Fragmentation landscape of cell-free DNA revealed by deconvolutional analysis of end motifs.

Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.

Fragmentomics of urinary cell-free DNA in nuclease knockout mouse models.

Urinary cell-free DNA (ucfDNA) is a potential biomarker for bladder cancer detection. However, the biological characteristics of ucfDNA are not well understood. We explored the roles of deoxyribonuclease 1 (DNASE1) and deoxyribonuclease 1-like 3 (DNASE1L3) in the fragmentation of ucfDNA using mouse models. The deletion of Dnase1 in mice (Dnase1-/-) caused aberrations in ucfDNA fragmentation, including a 24-fold increase in DNA concentration, and a 3-fold enrichment of long DNA molecules, with a relative decrease of fragments with thymine ends and reduction of jaggedness (i.e., the presence of single-stranded protruding ends). In contrast, such changes were not observed in mice with Dnase1l3 deletion (Dnase1l3-/-). These results suggested that DNASE1 was an important nuclease contributing to the ucfDNA fragmentation. Western blot analysis revealed that the concentration of DNASE1 protein was higher in urine than DNASE1L3. The native-polyacrylamide gel electrophoresis zymogram showed that DNASE1 activity in urine was higher than that in plasma. Furthermore, the proportion of ucfDNA fragment ends within DNase I hypersensitive sites (DHSs) was significantly increased in Dnase1-deficient mice. In humans, patients with bladder cancer had lower proportions of ucfDNA fragment ends within the DHSs when compared with participants without bladder cancer. The area under the curve (AUC) for differentiating patients with and without bladder cancer was 0.83, suggesting the analysis of ucfDNA fragmentation in the DHSs may have potential for bladder cancer detection. This work revealed the intrinsic links between the nucleases in urine and ucfDNA fragmentomics.

Evaluation of a multidisciplinary care model to improve quality of life in rheumatoid arthritis: a randomised controlled trial.

BACKGROUND AND PURPOSE: Health-Related Quality of Life (HR-QOL) is an important patient-reported domain in patients with rheumatoid arthritis (RA). The uptake of multidisciplinary team (MDT) care in RA is generally low, due to initial high demand for resources. We hypothesised that whilst pharmacological treatments are effective in controlling disease activity, a multipronged intervention in an MDT may have a positive impact on HR-QOL. METHODS: This was a single-centre randomized parallel group, single-blind controlled trial of MDT vs. usual care in an established RA clinic. Data were collected through face-to-face questionnaires, medical records review, and joint counts by a blinded assessor at 0, 3 and 6 months. Adult RA patients were randomly assigned in a single visit to a 6-member MDT (rheumatologist, nurse, social worker, physiotherapist, occupational therapist, and podiatrist) or usual care. MDT providers prescribed medications and counselled patients on managing flares, medication adherence, coping, joint protection, exercise, footwear. The primary outcome was minimal clinically important difference (MCID) in HR-QOL (increase in European QOL-5-Dimension-3-Level, EQ-5D-3L by 0.1) at six months. RESULTS: 140 patients (86.3% female, 53.4% Chinese, median (IQR) age 56.6 (46.7, 62.4) years); 70 were randomized to each arm. Median (IQR) disease duration was 5.5 (2.4, 11.0) years and disease activity in 28 joints (DAS28) was 2.87 (2.08, 3.66). 123 patients completed the study. Twenty-six (40.6%) MDT vs. 23 (34.3%) usual care patients achieved an MCID in EQ-5D-3L, OR 1.3 (0.6, 2.7). In multivariable logistic regression, baseline EQ-5D-3L was the only predictor of achieving MCID. There was more disease modifying anti-rheumatic drug escalation in MDT (34.4% vs. 19.4%). Patients with high disease activity were more likely to achieve MCID in the MDT arm. CONCLUSIONS: A single visit by stable patients with low disease activity to an MDT failed to achieve MCID in the EQ-5D-3L; however, did achieve small but significant improvements in the EQ-5D-3L, DAS28, pain, coping and self-efficacy. To be sustainable, MDT care should be targeted at patients with high disease activity or those with a new diagnosis of RA. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov, identifier: NCT03099668.

