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Introduction: Effective communication between doctors and patients is crucial for the well-being of individuals diagnosed with cancer. This study aimed to develop and validate a cancer-specific Doctor-Patient Communication Satisfaction Scale (DPCSS-Cancer) from the patients' perspective., Methods: Initial items were generated through literature review. Content validity was assessed via feedback from five experts, while face validity was determined through cognitive interviews with 13 patients. The revised DPCSS-Cancer was subsequently tested in a sample of 200 cancer patients to assess test-retest stability, internal consistency, factor structure, and criterion-related validity., Results: The development process resulted in a 15-item DPCSS-Cancer across two dimensions, using a 4-point rating scale (1 = strongly disagree to 4 = strongly agree). The item-level Content Validity Index (I-CVI) ranged from 0.8 to 1.0, with a scale-level CVI of 0.96. Following expert and patient feedback, no items were eliminated, but modifications were made to item wording. In formal testing, the overall Cronbach's alpha was 0.96, with 0.89 for the first dimension and 0.95 for the second. Test-retest reliability was established at 0.82. The two-dimensional structure was partially confirmed. Criterion-related validity was supported through a significant positive correlation with a measure of trust in the physician (r = 0.86). Factors contributing to higher DPCSS-Cancer scores were identified., Conclusion: The DPCSS-Cancer shows satisfactory reliability and validity, making it a viable patient-reported outcome measure for assessing cancer patients' satisfaction with doctor-patient communication., Competing Interests: Declarations Ethics approval The study was approved by The Chang Gung Memorial Hospital's Human Research Ethics Committee (Case number: 202001084B0). Consent to participate Informed consent was obtained from all individual participants included in the study. Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neonicotinoid insecticides (NEOs) dominate the global pesticide market because of their low cost and effectiveness. However, epidemiological studies regarding the potential adverse health effects of exposure to NEOs before birth and in early childhood are limited. Therefore, this study investigated the associations between NEO exposure before birth and during early childhood and neurodevelopment. A total of 273 mother-child pairs were enrolled in this study. Mothers provided urine samples in the third trimester and breast milk during the first and third months of lactation. Their children provided urine samples and were evaluated for neurodevelopment by using the Bayley Scales of Infant and Toddler Development, Third Edition at 2-3 years (N = 96) and the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) at 4-6 years (N = 63). The sum of the concentrations of seven NEOs (ΣNEOs) and the relative potency factor of NEOs, based on comparison with imidacloprid (IMI RPF ), were used to assess total exposure to NEOs. Multivariate linear regression analyses were conducted to assess the associations between prenatal and childhood exposure to NEOs and neurodevelopment. The results of the analysis revealed that clothianidin (CLO) and thiamethoxam were the most common NEOs to which children in the Taipei metropolitan area were exposed and that exposure concentrations were high in the Taipei metropolitan area. Imidacloprid was the most frequently detected NEO during the postnatal period. Additionally, exposure to NEOs through breast milk was low. Exposure to CLO, ΣNEOs, and IMI RPF in boys aged 4-6 years was negatively correlated with WPPSI-IV Fluid Reasoning Index. The results of this study indicate that exposure during the third trimester to NEOs does not affect neurodevelopment but that childhood exposure to NEOs may, especially for boys. Further studies with larger sample sizes are required to confirm the sex-specific associations between NEO exposure and neurodevelopment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The association of anosmia/ageusia with a positive severe respiratory syndrome coronavirus 2 (SARS-CoV-2) test is well-established, suggesting these symptoms are reliable indicators of coronavirus disease 2019 (COVID-19) infection. This study investigates the clinical characteristics and systemic inflammatory markers in hospitalized COVID-19 patients in Taiwan, focusing on those with anosmia/ageusia. We conducted a retrospective observational study on 231 hospitalized COVID-19 patients (alpha variant) from April to July 2021. Clinical symptoms, dyspnea grading, and laboratory investigations, including neutrophil-lymphocyte ratios (NLRs), platelet-lymphocyte ratios (PLRs), and ANDC scores (an early warning score), were analyzed. Cough (64.1%), fever (58.9%), and dyspnea (56.3%) were the most common symptoms, while anosmia/ageusia affected 9% of patients. Those with anosmia/ageusia were younger, had lower BMI, lower systemic inflammatory markers, and better ANDC scores than those without these symptoms. Female patients exhibited lower NLR values and ANDC scores compared to male patients (all p < 0.05). Multivariable regression analysis demonstrated significant associations between NLR and CRP and ferritin levels (all p < 0.01), and between PLR and ESR and ferritin levels (p < 0.01). Categorized ANDC scores significantly correlated with the total hospital length of stay (all p < 0.05). Despite ethnic differences in the prevalence of anosmia/ageusia, our study highlights similar clinical presentations and inflammatory profiles to those observed in Western countries. The ANDC score effectively predicted hospital stay duration. These findings suggest that anosmia/ageusia may be associated with less severe disease and a lower inflammatory response, particularly in younger and female patients. The ANDC score can serve as a valuable prognostic tool in assessing the severity and expected hospital stay of COVID-19 patients., (© 2024. The Author(s).)

Background: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear., Object: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD)., Methods: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD., Results: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs., Conclusions: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Childhood and adolescent mental health problems may increase the global burden of disease. Neurotoxic metals are associated with inflammation and cytotoxicity in the brain. In addition, prenatal phthalate ester (PAE) exposure is associated with cognitive function deficits. However, the effect of co-exposure to toxic metals, PAEs, and their association with child behavior is less well studied. Hence, we aimed to investigate prenatal co-exposure to the metals and PAEs and the consequent behavioral outcomes in early childhood., Methods: We followed pregnant women and their newborns from the Taiwan Maternal and Infant Cohort Study between 2015 and 2017, with a focus on women from the central, southern, and eastern areas of Taiwan. We quantified maternal urinary concentrations of metals and metabolites of PAEs as surrogates of prenatal exposure. We recorded the Child Behavior Checklist scores according to caregiver reports at 4 years of age, and identified Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-oriented problems., Results: Ultimately, 408 children were included in the statistical analysis. Maternal urinary copper levels were significantly associated with depressive problems (odds ratio [OR] = 2.13) in children. Maternal urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) were also significantly associated with depressive symptoms (odds ratio [OR] = 1.51 and 1.53, respectively). Further analysis considering prenatal co-exposure to metals and PAEs showed that co-exposure to these materials was significantly associated with autism spectrum problems (OR = 3.11)., Conclusions: We observed that prenatal single exposure or co-exposure to metals and PAEs may play a role in some DSM-5-oriented problems in children at 4 years of age. Reduction of exposure to toxic metals and PAEs in pregnancy is suggested to prevent increased mental health problems in children., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Previous studies have shown associations between prenatal phthalate exposure and neurobehavioral changes in children. However, few studies have focused on neonatal neurobehavioral development. This study aimed to examine the associations between prenatal phthalate exposure and neonatal neurobehavioral development in the early days of life after birth. This cohort study included 283 mother-infant pairs who participated in the Taiwan Mother Infant Cohort Study during 2012-2015. Each mother was interviewed, and urine samples were collected during the third trimester of pregnancy (weeks 29-40). Eleven common phthalate metabolites in maternal urine were analyzed. The Chinese version of the Neonatal Neurobehavioral Examination was used to evaluate early infant neurobehavioral development within five days of birth. We performed multiple linear regressions to explore the associations between phthalate exposure and neonatal neurobehavioral development. Sex differences in the association between phthalate metabolites and neonatal neurobehaviors were noted. Among girls, tertiles of phthalate metabolite concentrations were associated with worse behavioral responses and tone and motor patterns in the high-molecular-weight phthalate (HMW) and low-molecular-weight phthalate (LMW) groups. Girls in the highest tertile of di-2-ethylhexyl phthalate (DEHP) and mono-isobutyl phthalate (MiBP) had a negative association with tone and motor patterns. Girls in the highest tertile of mono-n-butyl phthalate (MnBP) and MiBP showed a negative association with behavioral responses. In contrast, tertiles of phthalate metabolite exposure were associated with improved neurobehaviors in mono-methyl phthalate (MMP) among boys. The highest tertile of MMP was positively associated with behavioral responses, primitive reflexes, and tone and motor patterns. Our findings suggest that maternal phthalate exposure affects neonatal neurobehavioral development in a sex-specific manner. Despite the relatively small sample size, our findings add to the existing research linking maternal phthalate exposure to neonatal neurobehavioral development. Additional research is needed to determine the potential long-term effects of prenatal phthalate exposure on children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chronic kidney disease (CKD) is a chronic and often irreversible disease that requires active self-care to mitigate adverse outcomes. This study aimed to analyze the associations of demographic and disease data, frailty, health literacy (HL), and CKD self-care (CKDSC) in patients with CKD. We conducted a cross-sectional study at two hospitals in Taiwan. A total of 144 CKD patients with a mean age of 66.8 ± 9.1 years were included in the study. Among them, 79.2% were in CKD G3, and the mean time since diagnosis of CKD was 86 ± 48 months. Approximately 62.5% were identified as non-frail. The mean of HL and CKDSC were 11.76 ± 4.10 and 62.12 ± 9.31. In multivariate linear regression analysis, age ≥ 65 years (odds ratio (OR) = 5.67, 95% confidence interval (CI) 1.59-9.75), non-frailty (OR = 2.19, 95% CI 0.02-5.40), and high critical HL (OR = 1.43, 95% CI 0.13-2.90) showed significant positive correlation with CKDSC. Therefore, management of patients with CKD should focus on the young population, reinforcing health education strategies that improve critical HL and preventing frailty that may interfere with self-care. In addition, the patient's social support resources should be expanded to achieve the goal of CKDSC.

