Publications by authors named "Chao A Hsiung"

173 Publications

Metformin and the risk of anemia of advanced chronic kidney disease in patients with Type 2 Diabetes mellitus.

J Clin Pharmacol 2021 Sep 12. Epub 2021 Sep 12.

Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.

This retrospective cohort study determines whether metformin monotherapy or combination therapies can decrease anemia risk in the progress of advanced chronic kidney disease for patients with type 2 diabetes mellitus. The dataset was obtained from the National Health Insurance Research Database, containing 1 million randomly selected beneficiaries. After matching, 9,303 pairs (1:1) of metformin and non-metformin users were acquired. Every patient was individually recorded from 1997 to 2012 to identify anemia incidence (hemoglobin lower than 9gm/dL). Cox regression model were used to compute hazard ratios and 95% confidence intervals (CIs). There were 305(0.7%) and 76(0.8%) erythropoietin-stimulating agent (ESA) cases in the metformin and non-metformin cohorts over a mean follow-up period of 6.8 and 5.6 years. After matching, the use of metformin decreased the risk of usage of ESA with an adjusted hazard ratio of 0.76(95%CI: 0.45-1.29) for dosage of less than 357g to 0.30(95%CI: 0.17-0.56) for more than 1,368g. The combination of metformin and dipeptidyl peptidase-4 inhibitors decreased with the hazard ratio of 0.42(95%CI:0.18-0.99), compared to metformin alone. Metformin combined with dipeptidyl peptidase-4 inhibitors is superior to metformin monotherapy or non-metformin antidiabetic therapies for reducing the risk of anemia in the progress of advanced chronic kidney disease among patients with type 2 diabetes. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jcph.1965DOI Listing
September 2021

Assessment of incident frailty hazard associated with depressive symptoms in a Taiwanese longitudinal study.

Int Psychogeriatr 2021 Jul 19:1-10. Epub 2021 Jul 19.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

Objectives: To estimate the risks of depressive symptoms for developing frailty, accounting for baseline robust or pre-frailty status.

Design: An incident cohort study design.

Setting: Community dwellers aged 55 years and above from urban and rural areas in seven regions in Taiwan.

Participants: A total of 2,717 participants from the Healthy Aging Longitudinal Study in Taiwan (HALST) were included. Subjects with frailty at baseline were excluded. The average follow-up period was 5.9 years.

Measurements: Depressive symptoms were measured by the 20-item Center for Epidemiological Studies Depression (CES-D) Scale. Frailty was assessed using the Fried frailty measurement. Participants were stratified by baseline robust or pre-frailty status to reduce the confounding effects of the shared criteria between depressive symptoms and frailty. Overall and stratified survival analyses were conducted to assess risks of developing frailty as a result of baseline depressive symptoms.

Results: One hundred individuals (3.7%) had depressive symptoms at baseline. Twenty-seven individuals (27.0%) with depressive symptoms developed frailty, whereas only 305 out of the 2,617 participants (11.7%) without depressive symptoms developed frailty during the follow-up period. After adjusting for covariates, depressive symptoms were associated with a 2.6-fold (95% CI 1.6, 4.2) increased hazard of incident frailty. The patterns of increased hazard were also observed when further stratified by baseline robust or pre-frailty status.

Conclusions: Depressive symptoms increased the risk of developing frailty among the older Asian population. The impact of late-life depressive symptoms on physical health was notable. These findings also replicated results from Western populations. Future policies on geriatric public health need to focus more on treatment and intervention against geriatric depressive symptoms to prevent incident frailty among older population.
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http://dx.doi.org/10.1017/S1041610221000806DOI Listing
July 2021

Association between Alzheimer's disease genes and trajectories of cognitive function decline in Han Chinese in Taiwan.

Aging (Albany NY) 2021 07 2;13(13):17237-17252. Epub 2021 Jul 2.

Faculty of Medicine, National Yang-Ming University Schools of Medicine, Taipei, Taiwan.

Genetic background has been considered one of the important contributors to the rate of cognitive decline among patients with Alzheimer's disease (AD). We conducted a 4-year longitudinal follow-up study, recruited 255 AD and 44 mild cognitive impairment (MCI) patients, and used a data-driven trajectory analysis to examine the influence of selected AD risk genes on the age for and the rate of cognitive decline in Han Chinese population. Genotyping of selected single-nucleotide polymorphisms in the , , , , , and genes was conducted, and a Bayesian hierarchical model was fitted to analyze the trajectories of cognitive decline among different genotypes. After adjusting for sex and education years, the ε4 allele was associated with an earlier mean change of -2.39 years in the age at midpoint of cognitive decline, the G allele in rs3764650 was associated with an earlier mean change of -1.75 years, and the T allele in rs3737529 was associated with a later mean change of 2.6 years. Additionally, the rate of cognitive decline was associated with the ε4 allele and rs3737529. In summary, and might be the most important genetic factors related to cognitive decline in Han Chinese population.
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http://dx.doi.org/10.18632/aging.203204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312434PMC
July 2021

Clinical and epidemiological features in hospitalized young children with acute gastroenteritis in Taiwan: A multicentered surveillance through 2014-2017.

J Formos Med Assoc 2021 Jun 21. Epub 2021 Jun 21.

Institute of Population Health Sciences, National Health Research Institutes, Taiwan.

Background/purpose: Acute gastroenteritis (AGE) remains a significant health issue in children. The worldwide evolution of pediatric AGE pathogens had been recorded since the introduction of rotavirus vaccine. Ten years after the rotavirus vaccine was introduced to the private sectors in Taiwan, a nationwide study was conducted to elucidate the epidemiological changes among major AGE pathogens.

