Montreal cognitive assessment as a screening instrument for cognitive impairment in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is an increasingly used screening tool for cognitive impairment. The aim of this study was to examine how MoCA performed in identifying cognitive impairment (CI) domains in SLE patients compared with formal standardized neuropsychological testing (NPT). Factors related to SLE disease, immunologic and psychological state associated with CI were also explored. METHODS: This cross-sectional study recruited 50 SLE patients without overt neuropsychiatric manifestations from April 2017 to May 2018. The patients were evaluated with MoCA, formal NPT and the Depression, Anxiety, and Stress Scales (DASS) 42-item self-report questionnaire. Values of sensitivity and specificity were computed for different cut-offs of MoCA within each cognitive domain of NPT and descriptive analysis was used to identify the factors affecting cognitive function. RESULTS: The median score for MoCA was 27.5 (range 22-30). Using a MoCA cutoff of <26, 18 (36%) were identified to have CI using NPT compared to 8 (16%) using MoCA. The most frequently affected cognitive domain was executive functioning with 15 affected patients. Sensitivities and specificities of the MoCA range from 50% to 100% and 5.7% to 16.7%, respectively, across cognitive domains. A lower MoCA cutoff of <25 improve sensitivity of identifying impairment in executive functioning from 60% to 80%. In univariate analysis, DASS scores, disease activity, presence of antiphospholipid antibodies, presence of concurrent autoimmune disease, current, and cumulative corticosteroid therapy did not predict cognitive performance. CONCLUSION: MoCA may be a useful screening tool to identify the most frequently affected cognitive domain which is executive functioning using a lower cutoff of <25 in SLE patients without overt neuropsychiatric manifestations.

Lessons Learnt from the COVID-19 Pandemic: Starting Residency in a Foster Institution.

In Singapore, the Ministry of Health (MOH) raised the public health response level from DORSCON (Disease Outbreak Response System Condition) 'Yellow' to 'Orange' on 7 February 2020. This instituted strict movement restrictions for all healthcare workers to minimise cross-institutional transmission of COVID-19, creating a unique scenario where many residents physically located in different healthcare institutions at the start of DORSCON Orange were unable to return to their matched Sponsoring Institutions (SIs) to begin residency training in July 2020. Residents faced multiple administrative and emotional challenges as a result of freezing of cross-institutional movement. These challenges included concerns with regards to meeting training requirements (due to different modes of assessment, and posting structures between the 3 SIs) and concerns with regards to emotional support (due to starting residency in an unfamiliar environment where the resident may have less pre-existing connections/support). These challenges were swiftly addressed by the strong support of foster and parent institutions, and close communication between the leadership of the 3 SIs. Lessons learnt from the current pandemic include the need for a common online platform across the 3 SIs with regards to assessment forms, importance of sharing teaching materials between the different SIs and the need for close collaboration between parent and foster SIs with regards to balancing training requirements versus the needs posed by a pandemic situation on the healthcare structure.

Perceived Stress, Stigma, Traumatic Stress Levels and Coping Responses amongst Residents in Training across Multiple Specialties during COVID-19 Pandemic-A Longitudinal Study.

This study aimed to explore changes in psychological responses (perceived stress, traumatic stress, stigma, coping) over time in residents, as well as their predictors. The level of perceived stress, traumatic stress, stigma, and coping responses were assessed using the Perceived Stress Scale, Impact of Event-Revised, Healthcare Workers Stigma Scale, and Brief Coping Orientation to Problems Experienced (COPE) Inventory, respectively. We collected responses from 274 residents at baseline and 221 residents at 3 months follow-up (timepoint 2) from the National Healthcare Group (NHG) residency programs in Singapore. All residents reported lower perceived stress and lower perceived stigma compared to baseline. Use of avoidance coping was associated with all three psychological responses (perceived stress, traumatic stress, and stigma) across the two timepoints. Compared to baseline, specific factors associated with perceived stress and traumatic stress at timepoint 2 were living alone, less problem solving, and seeking social support. Residency programs should encourage active coping strategies (e.g., seeking social support, positive thinking, problem solving) among residents, and proactively identify residents who may be at higher risk of psychological sequelae due to circumstances that contribute to isolation.

