International cancer seminars: a focus on kidney cancer.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

Geographic differences in the associations between impaired glucose regulation and cardiovascular risk factors among young adults.

AIMS: To assess geographic differences in the association between BMI, blood pressure and lipid levels with impaired glucose regulation among young adults from various geographical regions. METHODS: This was a cross-sectional study including data from 6987 participants aged ≤ 30 years from India, Singapore, Australia, Greenland, Kenya and Tanzania. Impaired glucose regulation was determined by the 75-g oral glucose tolerance test. For each geographical region, BMI, blood pressure and lipids were examined and compared between participants with normal glucose tolerance and those with impaired glucose regulation. Multiple logistic regression models were used to assess the association between risk factors and impaired glucose regulation. RESULTS: Indian and East African people had a higher prevalence of impaired glucose regulation compared with participants from other regions, despite their lower BMI. Compared with the other regions, blood pressure was lower among Indian and Singaporean people but higher in those from Greenland. Greenlanders had the highest, while Indian and East-African people, had the lowest level of HDL cholesterol. BMI was positively associated with impaired glucose regulation in all regions, and there were no statistically significant geographic differences. In the Indian, Singaporean and Australian participants, there was a positive association between blood pressure and impaired glucose regulation. Triglycerides were positively associated with and HDL cholesterol had no association with impaired glucose regulation in all geographical regions. CONCLUSIONS: Higher BMI and triglyceride levels were positively associated with prevalent impaired glucose regulation in all geographical regions. There were geographic differences in the association between impaired glucose regulation and blood pressure and lipids, probably reflecting environmental and genetic factors.

Effectors of alcohol-induced cell killing in Drosophila.

Heavy alcohol consumption provokes an array of degenerative pathologies but the signals that couple alcohol exposure to regulated forms of cell death are poorly understood. Using Drosophila as a model, we genetically establish that the severity of ethanol challenge dictates the type of death that occurs. In contrast to responses seen under acute exposure, cytotoxic responses to milder challenges required gene encoding components of the apoptosome, Dronc and Dark. We conducted a genome-wide RNAi screen to capture targets that specifically mediate ethanol-induced cell death. One effector, Drat, encodes a novel protein that contains an ADH domain but lacks essential residues in the catalytic site. In cultured cells and neurons in vivo, depletion of Drat conferred protection from alcohol-induced apoptosis. Adults mutated for Drat showed both improved survival and enhanced propensities toward sedation after alcohol challenge. Together, these findings highlight novel effectors that support regulated cell death incited by alcohol stress in vitro and in vivo.

Association between the APOA2 promoter polymorphism and body weight in Mediterranean and Asian populations: replication of a gene-saturated fat interaction.

OBJECTIVE: The APOA2 gene has been associated with obesity and insulin resistance (IR) in animal and human studies with controversial results. We have reported an APOA2-saturated fat interaction determining body mass index (BMI) and obesity in American populations. This work aims to extend our findings to European and Asian populations. METHODS: Cross-sectional study in 4602 subjects from two independent populations: a high-cardiovascular risk Mediterranean population (n = 907 men and women; aged 67 ± 6 years) and a multiethnic Asian population (n = 2506 Chinese, n = 605 Malays and n = 494 Asian Indians; aged 39 ± 12 years) participating in a Singapore National Health Survey. Anthropometric, clinical, biochemical, lifestyle and dietary variables were determined. Homeostasis model assessment of insulin resistance was used in Asians. We analyzed gene-diet interactions between the APOA2 -265T>C polymorphism and saturated fat intake (C polymorphism on body-weight-related measures was modulated by saturated fat in Mediterranean and Asian populations.

Singapore's burden of disease and injury 2004.

