Sensory Health for Residents with Dementia in Care Homes in England: A Knowledge, Attitudes, and Practice Survey.

BACKGROUND: Most residents with dementia (RwD) in long-term care (LTC) facilities experience hearing and vision problems, yet these sensory deficits, which are associated with poor outcomes, are frequently under-recognized or incompletely managed. OBJECTIVE: We investigated the knowledge, attitudes, and practice (KAP) of LTC facility staff in England regarding sensory-cognitive health of RwD. DESIGN: A cross-sectional survey using self-administered online or mail-in questionnaires. SETTING AND PARTICIPANTS: The study included 117 LTC facilities throughout England, involving 887 staff of different grades (managers, n=79; nurses/allied health professionals, n=160; care workers, n=648). METHODS: Using a sampling frame of all LTC facilities nationwide, we included a stratified random selection of facilities, surveying staff regarding KAP of sensory-cognitive health. Analysis was descriptive, followed by a regression model for predictors of overall KAP capacity of staff, based on a Rasch analysis of survey items. RESULTS: Staff of all grades reported high knowledge and awareness of sensory-health concerns amongst RwD, but training opportunities were infrequent and most front-line staff felt they lacked the skills necessary to support the use of hearing and vision aids. The most reported reason for poor use of hearing aids/glasses related to lack of maintenance and care procedures (ie, broken and lost devices), and poor adherence support (ie, not tolerating the devices). Staff willingness to receive training was high. Most managers reported that training in communication skills and "sensory-friendly" environments was not provided. Finally, higher overall KAP capacity of staff was predicted by smaller facility size and public, rather than private, facility type. CONCLUSIONS AND IMPLICATIONS: Training and practice of sensory health care in RwD in LTC in England is lacking. To improve sensory-cognitive care for LTC RwD, there is a clear need for (1) practice recommendations and (2) multifaceted interventions that include staff training, tailored sensory support, and environmental modification.

The British Society for Rheumatology Biologics Registers in Ankylosing Spondylitis (BSRBR-AS) study: Protocol for a prospective cohort study of the long-term safety and quality of life outcomes of biologic treatment.

BACKGROUND: Axial spondyloarthropathy typically has its onset in early adulthood and can impact significantly on quality of life. In the UK, biologic anti-tumour necrosis factor therapy is recommended for patients who are unresponsive to non-steroidal anti-inflammatory drugs. There remain several unresolved issues about the long-term safety and quality of life outcomes of biologic treatment in axial spondyloarthropathy. Long-term "real-world" surveillance data are required to complement data from randomised controlled trials. METHODS/DESIGN: We are conducting a UK-wide prospective cohort study of patients with axial spondyloarthropathy who are naïve to biologic therapy at the time of recruitment. Those about to commence anti-tumour necrosis factor biologic therapy will enter a "biologic" sub-cohort with other patients assigned to a "non-biologic" sub-cohort. The primary objective is to determine whether the use of biologic therapy is associated with an increased risk of serious infection, while secondary objectives are to assess differences in malignancy, serious comorbidity, all-cause mortality but also assess impact on specific clinical domains (physical health, mental health and quality of life) including work outcomes between biologic and non-biologic patient cohorts. Patients will be followed-up for up to 5 years. Data are obtained at baseline and at standard clinical follow-up visits - at 3, 6 and 12 months and then annually for the biologic cohort and annually for the non-biologic cohort. This study will also collect biological samples for genetic analysis. DISCUSSION: Although biologic therapy is widely used for ankylosing spondylitis patients who are unresponsive to non-steroidal anti-inflammatory drugs, the majority of the available safety information comes from rheumatoid arthritis, where increased infection risk has consistently been shown. However, given the typical demographic differences between rheumatoid arthritis and axial spondyloarthropathy patients, it is important to develop an epidemiologically rigorous cohort of patients receiving biologic therapy to effectively evaluate outcomes with regard not only to safety but also to quantify benefits across clinical, psychosocial and work outcomes. CLINICAL TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was not required or obtained.

Global prevalence of ankylosing spondylitis.