We determined the urinary levels of acrylamide (AA) metabolites of the general Taiwanese population, explore the association between AA internal exposure and dietary intake frequency, and assess the health risk. Urine samples and dietary questionnaires were collected from the subjects of the Nutrition and Health Survey in Taiwan. AA metabolite [N-acetyl-S-(propionamide)-cysteine (AAMA)] concentrations were analyzed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-ToF-MS). Multiple regression was used to examine associations between AA metabolite levels and dietary patterns. A total of 706 subjects were studied. We found that per increase in weekly frequency of sweetened beverages in the 6-11-years group (β = 0.322, p = 0.018) and oily snacks intakes in the 12-18-years group (β = 0.335, p = 0.012) will increase 10 β of urinary AAMA concentrations. Assuming that 50% of the AA intake is excreted as urinary AAMA, the Monte Carlo simulation showed that 1.75-19.48% among all age groups have exceeded the reference dose of 2 μg/kg-body weight/day., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To determine if both gestational diabetes mellitus (GDM) and maternal overweight/obesity are independently associated with delivery of large-for-gestational-age (LGA) babies in Taiwan., Materials and Methods: Anthropometric parameters were measured and 75-g oral glucose-tolerance tests were administered to a cohort of 1428 pregnant women at 24-28 weeks gestation at nine hospitals in Taiwan. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Study Groups criteria. Reported pre-pregnancy BMI and measured BMI during pregnancy were recorded at the late stage of the second trimester and the third trimester. Neonatal anthropometrics were measured at delivery. Primary outcome was LGA, defined in this study as having a birth weight ≥90th percentile for gestational age defined by WHO or a Chinese growth reference, taking into consideration the racial/ethnic and environmental differences in growth around the world. Multiple logistic regression was used to examine associations of GDM and maternal overweight/obesity with outcomes., Results: Based on WHO growth reference definition of LGA, subjects with pre-pregnancy BMI ≥24 and pregnancy BMI >28.4 were found to be 2.46 times (0.76-7.97) and 3.28 times (1.01-10.60), respectively, more likely to deliver LGA babies than subjects with normal pre-pregnancy and pregnancy BMIs. Compared to those without GDM, subjects with GDM were 7.55 (1.62-35.25) times more likely to deliver LGA babies. The odds ratios for delivering a baby with a birth weight ≥90th percentile were 11.40 (1.65-78.75) for those with GDM alone, 4.10 (1.07-15.65) for those with overweight/obesity alone and 15.75 (1.30-190.40) for those with both GDM and overweight/obesity, compared to those with no GDM and no overweightness. Women with both pre-pregnancy and pregnancy overweightness/obesity were 3.64 (1.07-12.34) times more likely to deliver LGA. The above results remained similar when analyzing data based on Chinese growth reference definition of LGA., Conclusion: Maternal overweightness/obesity and GDM are independently associated with LGA. Their combination had a greater impact than either one alone., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

