Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. METHOD: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. RESULTS: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. CONCLUSION: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Association between neighborhood availability of physical activity facilities and cognitive performance in older adults.

The existing evidence on the contextual influence of the availability of local facilities for physical activity on the cognitive health of elderly residents is sparse. This study examined the association between neighborhood physical activity facilities and cognitive health in older individuals. A cohort study of community-dwelling older adults was performed using baseline data and follow-up data from the Taiwan Biobank. Cognitive health was measured in 32,396 individuals aged 60-70 years using the Mini-Mental State Examination (MMSE) with follow-up information on 8025 participants. The district was used as the proxy for local neighborhood. To determine neighborhood physical activity facilities, school campuses, parks, activity centers, gyms, swimming pools, and stadiums were included. Multilevel linear regression models were applied to examine the associations of neighborhood physical activity facilities with baseline MMSE and MMSE decline during follow-up, with adjustment for individual factors and neighborhood socioeconomic characteristics. Multilevel analyses revealed that there was a neighborhood-level effect on cognitive health among older adults. After adjusting for compositional and neighborhood socioeconomic characteristics, baseline MMSE was higher in individuals living in the middle- (beta = 0.12, p-value = 0.140) and high-density facility (beta = 0.22, p-value = 0.025) groups than in the low-density group (p-value for trend-test = 0.031). MMSE decline during follow-up was slower in the middle- (beta = 0.15, p-value = 0.114) and high-density facility (beta = 0.27, p-value = 0.052) groups than in the low-density group (p-value for trend-test = 0.032). Greater neighborhood availability of physical activity facilities was associated with better cognitive health among older residents. These findings have implications for designing communities and developing strategies to support cognitive health of an aging population.

Associations of polygenic risks, depression, and obesity-related traits in Taiwan Biobank.

BACKGROUND: The comorbidity of obesity and major depressive disorder (MDD) may be attributable to a bidirectional relationship and shared genetic influence. We aimed to examine the polygenic associations between obesity and MDD and to characterize their corresponding impacts on the obesity mechanism. METHODS: Genome-wide genotyping was available in 106,604 unrelated individuals from Taiwan Biobank. Polygenic risk score (PRS) for body mass index (BMI) and MDD was derived to evaluate their effects on obesity-related traits. Stratified analyses were performed for the modified effect of depression on the polygenic associations. RESULTS: The MDD PRS was positively associated with waistline (beta in per SD increase in PRS = 0.12), hipline (beta = 0.08), waist-hip ratio (WHR) (beta = 0.05), body fat rate (beta = 0.08), BMI (beta = 0.05), overweight (OR = 1.02 for BMI ≥ 25), and obesity (OR = 1.05 for BMI ≥ 30). For the synergism between depression and BMI PRS, the presence of active depression symptoms defined by the PHQ-4 (p for interaction < 0.05 for waistline, WHR, and BMI) was more salient than lifetime MDD. LIMITATIONS: Limitations include recall bias for MDD due to a retrospective self-reporting questionnaire, a low response rate of the PHQ-4 for evaluating active psychological symptoms, and limited generalizability to non-Taiwanese ancestries. CONCLUSIONS: The shared genetic etiology of obesity and depression was demonstrated. The amplified effect of BMI polygenic effect on obesity for individuals with active depressive symptoms was also characterized. The study may be helpful for designing public health interventions to reduce the disease burden caused by obesity and depression.

Intracellular Accumulation of IFN-λ4 Induces ER Stress and Results in Anti-Cirrhotic but Pro-HCV Effects.

