used previously published data on the frequency of HLA-DBP1*0401 and PI*Z alleles. The relationship between GPA incidence, latitude and population HLA-DPB1*0401 and PI*Z allele frequencies was assessed by linear regression. RESULTS: On multivariate analysis GPA incidence was associated with HLA-DPB1*0401 allele frequency (P = 0.001) but not with PI*Z allele frequency or latitude. CONCLUSION: HLA-DPB1*0401 is a GPA susceptibility allele and HLA-DPB1*0401 population allele frequencies may help explain variations in GPA incidence described in the literature.

Amino Acid Intakes Are Inversely Associated with Arterial Stiffness and Central Blood Pressure in Women.

BACKGROUND: Although data suggest that intakes of total protein and specific amino acids (AAs) reduce blood pressure, data on other cardiovascular disease risk factors are limited. OBJECTIVE: We examined associations between intakes of AAs with known mechanistic links to cardiovascular health and direct measures of arterial stiffness, central blood pressure, and atherosclerosis. METHODS: In a cross-sectional study of 1898 female twins aged 18-75 y from the TwinsUK registry, intakes of 7 cardioprotective AAs (arginine, cysteine, glutamic acid, glycine, histidine, leucine, and tyrosine) were calculated from food-frequency questionnaires. Direct measures of arterial stiffness and atherosclerosis included central systolic blood pressure (cSBP), mean arterial pressure (MAP), augmentation index (AI), pulse wave velocity (PWV), and intima-media thickness (IMT). ANCOVA was used to assess the associations between endpoints of arterial stiffness and intake (per quintile), adjusting for potential confounders. RESULTS: In multivariable analyses, higher intakes of total protein and 7 potentially cardioprotective AAs were associated with lower cSBP, MAP, and PWV. Higher intakes of glutamic acid, leucine, and tyrosine were most strongly associated with PWV, with respective differences of -0.4 ± 0.2 m/s (P-trend = 0.02), -0.4 ± 0.2 m/s (P-trend = 0.03), and -0.4 ± 0.2 m/s (P-trend = 0.03), comparing extreme quintiles. There was a significant interaction between AA intakes and protein source, and higher intakes of AAs from vegetable sources were associated with lower central blood pressure and AI. Higher intakes of glutamic acid, leucine, and tyrosine from animal sources were associated with lower PWV. CONCLUSIONS: These data provide evidence to suggest that intakes of several AAs are associated with cardiovascular benefits beyond blood pressure reduction in healthy women. The magnitude of the observed associations was similar to those previously reported for other lifestyle factors. Increasing intakes of these AAs could be an important and readily achievable way to reduce cardiovascular disease risk.

Genetic and Environmental Factors in Age-Related Hearing Impairment.

Age-related hearing impairment (ARHI) is a common condition with complex etiology but a recognized genetic component. Heritability estimates for pure tone audiogram-determined hearing ability lie in the range 26-75%. The speech-in-noise (SIN) auditory test, however, may be better at encapsulating ARHI symptoms, particularly the diminished ability to segregate environmental sounds into comprehendible auditory streams. As heritability of SIN has not previously been reported, we explored the genetic and environmental contributions to ARHI determined by SIN in 2,076 twins (87.8% female) aged 18-87 (mean age 54.4). SIN was found to be significantly heritable (A, unadjusted for age=40%; 95% confidence intervals, CI=32%-47%). With age adjustment, heritability fell (A=25%; 95% CI=16-33%), and a relatively strong influence of environmental exposure unshared within twin siblings was identified (E=75%). To explore the environmental aspects further, we assessed the influence of diet (through the Food Frequency Questionnaire, FFQ), smoking (through self-report and cotinine metabolite levels) and alcohol intake (through the FFQ). A negative influence of high cholesterol diet was observed after adjustment (p=.037). A protective effect of raised serum high-density lipoprotein (HDL) cholesterol levels was observed after adjustment (p=.004). This study is the first assessment of the genetic and environmental influence on SIN perception. The findings suggest SIN is less heritable than pure tone audiogram (PTA) ability and highly influenced by the environment unique to each twin. Furthermore, a possible role of dietary fat in the etiology of ARHI is highlighted.