The Taiwan Maternal and Infant Cohort Study (TMICS) was launched with the aim to assess the effects of prenatal exposure to phthalic acid esters (PAEs) on infant health. A total of 1102 pregnant women were enrolled in this study from 2012 to 2015. All participants completed a structured questionnaire, and provided urine specimens. The urinary concentrations of PAE metabolites in the third trimester were measured using liquid chromatography-electrospray ionization tandem mass spectrometry. Generalized additive model-penalized regression splines and logistic regression models were employed to determine the risk for low birth weight (LBW) or small for gestational age (SGA) among pregnant women exposed to PAEs. After adjustments for other covariates, each incremental unit of ln-transformed mono-n-butyl phthalate (MnBP) for pregnant women increased the odds of SGA in male neonates by 1.44 (95% CI: 0.92-2.23). An inverse association between SGA and maternal MnBP exposure level was observed in female neonates. An increase in one ln-transformed MnBP concentration unit decreased the risk of female SGA to 0.50 (95% CI: 0.24-0.97). In the penalized regression splines, increased risks of LBW/SGA in male neonates were presented while pregnant women exposed to increased MnBP levels. However, an association in the opposite direction was observed between maternal MnBP and LBW or SGA for male and female neonates. This study indicated that high maternal MnBP exposure in the third trimester was associated with LBW or SGA for male infants. Adverse effects on susceptible populations exposed to high levels of PAEs should be of concern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in ~7% of school-aged children. The role of endocrine-disrupting chemicals (EDC) and oxidative stress in ADHD etiology are not clear., Objective: Assessment of the associations between simultaneous exposure to multiple compounds and ADHD in children., Methods: The case-control study included 76 clinically diagnosed ADHD cases and 98 controls, aged 4-15 years old. Concentrations quartiles of urinary metabolites of acrylamide, acrolein, nonylphenol, phthalates, and organophosphate pesticides and biomarkers of oxidative stress were used to fit logistic regressions for each compound and weighted quantiles sum (WQS) regression for the mixture., Results: Positive dose-response relationships with ADHD were observed for 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) (odds ratio(OR) Q4  = 3.73, 95%CI [1.32, 11.04], p trend  = 0.003), dimethyl phosphate (DMP) (OR Q4  = 4.04, 95%CI [1.34, 12.94], p trend  = 0.014) and diethyl phosphate (OR Q4  = 2.61, 95%CI = [0.93, 7.66], p trend  = 0.030), and for the mixture of compounds (OR WQS  = 3.82, 95%CI = [1.78, 8.19]) with the main contributions from HNE-MA (28.9%) and DMP (18.4%)., Conclusions: The dose-response relationship suggests enhanced susceptibility to EDC burden in children even at lower levels, whereas the main risk is likely from organophosphate pesticides. HNE-MA is recommended as a sensitive biomarker of lipid peroxidation in the further elucidation of the oxidative stress role in ADHD etiology., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In 2011, phthalates, mainly di-(2-ethylhexyl) phthalate (DEHP), were found to have been added to a variety of foods in Taiwan, increasing the risk of microalbuminuria in children. Exposure to melamine perhaps modifies that risk. This prospective cohort study investigates whether renal injury resulting from exposure to DEHP-tainted foods from the 2011 Taiwan Food Scandal is reversed over time. The temporal and interactive effects of past daily DEHP intake, current daily DEHP intake, and urinary melamine levels on oxidative stress and renal injury were also examined. Two hundred possibly DEHP-affected children (aged < 18 years) were enrolled in the first survey wave (August 2012-January 2013), with 170 and 159 children in the second (July 2014-February 2015) and third waves (May 2016-October 2016), respectively. The first wave comprised questionnaires that were used to collect information about possible past daily DEHP intake from DEHP-tainted foods. One-spot first morning urine samples were collected to measure melamine levels, phthalate metabolites, and markers indicating oxidative stress (malondialdehyde and 8-oxo-2'-deoxyguanosine), and renal injury (albumin/creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase) in all three waves. Generalized estimating equation (GEE) modeling revealed that both past daily DEHP intake and time might affect urinary ACR. However, most interactions were negative and significant correlation was observed only during the second wave (P for interaction = 0.014) in the group with the highest past daily DEHP intake (>50 μg/kg/day). Urinary melamine levels were found to correlate significantly with both urinary ACR and oxidative stress markers. The highest impact associated with exposure to DEHP-tainted foods in increasing urinary ACR of children was observed during the first wave, and the effect may partially diminish over time. These results suggest that continuous monitoring of renal health and other long-term health consequences is required in individuals who were affected by the scandal in 2011., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Tonsillectomy has been suggested as an intervention to resolve psoriasis., Objective: This study aimed to investigate the subsequent risk of psoriasis in patients who received tonsillectomy., Methods: We used data from the Taiwan National Health Insurance Research Database. The tonsillectomy group (case group) and the tonsillectomy-free group (comparison group) were matched at a ratio of 1:4 by demographic data, comorbidities, medical confounders, and the index date. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: We identified 2021 patients as the case group and matched 8084 individuals as the comparison group. The adjusted HR (aHR) of psoriasis was 0.43 (95% CI, 0.22-0.87; P < .05). The study population is composed of a mainly male (65%) and young population (mostly younger than 50 years). Notably, patients with rheumatoid arthritis increased the risk of psoriasis (aHR, 3.97; 95% CI, 1.17-13.48; P < .05). In our stratification analysis, the risk of psoriasis decreased in almost all subgroups., Limitation: Our database did not include information on genome and the subtypes of psoriasis., Conclusion: Our study showed a decreased risk of psoriasis in the tonsillectomy group after adjustment for baseline characteristics, comorbidities, and medical confounders compared with the reference group., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: The prevalence of atopic dermatitis has substantially increased in recent decades, and atopic dermatitis could lead to allergic airway inflammation later in life. A previous study found that inorganic arsenic exposure was associated with allergic airway inflammation in children aged 8 to 14 years. However, the association between prenatal exposure to arsenic and other metals and the risk of atopic dermatitis among young children remains unknown., Objective: To assess the association between prenatal exposure to arsenic and other metals and the occurrence of atopic dermatitis in children at age 4 years., Design, Setting, and Participants: In total, 1152 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 586 mothers and children aged 4 years participated in follow-up questionnaire interviews from August 2016 to January 2019. After excluding 216 participants with missing data, the final statistical analysis of follow-up data included 370 mother and child pairs from the central and eastern regions of Taiwan. Data were analyzed from February 2 to August 12, 2021., Exposures: Arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc during pregnancy., Main Outcomes and Measures: The outcome was parent-reported atopic dermatitis history among children aged 4 years. The presence of atopic dermatitis was defined as a positive response to the question, "Has your child ever had atopic dermatitis diagnosed by a physician?" During the initial TMICS study period, concentrations of arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc were measured in maternal urine during the third trimester of pregnancy using an inductively coupled plasma mass spectrometer. Estimated total inorganic arsenic exposure was calculated using a model that included data on both total arsenic and arsenic species (arsenite, arsenate, monomethylarsonate, and dimethylarsenate) obtained from a previous TMICS cohort., Results: Among 370 children included in the analysis, the mean (SD) age was 3.94 (0.59) years; 208 children (56.2%) were male, and 267 children (72.2%) were from the central region of Taiwan. A total of 110 children (29.7%) had atopic dermatitis at age 4 years. Maternal estimated total inorganic arsenic exposure during pregnancy was associated with increased odds of atopic dermatitis among children at age 4 years (odds ratio [OR], 2.42 [95% CI, 1.33-4.39] for every doubled increase of total inorganic arsenic) after adjusting for parental allergies, child's sex, geographic area, maternal educational level, and exposure to tobacco smoke. Every increased unit in the weighted quantile sum index of maternal metal exposure was significantly associated with atopic dermatitis (OR, 1.63; 95% CI, 1.28-2.07). Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal mixture index., Conclusions and Relevance: This cohort study found that prenatal exposure to inorganic arsenic and coexposure to inorganic arsenic and cadmium were associated with a higher risk of atopic dermatitis in young children. These findings suggest that prevention of exposure to inorganic arsenic and cadmium during pregnancy may be helpful for the control of atopic dermatitis and other potential allergies in children.

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 μg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.

Background: Exposure to either melamine or phthalate, two common toxicants, during pregnancy may cause adverse health effects, including kidney damage., Objectives: We investigated the independent and interactive effect of exposure to melamine and phthalates, particularly di-(2-ethylhexyl) phthalate (DEHP), on markers of early renal injury in women their third trimester of pregnancy in one nationwide birth cohort, the Taiwan Maternal and Infant Cohort Study (TMICS)., Methods: Between October, 2012 and May, 2015, participants were administered questionnaires, physical examinations, and blood and urine tests during their third trimester. One-spot overnight urine specimens were used to simultaneously measure melamine, 11 phthalate metabolites, and two markers of renal injury, microalbumin and N-acetyl-beta-D-glucosaminidas (NAG). Estimated daily DEHP intake was calculated based on measurement of three urinary DEHP metabolites. Microalbuminuria was defined as having a urinary albumin/creatinine ratio (ACR) higher than 3.5 mg/mmol., Results: Total 1433 pregnant women were analyzed. The median value for urinary melamine was 0.63 μg/mmol Cr and estimated DEHP intake was 1.84 μg/kg/day. We found subjects in the highest quartile of estimated DEHP intake to have significantly higher urinary ACR (β = 0.095, p = 0.043) and the prevalence of microalbuminuria (adjusted OR = 1.752, 95% confidence interval = 1.118-2.746), compared to those in the lowest quartile. In addition, there was a significant interactive effect between urinary melamine and estimated DEHP intake on urinary ACR and NAG., Conclusion: Our results suggest these two ubiquitous chemicals together may be associated with markers of early kidney injury in pregnant women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We investigated the correlation between a history of human papillomavirus (HPV) infection and alopecia areata risk., Methods: The study cohort comprised 30,001 patients with newly diagnosed HPV infection between 2000 and 2012; and with use of computer-generated randomly numbers, patients not had HPV infection were randomly selected as the comparison cohort. HPV infection cohort were matched to comparison individuals at a 1:1 ratio by age, gender and index year. All study individuals were followed up until they developed alopecia areata, withdraw from the insurance program, lost to follow-up, or until the end of 2013. Cox proportional hazards regression analysis was used to analyze the risk of alopecia areata with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort., Results: The adjusted hazard ratio (aHR) of alopecia areata for HPV patients relative to controls was 2.55 (95% C.I. = 1.88-3.47) after adjusting sex, age and comorbidities. Subgroup analysis indicated that patients with HPV infections had a significantly greater risk of alopecia areata for both genders, all age subgroups, and those with mental disorder diseases., Conclusions: A history of HPV infection is associated with the development of subsequent alopecia areata in Taiwanese subjects., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: To identify different classes of change pattern/ trajectory of tobacco smoking behaviour after diagnosis of lung cancer using multi-wave data and to explore factors associated with the class membership., Design: This is a multi-wave observational study., Methods: Smoking behaviour data were collected at diagnosis and then every month for 6 months from 133 newly diagnosed people with lung cancer who had recently quit smoking or continued to smoke at diagnosis. These patients were recruited from three medical centres and data were collected from May 2014 to January 2017. Smoking behaviour was assessed based on patients' self-reports on whether they smoked during the last month (yes/no) for a total of seven times. Mixture latent Markov model and logistic regression were used to analyse data., Results: Two latent classes of smoking trajectory were identified among recent quitters or current smokers of people with lung cancer, namely "perseverance for abstinence" and "indecisive for abstinence." Patients who were younger age (OR = 0.95, p = 0.026), exposure to second-hand smoke (OR = 3.35, p = 0.012) and lower self-efficacy for not smoking (OR = 0.96, p = 0.011) were more likely to belong to the class of "indecisive for abstinence.", Conclusions: Heterogeneous classes of smoking trajectory existed in newly diagnosed people with lung cancer. The risk factors associated with a less favourable smoking trajectory can be incorporated into tailored smoking-cessation programs for patients newly diagnosed with lung cancer., Impact: The dynamic trajectory of smoking behaviour had not been adequately explored among newly diagnosed people with lung cancer. Two classes of smoking trajectory and the predictors associated with the class membership were identified. These findings suggest that the diagnosis of cancer is a teachable moment for smoking cessation. Patients with younger age, lower self-efficacy of not smoking and exposure to second-hand smoke at home need special attention., (© 2020 John Wiley & Sons Ltd.)