IFNL3/IFNL4 polymorphisms are inversely associated with the risk of chronic hepatitis C virus (HCV) infection and cirrhosis, two major risk factors for developing hepatocellular carcinoma (HCC). To further explore these inverse associations and their molecular underpinnings, we analyzed IFNL3/IFNL4 polymorphisms represented by the IFNL4 genotype (presence of rs368234815-dG or rs12979860-T alleles) in HCV patients: 2969 from Japan and 2931 from Taiwan. IFNL4 genotype was associated with an increased risk of HCV-related HCC (OR=1.28, 95%CI=1.07-1.52, P=0.0058) in the general population of Japanese patients, but not in Taiwanese patients who achieved treatment-induced viral clearance. IFNL4 genotype was also associated with a decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwanese patients). We then engineered HepG2 cells to inducibly express IFN-λ4 in the presence or absence of interferon lambda receptor 1 (IFNLR1). Induction of IFN-λ4 resulted in its intracellular accumulation, mainly in lysosomes and late endosomes, and increased ER stress, leading to apoptosis and reduced proliferation. We identified the very-low-density lipoprotein receptor (VLDLR), which facilitates HCV entry into hepatocytes, as a transcript induced by IFN-λ4 but not IFN-λ3. Our results suggest that the molecular mechanisms underlying the anti-cirrhotic but pro-HCV associations observed for IFNL3/IFNL4 polymorphisms are, at least in part, contributed by intracellular accumulation of IFN-λ4 causing ER stress in hepatic cells.

Postdiagnosis Aspirin Use Associated With Decreased Biliary Tract Cancer-Specific Mortality in a Large Nationwide Cohort.

BACKGROUND AND AIMS: Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH AND RESULTS: Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P < 0.001; nonusers as a reference). Cancer-specific mortality was lower with postdiagnosis aspirin use in patients with all major BTC subtypes. CONCLUSIONS: The nationwide study revealed that postdiagnosis aspirin use was associated with improved BTC-specific mortality of various subtypes. The findings suggest that additional randomized trials are required to investigate aspirin's efficacy in BTC.

Genetic variants associated with serum alanine aminotransferase levels among patients with hepatitis C virus infection: A genome-wide association study.

Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome-wide association study was performed to identify single-nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT-associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti-HCV seropositive patients was used for genome-wide SNP array to examine the associations with baseline ALT levels. SNPs <10-5 were further tested for associations with serial ALT levels then validated in 486 anti-HCV seropositives. Multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals of SNPs associated with ALT. The SNP was evaluated for HCC risk by using Cox's proportional hazards models. After quality control, 803 participants with 564,464 SNPs were included in the analysis. Of these, 12 SNPs were associated with ALT (p < 10-5 ). Among the participants, 158 (19.7%) had ALT persistently ≤15 U/L, 327 (40.7%) ever >15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow-up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p < .05). The A allele (vs C) of rs568800 was associated with ALT >15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11-1.78) and 1.86 (1.34-2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90-4.89) for AC and 2.64 (1.13-6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals.

Large-scale genome-wide association study identifies HLA class II variants associated with chronic HBV infection: a study from Taiwan Biobank.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations. AIMS: To explore genetic variants associated with chronic HBV infection. METHODS: The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole-genome genotyping by Axiom-Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method. RESULTS: Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10-35 ) was significantly associated with HBV chronicity (Pcorrected  < 8.6 × 10-8 ). Imputation analyses showed that HLA-DPA1*02:02 and HLA-DPB1*05:01 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09-1.89) and 1.61 (1.29-2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA-DRB1*13:02, HLA-DQA1* 01:02 and HLA-DQB1*06:09 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17-0.58), 0.70 (0.56-0.87) and 0.33 (0.18-0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein. CONCLUSIONS: HLA class II variants are relevant for chronicity after HBV acquisition.

A high-resolution HLA imputation system for the Taiwanese population: a study of the Taiwan Biobank.

An imputation algorithm for human leukocyte antigen (HLA) is helpful for exploring novel disease associations. However, population-specific HLA imputation references are essential for achieving high imputation accuracy. In this study, a subset of 1012 individuals from the Taiwan Biobank (TWB) who underwent both whole-genome SNP array and NGS-based HLA typing were used to establish Taiwanese HLA imputation references. The HIBAG package was used to generate the imputation references for eight HLA loci at a two- and three-field resolution. Internal validation was carried out to evaluate the call threshold and accuracy for each HLA gene. HLA class II genes found to be associated with rheumatoid arthritis (RA) were validated in this study by the imputed HLA alleles. Our Taiwanese population-specific references achieved average HLA imputation accuracies of 98.11% for two-field and 98.08% for three-field resolution. The frequency distribution of imputed HLA alleles among 23,972 TWB subjects were comparable with PCR-based HLA alleles in general Taiwanese reported in the allele frequency net database. We replicated four common HLA alleles (HLA-DRB1*03:01, DRB1*04:05, DQA1*03:03, and DQB1*04:01) significantly associated with RA. The population-specific references provide an informative tool to investigate the associations of HLA variants and human diseases in large-scale population-based studies.