INTRODUCTION: The Singapore Burden of Disease (SBoD) Study 2004 provides a comprehensive and detailed assessment of the size and distribution of health problems in Singapore. It is the first local study to use disability-adjusted life years (DALYs) to quantify the total disease burden. METHODS: The SBoD study applied the methods developed for the original Global Burden of Disease study to data specific to Singapore to compute the DALYs. DALY is a summary measure of population health that combines time lost due to premature mortality (years of life lost [YLL]) with time spent in ill-health (broadly-termed disability) arising from incident cases of disease or injury (years of life lost due to disability [YLD]). DALYs, stratified by gender and age group, were calculated for more than 130 specific health conditions for the Singapore resident population for the year 2004. RESULTS: In 2004, diabetes mellitus, ischaemic heart disease and stroke were the top three leading causes of premature death and ill-health in Singapore, and together accounted for more than one-quarter (28 percent) of the total disease burden (in DALYs). Morbidity burden (YLD) was responsible for 52 percent of the total DALYs, with diabetes mellitus, anxiety and depression, and Alzheimer's disease and other dementias being the main sources of the total YLDs. Ischaemic heart disease, stroke and lung cancer were the major contributors to the premature mortality burden (YLL). CONCLUSION: This study provides an objective and systematic assessment of the fatal and nonfatal health conditions in Singapore to support priority setting in public health policies and research.

Mortality among tuberculosis patients on treatment in Singapore.

OBJECTIVE: To identify the risk factors associated with mortality among tuberculosis (TB) patients on treatment in Singapore. DESIGN: A retrospective cohort study of 7433 TB patients notified and started on TB treatment from 2000 to 2006 was conducted. Cox regression analysis was used to determine independent risk factors for mortality. RESULTS: Of 7433 patients who started TB treatment between 2000 and 2006, there were 884 deaths (11.9%) from any cause. Older age, male sex, being in a long-term care facility, having comorbidity, absence of cough, more than one site of TB, bacteriologically confirmed laboratory results, resistance to at least isoniazid (INH) and rifampicin (RMP) and absence of cavity were strongly associated with all-cause mortality among TB patients. A total of 203 patients (2.7%) died of TB. Risk factors for death due to TB were older age, male sex, Malay ethnicity, being in a long-term care facility, absence of cough, more than one site of TB, bacteriologically confirmed laboratory results and resistance to at least INH and RMP or to at least INH but not RMP. CONCLUSION: It is important to identify TB patients with risk factors related to mortality so that appropriate and timely interventions can be instituted to prevent deaths among TB patients.

22q11.2 deletion syndrome in Singapore (2000-2003): a case for active ascertainment.

INTRODUCTION: The 22q11 deletion syndrome (22q11DS) is associated with many congenital structural anomalies, notably cardiac defects (conotruncal anomalies) and velopharyngeal insufficiency, as well as neurodevelopmental and psychiatric findings in later life. Recent studies have tried to ascertain the true population incidence of this condition. However, this is difficult due to possible under-ascertainment from incomplete genetic testing in possible cases. The aim of this study is to investigate the local incidence and association of this deletion syndrome with other congenital structural anomalies, with emphasis on cardiac defects. METHODS: Data of 22q11 deletion cases born in 2000-2003 were retrieved from the Singapore National Birth Defects Registry (NBDR) and analysed. Data of congenital cardiac defect cases notified to NBDR in the same period were also retrieved and compared with the deletion cases. RESULTS: There were a total of 17 cases of 22q11DS in the four-year period 2000-2003, giving an overall incidence of 1.02 per 10,000 live-births or one in 9,804 births. 94 percent (16/17 cases) were associated with other structural anomalies, and of these, 68.8 percent (11/16 cases) had single system anomalies. Cardiac anomalies were the most common (100 percent). The deletion contributed to 0.86 percent (one in 116 cases) of all cardiac defects born during the same period. A higher contribution of this deletion was noted for interrupted aortic arch (10 percent), pulmonary atresia (12.7 percent) and truncus arteriosus (11.1 percent). CONCLUSION: In view of the high proportion of this deletion among certain cardiac defects, genetic testing should be made available to investigate the true burden and contribution of this deletion. As more genetic testing is done for this deletion, we are likely to see an increase in incidence, reflecting the true prevalence of this condition.

