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Pharmacokinetics of propofol infusion in Asian patients undergoing coronary artery bypass grafting

Lee HS, Khoo YM, Chua BC, Ng AS, Tan SS, Chew SL

Ther Drug Monit, 1995 Aug;17(4):336-41.
PMID: 7482686

The pharmacokinetics of propofol was studied in 11 Asian patients with fentanyl-isoflurane anaesthesia during cardiopulmonary bypass (CPB) and undergoing elective coronary artery bypass grafting (CABG). Instead of the usual increments of morphine and a benzodiazepine, propofol (4 mg/kg/h) was initiated at the start of CPB and ceased at CPB separation. Whole blood propofol concentrations were determined during and postinfusion using high-performance liquid chromatography with fluorescence detection. Data from four patients seemed to fit a two-compartment model, whereas those from seven patients were significantly (F test, p < 0.05) better fitted to a three-compartment model. The pharmacokinetic parameters were as follows: The mean (SD) of the initial distribution phase t1/2 pi, intermediate distribution phase t1/2 alpha, and elimination phase t1/2 beta were 2.22 (1.04) min, 42.9 (16.4) min, and 370 (138) min, respectively. The mean clearance of 1.31 (0.50) L/min was lower than those reported from other studies, whereas the mean blood concentration of 2.2 (1.0) mg/L at the 1-h infusion period was higher. The mean calculated apparent Css was 3.9 (1.5) mg/L. The low clearance is likely to be due to hemodynamic changes during CPB and CABG, thereby affecting drug distribution and blood flow to the liver.
Early experience with the copper 7, copper T220C and multiload 250 intrauterine devices

Goh TH, Tan CH, Lim SM, Chew SC, Hutapea H, Iskandar J

Med J Malaysia, 1978 Jun;32(4):304-7.
PMID: 732628
A case-control study of cervix cancer in Singapore

Cuzick J, De Stavola B, McCance D, Ho TH, Tan G, Cheng H, et al.

Br. J. Cancer, 1989 Aug;60(2):238-43.
PMID: 2548559

Cervix cancer is about twice as common in Asia as in the Western world and its incidence varies among different Asian ethnic groups. A study based in Singapore, the population of which comprises Chinese, Indians and Malaysians, offers the opportunity to evaluate whether the same risk factors are important in this part of the world as in the West. A total of 135 cases and an equal number of controls were interviewed and details concerning reproductive and sexual history, smoking, hygiene, socio-economic status and education were collected. Seventy-three cases had invasive cancer while 62 had micro-invasive disease or CIN III. The most important risk factors were parity and number of sexual partners. Smoking was rare in cases and controls and did not appear to be an important determinant of risk. Of the socio-economic factors, education appeared most predictive and lowered the risk. Age at first intercourse was strongly correlated with education (positively) and parity (negatively), but not with number of sexual partners. Biopsies were available for HPV DNA analysis in 38 cases and 37% were positive, mostly for HPV type 16. All these factors gave similar risks in invasive and preinvasive disease.
Homeostasis model assessment in a population with mixed ethnicity: the 1992 Singapore National Health Survey

Tai ES, Lim SC, Chew SK, Tan BY, Tan CE

Diabetes Res Clin Pract, 2000 Aug;49(2-3):159-68.
PMID: 10963828 DOI: 10.1016/s0168-8227(00)00152-2

We studied insulin resistance and beta-cell function with reference to ethnic group, glucose tolerance and other coronary artery disease risk factors in a cross section of the Singapore population which comprises Chinese, Malays and Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure, anthropometric data, blood lipids, glucose and insulin were assayed in the fasting state. Glucose and serum insulin were measured 2 h after an oral glucose challenge. Insulin resistance and beta-cell function were calculated using homeostasis model assessment. Asian Indians had higher insulin resistance than Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were associated with greater insulin resistance and impaired beta-cell function compared to normal glucose tolerance (NGT). Insulin resistance was positively correlated with blood pressure in women and total cholesterol, LDL cholesterol and triglyceride in both men and women. It was negatively correlated with HDL cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no significant correlations with the cardiovascular risk factors studied. It appears that both impaired beta-cell function and insulin resistance are important for the development of hyperglycemia whereas insulin resistance alone seems more important in the development of coronary artery disease as it correlates with several known coronary artery disease risk factors.
Fulltext Can dietary factors explain differences in serum cholesterol profiles among different ethnic groups (Chinese, Malays and Indians) in Singapore?