Methods: From January 2014 to December 2017, children younger than 5 years old, hospitalized with AGE at 10 hospitals across Taiwan were enrolled. Stool specimens were tested for Salmonella spp., Campylobacter spp., Clostridiodes difficile, norovirus, and rotavirus by polymerase chain reaction (PCR). The epidemiological and clinical information was collected.

Results: Enteric pathogen were detected in 1983 (42.2%) of 4700 subjects, with Salmonella spp. (12.5%) being the leading cause of AGE, followed by norovirus (11.2%), rotavirus (8.7%), C. difficile (4.2%), Campylobacter spp. (1.0%), and a mixture of at least 2 of 5 above-mentioned pathogens (4.6%). The case distributions varied across different regions. In eastern Taiwan, rotavirus (21/131, 16.0%) remained the most common pathogen detected. The rotavirus vaccine uptake rate is significantly lower in patients with rotavirus AGE. Besides, rotavirus AGE frequently occurred in children with foreign parent(s), Taiwanese indigenous people, and those with the household monthly income < NT$ 60,000.

Conclusion: Salmonella spp. and norovirus were two major pathogens of pediatric AGE in Taiwan during 2014-17. Providing low-to middle-income households with free rotavirus vaccine nationwide and an industry-led act to reduce salmonellosis should be considered by the authorities.
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http://dx.doi.org/10.1016/j.jfma.2021.06.001DOI Listing
June 2021

Longitudinal changes in physical and mental health of older adults with chronic hepatitis B infection: Trajectories and predictors.

Prev Med Rep 2021 Sep 2;23:101432. Epub 2021 Jun 2.

Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.

Despite the increasing health burden of chronic hepatitis B (CHB) in aging populations, little is known about the course of health-related quality of life (HRQoL) changes. We aimed to assess individual-level longitudinal HRQoL changes in elderly patients with CHB and to examine their correlates. A prospective 5.1 years-cohort study was conducted in community-dwelling adults aged 55 years with hepatitis B surface antigen-positive. Participants underwent serial measurement of HRQoL using the short-form (12) health survey version 2. Of 503 participants, 82.7% remained in good physical health throughout the study period, whereas 9.1% had declining physical health and 8.2% were in poor physical health. We likewise identified three trajectories of mental health changes ("good mental health" [86.9%], "declining mental health" [6.8%], and "poor mental health" [6.4%]). Three baseline characteristics were independently associated with a lower likelihood of remaining physically or mentally healthy: sarcopenic obesity (odds ratio [OR] with 95% confidence interval [95% CI] of 7.5 [2.8-20.5] for poor physical health, 3.1 [1.1-8.4] for declining physical health, 4.3 [1.4-13.0] for poor mental health), a higher number of metabolic abnormalities (OR [95% CI] of 3.6 [1.6-8.0] for poor physical health) and depressed mood (OR [95% CI] of 21.7 [5.8-81.0] for poor physical health, 5.3 [1.4-19.9] for declining physical health, 83.1 [19.7-350.2] for poor mental health, 13.6 [2.9-64.8] for declining mental health). In conclusion, in a cohort of elderly patients with CHB, we demonstrated the heterogeneity and nonlinearity of HRQoL changes and their associations with variations in specific extrahepatic organs/systems.
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http://dx.doi.org/10.1016/j.pmedr.2021.101432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193133PMC
September 2021

Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan.

Sci Rep 2021 Apr 26;11(1):8899. Epub 2021 Apr 26.

School of Public Health, College of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.

Patients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%-89.9%) and 76.7% (95% CI = 37.2%-99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%-57.7%) and 49.3% (95% CI = 21.9%-84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.
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http://dx.doi.org/10.1038/s41598-021-88289-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076276PMC
April 2021

Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose.

Diabetologia 2021 Jul 12;64(7):1613-1625. Epub 2021 Apr 12.

Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Aims/hypothesis: An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses.

Methods: We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data.

Results: Our meta-analysis identified 18 significant (p < 5 × 10) and independent SNPs for fasting glucose. Interestingly, all 18 SNPs were meQTLs. The MR analysis identified seven CpGs near the G6PC2 gene that mediated the effects of a significant SNP (rs2232326) in the gene on fasting glucose. The MR effects for two CpGs were replicated using summary data based on the European population, using an exonic SNP rs2232328 in G6PC2 as the instrument.

Conclusions/interpretation: Our analysis results suggest that rs2232326 and rs2232328 in G6PC2 may affect DNA methylation at CpGs near the gene and that the methylation may have downstream effects on fasting glucose. Therefore, SNPs in G6PC2 and CpGs near G6PC2 may reside along the pathway that influences fasting glucose levels. This is the first study to report CpGs near G6PC2, an important gene for regulating insulin secretion, mediating the effects of GWAS-significant SNPs on fasting glucose.
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http://dx.doi.org/10.1007/s00125-021-05449-9DOI Listing
July 2021

Medical care needs for patients receiving home healthcare in Taiwan: Do gender and income matter?

PLoS One 2021 25;16(2):e0247622. Epub 2021 Feb 25.

Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London, London, United Kingdom.