Background: This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk., Materials and Methods: The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort., Results: The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44-4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58-5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results., Conclusion: A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later., Implications for Practice: In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients., (© 2020 AlphaMed Press.)

Purpose: To investigate the change in the prevalence of reduced visual acuity (VA) in Taiwanese school children after a policy intervention promoting increased time outdoors., Design: Prospective cohort study based on the Taiwan School Student Visual Acuity Screen (TSVAS) by the Ministry of Education in Taiwan., Participants: All school children from grades 1 through 6 were enrolled in the TSVAS from 2001 through 2015., Methods: The TSVAS requires each school in Taiwan to perform measurements of uncorrected VA (UCVA) on all students in grades 1 through 6 every half year using a Tumbling E chart. Reduced VA was defined as UCVA of 20/25 or less. Data from 1.2 to 1.9 million primary school children each year were collected from 2001 through 2015. A policy program named Tian-Tian 120 encouraged schools to take students outdoors for 120 minutes every day for myopia prevention. It was instituted in September 2010. To investigate the impact of the intervention, a segmented regression analysis of interrupted time series was performed., Main Outcome Measures: Prevalence of reduced VA., Results: From 2001 to 2011, the prevalence of reduced VA of school children from grades 1 through 6 increased from 34.8% (95% confidence interval [CI], 34.7%-34.9%) to 50.0% (95% CI, 49.9%-50.1%). After the implementation of the Tian-Tian 120 outdoor program, the prevalence decreased continuously from 49.4% (95% CI, 49.3%-49.5%) in 2012 to 46.1% (95% CI, 46.0%-46.2%) in 2015, reversing the previous long-term trend. For the segmented regression analysis controlling for gender and grade, a significant constant upward trend before the intervention in the mean annual change of prevalence was found (+1.58%; standard error [SE], 0.08; P < 0.001). After the intervention, the trend changed significantly, with a constant decrease by -2.34% annually (SE, 0.23; P < 0.001)., Conclusions: Policy intervention to promote increased time outdoors in schools was followed by a reversal of the long-term trend toward increased low VA in school children in Taiwan. Because randomized trials have demonstrated outdoor exposure slowing myopia onset, interventions to promote increased time outdoors may be useful in other areas affected by an epidemic of myopia., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Sexual dysfunction has been reported in women following treatment for gynecological cancer. However, the actual sexual activities adopted by these women are not well understood. The aims of this study were to (1) explore a relatively new concept, diversity of sexual activities (DSA), and (2) identify factors associated with DSA in women with gynecological cancer., Methods: This cross-sectional study included 136 Taiwanese long-term partnered women with gynecologic cancer treated in a large medical center. DSA was measured with the Diversity of Sexual Activities Scale, which assesses the number of sexual activities adopted in the past 6 months. Covariates included sexual knowledge and sexual attitudes, perceived changes in relationships of intimacy since treatment, and demographic and clinical factors., Results: The mean age of participants was 51.2 years (SD = 8.66); cancer diagnoses were cervical (50.7%), endometrial (31.6%), and ovarian (17.6%). The mean number of sexual activities was 2.88 (SD = 2.63); 29.4% of participants had no physical contact with their partners after treatment. The participants reported a significantly decreased overall satisfaction toward adopted sexual activities after cancer treatment. Lower DSA was associated with older age and receiving a combination of chemotherapy and radiotherapy., Conclusions: Cancer treatment has a significant impact on sexual activity in women with gynecological cancer. Around 30% of participants reported not having any physical contact with their partners since receiving cancer treatment. Sexual rehabilitation counseling that emphasizes alternative forms of sexual expression is suggested., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: The association between human papillomavirus (HPV) infection status and the natural process of kidney diseases has been neglected as an area of research. Further studies are needed to clarify factors that may alter the progression of end-stage kidney disease (ESKD)., Objective: To describe the rates of ESKD among patients with and without HPV infection., Design, Setting, and Participants: In this nationwide, population-based retrospective cohort study, data were collected from the National Health Insurance Research Database of Taiwan. A total of 76 088 individuals with HPV infection were enrolled from January 1, 2000, to December 31, 2012, and compared with a control group of 76 088 individuals who had never been diagnosed with HPV infection (at a 1:1 ratio propensity-score matched by age, sex, index year, and comorbidities) in the context of the risk of developing ESKD. Statistical analysis was performed between November 2019 and July 2020., Exposures: HPV infection was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes., Main Outcomes and Measures: The main outcome was ESKD, as recorded in the Catastrophic Illness Patients database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs, with the control group as a reference., Results: Of 152 176 individuals (79 652 [52.3%] women; mean [SD] age, 34.4 [19.1] years), 76 088 individuals (50.0%) had HPV and 463 individuals (0.3%) developed ESKD. Incidence of ESKD was lower in individuals with HPV history than in those without HPV history (3.64 per 10 000 person-years vs 4.80 per 10 000 person-years). In the fully adjusted multivariate Cox proportional hazards regression model, individuals with a history of HPV infection had a significant decrease in risk of ESKD (adjusted HR, 0.72; 95% CI, 0.60-0.87) after adjusting for demographic characteristics, comorbidities, and comedications. In the subgroup analysis, individuals ages 50 to 64 years with HPV infection had a statistically significantly lower risk of ESKD compared with individuals ages 50 to 64 years with no HPV infection (adjusted HR, 0.48; 95% CI, 0.34-0.68; P < .001), while there was no significant reduction in risk for the other age groups (ie, 0-19, 20-49, and 65-100 years)., Conclusions and Relevance: In this study, a history of HPV infection was associated with a lower risk of subsequent ESKD. The mechanism behind this protective association remains uncertain. Future studies are required to clarify the possible biological mechanisms.

