The therapeutic landscape for COVID-19 and post-COVID-19 medications from genetic profiling of the Vietnamese population and a predictive model of drug-drug interaction for comorbid COVID-19 patients.

Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.

Depression in Final-Year Medical Students in Ho Chi Minh City, Vietnam: The Role of Career-Choice Motivation.

OBJECTIVES: Depression in medical students is concerning, potentially fueled by many stressors including career choice-relating stress. Choosing Medicine is a life-long commitment, and low intrinsic motivation or excessive dependence on family can complicate this decision and adding stress throughout their training. This stress intensifies in the final year, as students lacking personal drive struggle to see themselves continuing the career. Given limited studies on this crucial topic in Asia and Vietnam, we explored direct linkage between career choice motivation and depression in final-year medical students. METHODS: A cross-sectional study was conducted with 569 final-year students between June and July 2020. The Vietnamese Patient Health Questionnaire 9 (PHQ-9) and 16-item CCM questionnaire were used as survey tools. Univariate analysis was used for descriptive statistics (absolute and relative frequency, mean (M), standard deviation (SD). Multinomial logistic regression models were used to explore the relationship between variables using STATA 5.1. RESULTS: The depression among participants was about 24.6% (PHQ-9 cut-off ≥ 12). No difference in gender was found regarding depression. The most acknowledged motivator is securing employment (M = 4.14, SD = 1.02) and the least is parental wishes (M = 3.17, SD = 1.32). Familial influence on career choice significantly increased odds of having "moderately-severe depression" (OR = 1.17, 95% CI 1.04-1.32) and "severe depression" (OR = 1.36, 95% CI 1.10-1.68), whereas, career-choice motivators including satisfaction (OR = .76, 95% CI .60-.97), self-competence (OR = .80, 95% CI .66-.97) and career success (OR = .84, 95% CI .71-.99) were found to be protective factors for depression. CONCLUSIONS: Roughly a quarter of final-year medical students encountered depression. Occupational security ranked as the primary motivator, with parental wish being the least. Familial influence heightened depression risk, while career prospects, satisfaction and self-efficacy acted as protective factors. Medical career paths should align with intrinsic motivations and personal interests for better mental health outcomes.

A study of genetic variants associated with skin traits in the Vietnamese population.

BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.

Endovascular treatment for acute ischemic stroke beyond the 24-h time window: Selection by target mismatch profile.

INTRODUCTION: Endovascular treatment for acute ischemic stroke patients with large vessel occlusion (LVO) has been established as a promising clinical intervention within a late time window of 6-24 h after symptom onset. Patients with slow progression, however, may still benefit from endovascular treatment beyond the 24-h time window (very late window). AIM: The aim of this study is to report insight into the potential clinical benefits of endovascular treatment for acute ischemic stroke beyond 24 h from symptom onset. METHODS: A retrospective analysis was performed on consecutive patients undergoing endovascular treatment for acute anterior circulation LVO ischemic stroke beyond 24 h. Participants were recruited between July 2019 and November 2020. Patients were selected based on the DAWN/DEFUSE 3 criteria (Perfusion-RAPID, iSchemaView) and patients receiving treatment beyond 24 h were compared to a group of patients receiving endovascular treatment between 6 and 24 h after symptom onset. The primary outcome was the proportion of patients with functional independence at 90 days (modified Rankin Scale score of 0-2). The secondary outcomes were shift modified Rankin Scale (mRS) analysis and successful reperfusion was defined by thrombolysis in cerebral infarction (TICI) 2b-3 on the final procedure. Safety outcomes were symptomatic intracranial hemorrhage and death at the 90-day follow-up. Propensity score (PS)-matched analyses were employed to rectify the imbalanced baseline characteristics between the two groups. RESULTS: A total of 166 patients were recruited with a median age of 63.0 (56.0-69.0) and 28.9% of all patients were females. Patients in the beyond 24-h group had a longer onset-to-groin time (median = 27.2 vs 14.3 h, p < 0.001) than those in the 6- to 24-h group. There were no statistically significant differences between the two groups in National Institutes of Health Stroke Scale (NIHSS) (median = 12.0 vs 15.0, p = 0.37), perfusion imaging characteristics (core: median = 11.0 vs 9.0 mL, p = 0.86; mismatch volume: median = 106.0 vs 96.0, p = 0.44; mismatch ratio = 6.46 vs 7.24, p = 0.91), and perfusion-to-groin time (median = 72.5 vs 76.0 min, p = 0.77). No significant differences were noted among patients between the two groups in the primary endpoint functional independence analysis (50.0% vs 46.6%, p = 0.77) and in the safety endpoint analysis: mortality (15.0% vs 11.0%, p = 0.71) or symptomatic hemorrhage (0% vs 3.42%, p > 0.999). In PS-matched analyses, there were no significant differences among patients between the two groups in functional independence (50.0% vs 54.8%, p = 0.74), mortality (16.7% vs 9.68%, p = 0.50), or symptomatic hemorrhage (0% vs 6.45%, p = 0.53). CONCLUSION: Endovascular treatment can be performed safely and effectively in LVO patients beyond 24 h from symptom onset when selected by target mismatch profile. The clinical outcome of these patients was comparable to those treated in the 6- to 24-h window. Larger studies are needed to confirm these findings.

