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Data on specific causes of mortality in South East Asians with type 2 diabetes mellitus (T2DM) remain scarce. We followed 2061 outpatients with T2DM (Chinese 63%, Malays 20%, and Asian Indians 17%) for an average of 5.5 (standard deviation = 2.9) years and identified 365 death events by data linkage with national death registry. Cardiovascular disease was the main cause of mortality (44%), followed by renal disease (17%), infection (17%), cancer (14%), and others causes (8%). Survival analyses revealed that risks for all-cause and cause-specific mortality vary greatly among ethnic groups. Presence of diabetic kidney disease was an independent risk factor for death attributable to cardiovascular disease, renal disease, and infection, while HbA1c level predicted all major causes of deaths even after accounting for multiple other risk factors. These data reinforce the importance of glycemic control and prevention of diabetic kidney disease for mitigation of mortality burden in multiethnic Asians with T2DM.

Background Cognitive training can improve cognition in healthy older adults. Objective The objectives are to evaluate the implementation of community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults. Methods A single-blind randomized controlled trial with baseline and follow-up assessments was conducted at two community centers in Singapore. Healthy community-dwelling adults aged 55 years and older participated in a 10-week CCT program with 2-hour instructor-led group classes twice a week. Participants used a mobile app to play games targeting attention, memory, decision making, visuospatial abilities, and cognitive flexibility. Implementation was assessed at the participant, provider, and community level (eg, reach, implementation, and facilitators and barriers). Effectiveness measures were the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Color Trails Test 2 (CTT-2), Berg Balance Scale, and GAITRite walkway measures (single and dual task gait speed, dual task cost, and single and dual task gait variability index [GVI]). Results A total of 94 healthy community-dwelling adults participated in the CCT program (mean age 68.8 [SD 6.3] years). Implementation measures revealed high reach (125/155, 80.6%) and moderate adherence but poor penetration of sedentary older adults (43/125, 34.4%). The effectiveness data were based on intention-to-treat (ITT) and per-protocol (PP) analysis. In the ITT analysis, single task GVI increased (b=2.32, P=.02, 95% CI [0.30 to 4.35]) and RBANS list recognition subtest deteriorated (b=–0.57, P=.01, 95% CI [–1.00 to –0.14]) in both groups. In the PP analysis, time taken to complete CTT-2 (b=–13.5, P=.01, 95% CI [–23.95 to –3.14]; Cohen d effect size = 0.285) was faster in the intervention group. Single task gait speed was not statistically significantly maintained in the intervention group (b=5.38, P=.06, 95% CI [–0.30 to 11.36]) and declined in the control group (Cohen d effect size = 0.414). PP analyses also showed interaction terms for RBANS list recall subtest (b=–0.36, P=.08, 95% CI [–0.75 to 0.04]) and visuospatial domain (b=0.46, P=.08, 95% CI [–0.05 to 0.96]) that were not statistically significant. Conclusions CCT can be implemented in community settings to improve attention and executive function among healthy older adults. Findings help to identify suitable healthy aging programs that can be implemented on a larger scale within communities. Trial Registration ClinicalTrials.gov NCT04439591; https://clinicaltrials.gov/ct2/show/NCT04439591

Background Pulse wave velocity (PWV), central pulse pressure and augmentation index are arterial stiffness- related hemodynamic parameters but their associations with renal outcome are still controversial. We hereby aim to study, 1) which hemodynamic parameter is independently associated with progressive chronic kidney disease (CKD), 2) the association of 3-year change in PWV with CKD progression and, 3) the additive predictive value of PWV for progressive CKD. Methods Carotid- femoral PWV, central pulse pressure and augmentation index were measured in 1444 participants with type 2 diabetes at baseline and 3 years apart. Progressive CKD was defined as confirmed eGFR decline 40% or greater. Results In the follow-up, 102 participants experienced progressive CKD. All 3 hemodynamic parameters were significantly associated with progressive CKD In univariable analysis. However, only PWV remained statistically significant after adjustment for known clinical risk factors and the other 2 hemodynamic parameters (OR 1.14 [95% CI 1.01–1.29] per m/s increment). One m/s regression (decrement) in PWV in the 3-year follow-up was associated with 26% lower adjusted- risk of progressive CKD (OR 0.74, 95% CI 0.56–0.97). Adding PWV onto traditional risk factor- based model significantly improved classification (net reclassification improvement 0.25, 95% CI 0.05–0.45, P = 0.01) and positive prediction rate (24.5 to 32.3%). Conclusions Of 3 arterial stiffness- related hemodynamic parameters, only PWV is independently associated with progressive CKD. PWV may be a potential intervention target to mitigate risk of CKD progression and also a biomarker to improve risk-stratification of adverse renal outcome in individuals with type 2 diabetes.