Studies about medical care needs for home healthcare (HHC) previously focused on disease patterns but not gender and income differences. We used the Taiwan National Health Research Insurance Database from 1997 to 2013 to examine trends in medical care needs for patients who received HHC, and the gender and income gaps in medical care needs, which were represented by resource utilization groups (RUG). We aimed to clarify three questions: 1. Are women at a higher level of medical care needs for HHC than men, 2. Does income relate to medical care needs? 3. Is the interaction term (gender and income) related to the likelihood of medical care needs? Results showed that the highest level of medical care need in HHC was reducing whereas the basic levels of medical care need for HHC are climbing over time in Taiwan during 1998 and 2013. The percentages of women with income-dependent status in RUG1 to RUG4 are 26.43%, 26.24%, 30.68%, and 32.07%, respectively. Women were more likely to have higher medical care needs than men (RUG 3: odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10-1.25; RUG4: OR = 1.13, 95% CI = 1.06-1.22) in multivariates regression test. Compared to the patients with the high-income status, patients with the income-dependent status were more likely to receive RUG3 (OR = 2.34, 95% CI = 1.77-3.09) and RUG4 (OR = 1.98, 95% CI = 1.44-2.71). The results are consistent with the perspectives of fundamental causes of disease and feminization of poverty theory, implying gender and income inequalities in medical care needs. Policymakers should increase public spending for delivering home-based integrated care resources, especially for women with lower income, to reduce the double burden of female poverty at the higher levels of medical care needs for HHC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247622PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906386PMC
August 2021

Late-onset epilepsy and subsequent increased risk of dementia.

Aging (Albany NY) 2021 01 10;13(3):3573-3587. Epub 2021 Jan 10.

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.

Inflammation is considered as a key pathogenesis factor of dementia and epilepsy. However, epilepsy's association with dementia, particularly its role in the development of dementia, remains unclear. To evaluate the association between epilepsy and the risk of dementia, in Taiwan, we have now conducted a retrospective cohort study comprising 675 individuals (age, ≥50 years) with epilepsy and 2,025 matched control subjects without epilepsy. In order to match individuals diagnosed with epilepsy with those with no diagnosis of epilepsy (comparison cohort), we utilized exact matching at a ratio of 1:3. Compared with those in the comparison cohort, individuals in the epilepsy cohort had a significantly increased risk of developing dementia (adjusted hazard ratio = 2.87, < 0.001). A similar result has been observed after stratifying for sex (adjusted hazard ratio in males = 2.95, < 0.001; adjusted hazard ratio in females = 2.66, < 0.001). To conclude, based on these data, epileptic individuals ≥50 years were at a greater risk of developing dementia than people who do not have epilepsy, which indicates that a diagnosis of epilepsy presents a greater risk for the development of dementia.
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http://dx.doi.org/10.18632/aging.202299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906153PMC
January 2021

Whole genome sequence analyses of eGFR in 23,732 people representing multiple ancestries in the NHLBI trans-omics for precision medicine (TOPMed) consortium.

EBioMedicine 2021 Jan 6;63:103157. Epub 2021 Jan 6.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Background: Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants.

Methods: We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity.

Findings: When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10, nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants.

Interpretation: This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.
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http://dx.doi.org/10.1016/j.ebiom.2020.103157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804602PMC
January 2021

The Association between Home Healthcare and Burdensome Transitions at the End-of-Life in People with Dementia: A 12-Year Nationwide Population-Based Cohort Study.

Int J Environ Res Public Health 2020 12 10;17(24). Epub 2020 Dec 10.

Centre for Dementia Palliative Care Research, Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London, London W1T 7NF, UK.

Background: For people with dementia, burdensome transitions may indicate poorer-quality end-of-life care. Little is known regarding the association between home healthcare (HHC) and these burdensome transitions. We aimed to investigate the impact of HHC on transitions and hospital/intensive care unit (ICU) utilisation nearing the end-of-life for people with dementia at a national level.

Methods: A nested case-control analysis was applied in a retrospective cohort study using a nationwide electronic records database. We included people with new dementia diagnoses who died during 2002-2013 in whole population data from the universal healthcare system in Taiwan. Burdensome transitions were defined as multiple hospitalisations in the last 90 days (early transitions, ET) or any hospitalisation or emergency room visit in the last three days of life (late transitions, LT). People with (cases) and without (controls) burdensome transitions were matched on a ratio of 1:2. We performed conditional logistic regression with stratified analyses to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) of the risks of transitions.

Results: Among 150,125 people with new dementia diagnoses, 61,399 died during follow-up, and 31.1% had burdensome transitions (50% were early and 50% late). People with ET had the highest frequency of admissions and longer stays in hospital/ICU during their last year of life, while people with LT had fewer hospital/ICU utilisation than people without end-of-life transitions. Receiving HHC was associated with an increased risk of ET (OR = 1.14, 95 % CI: 1.08-1.21) but a decreased risk of LT (OR = 0.89, 95 % CI 0.83-0.94). In the people receiving HHC, however, those who received longer duration (e.g., OR = 0.50, 95 % CI: 0.42-0.60, >365 versus ≤30 days) or more frequent HHC or HHC delivered closer to the time of death were associated with a remarkably lower risk of ET.

Conclusions: HHC has differential effects on early and late transitions. Characteristics of HHC such as better continuity or interdisciplinary coordination may reduce the risk of transitions at the end-of-life. We need further studies to understand the longitudinal effects of HHC and its synergy with palliative care, as well as the key components of HHC that achieve better end-of-life outcomes.
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http://dx.doi.org/10.3390/ijerph17249255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764349PMC
December 2020

Nonpolio Enterovirus Activity during the COVID-19 Pandemic, Taiwan, 2020.

