Identifying Axial Spondyloarthritis in Patients With Inflammatory Bowel Disease Using Computed Tomography.

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.

Prevalence of undiagnosed axial spondyloarthritis in inflammatory bowel disease patients with chronic back pain: secondary care cross-sectional study.

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.

Early identification of axial spondyloarthritis in a multi-ethnic Asian population.

INTRODUCTION/OBJECTIVES: To address the diagnostic delay in axial spondyloarthritis (axSpA), we have cross-culturally adapted the Hamilton axSpA questionnaire, a self-administered screening questionnaire, in the Singapore population. In this study, we compared the performance of various scoring methods for this questionnaire in detecting axSpA. METHOD: The questionnaire was self-administered by eligible subjects. Scoring methods included method A, the original questionnaire scoring, and methods B-E, scoring developed based on the Assessment of SpondyloArthritis International Society (ASAS) criteria for inflammatory back pain (IBP) and the referral, classification and both referral and classification of axSpA, respectively. The reference standard was diagnosis by a rheumatologist. Since the ASAS criteria-based scoring methods were mainly based on clinical axSpA features, self-report and rheumatologist-assessment of clinical axSpA features were also compared in subjects with axSpA. RESULTS: Of 1418 subjects (age: 54 ± 14 years, female: 73%) recruited, 46 were diagnosed with axSpA by a rheumatologist. Sensitivities of methods A-E were 35%, 61%, 63%, 48% and 83%, respectively. Self-report of clinical axSpA features exceeded rheumatologist-assessment for arthritis (83 vs 26%), good response to NSAIDs (37 vs 30%), enthesitis (35 vs 30%), dactylitis (20 vs 2%) and family history for axSpA (13 vs 4%). The reverse was true for IBP (41 vs 63%) and uveitis (4 vs 15%). CONCLUSIONS: A self-administered questionnaire using the ASAS referral and classification criteria-based scoring yielded relatively high sensitivity in detecting axSpA in subjects newly referred to rheumatology clinics. This supports its evaluation as a screening and referral tool in the general population in future studies. Key Points • A self-administered questionnaire could be used as a screening and referral tool. • ASAS referral and classification criteria-based scoring yielded relatively high sensitivity. • Inaccurate perception of clinical axSpA features was observed in axSpA patients.

Needlestick injuries: the role of safety-engineered devices in prevention.

The first documented mention of a needlestick injury (NSI) in the medical literature appeared in 1906. Despite growth in academic and clinical interest for NSI prevention, a global report identified that approximately 3 million healthcare workers have suffered percutaneous exposure to blood-borne pathogens. Legislation is an important component of NSI prevention. Unfortunately, the impact of legislation may not always reduce the incidence of NSI as much as expected. Safety-engineered device (SED) implementation has demonstrated a substantial reduction in NSI rates compared with non-SEDs. More importantly, passive SEDs are 10 times less likely to be connected with an NSI incident.

Cross-cultural adaptation of the Hamilton axial spondyloarthritis questionnaire and development of a Chinese version in a multi-ethnic Asian population.

OBJECTIVE: To cross-culturally adapt the Hamilton axial spondyloarthritis (axial SpA) screening questionnaire and develop a Chinese version for use in a multi-ethnic Asian population in Singapore. METHODS: Consenting participants newly referred from primary care to a rheumatology specialist outpatient clinic for evaluation of possible axial SpA were studied. The original axial SpA questionnaire was revised based on inputs from cognitive debriefing interviews (CDIs) and discussions with an expert panel of rheumatologists and the developer. Forward and back translations of the adapted English version were also reviewed by the expert panel and the developer. The common translation produced was tested in CDIs with Chinese-speaking participants. Adapted English and Chinese versions were pilot-tested in a separate group of similar participants. RESULTS: Participants were recruited for English (n = 25) and Chinese CDIs (n = 15, relatively older and less frequently presented with axial SpA symptoms), respectively. Alternative terms and explanatory notes were added to difficult medical terms to improve the understandability of the adapted English version. English medical terms were retained in the Chinese version. Pilot-testing of the adapted axial SpA questionnaire was performed on 116 participants, all of whom reported ease of comprehension with both adapted versions. Only one participant was diagnosed with axial SpA, who also scored positive on the adapted axial SpA questionnaire. CONCLUSION: The adapted axial SpA questionnaire demonstrated good sensitivity in the pilot-testing and appears to be a promising tool for facilitating early identification of axial SpA cases in the multi-ethnic Asian population.

