Prevalence and Factors Associated with Concomitant Chinese Medicine Use by Rheumatoid Arthritis Patients in A Multi-Ethnic Asian Population / 中国结合医学杂志

OBJECTIVE@#To determine the prevalence, factors associated with and patterns of concomitant Chinese medicine (CM) with Western treatment use among patients with rheumatoid arthritis (RA) in a tertiary referral centre (Singapore General Hospital) in Singapore.@*METHODS@#We conducted a cross-sectional interviewer-administered survey of a consecutive sample of patients with RA in Singapore General Hospital centre regarding their CM use including data on patient demographics, disease characteristics, concomitant use of CM and reasons, concerns and disclosure patterns from March to August 2015. Univariate and multivariate logistic regression analyses were performed to determine the associations of CM use.@*RESULTS@#Prevalence of CM use among the 258 patients surveyed (male: female 42: 216; Chinese: Malay: Indian 191: 29: 34; mean age: 61 years; mean duration of RA: 10 years) was 46.1% (119/258). On multivariate analysis, Chinese ethnicity (OR, 95% CI: 4.11, 1.49-11.36), Chinese speakers (OR, 95% CI: 2.35, 1.03-5.54), middle-income group (OR, 95% CI: 2.53, 1.01-6.31) and greater learned helplessness (OR, 95% CI: 1.13, 1.04-1.22) were significantly associated with CM use. More CM users disclosed their CM use to CM physicians (87.3%, 96/110), sought advice from them on treatment interactions (59.4%, 57/96) and how best to combine treatments (49.0%, 47/96) than did so with rheumatologists (42.0%, 50/119; 40.0%, 20/50; and 42.0%, 21/50, respectively). Forty-two percentage (29/69) of patients who concealed CM use from rheumatologists because their rheumatologists did not specifically enquire about CM use.@*CONCLUSIONS@#Concomitant CM use among patients with RA treated in a tertiary referral centre in Singapore is high but voluntary disclosure is low. The associations identified can help doctors identify and enquire about CM use, minimizing potential adverse interactions.

Maternal and Fetal Outcomes in Systemic Lupus Erythematosus Pregnancies

INTRODUCTION@#To describe the maternal and fetal outcomes in systemic lupus erythematosus (SLE) pregnancies followed-up in a single tertiary referral centre.@*METHODS@#We performed a retrospective cohort study of 75 SLE pregnancies who were followed up in Singapore General Hospital over a 16-year period from 2000 to 2016. Adverse fetal and maternal outcomes including preterm delivery, miscarriages, fetal growth restriction, congenital heart block, neonatal lupus, pre-eclampsia and SLE flares were obtained from the medical records.@*RESULTS@#The mean age at conception was 32 years old (SD 3.8). The mean SLE disease duration was 5.9 years (SD 5.2). The majority (88%) had quiescent SLE disease activity at baseline. Most pregnancies resulted in a live birth (74.7%). The mean gestational age at birth was 37.4 weeks (SD 3.4). Adverse fetal outcomes occurred in 53.3%. Preterm delivery (33.9%), miscarriages (20%) and fetal growth restriction (17.3%) were the most frequent adverse fetal outcomes. There was 1 neonatal death and SLE flares occurred in a third (33%). In the subgroup of SLE pregnancies with antiphospholipid syndrome, there were higher SLE flare rates (40%) and adverse fetal outcomes occurred in 8 pregnancies (80%). There were no predictive factors identified for all adverse fetal and maternal outcomes. In the subgroup analysis of preterm delivery, anti-Ro (SS-A) antibody positivity and hydroxychloroquine treatment were associated with a lower risk of preterm delivery.@*CONCLUSION@#Although the majority had quiescent SLE disease activity at baseline, SLE pregnancies were associated with high rates of adverse fetal and maternal outcomes.