Emerg Infect Dis 2021 01 1;27(1). Epub 2020 Dec 1.

In Taiwan, lower nonpolio enterovirus activity during the coronavirus disease pandemic in 2020 compared with 2014-2019 might be attributable to adherence to nonpharmaceutical interventions. The preventable fraction among unexposed persons indicated that 90% of nonpolio enterovirus activity might have been prevented during 2014-2019 by adopting the same measures enforced in 2020.
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http://dx.doi.org/10.3201/eid2701.203394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774568PMC
January 2021

Exposure to endocrine disruptor alkylphenols and the occurrence of endometrial cancer.

Environ Pollut 2020 Dec 27;267:115475. Epub 2020 Aug 27.

National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Institute of Environmental Medicine, College of Public Health, China Medical University and Hospital, Taichung, Taiwan; Department of Public Health, National Defense Medical Center, Taipei, Taiwan; Department of Safety, Health, and Environmental Engineering, National United University, Miaoli, Taiwan. Electronic address:

Exposure to environmental chemicals with oestrogenic effects has been associated with the development of endometrial cancer (EMCa). EMCa has become the most commonly diagnosed cancer of the female genital tract. To further understand the potential association between exposure to environmental endocrine disruptors and the occurrence of EMCa, we performed a case-control study between 2011 and 2014. We aimed to detect and compare concentrations of a known hormone disruptor, alkylphenol, between women diagnosed with either EMCa or uterine leiomyoma, and those who did not have either of these. Subjects were women diagnosed with either EMCa or uterine leiomyoma (LM) and healthy controls. A structured questionnaire was administered to collect information on lifestyle and health status. Gas chromatography/mass spectrometry was used to measure urinary NP and OP concentrations in participants. Multiple regression analysis was used to examine the association between exposure and outcomes. Overall, 397 women were recruited, including 49 with EMCa, 247 with LM, and 101 controls. Among them, 73.6% showed detectable levels of NP and 61.0% showed detectable levels of OP. The EMCa group had a significantly higher NP concentration than the control group. Higher OP concentrations were also found in participants with EMCa than those with LM and controls. In addition, women in the upper tertile of the NP group had a significantly increased risk of EMCa occurrence (odds ratio [95% confidence interval] = 4.47 [1.69-11.84] for EMCa vs. control). The same was found in the group of women with more than the median level of OP (odds ratio [95% confidence interval] = 4.32 [2.01-9.30] for EMCa vs. LM). Stratification of pre- and post-menopausal groups resulted in a similar association. The results show that NP/OP exposure is associated with EMCa. Further investigations and exposure minimisation are suggested.
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http://dx.doi.org/10.1016/j.envpol.2020.115475DOI Listing
December 2020

HOme-based Longitudinal Investigation of the multidiSciplinary Team Integrated Care (HOLISTIC): protocol of a prospective nationwide cohort study.

BMC Geriatr 2020 11 27;20(1):511. Epub 2020 Nov 27.

Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, 350, Taiwan.

Background: The use of home health care (HHC) is increasing worldwide. This may have an impact not only on patients and their caregivers' health but on care resource utilization and costs. We lack information on the impact of HHC on the broader dimensions of health status and care resource utilization. More understanding of the longitudinal HHC impact on HHC patients and caregivers is also needed. Moreover, we know little about the synergy between HHC and social care. Therefore, the present study aims to observe longitudinal changes in health, care resource utilization and costs and caregiving burden among HHC recipients and their caregivers in Taiwan.

Methods: A prospective cohort study "Home-based Longitudinal Investigation of the Multidisciplinary Team Integrated Care (HOLISTIC)" will be conducted and 600 eligible patient-caregiver dyads will be recruited and followed with comprehensive quantitative assessments during six home investigations over two years. The measurements include physical function, psychological health, cognitive function, wellbeing, shared decision making and advance care planning, palliative care and quality of dying, caregiving burden, continuity and coordination of care, care resource utilization, and costs.

Discussion: The HOLISTIC study offers the opportunity to comprehensively understand longitudinal changes in health conditions, care resource utilization and costs and caregiving burden among HHC patients and caregivers. It will provide new insights for clinical practitioners and policymakers.

Trial Registration: ClinicalTrials.gov Identifier is NCT04250103 which has been registered on 31st January 2020.
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http://dx.doi.org/10.1186/s12877-020-01920-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694342PMC
November 2020

Clinical characteristics and risk factors for children with norovirus gastroenteritis in Taiwan.

J Microbiol Immunol Infect 2020 Aug 11. Epub 2020 Aug 11.

Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan. Electronic address:

Background: Norovirus is a common acute gastroenteritis (AGE) pathogen across all age groups worldwide, which is difficult to differentiate from other pathogens. This study aimed to understand the clinical characteristics and risk factors of norovirus gastroenteritis among children in Taiwan.

Methods: A prospective AGE surveillance study was conducted in children aged ≤5 years who were hospitalized in 10 major hospitals in Taiwan between 2014 and 2017. The non-AGE control group included healthy children who were matched based on age, gender, season, and geographic area.

Results: Overall, 674 norovirus gastroenteritis patients were enrolled. Fever (p < 0.001), mucoid stool (p < 0.001), and bloody stool (p < 0.001) occurred less frequently among norovirus gastroenteritis patients. Norovirus gastroenteritis patients yielded lower CRP values on admission (21.78 ± 36.81 vs. 46.26 ± 58.12 mg/L, p < 0.001) than non-norovirus controls. Norovirus gastroenteritis patients were associated with higher direct contact rates with AGE patients within 1 week (30.5% vs. 0.97%, p < 0.001), lower hand wash rates before meals (21.6% vs. 15.4%, p = 0.001), lower human milk (15.8% vs. 19.8%, p = 0.045) and guava consumption rates (17.8% vs. 24.3%, p = 0.002) than non-AGE participants.