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 3 ], thyroxine [T 4 ], and free T 4 ) 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 3 (β = -0.013, p = 0.047), T 4 (β = -0.016, p = 0.006), free T 4 (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 4 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., Competing Interests: Declaration of competing interest The authors declare that no competing interests exist. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: This study investigated whether patients with a history of human papillomavirus (HPV) infection are at increased risk of developing psoriasis., Methods: We enrolled 66 274 patients with HPV infection between 1997 and 2013 from the Taiwan National Health Insurance Research Database, and compared them with control individuals who had never been diagnosed with HPV infection (at a 1:4 ratio matched by age, sex and index year) in relation to the risk of developing psoriasis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with the control group as reference., Results: The adjusted hazard ratio (aHR) was 1.177 (95% CI, 1.010-1.373) after adjusting for demographic characteristics, comorbidities, dermatology-related outpatient visits and medications. The HPV group had an increased risk of psoriasis compared with the control group in all of the different age groups. The P-value for interaction between age and exposure of HPV is 0.009 in our sub-group analysis., Conclusions: A higher risk of psoriasis was found after HPV infection, and age acted as an effect modifier between the HPV infection and risk of psoriasis., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Exposure to occupational noise might increase the risk of hypertension. However, limited cohort studies have investigated the relationship between time-varying exposure to occupational noise and the development of hypertension., Methods: We conducted a 17-year cohort study involving 2459 workers to assess the relationship between time-varying exposure to occupational noise and incident hypertension in the aerospace industry. We performed an extended Cox proportional hazard model considering occupational noise exposure as time-varying covariates. Furthermore, we employed the distributed lag nonlinear models (DLNMS) to examine the exposure-response relationship., Results: In the extended Cox proportional model, as workers were exposed to noise over 80 dBA, the hazard ratios (HRs) of hypertension significantly increased with a noise increase of 5 dBA (HR = 1.16, 95% CI: 1.04-1.29). In exposure-response associations, the HRs of hypertension steadily increased between noise levels of 82 and 106 dBA (HRs ranged from 1.04 to 1.46). After additionally adjusting for personal protection equipment (PPE), the HRs decreased dramatically between 107 and 124 dBA (HRs ranged from 1.45 to 1.00)., Conclusions: Our study refined the exposure assessment by integrating time-varying exposures to occupational noise and taking work history into consideration. Our findings suggested that workers exposed to noise levels between 82 and 106 dBA for 3-17 years may increase the risk of hypertension with a non-linear exposure-response pattern. We further provided evidence that workers wearing PPE could effectively reduce noise exposure and avoid the development of hypertension., Competing Interests: Declaration of competing interest The work was supported by China Medical University (CMU 107-Z-04), Taichung, TAIWAN and National of Science Council (NSC102-2314-B-039-025), Taipei, TAIWAN. The authors declare they have no actual or potential competing financial interests., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Continued smoking after receiving a diagnosis of cancer seriously affects disease prognosis and survival. The prevalence and risk factors of continued smoking among patients with newly diagnosed lung cancer are unknown in Taiwan., Purpose: The aims of this study were to assess the smoking status of patients with newly diagnosed lung cancer and to identify the characteristics that are associated with different smoking statuses., Methods: Baseline data of a longitudinal study on smoking behaviors after lung cancer diagnosis were analyzed in this study. Patients were consecutively recruited from three medical centers in northern Taiwan. A structured questionnaire and medical chart reviews were used to collect data. Multinomial logistic regression analysis was used to examine the factors associated with continuing to smoke after being diagnosed with lung cancer., Results: Among the 406 patients with newly diagnosed lung cancer who were recruited, 47.0% were never-smokers and 53.0% were ever-smokers. Among the second group, 38% were former smokers, 18% were recent quitters, and 44% were current smokers. Compared with former smokers, current smokers were more likely to be younger (OR = 1.05), to not exercise regularly (OR = 2.74), to currently live with smokers (OR = 2.48), and to have lower self-efficacy for refusing to smoke (OR = 0.95). Compared with recent quitters, current smokers were more likely to have lower self-efficacy for refusing to smoke., Conclusions/implications for Practice: A significant proportion of ever-smoker lung cancer patients in Taiwan will continue to smoke after receiving their diagnosis. Variables known to modify the risk factors associated with continued smoking such as regular exercise and better refusal self-efficacy should be considered and incorporated into future smoking cessation programs for patients with lung cancer.

Parabens are a group of esters of parahydroxybenzoic acid and are utilized as antimicrobial preservatives in the majority of personal care products (PCPs). Epidemiological studies regarding the adverse effects of parabens on fetuses are still limited. The aim of this study was to determine the association between maternal paraben exposure and birth outcomes. One hundred and ninety-nine pregnant women were enrolled, and maternal urine was collected in the third trimester. The urine concentrations of four parabens (methyl (MP), ethyl (EP), propyl (PP), and butyl (BP)) were determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the association between paraben exposure levels and birth outcomes. A causal mediation analysis was conducted to determine the mediation effect of oxidative stress on birth outcomes. The geometric means of urinary MP, EP, PP, and BP were 51.79, 1.26, 4.21, and 1.25 μg/g cre., respectively. In the penalized regression splines, sex-specific associations between maternal MP levels and birth outcomes were observed; a downward curvature was observed between the MP level and birth weight, length, head circumference, and thoracic circumference among female newborns. Pregnant women in the group with MP levels above the third quartile had neonates with significantly lower body weight (β = -215.98 g, p value = 0.02) compared to those in the group with MP levels lower than the third quartile. No significant mediation of oxidative stress was observed between maternal MP exposure and female birth weight. The estimated proportion mediated ranged from -6% to 15%. The negative association between maternal paraben exposure and female birth outcomes in relation to child development should be carefully considered., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

This study determined whether maternal bisphenol A (BPA) exposure influences birth outcomes through oxidative stress and estimated the daily intake of BPA through breast milk for infants. One hundred and eighty-six pregnant women without pregnancy complications were enrolled and maternal urine was collected in the third trimester. Postnatal breast milk was collected in the first and third months after delivery. Concentrations of BPA were determined through ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the effects of BPA exposure and oxidative stress levels on birth outcomes. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to maternal BPA exposure on birth outcomes. The daily intake of BPA in breast milk was calculated using probabilistic risk assessment methods. The geometric means (geometric standard deviation) of BPA levels for maternal urine and first- and third-month breast milk were 2.19 (2.88) μg/g creatinine., 1.35 (3.53) ng/g, and 3.17 (2.97) ng/g, respectively. No significant mediation existed among maternal BPA exposure, oxidative stress level, and neonatal head circumference. Three percent of 1-monthold babies and 1% of 3-month-old babies exceeded the BPA tolerable daily intake of 4 μg/kg-bw/day proposed by the European Food Safety Authority. This study revealed the BPA exposure profile for pregnant women and infants in northern Taiwan. The marginally significant correlation between maternal BPA exposure and neonatal head circumference should be considered., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Data on clinical outcome after drug-eluting stent (DES) vs. bare-metal stent (BMS) implantation in patients with end-stage renal disease (ESRD) under hemodialysis are limited and controversial.Methods and Results:We identified 4,970 patients under chronic hemodialysis from Taiwan National Health Insurance Research Database (NHIRD) who had their first coronary stenting between 1 January 2007 and 31 December 2012. After 1:1 propensity score matching, we evaluated clinical outcomes for 1,151 patients in the DES group and 1,151 patients in the matched BMS group. We used ICD-9 CM codes or operation code to identify all outcomes in the study cohort after the index procedure. Primary outcomes including composite endpoints of mortality, non-fatal myocardial infarction (MI), non-fatal stroke, and revascularization after the index procedure were similar in both groups (HR, 0.94; 95% CI: 0.81-1.09; P=0.399). The results were consistent in various generations of DES vs. BMS groups. Secondary outcomes including mortality, non-fatal MI, non-fatal stroke, revascularization, cardiovascular death, hospitalization for heart failure, peptic ulcer bleeding or blood transfusion were similar in both groups, except for a lower risk of peptic ulcer disease in the DES group (HR, 0.59; 95% CI: 0.41-0.83; P=0.003) than the BMS group., Conclusions: In patients on chronic hemodialysis, implantation of DES did not have a better clinical outcome than BMS.

Background: Air pollution may cause specific genetic or epigenetic abnormalities and lead to the development of uterine fibroids (UFs). However, there have been limited studies evaluating the relationship between air pollutant exposure and the development of UFs., Methods: We conducted a 10-year cohort-based case-control study in Taiwan from 2001 to 2010 using National Health Institute Research Database (NHIRD) to assess the association between air pollution and the UFs development among Taiwanese women. The case group consisted of 11,028 women newly diagnosed with UFs during the study period and the control group was 44,112 women aged 25-45 years using density sampling with a 1:4 matching on the date of birth from 224,675 women in 2001-2010. The average age of onset was 36 ± 4.37 years old. Daily concentrations of PM 2.5 were estimated by linear mixed-effects model integrating aerosol optical depth (AOD) and meteorological variables; daily concentrations of O 3 , CO, NO 2 and SO 2 were calculated by the Inverse Distance Weighting (IDW). The annual cumulative exposure to air pollutants during the study period was calculated corresponding to residential zip codes., Results: In the conditional logistic regression adjusting for confounders, the adjusted odds ratio (aOR) for UFs per 10 μg/m 3 increase in PM 2.5 was 1.105 (95% confidence interval: 1.069, 1.141), per 10 ppb increase in O 3 was 1.075 (95% confidence interval: 1.039, 1.113), respectively., Conclusions: Our study suggests that exposure to PM 2.5 and O 3 may increase the risk of developing UFs. Further studies are needed to confirm this novel finding., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Recent genetic progress has allowed for the molecular diagnosis of Parkinson's disease. However, genetic causes of PD vary widely in different ethnicities. Mutational frequencies and clinical phenotypes of genes associated with PD in Asian populations are largely unknown. The objective of this study was to identify the mutational frequencies and clinical spectrums of multiple PD-causative genes in a Taiwanese PD cohort., Methods: A total of 571 participants including 324 patients with early-onset parkinsonism (onset age, <50 years) and 247 parkinsonism pedigrees were recruited at a tertiary referral center in Taiwan from 2002 to 2017. Genetic causes were identified by an integrated approach including gene dosage analysis, a targeted next-generation sequencing panel containing 40 known PD-causative genes, repeat-primed polymerase chain reaction, and whole-exome sequencing analysis., Results: Thirty of the 324 patients with early-onset parkinsonism (9.3%) were found to carry mutations in Parkin, PINK1, or PLA2G6 or had increased trinucleotide repeats in SCA8. Twenty-nine of 109 probands with autosomal-recessive inheritance of parkinsonism (26.6%) were found to carry mutations in Parkin, PINK1, GBA, or HTRA2. The genetic causes for the 138 probands with an autosomal-dominant inheritance pattern of parkinsonism were more heterogeneous. Seventeen probands (12.3%) carried pathogenic mutations in LRRK2, VPS35, MAPT, GBA, DNAJC13, C9orf72, SCA3, or SCA17. A novel missense mutation in the UQCRC1 gene was found in a family with autosomal-dominant inheritance parkinsonism via whole-exome sequencing analysis., Conclusions: Our findings provide a better understanding of the genetic architecture of PD in eastern Asia and broaden the clinical spectrum of PD-causing mutations. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