2018 update of the APLAR recommendations for treatment of rheumatoid arthritis.

AIM: To update recommendations based on current best evidence concerning the treatment of rheumatoid arthritis (RA), focusing particularly on the role of targeted therapies, to inform clinicians on new developments that will impact their current practice. MATERIALS AND METHODS: A search of relevant literature from 2014 to 2016 concerning targeted therapies in RA was conducted. The RA Update Working Group evaluated the evidence and proposed updated recommendations using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, to describe the quality of evidence and strength of recommendations. Recommendations were finalized through consensus using the Delphi technique. RESULTS: This update provides 16 RA treatment recommendations based on current best evidence and expert clinical opinion. Recommendations 1-3 deal with the use of conventional synthetic disease-modifying antirheumatic drugs. The next three recommendations (4-6) cover the need for screening and management of infections and comorbid conditions prior to starting targeted therapy, while the following seven recommendations focus on use of these agents. We address choice of targeted therapy, switch, tapering and discontinuation. The last three recommendations elaborate on targeted therapy for RA in special situations such as pregnancy, cancer, and major surgery. CONCLUSION: Rheumatoid arthritis remains a significant health problem in the Asia-Pacific region. Patients with RA can benefit from the availability of effective targeted therapies, and these updated recommendations provide clinicians with guidance on their use.

2018 update of the APLAR recommendations for treatment of rheumatoid arthritis

To update recommendations based on current best evidence concerning the treatment of rheumatoid arthritis (RA), focusing particularly on the role of targeted therapies, to inform clinicians on new developments that will impact their current practice. A search of relevant literature from 2014 to 2016 concerning targeted therapies in RA was conducted. The RA Update Working Group evaluated the evidence and proposed updated recommendations using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, to describe the quality of evidence and strength of recommendations. Recommendations were finalized through consensus using the Delphi technique. This update provides 16 RA treatment recommendations based on current best evidence and expert clinical opinion. Recommendations 1­3 deal with the use of conventional synthetic disease­modifying antirheumatic drugs. The next three recommendations (4­6) cover the need for screening and management of infections and comorbid conditions prior to starting targeted therapy, while the following seven recommendations focus on use of these agents. We address choice of targeted therapy, switch, tapering and discontinuation. The last three recommendations elaborate on targeted therapy for RA in special situations such as pregnancy, cancer, and major surgery. Rheumatoid arthritis remains a significant health problem in the Asia­Pacific region. Patients with RA can benefit from the availability of effective targeted therapies, and these updated recommendations provide clinicians with guidance on their use.

Singapore Chapter of Rheumatologists consensus statement on the eligibility for government subsidy of biologic disease modifying anti-rheumatic agents for the treatment of psoriatic arthritis.

AIM: In Singapore, patients with psoriatic arthritis (PsA) constitute a significant disease burden. There is good evidence for the efficacy of anti-tumor necrosis factor (anti-TNF) in PsA; however cost remains a limiting factor. Non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) hence remain the first-line treatment option in PsA in spite of limited evidence. The Singapore Chapter of Rheumatologists aims to develop national guidelines for clinical eligibility for government-assisted funding of biologic disease modifying anti- rheumatic drugs (bDMARDs) for PsA patients in Singapore. METHODS: Evidence synthesis was performed by reviewing seven published guidelines on use of biologics for PsA. Using the modified Research and Development/University of California at Los Angeles Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations. RESULTS: Ten recommendations were formulated relating to initiation, continuation and options of bDMARD therapy. The panellists agreed that a bDMARD is indicated if a patient has active PsA with at least five swollen and tender joints, digits or entheses and has failed two nbDMARD strategies at optimal doses for at least 3 months each. Any anti-TNF may be used and therapy may be continued if an adequate PsARC response is achieved by 3 months after commencement. CONCLUSION: The recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARD usage accessible and equitable to eligible patients in Singapore.