The MMSE is used to screen for cognitive impairment and estimate dementia severity. In clinical settings, conventional cut-off scores have been used to distinguish between dementia stages. However, these scores have not been validated for different populations. This study maps scores from the modified version of the MMSE to dementia stages delineated by the Diagnostic and Statistical Manual of Mental Disorders-3rd revised edition (DSM-III-R), the Clinical Dementia Rating (CDR) and Functional Assessment Staging Test (FAST). We used cross-sectional data from a tertiary hospital memory clinic. Subjects were stratified into “primary education and below” (PE) or “secondary education and above” (SE). Receiving operating characteristic (ROC) analyses and Cohen's κ were performed to determine MMSE cut-off scores for dementia stages. Our derived cut-off scores were lower compared to the conventional scores. Scores also differed between subjects of different education levels. MMSE cut-off scores were 19, 15, and 9 for CDR stages 1, 2, and 3 respectively in PE subjects, and 23, 17, and 10 for SE subjects. Cut-off scores were comparable for staging by DSM-III-R Criteria and FAST. There is a need for locally derived stage-specific MMSE cut-off scores for the Asian population adjusted for education.

Background:Although foreign domestic workers (FDWs) play a significant role in caring for frail seniors in Singapore and are vulnerable to caregiving burden, there has been little research conducted hitherto. We explored caregiver burden and its determinants in this study.Methods:FDWs (N = 221, Mage = 32.3, SD = 6.23) recruited from a hospital geriatric unit completed the Zarit Burden Interview (ZBI) administered in English, Bahasa Melayu, or Burmese. Univariate and multivariate regression were employed to investigate factors influencing caregiving burden in FDWs.Results:Majority were Indonesians (60.0%), married (57.5%) with children (62.4%), with secondary-level education (59.7%), and providing care for >1 year (79.9%). Importantly, 25.1% reported physical health problems and 23.1% encountered language difficulties with employers. Univariate analysis revealed three significant factors associated with caregiving burden: nationality (p < 0.001), lack of privacy (p = 0.029), and caring for persons with dementia (PWD) (p = 0.001). On multivariate regression, FDWs who cared for PWD were 5.47 times (p = 0.013) more likely to experience burden, while FDWs who encountered language difficulties were 5.46 times (p = 0.030) more likely to experience burden. Filipinos FDWs were 9.73 times more likely to express burden (p < 0.001) compared to their Indonesian and Burmese counterparts.Conclusion:The study highlights caregiver burden in FDWs and potential ways to alleviate it by empowering FDWs with dementia-specific caregiving skills, providing language training opportunities, and supporting particular FDW ethnic groups with more emotional and practical help.

AIMS Older adults who live alone are vulnerable physically, emotionally and socially. However, there is a trend towards children not living with their parents. We studied the willingness of teenagers today to live with and care for their aged parents tomorrow, and the reasons for their decision. METHODS A convenient sample of 1405 teenage students (M age = 14.9 ± 1.30) in the north region of Singapore completed a purpose-designed questionnaire. Structural equation modeling was used to explore the relationships between teenagers' closeness to grandparents, challenges faced living with grandparents, positive and negative perceptions towards aging, and willingness to stay with aged parents in the future, stratified by sex. Thematic analysis was used to understand the reasons for their choice. RESULTS The majority (85.6%) chose to live with their parents, and the significant predictors were "closeness to grandparents" (P = 0.034) and "positive perceptions towards aging" (P

OBJECTIVE Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes. RESEARCH DESIGN AND METHODS We employed a transethnic approach with a cohort of Asian origin (Singapore) (N = 2,061) and a cohort of European origin (France) (N = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality. RESULTS A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5–12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3–10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02–2.11], 2.28 [1.62–3.21], and 4.64 [3.39–6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15–2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09–3.42] and adjusted HR 1.49 [1.14–1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor. CONCLUSIONS Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.