Purpose: The aim of the study was to investigate the effect of elastic band exercise activities on lower extremity rehabilitation in elderly patients subjected to an elastic band exercise intervention 2 and 4 weeks after total knee arthroplasty., Design: A quasiexperimental study was conducted. Participants were recruited from southern Taiwan who were over 65 years old and had a first unilateral total knee arthroplasty for osteoarthritis., Methods: The control and experimental groups comprised 25 patients each. The control group received conventional treatment after total knee arthroplasty; by contrast, the experimental group engaged in elastic band exercise activities demonstrated by instructors, in addition to receiving conventional treatment. Effects of the lower extremity rehabilitation of the two groups were evaluated 2 and 4 weeks after total knee arthroplasty., Findings: Most of the participants were above 70 years of age, 17 of whom were in the control group (68%) and 16 in the experimental group (64%). The active and passive knee flexion angles of the experimental group were greater than those of the control group (p < .001) 2 and 4 weeks after surgery. The muscle strength of the quadriceps of the experimental group was higher than that of the control group (p < .001) 2 and 4 weeks after surgery. The experimental group exhibited significantly higher physical function than that of the control group 2 and 4 weeks after surgery (p < .001)., Conclusions: The elastic band exercise program shows promising effects on improving the lower limb rehabilitation of elderly patients with total knee arthroplasty., Clinical Relevance: Healthcare professionals who work with elderly patients with total knee arthroplasty may consider recommending and implementing the elastic band exercise program as a home rehabilitation method for this population. However, we recommend further testing of the long-term effects of this program on a larger population.

One-fourth of the human population is estimated to have been exposed to Mycobacterium tuberculosis ( Mtb ) and carries the infection in its latent form. This latent infection presents a lifelong risk of developing active tuberculosis (TB) disease, and persons with latent TB infection (LTBI) are significant contributors to the pool of active TB cases. Genetic polymorphisms among hosts have been shown to contribute to the outcome of Mtb infection. The SP110 gene, which encodes an interferon-induced nuclear protein, has been shown to control host innate immunity to Mtb infection. In this study, we provide experimental data demonstrating the ability of the gene to control genetic susceptibility to latent and active TB infection. Genetic variants of the SP110 gene were investigated in the Taiwanese population (including 301 pulmonary TB patients, 68 LTBI individuals, and 278 healthy household contacts of the TB patients), and their association with susceptibility to latent and active TB infection was examined by performing an association analysis in a case-control study. We identified several SNPs (rs7580900, rs7580912, rs9061, rs11556887, and rs2241525) in the SP110 gene that are associated with susceptibility to LTBI and/or TB disease. Our studies further showed that the same SNPs may have opposite effects on the control of susceptibility to LTBI versus TB. In addition, our analyses demonstrated that the SP110 rs9061 SNP was associated with tumor necrosis factor- α (TNF α ) levels in plasma in LTBI subjects. The results suggest that the polymorphisms within SP110 have a role in controlling genetic susceptibility to latent and active TB infection in humans. To the best of our knowledge, this is the first report showing that the SP110 variants are associated with susceptibility to LTBI. Our study also demonstrated that the identified SP110 SNPs displayed the potential to predict the risk of LTBI and subsequent TB progression in Taiwan.

Background: Nurses are expected to play an important role in smoking reduction education. Although the smoking ban was enacted in Taiwan in 1997, which included the introduction of smoking-free areas around the entrances of hospitals, many smokers are still found near hospitals. Few smoking reduction programs have been initiated around hospital entrances. The aim of this study was to examine the impacts of an innovative smoking reduction education program, which was conducted by nursing students around the entrances of a teaching hospital. Methods: A prospective pre- and post-test study design was used. The smoking reduction education program consisted of posters, audio broadcasts, and dramatic performances that provided information and resources related to smoking reduction. Outcome variables included the number of smokers, number of cigarette butts on the ground, and the experiences from nursing students after conducting the program. Results: After adjusting for weather and temperature, the number of smokers decreased significantly in the afternoon and during the whole day after the implementation of the program. The number of cigarette butts significantly decreased during the implementation of the program. Conclusion: The findings reveal that alternative smoking reduction programs initiated around hospital entrances significantly reduced both the number of smokers and cigarette butts on the ground. Nursing students shared their positive experiences in conducting this study.

Loss of function mutations in RAB39B were recently linked to X-linked recessive early-onset Parkinsonism with variable degrees of intellectual dysfunction. Postmortem examination of the brain biopsy from a patient carrying the gene deletion revealed widespread α-synuclein pathology. However, subsequent analyses reported conflict results to replicate the role of RAB39B mutations in patients with early-onset Parkinsonism. The aim of this study was to address the genetic contribution of RAB39B in early-onset and familial Parkinson's disease (PD) in a Taiwanese population. Among 466 subjects, we sequenced both the exons and exon-intron boundaries of RAB39B from 235 patients with early-onset PD (age of onset <50 years), 119 probands with familial PD, and 112 ethnicity-matched control subjects. We did not find any coding variants or previously reported mutations, suggesting that RAB39B mutations are not a common cause of early-onset or familial PD in our Taiwanese population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In May 2011, di(2-ethylhexyl) phthalates (DEHP) and, to a lesser extent, di-iso-nonyl phthalate (DiNP) were found to have been illegally used for many years in Taiwan as clouding agents in foods including sports drinks, juice beverages, tea drinks, fruit jam/nectar/jelly, and health or nutrient supplements., Objective: To estimate the DEHP exposure for the study participants for the follow-up epidemiological study and health risk assessment., Methods: A total of 347 individuals possibly highly exposed to phthalate-tainted foods participated in the study. Exposure assessment was performed based on the participants' responses to a structured questionnaire, self-report of exposure history, urinary metabolite concentrations, and DEHP concentration information in 2449 food records. A Bayesian statistical approach using Markov chain Monte Carlo simulation was employed to deal with the uncertainties in the DEHP concentrations of the contaminated foods and the participants' likelihood of being exposed., Results: An estimated 37% and 15% of children younger than 12 years old were exposed to DEHP at medium (20-50 μg / kg&#95;bw / day) and high AvDIs (50-100 μg / kg&#95;bw / day), respectively, prior to the episode (9% and 3% in adults, respectively). Moreover, 11% of children and 1% of adults were highly exposed (> 100 μg / kg&#95;bw / day), with a maximum of 414.1 μg / kg&#95;bw / day and 126.4 μg / kg&#95;bw / day, respectively., Conclusions: The phthalate exposure-associated adverse health effects for these participants warrant further investigation. The estimation procedure may be applied to other exposure assessment with various sources of uncertainties.