Attitudes and Behaviors of Patients With Rheumatic Diseases During the Early Stages of the COVID-19 Outbreak.

OBJECTIVE: To evaluate attitudes and behaviors of patients with rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: An online survey delivered by text message to 4695 patients on follow-up at a tertiary rheumatology center. Latent class analysis was performed on the survey variables. RESULTS: There were 2239 (47.7%) who responded to the survey and 3 clusters were identified. Cluster 3 (C3) was defined by patients who were most worried about COVID-19, more likely to wear face masks, and more likely to alter or stop their medications. Patients in C3 were more likely to be female, Malay, and unemployed. CONCLUSION: We identified 3 clusters with different healthcare beliefs and distinct sociodemographics.

An evaluation of the effectiveness of teaching anatomy to rheumatologists through combined musculoskeletal sonoanatomy and human cadaveric dissection.

OBJECTIVE: Our aim was to evaluate the effectiveness of teaching anatomy through combined musculoskeletal sonoanatomy and human cadaveric dissection for rheumatologists practising musculoskeletal US. METHODS: The principal focus was on scanning and then dissecting relevant musculoskeletal structures. Outcomes measured included confidence levels and objective knowledge. A mixed-methods approach of evaluation and descriptive statistical data analysis was performed. RESULTS: The change in confidence ratings by delegates after the teaching event as represented by the mean difference (s.d.) (s.e.m.) for identification of surface anatomy was 1.846 (1.281) (0.355), with Student's paired t = 5.196 and P=0.000223. The mean difference (s.d.) (s.e.m) for performing IA injections was 1.538 (1.266) (0.351), with Student's paired t = 4.382, P=0.001, and for recognizing sonoanatomical structures it was 1.769 (1.235) (0.343), with Student's paired t = 5.165 and P= 0.000235. There was a significant increase in correct identification of anatomical and sonoanatomical knowledge in the pre- and post-course assessments. Rotator cuff interval region improved from 13 to 73%, P = 0.004; knee tendons insertion sites from 47 to 93%, P = 0.016; and muscles not adjacent to joints from 27 to 93%, P = 0.002. CONCLUSION: Dissection of joints enabled a three-dimensional relational mind map of the relevant regions of the human body, producing clarity in understanding regional relational topographic anatomy and sonoanatomy. The combination of US and cadaveric dissection improved learners' satisfaction, confidence and knowledge in areas where soft tissue complaints are common, which is likely to lead to accurate early diagnosis and cost-conscious, better overall care.

Burden and management of gout in a multi-ethnic Asian cohort.

Gout has significant impact on the quality of life with over-utilisation of health resources. While lowering serum urate (SU) to ≤ 360 µmol/L improves clinical outcomes, this is usually not achieved. We describe the burden of gout and determine predictors of achieving SU target in gout patients in Singapore. This was a cross-sectional study of 282 gout patients from a Singapore hospital rheumatology service. Sociodemographic and lifestyle factors, co-existing medical conditions and medications, gout history and severity, SU levels and treatment were obtained. Patients with SU ≤ 360 µmol/L were compared with those > 360 µmol/L to determine factors associated with achieving SU target. Descriptive statistics and multivariate model were used. Severe disease was reported in 50%, with emergency attendances and hospitalisations in 33% and 19% respectively, and unemployment in 32%. Only 22% were at SU target and 67% on urate-lowering therapy (ULT) at recruitment. Hypertension, dyslipidaemia, chronic kidney disease and diabetes were prevalent in 56.7%, 48.2%, 32.3% and 18.8%, respectively. Malays had more comorbidities compared to Chinese participants. In multivariate analysis, ULT prescription and ≥ 2 comorbidities were associated with reaching SU target with odds ratios of 3.92 [95% confidence interval (CI) (1.75-8.71)] and 2.65 [95% CI (1.59-4.43)] respectively, independent of age, tophi, disease duration, body mass index, alcohol and diuretic use. Patients with gout have high disease burden resulting in significant healthcare utilisation. SU control is sub-optimal hence the use of ULT remains key in achieving SU target. Patients with other comorbidities are more likely to reach target than those with only gout as a single diagnosis.