OBJECTIVES: For effective health care provision, knowledge of disease prevalence is paramount. There has been no systematic endeavour to establish continent-based AS estimates, however, prevalence is thought to vary by country and background HLA-B27 prevalence. This study aimed to estimate AS prevalence worldwide and to calculate the expected number of cases. METHODS: A systematic literature search was conducted. Prevalence data were extracted and used to calculate the mean prevalence by continent and the expected number of cases based on country-specific prevalence (or, if missing, the prevalence from neighbouring countries). A second estimate was made using the prevalence from countries with similar HLA-B27 prevalences if a country-specific prevalence estimate was not available. RESULTS: The mean AS prevalence per 10,000 (from 36 eligible studies) was 23.8 in Europe, 16.7 in Asia, 31.9 in North America, 10.2 in Latin America and 7.4 in Africa. Additional estimates, weighted by study size, were calculated as 18.6, 18.0 and 12.2 for Europe, Asia and Latin America, respectively. There were sufficient studies to estimate the number of cases in Europe and Asia, calculated to be 1.30-1.56 million and 4.63-4.98 million, respectively. CONCLUSION: This study represents the first systematic attempt to collate estimates of AS prevalence into a single continent-based estimate. In addition, the number of expected cases in Europe and Asia was estimated. Through reviewing the current literature, it is apparent that the continuing conduct of epidemiological studies of AS prevalence is of great importance, particularly as diagnostic capabilities improve and with the recent development of the criteria for axial SpA.

Kinematic, kinetic and electromyographic response to customized foot orthoses in patients with tibialis posterior tenosynovitis, pes plano valgus and rheumatoid arthritis.

OBJECTIVE: To describe the effect of customized foot orthoses (FOs) on the kinematic, kinetic and EMG features in patients with RA, tibialis posterior (TP) tenosynovitis and associated pes plano valgus. METHODS: Patients with RA and US-confirmed tenosynovitis of TP underwent gait analysis, including three-dimensional (3D) kinematics, kinetics, intramuscular EMG of TP and surface EMG of tibialis anterior, peroneus longus, soleus and medial gastrocnemius. Findings were compared between barefoot and shod with customized FO conditions. RESULTS: Ten patients with RA with a median (range) disease duration of 3 (1-18) years were recruited. Moderate levels of foot pain and foot-related impairment and disability were present with moderately active disease states. Altered timing of the soleus (P = 0.05) and medial gastrocnemius (P = 0.02) and increased magnitude of tibialis anterior (P = 0.03) were noted when barefoot was compared with shod with FO. Trends were noted for reduced TP activity in the contact period (P = 0.09), but this did not achieve statistical significance. Differences in foot motion characteristics were recorded for peak rearfoot eversion (P = 0.01), peak rearfoot plantarflexion (P < 0.001) and peak forefoot abduction (P = 0.02) in the shod with FOs compared with barefoot conditions. No differences in kinetic variables were recorded. CONCLUSION: This study has demonstrated, for the first time, alterations in muscle activation profiles and foot motion characteristics in patients with RA, pes plano valgus and US-confirmed TP tenosynovitis in response to customized FOs. Complex adaptations were evident in this cohort and further work is required to determine whether these functional alterations lead to improvements in patient symptoms.

The effectiveness of a multidisciplinary foot care program for children and adolescents with juvenile idiopathic arthritis: an exploratory trial.

OBJECTIVES: To evaluate the effectiveness of multidisciplinary foot-care, and to evaluate the methodological considerations of a trial of multidisciplinary care in juvenile idiopathic arthritis. DESIGN: Exploratory randomised controlled trial. SUBJECTS/PATIENTS: Children/adolescents with juvenile idio-pathic arthritis and inflammatory joint disease affecting the foot/ankle. METHODS: Standard medical care was compared with a 12 month program of multidisciplinary foot-care informed by musculoskeletal ultrasound. This program was centred on strict disease control through rigorous examination and interventions delivered by a team comprised of a paediatric rheumatologist, podiatrist, physiotherapist and musculoskeletal ultrasonographer. Patients were assessed on foot impairment and disability scores using the Juvenile Arthritis Foot Disability Index. RESULTS: Forty-four participants, aged 3-17 years were randomly assigned to receive the experimental (n = 21) or usual care (n = 23) interventions. There was an overall improvement in levels of foot related impairments in both groups over 12 months. Between-group differences in change scores for the Juvenile Arthritis Foot Disability Index were not statistically significant at 6 or 12 month follow-ups. CONCLUSION: The integrated multidisciplinary foot care interventions described in this trial were safe, but did not improve foot impairment levels relative to usual care. This trial identified several methodological challenges including recruitment/retention, difficulties with outcome tools and potential confounders.

Tibialis posterior tenosynovitis and associated pes plano valgus in rheumatoid arthritis: electromyography, multisegment foot kinematics, and ultrasound features.