Overlapping Stevens-Johnson Syndrome and DRESS Syndrome Caused by Phenobarbital: A Vietnamese Case Report.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and Stevens-Johnson Syndrome (SJS) are severe cutaneous adverse reactions to drugs. Those reactions which are rare in children can be especially severe and challenging to diagnose and manage. Herein we present a 59-month-old male who presented with a rash, fever, and multiple organ dysfunction initiation of Phenobarbital for epilepsy. Diagnosis of ovelaping SJS and DRESS syndrome had been made based on clinical manifestations accompanied with skin biopsy according to RegisSCAR diagnostic criteria. A therapy with intravenous immune globulin (IVIG), corticosteroids and supportive care was given successfully for the patient. This case underscored the significance of promptly and effectively recognizing and managing these intricate reactions.

A comprehensive evaluation of polygenic score and genotype imputation performances of human SNP arrays in diverse populations.

Regardless of the overwhelming use of next-generation sequencing technologies, microarray-based genotyping combined with the imputation of untyped variants remains a cost-effective means to interrogate genetic variations across the human genome. This technology is widely used in genome-wide association studies (GWAS) at bio-bank scales, and more recently, in polygenic score (PGS) analysis to predict and stratify disease risk. Over the last decade, human genotyping arrays have undergone a tremendous growth in both number and content making a comprehensive evaluation of their performances became more important. Here, we performed a comprehensive performance assessment for 23 available human genotyping arrays in 6 ancestry groups using diverse public and in-house datasets. The analyses focus on performance estimation of derived imputation (in terms of accuracy and coverage) and PGS (in terms of concordance to PGS estimated from whole-genome sequencing data) in three different traits and diseases. We found that the arrays with a higher number of SNPs are not necessarily the ones with higher imputation performance, but the arrays that are well-optimized for the targeted population could provide very good imputation performance. In addition, PGS estimated by imputed SNP array data is highly correlated to PGS estimated by whole-genome sequencing data in most cases. When optimal arrays are used, the correlations of PGS between two types of data are higher than 0.97, but interestingly, arrays with high density can result in lower PGS performance. Our results suggest the importance of properly selecting a suitable genotyping array for PGS applications. Finally, we developed a web tool that provides interactive analyses of tag SNP contents and imputation performance based on population and genomic regions of interest. This study would act as a practical guide for researchers to design their genotyping arrays-based studies. The tool is available at: https://genome.vinbigdata.org/tools/saa/ .

Sex differences in total cholesterol of Vietnamese adults.

BACKGROUND: The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors. METHODS: Participants (n = 14706, 50.9% females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods. RESULTS: Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight. CONCLUSION: There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.

Clinical evaluation of RB1 genetic testing reveals novel mutations in Vietnamese patients with retinoblastoma.

Clinical evaluation of the genetic testing strategy is essential for ensuring the correct determination of mutation carriers. The current study retrospectively analyzed genetic and clinicopathological data from 62 Vietnamese patients with retinoblastoma (RB) referred to the Vinmec Hi-Tech Center for RB transcriptional corepressor 1 (RB1) genetic testing between 2017 and 2019. The present study aimed to evaluate the sensitivity of the Next Generation Sequencing (NGS) method to identify novel RB1 mutations, and to consider using age at diagnosis as a risk factor. Genomic DNA was analyzed with custom panel based targeted NGS. NGS was performed on the Beijing Genomics Institute (BGI) sequencing platform, and pathogenic or likely pathogenic variants were confirmed by Sanger sequencing, quantitative PCR (qPCR) or Multiplex Ligation-dependent Probe Amplification assay (MLPA). Constitutional RB1 variants were identified in 100% (25/25) of the bilateral cases, while several common previously reported RB1 mutations were also recorded. In addition, in Vietnamese patients with RB, nine novel RB1 mutations were identified. Children aged between 0-36 months were more likely to be RB1 carriers compared with those aged >36 months. The current findings indicated that the NGS method implemented in the Vinmec Hi-Tech Center was highly accurate, and age at diagnosis may be used to assess the risk of hereditary RB. Furthermore, the newly identified RB1 mutations may provide additional data to improve the current understanding of the mechanisms underlying RB1 inactivation and the development of rapid assays for detecting RB1 mutations. Overall, the present study suggested that NGS may be applied for detecting germline RB1 mutations in routine clinical practice.