The Impact of the Off-site Monitoring Clinic (Virtual Monitoring Clinic) on the Practice of Outpatient Rheumatology in a Tertiary Centre during the COVID-19 Pandemic

The ongoing pandemic in Singapore is part of a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To control the spread of COVID-19 and prevent the healthcare system from being overwhelmed, 'circuit breaker' measures were introduced between 7 April and 1 June 2020 in Singapore. There is thus a crucial need for innovative approaches to the provision and delivery of healthcare in the context of safe-distancing by harnessing telemedicine, especially for patients with chronic diseases who have traditionally been managed in tertiary institutions. We present a summary of how the Virtual Monitoring Clinic has benefited the practice of our outpatient rheumatology service during the COVID-19 pandemic. The virtual consultations address the need for safe-distancing by limiting face-to-face appointments and unnecessary exposure of patients to the hospital where feasible. This approach ensures that the patients are monitored appropriately for drug toxicities and side-effects, maintained on good disease control, and provided with patient education.

A systematic review of the association of obesity with the outcomes of inflammatory rheumatic diseases

This was a systematic review of the literature on the association between obesity and the outcome of inflammatory rheumatic diseases. We conducted a literature search using PubMed®, Embase and PsycINFO®. Articles were classified into three categories based on the effects of obesity on the outcomes of inflammatory rheumatic diseases. The subject population, country, type of studies, number of patients, measurement of obesity and outcomes assessed were presented. Quality was appraised using Kmet et al's criteria. 4,331 articles were screened and 60 were relevant to the objective. Obesity had a negative, positive and neutral association with outcomes of inflammatory rheumatic diseases in 38 (63.3%) studies with 57,612 subjects, 11 (18.3%) studies with 3,866 subjects, and 11 (18.3%) studies with 3,834 subjects, respectively. In most studies, the disease population had been diagnosed with rheumatoid arthritis (RA). Tumour necrosis factor-α inhibitors were mostly associated with negative outcomes. More studies examining subjects outside Europe and North America and diseases other than RA are warranted.

Making Clinical Practice Guidelines Pragmatic: How Big Data and Real World Evidence Can Close the Gap

Clinical practice guidelines (CPGs) have become ubiquitous in every field of medicine today but there has been limited success in implementation and improvement in health outcomes. Guidelines are largely based on the results of traditional randomised controlled trials (RCTs) which adopt a highly selective process to maximise the intervention's chance of demonstrating efficacy thus having high internal validity but lacking external validity. Therefore, guidelines based on these RCTs often suffer from a gap between trial efficacy and real world effectiveness and is one of the common reasons contributing to poor guideline adherence by physicians. "Real World Evidence" (RWE) can complement RCTs in CPG development. RWE-in the form of data from integrated electronic health records-represents the vast and varied collective experience of frontline doctors and patients. RWE has the potential to fill the gap in current guidelines by balancing information about whether a test or treatment works (efficacy) with data on how it works in real world practice (effectiveness). RWE can also advance the agenda of precision medicine in everyday practice by engaging frontline stakeholders in pragmatic biomarker studies. This will enable guideline developers to more precisely determine not only whether a clinical test or treatment is recommended, but for whom and when. Singapore is well positioned to ride the big data and RWE wave as we have the advantages of high digital interconnectivity, an integrated National Electronic Health Record (NEHR), and governmental support in the form of the Smart Nation initiative.

Resident research: why some do and others don't

<p><b>INTRODUCTION</b>Although research is widely considered to be a relevant and essential skill to resident development, the actual participation rate of residents in research remains low, and the factors associated with participation are unclear.</p><p><b>METHODS</b>We examined the participation rate of junior residents in research, and their attitudes and perceived barriers toward research, via an anonymised survey carried out from October to November 2013. The residents were from an established Accreditation Council for Graduate Medical Education-accredited internal medicine residency training programme in Singapore.</p><p><b>RESULTS</b>The overall response rate was 64.1% (82/128 residents). The most frequently cited barrier was lack of time. Only a third of the residents surveyed were actively participating in research. Those with postgraduate qualifications were more likely to be involved in research (odds ratio 4.71, p = 0.015). Among the 82 residents, 40.2% reported an interest in research as part of their career; these were mainly graduates from overseas universities or postgraduates. A belief that research is an intrinsically valuable activity distinguished residents who chose research as a career path from those who were undecided (p = 0.004). The belief that research is a means to better clinical practice also divided those who chose research from those who rejected it (p = 0.02).</p><p><b>CONCLUSION</b>Our findings suggest that specific beliefs determine the level of research activity and career interest among residents. Novel strategies may be incorporated in training programmes to improve the interest and participation of residents in research, and to facilitate the development of academic clinicians.</p>

