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Background. Using conventional esophagogastroduodenoscopy (EGD) to evaluate the infrapapillary area is not feasible. The use of sedative EGD may enable endoscopists to investigate the infrapapillary condition of the duodenum. In this study, we aimed to evaluate lesions in the infrapapillary regions by using sedative EGD. Methods. In this retrospective observational study, we used the data of patients who underwent sedative EGD examinations at a tertiary hospital in southern Taiwan. The endoscopists evaluated the esophagus, stomach, and proximal duodenum and then attempted to explore the infrapapillary portion of the duodenum as deeply as possible. We assessed the success rate for the exploration of infrapapillary areas. Furthermore, we analyzed specific clinical findings of sedative EGD examination. Results. In total, 2973 patients underwent sedative EGD between November 1, 2010, and December 31, 2011. For 2632 of these patients, it was their first sedative EGD examination. In 2511 patients (95.4%), the exploration of the infrapapillary areas was successful. In approximately 10% of the patients, specific findings were detected over the infrapapillary region, and 7 of these patients exhibited clinically significant findings (i.e., gallbladder cancer with metastasis, periampullary Vater adenoma, natural killer cell enteropathy, villous adenoma with moderate dysplasia, infrapapillary duodenal adenoma with dysplasia, duodenal perforation with tumor-like formation, and follicular lymphoma). No patient experienced minor or major adverse reactions during the sedative EGD procedure. Conclusions. The current study provided evidence that sedative EGD examination enables a safe, comfortable, and effective endoscopic examination of deeper sections of the duodenum to evaluate the papillary and infrapapillary regions. [ABSTRACT FROM AUTHOR]

Drug lag—delayed approval or reimbursement—is a major barrier to accessing cutting‐edge drugs. Unlike approval lag, reimbursement lag is under‐researched. We investigated the key determinants of reimbursement lag under Taiwan National Health Insurance (NHI), and compared this lag with those in the United Kingdom, Canada, Australia, Japan, and South Korea. Using retrospective data on 190 new NHI‐reimbursed drugs from 2007 to 2014, we studied reimbursement lag in Taiwan vs. other countries, and investigated associated factors using generalized linear models (GLMs). The median reimbursement lags during before ("first‐generation") and after ("second‐generation") NHI drug reimbursement scheme in Taiwan were 378 and 458 days, respectively. The "first‐generation" lag was shorter only than that in South Korea, whereas the "second‐generation" lag only exceeded those of the United Kingdom and Japan. In GLM models, higher drug expenditure and the introduction of the "second‐generation" NHI were two statistically significant parameters associated with reimbursement lag among antineoplastic and immunomodulating agents. For other drug classes, the reimbursement price proposed by pharmaceutical companies and use of price‐volume agreements were two statistically significant parameters associated with longer reimbursement lags. The current reimbursement lag in Taiwan is longer than 1 year, but only longer than those of the United Kingdom and Japan. The determinants differ between drug categories. A specific review process for antineoplastic and immunomodulating drugs may expedite reimbursement. There is a clear need for systematic data collection and analysis to ascertain factors associated with reimbursement lag and thereby inform future policy making. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization reported that more than 10 % of women are severely affected by infertility, making the condition a major worldwide public health problem. Lead (Pb), cadmium (Cd), and arsenic (As) are environmental pollutants that may contribute to reproductive disorders. This cross-sectional study investigated the association between blood concentrations of Pb, Cd, and As and risk factors for infertility in women.Methods: Women who were infertile (N = 310) or pregnant (N = 57) were recruited from the gynecology and obstetrics department of a hospital. The participants were interviewed to obtain their sociodemographic, reproductive, and lifestyle information. The concentrations of Pb, Cd, and As in their blood samples were measured using inductively coupled plasma mass spectrometry.Results: Our findings suggested that the concentrations of Pb and As, but not Cd, were significantly higher in the blood of infertile women than in that of pregnant women. A higher percentage of the infertile women consumed more alcohol, used Chinese herbal medicine more frequently, and lacked physical activity compared with the pregnant women. After accounting for potentially relevant predictors, we observed that blood Pb levels might be elevated by using Chinese herbal medicine 1-6 times per week (aOR = 2.82, p = 0.05). In addition, engaging in physical activity 1-2 times per week (aOR = 0.37, p = 0.05) might assist in reducing Pb accumulation in infertile women, though the p value was borderline.Conclusions: Lack of physical activity and frequent use of Chinese herbal medicine may be associated with elevated blood Pb levels in infertile women. Chinese herbal medicine use was observed to increase the Pb body burden of both infertile and pregnant women in this study. The risk-benefit for Chinese herbal medicine intake should be evaluated by women of childbearing age. [ABSTRACT FROM AUTHOR]