Data concerning the effects of prenatal exposures to nonylphenol (NP) and oxidative stress on neonatal birth outcomes from human studies are limited. A total of 146 pregnant women were studied (1) to investigate the association between prenatal NP exposure and maternal oxidative/nitrative stress biomarkers of DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua)) and lipid peroxidation (8-iso-prostaglandin F2α (8-isoPF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) and (2) to explore the associations among oxidative stress biomarkers, NP exposure, and neonatal birth outcomes, including gestational age, birth weight, length, Ponderal index, and head and chest circumferences. NP significantly increased the 8-OHdG and 8-NO2Gua levels. All infants born to mothers with urinary 8-OHdG levels above the median exhibited a significantly shorter gestational duration (Badjusted = -4.72 days; 95% CI: -8.08 to -1.36 days). No clear association was found between NP levels and birth outcomes. Prenatal 8-OHdG levels might be a novel biomarker for monitoring fetal health related to NP exposure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to examine the effects of self-esteem and social support on quality of life (QoL) in stage I and II cervical cancer survivors., Method: The sample consisted of 110 participants who had been diagnosed with stage I-II cervical cancer and had completed their treatment 5 years or more before data collection. Each participant completed four structured questionnaires: a demographic-disease survey, the Rosenberg Self-Esteem Scale, Medical Outcomes Study Social Support Survey, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30. Data were analyzed using descriptive statistics, independent sample t-test, one-way ANOVA, and hierarchical multiple linear regression analyses., Results: The participants' mean age was 60.74 ± 10.69 years. Better QoL was significantly associated with younger age, higher self-esteem, and stronger social support; in addition, social support buffered the effect of self-esteem on global QoL. Together, five variables (age, time since treatment, self-esteem, social support, and the interaction term of self-esteem and social support) explained 36% of the variance in global QoL, with self-esteem being the strongest predictor., Conclusions: The results of this study advance current knowledge of QoL in cervical cancer survivors by demonstrating that survivors with low self-esteem and social support tend to have lower QoL than those with low self-esteem but high social support. Health professionals should help survivors seek support and provide appropriate strategies to expand their social networks and enhance their self-esteem to improve their global QoL after cervical cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Prenatal exposure and the health effects of that exposure have been intensively studied for a variety of environmental pollutants and trace elements. However, few studies have compared susceptibilities among the three trimesters of gestation. Manganese (Mn) is a naturally occurring and abundant trace element in the environment. Although the effects of Mn on animals are well documented, knowledge of the effects of Mn exposure on pregnant women and fetuses remains limited. A longitudinal study was conducted by collecting blood samples during all three trimesters, and Mn exposure was completely characterized during gestation. The aims of this study were to examine the effects of maternal Mn exposure on neonatal birth outcomes and to explore the critical stage of these effects. In total, 38, 76 and 76 samples were obtained from singleton pregnant women in their first, second and third trimesters, respectively. The cohort of pregnant women was selected at a medical center in northern Taiwan. Erythrocyte samples were collected during the first, second and third trimesters of gestation. Erythrocyte Mn concentrations were measured by inductively coupled plasma mass spectrometry. Neonatal birth outcomes were evaluated immediately after delivery. A multivariate regression model was used to determine the associations between maternal Mn levels in erythrocytes in each trimester and neonatal birth outcomes. The geometric mean concentrations of Mn were 2.93 μg/dL, 3.96 μg/dL and 4.41 μg/dL in the first, second and third trimesters, respectively. After adjusting for potential confounders, a consistently negative association was found between maternal Mn levels throughout the three trimesters and birth outcomes. Log-transformed Mn levels in maternal erythrocytes in the second trimester were significantly associated with neonatal birth weight, head and chest circumferences, respectively (β=-556.98 g, p=0.038; β=-1.87 cm, p=0.045; β=-2.74 cm, p=0.024). Despite the limited sample size in the first trimester, negative effects of maternal Mn levels on birth weight (β=-1108.95 g, p<0.01) and chest circumference (β=-4.40 cm, p=0.019) were also observed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Coronary heart disease (CHD) remains the principal cause of excessive natural deaths in bipolar patients; however, electrocardiogram analyses and clinical features predicting CHDs in elderly bipolar patients remain limited. We sought to examine the relationship between CHDs, as determined by electrocardiogram, and clinical characteristics., Methods: We recruited bipolar I outpatients Diagnostic Statistical Manual of Mental Health (DSM-IV) who were more than 60 years old and had at least one psychiatric admission. Subjects were divided into two groups based on the presence or absence of CHD diagnosed by electrocardiogram analysis at entry of study. Clinical data were obtained by a combination of interviewing patients and family members and retrospectively reviewing medical records of the most recent acute psychiatric hospitalization., Results: Eighty patients with bipolar disorder were enrolled. A total of 20 (25%) in the study had CHDs. The mean age at the time of entry into study was 67.6 ± 5.5 years old in group with CHD and 66.8 ± 6.8 years old in that without CHD. Among the clinical characteristics examined, higher mean levels of serum sodium and thyroxine during the acute affective phase as well as more first-degree family history with bipolar disorder were related to having CHD, particularly the serum sodium level., Conclusions: About one fourth of old bipolar patients have CHDs in both Asian and Western populations. Aging patients with bipolar disorder may have unique clinical factors (e.g., hypernatremia or elevated thyroxine) related CHDs that could warrant special attention in their psychiatric and medical care to minimize cardiovascular disease and mortality., (© The Author(s) 2015.)

A recent collaborative study that combined linkage analysis with whole-genome sequencing of family members of multiplex families with multiple system atrophy (MSA) has identified COQ2 gene as a causative gene for MSA. The common variant, c.T1178C (p.V393A, rs148156462), in the COQ2 gene was found to be associated with an increased risk of sporadic MSA. There is overlapping clinical characteristics between MSA and Parkinson's disease (PD), and the pathologic hallmark of both diseases is α-synucleinopathy. We therefore aim to analyze the COQ2 p.V393A variant in a large Taiwanese cohort with PD patients. We genotyped COQ2 p.V393A variant in a total of 1005 participants, comprising 500 patients with PD and 505 age/gender-matched control subjects. The frequency of TC/CC genotype was comparable between PD patients and control subjects (odds ratio: 0.81, 95% confidence interval: 0.42-1.56, p = 0.53). COQ2 p.V393A variant is not a genetic risk factor for PD, suggesting its specificity in disease susceptibility to MSA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Mutations in the angiogenic factor, angiogenin (ANG), have been identified in patients with both familial and sporadic amyotrophic lateral sclerosis (ALS) and are thought to have a neuroprotective function. Parkinsonism has been noted in kindreds with ANG mutations and variants in the ANG gene have been found to associate with PD in two Caucasian populations. We therefore hypothesized that mutations in ANG may also contribute to idiopathic Parkinson's disease (PD). We sequenced ANG gene in a total of 1498 participants comprising 750 PD patients and 748 age/gender matched controls from Taiwan. We identified one novel synonymous substitution, c.C100T (p.L10L), in a single heterozygous state in one PD patient, which was not observed in controls. The clinical phenotypes and [99mTc]-TORDAT-SPECT images of the p.L10L carrier were similar to that seen in idiopathic PD. In addition, we also identified one common variant, c.T330G (p.G110G, rs11701), which was previously reported to associate with PD risk in Caucasians. However, the frequency of TG/GG genotype was comparable between PD cases and controls (odds ratio: 0.85, 95% confidence interval: 0.29-2.55, P = 0.78). Our results did not support that ANG rs11701 variant is a genetic risk factor for PD in our population. We conclude that mutations in ANG are not a common cause for idiopathic PD.

Objectives: A community-based health promotion program (CBHP) might be beneficial for the elderly, but evidence is limited. We therefore examined the effect of a CBHP on change of lifestyle, physiological indicators and depression score among seniors in 2 rural areas., Methods: A prospective quasi-experimental design involved a total of 520 senior participants living in 6 rural villages, who were clustered and conveniently assigned to 2 intervention groups. Senior nursing students were the interveners for group 1 and community peer supporters for group 2. The primary outcome measure was the change in health-related behavior measured on the geriatric health promotion scale (GHPS). The secondary outcome comprised changes in the short form of the Chinese geriatric depression scale (CGDS-15), fasting blood sugar, total cholesterol, waist circumference and blood pressure. Paired-t test and analysis of covariance were used for statistical inspection., Results: Most of the participants were retired farmers or fishermen >75years of age who had little education. The total scores and all subscales of GHPS, along with some physiological indicators, improved significantly between pretest and post-test in both groups. After adjustment for confounders, intervention in group 1 was more effective than that in group 2 regarding self-protection behaviors. Systolic and diastolic blood pressure was significantly lower in group 2., Conclusions: CBHP programs are valuable for improving healthy lifestyle, fasting blood sugar, blood pressure and depression score among seniors. The low cost and effectiveness of incorporating multidisciplinary resources to help rural elders to maintain a healthy status and a healthier lifestyle., (Copyright © 2014 Elsevier Inc. All rights reserved.)