Validity of a Revised Short Form-12 Health Survey Version 2 in Different Ethnic Populations

<p><b>INTRODUCTION</b>The Short Form-12 version 2 (SF-12v2) is a shorter version of the Short Form-36 version 2 (SF-36v2) for assessing health-related quality of life. As the SF-12v2 could not be resolved into the physical- and mental-component summary score (PCS and MCS, respectively) in the general population of Singapore, this study aims to determine and validate the Singapore SF-12 version 2 (SG-12v2).</p><p><b>MATERIALS AND METHODS</b>The SG- 12v2 was generated using the same methodology as the SF-12v2. Bootstrap analysis was used to determine if the SG-12v2 were significantly different from the SF-12v2. Content validity was assessed using percentage of variance (R²) of the Singapore version of SF-36v2 PCS and MCS explained by the SG-12v2 items. Agreement between the SF-36v2 and the SG-12v2 was assessed using Bland-Altman diagrams. Criterion validity was demonstrated if effect size differences between SF-36v2 and SG-12v2 were small (Cohen's criteria). Known-group validity of SG-12v2 was reported for participants with and without chronic diseases.</p><p><b>RESULTS</b>Five items differed between the SG-12v2 and SF-12v2. Bootstrap analysis confirmed that SG-12v2 and SF-12v2 were significantly different. The SG12v2 explained 94% and 79% of the R² of the SF-36v2 PCS and MCS, respectively. Agreement was good and effect size differences were small (<0.3). Participants with chronic diseases reported lower SG-12v2 scores compared to participants without chronic diseases.</p><p><b>CONCLUSION</b>The SG-12v2 offers advantage over the SF-12v2 for use in the general population of Singapore. The SG-12v2 is a valid measure and will be particularly useful for large population health surveys in Singapore.</p>

Normative Data for the Singapore English and Chinese SF-36 Version 2 Health Survey

<p><b>INTRODUCTION</b>The aim of this study is to report normative data for the Short-Form 36 version 2 (SF-36v2) for assessing health-related quality of life, in the Singapore general population.</p><p><b>MATERIALS AND METHODS</b>Data for English and Chinese-speaking participants of the Singapore Prospective Study Programme were analysed. The SF-36v2 scores were norm-based with the English-speaking Singapore general population as reference and reported by age (in decades), gender and ethnicity as well as for the 5 most prevalent chronic medical conditions. Scores were reported separately for the English and Chinese language versions.</p><p><b>RESULTS</b>A total of 6151 English-speaking (61.5% Chinese and 19.2% Malay) and 1194 Chinese-speaking participants provided complete data. Mean (SD) age of all participants was 49.6 (12.58) years with 52.4% being women. In both languages, women reported lower scores than men on all scales. Among the chronic medical conditions, stroke had the largest impact on all English SF-36v2 scales and on 3 Chinese SF-36v2 scales (role-physical, general health and social functioning).</p><p><b>CONCLUSION</b>We have provided detailed normative data for the Singapore English and Chinese SF-36v2, which would be valuable in furthering HRQoL research in Singapore and possibly the region.</p>

Height and mental health and health utility among ethnic Chinese in a polyclinic sample in Singapore