Background: Nonylphenol (NP) has been proven as an endocrine disrupter and had the ability to interfere with the endocrine system. Though the health effects of NP on pregnant women and their fetuses are sustained, these negative associations related to the mechanisms of regulation for estrogen during pregnancy need to be further clarified. The objective of this study is to explore the association between maternal NP and hormonal levels, such as estradiol, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and progesterone. Methods: A pregnant women cohort was established in North Taiwan between March and December 2010. Maternal urine and blood samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. A mixed-effects model using a generalised estimating equation (GEE) was applied to assess the associations between maternal NP concentration and plasma hormones throughout the three trimesters. Results: In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27, 4.21, and 4.10 µg/g cre. in the first, second, and third trimesters respectively. A natural log-transformation of urinary NP concentrations were significantly associated with LH in the GEE model (β = −0.23 mIU/ml, p<0.01). Conclusion: This perspective cohort study demonstrates that negative association occurs between maternal NP exposure and plasma LH levels. The estrogen-mimic effect of NP might influence the negative feedback on LH during pregnancy. [ABSTRACT FROM AUTHOR]

Lead (Pb) exposure increases the risks of neurodevelopmental disorders in children. Child-specific activities and land use scenarios may lead to elevated opportunities for Pb exposure through the soil. Therefore, we investigated hair and fingernail Pb concentrations among young children in northern Taiwan, in relation to soil Pb pollution and land use characteristics. We also explored the effect of the Pb exposure burden and land use scenarios on neurobehavioral development. In total, 139 healthy children under 3 years of age were recruited in October 2011 to April 2014. Pb levels in hair and fingernail samples were determined using an inductively coupled plasma/mass spectrometer. Pb concentrations in soils and land use types surrounding the children's homes were accessed by a geographic information system to identify any associations with hair Pb levels. The Bayley Scales of Infant and Toddler Development (Bayley-III) were used to evaluate the cognitive, language, and motor development of the children. A multivariable regression model was performed to assess the effects of soil Pb levels and land-use status on Pb exposure in children, as well as associations of Pb exposure and land-use scenarios with neurodevelopmental abilities. Geometric mean Pb concentrations in hair, fingernails, and soil were 2.9 ± 4.8 μg/g, 0.8 ± 5.1 μg/g, and 20.8 ± 4.3 mg/kg, respectively. The multivariable analysis indicated that soil Pb concentrations and green areas around residences had potential links with Pb exposure among children in northern Taiwan. Hair Pb concentrations were negatively associated with expressive language scores. Soil Pb exposure was positively associated with hair Pb concentrations. Land use types around the children's homes in northern Taiwan were associated with their neurodevelopment. Increased green areas were negatively associated with hair Pb concentrations. Living near a highway may have had negative impacts on gross motor scores. A healthy residence can avoid potential health risks for children during their early life. [Display omitted] • Soil Pb levels were positively associated with hair Pb concentrations. • Soil Pb and green areas surrounding homes had potential links with Pb exposure. • Hair Pb concentrations were negatively associated with expressive language scores. • Living near a highway had a negative impact on gross motor scores. • Healthy residences can avoid potential health risks for children in early life. [ABSTRACT FROM AUTHOR]

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. 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. 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). Our findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products. Image 1 • A longitudinal cohort study assessed phthalate exposure and thyroid and growth hormone levels. • MMP was negatively related to T 3 , T 4 , free T 4 , and IGF-BP3. • MEP was negatively related to IGF-1 and IGF-BP3. Capsule : Urinary phthalate metabolite levels are associated with thyroid and growth hormones in children exposed to phthalate-tainted products. [ABSTRACT FROM AUTHOR]

Highlights: [•] A cohort of pregnant women was established and followed until delivery. [•] Maternal NP exposure profile throughout three trimesters was characterized. [•] For multiparas and primiparas, urinary NP levels were not significantly different during gestation. [•] Second-trimester NP level is associated with a risk of low neonatal weight, especially for primiparas. [Copyright &y& Elsevier]