Conclusions: Body temperature, stool characteristics, and CRP value can help distinguish the norovirus from other pathogens. The major risk factor of norovirus AGE is contact with AGE patient. Higher frequency of hand wash, human milk, and guava intake may be protective against norovirus gastroenteritis.
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http://dx.doi.org/10.1016/j.jmii.2020.07.013DOI Listing
August 2020

The potential role of pneumococcal conjugate vaccine in reducing acute respiratory inflammation in community-acquired pneumococcal pneumonia.

J Biomed Sci 2020 Aug 19;27(1):88. Epub 2020 Aug 19.

Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138, Sheng Li Road, North Dist, Tainan, 70403, Taiwan.

Background: Pneumococcal conjugate vaccine (PCV) reduces both invasive pneumococcal disease (IPD) and other pneumococcal infections worldwide. We investigated the impact of stepwise implementation of childhood PCV programs on the prevalence of pneumococcal pneumonia, severity of acute inflammation, and associations between breakthrough pneumonia and pneumococcal serotypes in Taiwan.

Methods: In total, 983 children diagnosed with community-acquired pneumococcal pneumonia were enrolled between January 2010 and December 2015.

Results: Proportions of pneumococcal vaccinations increased each year in age-stratified groups with PCV7 (32.2%) as the majority, followed by PCV13 (12.2%). The proportion of pneumococcal pneumonia decreased each year in age-stratified groups, especially in 2-5 year group. Serotype 19A is the leading serotype either in vaccinated (6.4%) or unvaccinated patients (5.2%). In particular, vaccinated patients had significantly higher lowest WBC, lower neutrophils, lower lymphocytes and lower CRP values than non-vaccinated patients (p < 0.05). After stratifying patients by breakthrough infection, those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia disease (p < 0.05).

Conclusion: Systematic childhood pneumococcal vaccination reduced the prevalence of community-acquired pneumococcal pneumonia, especially in 2-5 year group. Serotype 19A was the major serotype for all vaccine types in patients with pneumococcal pneumonia and severity of acute inflammatory response was reduced in vaccinated patients.
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http://dx.doi.org/10.1186/s12929-020-00680-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435222PMC
August 2020

The effect of preventing subclinical transmission on the containment of COVID-19: Mathematical modeling and experience in Taiwan.

Contemp Clin Trials 2020 09 6;96:106101. Epub 2020 Aug 6.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan. Electronic address:

The control strategies preventing subclinical transmission differed among countries. A stochastic transmission model was used to assess the potential effectiveness of control strategies at controlling the COVID-19 outbreak. Three strategies included lack of prevention of subclinical transmission (Strategy A), partial prevention using testing with different accuracy (Strategy B) and complete prevention by isolating all at-risk people (Strategy C, Taiwan policy). The high probability of containing COVID-19 in Strategy C is observed in different scenario, had varied in the number of initial cases (5, 20, and 40), the reproduction number (1.5, 2, 2.5, and 3.5), the proportion of at-risk people being investigated (40%, 60%, 80%, to 90%), the delay from symptom onset to isolation (long and short), and the proportion of transmission that occurred before symptom onset (<1%, 15%, and 30%). Strategy C achieved probability of 80% under advantageous scenario, such as low number of initial cases and high coverage of epidemiological investigation but Strategy B and C rarely achieved that of 60%. Considering the unsatisfactory accuracy of current testing and insufficient resources, isolation of all at-risk people, as adopted in Taiwan, could be an effective alternative.
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http://dx.doi.org/10.1016/j.cct.2020.106101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409788PMC
September 2020

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children.

Vaccine 2020 09 5;38(41):6435-6441. Epub 2020 Aug 5.

Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan. Electronic address:

Background: Two rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries.

Methods: From February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8-59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 - odds ratio of vaccination) × 100%.

Results: Totally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls.

Conclusions: Both vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.
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http://dx.doi.org/10.1016/j.vaccine.2020.07.067DOI Listing
September 2020

Decreased levels of urinary di-2-ethylhexyl phthalate (DEHP) metabolites and biomarkers of oxidative stress in children exposed to DEHP-tainted foods in Taiwan in 2011: A 44-month follow-up.

Environ Pollut 2020 Nov 16;266(Pt 2):115204. Epub 2020 Jul 16.

Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

A major health scandal involving DEHP-tainted (di-2-ethylhexyl phthalate) foodstuffs occurred in Taiwan in 2011. We investigated temporal relationships between urinary DEHP metabolites and biomarkers of oxidative stress in two cohorts of potentially affected children during that food scandal. One cohort was collected from Kaohsiung Medical University Hospital in southern Taiwan between May and June of 2011 (the KMUH cohort). This cohort was followed up at 2, 6, and 44 months. The other cohort was collected from a nationwide health survey conducted by Taiwan's National Health Research Institutes (the NHRI cohort) for potentially affected people between August 2012 and January 2013. Both cohorts only included children 10 years old and younger who had provided enough urine for analysis of urinary DEHP oxidative metabolites and two markers of oxidative stress: 8-oxo-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The KMUH cohort had a simultaneous and significant decrease in urinary DEHP metabolites, 8-OHdG, and MDA, with the lowest concentrations found at the 6-month follow up and maintained until the 44-month follow up, consistent with those from NHRI cohort at ∼15-18 months post-scandal (p > 0.05). There were decreases in both DEHP metabolites and oxidative stress markers across the populations, but no association was observed between DEHP metabolites and oxidative stress markers in individuals in the two cohorts. Continued follow-up is needed to determine long-term health consequences in these children.
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http://dx.doi.org/10.1016/j.envpol.2020.115204DOI Listing
November 2020

Real-time dengue forecast for outbreak alerts in Southern Taiwan.