Singapore chapter of rheumatologists' updated consensus statement on the eligibility for government subsidization of biologic and targeted therapy for the treatment of psoriatic arthritis.

AIM: There have been major advances in biologic treatment options for psoriatic arthritis (PsA) since the publication of the 2015 consensus recommendations by the Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore, for government-assisted funding, thus warranting a revision of this guideline. METHODS: Recent trials and nine published guidelines on the use of biologic therapy for PsA were reviewed. Based on the synthesized evidence, a task force panel (TFP), consisting of 10 practicing rheumatologists in Singapore, rated the statements pertaining to the use of biologic therapy, using a modified Delphi approach. Consensus was obtained if >70% agreed on a statement. RESULTS: The TFP agreed on 10 recommendations pertaining to the initiation, choice and continuation of biologic therapy. A biologic is indicated in patients with PsA: (a) with at least three swollen and tender joints, digits or entheses; and (b) who have failed at least two conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) strategies for a minimum of 3 months each. Any approved drug class including tumor necrosis factor inhibitors, interleukin-17 inhibitors (IL-17i), IL-12/23i or targeted synthetic DMARDs may be considered as first-line treatment, and continued only if a response is achieved by 6 months. CONCLUSION: These recommendations developed through a formal consensus method may be useful to guide funding considerations for appropriate and equitable use of biologic therapy for eligible patients with PsA.

Update on recommendations for eligibility of government subsidization of biologic disease-modifying antirheumatic drugs for the treatment of axial spondyloarthritis in Singapore.

AIMS: The field of axial spondyloarthritis (axSpA) has undergone significant changes recently in particular with disease classification, assessment of disease activity and increased treatment options for biologics. In order to reflect these developments, we aimed to update the local consensus recommendations for subsidization of biologics. METHODS: A modified Delphi approach was used. Six published guidelines from major rheumatology societies and healthcare authorities on axSpA were reviewed. Findings were synthesized and used in formulating updated recommendation statements. Recommendations were rated by 10 practicing rheumatologists in Singapore. Consensus was reached if there was more than 70% agreement or disagreement. RESULTS: Ten statements achieved consensus. Patients may be considered for subsidization of biologic therapy if they fulfill the Assessment of Spondyloarthritis International Society or modified New York criteria, with persistently active disease (defined either by Ankylosing Spondylitis Disease Activity Score ≥ 2.1 or Bath Spondylitis Disease Activity Index ≥ 4), despite 4 weeks of full-dose non-steroidal anti-inflammatory drugs and regular exercise. Either tumor necrosis factor inhibitors or interleukin 17 inhibitors may be used as first-line therapy, and should be continued if adequate response is achieved at 6 months. CONCLUSION: Recommendation statements were formulated through a formal consensus process by local experts with a view to assist relevant authorities in funding considerations and for use in clinical practice.

Sociodemographic factors as determinants of disease, disability and quality of life trajectories in early rheumatoid arthritis: A multi-ethnic inception cohort study.

OBJECTIVE: This study aims to describe the association between sociodemographic factors and trajectories of disease, disability and health-related quality of life (HRQoL) in early rheumatoid arthritis (ERA). METHODS: Data were collected prospectively over 3 years in the Singapore Early Arthritis Cohort study. Trajectories were modeled using multi-trajectory group-based trajectory modeling (GBTM) and determinants of trajectory membership were identified using multinomial logistic regression. RESULTS: Two hundred and thirteen patients were included: 58.2% Chinese, 16.4% Malay, 21.6% Indian, mean (SD) age 51.3 (12.6) years and symptom duration 21.8 (15.3) weeks. In the multi-trajectory analysis, three groups of disease trajectories and corresponding disability and HRQoL trajectories were identified: group 1 (moderate disease rapid response, 49.9%), group 2 (high disease rapid response, 31.1%) and group 3 (high disease slow response, 19.1%). Malay patients had higher relative risk ratio (RRR) of being in trajectory groups 2 and 3 compared to group 1 (RRR = 2.30, 95% CI 1.05-3.98 and RRR = 4.02, 95% CI 1.45-6.43, respectively) while patients with tertiary education had lower relative risk (RRR = 0.56, 95% CI 0.45-0.89 and RRR = 0.33, (95% CI 0.14-0.83, respectively). In the analysis of individual outcomes, ethnicity, education level and body mass index were determinants of the heterogeneous disease activity trajectories. Gender and education level were determinants of the disability trajectories. Only gender was a determinant of the HRQoL trajectories. Further, 96.2% of the patients were treated with conventional synthetic disease-modifying antirheumatic drugs. CONCLUSION: Disparities in sociodemographic factors should be taken into consideration in formulating treatment strategies in ERA.