There is evidence that cardiorespiratory fitness and physical activity significantly reduce cardiovascular risks in adults. A better understanding of the association between cardiorespiratory fitness, physical activity, and childhood obesity is vital in assessing the benefits of interventions to prevent obesity. This study was to examine the relationship between physical activity, body mass index, and cardiorespiratory fitness levels in Taiwanese children. A cross-sectional study was designed. Study participants consisted of 2419 school children (1230 males and 1189 females) aged 12 years old living in a southern Taiwan county with one the highest countrywide rates of childhood obesity. The weight status of the participants was defined as underweight, normal, overweight, or obese according to specific criteria. Cardiorespiratory fitness was then assessed by an 800-m run. Participants were queried on their physical activity habits via a questionnaire survey. The overall prevalence of overweight/obesity was 29.6%. Normal, underweight and overweight boys and girls had an increased odds ratio of being categorized with higher cardiorespiratory fitness than obese one for both gender. A significantly higher level of cardiorespiratory fitness was found in children who engaged in regular physical activity than in children who engaged only in irregular physical activity. Obese children are more likely to lack cardiorespiratory fitness. Physically active children have significantly better cardiorespiratory fitness levels than inactive children. This study supports the conclusion that BMI and physical activity are significantly correlated with cardiorespiratory fitness levels. Findings may provide educational professionals with information to assist their developing effective health promotion programs to healthy weight and improving cardiorespiratory fitness for children.

Patients with Parkinson's disease (PD) have hypovitaminosis D status and genetic variants of vitamin D receptor (VDR) gene are recently shown to be associated with PD in a large-scale genome-wide association study in a Caucasian population. Few studies examined VDR genetic variants in large-scale Asian patients with PD. We therefore genotyped 6 VDR genetic variants in a total of 1492 Taiwanese subjects, including 700 patients with PD and 792 age and/or gender matched control subjects. We did not observe any significant associations between the studied genetic variants of VDR and the risk of PD. Our data suggest that genetic variations of the VDR gene did not play a major role in a Taiwanese PD population. Further studies of VDR and its interaction with serum vitamin D levels are warranted to clarify the potential role of vitamin D in PD pathogenesis., (Copyright © 2014. Published by Elsevier Inc.)

A recently published genome-wide association study in Caucasian and Asian populations showed a significant association between the bone marrow stromal cell antigen 1 (BST1) SNP rs11724635 and increased risk for Parkinson's disease (PD). To investigate whether BST1 rs11724635 increases the risk of PD, either by itself or in combination with environmental factors, we performed an association analysis of BST1 rs11724635 in a large cohort of Taiwanese patients with PD and age matched controls. The study used TaqMan genotyping, logistic regression, and haplotype methods. The genotype distribution of rs11724635 in PD patients (N = 468; p = 0.50) and control subjects (N = 487; p = 0.44) was consistent with Hardy-Weinberg equilibrium. Compared with the AA genotype, the frequency of both CA and CC genotypes was not significantly different between the patient and control groups. The adjusted odd ratios (ORs) for CA and CC were not statistically significant (CA: OR = 0.962, 95% CI = 0.643-1.439, p = 0.850; CC: OR = 0.992, 95% CI = 0.654-1.503, p = 0.969). Of note, ever use of well water before the onset of PD symptoms had an impact on the occurrence of PD through interactions with BST1 rs11724635 AC (OR = 1.453, p = 0.024) and CC (OR = 1.623, p = 0.008). Our results show that the BST1 rs11724635 polymorphism alone is not associated with the development of PD, but it can interact with well water drinking to increase the risk of PD in this Taiwanese population., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background and Purpose: Recent genome-wide association studies have shown associations between multiple genetic variants and primary restless legs syndrome (RLS). Their roles in end stage renal disease (ESRD) related secondary RLS are not clear and studies in Asian populations are scarce. The association between candidate genetic variants and uremic RLS was investigated in a large cohort of Taiwanese dialysis patients., Methods: Sixteen RLS-related genetic variants at six loci, including MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, TOX3/BC034767 and the intergenic region of chromosome 2p14, in a total of 993 ESRD patients (259 subjects with and 734 subjects without RLS) were genotyped using TaqMan genotyping assays. Multivariate logistic regression analysis was used to test for associations between the genotypes and RLS in ESRD. Power calculations were completed using the CATs Genetic Power Calculator with settings of a multiplicative genetic model., Results: A modest association between the PTPRD variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03-2.23, P = 0.03) and a trend that TOX3/BC034767 variant rs3104767 may associate with the occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95% CI 0.97-3.11, P = 0.06). No associations between other genetic variants and risk and severity of RLS were observed in our ESRD cohort., Conclusions: The genetic variants of primary RLS candidate genes did not play a major role in our uremic RLS populations. The ethnic difference and heterogeneous etiologies underlying renal failure may partly explain the minor genetic contribution to uremic RLS in our populations. Further studies for other ethnicities will be of worth., (© 2014 The Author(s) European Journal of Neurology © 2014 EFNS.)

Recent genome-wide association studies of Parkinson's disease (PD) in Caucasian populations have identified two new susceptibility loci, GAK and HLA-DRA; however, only limited information exists regarding the involvement of these genes in PD risk in other ethnic groups. Here, we examined whether these genetic effects were consistent in a Taiwanese PD population. In a total 900 participants, including 448 PD patients and 452 control subjects, we genotyped the rs11248051 and rs1564282 variants of GAK, and the rs3129882 variant of HLA-DRA. Logistic regression analysis was used to test for associations between genotype and PD under an additive model, adjusting for age and gender. Subjects with CT/TT genotypes of GAK rs11248051 had a modestly increased association with PD compared to those with CC genotype (OR = 1.37; 95% CI = 1.09, 1.87; P = 0.03). Carriers and non-carriers exhibited indistinguishable phenotypes in regards to clinical presentation and onset age. We observed no association between PD risk and GAK rs1564282 or HLA-DRA rs3129882 variant. The different genetic effects between Taiwanese and Caucasian populations may come from differences in population structure and geographic region-specific genetic-environmental interactions. In conclusion, our results supported the association between the rs11248051 variant in GAK and PD risk in a Taiwanese population. Future functional studies of GAK in neuronal degeneration are warranted to unravel its role in the pathogenetic mechanism of PD., (Copyright © 2013 Wiley Periodicals, Inc.)

The aggressiveness of end-of-life (EOL) cancer care has often been analysed by the occurrence of several indicators, separately or aggregately. Whether aggressive EOL cancer care has different subtypes is unknown. This study sought to identify distinct subtypes of aggressive EOL care based on usage patterns of aggressive EOL-care indicators and to explore demographic, disease and treatment factors associated with the identified subtypes. This retrospective study linked data from 2001 to 2006 from three Taiwanese databases: National Registration of Death Database, Cancer Registration System and National Health Insurance claims database. Adult cancer patients (N=203,642) who died in 2001-2006 were selected. For these cancer patients' last month of life, we analysed eight indicators of aggressive EOL care: receiving chemotherapy, >1 emergency room visit, >1 hospitalisation, hospitalisation for >14 days, intensive care unit admission, received cardiopulmonary resuscitation, received intubation and received mechanical ventilation. Subtypes of aggressive EOL care were identified by latent class analysis. Among the study population, only 22.3% were treated by medical oncologists. Based on their profiles of EOL care, deceased cancer patients were classified into three subgroups: 'not aggressive' (45%), 'intent to sustain life' (33%) and 'symptom crisis' group (22%). Patients assigned to the 'intent to sustain life' group were less likely to have metastatic disease and to receive hospice care in the last year of life, but more likely to be cared for by non-medical oncologists, to die within 2 months after diagnosis and to die in hospital. EOL cancer care may be improved by understanding factors related to different subtypes of aggressive EOL care., (Copyright © 2013 Elsevier Ltd. All rights reserved.)