Institute of Epidemiology and Preventive Medicine

Taipei, Taiwan

Institute of Epidemiology and Preventive Medicine

Taipei, Taiwan
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Weng T.C.,National Taiwan University | Chan T.C.,Academia Sinica, Taiwan | Chang C.K.J.,Institute of Epidemiology and Preventive Medicine | Wang W.W.,Institute of Epidemiology and Preventive Medicine | And 7 more authors.
PLoS ONE | Year: 2015

School children may transmit pathogens with cluster cases occurring on campuses and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City Government officials developed a School-based Infectious Disease Syndromic Surveillance System (SIDSSS). Teachers and nurses from preschools to universities in all 12 districts within Taipei are required to daily report cases of symptomatic children or sick leave requests through the SID-SSS. The pre-diagnosis at schools is submitted firstly as common pediatric disease syndrome-groups and re-submitted after confirmation by physicians. We retrieved these data from January 2010 to August 2011 for spatio-temporal analysis and evaluated the temporal trends with cases obtained from both the Emergency Department-based Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and influenza-like illness (ILI) were the two most reported syndrome groups (77.6% and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis judgments made by school teachers and nurses showed high consistency with physicians' clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly, the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance systems had the best correlation reaching 0.98 and 0.95, respectively (p<0.01). Spatio-temporal analysis observed the patterns of EVI and ILI both diffuse from the northern suburban districts to central Taipei, with ILI spreading faster. This novel system can identify early suspected cases of two important pediatric infections occurring at schools, and clusters from schools/families. It was also cost-effective (95.5% of the operation cost reduced and 59.7% processing time saved). The timely surveillance of mild EVI and ILI cases integrated with spatial analysis may help public health decision-makers with where to target for enhancing surveillance and prevention measures to minimize severe cases. © 2015 Weng et al.


Sung F.-Y.,Institute of Epidemiology and Preventive Medicine | Lan C.-Y.,Institute of Epidemiology and Preventive Medicine | Huang C.-J.,Institute of Epidemiology and Preventive Medicine | Liu C.-J.,National Taiwan University Hospital | And 3 more authors.
Hepatology | Year: 2016

To evaluate how hepatitis B virus (HBV) genetic variation affected progression from chronic carrier state to hepatocellular carcinoma (HCC), we analyzed HBV full-length sequences in blood obtained <1-20 years before diagnosis from 117 HCC cases and 118 controls nested in a cohort of 4,841 HBV carriers, for whom HBV genotypes B and C are predominant. The relationship between each viral single-nucleotide polymorphism (SNP) and HCC development was assessed using ordinal logistic models according to five periods of time to diagnosis (TTD). Thirty-one HBV-SNPs showed significant association with TTD after adjustment for HBV genotype, 24 of which could also be analyzed with an extended analysis on the full-length data in conjunction with 512 partial sequences (nucleotides 2,436-1,623) from the cohort. The obtained 10 robust candidate HBV-SNPs (P ≤ 0.0304), which showed odds ratios ranging from 1.89 to 8.68, were further confirmed in 163 GenBank HBV-HCC sequences from nine Asia regions, assayed after HCC diagnosis, representing the end stage of progressive hepatic diseases. The prevalence of these HBV-SNPs and their cumulative number, presented in terms of mutation score, increased with time approaching HCC diagnosis, with an odds ratio of 2.17, 4.21, 8.15, and 19.15, respectively, for the mutation score of 1, 2, 3, and ≥4 versus 0. The mutation score for predicting short-term HCC risk outperformed other factors, including HBV-DNA levels, viral genotype, and various combinations of risk factors, and revealed increasing accuracy with shorter TTD (<4.5 years before diagnosis: area under the curve = 0.83-0.89; sensitivity = 72.7%-94.1%; specificity = 58.3%-70.5%; conditioned on optimized cutoff for genotype B and C, respectively). Conclusions: Our work highlights the importance of identifying and tracking viral mutations for monitoring hepatitis B progression and early detection of HCC. (Hepatology 2016) © 2016 by the American Association for the Study of Liver Diseases.