Singapore Chapter of Rheumatologists updated consensus statement on the eligibility for government subsidization of biologic and targeted-synthetic therapy for the treatment of rheumatoid arthritis.

INTRODUCTION: Approximately 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARDs). However, widespread use of biologic DMARDs (bDMARDs) and targeted-synthetic (tsDMARDs) is limited by cost. We formulated updated recommendations for eligibility criteria for government-assisted funding of bDMARDs/tsDMARDs for RA patients in Singapore. MATERIALS AND METHODS: Published guidelines regarding use of bDMARD and tsDMARDs were reviewed. We excluded those without a systematic literature review, formal consensus process or evidence grading. Separately, unpublished national reimbursement guidelines were included. RESULTS: Eleven recommendations regarding choice of disease activity measure, initiation, order of selection and continuation of bDMARD/tsDMARDs were formulated. A bDMARD/tsDMARD is indicated if a patient has: (a) at least moderately active RA with a Disease Activity Score in 28 joints/erythrocyte sedimentation rate (DAS28-ESR) score of ≥3.2; (b) failed ≥2 csDMARD strategies, 1 of which must be a combination; (c) received an adequate dose regimen of ≥3 months for each strategy. For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered. If a first-line TNFi fails, options include another TNFi, non-TNFi biologic or tsDMARDs. If a first-line non-TNFi biologic or tsDMARD fails, options include TNFi or another non-TNF biologic or tsDMARD. For continued bDMARD/tsDMARD subsidization, a patient must have a documented DAS28-ESR every 3 months and at least a moderate European League Against Rheumatism response by 6 months. CONCLUSION: These recommendations are useful for guiding funding decisions, making bDMARD/tsDMARDs usage accessible and equitable in RA patients who fail csDMARDs.

A cross-sectional study on factors associated with poor work outcomes in patients with axial spondyloarthritis in Singapore.

AIM: Axial spondyloarthritis (axSpA) affects patients in the prime of their economic productivity. We aim to identify factors associated with poor work productivity in patients with axSpA in Singapore. METHODS: A cross-sectional study was performed in two tertiary centers in Singapore. Consecutive adult patients ≥21 years fulfilling Assessment in Spondyloarthritis International Society (ASAS) 2009 criteria for axSpA were recruited. Data on social demographics, clinical, treatment modalities and patient-reported outcome measures (PROMs) were collected. Work productivity was assessed by the Work Productivity and Activity Impairment scale (WPAI:SpA). Factors associated with presenteeism, absenteeism, work productivity loss and activity impairment were evaluated. RESULTS: A total of 156 patients with axSpA were included: 72.4% employed, 80.1% male, 86.5% Chinese, median (Q1:Q3) age and duration of illness 36.7 (28.7:47.9) years, and 6.3 (1.6:12.2) years respectively. The mean (SD) activity impairment was 28.2% (24.3%). Among employed patients, mean (SD) absenteeism, presenteeism and work productivity loss was 4.5% (13.7%), 24.9% (19.9%) and 27.6% (23.2%), respectively. In multivariable analysis, absenteeism was associated with disease duration (P = .02) and EuroQol-5D (EQ-5D) (P = .04). Presenteeism was associated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 (P = .04), Bath Ankylosing Spondylitis Functional Index (BASFI) (P < .01) and EQ-5D (P = .02). Work productivity loss was associated with BASFI (P = .02) and EQ-5D (P < .01). Activity impairment was associated with age (P = .04), BASDAI ≥ 4 (P < .01), BASFI (P < .01), EQ-5D (P < .01). CONCLUSION: Active disease, reduced physical function and poorer quality of life are associated with reduced work productivity in patients with axSpA in Singapore. Addressing these factors can potentially improve work productivity in patients with axSpA.