Gastroschisis and omphalocele in Singapore: a ten-year series from 1993 to 2002.

INTRODUCTION: Two of the most common malformations of the anterior abdominal wall include gastroschisis and omphalocele, both of which are associated with high morbidity and mortality. Studies have shown an increase in both conditions worldwide. These two conditions are considered separate entities because of their differences in epidemiology, physical characteristics and associations with other structural anomalies and chromosomal aberrations. This is the first local study to examine these two conditions. METHODS: Data of anterior abdominal wall defect cases of patients born during the period 1993-2002 were retrieved from the National Birth Defects Registry and analysed. RESULTS: There were a total of 121 cases of anterior abdominal wall defects in the ten-year period from 1993 to 2002, giving an overall incidence of 2.63 per 10,000 livebirths. The individual incidences of gastroschisis (n = 21) and omphalocele (n = 100) were 0.46 and 2.17 per 10,000 livebirths, respectively. 33 percent of women with foetal gastroschisis were younger than 25 years of age, and 31 percent of women with foetal omphalocele were older than 35 years of age. This was statistically significant when compared to the general obstetric population. Incidence of omphalocele was lowest among the Indian population. Total aneuploidy rate was 14.9 percent (18/121 cases), with omphalocele having a higher aneuploidy rate than gastroschisis (17 percent versus 4.8 percent). Omphaloceles are also more likely to be associated with cardiac defects (p-value equals 0.02). CONCLUSION: Our studies are consistent with the worldwide trend of an increasing prevalence of anterior abdominal wall defects. The race-specific differences suggest genetic and environmental factors that warrant further studies.

Educational inequalities associated with health-related behaviours in the adult population of Singapore.

INTRODUCTION: Socioeconomic differences in health-related behaviours have been widely studied in the Western populations, but are seldom considered in Asian populations. We examined the effect of education attainment on health-related behaviours (physical activity, cigarette smoking and alcohol consumption) among non-institutionalised Singaporeans aged 18-69 years. METHODS: We used data from the Singapore National Health Survey 2004. Information on physical activity, cigarette smoking, alcohol consumption and sociodemographic characteristics was collected from 4,084 adults. Age-adjusted prevalence of the three health-related behaviours by educational attainment was calculated by the direct method. Logistic regression models, adjusted for age, gender, ethnic group and employment status, were used to estimate the odds ratio and 95% confidence interval, in order to study the prevalence of health-related behaviours according to educational attainment. RESULTS: The prevalence of physical inactivity, daily smoking and regular alcohol consumption was found to be consistently highest among men and women with the least education. Prevalence of physical inactivity and smoking was inversely related to educational attainment for both genders. However, no clear gradient was found between education and alcohol consumption for men and women. CONCLUSION: Less-educated Singaporeans were more likely to smoke daily, drink alcohol regularly or not to exercise regularly. Health promotion policies or programmes aimed at encouraging healthy lifestyles in the Singapore population should take into account the educational inequalities in these health-related behaviours.

A national study of the epidemiology of pneumococcal disease among hospitalised patients in Singapore: 1995 to 2004.

INTRODUCTION: Infections with Streptococcus pneumoniae cause significant morbidity and mortality. In this study, we describe the epidemiology of pneumococcal disease based on hospitalisation rates for all age groups in Singapore. This is important for evaluating prevention and control strategies of pneumococcal disease. METHODS: We conducted a retrospective study of hospitalisation cases admitted to all public and private hospitals from 1995 to 2004. 4,275 hospitalisation records were extracted, based on the International Classification of Diseases, Ninth Revision (ICD-9) codes for pneumococcal disease. We analysed the demographics, type of pneumococcal disease, length of stay and case fatality of these cases. RESULTS: Our study showed that the mean annual hospitalisation rate for pneumococcal disease was 10.9 per 100,000 population from 1995 to 2004. The mean annual hospitalisation rate was highest in the young and the elderly. CONCLUSION: Baseline information on the epidemiology of pneumococcal disease is important for the formulation and evaluation of a national prevention and control programme.

Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore.

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.

Changes in the levels of major cardiovascular risk factors in the multi-ethnic population in Singapore after 12 years of a national non-communicable disease intervention programme.

INTRODUCTION: The National Healthy Lifestyle Programme, a population-wide non-communicable disease intervention programme, was started in 1992. A National Health Survey is carried out every six years to evaluate the impact of this programme on the cardiovascular risk factor profile of the resident population of Singapore. METHODS: The 2004 National Health Survey (NHS 04) was a population-based survey carried out over a period of four months from September to December 2004. A combination of disproportionate stratified sampling and systematic sampling was used to select a representative sample (n=7,078) for the survey. The reference population comprised 2.4 million multi-racial Singaporeans aged 18-69 years. Anthropometric and blood pressure measurements were carried out on all subjects and blood samples were taken for biochemical analysis. The results were compared with those of a similar survey conducted in 1998. RESULTS: A total of 4,084 Singapore residents took part in the survey, giving a response rate of 57.7 percent. The age-standardised prevalence of hypertension (greater than or equal to 140/90 mmHg) in Singapore residents aged 30-69 years decreased from 28.0 percent in 1998 to 24.0 percent (p-value is less than 0.001) in 2004. The prevalence of high total cholesterol (greater than or equal to 6.2 mmol/L) among those aged 18-69 years fell from 26.0 percent in 1998 to 18.1 percent (p-value is less than 0.001) in 2004. The prevalence of diabetes mellitus in residents aged 18-69 years in 2004 was 7.8 percent, compared to the 1998 level of 9.5 percent (p-value is less than 0.01). The level of obesity (body mass index is greater than or equal to 30 kg/sqm) increased slightly from 6.2 percent in 1998 to 6.8 percent (p-value equals 0.1627). The prevalence of daily smoking decreased from 15.0 percent in 1998 to 12.5 percent in 2004 (p-value is less than 0.001), while that of regular exercise increased from 17.0 percent to 25.0 percent (p-value is less than 0.001). Ethnic differences in the prevalence of diabetes mellitus, hypertension, hypercholesterolaemia, and exercise were observed. CONCLUSION: The NHS 04 results suggest that the National Healthy Lifestyle Programme significantly decreased daily smoking, high blood cholesterol and hypertension, and increased regular exercise over 1998 levels. The results also suggest that the programme stabilised the prevalence of obesity and diabetes mellitus.

Treatment outcome of Singapore residents with pulmonary tuberculosis in the first year after introduction of a computerised treatment surveillance module.

INTRODUCTION: A key intervention of the Singapore Tuberculosis Elimination Programme (STEP) was the introduction in 2001 of a computerised treatment surveillance module (TSM) for the real-time monitoring of the treatment progress of the country's notified tuberculosis (TB) cases until a final outcome. We report the treatment outcome as at December 31, 2002 for the cohort of Singapore residents with new and relapsed pulmonary TB in whom treatment was commenced in 2001. METHODS: Each TB notification will activate the TSM, which requires a return on the patient's treatment progress, treatment delivery mode and the treating physician's management decision at each clinic visit to the STEP Registry until an outcome is reached. RESULTS: There were 1,354 Singapore residents with new or relapsed pulmonary TB who started treatment in 2001. Of these, 620 (45.8 percent) underwent directly-observed therapy (DOT) at their nearest polyclinic. As at December 31, 2002 , 79 percent of patients completed treatment, nine percent died (two percent from TB), nine percent interrupted treatment (they were either lost to follow-up or refused treatment), 1.8 percent were still on treatment, 0.6 percent left the country, and 0.5 percent had permanent cessation of treatment due to drug reactions. Factors associated with treatment completion were Chinese ethnicity (odds-ratio [OR] 1.5, 95 percent confidence interval [Cl] 1.1-2, p-value is 0.02), age younger than 65 years (OR 1.8, 95 percent Cl 1.3-3.0, p-value is 0.003) and the use of DOT (OR 3.1, 95 percent Cl 2.3-4.1, p-value is less than 0.05). CONCLUSION: The findings from the TSM's first year provide a baseline for future programme evaluation.