OBJECTIVE: To compare electromyographic (EMG), kinematic, kinetic, and ultrasound (US) features of pes plano valgus associated with US-confirmed tibialis posterior (TP) tenosynovitis in rheumatoid arthritis (RA) and healthy control subjects. METHODS: In this cross-sectional study, patients with RA and US-confirmed tenosynovitis of TP underwent gait analysis, including 3-dimensional kinematics, kinetics, and intramuscular EMG of TP, and findings were compared with a group of healthy individuals. The RA group also underwent B mode and power Doppler US scanning of the TP tendon to assess and score levels of pathology. RESULTS: Ten patients with RA, median (range) disease duration of 3 years (1-18 years), and 5 control subjects were recruited. Compared to control subjects, the RA patients walked slower and presented with moderate levels of foot-related disability. The mean ± SD Disease Activity Score in 28 joints was 4.6 ± 1.6. Increased magnitude of TP activity was recorded in the RA group compared to controls in the contact period of stance (P = 0.007), in conjunction with reduced ankle joint power (P = 0.005), reduced navicular height in the medial arch (P = 0.023), and increased forefoot dorsiflexion (P = 0.027). TP tendon thickening, fluid, and power Doppler signal were observed in the majority of patients. CONCLUSION: This study has demonstrated, for the first time, increased TP EMG activity in the presence of US-confirmed TP tenosynovitis in RA. Altered muscle function occurred in conjunction with suboptimal mechanics, moderate levels of tendon pathology, and active disease. Targeted therapy may be warranted to reduce inflammation and mechanically off-load diseased tendon states.

Frequent discordance between clinical and musculoskeletal ultrasound examinations of foot disease in juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the levels of agreement from independent clinical examination (CE) by a pediatric rheumatologist and podiatrist and an ultrasound (US) examination of articular and periarticular foot disease in juvenile idiopathic arthritis (JIA). METHODS: Thirty patients with JIA and a history of foot disease underwent CE and US examination of 24 foot joints, 10 tendons, and 6 periarticular soft tissues. Each site was examined independently by a rheumatologist and a podiatrist for synovitis and tenderness/swelling. The same sites were examined independently by a sonographer for effusion, synovial hypertrophy, power Doppler (PD) signal, tenosynovitis, or abnormal tendon thickening. Agreement was estimated using Cohen's unweighted kappa with corresponding 95% confidence intervals. RESULTS: Seven hundred twenty joints, 300 tendons, and 180 soft tissue sites were examined. Clinically detected synovitis, tenderness, and swelling were recorded in 42 (5.8%), 78 (10.8%), and 73 joints (10.1%), respectively. US-detected effusions, synovial hypertrophy, and PD signal were recorded in 88 (12.2%), 47 (6.5%), and 12 joints (1.7%), respectively. Subclinical foot disease was found in 52 joints (7.2%), 5 tendons (1.6%), and 4 soft tissue sites (2.2%). Agreement was consistently less than moderate (κ = <0.4) for each clinical and US interaction. CONCLUSION: This study uniquely demonstrated an interprofessional evaluation of foot disease in JIA. Interobserver agreement was less than acceptable for CE versus US, and subclinical foot disease is common in joints and periarticular soft tissues. US may be a useful tool to aid CE of the foot in JIA patients.

The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD).

OBJECTIVE: To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. METHODS: Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. RESULTS: The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. CONCLUSIONS: The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.

Clinical utility of ultrasonography in spondyloarthropathies.

Since the introduction of ultrasonography by Professor Ian Donald in Glasgow as a tool for imaging in medicine, it has become an important technology for imaging the musculoskeletal system. Musculoskeletal ultrasonography is a powerful adjunct to clinical examination that can detect subclinical abnormalities of soft tissues, tendons, and ligaments; it is also an important tool for the objective assessment of synovitis and bone erosion. Enthesitis, the hallmark of spondyloarthropathies, can be readily imaged using ultrasound. Furthermore, the characteristic soft tissue abnormalities and bone erosions seen in psoriatic arthritis, for example, are easily detected. The axial skeleton is a complex structure that currently is not very amenable to ultrasound imaging, but advances have been made in its use to image sacroiliac joints and semiquantify active sacroiliitis. Technological advances currently being made in ultrasonography will provide exciting new possibilities for the application of this imaging modality to the spondyloarthropathies.

Investigating the genetic association between ERAP1 and ankylosing spondylitis.

A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conducted a series of experiments to try to identify the primary genetic association(s) with ERAP1. We replicated the original associations in an independent set of 730 patients and 1021 controls, resequenced ERAP1 to define the full extent of coding polymorphisms and tested all variants in additional association studies. The genetic association with ERAP1 was independently confirmed; the strongest association was with rs30187 in the replication set (P = 3.4 x 10(-3)). When the data were combined with the original WTCCC-TASC study the strongest association was with rs27044 (P = 1.1 x 10(-9)). We identified 33 sequence polymorphisms in ERAP1, including three novel and eight known non-synonymous polymorphisms. We report several new associations between AS and polymorphisms distributed across ERAP1 from the extended case-control study, the most significant of which was with rs27434 (P = 4.7 x 10(-7)). Regression analysis failed to identify a primary association clearly; we therefore used data from HapMap to impute genotypes for an additional 205 non-coding SNPs located within and adjacent to ERAP1. A number of highly significant associations (P < 5 x 10(-9)) were identified in regulatory sequences which are good candidates for causing susceptibility to AS, possibly by regulating ERAP1 expression.