Adaptation and validation of a measure of health literacy in Taiwan: The Newest Vital Sign.

BACKGROUND: Health literacy (HL) refers to the ability to obtain, read, understand, and use basic health care information required to make appropriate health decisions and follow instructions for treatment. The Newest Vital Sign (NVS) is an instrument developed for assessing aspects of HL relevant to reading and numeracy skills. This study aimed to develop a traditional Chinese version of the NVS (NVS-TC) and assess its feasibility, reliability, and validity in Taiwanese patients with type 2 diabetes. METHODS: The original NVS was translated into traditional Chinese in accordance with established guidelines. A cognitive testing procedure was subsequently performed to evaluate the ease of understanding and acceptability of the test in 30 patients with diabetes. Thereafter, a quantitative survey (N = 232) was administered for validating the NVS-TC against the accepted standard tests of HL and participant education level. RESULTS: The internal consistency (Cronbach's α) was 0.76. In accordance with a priori hypotheses, we found strong associations between the NVS-TC and objective HL and weaker associations between the NVS-TC and subjective HL. The known group validity of the NVS-TC was demonstrated through multivariate regression analyses, which showed that educational differences in the NVS-TC scores remained significant after adjustment for age, gender, and working in healthcare. CONCLUSIONS: The results suggest that the NVS-TC is a reliable and valid tool that facilitates international comparable HL research in Taiwan. The NVS-TC can be used to investigate the role of HL in health care and can be easily incorporated into daily clinical practice for diabetes management.

Stages of change concept of the transtheoretical model for healthy eating links health literacy and diabetes knowledge to glycemic control in people with type 2 diabetes.

AIMS: Health literacy has been recognized as a key construct associated with clinical outcomes; however, few studies have explored the mechanism underlying the association. The transtheoretical model (TTM) has long been considered a useful conceptualization in the process of intentional behavior change. Stages of change lies at the heart of the TTM as studies of change have found that people move through a series of stages when modifying behavior. This study focuses on the role of knowledge and stages of change (SOC) as serial mediators linking health literacy to glycemic control. METHODS: In this cross-sectional survey, a total of 232 patients with type 2 diabetes participated in this study. Participants completed questionnaires for assessing health literacy, readiness to consume healthy foods, and a dietary knowledge test specific to diabetes. RESULTS: Low health literacy was significantly associated with worse glycemic control. Statistical evaluation supported the serial mediation model, in which knowledge and SOC formed a serial mediation chain that accounted for the indirect effect of health literacy on glycemic control. In other words, dietary knowledge significantly motivated participants to move into the later stages of behavior change, which in turn improved the outcome of glycemic control. CONCLUSIONS: The results indicate that the ordering of mediators in the pathway between health literacy and health outcome may be complex, help explain the conflicting results of the past, and form a basis for the development of interventions promoting self-management of diabetes through glycemic control.

An evaluation of the 25 by 25 goal for premature cardiovascular disease mortality in Taiwan: an age-period-cohort analysis, population attributable fraction and national population-based study.

OBJECTIVES: The aim of the 25 by 25 goal is to reduce mortality from premature non-communicable diseases by 25% before 2025. Studies have evaluated the 25 by 25 goal in many countries, but not in Taiwan. The aim of this study was to estimate the 25 by 25 goal for premature mortality from cardiovascular diseases in Taiwan. METHODS: We applied the age-period-cohort model to project the incidence of premature death from cardiovascular disease from 2015 to 2024 and used the population attributable fraction to estimate the contributions of targeted risk factors. The probability of death was used to estimate the percent change. RESULTS: The percent change in business-as-usual trend during 2010-2024 was only a 6% (range 1.7-10.7%) lower risk of premature mortality from cardiovascular disease among men. The greatest reduction in the risk of mortality occurred with a 30% reduction in the prevalence of smoking; however, there was only a 14.5% (10.6-18.3%) decrease in percent change and in the corresponding number of men (3706: range 3543-3868) who were prevented from dying. More than a 25% reduction in the percent change of premature cardiovascular disease mortality among women was achieved without control of any risk factor. To reach a 25% reduction in men before 2025, there needs to be a 70% reduction in the prevalence of smoking to reduce mortality by 26.2% (22.9-29.3%). CONCLUSIONS: Cigarette smoking is the primary target in the prevention of cardiovascular disease. Through the stringent control of smoking, the goal of a 25% reduction in premature mortality from cardiovascular disease may be achieved before 2025 in Taiwan.