Background Haptoglobin (Hp) is an abundant plasma protein with anti-oxidant properties. Hp polymorphism is associated with cardio-metabolic dysfunction but the allele conferring risk of developing acute myocardial infarction (AMI) in type 2 diabetes (T2D) patients is unclear. This study aimed to investigate the association of Hp phenotype (Hp 1-1, 2-1 and 2-2) with incident AMI in Chinese T2D patients. Methods This prospective study included Chinese T2D participants from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) and Diabetic Nephropathy (DN) cohorts. Information on incidence of non-fatal AMI was collected by data linkage with the Singapore Myocardial Infarction Registry. Hp phenotype was determined using enzyme-linked immunosorbent assay. Cox proportional hazards regression models were used to evaluate the association of Hp phenotype with incident AMI, adjusted for traditional risk factors separately in two cohorts, then meta-analysed. Results In total, 2324 Chinese participants (SMART2D; N = 1034, mean age [SD] of 59 [11]) and (DN: N = 1290, mean age [SD] of 58 [12]) were included in this study. There were total of 30 (56 events per 10,000 patient-years) and 99 (128 events per 10,000 patient-years) AMI events in SMART2D and DN cohorts respectively. In meta-analysis, presence of Hp 1 allele conferred 43% (hazard ratio [HR] = 1.43 [95% CI 1.10–1.87], P = 0.008, Phet = 0.413) increased risk of incident AMI, independent of age, sex, smoking, body mass index, HbA1c, diabetes duration, lipids, hypertension, renal function and usage of insulin and RAS antagonist. In adjusted model, compared to Hp 2-2 groups, individuals with Hp 1-1 (HR = 2.18 [95% CI 1.19–3.76], P = 0.010, Phet = 0.193) and Hp 2-1 (HR = 1.45 [95% CI 0.98–2.14], P = 0.065, Phet = 0.576) were at a higher risk of incident AMI. Moreover, compared to Hp 2-2 groups, non-Hp 2-2 groups (Hp 1-1 and Hp 2-1) were at 55% increased risk of incident AMI (HR = 1.55 [95% CI 1.07–2.24], P = 0.021, Phet = 0.940). Conclusions Hp 1-1 phenotype was associated with increased risk of incident AMI, independent of traditional risk factors, in Chinese patients with T2D. Hp phenotyping may allow for identification of T2D individuals at higher risk for onset of AMI. However, further studies are needed to understand the underlying mechanism between Hp alleles and risk for AMI. Electronic supplementary material The online version of this article (10.1186/s12933-019-0867-4) contains supplementary material, which is available to authorized users.

Background: Frailty and cognitive impairment are closely related in sharing several possible underlying pathophysiological mechanisms. There is a lack of clarity in published literature on whether cerebral infarcts or Alzheimer’s pathology accounts for the frailty phenotype in patients with mild Alzheimer’s disease (AD). Therefore, we investigated the structural neuroimaging predictors of frailty in mild AD patients to better elucidate the underlying pathophysiology. Methods: We recruited subjects who satisfied inclusion criteria from a clinical database of patients attending a tertiary hospital memory clinic between 2012 and 2017. AD patients with Clinical Dementia Rating (CDR) 0.5 and 1.0 who had undergone MRI brain were included. Frailty Index (FI-CGA) was utilised for frailty assessment, and visual MRI rating scales were used by blinded raters to quantify the brain lesions. Results: A total of 342 mild AD patients with a mean age of 75.79 ± 7.18 were studied. A multivariate linear regression model adjusted for demographics, cognitive scores and functional status revealed only deep white matter hyperintensities (DWMH) but none other brain lesions to be significantly and positively correlated with FI-CGA (β = 0.178, SE = 0.047, p ≤ 0.001) This model which comprised age, CDR sum of boxes, basic activities of living and DWMH, accounted for 47.5% of the FI-CGA variance in the study population. Conclusions: The study has revealed DWMH to be independently associated with frailty in mild AD patients. With the current understanding of the aetiology of DWMH, control of vascular risk factors is vital to preventing and ameliorating frailty in patients with mild AD.

Aim To study whether plasma fibroblast growth factor 21 independently predicts the risk of end-stage renal disease in Asian people with Type 2 diabetes. Methods In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end-stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end-stage renal disease was studied using survival analyses. Results Participants were aged 60 ± 10 years, with an average diabetes duration of 12 years. Their estimated GFR was 73 ± 28 ml/min/1.73 m2 and 62% had albuminuria at baseline. A total of 179 incident end-stage renal disease cases were identified. Plasma fibroblast growth factor 21 interacted with sex in its association with end-stage renal disease (Pinteraction = 0.003). A 1-sd increment in fibroblast growth factor 21 (natural log-transformed) was associated with a 1.32-fold (95% CI 1.05-1.66, P = 0.02) increased hazard for end-stage renal disease in women, after adjustment for traditional risk factors including estimated GFR and albuminuria. Taking death as a competing risk did not materially change the outcome [sub-distribution hazard ratio 1.35 (95% CI 1.11-1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end-stage renal disease risk in men after adjustment for baseline estimated GFR and albuminuria [hazard ratio 1.07 (95% CI 0.89-1.28, P = 0.49)]. Conclusions Plasma fibroblast growth factor 21 level independently predicted risk of progression to end-stage renal disease in women with Type 2 diabetes. The pathophysiological relationships among FGF21, sex and renal progression warrant further study.