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA.

BACKGROUND: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. METHODS/DESIGN: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted.A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken. TRIAL REGISTRATION NUMBER: UKCRN5045.

Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series.

OBJECTIVES: It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS. METHODS: The UK case-control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian-Laird test was used to calculate random effects pooled odds ratios (ORs). RESULTS: In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10(-5), OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 x 10(-9), OR approximately 1.2) but also with rs11209026 (P < 10(-10), OR approximately 0.6). CONCLUSIONS: IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS.

Unintended benefits of immunosupression on autoimmune disease due to chemoradiation therapy for head and neck cancer.

The immune system is an important factor in the host's defenses against cancer. Immunosupression by radiation and/or chemotherapy is often associated with systemic and hematologic complications, opportunistic infections, and the development of malignancies, but immunosupression can also have beneficial effects, which are sometimes incidental. We report 2 patients with autoimmune diseases where immunosupression had beneficial effects. The first case is about a patient with carcinoma of the tonsil, with severe rheumatoid arthritis, who was treated with chemoradiation, which resulted in remission of his arthritis. The second case is about a patient with severe atopic eczema who was on long-term treatment with psoralen and ultraviolet A radiation and azathioprine; the patient developed metastatic carcinoma of the lip, which was treated with surgery and radiation that resulted in complete remission of his eczema.

Inflammatory suppression rapidly attenuates microvascular dysfunction in rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with greater risk of cardiovascular morbidity and mortality, the inflammatory component of RA being strongly linked to this excess risk. Endothelial dysfunction is linked to atherosclerosis and has been demonstrated in larger vessels in RA. In this pilot study, we determined for the first time whether skin microvascular function was impaired in patients with active RA and also determined its response to anti-inflammatory treatment. This was assessed non-invasively using laser Doppler imaging combined with iontophoresis of the vasodilators acetylcholine (ACh, endothelium dependent) and sodium nitroprusside (SNP, endothelium independent) to the forearm. Eight RA patients admitted for acute flare-ups were assessed before and following anti-inflammatory treatment. Standard laboratory indices were obtained along with pain perception (VAS). A control group of eight subjects was included for baseline comparison. Compared to this group, vascular function was substantially and significantly (P<0.00001) lower in RA patients. Following treatment, as CRP and VAS decreased, vascular function improved for both ACh (P<0.00001) and SNP (P=0.001), this improvement being significantly greater for ACh (P<0.001). Vascular dysfunction is evident in RA patients, even at the level of the cutaneous microcirculation, but improves as inflammation regresses. Assessment of cutaneous vascular function may be a useful, non-invasive surrogate indicator of vascular risk in RA, inclusive of myocardial microvascular abnormalities.

Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis.

Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional characteristics of psoriatic arthritis (PsA)-derived and rheumatoid arthritis (RA)-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to evaluate their potential role in arthritis. Circulating peripheral blood (PB) pDC numbers were significantly reduced in PsA patients (P = 0.0098) and RA patients (P = 0.0194), and mDCs were significantly reduced in RA patients (P = 0.0086) compared with healthy controls. The number of circulating mDCs in RA PB was significantly inversely correlated to C-reactive protein (P = 0.021). The phenotype of both DC subsets in PsA PB and RA PB was immature as compared with healthy controls. Moreover, CD62L expression was significantly decreased on both mDCs (PsA, P = 0.0122; RA, P = 0.0371) and pDCs (PsA, P = 0.0373; RA, P = 0.0367) in PB. Both mDCs and pDCs were present in PsA synovial fluid (SF) and RA SF, with the mDC:pDC ratio significantly exceeding that in matched PB (PsA SF, P = 0.0453; RA SF, P = 0.0082). pDCs isolated from RA SF and PsA SF displayed an immature phenotype comparable with PB pDCs. RA and PsA SF mDCs, however, displayed a more mature phenotype (increased expression of CD80, CD83 and CD86) compared with PB mDCs. Functional analysis revealed that both SF DC subsets matured following toll-like receptor stimulation. pDCs from PB and SF produced interferon alpha and tumour necrosis factor alpha on TLR9 stimulation, but only SF pDCs produced IL-10. Similarly, mDCs from PB and SF produced similar tumour necrosis factor alpha levels to TLR2 agonism, whereas SF mDCs produced more IL-10 than PB controls. Circulating DC subset numbers are reduced in RA PB and PsA PB with reduced CD62L expression. Maturation is incomplete in the inflamed synovial compartment. Immature DCs in SF may contribute to the perpetuation of inflammation via sampling of the inflamed synovial environment, and in situ presentation of arthritogenic antigen.