Chie W.-C.,Institute of Epidemiology and Preventive Medicine
Hepatology | Year: 2016

Despite immunoprophylaxis, hepatitis B virus (HBV) transmission in highly viremic mothers remains a global health issue. Using quantitative maternal surface antigen (HBsAg) to predict HBV infection in infants has not been investigated. We enrolled 526 mother-infant pairs with positive maternal HBsAg under current immunoprophylaxis. Maternal viral load and quantitative HBsAg were measured in the peripartum period. Infant HBsAg seropositivity for more than 6 months was defined as chronic infection. Rates of chronic infection in infants at various maternal HBsAg levels were estimated using a multivariate logistic regression model. Results showed that maternal HBsAg was positively correlated with maternal viral load (r = 0.69; P < 0.001) and accurately predicted maternal viral load above 6, 7, and 8 log10 IU/mL with an area under the receiver operating characteristic curve (AUC) of 0.97, 0.98, and 0.95. Nineteen infants were chronically infected. After adjustment for the other risk factor, maternal HBsAg level was significantly associated with risk of infection (adjusted odds ratio for each log10 IU/mL increase, 15.02; 95% confidence interval [CI], 3.89-57.94; P < 0.001). The AUC for predicting infection by quantitative maternal HBsAg was comparable to that by maternal viral load (0.89 vs. 0.87; P = 0.459). Estimated rates of infection at maternal HBsAg levels of 4, 4.5, and 5 log10 IU/mL were 2.4% (95% CI, 0.1-4.6; P = 0.04), 8.6% (95% CI, 4.5-12.7; P < 0.001), and 26.4% (95% CI, 12.6-40.2; P < 0.001). Conclusion: Quantitative maternal HBsAg predicts infection in infants as well as maternal viral load does. Antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10 IU/mL to interrupt mother-to-infant transmission. (Hepatology 2016) © 2016 by the American Association for the Study of Liver Diseases.


Chen W.J.,Institute of Epidemiology and Preventive Medicine | Chen W.J.,National Taiwan University Hospital | Ting T.-T.,Institute of Epidemiology and Preventive Medicine | Ting T.-T.,National Health Research Institute | And 4 more authors.
Journal of Food and Drug Analysis | Year: 2013

The popularity of ketamine for recreational use among young people began to increase, particularly in Asia, in 2000. To gain more knowledge about the use of ketamine among high-risk individuals, a respondent-driven sampling (RDS) was implemented among regular alcohol and tobacco users in the Taipei metropolitan area from 2007 to 2010. The sampling was initiated in three different settings (i.e., 2 in the community and 1 in a clinic) to recruit seed individuals. Each participant was asked to refer one to five friends known to be regular tobacco smokers and alcohol drinkers to participate in the present study. Incentives were offered differentially upon the completion of an interview and successful referral. Information pertaining to drug use experience was collected by an audio computer-assisted self-interview instrument. Software built for RDS analyses was used for data analyses. Of the 1,115 participants recruited, about 11.7% of the RDS respondents reported ever having used ketamine. Positive expectancy of ketamine use was positively associated with ketamine use; by contrast, negative expectancy was inversely associated with ketamine use. Decision-making characteristics as measured on the Iowa Gambling Task (IGT) using reinforcement learning models revealed that ketamine users learned less from the most recent event than both tobacco- and drug-naïve controls and regular tobacco and alcohol users. These findings about ketamine use among young people have implications for its prevention and intervention. Copyright © 2013, Food and Drug Administration, Taiwan.


PubMed | National Health Research Institute, Institute of Epidemiology and Preventive Medicine, National Yang Ming University and National Taiwan University Hospital
Type: Journal Article | Journal: Journal of food and drug analysis | Year: 2014

The popularity of ketamine for recreational use among young people began to increase, particularly in Asia, in 2000. To gain more knowledge about the use of ketamine among high risk individuals, a respondent-driven sampling (RDS) was implemented among regular alcohol and tobacco users in the Taipei metropolitan area from 2007 to 2010. The sampling was initiated in three different settings (i.e., two in the community and one in a clinic) to recruit seed individuals. Each participant was asked to refer one to five friends known to be regular tobacco smokers and alcohol drinkers to participate in the present study. Incentives were offered differentially upon the completion of an interview and successful referral. Information pertaining to drug use experience was collected by an audio computer-assisted self-interview instrument. Software built for RDS analyses was used for data analyses. Of the 1,115 subjects recruited, about 11.7% of the RDS respondents reported ever having used ketamine. Positive expectancy of ketamine use was positively associated with ketamine use; in contrast, negative expectancy inversely associated with ketamine use. Decision-making characteristics as measured on the Iowa Gambling Task using reinforcement learning models revealed that ketamine users learned less from the most recent event than both tobacco- and drug-nave controls and regular tobacco and alcohol users. These findings about ketamine use among young people have implications for its prevention and intervention.