PLoS Negl Trop Dis 2020 07 27;14(7):e0008434. Epub 2020 Jul 27.

Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.

Dengue fever is a viral disease transmitted by mosquitoes. In recent decades, dengue fever has spread throughout the world. In 2014 and 2015, southern Taiwan experienced its most serious dengue outbreak in recent years. Some statistical models have been established in the past, however, these models may not be suitable for predicting huge outbreaks in 2014 and 2015. The control of dengue fever has become the primary task of local health agencies. This study attempts to predict the occurrence of dengue fever in order to achieve the purpose of timely warning. We applied a newly developed autoregressive model (AR model) to assess the association between daily weather variability and daily dengue case number in 2014 and 2015 in Kaohsiung, the largest city in southern Taiwan. This model also contained additional lagged weather predictors, and developed 5-day-ahead and 15-day-ahead predictive models. Our results indicate that numbers of dengue cases in Kaohsiung are associated with humidity and the biting rate (BR). Our model is simple, intuitive and easy to use. The developed model can be embedded in a "real-time" schedule, and the data (at present) can be updated daily or weekly based on the needs of public health workers. In this study, a simple model using only meteorological factors performed well. The proposed real-time forecast model can help health agencies take public health actions to mitigate the influences of the epidemic.
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http://dx.doi.org/10.1371/journal.pntd.0008434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384612PMC
July 2020

Reading activity prevents long-term decline in cognitive function in older people: evidence from a 14-year longitudinal study.

Int Psychogeriatr 2021 01 5;33(1):63-74. Epub 2020 Jun 5.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Objective: This study examined the effect of daily life reading activity on the risk of cognitive decline and whether the effect differs regarding education levels.

Design: A longitudinal study with 6-, 10-, and 14-year follow-up.

Setting: Face-to-face interviews with structured questionnaires at home.

Participants: A representative sample of 1,962 Taiwanese community-dwelling older persons aged 64 and above, followed up in four waves of surveys over 14 years.

Measurements: Baseline reading frequencies were measured based on a scale of leisure activity. The Short Portable Mental Status Questionnaire was used to measure cognitive performance. We performed logistic regression to assess associations between baseline reading and later cognitive decline. Interaction terms between reading and education were to compare the reading effects on cognitive decline at different education levels.

Results: After adjusting for covariates, those with higher reading frequencies (≥1 time a week) were less likely to have cognitive decline at 6-year (adjusted odds ratio [AOR]: 0.54; 95% confidence interval [CI]: 0.34-0.86), 10-year (AOR: 0.58, 95% CI: 0.37-0.92), and 14-year (AOR: 0.54, 95% CI: 0.34-0.86); in a 14-year follow-up, a reduced risk of cognitive decline was observed among older people with higher reading frequencies versus lower ones at all educational levels.

Conclusions: Reading was protective of cognitive function in later life. Frequent reading activities were associated with a reduced risk of cognitive decline for older adults at all levels of education in the long term.
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http://dx.doi.org/10.1017/S1041610220000812DOI Listing
January 2021

Characterization of phthalate exposure in relation to serum thyroid and growth hormones, and estimated daily intake levels in children exposed to phthalate-tainted products: A longitudinal cohort study.

Environ Pollut 2020 Sep 24;264:114648. Epub 2020 Apr 24.

School of Food Safety, College of Nutrition, Taipei Medical University, Taipei, Taiwan. Electronic address:

Background: No information is available on the long-term effects on thyroid and growth hormones of children exposed to phthalate-tainted products, despite the infamous 2011 Taiwan phthalate episode. We investigated estimated daily intake levels and their long-term effects on serum thyroid and growth hormone levels in children.

Methods: We recruited 166 children (2-18 years old) in three visits who provided specimens and filled out a questionnaire from the Risk Assessment of Phthalate Incident in Taiwan (RAPIT) project study from 2012 to 2016. Morning spot urine samples were analyzed for nine phthalate metabolites. Serum thyroid (triiodothyronine [T], thyroxine [T], and free T) and growth hormone (insulin-like growth factor-1 [IGF-1] and its binding protein 3 [IGF-BP3]) levels were measured. A generalized estimating equation model was used to evaluate associations between phthalate metabolite levels and children's thyroid and growth hormone levels.

Results: The median metabolite levels of monomethyl phthalate (MMP), Σdibutyl phthalate (DBP), and Σdi-(2-ethylhexyl) phthalate (DEHP) at visits 1, 2, and 3 were 6.59, 10.5, and 21.0 ng/mL, 0.15, 0.24, and 0.20 nmol/mL, and 0.15, 0.17, and 0.12 nmol/mL, respectively. After adjusting for potential confounding factors, we found that levels of urinary MMP were negatively associated with T (β = -0.013, p = 0.047), T (β = -0.016, p = 0.006), free T (β = -0.012, p = 0.002), and IGF-BP3 (β = -0.025, p = 0.003). Urinary mono-ethyl phthalate (MEP) was negatively associated with IGF-1 (β = -0.027, p = 0.029) and IGF-BP3 (β = -0.016, p = 0.018). In addition, serum free T was positively associated with urinary mono-2-ethyl-5-hydroxy hexyl phthalate (MEHHP) (β = 0.016, p = 0.043), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 0.015, p = 0.024), and ΣDEHPm (β = 0.019, p = 0.020).