2018 APLAR axial spondyloarthritis treatment recommendations.

INTRODUCTION: Despite the availability of axial spondyloarthritis (SpA) recommendations proposed by various rheumatology societies, we considered that a region-specific guideline was of substantial added value to clinicians of the Asia-Pacific region, given the wide variations in predisposition to infections and other patient factors, local practice patterns, and access to treatment across countries. MATERIALS AND METHODS: Systematic reviews were undertaken of English-language articles published between 2000 and 2016, identified from MEDLINE using PubMed, EMBASE and Cochrane databases. The strength of available evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Recommendations were developed through consensus using the Delphi technique. RESULTS: Fourteen axial SpA treatment recommendations were developed based on evidence summaries and consensus. The first 2 recommendations cover non-pharmacological approaches to management. Recommendations 3 to 5 describe the following: the use of non-steroidal anti-inflammatory drugs as first-line symptomatic treatment; the avoidance of long-term corticosteroid use; and the utility of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for peripheral or extra-articular manifestations. Recommendation 6 refers to the indications for biological DMARDs (bDMARDs). Recommendation 7 deals specifically with screening for infections endemic to Asia, prior to use of bDMARDs. Recommendations 7 to 13 cover the role of bDMARDs in the treatment of active axial SpA and include related issues such as continuing therapy and use in special populations. Recommendation 14 deals with the utility of surgical intervention in axial SpA. CONCLUSION: These recommendations provide up-to-date guidance for treatment of axial SpA to help meet the needs of patients and clinicians in the Asia-Pacific region.

2018 APLAR axial spondyloarthritis treatment recommendations

Despite the availability of axial spondyloarthritis (SpA) recommendations proposed by various rheumatology societies, we considered that a region-specific guideline was of substantial added value to clinicians of the Asia-Pacific region, given the wide variations in predisposition to infections and other patient factors, local practice patterns, and access to treatment across countries.Systematic reviews were undertaken of English-language articles published between 2000 and 2016, identified from MEDLINE using PubMed, EMBASE and Cochrane databases. The strength of available evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Recommendations were developed through consensus using the Delphi technique.Fourteen axial SpA treatment recommendations were developed based on evidence summaries and consensus. The first 2 recommendations cover non-pharmacological approaches to management. Recommendations 3 to 5 describe the following: the use of non-steroidal anti-inflammatory drugs as first-line symptomatic treatment; the avoidance of long-term corticosteroid use; and the utility of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for peripheral or extra-articular manifestations. Recommendation 6 refers to the indications for biological DMARDs (bDMARDs). Recommendation 7 deals specifically with screening for infections endemic to Asia, prior to use of bDMARDs. Recommendations 7 to 13 cover the role of bDMARDs in the treatment of active axial SpA and include related issues such as continuing therapy and use in special populations. Recommendation 14 deals with the utility of surgical intervention in axial SpA.These recommendations provide up-to-date guidance for treatment of axial SpA to help meet the needs of patients and clinicians in the Asia-Pacific region.

Clinical Characteristics of Patients with Spondyloarthritis in Japan in Comparison with Other Regions of the World.

OBJECTIVE: To delineate clinical characteristics of patients with spondyloarthritis (SpA) in Japan in comparison to other areas of the world. METHODS: Using the ASAS-COMOSPA (Assessment of Spondyloarthritis international Society-COMOrbidities in SPondyloArthritis) data, an international cross-sectional observational study of patients with SpA, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Japan, other Asian countries (China, Singapore, South Korea, Taiwan), and non-Asian countries (Europe, the Americas, Africa). Patient characteristics, including diagnosis and treatment, were compared. RESULTS: Among 3984 patients included in the study, 161 were from centers in Japan, 933 from other Asian countries, and 2890 from other regions. Of patients with SpA in Japan, 42 (26.1%) had peripheral SpA, substantially more than in other countries. This trend was explained by the predominance of psoriatic arthritis (PsA) among Japanese patients with SpA. In contrast to the relatively low number in Japan, 54% of patients from other Asian countries had pure axial SpA (axSpA) without peripheral features. HLA-B27 testing, considered an integral part of the classification of axSpA, was performed in only 63.6% of Japanese patients with axSpA. More than half of Japanese patients with axSpA were classified using imaging criteria. CONCLUSION: In our study, there was a more substantial number of peripheral SpA cases observed in Japan compared to other parts of Asia and other regions of the world. Aside from ethnic differences, increasing recognition of PsA in Japan, as well as a potential underdiagnosis of axSpA due to the insufficient use of HLA-B27 testing, may partly explain regional discrepancies.