<p><b>INTRODUCTION</b>Whether fi nal height is associated with quality of life and mental health is a matter of epidemiological and medical concern. Both social and biological explanations have been previously proposed. This study aims to assess the associations in ethnic Chinese in Singapore.</p><p><b>MATERIALS AND METHODS</b>A cross-sectional study of 4414 respondents aged at least 21 years seen at a major polyclinic was performed. Socioeconomic and behavioural features of the sample and the Singapore population of similar ages were comparable. Height was measured by clinic nurses using an ultrasonic height senor. Participants were interviewed for socioeconomic, behavioural, health and quality of life information. Clinical morbidity data was collected from the participants' treating physicians. The SF-6D utility index and its Mental Health domain were the main endpoints. Linear and ordinal logistic regression models were used to analyse the utility index and the Mental Health scores, respectively.</p><p><b>RESULTS</b>Having adjusted for age and gender, the Mental Health domain (P <0.01) was associated with height but the utility index was not. Further adjustment for health, socioeconomic and behavioural covariates made little difference. Analyses based on height categories showed similar trends.</p><p><b>CONCLUSION</b>Adult height has a positive association with mental health as measured by the SF-6D among ethnic Chinese in Singapore. Socioeconomic status and known physical health problems do not explain this association. Adult height had no association with SF-6D utility index scores.</p>

Polyarthritis in four patients with chikungunya arthritis

The incidence of chikungunya infection in Singapore has been on the rise since the first reported case in 2006. Acute polyarthritis, a common manifestation among affected patients, may precede fever and present with debilitating arthritis to rheumatologists, orthopaedists, internists and primary care physicians. The diagnosis of chikungunya infection requires careful history taking and a high index of suspicion, with supporting evidence from the reverse transcription-polymerase chain reaction or the chikungunya IgM serology test. Treatment of chikungunya arthritis usually involves non-steroidal anti-inflammatory drugs. Rarely, polyarthritis in chikungunya may persist even after resolution of the acute infection, necessitating treatment with disease-modifying anti-rheumatic drugs. In this article, we present the different manifestations of chikungunya arthritis in our local setting and review the literature.

Asian adaptation and validation of an English version of the multiple sclerosis international quality of life questionnaire (MusiQoL)

<p><b>INTRODUCTION</b>The Multiple Sclerosis International Quality of Life questionnaire (MusiQoL) is a self-administered, multi-dimensional, patient-based health-related quality of life (HRQoL) instrument. With increasing prevalence of multiple sclerosis (MS) in Asian countries, a valid tool to assess HRQoL in those patients is needed. The aim of this study was to evaluate patient acceptability, content validity and psychometric properties of an Asian version of the English MusiQoL in Singapore, Malaysia and India.</p><p><b>MATERIALS AND METHODS</b>English speaking patients older than 18 years of age with a defi nite diagnosis of MS were included. The self-administered survey material included the adapted HRQoL questionnaire, a validated generic HRQoL questionnaire: the short-form 36 (SF-36), as well as a checklist of 14 symptoms. We assessed the internal and external validity of the adapted MusiQoL.</p><p><b>RESULTS</b>A total of 81 patients with MS were included in the study. The questionnaire was generally well accepted. In the samples from Malaysia and Singapore, all scales exhibited good internal consistency (Cronbach's alpha >0.70). Correlation to SF-36 was generally good, demonstrating high construct validity (P <0.001) in some aspects of the MusiQoL.</p><p><b>CONCLUSION</b>The Asian adaptation of the English version of the MusiQoL in evaluating HRQoL seems to be a valid, reliable tool with adequate patient acceptability and internal consistency.</p>

Measurement properties of the Chinese language version of the functional assessment of cancer therapy-general in a Singaporean population

