Semi-quantitative indices of 2-[18F]FDG PET/CT in assessing cardiovascular and non-cardiovascular manifestations of IgG4-related disease and treatment response.

BACKGROUND: IgG4-related disease (IgG4-RD) is a heterogeneous autoimmune disorder characterised by inflammatory lesions. Diagnostic imaging, such as 2-[18F]FDG PET/CT, is critical in evaluation of the disease, especially for potentially lethal cardiovascular manifestations. This retrospective study examines the usefulness of semi-quantitative parameters of 2-[18F]FDG PET/CT in monitoring IgG4-RD in patients with and without cardiovascular manifestations. METHODS: Patients diagnosed with IgG4-RD who underwent a 2-[18F]FDG PET/CT scan were identified and classified based on presence or absence of cardiovascular disease. Clinical and laboratory data were extracted and compared to three 2-[18F]FDG PET/CT semi-quantitative parameters: maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Tissue-to-background blood (TBR) values were also evaluated for cardiovascular manifestations. These data were also compared in patients before and after receiving immunosuppressive therapy. RESULTS: Forty-six patients identified were divided into an eight member subgroup of patients with cardiovascular manifestations, and a thirty-eight member subgroup of patients without. Patients with cardiovascular lesions were most frequently identified incidentally on imaging evaluation for other diseases (37.5%), with none presenting with chest pain or other cardiovascular symptoms. Ten patients with pre-treatment and post-treatment 2-[18F]FDG PET/CT scans demonstrated significant decreases in all semi-quantitative parameters, with no significant decrease in total IgG or ESR. The decrease in SUVmax, MTV, TLG following therapy was replicated in patients with and without cardiovascular manifestations. CONCLUSION: 2-[18F]FDG PET/CT is an important investigation to determine all sites of involvement in this multisystemic disease and to rule out life-threatening cardiovascular manifestations even in the absence of symptoms. Semi-quantitative parameters such as SUVmax, MTV, TLG, and TBR are useful in assessing treatment response in patients. There are no serological substitutes that can quantify the extent of disease involvement like 2-[18F]FDG PET/CT.

Evaluating the educational environment in a residency programme in Singapore: can we help reduce burnout rates?

INTRODUCTION: The educational environment (EE) reflects the quality of a residency programme and has an association with burnout. Studying the EE allows for interventions to target specific weaknesses. We aimed to measure the EE of an internal medicine residency programme in Singapore, compare the perceptions between genders, residency grades and levels of work experience, and identify specific areas of weaknesses for intervention in hopes of reducing residency burnout rates in Singapore. METHODS: This study took place between October and December 2017. We adopted a mixed methods approach, quantitatively using the Postgraduate Hospital Educational Environment Measure (PHEEM), and qualitative exploration using semi-structured focus group discussion. RESULTS: A total of 136 (88.9%) out of 153 residents responded. Our total PHEEM scores (112.23 ± 16.71), along with the scores for all three subscales, were higher than those of institutions in previous studies. There were no differences in overall PHEEM and subscale scores between genders, residency grades or levels of work experience. However, there were differences for individual questions, which were explored in the focus group discussion. Senior residents juggling heavier workloads, responsibilities and examinations appeared to be most prone to burnout. We identified three recurring themes that contributed to a poor EE in our programme: excessive workload, poor faculty relationships and differing unmet needs. CONCLUSION: Although our programme had a good EE, there were also areas of weaknesses revealed by specific questions, possibly contributing to burnout. We hope to implement interventions to these areas and subsequently assess for longitudinal changes in EE and burnout rates.

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.

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.

Using the Postgraduate Hospital Educational Environment Measure to Identify Areas for Improvement in a Singaporean Residency Program.

BACKGROUND: Attributes of the clinical learning environment (CLE) are a measure of quality in postgraduate medical education, and assessing the CLE is a component of the New Accreditation System being introduced in Singapore by the Accreditation Council for Graduate Medical Education International. There is a dearth of published studies of CLE quality in Singapore. OBJECTIVE: Our study had 3 aims: (1) to measure the CLE in 1 Singaporean residency program; (2) to compare trainee perceptions by sex, training level, and experience; and (3) to identify areas for improvement. METHODS: Between October and December 2017, we conducted a mixed assessment of the CLE in an internal medicine program in Singapore, using the Postgraduate Hospital Educational Environment Measure (PHEEM) and qualitative exploration using a focus group. RESULTS: Of 153 IM residents, 136 (89%) provided PHEEM responses and 8 participated in the focus group. Total PHEEM scores and scores for the 3 subscales were higher than published data on the use of the PHEEM in international settings. Exploration of selected PHEEM responses via a focus group identified attributes associated with negative perceptions of the CLE: excessive workload, inadequate faculty presence in the CLE, and unmet trainee needs. It also suggested senior residents' clinical workloads, greater responsibilities, and pending examinations may contribute to their less positive perceptions of the CLE. CONCLUSIONS: Our analysis using the PHEEM showed overall positive perceptions of the CLE, along with areas for improvement amenable to interventions. Our approach has relevance to an accreditation model with ongoing evaluation of the CLE.

Risk factors for cytomegalovirus disease in systemic lupus erythematosus (SLE): a systematic review.