Factors affecting the natural decay of hepatitis B surface antigen in children with chronic hepatitis B virus infection during long-term follow-up.

OBJECTIVE: To investigate the factors predicting spontaneous clearance of hepatitis B surface antigen (HBsAg) in a long-term, prospectively followed cohort from childhood into adult life. STUDY DESIGN: Children with chronic hepatitis B virus (HBV) infection without treatment were followed longitudinally every 6 months. At each visit, liver profiles and HBV markers were assessed. Hepatitis B vaccination history and the maternal HBV markers also were studied. RESULTS: A total of 349 children (205 male) were followed for 20.6 ± 4.4 years with initial ages of 8.4 ± 3.9 years; 42 (12.0%) cleared HBsAg spontaneously. The HBsAg titers decayed with age, with an average annual clearance rate of 0.58%. Children had a lower annual HBsAg decay rate if their mothers are HBsAg carriers (P < .001). Hepatitis B e antigen-seroconversion is a favorable predictor for spontaneous HBsAg clearance (P = .04). Those with HBsAg titer ≤1000 IU/mL at enrollment during childhood have a higher rate of HBsAg clearance (hazard ratio = 5.23; P < .001). Using HBsAg titer ≤1000 IU/mL to predict HBsAg clearance, the sensitivity is 38.1%, specificity is 90.6%, positive predictive value is 35.6%, and negative predictive value is 91.4%. CONCLUSIONS: During long-term follow-up, spontaneous HBsAg clearance is most likely to occur in a patient born to a non-HBsAg-carrier mother, is a hepatitis B e antigen-seroconverter, and had an initial HBsAg level ≤1000 IU/mL.

Incidence of first onset alcohol use disorder: a 16-year follow-up in the Taiwanese aborigines.

PURPOSE: To investigate the incidence and cumulative risk of first onset alcohol use disorder (AUD) in a 16-year follow-up among Taiwanese aboriginal populations. METHODS: Participants included in this study were cohort subjects free from any AUD at phase 1 survey (n = 428 for DSM-3-R and 451 for DSM-4) of the Taiwan aboriginal study project conducted in 1986-1988. They were reassessed approximately 16 years later, with a response rate of 98.8 %. A Chinese version of the WHO schedules for clinical assessment in neuropsychiatry was employed to assess the lifetime drinking history and AUD. RESULTS: Age-standardized annual incidence rates of AUD in all groups were 2.26 and 1.75 % according to DSM-3-R and DSM-4, respectively. The overall incidence rates of AUD were comparable to most of other studies in Caucasian populations, but the sex ratios of women to men were higher in this study (1:2-3) than in the latter (1:6). The incidence of AUD was higher with DSM-3-R than with DSM-4 criteria in this study, attributable to the exclusion of physical/psychological harm in DSM-4 alcohol abuse. The cumulative risks of DSM-4 AUD in this study were very high, being 72.2 ± 19.8 for men and 48.7 ± 8.2 for women up to the age of 65 years. CONCLUSIONS: High incidence rates and cumulative risks of AUD in Taiwanese aborigines demand effective prevention strategy.

Fifteen-year population attributable fractions and causal pies of risk factors for newly developed hepatocellular carcinomas in 11,801 men in Taiwan.

Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ∼15% (or ∼5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions.

Baseline human papillomavirus infection, high vaginal parity, and their interaction on cervical cancer risks after a follow-up of more than 10 years.