NEDD4-induced degradative ubiquitination of phosphatidylinositol 4-phosphate 5-kinase α and its implication in breast cancer cell proliferation.

Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members generate phosphatidylinositol 4,5-bisphosphate (PIP2), a critical lipid regulator of diverse physiological processes. The PIP5K-dependent PIP2 generation can also act upstream of the oncogenic phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Many studies have demonstrated various mechanisms of spatiotemporal regulation of PIP5K catalytic activity. However, there are few studies on regulation of PIP5K protein stability. Here, we examined potential regulation of PIP5Kα, a PIP5K isoform, via ubiquitin-proteasome system, and its implication for breast cancer. Our results showed that the ubiquitin ligase NEDD4 (neural precursor cell expressed, developmentally down-regulated gene 4) mediated ubiquitination and proteasomal degradation of PIP5Kα, consequently reducing plasma membrane PIP2 level. NEDD4 interacted with the C-terminal region and ubiquitinated the N-terminal lysine 88 in PIP5Kα. In addition, PIP5Kα gene disruption inhibited epidermal growth factor (EGF)-induced Akt activation and caused significant proliferation defect in breast cancer cells. Notably, PIP5Kα K88R mutant that was resistant to NEDD4-mediated ubiquitination and degradation showed more potentiating effects on Akt activation by EGF and cell proliferation than wild-type PIP5Kα. Collectively, these results suggest that PIP5Kα is a novel degradative substrate of NEDD4 and that the PIP5Kα-dependent PIP2 pool contributing to breast cancer cell proliferation through PI3K/Akt activation is negatively controlled by NEDD4.

The importance of waist circumference and body mass index in cross-sectional relationships with risk of cardiovascular disease in Vietnam.

BACKGROUND: Waist circumference (WC) is an indicator of intra-abdominal adipose tissue, high levels of which confer an increased risk of cardiometabolic disease. Population data on WC should be more informative than data on body mass index (BMI), which is a general indicator of body size. This study aimed to evaluate the importance of WC relative to BMI in cross-sectional relationships with blood pressure (BP), glucose, and total cholesterol (TC) in the adult population of Vietnam. METHODS: The data were collected in a population-based survey conducted during 2009-10 using the "WHO STEPwise approach to surveillance of risk factors for non-communicable disease" (STEPS) methodology. The survey participants (n = 14 706 aged 25 to 64 years) were selected by multi-stage stratified cluster sampling from eight provinces representative of the eight geographical regions of Vietnam. All measurements were performed in accordance with the STEPS protocols. All analyses were performed using complex survey methods. RESULTS: The measurements of WC and BMI were highly correlated (men r = 0.80, women r = 0.77). For men, the strongest and predominant associations with BP, glucose, and TC were for WC or an index based on WC. For women, this was true for glucose but BMI was more important for BP and TC. WC or an index based on WC provided better discrimination than BMI of hypertension and elevated glucose, and of raised TC for men. Information on four new anthropometric indices did not improve model fit or subject discrimination. CONCLUSION: For BP/hypertension, glucose/elevated glucose, and TC/raised TC, WC was more informative than BMI for Vietnamese men, but both WC and BMI were important for Vietnamese women. Both WC and BMI need to be assessed for estimation of CVD risk in Vietnam.

National survey of risk factors for non-communicable disease in Vietnam: prevalence estimates and an assessment of their validity.