Food Preference Patterns in a UK Twin Cohort.

Food liking-disliking patterns may strongly influence food choices and health. Here we assess: (1) whether food preference patterns are genetic/environmentally driven; and (2) the relationship between metabolomics profiles and food preference patterns in a large population of twins. 2,107 individuals from TwinsUK completed an online food and lifestyle preference questionnaire. Principle components analysis was undertaken to identify patterns of food liking-disliking. Heritability estimates for each liking pattern were obtained by structural equation modeling. The correlation between blood metabolomics profiles (280 metabolites) and each food liking pattern was assessed in a subset of 1,491 individuals and replicated in an independent subset of monozygotic twin pairs discordant for the liking pattern (65 to 88 pairs). Results from both analyses were meta-analyzed. Four major food-liking patterns were identified (Fruit and Vegetable, Distinctive Tastes, Sweet and High Carbohydrate, and Meat) accounting for 26% of the total variance. All patterns were moderately heritable (Fruit and Vegetable, h(2)[95% CI]: 0.36 [0.28; 0.44]; Distinctive Tastes: 0.58 [0.52; 0.64]; Sweet and High Carbohydrate: 0.52 [0.45, 0.59] and Meat: 0.44 [0.35; 0.51]), indicating genetic factors influence food liking-disliking. Overall, we identified 14 significant metabolite associations (Bonferroni p < 4.5 × 10(-5)) with Distinctive Tastes (8 metabolites), Sweet and High Carbohydrate (3 metabolites), and Meat (3 metabolites). Food preferences follow patterns based on similar taste and nutrient characteristics and these groupings are strongly determined by genetics. Food preferences that are strongly genetically determined (h(2) ≥ 0.40), such as for meat and distinctive-tasting foods, may influence intakes more substantially, as demonstrated by the metabolomic associations identified here.

The prevalence of axial spondyloarthritis in the UK: a cross-sectional cohort study.

BACKGROUND: Accurate prevalence data are important when interpreting diagnostic tests and planning for the health needs of a population, yet no such data exist for axial spondyloarthritis (axSpA) in the UK. In this cross-sectional cohort study we aimed to estimate the prevalence of axSpA in a UK primary care population. METHODS: A validated self-completed questionnaire was used to screen primary care patients with low back pain for inflammatory back pain (IBP). Patients with a verifiable pre-existing diagnosis of axSpA were included as positive cases. All other patients meeting the Assessment of SpondyloArthritis international Society (ASAS) IBP criteria were invited to undergo further assessment including MRI scanning, allowing classification according to the European Spondyloarthropathy Study Group (ESSG) and ASAS axSpA criteria, and the modified New York (mNY) criteria for ankylosing spondylitis (AS). RESULTS: Of 978 questionnaires sent to potential participants 505 were returned (response rate 51.6 %). Six subjects had a prior diagnosis of axSpA, 4 of whom met mNY criteria. Thirty eight of 75 subjects meeting ASAS IBP criteria attended review (mean age 53.5 years, 37 % male). The number of subjects satisfying classification criteria was 23 for ESSG, 3 for ASAS (2 clinical, 1 radiological) and 1 for mNY criteria. This equates to a prevalence of 5.3 % (95 % CI 4.0, 6.8) using ESSG, 1.3 % (95 % CI 0.8, 2.3) using ASAS, 0.66 % (95 % CI 0.28, 1.3) using mNY criteria in chronic back pain patients, and 1.2 % (95 % CI 0.9, 1.4) using ESSG, 0.3 % (95 % CI 0.13, 0.48) using ASAS, 0.15 % (95 % CI 0.02, 0.27) using mNY criteria in the general adult primary care population. CONCLUSIONS: These are the first prevalence estimates for axSpA in the UK, and will be of importance in planning for the future healthcare needs of this population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76873217.

Low back and common widespread pain share common genetic determinants.