Deurenberg-Yap M, Li T, Tan WL, van Staveren WA, Chew SK, Deurenberg P

Asia Pac J Clin Nutr, 2001;10(1):39-45.
PMID: 11708607

In Singapore. there exists differences in risk factors for coronary heart disease among the three main ethnic groups: Chinese, Malays and Indians. This study aimed to investigate if differences in dietary intakes of fat, types of fat, cholesterol, fruits, vegetables and grain foods could explain the differences in serum cholesterol levels between the ethnic groups. A total of 2408 adult subjects (61.0% Chinese, 21.4% Malays and 17.6% Indians) were selected systematically from the subjects who took part in the National Health Survey in 1998. The design of the study was based on a cross-sectional study. A food frequency questionnaire was used to assess intakes of energy, total fat, saturated fat, polyunsaturated fat, monounsaturated fat, cholesterol, fruits, vegetables and cereal-based foods. The Hegsted score was calculated. Serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol were analysed and the ratio of total cholesterol to high density lipoprotein cholesterol was computed. The results showed that on a group level (six sex-ethnic groups), Hegsted score, dietary intakes of fat, satutrated fat, cholesterol, vegetables and grain foods were found to be correlated to serum cholesterol levels. However, selected dietary factors did not explain the differences in serum cholesterol levels between ethnic groups when multivariate regression analysis was performed, with adjustment for age, body mass index, waist-hip ratio, cigarette smoking, occupation, education level and physical activity level. This cross-sectional study shows that while selected dietary factors are correlated to serum cholesterol at a group level, they do not explain the differences in serum cholesterol levels between ethnic groups independently of age, obesity, occupation, educational level and other lifestyle risk factors.
Diabetes mellitus abolishes ethnic differences in cardiovascular risk factors: lessons from a multi-ethnic population

Tan CE, Emmanuel SC, Tan BY, Tai ES, Chew SK

Atherosclerosis, 2001 Mar;155(1):179-86.
PMID: 11223440 DOI: 10.1016/s0021-9150(00)00534-7

AIMS: To compare cardiovascular risk factors in diabetic subjects of different ethnic groups, and between new and known diabetic subjects, in the Singapore National Health Survey '92.

METHODS: Disproportionate stratified sampling followed by systematic sampling were used in 3568 (total) respondents of whom 2743 were non-diabetics, 179 newly diagnosed diabetics and 150 known diabetics. Amongst the diabetics, there were 185 Chinese, 66 Malays and 78 Asian Indians. Diagnosis of diabetes mellitus (DM) was based on the 2 h glucose alone, after a 75 g oral glucose tolerance test. Blood pressure (BP), lipid profile, glucose, insulin and anthropometric indices were obtained from all subjects.

RESULTS: Subjects with diabetes (new and known) exhibited significantly higher triglyceride (TG), lower high density lipoprotein cholesterol (HDL-C) and low density lipoprotein (LDL)/apolipoprotein B (apo B) ratio (LDL size) compared with normoglycaemic subjects. They were more obese (generalised and central) and had higher systolic and diastolic BP. There was no difference in lipid risk factors between the two groups with diabetes although those with new diabetes were more obese whilst those with known diabetes had higher fasting glucose. Amongst subjects with diabetes, there were no significant differences between ethnic groups in TG, HDL-C, LDL/apo B ratio, or waist to hip ratio (WHR). Female Malays with diabetes had higher total cholesterol and were more obese whilst male Asian Indians with diabetes had higher fasting insulin.