Conclusions: Our findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products.
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http://dx.doi.org/10.1016/j.envpol.2020.114648DOI Listing
September 2020

Metformin Treatment Is Associated with a Decreased Risk of Nonproliferative Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study.

J Diabetes Res 2020 19;2020:9161039. Epub 2020 Apr 19.

Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.

Purpose: To assess the relationship between metformin use and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate the effect of metformin dosage on reducing the incidence of DR.

Methods: The study population included patients with newly diagnosed T2DM, who were aged ≥20 years and prescribed with antidiabetic drug therapy lasting ≥90 days, as identified using the National Health Insurance Research Database between 2000 and 2012. We matched metformin users and nonusers by a propensity score. Cox proportional hazard regression analyses were used to compute and compare the risk of developing nonproliferative diabetic retinopathy (NPDR) in metformin users and nonusers.

Results: Overall, 10,044 T2DM patients were enrolled. Metformin treatment was associated with a lower risk of NPDR (aHR 0.76, 95% CI 0.68-0.87) and sight-threatening diabetic retinopathy (STDR, aHR 0.29, 95% CI 0.19-0.45); however, the reduction in risk was borderline significant for STDR progression among NPDR patients (aHR 0.54, 95% CI 0.28-1.01). Combination therapy of metformin and DPP-4i exhibited a stronger but inverse relationship with NPDR development (aHR 0.32, 95% CI 0.25-0.41), especially at early (<3 months) stages of metformin prescription. These inverse relationships were also evident at different metformin doses and in adapted Diabetes Complications Severity Index scores (aDCSI). Moreover, combination therapy of metformin with sulfonylureas was associated with an increased risk of NPDR.

Conclusion: Metformin treatment in patients with T2DM was associated with a reduced risk of NPDR, and a potential trend was found for a reduced STDR risk in patients who had previously been diagnosed with NPDR. Combining metformin with DPP-4i seemingly had a significantly beneficial effect against NPDR risk, particularly when aDCSI scores were low, and when metformin was prescribed early after T2DM diagnosis. These results may recommend metformin for early treatment of T2DM.
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http://dx.doi.org/10.1155/2020/9161039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189314PMC
February 2021

Collateral Benefit of COVID-19 Control Measures on Influenza Activity, Taiwan.

Emerg Infect Dis 2020 08 27;26(8):1928-1930. Epub 2020 Apr 27.

Taiwan has strictly followed infection control measures to prevent spread of coronavirus disease. Meanwhile, nationwide surveillance data revealed drastic decreases in influenza diagnoses in outpatient departments, positivity rates of clinical specimens, and confirmed severe cases during the first 12 weeks of 2020 compared with the same period of 2019.
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http://dx.doi.org/10.3201/eid2608.201192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392415PMC
August 2020

Impact of cooking oil fume exposure and fume extractor use on lung cancer risk in non-smoking Han Chinese women.

Sci Rep 2020 04 21;10(1):6774. Epub 2020 Apr 21.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Smoking tobacco is the major risk factor for developing lung cancer. However, most Han Chinese women with lung cancer are nonsmokers. Chinese cooking methods usually generate various carcinogens in fumes that may inevitably be inhaled by those who cook the food, most of whom are female. We investigated the associations of cooking habits and exposure to cooking fumes with lung cancer among non-smoking Han Chinese women. This study was conducted on 1,302 lung cancer cases and 1,302 matched healthy controls in Taiwan during 2002-2010. Two indices, "cooking time-years" and "fume extractor use ratio," were developed. The former was used to explore the relationship between cumulative exposure to cooking oil fumes and lung cancer; the latter was used to assess the impact of fume extractor use for different ratio-of-use groups. Using logistic models, we found a dose-response association between cooking fume exposure and lung cancer (odds ratios of 1, 1.63, 1.67, 2.14, and 3.17 across increasing levels of cooking time-years). However, long-term use of a fume extractor in cooking can reduce the risk of lung cancer by about 50%. Furthermore, we provide evidence that cooking habits, involving cooking methods and oil use, are associated with risk of lung cancer.
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http://dx.doi.org/10.1038/s41598-020-63656-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174336PMC
April 2020

Long-Term Exposure to Ambient Hydrocarbons Increases Dementia Risk in People Aged 50 Years and above in Taiwan.

Curr Alzheimer Res 2019 ;16(14):1276-1289

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.

Background: Alzheimer's disease, the most common cause of dementia among the elderly, is a progressive and irreversible neurodegenerative disease. Exposure to air pollutants is known to have adverse effects on human health, however, little is known about hydrocarbons in the air that can trigger a dementia event.

Objective: We aimed to investigate whether long-term exposure to airborne hydrocarbons increases the risk of developing dementia.

Method: The present cohort study included 178,085 people aged 50 years and older in Taiwan. Cox proportional hazards regression analysis was used to fit the multiple pollutant models for two targeted pollutants, including total hydrocarbons and non-methane hydrocarbons, and estimated the risk of dementia.