<p><b>INTRODUCTION</b>Health-related quality of life is an important aspect of health outcome. The assessment of it must be done by validated instruments. There is no published data on the validity, reliability and sensitiveness to change of the official Chinese translation of the Functional Assessment of Cancer Therapy-General (version 4; FACT-G).</p><p><b>MATERIALS AND METHODS</b>A Chinese questionnaire package comprising the FACT-G and Functional Living Index-Cancer (FLIC, which was translated, modified and validated in Singapore) was filled in by 165 ethnic Chinese patients recruited from the National Cancer Centre, Singapore. Four weeks later, the patients were assessed again by a postal questionnaire survey.</p><p><b>RESULTS</b>The FACT-G and FLIC total scores were strongly correlated (r = 0.85). The Physical, Social/Family, Emotional and Functional Well-being scales of the FACT-G converged to and diverged from FLIC components as conceptually expected. The FACT-G and its 4 scales also demonstrated known-groups validity in differentiating patients with different performance status (each P <0.001). Their internal consistency ranged from 0.81 to 0.93 and test-retest reliability ranged from 0.74 to 0.85. The FACT-G and its Physical, Emotional and Functional Well-being scales showed trends of change in relation to change in performance status. The Social/Family Well-being scale was sensitive to decline but not improvement in performance status.</p><p><b>CONCLUSIONS</b>The Chinese version of the FACT-G can be used to assess overall level and some specific aspects of health-related quality of life. However, researchers should be cautious in using this instrument to specifically investigate the social aspect of quality of life.</p>

Cross-cultural adaptation and validation of Singapore Malay and Tamil versions of the EQ-5D

<p><b>INTRODUCTION</b>The aims of this study were to cross-culturally adapt and evaluate the validity of the Singaporean Malay and Tamil versions of the EQ-5D.</p><p><b>MATERIALS AND METHODS</b>The EQ- 5D was cross-culturally adapted and translated using an iterative process following standard guidelines. Consenting adult Malay- and Tamil-speaking subjects at a primary care facility in Singapore were interviewed using a questionnaire (including the EQ-5D, a single item assessing global health, the SF-8 and sociodemographic questions) in their respective language versions. Known-groups and convergent construct validity of the EQ-5D was investigated by testing 30 a priori hypotheses per language at attribute and overall levels.</p><p><b>RESULTS</b>Complete data were obtained for 94 Malay and 78 Indian patients (median age, 54 years and 51 years, respectively). At the attribute level, all 16 hypotheses were fulfilled with several reaching statistical significance (Malay: 4; Tamil: 5). At the overall level, 42 of 44 hypotheses related to the EQ-5D/ EQ-VAS were fulfilled (Malay: 22; Tamil: 20), with 21 reaching statistical significance (Malay: 9; Tamil: 12).</p><p><b>CONCLUSION</b>In this study among primary care patients, the Singapore Malay and Tamil EQ-5D demonstrated satisfactory known-groups and convergent validity.</p>

Interleukin-18 promoter gene polymorphisms in Chinese patients with systemic lupus erythematosus: association with CC genotype at position -607

<p><b>INTRODUCTION</b>Interleukin-18 (IL-18) is a Th1 cytokine, which is postulated to play a role in systemic lupus erythematosus (SLE). Two single nucleotide polymorphisms (SNPs) in the IL-18 promoter gene region were found to influence the quantitative expression of the IL-18 protein. The aim of this study was to determine whether IL-18 promoter gene polymorphisms are associated with SLE.</p><p><b>MATERIALS AND METHODS</b>One hundred and thirteen Chinese SLE patients and 218 Chinese healthy individuals were recruited. Genomic DNA was extracted from peripheral venous blood. Sequence-specific primer PCR and restriction fragment length polymorphism (RFLP) analysis were used to genotype the DNA samples for SNP-137 and SNP- 607. The following genotypes were obtained: SNP(-607) AA, AC, CC and SNP(-137) GG, GC, CC. Plasma IL-18 concentrations of patients and control subjects were measured by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>the frequency of SNP-607/CC genotype was significantly higher in SLE patients (Pc < 0.05) while genotype SNP-607/AC was significantly decreased in SLE patients compared to the control group (Pc <0.05). Plasma IL-18 concentrations were significantly higher in SLE patients than in control subjects (P <0.05). Both patients and control subjects with CC and AC genotypes have significantly higher IL-18 concentrations than those with AA genotype.</p><p><b>CONCLUSION</b>The IL-18 promoter gene polymorphism SNP-607 C allele is associated with SLE and may result in the enhanced production of IL-18 protein in SLE and normal individuals.</p>

In vivo pro- and anti-inflammatory cytokines in normal and patients with rheumatoid arthritis