BACKGROUND: To estimate the prevalence of non-communicable disease (NCD) risk factors at a provincial level in Vietnam, and to assess whether the summary estimates allow reliable inferences to be drawn regarding regional differences in risk factors and associations between them. METHODS: Participants (n = 14706, 53.5 % females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Data were analysed using complex survey methods. RESULTS: Differences by sex in mean years of schooling (males 8.26 ± 0.20, females 7.00 ± 0.18), proportions of current smokers (males 57.70 %, females 1.73 %), and binge-drinkers (males 25.11 %, females 0.63 %), and regional differences in diet, reflected the geographical and socio-cultural characteristics of the country. Provinces with a higher proportion of urban population had greater mean levels of BMI (r = 0.82), and lesser proportions of active people (r = -0.89). The associations between the summary estimates were generally plausible (e.g. physical activity and BMI, r = -0.80) but overstated, and with some anomalous findings due to characterisation of smoking and hypertension by STEPS protocols. CONCLUSIONS: This report provides an extensive description of the sex-specific and regional distribution of NCD risk factors in Vietnam and an account of some health-related consequences of industrialisation in its early stages. The STEPS protocols can be utilized to provide aggregate data for valid between-population comparisons, but with important caveats identified.

Fruit and vegetable consumption in Vietnam, and the use of a 'standard serving' size to measure intake.

The aims of the present study were to provide nationally representative data on fruit and vegetable consumption in Vietnam, and to assess the accuracy of the reported numbers of 'standard servings' consumed. Data analysed were from a multi-stage stratified cluster survey of 14 706 participants (46·5 % males, response proportion 64·1 %) aged 25-64 years in Vietnam. Measurements were made in accordance with the WHO STEPwise approach to surveillance of non-communicable diseases (STEPS) protocols. Approximately 80 % of Vietnamese people reported having less than five servings of fruit and vegetables daily in a typical week. Fruit and vegetable intake reported in 'standard serving' sizes was positively correlated with levels of education completed and household income (P<0·001 for trend). The correlations between summary values for each province reflect some known demographic, geographical and climatic characteristics of the country. For example, provinces at higher latitude had higher mean servings of vegetables (r 0·90), and provinces with higher proportions of urban population had higher mean servings of fruit (r 0·40). In conclusion, about eight in ten Vietnamese people aged 25-64 years did not meet WHO recommendations for daily consumption of at least five servings of fruit and vegetables. On the basis of the consistency of the data collected with other estimates and with physical and demographic characteristics of the country, the WHO STEPS instrument has construct validity for measuring fruit and vegetable intake, but with two issues identified. The issues were seasonal variation in reporting and a limitation on the usefulness of the information for associative analyses.

Alcohol Consumption in Vietnam, and the Use of 'Standard Drinks' to Measure Alcohol Intake.

AIMS: To provide nationally representative data on alcohol consumption in Vietnam and to assess whether reported numbers of 'standard drinks' consumed have evidence of validity (particularly in rural areas where home-made alcohol is consumed from cups of varying size). METHODS: A nationally representative population-based survey of 14,706 participants (46.5% males, response proportion 64.1%) aged 25-64 years in Vietnam. Measurements were made in accordance with WHO STEPS protocols. Data were analysed using complex survey methods. RESULTS: Among men, 80% reported drinking alcohol during the last year, and 40% were hazardous/harmful drinkers. Approximately 60% of men and <5% of women had consumed alcohol during the last week, with one-in-four of the men reporting having consumed at least five standard drinks on at least one occasion. Numbers of standard drinks reported by men were associated with blood pressure/hypertension, particularly in rural areas (P < 0.001 for trend). Most of the calibration and discrimination possible from self-reported information on alcohol consumption was provided by binary responses to questions on whether or not alcohol had been consumed during the reference period. CONCLUSION: Alcohol use and harmful consumption were common among Vietnamese men but less pronounced than in Western nations. Self-reports of quantity of alcohol consumed in terms of standard drinks had predictive validity for blood pressure and hypertension even in rural areas. However, using detailed measures of consumption resulted in only minor improvements in prediction compared to simple measures.

Physical Activity in Vietnam: Estimates and Measurement Issues.