Results: Before controlling for multiple pollutants, hazard ratios with 95% confidence intervals for the overall population were 7.63 (7.28-7.99, p <0.001) at a 0.51-ppm increases in total hydrocarbons, and 2.94 (2.82-3.05, p <0.001) at a 0.32-ppm increases in non-methane hydrocarbons. The highest adjusted hazard ratios for different multiple-pollutant models of each targeted pollutant were statistically significant (p <0.001) for all patients: 11.52 (10.86-12.24) for total hydrocarbons and 9.73 (9.18-10.32) for non-methane hydrocarbons.

Conclusion: Our findings suggest that total hydrocarbons and non-methane hydrocarbons may be contributing to dementia development.
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http://dx.doi.org/10.2174/1567205017666200103112443DOI Listing
October 2020

Predicting Lung Cancer Occurrence in Never-Smoking Females in Asia: TNSF-SQ, a Prediction Model.

Cancer Epidemiol Biomarkers Prev 2020 02 17;29(2):452-459. Epub 2019 Dec 17.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Background: High disease burden suggests the desirability to identify high-risk Asian never-smoking females (NSF) who may benefit from low-dose CT (LDCT) screening. In North America, one is eligible for LDCT screening if one satisfies the U.S. Preventive Services Task Force (USPSTF) criteria or has model-estimated 6-year risk greater than 0.0151. According to two U.S. reports, only 36.6% female patients with lung cancer met the USPSTF criteria, while 38% of the ever-smokers ages 55 to 74 years met the USPSTF criteria.

Methods: Using data on NSFs in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma and the Taiwan Biobank before August 2016, we formed an age-matched case-control study consisting of 1,748 patients with lung cancer and 6,535 controls. Using these and an estimated age-specific lung cancer 6-year incidence rate among Taiwanese NSFs, we developed the Taiwanese NSF Lung Cancer Risk Models using genetic information and simplified questionnaire (TNSF-SQ). Performance evaluation was based on the newer independent datasets: Taiwan Lung Cancer Pharmacogenomics Study (LCPG) and Taiwan Biobank data after August 2016 (TWB2).

Results: The AUC based on the NSFs ages 55 to 70 years in LCPG and TWB2 was 0.714 [95% confidence intervals (CI), 0.660-0.768]. For women in TWB2 ages 55 to 70 years, 3.94% (95% CI, 2.95-5.13) had risk higher than 0.0151. For women in LCPG ages 55 to 74 years, 27.03% (95% CI, 19.04-36.28) had risk higher than 0.0151.

Conclusions: TNSF-SQ demonstrated good discriminative power. The ability to identify 27.03% of high-risk Asian NSFs ages 55 to 74 years deserves attention.

Impact: TNSF-SQ seems potentially useful in selecting Asian NSFs for LDCT screening.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1221DOI Listing
February 2020

Long-term ambient hydrocarbons exposure and incidence of ischemic stroke.

PLoS One 2019 4;14(12):e0225363. Epub 2019 Dec 4.

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.

Exposure to air pollutants is known to have adverse effects on human health; however, little is known about the association between hydrocarbons in air and an ischemic stroke (IS) event. We investigated whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increased IS risk. This retrospective cohort study included 283,666 people aged 40 years or older in Taiwan. Cox proportional hazards regression analysis was used to fit single- and multiple-pollutant models for two targeted pollutants, total hydrocarbons (THC) and nonmethane hydrocarbons (NMHC), and estimated the risk of IS. Before controlling for multiple pollutants, hazard ratios (HRs) of IS with 95% confidence intervals for the overall population were 2.69 (2.64-2.74) at 0.16-ppm increase in THC and 1.62 (1.59-1.66) at 0.11-ppm increase in NMHC. For the multiple-pollutant models controlling for PM2.5, the adjusted HR was 3.64 (3.56-3.72) for THC and 2.21 (2.16-2.26) for NMHC. Our findings suggest that long-term exposure to THC and NMHC may be a risk factor for IS development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225363PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892494PMC
March 2020

Phthalate exposure and prostate cancer in a population-based nested case-control study.

Environ Res 2020 02 8;181:108902. Epub 2019 Nov 8.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan. Electronic address:

Background: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence.

Methods: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence.

Results: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm.

Conclusions: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.
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http://dx.doi.org/10.1016/j.envres.2019.108902DOI Listing
February 2020

Incidence of retinal vein occlusion with long-term exposure to ambient air pollution.

PLoS One 2019 24;14(9):e0222895. Epub 2019 Sep 24.

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.

This study aimed to investigate whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increases the risk of developing retinal vein occlusion (RVO) among the population of Taiwan. A retrospective cohort study involving 855,297 people was conducted. Cox proportional hazards regression analysis fitted the multiple pollutant models for two targeted pollutants, including total hydrocarbons (THC), nonmethane hydrocarbons (NMHC) were used, and the risk of RVO was estimated. The chi-squared test and one-way analysis of variance were used to test differences in demographics and comorbidity distribution among tertiles of the targeted pollutants. Before controlling for multiple pollutants, hazard ratios for the overall population were 19.88 (95% CI: 17.56-22.50) at 0.51-ppm increases in THC and 4.33 (95% CI: 3.97-4.73) at 0.27-ppm increases in NMHC. The highest adjusted hazard ratios for different multiple pollutant models of each targeted pollutant were statistically significant (all p values were ≤0.05) for all patients at 29.67 (95% CI: 25.57-34.42) for THC and 16.24 (95% CI: 14.14-18.65) for NMHC. Our findings suggest that long-term exposure to THC and NMHC contribute to RVO development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222895PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759191PMC
April 2020
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