Introduction The 2015 sepsis definitions suggest using the quick SOFA score for risk stratification of sepsis patients among other changes in sepsis definition. Our aim was to validate the q sofa score for diagnosing sepsis and comparing it to traditional scores of pre ICU admission sepsis outcome prediction such as EWS and SIRS in our setting in order to predict mortality and length of stay. Methods This was a retrospective cohort study. We retrospectively calculated the q sofa, SIRS and EWS scores of all ICU patients admitted with the diagnosis of sepsis at our center in 2015. This was analysed using STATA 12. Logistic regression and ROC curves were used for analysis in addition to descriptive analysis. Results 58 patients were included in the study. Based on our one year results we have shown that although q SOFA is more sensitive in predicting LOS in ICU of sepsis patients, the EWS score is more sensitive and specific in predicting mortality in the ICU of such patients when compared to q SOFA and SIRS scores. Conclusion In conclusion, we find that in our setting, EWS is better than SIRS and q SOFA for predicting mortality and perhaps length of stay as well. The q Sofa score remains validated for diagnosis of sepsis.

Background: Data arising from the Edinburgh Postnatal Depression Scale (EPDS), used as screening tool for perinatal depression, have been analysed as unidimensional in some studies and multidimensional in others. This study evaluates the dimensionality and item properties of the EPDS. Methods: 920 women recruited in antenatal clinics from two government tertiary hospitals completed the English EPDS between 26 and 28 weeks of pregnancy. Classical test theory and factor analyses were used to evaluate dimensionality. Item response theory was used to investigate item functioning. Results: The EPDS was essentially unidimensional. It has a common factor, ‘antenatal dysphoria’ and 3 subdomains ‘depressive’ (items 7–10), ‘anxiety’ (items 3–5) and ‘anhedonic symptoms’ (items 1, 2). Item 8 (I have felt sad or miserable) (discrimination = 3.13. SE = 0.24), item 9 (I have been so unhappy that I have been crying) (discrimination = 2.39. SE = 0.17) and item 10 (The thought of harming myself has occurred to me) (discrim...

All particle therapy systems are modular systems built with smaller subsystems. The various modules are (1) the beam production system, (2) the beam transport system, and (3) the beam delivery system as shown in Fig. 2.1.

Background Genomic imprinting is a process causing genes to be expressed according to parental origin. Imprinting acts to coordinate fetal and prenatal growth, as well as control postnatal adaptations. Studies on human imprinting are confounded by tissue availability, sampling variability and limitations posed by tissue-specific expression and cellular heterogeneity within tissues. The human umbilical cord is an easily available, embryonic-derived fetal tissue with the potential to overcome many of these limitations. Methods In a sensitive, gene-specific quantitative expression analysis, we show for the first time robust imprinted gene expression combined with methylation analysis in cords isolated from Asian Chinese full-term births. Results Linear regression analyses revealed an inverse correlation between expression of pleckstrin homology-like domain, family A, member 2 ( PHLDA2 ) with birth weight (BW). Furthermore, we observed significant down-regulation of the paternally expressed gene 10 ( PEG10 ) in low BW babies compared to optimum BW babies. This change in PEG10 gene expression was accompanied by concomitant methylation alterations at the PEG10 promoter. Conclusions These data are the first to demonstrate relative expression of an imprinted gene associated with epigenetic changes in non-syndromic fetal growth restriction in babies. They show that perturbed expression in compromised fetal growth may be associated with in utero modulation of the epigenetic state at the imprinting control regions and implicate specific imprinted genes as new biomarkers of fetal growth.