Low back (LBP) and chronic widespread musculoskeletal pain (CWP) both have a significant genetic component and are associated with increased body mass index (BMI). We examined whether LBP and CWP share common genetic factors, and to what extent this correlation is modified by the genetic factors influencing BMI. Genetic analysis of binary traits such as pain is not simple, particularly if their risk is associated with age or other quantitative traits. Implementing Falconer's polygenic threshold concept for dichotomous traits inheritance, we developed new software to examine the extent of the genetic influence on LBP and CWP under age and BMI dependence. The analysis was conducted on 3266 and 2256 UK female twins, assessed for LBP and CWP, respectively. Analysis of the liability scores with threshold to LBP and CWP established substantial contribution of genetic factors to their variation (h(2) > 0.60, p<0.004-0.0003) and covariation (p=3.1E-08). Some 39% of the CWP and 70% of the LBP heritability estimates were attributable to genetic effects shared by both phenotypes, and 40% and 67% of the residual variation is caused by environmental factors simultaneously affecting both pain syndromes. However, contribution of BMI to variation/covariation of both pain phenotypes-although statistically highly significant (p∼10-7)-was not determinative.

90-day mortality after 409,096 total hip replacements for osteoarthritis, from the National Joint Registry for England and Wales: a retrospective analysis.

BACKGROUND: Death within 90 days after total hip replacement is rare but might be avoidable dependent on patient and treatment factors. We assessed whether a secular decrease in death caused by hip replacement has occurred in England and Wales and whether modifiable perioperative factors exist that could reduce deaths. METHODS: We took data about hip replacements done in England and Wales between April, 2003, and December, 2011, from the National Joint Registry for England and Wales. Patient identifiers were used to link these data to the national mortality database and the Hospital Episode Statistics database to obtain details of death, sociodemographics, and comorbidity. We assessed mortality within 90 days of operation by Kaplan-Meier analysis and assessed the role of patient and treatment factors by Cox proportional hazards model. FINDINGS: 409,096 primary hip replacements were done to treat osteoarthritis. 1743 patients died within 90 days of surgery during 8 years, with a substantial secular decrease in mortality, from 0·56% in 2003 to 0·29% in 2011, even after adjustment for age, sex, and comorbidity. Several modifiable clinical factors were associated with decreased mortality according to an adjusted model: posterior surgical approach (hazard ratio [HR] 0·82, 95% CI 0·73-0·92; p=0·001), mechanical thromboprophylaxis (0·85, 0·74-0·99; p=0·036), chemical thromboprophylaxis with heparin with or without aspirin (0·79, 0·66-0·93; p=0·005), and spinal versus general anaesthetic (0·85, 0·74-0·97; p=0·019). Type of prosthesis was unrelated to mortality. Being overweight was associated with lower mortality (0·76, 0·62-0·92; p=0·006). INTERPRETATION: Postoperative mortality after hip joint replacement has fallen substantially. Widespread adoption of four simple clinical management strategies (posterior surgical approach, mechanical and chemical prophylaxis, and spinal anaesthesia) could, if causally related, reduce mortality further. FUNDING: National Joint Registry for England and Wales.

The prevalence of inflammatory back pain in a UK primary care population.

OBJECTIVE: Inflammatory back pain (IBP) is the earliest and most common symptom of axial SpA. However, there is very little information about the prevalence of IBP in the UK. In this cross-sectional cohort study we examined the prevalence of IBP in a UK primary care population using three published IBP criteria. METHODS: Potential participants aged 18-80 years were identified from the records of a large general practice in Norfolk, UK, with 17 177 patients. Read codes were used to identify those who had consulted their general practitioner on at least one occasion with back pain. A self-completed screening questionnaire was sent to a sample of 978 patients, enquiring about symptoms of IBP and extra-spinal manifestations of SpA. Questionnaire responses were used to determine whether patients met the Assessment of SpondyloArthritis international Society (ASAS), Calin and Berlin IBP criteria. RESULTS: Five hundred and five completed questionnaires were returned (response rate 51.6%). The median age of respondents was 60 years [interquartile range (IQR) 48-67] and 44.8% were male. The minimum prevalence of IBP among patients with at least one previous consultation for back pain was 7.7% (95% CI 6.2, 9.5) using the ASAS criteria, 13.5% (11.5, 15.8) using the Calin criteria and 15.4% (13.3, 17.8) using the Berlin criteria. There was no significant difference in prevalence between men and women, and between different age groups. Extrapolated to the practice population as a whole, the minimum prevalence of IBP in a UK primary care population is 1.7-3.4%. CONCLUSION: The prevalence of IBP varies significantly depending on the criteria used for classification.