<p><b>INTRODUCTION</b>Rheumatoid arthritis (RA) is a chronic, deforming arthritis that can lead to disabilities and poor quality of life. Cytokines are protein mediators of inflammation and are produced as a result of the activation of various cellular reactions. They are the final mediators and/or regulators of the inflammatory process.</p><p><b>MATERIALS AND METHODS</b>The sera from 64 RA patients were assayed for both Th-1 and Th-2 related cytokines and soluble TNF-alpha receptors (IFN-gamma, TGF-beta, TNF-alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, sTNF-R1 and sTNFR2) using ELISA.</p><p><b>RESULTS</b>The pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-18 and TNF- alpha) were significantly elevated in RA patients, while TGF-beta, an immunomodulatory cytokine, was elevated in control individuals. When the RA patients were categorised as active or inactive based on DAS scores, similar cytokines profiles were observed in both RA sub-groups. However, assays of sTNF-R1 and sTNFR-2 were noted to be significantly elevated in inactive RA patients when compared to active patients.</p><p><b>CONCLUSION</b>Our findings indicate that local production of cytokine inhibitors is capable of diminishing disease activity and cytokine activity.</p>

The value of joint aspirations in the diagnosis and management of arthritis in a hospital-based rheumatology service

<p><b>INTRODUCTION</b>Although joint aspiration with synovial fluid analysis is useful in the diagnosis of crystal or septic arthritis, the frequency with which it provides a diagnosis or aids subsequent management of patients with arthritis has not been well quantified. We therefore evaluated the usefulness of joint aspiration in the diagnosis and management of patients with arthritis in a hospital-based rheumatology service.</p><p><b>MATERIALS AND METHODS</b>We reviewed records of all patients with joint aspiration performed by an inpatient rheumatology service in a tertiary referral hospital from November 2003 to December 2004. Data were extracted on the frequency with which joint aspiration provided a diagnosis or aided management.</p><p><b>RESULTS</b>Among 76 patients [mean +/- standard deviation (SD), 60.9 +/- 15.9 years; 41 males, 35 females, Chinese (50), Malay (20), Indian (4) and others (2)] with 86 joint aspirations, a definitive diagnosis was obtained in 44% of procedures which showed gout (n = 28), septic arthritis (n = 8) or pseudogout (n = 2). In another 47% of procedures, joint aspiration aided diagnosis by allowing categorisation of synovial fluid as inflammatory (n = 25), non-inflammatory (n = 16) or blood-stained (n = 2). Joint(s) aspirated were knees (71%), ankles (15%), elbows (8%), shoulders (2%) and wrists, metacarpo-phalangeal and metatarso-phalageal (approximately 1% each).</p><p><b>CONCLUSION</b>Joint aspiration provides a definitive diagnosis or information that aids diagnosis in a significant number of patients in a hospital-based rheumatology service.</p>

Health-related quality of life in patients with systemic lupus erythematosus: an update

With improvements in mortality in systemic lupus erythematosus (SLE), the functional status of these patients, assessed using health-related quality of life (HRQoL) instruments, is increasingly being recognised as an important outcome measure in clinical research. Domains of HRQoL of particular importance to SLE patients include fatigue, ability to work, good health, independence, social and family life, learned helplessness (reflecting the unpredictability of lupus), pain and the home environment. The SF-36 currently appears to be the best available generic instrument for the assessment of HRQoL in SLE, and is likely to be complemented by several newly-developed disease-specific HRQoL instruments. It has been shown that SLE patients have poorer functional status than the general population, and that specific manifestations of SLE (disease activity, previous renal involvement and fibromyalgia) may influence HRQoL. HRQoL in SLE patients has been improved by (1) psycho-educational interventions including telephone counselling, a self-help course, group psychotherapy; (2) therapies including Riquent, belimumab, mycophenolate mofetil, dehydroepiandrosterone, oestrogen therapy and a cholesterol- lowering diet. Additional research is needed to identify strategies which can improve HRQoL in SLE patients.