Public health measures implemented during the SARS outbreak in Singapore, 2003.

The SARS outbreak hit Singapore between March and May 2003. Public health control measures were applied along three fronts; prevention and control within healthcare settings, community and at the borders. Nosocomial spread composed majority of SARS cases in Singapore. To prevent infection within healthcare facilities, cases were centralized in a SARS-designated hospital, a no-visitors rule was applied and movement of patients and healthcare staff were restricted. For triaging purposes, fever clinics were established. A dedicated ambulance service was used to transport possible cases to the SARS-designated hospital. Hospitals were surveyed for fever clusters. The challenge was to identify cases with atypical presentation. Effective and safe discharge criteria were established from the lessons learnt. To prevent community spread, contacts of cases were stringently traced, quarantined in their homes and monitored daily. For prompt identification of a case and to reduce the time between onset of symptoms and isolation, the Infectious Diseases Act was amended. A large wholesale market closure resulted in massive quarantine thereby limiting the spread of infection. A mass education campaign was implemented in order to educate and raise awareness of the public. At all air, sea and land points-of-entry, exit and entry screening took place that resulted in zero importation and exportation of SARS cases after implementation of screening. Coordinated effort of the cross sectional inter-ministerial collaboration and strong coordination by the Task Force and commitment from different professionals made it possible to conquer the disease.

Oyster-associated outbreaks of Norovirus gastroenteritis in Singapore.

Outbreaks of gastroenteritis associated with the consumption of raw imported half-shelled frozen oysters occurred in Singapore between 16 Dec 2003 and 04 Jan 2004. A total of 305 cases were reported with clinical symptoms of diarrhoea (94%), abdominal cramps (72%), vomiting (69%) and fever (54%). The median incubation period was 30.8h and the duration of illness was 2-3 days. The overall relative risk of oyster consumption was 14.1 (95% CI: 8.3-24.0, P<0.001). Stool and oyster samples tested negative for common bacterial pathogens, including Vibrio parahaemolyticus. However, stool samples were positive for the presence of Norovirus group II RNA via RT PCR while oyster samples indicated the presence of Norovirus particles by electron microscopy. The clinical and epidemiological features were suggestive of Norovirus gastroenteritis and were subsequently confirmed by laboratory tests of stools and implicated oysters. Steps have been taken to ensure that food outlets do not thaw frozen oysters and serve them raw.

Birth defects in Singapore: 1994-2000.

INTRODUCTION: To study characteristics of birth defect cases among live births, stillbirths and abortions in Singapore between 1994 and 2000. METHODS: Index cases for the National Birth Defects Registry (NBDR) were obtained from all neonatal nurseries in Singapore, all hospital discharge summaries, cytogenetic and pathology reports from all pathology laboratories in Singapore, and from the compulsory reporting of all termination of pregnancy cases and stillbirths delivered. Further information was obtained from case notes retrieved from the medical record offices, antenatal clinics, cytogenetic laboratories, pathology departments and the Registry of Births and Deaths. The notified cases (live births, stillbirths and abortions) between 1994 and 2000 were extracted from the NBDR and analysed with regard to ethnicity, maternal age, trend over the seven years and types of birth defects using the British Paediatric Association Classification. RESULTS: Between 1994 and 2000, a total of 7,870 cases (6,278 births and 1,592 abortuses) were notified, giving a rate of 23.99 birth defect cases per 1000 live births. There was a decreasing trend in birth defect incidence (19.76 to 16.85 per 1,000 live births) among live births and stillbirths and an increasing trend of abortion (3.25 to 7.57 per 1,000 live births) for birth defects. Malays had a higher rate of congenital defects at birth (24.4/1,000 live births) compared to Chinese (18.4/1,000 births). The 25-29 years age group had the lowest overall rate (22.6/1,000 live births) compared to the 19 years and below group at 31.6/1,000 live births and the 45-49 years group at 126.6/1,000 live births. The five most common groups of anomalies (per 1,000 live births) were those of heart (9.07), musculoskeletal (4.98), chromosomal (4.35), urinary (3.12) and nervous systems (2.90). The five most common aborted anomalies (per 1,000 live births) were those of chromosomal (2.40), nervous (1.23), heart (0.95), musculoskeletal (0.85) and urinary systems (0.36). CONCLUSION: There was an increasing trend of abortion for birth defects, accompanied by a falling trend in the congenital anomalies of live births. Both extremes of maternal age were at higher risk of non-chromosomal birth defects while advanced maternal age was at higher risk of chromosomal defects.