Validation of the Chinese Manchester foot pain and disability index (C-MFPDI) among patients with inflammatory arthritis.

BACKGROUND: The Manchester Foot Pain and Disability Index (MFPDI) is a patient-reported outcome tool used to measure foot pain and foot-related disability. The English version of the MFPDI has been successfully translated into other European languages, but there was no Chinese version to use in Chinese-speaking communities. The cross-sectional correlational study aimed to translate the MFPDI from English into simplified Chinese (C-MFPDI) and to test its psychometric properties among people with inflammatory arthritis in Singapore. METHODS: The MFPDI was translated from English into Chinese using a forward-backward translation framework and was administered to 100 Chinese-speaking people with inflammatory arthritis. From the original 100 participants, 30 participants re-evaluated the C-MFPDI after 2 weeks. A Visual Analogue Scale and the Taiwan Chinese Foot Function Index in simplified Chinese were used to evaluate concurrent validity with the C-MFPDI. Health-related quality of life was assessed using the Chinese version of the European Quality of Life-5 Dimension to test construct validity. RESULTS: The C-MFPDI had a high translation equivalent rate (96.3%) and content validity index (0.92), good internal consistency (Cronbach's α = 0.90) and test-retest reliability (ICC = 0.87). The concurrent validity of the C-MFPDI was demonstrated to be acceptable through its significantly moderate to strong positive correlations with the Taiwan Chinese Foot Function Index (r = 0.62-0.72, p < 0.01) and Visual Analogue Scale foot pain (r = 0.65, p < 0.01). The C-MFPDI total scores were moderately negatively associated with Chinese European Quality of Life-5 Dimension utility scores (r = - 0.40, p < 0.01). CONCLUSION: The C-MFPDI had good psychometric properties. The C-MFPDI can be used to assess disabling foot pain, impairment and disability in Chinese-speaking people with inflammatory arthritis.

Predicting flares in patients with stable systemic lupus erythematosus.

OBJECTIVES: Data on flares in Asian patients with systemic lupus erythematosus (SLE) are scarce. Here, we aim to identify the baseline predictors of flares in a cohort of Southeast Asian patients with SLE. METHODS: Consecutive adult patients with prevalent SLE according to the 1997 ACR or 2012 SLICC criteria were enrolled and followed three-monthly. Clinical and laboratory data were collected at every visit using a standardised protocol. Flares were defined using the SELENA-SLEDAI Flare Index (SFI). Baseline predictors of flare in patients with stable disease (SLE Disease Activity Index-2K (SLEDAI-2K) of ≤ 4) were determined using Cox proportional hazards. RESULTS: Of the 210 patients recruited, 148 (70.5%) were Chinese. The median (IQR) SLEDAI-2K at entry was 2 (0-4) and the median (IQR) disease duration was 10 (4.4-16.4) years. At baseline, 152 (72.4%) patients had stable disease. After a median (IQR) follow-up of 31.5 (24.1-36.3) months, 109 (51.9%) flared. Stable patients who flared tended to be in the lowest tertile of age (HR 3.08, 95% CI 1.72-5.48, p < 0.01), had thrombocytopenia (HR 5.01, 95% CI 1.32-18.99, p = 0.02), hypocomplementemia (HR 3.35, 95% CI 1.54-7.30, p < 0.01) and had the highest baseline prednisolone doses (HR 2.39, 95% CI 1.28-4.46, p = 0.01). Conversely, patients in the lowest tertile of disease duration tended not to flare (HR 0.41, 95% CI 0.21-0.80, p = 0.01). CONCLUSION: Flares are common in Asian SLE patients with initial stable disease. Close monitoring is needed for patients who are younger, with longer disease duration, thrombocytopenia, hypocomplementemia, or who required a higher baseline prednisolone dose.