PubMed | National Taipei University, NTU Hospital, National Yang Ming University, Academia Sinica, Taiwan and Institute of Epidemiology and Preventive Medicine
Type: Journal Article | Journal: PloS one | Year: 2015

School children may transmit pathogens with cluster cases occurring on campuses and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City Government officials developed a School-based Infectious Disease Syndromic Surveillance System (SID-SSS). Teachers and nurses from preschools to universities in all 12 districts within Taipei are required to daily report cases of symptomatic children or sick leave requests through the SID-SSS. The pre-diagnosis at schools is submitted firstly as common pediatric disease syndrome-groups and re-submitted after confirmation by physicians. We retrieved these data from January 2010 to August 2011 for spatio-temporal analysis and evaluated the temporal trends with cases obtained from both the Emergency Department-based Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and influenza-like illness (ILI) were the two most reported syndrome groups (77.6% and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis judgments made by school teachers and nurses showed high consistency with physicians clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly, the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance systems had the best correlation reaching 0.98 and 0.95, respectively (p<0.01). Spatio-temporal analysis observed the patterns of EVI and ILI both diffuse from the northern suburban districts to central Taipei, with ILI spreading faster. This novel system can identify early suspected cases of two important pediatric infections occurring at schools, and clusters from schools/families. It was also cost-effective (95.5% of the operation cost reduced and 59.7% processing time saved). The timely surveillance of mild EVI and ILI cases integrated with spatial analysis may help public health decision-makers with where to target for enhancing surveillance and prevention measures to minimize severe cases.


Chan T.-C.,Academia Sinica, Taiwan | Hwang J.-S.,Academia Sinica, Taiwan | Chen R.-H.,National Taiwan University | King C.-C.,Institute of Epidemiology and Preventive Medicine | Chiang P.-H.,National Health Research Institute
BMC Public Health | Year: 2014

Severe epidemics of enterovirus have occurred frequently in Malaysia, Singapore, Taiwan, Cambodia, and China, involving cases of pulmonary edema, hemorrhage and encephalitis, and an effective vaccine has not been available. The specific aim of this study was to understand the epidemiological characteristics of mild and severe enterovirus cases through integrated surveillance data. Methods. All enterovirus cases in Taiwan over almost ten years from three main databases, including national notifiable diseases surveillance, sentinel physician surveillance and laboratory surveillance programs from July 1, 1999 to December 31, 2008 were analyzed. The Pearson's correlation coefficient was applied for measuring the consistency of the trends in the cases between different surveillance systems. Cross correlation analysis in a time series model was applied for examining the capability to predict severe enterovirus infections. Poisson temporal, spatial and space-time scan statistics were used for identifying the most likely clusters of severe enterovirus outbreaks. The directional distribution method with two standard deviations of ellipse was applied to measure the size and the movement of the epidemic. Results: The secular trend showed that the number of severe EV cases peaked in 2008, and the number of mild EV cases was significantly correlated with that of severe ones occurring in the same week [r = 0.553, p < 0.01]. These severe EV cases showed significantly higher association with the weekly positive isolation rates of EV-71 than the mild cases [severe: 0.498, p < 0.01 vs. mild: 0.278, p < 0.01]. In a time series model, the increase of mild EV cases was the significant predictor for the occurrence of severe EV cases. The directional distribution showed that both the mild and severe EV cases spread extensively during the peak. Before the detected spatio-temporal clusters in June 2008, the mild cases had begun to rise since May 2008, and the outbreak spread from south to north. Conclusions: Local public health professionals can monitor the temporal and spatial trends plus spatio-temporal clusters and isolation rate of EV-71 in mild and severe EV cases in a community when virus transmission is high, to provide early warning signals and to prevent subsequent severe epidemics. © 2014 Chan et al.; licensee BioMed Central Ltd.