The relationship between benign joint hypermobility syndrome and psychological distress: a systematic review and meta-analysis.

OBJECTIVE: This study examines the reported evidence of an association between benign joint hypermobility syndrome (BJHS) and psychological symptoms. METHODS: A systematic review of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed, Cochrane Library) and unpublished research databases (OpenGrey, the World Health Organization (WHO) International Clinical Trials Registry Platform, Current Controlled Trials, the UK National Research Register Archive) was performed from their inception to January 2013. Studies assessing the prevalence and incidence of psychological conditions for people diagnosed with BJHS were included. Meta-analysis assessing the odds ratio (OR) and standardized mean difference in severity of psychological conditions was performed. Methodological quality was assessed using the Critical Appraisal Skills Programme (CASP) appraisal tools. RESULTS: Fourteen papers including 3957 participants, 1006 people with and 2951 controls without BJHS were eligible. The overall methodological quality was moderate. The results indicated that people with BJHS experience significantly greater perceptions of fear and more intense fear (P < 0.05) and have a higher probability of demonstrating agoraphobia (P < 0.05), anxiety (OR 4.39, 95% CI 1.92, 10.40), depression (OR 4.10, 95% CI 1.79, 9.41) and panic disorders (OR 6.72, 95% CI 2.22, 20.35) than those without BJHS (P ≤ 0.005). Neither anxiety nor depression have been assessed in childhood populations. CONCLUSION: People with BJHS commonly exhibit a range of symptoms related to anxiety and depression. Considerable emotional symptoms accompany BJHS. Further study is warranted to explore how these results relate to non-Mediterranean populations and children. However, the data suggest that targeting psychological symptoms could be an important approach to managing the range of symptoms reported in these patients.

Intakes of anthocyanins and flavones are associated with biomarkers of insulin resistance and inflammation in women.

Although laboratory data suggest that several flavonoid subclasses are involved in glucose metabolism, limited clinical and epidemiologic data are available. The current study examined associations between habitual intake of flavonoid subclasses, insulin resistance, and related inflammatory biomarkers. In a cross-sectional study of 1997 females aged 18-76 y, intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids, flavonols, flavones) were calculated from food frequency questionnaires using an extended USDA database. Fasting serum glucose, insulin, high-sensitivity C-reactive protein (hs-CRP; n = 1432), plasminogen activator inhibitor-1 (n = 843), and adiponectin (n = 1452) concentrations were measured. In multivariable analyses, higher anthocyanin and flavone intake were associated with significantly lower peripheral insulin resistance [homeostasis model assessment of insulin resistance; quintile 5 (Q5) to Q1 = -0.1, P-trend = 0.04 for anthocyanins and flavones] as a result of a decrease in insulin concentrations (Q5-Q1 = -0.7 µU/mL, P-trend = 0.02 anthocyanins; Q5-Q1 = -0.5 µU/mL, P-trend = 0.02 flavones). Higher anthocyanin intake was also associated with lower hs-CRP concentrations (Q5-Q1 = -0.3 mg/L, P-trend = 0.04), whereas those in the highest quintile of flavone intake had improved adiponectin concentrations (Q5-Q1 = 0.7 µg/L, P-trend = 0.01). Anthocyanin-rich foods were also associated with lower insulin and inflammation levels. No significant associations were observed for total or other flavonoid subclasses. Higher intakes of both anthocyanins and flavones were associated with improvements in insulin resistance and hs-CRP. These associations were found with intakes readily achieved in the diet. The observed reduction in insulin concentrations was similar to that reported previously for other lifestyle factors. Dose-response trials are needed to ascertain optimal intakes for the potential reduction of type 2 diabetes risk.