INTRODUCTION: Our aims were to provide the first national estimates of physical activity (PA) for Vietnam, and to investigate issues affecting their accuracy. METHODS: Measurements were made using the Global Physical Activity Questionnaire (GPAQ) on a nationally-representative sample of 14706 participants (46.5% males, response 64.1%) aged 25-64 years selected by multi-stage stratified cluster sampling. RESULTS: Approximately 20% of Vietnamese people had no measureable PA during a typical week, but 72.9% (men) and 69.1% (women) met WHO recommendations for PA by adults for their age. On average, 52.0 (men) and 28.0 (women) Metabolic Equivalent Task (MET)-hours/week (largely from work activities) were reported. Work and total PA were higher in rural areas and varied by season. Less than 2% of respondents provided incomplete information, but an additional one-in-six provided unrealistically high values of PA. Those responsible for reporting errors included persons from rural areas and all those with unstable work patterns. Box-Cox transformation (with an appropriate constant added) was the most successful method of reducing the influence of large values, but energy-scaled values were most strongly associated with pathophysiological outcomes. CONCLUSIONS: Around seven-in-ten Vietnamese people aged 25-64 years met WHO recommendations for total PA, which was mainly from work activities and higher in rural areas. Nearly all respondents were able to report their activity using the GPAQ, but with some exaggerated values and seasonal variation in reporting. Data transformation provided plausible summary values, but energy-scaling fared best in association analyses.

Phosphorylation of phosphatidylinositol 4-phosphate 5-kinase γ by Akt regulates its interaction with talin and focal adhesion dynamics.

The type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members and their lipid product, phosphatidylinositol 4,5-bisphosphate (PIP2) are important regulators of actin cytoskeleton. PIP5Kγ 90kDa (PIP5Kγ90), an isoform of PIP5K, localizes to focal adhesions (FAs) and is activated via its interaction with the cytoskeletal protein, talin. Currently, regulatory signaling pathways of talin-PIP5Kγ90 interaction related to FA dynamics and cell motility are not well understood. Considering the presence of Akt consensus motifs in PIP5Kγ90, we examined a potential link of Akt activation to talin-PIP5Kγ90 interaction. We found that Akt phosphorylated PIP5Kγ90 specifically at serine 555 (S555) in vitro and in epidermal growth factor (EGF)-treated cells phosphoinositide 3-kinase-dependently. EGF treatment suppressed talin-PIP5Kγ90 interaction and PIP2 levels. Similarly, a phosphomimetic mutant (S555D), but not non-phosphorylatable mutant (S555A), of PIP5Kγ90 had reduced talin binding affinity, lowered PIP2 levels, and was dislocated from FAs. The S555D mutant also caused decreases in actin stress fibers and vinculin-positive FAs. Moreover, assembly and disassembly of FAs were enhanced by S555D expression and EGF-induced cell migration was relatively low in S555A-expressing cells compared to wild-type-expressing cells. PIP5Kγ87, a PIP5Kγ splice variant lacking the talin binding motif, was phosphorylated by Akt, which, however, hardly affected PIP2 levels. Taken together, our results suggested that Akt-mediated PIP5Kγ90 S555 phosphorylation is a novel regulatory point for talin binding to control PIP2 level at the FAs, thereby modulating FA dynamics and cell motility.

Declining Prevalence of Tobacco Smoking in Vietnam.

INTRODUCTION: To supplement limited information on tobacco use in Vietnam, data from a nationally-representative population-based survey was used to estimate the prevalence of smoking among 25-64 year-olds. METHODS: This study included 14,706 participants (53.5% females, response proportion 64%) selected by multi-stage stratified cluster sampling. Information was collected using the World Health Organization STEPwise approach to surveillance of risk factors for non-communicable disease (STEPS) questionnaire. Smoking prevalence was estimated with stratification by age, calendar year, and birth year. RESULTS: Prevalence of ever-smoking was 74.9% (men) and 2.6% (women). Male ever-smokers commenced smoking at median age of 19.0 (interquartile range [IQR]: 17.0, 21.0) years and smoked median quantities of 10.0 (IQR: 7.0, 20.0) cigarettes/day. Female ever-smokers commenced smoking at median age of 20.0 (IQR: 18.0, 26.0) years and smoked median quantities of 6.0 (IQR: 4.0, 10.0) cigarettes/day. Prevalence has decreased in recent cohorts of men (p = .001), and its inverse association with years of education (p < .001) has strengthened for those born after 1969 (interaction p < .001). At 60 years of age, 53.0% of men who had reached that age were current smokers and they had accumulated median exposures of 39.0 (IQR: 32.0, 42.0) years of smoking and 21.0 (IQR: 11.5, 36.0) pack-years of cigarettes. The proportion of ever-smokers has decreased consistently among successive cohorts of women (p < .001). CONCLUSIONS: Smoking prevalence is declining in recent cohorts of men, and continues to decline in successive cohorts of women, possibly in response to anti-tobacco initiatives commencing in the 1990s. Low proportions of quitters mean that Vietnamese smokers accumulate high exposures despite moderate quantities of cigarettes smoked per day.