Huang M.-C.,Taipei City Hospital | Huang M.-C.,Taipei Medical University | Schwandt M.L.,U.S. National Institutes of Health | Chester J.A.,Purdue University | And 12 more authors.
Neuropsychopharmacology | Year: 2014

Alcohol withdrawal is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction. The FKBP5 gene codes for a co-chaperone, FK506-binding protein 5, that exerts negative feedback on HPA axis function. This study aimed to examine the effects of single-nucleotide polymorphisms (SNPs) of the FKBP5 gene in humans and the effect of Fkbp5 gene deletion in mice on alcohol withdrawal severity. We genotyped six FKBP5 SNPs (rs3800373, rs9296158, rs3777747, rs9380524, rs1360780, and rs9470080) in 399 alcohol-dependent inpatients with alcohol consumption 48 h before admission and recorded scores from the Clinical Institute Withdrawal Assessment-Alcohol revised (CIWA-Ar). Fkbp5 gene knockout (KO) and wild-type (WT) mice were assessed for alcohol withdrawal using handling-induced convulsions (HICs) following both acute and chronic alcohol exposure. We found the minor alleles of rs3800373 (G), rs9296158 (A), rs1360780 (T), and rs9470080 (T) were significantly associated with lower CIWA-Ar scores whereas the minor alleles of rs3777747 (G) and rs9380524 (A) were associated with higher scores. The haplotype-based analyses also showed an association with alcohol withdrawal severity. Fkbp5 KO mice showed significantly greater HICs during withdrawal from chronic alcohol exposure compared with WT controls. This study is the first to show a genetic effect of FKBP5 on the severity of alcohol withdrawal syndrome. In mice, the absence of the Fkbp5 gene enhances sensitivity to alcohol withdrawal. We suggest that FKBP5 variants may trigger different adaptive changes in HPA axis regulation during alcohol withdrawal with concomitant effects on withdrawal severity. © 2014 American College of Neuropsychopharmacology. All rights reserved.


Kuo P.-H.,Institute of Epidemiology and Preventive Medicine | Kuo P.-H.,National Taiwan University | Kuo P.-H.,National Cheng Kung University | Kao C.-F.,Institute of Epidemiology and Preventive Medicine | And 6 more authors.
Journal of Clinical Psychopharmacology | Year: 2011

Background: Schizophrenic patients have a high prevalence of metabolic adversities. Previous studies have suggested some candidate genes for obesity-and metabolic-related traits, including the insulin-induced gene (INSIG2), melanocortin 4 receptor gene (MC4R), and leptin and leptin receptor genes (LEP and LEPR). We aimed to investigate the associations between these genes and metabolic disturbances in patients with schizophrenia in Taiwan. Methods: Patients with a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were recruited from 36 community psychiatric rehabilitation centers or hospitals in Taipei. A total of 650 subjects were enrolled, and 577 were included in the genetic analyses. The anthropometric (body mass index, waist circumference [WC], and blood pressure) and biochemical measurements (fasting plasma glucose, insulin, triglyceride, high-density lipoprotein cholesterol, and Homeostasis Model of Assessment-Insulin Resistance index [HOMA-IR]) were assessed. Seven loci in the 4 genes were genotyped using standard TaqMan assays. Genetic association analyses were conducted for binary and quantitative measurements of the previously mentioned traits. Obese patients with schizophrenia exhibited more metabolic disturbances than nonobese patients. RESULTS AND Conclusions: Our data showed that INSIG2 was significantly associated with fasting plasma glucose (for rs17587100, P < 0.0001), MC4R was associated with WC (for rs2229616, P = 0.005), and LEP was associated with body mass index and WC (for rs7799039, P < 0.01). In addition, these loci showed suggestive associations with traits including high-density lipoprotein cholesterol and triglyceride, metabolic syndrome, insulin level, and HOMA-IR index (P = 0.05). In addition to the effect from antipsychotic medications and an unhealthy lifestyle, genetic factors also contribute to the high prevalence of obesity and metabolic disturbances in patients with schizophrenia, especially genes involved in metabolic-related pathways. © 2011 by Lippincott Williams & Wilkins.

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