BACKGROUND: Cytomegalovirus (CMV) is an opportunistic pathogen causing reactivation and disease in Systemic Lupus Erythematosus (SLE) patients. This study aims to systematically review the literature for risk factors associated with CMV disease in SLE patients, in order to identify those more susceptible to CMV infection during their treatment. METHODS: A systematic review was conducted on 4 different search engines and via hand search until May 2017. Studies were included after quality assessment via the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields (HTA KMET). RESULTS: Two studies on CMV disease were included. Elevated CMV viral load, higher steroid doses, use of immunosuppressants and disease duration were the most commonly associated risk factors for CMV disease. CONCLUSION: High CMV viral loads, longer SLE disease duration and higher steroid doses were associated with CMV disease. Further studies studying the risk of treatment drugs and role of interventions in the development of CMV infection are needed.

Risk factors for cytomegalovirus disease in systemic lupus erythematosus (SLE): a systematic review

Abstract Background: Cytomegalovirus (CMV) is an opportunistic pathogen causing reactivation and disease in Systemic Lupus Erythematosus (SLE) patients. This study aims to systematically review the literature for risk factors associated with CMV disease in SLE patients, in order to identify those more susceptible to CMV infection during their treatment. Methods: A systematic review was conducted on 4 different search engines and via hand search until May 2017. Studies were included after quality assessment via the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields (HTA KMET). Results: Two studies on CMV disease were included. Elevated CMV viral load, higher steroid doses, use of immunosuppressants and disease duration were the most commonly associated risk factors for CMV disease. Conclusion: High CMV viral loads, longer SLE disease duration and higher steroid doses were associated with CMV disease. Further studies studying the risk of treatment drugs and role of interventions in the development of CMV infection are needed.

Validity and reliability of the Short Form 36 Health Surveys (SF-36) among patients with spondyloarthritis in Singapore.

The Short Form 36 Health Survey (SF-36) is a popular health-related quality of life (HrQoL) tool. However, few studies have assessed its psychometric properties in patients with spondyloarthritis (SpA). We therefore aimed to assess the reliability and validity of the SF-36 in patients with SpA in Singapore. Cross-sectional data from a registry of 196 SpA patients recruited from a dedicated tertiary referral clinic in Singapore from 2011 to 2014 was used. Analyses were guided by the COnsensus-based Standards for the selection of health Measurement INstruments framework. Internal consistency reliability was assessed using Cronbach's alpha. Construct validity was assessed through 33 a priori hypotheses by correlations of the eight subscales and two summary scores of SF-36 with other health outcomes. Known-group construct validity was assessed by comparison of the means of the subscales and summary scores of the SF-36 of SpA patients and the general population of Singapore using student's t tests. Among 196 patients (155 males (79.0 %), median (range) age: 36 (17-70), 166 Chinese (84.6 %)), SF-36 scales showed high internal consistency ranging from 0.88 to 0.90. Convergent construct validity was supported as shown by fulfillment of all hypotheses. Divergent construct validity was supported, as SF-36 MCS was not associated with PGA, pain and HAQ. Known-group construct validity showed SpA patients had lower scores of 3.8-12.5 when compared to the general population at p < 0.001. This study supports the SF-36 as a valid and reliable measure of HrQoL for use in patients with SpA at a single time point.

Streptococcus pneumoniae bacteraemia due to parotitis in a patient with systemic sclerosis and secondary Sjögren's syndrome.

INTRODUCTION: Invasive pneumococcal disease is an uncommon and notifiable disease in Singapore. It is often associated with significant morbidity and mortality. We report a rare case of invasive pneumococcal bacteraemia due to parotitis in a patient with systemic sclerosis and secondary Sjögren's syndrome. We also present a retrospective review of Streptococcus pneumoniae bacteraemia cases in Singapore General Hospital from January 2011 to April 2016. CASE PRESENTATION: A 59-year-old Malay lady with a history of systemic sclerosis with secondary Sjögren's syndrome presented with fever and left parotid gland swelling. Clinical examination revealed poor salivary pooling and left parotid swelling without fluctuance. Ultrasound of the left parotid gland confirmed acute parotitis without evidence of abscess or sialolithiasis. Blood cultures were positive for S. pneumoniae. She was diagnosed to have invasive pneumococcal bacteraemia secondary to acute parotitis, and treated with intravenous benzylpenicillin with clearance of bacteraemia after 3 days. Upon discharge, her antibiotics were changed to intravenous ceftriaxone to facilitate outpatient parenteral antibiotic therapy for another 2 weeks. She responded favourably to antibiotics at follow-up, with no complications from the bacteraemia. A review of the microbiological records of the Singapore General Hospital revealed 116 cases of pneumococcal bacteraemia, most (80.3 %) of which were due to pneumonia. None were due to parotitis. CONCLUSION: S. pneumoniae parotitis and subsequent bacteraemia is rare. Prompt recognition of the disease and appropriate use of antibiotics are important. This case highlights that close communication between healthcare workers (microbiologist, rheumatologist and infectious disease specialist) is essential in ensuring good clinical outcomes in patients with a potentially fatal disease.

IgG4-related disease in Singapore: a description of two cases and review of the literature.

We describe a 42-year-old man who presented with painless obstructive jaundice, organomegaly and lymphadenopathy. Biopsy of the ampulla of Vater revealed the presence of increased populations of plasma cells which stained positively for immunoglobulin G4. He was treated with prednisolone and demonstrated significant clinical improvement 1 month later. A further case is described and a review of the literature is also provided.