Rinkoo Dalan1, Michelle Jong1, Siew-Pang Chan4,5, Robert Hawkins2, Robin Choo6, Brenda Lim1, May L Tan3, Melvin KS Leow1,61Department of Endocrinology, 2Department of Laboratory Medicine, 3Health Enrichment Centre, Tan Tock Seng Hospital, Singapore; 4School of Business, SIM University, Singapore; 5Faculty of Health Sciences, La Trobe University, Australia; 6Singapore Institute for Clinical Sciences, Brenner Centre for Molecular Medicine, SingaporeObjectives: To determine whether high-sensitivity C-reactive protein (hs-CRP) concentrations differ between Chinese, Malays, and Indians with and without type 2 diabetes mellitus and to look for an association with demographic, metabolic and therapeutic variables.Methods: Phase 1: We retrieved records of 50 Chinese, 51 Malay, and 67 Indian individuals who had routine health screening blood tests. Phase 2: We recruited 111 Chinese, 68 Malays, and 67 Indians with type 2 diabetes mellitus and measured their hs-CRP in addition to standard laboratory tests.Results: Phase 1: The median hs-CRP was 0.6 mg/L (0.2–6.2) in Chinese, 1.2 mg/L (0.2–7.9) in Malays, and 1.9 mg/L (0.2–10.0) in Indians. The Indians had higher hs-CRP compared to Chinese (P < 0.05) when adjusted for age, sex, body mass index (BMI), lipids, blood pressure, and smoking, and a significant correlation was seen between female sex, smoking status, fasting glucose and triglyceride concentration, and hs-CRP in all three ethnicities. Phase 2: The median hs-CRP was 1.2 mg/L (0.2–9.9) in Chinese, 2.2 mg/L (0.2–9.0) in Malays, and 2.3 mg/L (0.2–9.8) in Indians. Indians had higher hs-CRP when compared to Chinese (P < 0.05) and a significant correlation was seen between BMI, female gender, diabetes, and the use of metformin and hs-CRP in all three ethnicities (P < 0.05) when adjusted for the above variables and use of aspirin, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACE-I/ARB), statin, metformin, rosiglitazone, sulfonylurea, glinides, acarbose, and insulin.Conclusion: hs-CRP concentrations are significantly higher in Indians compared to the Chinese (in both the diabetic and nondiabetic individuals) after adjustment for the various demographic, metabolic, and therapeutic variables.Keywords: C-reactive protein, ethnicity, diabetes mellitus, cardiovascular disease

Background Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. Methods Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. Results A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients’ day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. Conclusion Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient’s progression to severe disease.

Background: HRQoL is an important outcome to guide and promote healthcare. Clinical and socioeconomic factors may influence HRQoL according to ethnicity.\ud \ud Methodology: A multiethnic cross-sectional national cohort (N = 7198) of the Singapore general population consisting of Chinese (N = 4873), Malay (N = 1167) and Indian (N = 1158) adults were evaluated using measures of HRQoL (SF-36 version 2), family functioning, health behaviours and clinical/laboratory assessments. Multiple regression analyses were performed to identify determinants of physical and mental HRQoL in the overall population and their potential differential effects by ethnicity. No a priori hypotheses were formulated so all interaction effects were explored.\ud \ud Principal Findings: HRQoL levels differed between ethnic groups. Chinese respondents had higher physical HRQoL (PCS) than Indian and Malay participants (p

Purpose To evaluate the possible associations between dietary factors and myopia. Design Cross-sectional study. Participants Eight hundred fifty-one Chinese schoolchildren from the Singapore Cohort Study of Risk Factors for Myopia. Methods Diet was assessed using a semiquantitative food-frequency questionnaire. Spherical equivalent (SE) refraction was assessed with an autorefractometer, and axial length (AL) by contact ultrasound A-scan biometry. Main Outcome Measures Myopia was defined as SE≤–0.5 diopters (D). Spherical equivalent and AL were analyzed by quartile groups. Results The mean age (±standard deviation) was 12.81±0.83 years, approximately half were male (422 children [49.6%]), and 653 (73.8%) children had myopia. In multivariate models, AL was longest in the highest quartile group of total cholesterol intake compared with the lowest (adjusted mean [95% confidence interval], 24.66 [24.62–24.71] mm vs. 24.32 [24.27–24.36] mm; P = 0.026, for trend) and was longest in the highest quartile group of saturated fat intake compared with the lowest (24.65 [24.60–24.70] vs. 24.36 [24.32–24.41] mm; P = 0.039, for trend). None of the nutrients was associated with SE or a diagnosis of myopia. Conclusions Higher saturated fat and cholesterol intake are associated with longer AL in otherwise healthy Singapore Chinese schoolchildren. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.