Prevalence of axial spondyloarthritis in patients with acute anterior uveitis: a cross-sectional study utilising MRI.

OBJECTIVE: Acute anterior uveitis (AAU) is the most common extra-articular manifestation of axial spondyloarthritis (axSpA). In this study, patients presenting with AAU were evaluated clinically and with MRI in order to estimate the prevalence of axSpA. METHODS: Consecutive patients presenting to a university teaching hospital between February 2014 and March 2015 with AAU were invited to participate. Those with a history of chronic back pain (CBP) beginning <45 years were evaluated clinically and with MRI of thoracolumbar spine and sacroiliac joints. RESULTS: Of 366 patients with AAU, 57 had a pre-existing diagnosis of axSpA; 77 others fulfilled the study eligibility criteria and 73 (95%) completed the study. Seventeen patients (23.3%) were diagnosed with axSpA by an experienced rheumatologist; of these, eight were human leucocyte antigen-B27 negative. Including those with a previous diagnosis, this equates to a minimum axSpA prevalence of 20.2%; one-quarter of patients were previously undiagnosed. CONCLUSION: This is the first study to actively search for the presence of axSpA in unselected patients presenting with AAU utilising MRI as an essential part of the assessment. There is a significant burden of undiagnosed axSpA in patients with AAU, but there does not appear to be a simple mechanism for screening. We recommend that ophthalmologists refer all patients with AAU with CBP, onset <45 years, to rheumatology for further evaluation.

Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis-findings from a United Kingdom cohort.

Objectives: To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort. Methods: All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug. Results: Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (s.d.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (s.d.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05). Conclusion: We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

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.

Is Etanercept 25 mg Once Weekly as Effective as 50 mg at Maintaining Response in Patients with Ankylosing Spondylitis? A Randomized Control Trial.

OBJECTIVE: To investigate, in a pilot randomized controlled trial, whether etanercept (ETN) 25 mg once weekly is effective at maintaining a clinical response in patients with ankylosing spondylitis (AS) who have responded to the standard 50 mg dose. METHODS: Adults with AS not responding to conventional therapies were prescribed ETN 50 mg once weekly for 6 months. Responders as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were randomly assigned to taper to 25 mg once weekly or continue on 50 mg and followed for a further 6 months. The primary outcome measure was maintenance of a 50% reduction in the BASDAI or fall in BASDAI by ≥ 2 units and a ≥ 2-unit reduction in BASDAI spinal pain as measured on a 10-point visual analog scale at 6 months postrandomization. RESULTS: Of 89 patients assessed for eligibility, 59 were enrolled; 47 (80%) had sufficient clinical response and were eligible for randomization, 24 were assigned to continue receiving ETN 50 mg, and 23 to taper to 25 mg. After 6 months, 20 (83%) of the 50 mg arm maintained clinical response compared with 12 (52%) of the 25 mg arm (a difference of -31%, 95% CI -58% - -5%). CONCLUSION: Although this pilot study demonstrates that treatment with ETN 25 mg was less effective at maintaining treatment response in the stepdown phase, 52% of participants maintained treatment response. Future research should address which patients are suitable for tapering.

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.

Validation of a patient self-reported screening questionnaire for axial spondyloarthropathy in a UK Population.

STUDY DESIGN: Cross-sectional cohort study. OBJECTIVE: The aim of this study was to develop and validate a patient-completed screening questionnaire for axial spondyloarthropathy for use in the United Kingdom. SUMMARY OF BACKGROUND DATA: Axial spondyloarthropathy (axial SpA) can be difficult to diagnose in the early stages of disease, leading to diagnostic delay and morbidity. Existing population screening tools lack sensitivity or have not been validated in the UK population. METHODS: Questionnaires were sent to 295 patients with definite ankylosing spondylitis (meeting modified New York criteria), nonradiographical axial SpA (sacroiliitis on magnetic resonance imaging), or mechanical back pain. Responses from 190 patients were analyzed. Binary logistic regression was used to develop a model differentiating inflammatory from mechanical pain. RESULTS: The final model (male sex, onset of symptoms by age 33 years, no radiation of pain, pain gets better as day goes on, pain increases with rest, and personal history of iritis) correctly classified 86% of cases with Nagelkerke R = 0.486. A numerical score (with 1 point assigned for each feature present) was calculated and receiver operating characteristic curve was constructed, with area under the curve of 0.911 (95% confidence interval: 0.87-0.96). A score of ≥3/6 had sensitivity of 75.6% and specificity of 87.9% for inflammation. CONCLUSION: We have developed a model that differentiates patients with ankylosing spondylitis/axial SpA from those with mechanical spinal disease and can be used as a self-completed screening tool.