CONCLUSION: Asian Indians had lower HDL-C and LDL/apo B ratio than Chinese or Malays amongst normoglycaemic subjects. However, these differences between ethnic groups were not seen in subjects with DM.
Fulltext Birth defects in Singapore: 1994-2000

Tan KH, Tan TY, Tan J, Tan I, Chew SK, Yeo GS

Singapore Med J, 2005 Oct;46(10):545-52.
PMID: 16172775

To study characteristics of birth defect cases among live births, stillbirths and abortions in Singapore between 1994 and 2000.
Seroprevalence of IgG antibodies against Chlamydia pneumoniae in Chinese, Malays and Asian Indians in Singapore

Koh WP, Taylor MB, Hughes K, Chew SK, Fong CW, Phoon MC, et al.

Int J Epidemiol, 2002 Oct;31(5):1001-7.
PMID: 12435775 DOI: 10.1093/ije/31.5.1001

BACKGROUND: Chlamydia pneumoniae, a bacterium that causes respiratory infections, is probably under-diagnosed. There is also interest in its possible role in the aetiology of coronary heart disease. This is the first population-based seroprevalence survey of C. pneumoniae infection in Singapore.

METHODS: A random sample of 1,068 people aged 18-69 years was selected from the participants of the Singapore National Health Survey conducted in 1998. Sera and data on certain clinical measurements and conditions had been collected. IgG antibodies for C. pneumoniae were detected using an indirect microimmunofluorescence test and positivity graded. Seropositivity was defined as IgG titre >/=1:16.

RESULTS: There were no statistically significant differences in the prevalence rates of seropositivity to C. pneumoniae for age group 18-69 years among the three ethnic groups, i.e. Chinese (males 76.7%, females 68.3%), Malays (males 75.4%, females 59.1%), and Asian Indians (males 74.6%, females 59.4%). The seropositivity rate for people aged 18-69 years in Singapore was 75.0% for males and 65.5% for females (difference of 9.5%, P < 0.001). In both genders combined, seropositivity increased from 46.5% in the age group 18-29 to reach a plateau of 78.9% in the age group 40-49, which remained stable to 60-69 years. There was no association of seropositivity with smoking, diabetes mellitus, hypertension or body mass index after adjustment for age and gender.

CONCLUSION: The high prevalence rates in our study population and the higher rate in males compared to females are consistent with studies from other parts of the world. No significant difference in prevalence rates was observed among Chinese, Malays and Indians. The pattern of rising and levelling off of seropositivity with age suggests that C. pneumoniae infection occurs early in life, and in older ages the high level of seropositivity is probably maintained by re-infections or chronic infections. Chlamydia pneumoniae infection was not found to be associated with the cardiovascular risk factors examined.
Fulltext Ethnic variations in female vulnerability after an acute coronary event

Mak KH, Kark JD, Chia KS, Sim LL, Foong BH, Ding ZP, et al.

Heart, 2004 Jun;90(6):621-6.
PMID: 15145860

OBJECTIVE: To determine the ethnic variation of short and long term female vulnerability after an acute coronary event in a population of Chinese, Indians, and Malays.
DESIGN: Population based registry.
PATIENTS: Residents of Singapore between the ages of 20-64 years with coronary events. Case identification and classification procedures were modified from the MONICA (monitoring trends and determinants in cardiovascular disease) project.
MAIN OUTCOME MEASURES: Adjusted 28 day case fatality and long term mortality.
RESULTS: From 1991 to 1999, there were 16 320 acute coronary events, including 3497 women. Age adjusted 28 day case fatality was greater in women (51.5% v 38.6%, p < 0.001), with a larger sex difference evident among younger Malay patients. This inequality between the sexes was observed in both the pre-hospitalisation and post-admission periods. Among hospitalised patients, women were older, were less likely to have suffered from a previous Q wave or anterior wall myocardial infarction, and had lower peak creatine kinase concentrations. Case fatality was higher among women, with adjusted hazard ratios of 1.64 (95% confidence interval (CI) 1.43 to 1.88) and 1.50 (95% CI 1.37 to 1.64) for 28 day and mean four year follow up periods. There were significant interactions of sex and age with ethnic group (p = 0.017). The adjusted hazards for mortality among Chinese, Indian, and Malay women versus men were 1.30, 1.71, and 1.96, respectively. The excess mortality among women diminished with age.
CONCLUSION: In this multiethnic population, both pre-hospitalisation and post-admission case fatality rates were substantially higher among women. The sex discrepancy in long term mortality was greatest among Malays and in the younger age groups.
Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore

Yeo KK, Tai BC, Heng D, Lee JM, Ma S, Hughes K, et al.