A cross-sectional study on factors associated with patient-physician discordance in global assessment of patients with axial spondyloarthritis: an Asian perspective.

AIM: To identify the factors associated with patient-physician discordance in patients with axial spondyloarthritis (axSpA) in an Asian population. METHODS: A cross-sectional study was conducted in two tertiary referral centers in Singapore. Patients with axSpA who fulfilled Assessment in Ankylosing Spondylitis International Working Group 2009 criteria for axSpA were included in the study. Socio-demographics, clinical, laboratory and patient-reported outcomes data were collected during study visits from 2014 to 2015. We performed univariate and multivariate linear regression analyses to evaluate the factors associated with patient-physician discordance, which we defined as the difference between Patient Global Assessment and Physician Global Assessment. RESULTS: Included in the study were 298 axSpA patients: 82% male, 81% Chinese, median age 40 (20-78) years, median disease duration 9 (0.1-48) years. 80% were on non-steroidal anti-inflammatory drugs and 23% on biologics. In univariate analysis, current age (ß: 0.18, ρ = 0.06), duration of disease (ß: 0.34, ρ = 0.03), post-secondary education level (ß: -10.82, ρ = 0.03), global pain score (ß: 0.33, ρ < 0.01), Bath Ankylosing Spondylitis Functional Index (ß: 2.80, ρ < 0.01), Ankylosing Spondylitis Disease Activity Score C-reactive protein (ß: 4.63, ρ < 0.01) and current use of biologics (ß: 10.97, ρ < 0.01) were associated with patient-physician discordance. In multivariate analysis, global pain score (ß: 0.32, ρ < 0.01), post-secondary education level (ß: -12.80, ρ = 0.01) and current biologics use (ß: 16.21, ρ < 0.01) were associated with patient-physician discordance. CONCLUSION: Higher global pain score, lower educational level and current biologics use were associated with greater patient-physician discordance. These factors should be considered during shared decision making.

Use of complementary and alternative medicines is associated with delay to initiation of disease-modifying anti-rheumatic drug therapy in early inflammatory arthritis.

OBJECTIVES: To study the predictors of complementary and alternative medicine (CAM) use in patients with early inflammatory arthritis (EIA), and its impact on delay to initiation of disease-modifying anti-rheumatic drugs (DMARD). METHODS: Data were collected prospectively from EIA patients aged ≥ 21 years. Current or prior CAM use was ascertained by face-to-face interview. Predictors of CAM use and its effect on time to DMARD initiation were determined by multivariate logistic regression and Cox proportional hazards, respectively. RESULTS: One hundred and eighty patients (70.6% female, 58.3% Chinese), of median (interquartile range [IQR]) age 51.1 (40.9-59.8) years and symptom duration 16.6 (9.2-26.6) weeks were included: 83.9% had rheumatoid arthritis, 57% were seropositive. Median (IQR) Disease Activity Score in 28-joints (DAS28) was 4.3 (2.8-5.7), modified Health Assessment Questionnaire (mHAQ) was 0.38 (0.0-0.88) and 41.3% were CAM users. Chinese race (odds ratio [OR] 5.76 [95%CI 2.53-13.1]), being non-English speaking (OR 2.68 [95% CI 1.18-6.09]), smoking (OR 3.35 [95% CI 1.23-9.15] and high DAS28 (OR 2.73 [95% CI 1.05-7.09] were independent predictors of CAM use. CAM users initiated DMARD later (median [IQR] 21.5 [13.1-30.4] vs. 15.6 [9.4-22.7] weeks in non-users, P = 0.005). CAM use and higher DAS28 were associated with a longer delay to DMARD initiation (hazard ratio [HR] 0.69, 95% CI 0.50-0.95 and 0.63, 95% CI 0.43-0.91, respectively) while higher mHAQ was associated with a shorter delay (HR 1.59, 95% CI 1.08-2.34) and race, education level, being non-English speaking, smoking and seropositivity were not associated. CONCLUSIONS: Healthcare professionals should be aware of the unique challenges in treating patients with EIA in Asia. Healthcare beliefs regarding CAM may need to be addressed to reduce treatment delay.