OBJECTIVES: Human papillomavirus (HPV) has been recognized as a major factor for cervical cancer causation. Other factors, relating to reproduction, are also important. This study aims to disentangle the roles of baseline HPV infection, high vaginal parity (defined as having ≥4 vaginal deliveries), and the interaction between the two in predicting cervical cancer risk. METHODS: The authors apply a newly developed causal-pie modeling technique to analyze a cohort of more than 10,000 women conducted in Taiwan with more than 10 years of follow-up. The rate ratios adjusted by age and menopausal status were further modeled by an additive Poisson regression with non-negative parameters. The index of causal-pie weight (CPW) was calculated to indicate the proportion of cervical cancer cases attributable to a particular class of causal pies. RESULTS: It was found that the CPWs are 36.3 % for baseline HPV infection, 35.6 % for baseline HPV infection and high vaginal parity, and 28.1 % for other factors. CONCLUSIONS: A causal-pie modeling based on a women cohort in Taiwan successfully disentangles the roles of virus factors and reproductive factors at study entry, independently or interactively, on subsequent cervical cancer risk.

The impact of media reporting of the suicide of a singer on suicide rates in Taiwan.

PURPOSE: To examine if widespread media reporting of the suicide of a young female singer by charcoal burning increased suicide rates, and to examine whether the suicide induced a high risk of imitation suicide by this method among the young female group. METHODS: Poisson time series autoregression model was applied to examine the relative risk of overall and subgroup (age, gender and method) suicides during the 2-week period after the initiation of media reporting of the celebrity suicide. RESULTS: We found a significant increase (adjusted relative risk = 1.17, p = 0.04) in suicide deaths following media reporting of the celebrity suicide. The increase in suicides was particularly significant among female and young age groups. A marked increase in suicide by charcoal burning among females (adjusted relative risk = 1.44, p < 0.0001) was further observed. CONCLUSIONS: Detailed description of a specific suicide method following celebrity suicides may induce extensive modeling effect, attracting wider age/sex groups to model the method. Our finding provides further support for restraining media reporting of celebrity suicide in suicide prevention.

Decreasing rate of biliary atresia in Taiwan: a survey, 2004-2009.

OBJECTIVES: The pathogenesis of biliary atresia (BA) is unclear, but epidemiological studies may help to elucidate possible causes. The goals of this study were to identify BA incidence changes in Taiwan in 2004-2009 and to survey the factors that might influence incidence changes to elucidate the possible causes of BA. METHODS: A Taiwan national registry system for BA has been established since 2004. By using data from the national registry system for BA, we identified BA incidence changes in 2004-2009. We also evaluated the correlations between BA incidences and estimated rotavirus vaccine coverage rates and between BA incidences and the gross domestic product. RESULTS: A total of 185 patients with BA were identified in 2004-2009 in Taiwan, whereas the number of live births was 1 221 189. Compared with the incidence of BA in 2004-2006 (1.79 cases per 10,000 live births), the incidence of BA in 2007-2009 (1.23 cases per 10,000 live births) was decreased significantly (P = .01). BA incidences were negatively correlated with the gross domestic product (P = .02) and marginally negatively correlated with rotavirus vaccine coverage rates (P = .07). CONCLUSIONS: A significant decrease in BA incidence in Taiwan since 2007 has been noted and may be related to improvements in the general socioeconomic status and the popularity of rotavirus vaccination. Although more evidence is needed to establish a direct correlation, this phenomenon may shed light on possible causes of and preventive interventions for BA.

Weighing the causal pies in case-control studies.

PURPOSE: Epidemiologists are familiar with the concepts of Rothman's causal pies. Using real data the Hoffman study showed recently how to calculate the "proportion of diseased subjects who develop the disease due to classes of sufficient causes" (PDCs). The PDC is actually an attributable-fraction index. It may be specific to a particular risk factor profile but it does not correspond to any given class of causal pies. In this study, we show how to estimate the "causal-pie weights" (CPWs), so that each and every class of causal pies has one and only one CPW attached to it. METHODS: To conform to Rothman's model, we apply a non-negative linear odds model to constrain all the odds ratios (ORs) to be equal to or greater than one, and the interactions between them to be additive or superadditive. Based on these constrained ORs, we calculate the population attributable fractions, and then the CPWs. We used a published case-control data to show the methodology. RESULTS: The CPWs succinctly quantify the relative importance of different classes of causal pies. CONCLUSIONS: The proposed method helps to clarify the multi-factorial and complex interactive effects in disease causation. It also provides important information for designing an efficient public health intervention strategy.