Diabetologia, 2006 Dec;49(12):2866-73.
PMID: 17021918 DOI: 10.1007/s00125-006-0469-z

AIMS/HYPOTHESIS: The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups.

METHODS: Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression.

RESULTS: Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77-7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk.

CONCLUSIONS/INTERPRETATION: Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.
Risk factors for Nipah virus infection among abattoir workers in Singapore

Chew MH, Arguin PM, Shay DK, Goh KT, Rollin PE, Shieh WJ, et al.

J Infect Dis, 2000 May;181(5):1760-3.
PMID: 10823780

During 10-19 March 1999, 11 workers in 1 of 2 Singaporean abattoirs developed Nipah-virus associated encephalitis or pneumonia, resulting in 1 fatality. A case-control study was conducted to determine occupational risk factors for infection. Case patients were abattoir A workers who had anti-Nipah IgM antibodies; control subjects were randomly selected abattoir A workers who tested negative for anti-Nipah IgM. All 13 case patients versus 26 (63%) of 41 control subjects reported contact with live pigs (P=.01). Swine importation from Malaysian states concurrently experiencing a Nipah virus outbreak was banned on 3 March 1999; on 19 March 1999, importation of Malaysian pigs was banned, and abattoirs were closed. No unusual illnesses among pigs processed during February-March were reported. Contact with live pigs appeared to be the most important risk factor for human Nipah virus infection. Direct contact with live, potentially infected pigs should be minimized to prevent transmission of this potentially fatal zoonosis to humans.
Intravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres versus acute stroke ready hospitals: Comparison of real-world clinical outcomes

Schee JP, Ang CL, Crystal Teoh SC, Tan HJ, Chew SH, Steven A, et al.

Med J Malaysia, 2023 Sep;78(5):594-601.
PMID: 37775485

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs).
MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05.
RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs.
CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.
The effects of ethnicity on disease patterns in 472 Orientals with systemic lupus erythematosus

Thumboo J, Fong KY, Chng HH, Koh ET, Chia HP, Leong KH, et al.

J Rheumatol, 1998 Jul;25(7):1299-304.
PMID: 9676760

OBJECTIVE: To determine the effects of ethnicity on disease manifestations in Oriental patients with systemic lupus erythematosus (SLE) and to describe the risk of developing renal or central nervous system (CNS) involvement with time.
METHODS: A retrospective study of 472 patients with SLE seen at the only Rheumatology Unit in Singapore. The effect of ethnicity on selected disease manifestations at diagnosis was assessed after adjusting for demographic variables using multiple logistic regression. The probability of developing selected disease manifestations with time was determined using the Kaplan-Meier product limit method.
RESULTS: At diagnosis, Malays had a higher risk of renal or CNS involvement than Chinese (OR 2.26, 95% CI 1.21 to 4.21, and OR 3.07, 95% CI 1.01 to 9.34, respectively), and Indians a lower risk of malar rash and a higher risk of oral ulcers than Chinese (OR 0.30, 95% CI 0.13 to 0.68, and OR 2.90, 95% CI 1.45 to 7.34, respectively). The prevalence of renal or CNS involvement in the entire cohort increased with time, reaching 75.6% (95% CI 66.1% to 85.0%) and 16.7% (95% CI 11.7% to 21.6%), respectively, after 18 years of disease.
CONCLUSION: Ethnicity influenced disease manifestations at diagnosis in this cohort of Oriental patients with SLE. Renal or CNS involvement developed in previously unaffected patients up to 18 years after diagnosis, highlighting the need for continued vigilance in patients with lupus.

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