Consensus development on eligibility of government subsidisation of biologic disease modifying anti-rheumatic agents for treatment of ankylosing spondylitis: The Singapore experience.

INTRODUCTION: The beneficial effects of biologic disease-modifying anti-rheumatic drugs (bDMARDs), such as tumour necrosis factor inhibitors (anti-TNF) in active ankylosing spondylitis (AS) are well established. The significant costs on patients in the absence of financial subsidization can limit their use. The objective was to describe a consensus development process on recommendations for government-assisted funding of biologic therapy for AS patients in Singapore. METHODS: Evidence synthesis followed by a modified RAND/UCLA Appropriateness Method (RAM) was used. Eleven rheumatologists rated indications for therapies for different proposed clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate 10 practice recommendations. RESULTS: It was agreed that a bDMARD (anti-TNF) is indicated if a patient has active AS with a Bath Ankylosing Spondylitis Activity Index (BASDAI) ≥ 4 and spinal pain of ≥ 4 cm on visual analogue scale (VAS) on two occasions at least 12 weeks apart, despite being on a minimum of two sequential non-steroidal anti-inflammatory drugs at maximal tolerated dose for at least 4 weeks, in addition to adherence to an appropriate physiotherapy program for at least 3 months. To qualify for continued biologic therapy, a patient must have documentation of response every 3 months and at least 50% improvement in BASDAI and reduction of spinal pain VAS ≥ 2 cm. CONCLUSION: A validated and feasible consensus process can enable pragmatic standardized recommendations to be developed for bDMARD subsidization for AS patients in a local Asian context.

Poorly controlled gout: who is doing poorly?

Gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals, is commonly seen in primary care and specialist clinics. In recent years, there has been a resurgence of interest in gout due to advances in therapies and the understanding of pathophysiology, with new guidelines being published by international bodies. However, there is still a gap between the goals of treatment and actual day-to-day practice. Barriers that result in poorly controlled gout include patient factors such as lack of understanding of the disease, stigma and nonadherence to treatment, as well as physician factors such as knowledge gaps, inadequate use of allopurinol and lack of ownership of the disease. The medical profession needs to do more to bridge the gap through physician and patient education, identification of treatment targets with appropriate use of drugs, and dissemination of guidelines.

APLAR rheumatoid arthritis treatment recommendations.

AIMS: Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue. MATERIALS AND METHODS: The AGREE II instrument and the ADAPTE Collaboration framework were applied to systematically identify, appraise, synthesize, and adapt international rheumatoid arthritis guidelines for use in the Asia-Pacific region. RESULTS: Forty rheumatoid arthritis treatment recommendations, based on evidence and expert opinion, were drafted and are presented in this report. CONCLUSION: The Asia Pacific of Associations for Rheumatology rheumatoid arthritis treatment recommendations are intended to serve as a reference for best practice management of rheumatoid arthritis in Asia-Pacific, focusing on local issues to ensure the delivery of basic care for these patients, and to improve their outcomes. In addition, the document will serve as a reference for national rheumatology associations in Asia-Pacific for developing guidelines in their respective countries.

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy.

BACKGROUND: Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. OBJECTIVE: To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. METHODS: Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. RESULTS: There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. CONCLUSION: Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.

Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis.