Services for people with ankylosing spondylitis in the UK--a survey of rheumatologists and patients.

OBJECTIVE: . To investigate the services offered to patients with AS in the UK in 2010. METHODS: Two thousand non-health-care professional members of the National Ankylosing Spondylitis Society (NASS) were sent a questionnaire asking about their experiences surrounding diagnosis, treatment and access to therapies (response rate 40%). A separate questionnaire was sent to a consultant rheumatologist in every acute NHS trust in the UK, asking about services offered to patients with AS (response rate 68%). RESULTS: Overall, there was a mean diagnostic delay of 8.57 years. Almost one-third (32.2%) of patients were not reviewed in secondary care. Non-attendance was associated with increasing age and longer disease duration. Twenty per cent of patients were taking anti-TNF drugs, but 18.8% of departments reported that their ability to give anti-TNF therapy was restricted (64% reported primary-care trust rationing and 14% lack of staff). Almost all rheumatology departments had access to MRI, but 70.9% still used X-ray radiographs as their first-line investigation. A minority (5.6%) of patients reported they had never seen a physiotherapist, but less than one-third could self-refer for treatment during a flare. CONCLUSION: This is the first study to explore the services available to people with AS in the UK. Almost one-third of patients are not seen in rheumatology departments and therefore may be under-treated. For those who are seen, access to anti-TNF drugs and other therapies remains an issue.

Teaching knee joint aspiration to medical students-an effective training with long-term benefits.

The objective of this study was to assess the effectiveness of undergraduate training in knee aspiration and to determine the impact this had on subsequent postgraduate clinical practice. This paper is a cohort study of undergraduate training with a cross-sectional questionnaire study of postgraduate practice. The study was held at the University of Cambridge and NHS hospitals in the Eastern Region Postgraduate Deanery (England). The main outcome measures are the undergraduate competence in practical skills in a simulated setting and the differences in postgraduate practice with or without prior undergraduate training in knee aspiration. Implementing an undergraduate training programme in knee aspiration resulted in student competence in this skill. Undergraduate teaching of knee aspiration also improved postgraduate clinical practice, significantly increasing trainee doctor confidence and also increasing the frequency with which knee aspiration was undertaken. Postgraduate reinforcement of learning was identified as an additional requirement. Undergraduate teaching of knee aspiration not only results in competent performance in end of course assessments but also improves postgraduate confidence that potentially translates into improved clinical practice.

Neuropathological consequences of delivering an adenoviral vector in the rat brain.

BACKGROUND: Adenoviruses have many advantages as vehicles for gene delivery to the central nervous system (CNS) and retrograde transport of vectors to axonally linked sites has been postulated as a method for targeting neurons in remote brain regions. To investigate optimisation of this we injected different doses of vector and have documented the neuropathological side effects. METHODS: Increasing doses of a first-generation adenoviral vector, expressing the lacZ gene, were inoculated in the rat striatum and beta-galactosidase expression was examined at the primary and secondary sites. Subsequently, at the highest dose of vector, transgene expression, the inflammatory response, tyrosine hydroxylase (TH) expression and the rotational behaviour of animals were studied over time. RESULTS: When a high dose of an adenoviral vector was delivered to the rat striatum, high levels of transgene expression were seen at 5 days in the injection site and in the substantia nigra. Smaller doses gave lower levels of expression with little expression detectable in the substantia nigra. At later time points, with the high dose, a marked reduction in transgene expression was detected and was accompanied by cytopathic damage, a strong inflammatory response and animal weight loss. This was associated with depletion in TH levels and abnormal motor behaviour in animals. CONCLUSIONS: Neuropathological damage in the dopaminergic system, caused by high doses of adenoviral vectors, has not previously been documented. To minimise damage and prolong transgene expression, it is important that the dose of vectors to be delivered is carefully optimised.