Measurable predictive factors for progression to AIDS among HIV-infected patients in Singapore.

INTRODUCTION: This study identifies measurable factors at the time of diagnosis that predict the progression to Acquired Immunodeficiency Syndrome (AIDS) among Human Immunodeficiency Virus (HIV)-infected patients in Singapore. MATERIALS AND METHODS: We carried out a retrospective study of 790 HIV-infected patients from 16 May 1985 to 31 December 2001. The end-point was the onset of AIDS-defining illness listed in the 1987 and 1991 revised Centers for Disease Control and Prevention criteria, but excluded CD4 cell counts as a criterion. Using the Kaplan-Meier method, AIDS-free survival curves were plotted for age groups at diagnosis, baseline CD4 counts and periods for utilisation of antiretroviral treatment. A Cox regression model was constructed to determine independent predictors of disease progression. RESULTS: Univariate analysis showed that patients of older age at diagnosis had a significantly higher risk of progression compared to younger patients, and patients with higher baseline CD4 cell counts had a lower risk of progression to AIDS. Adjusting for the simultaneous influence of several covariates on the rate of HIV progression to AIDS, multivariate analysis using the Cox model showed a significantly higher risk of progression for older patients at diagnosis, and the progressive lowering of risk with increasing baseline CD4 cell counts. CONCLUSIONS: This study found older age at diagnosis and baseline CD4 cell counts to be measurable predictors for HIV progression to AIDS at time of diagnosis. Identification of these risk factors enables physicians to provide counselling and advice, and to start appropriate treatment early. This could lower the risk of progression and improve survival.

A population-based study on the association between parental occupations and some common birth defects in singapore (1994-1998).

We sought to study the association between some common birth defects and parental occupations. The live births and congenital malformation born between January 1994 and December 1998 were obtained from the Singapore National Registry of Births and Deaths (the National Birth Defect Registry). The prevalence of overall birth defects among Singapore live births during the study period is 13.9 per 1,000 live births. The most frequent single coding defects were "bulbus cordis anomalies and anomalies of cardiac septal closure (BCA)," "congenital anomalies of urinary system (CUS)," "cleft palate and cleft lip (CPL)," and "certain congenital musculoskeletal deformities (CMD)." Using the "Legislators, Senior Officers & Managers" as reference and adjusting for possible confounders, there were significant associations for: (1) paternal "clerical workers" (adjusted RR 2.25) with the BCA; (2) maternal "professionals" with CUS (adjusted risk ratio [RR] 3.58); (3) paternal "production craftsmen and related workers" with both the BCA (adjusted RR 2.04), and the CMD (adjusted RR 2.83); (4) paternal "plant and machine operators and assemblers" with the BCA (adjusted RR 2.49), and the CUS (adjusted RR 5.19), and the CMD (adjusted RR 3.01). Paternal rather than maternal exposure might be more important in the causation of some common birth defects in Singapore.

Ethnic variations in female vulnerability after an acute coronary event.

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.