OBJECTIVE: Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter-observer reliability in scoring of synovitis. METHODS: Eight rheumatologists (Singapore) participated in a 1-day consensus meeting divided into: (i) still-image interpretation and consensus followed by; (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and European League Against Rheumatism (EULAR)-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). RESULTS: For B-mode still images, ICC was good at 0.75 (95% CI 0.66-0.82) while for PDUS images this was excellent at ICC = 0.88 (95% CI 0.83-0.92) with ICC improving by 12% for B-mode and 13% for PDUS respectively. During image acquisition and interpretation, B-mode scoring showed ICC = 0.75 (95% CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95% CI 0.48-0.72). The ICC for OMERACT PDUS composite synovitis scoring was good at 0.77 (95% CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and metatarsophalangeal joints, and no agreement at the knees (PABAK range -0.34 to 0.85). CONCLUSION: A consensus meeting was useful in improving interobserver variation in US synovitis scoring of still images, but image acquisition and interpretation especially in non-hand joints require further standardization.

Major trends in the manifestations and treatment of rheumatoid arthritis in a multiethnic cohort in Singapore.

We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990-1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.

Sphingosine kinase and sphingosine-1-phosphate receptors: novel therapeutic targets of rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic, destructive, autoimmune joint disease characterized by elevated levels of proinflammatory cytokine production. Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate. Synovial fluid of RA patients exhibits significantly higher levels of S1P than their non-inflammatory osteoarthritis counterparts. SphK blockade suppresses cytokines and MMP-9 release in RA peripheral blood mononuclear cells. In addition, downregulation of SphK1 either through a specific siRNA approach or transgenic human TNF-α SphK1-deficient mice (hTNF-α/SphK1(-/-)) exhibit significantly less synovial inflammation and joint pathology. By contrast, SphK2 modulation leads to disease exacerbation. These results clearly demonstrate that such anti- and proinflammatory potential of SphK1/2 modulation may alter the outcome in RA synovitis and raises the possibility that drugs that specifically target SphK1 activity may play a beneficial role in the treatment of RA and other autoimmune rheumatic diseases.

Urine sVCAM-1 and sICAM-1 levels are elevated in lupus nephritis.

AIM: We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM-1 (vascular) and sICAM-1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. METHODS: Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. CONCLUSION: Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis.

Recurrent fractures in an elderly patient with systemic lupus erythematosus.

Glucocorticoid-induced osteoporosis (GIO) is an important problem that remains undertreated, even by rheumatologists. We present a case of an elderly patient with systemic lupus erythematosus diagnosed more than 40 years ago, who suffered from recurrent fractures and attendant complications despite a bone mineral density (BMD) score in the osteopenic range and treatment with bisphosphonates. With improved treatment and outcome of lupus, an increasing number of elderly patients who are susceptible to osteoporotic fractures are expected. This case serves to highlight that rheumatic disease patients on steroids should be screened for GIO, as effective treatment and preventive measures are available. Teriparatide is a promising treatment for patients who have failed bisphosphonate treatment or who are at high risk for fracture. We should also bear in mind that BMD scores alone are not indicative of fracture risk, and other tools such as the WHO-FRAX (Fracture risk assessment tool), serum vitamin D3 levels and bone turnover markers should be used where appropriate. Other measures including attention to factors that contribute to falls should also be considered, necessitating a multi-disciplinary approach.

Severe cutaneous adverse reactions to drugs.

PURPOSE OF REVIEW: This paper updates the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis supported by relevant views about the pathogenesis. RECENT FINDINGS: Building on the thesis that Stevens-Johnson syndrome and toxic epidermal necrolysis are due to dermal cell apoptosis, molecular pathways that may lead to this have been proposed. Intravenous immunoglobulin is postulated to block apoptosis via the Fas pathway. Most series on the use of intravenous immunoglobulin in toxic epidermal necrolysis have been favourable. Tumour necrosis factor is also thought to be an important mediator of cell death in toxic epidermal necrolysis. There was impressive control of the progression of toxic epidermal necrolysis with intravenous anti-tumour necrosis factor antibody infliximab in two cases. Strong associations between human leukocyte antigen subtypes and severe cutaneous reactions due to allopurinol and carbamazepine have been described. SUMMARY: To date, there is no established treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis. With advancing knowledge of the pathogenesis, it is hoped that better forms of treatment may result.