• Exposure to DEHP increased the risk of early recurrent pregnancy loss. • Cumulative risks indices of phthalate related to early pregnancy loss. • New approaches of hazard index, relative potency and receptor effect posed for female reproduction. Phthalates, which are commonly used in flexible plastics and consumer products, have been reported to be toxic to reproductive and developmental function in mammals. Past studies have focused on the toxic effects on male reproduction, with only a few studies conducted on the risks that cumulative exposure to phthalates have on the female reproductive system. We recruited 260 patients with recurrent pregnancy loss (RPL) of unknown etiology and 203 controls from the clinics of Obstetrics and Gynecology at a medical center in southern Taiwan from 2013 to 2020. The daily intake of phthalates was estimated from urine samples using the back-calculation method, after which the cumulative risk was determined using multiple hazard indices, including a dose-addition model, a receptor effect model, and a hazard index approach. The patients with RPL had a significantly higher cumulative exposure to phthalates (p < 0.05) than did the controls with a hazard index above one. After adjusted logistic regression analysis, we found that the risk of RPL was strongly related to the higher quartiles of DEHP, the DEHP TEQ for the antiandrogenic effect and adverse effects of the female reproductive system and the ER α binding effect (p < 0.05). Our work suggests that more attentions should be paid to the adverse effects induced by phthalates on female reproduction, especially the effects caused by the cumulative exposure to phthalates in women of reproductive age. [ABSTRACT FROM AUTHOR]

Healthcare expenditure on pharmaceuticals, especially innovative oncology drugs, is escalating. Current knowledge on this topic is largely limited to studies conducted upon reimbursement of new drugs. We investigated how endogenous factors (e.g., changed reimbursement criteria, such as an expanded indication) and exogenous factors (e.g., competing drugs) affect the level and trends of innovative oncology drug utilization in the Taiwan National Health Insurance (NHI) system, both upon reimbursement and afterward. This retrospective longitudinal study analyzed monthly data (January 2009 to December 2014) from the NHI Research Database on the consumption (prescribing volume) of 15 innovative oncology drugs reimbursed by the NHI between 2007 and 2013. Effects of endogenous and exogenous factors on drug utilization were evaluated using interrupted time series analyses. In segmented regression analyses, changed drug prescribing volume after the indication expanded (endogenous factor) was statistically significant; however, drug volume did not change significantly after prescription restrictions changed. First-competitors and non-first-competitors (exogenous factors) were significantly associated with drug prescription levels or utilization rates. Taking sorafenib as an example, the post-reimbursement drug prescribing volume did not change significantly after its therapy line changed (endogenous factor), whereas the reimbursement of first-competitors (exogenous factor) was significantly associated with a lower level or usage rate of sorafenib. Utilization of innovative oncology drugs in Taiwan changed dramatically after NHI reimbursement, driven largely by expanded indications and new competitors. Drug utilization evaluations should investigate both endogenous and exogenous factors., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Objective: Cancers result in significant economic burdens on patients, health sectors and society. Reliable burden estimates will help guide resource allocation. This study aimed to perform a nationwide cost analysis of the direct and indirect costs of the top ten most costly cancers, and acute coronary syndrome (ACS), as a comparison, in Taiwan., Setting: A population-based cohort study., Participants: In total, 545 221 patients with newly diagnosed cancer (lung cancer, female breast cancer, colorectal cancer, liver cancer, oral cancer, leukaemia, prostate cancer, non-Hodgkin's lymphoma, gastric cancer and oesophageal cancer) and 170 879 patients with ACS between 2007 and 2014 were identified., Primary and Secondary Outcome Measures: Direct medical costs were calculated from claims recorded in the National Health Insurance Research Database . Indirect costs, comprising morbidity-associated and mortality-associated productivity losses, were estimated from public life expectancy, average wage and employment data. The costs incurred in the 3 years after diagnosis were assessed. As a comparison, the cost of ACS was also estimated using the same study frame. A cost driver analysis was conducted to identify factors impacting cancer costs., Results: The cancers with the highest mean direct medical costs and total costs were leukaemia (US$28 464) and oesophageal cancer (US$81 775), respectively. Indirect costs accounted for over 50% of the total economic burden of most cancers, except for prostate cancer and female breast cancer. The costs of ACS were lower than those of most cancers. From the cost driver analysis, older age at diagnosis significantly (p<0.05) decreased the total cost of cancer; in contrast, male, tumour metastasis, comorbidities and treatment in medical centres increased the costs., Conclusions: This study demonstrates the comprehensive economic burden of the top 10 most costly cancers in Taiwan. These results are valuable for optimising healthcare resource allocation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The effect of exposure to vinyl chloride monomer (VCM) on susceptibility to hepatotoxicity in children is unknown, although experimental studies have demonstrated a significantly increased risk of hepatocellular carcinoma in rodents exposed to VCM in early life. Epidemiological studies have revealed a high prevalence of liver fibrosis and abnormal liver function in workers exposed to high VCM levels. We aimed to assess the association among urinary thiodiglycolic acid (TDGA) level, abnormal liver function, and hepatic fibrosis in school-aged children living near a petrochemical complex. A total of 303 school-aged (6-13 years) children within 10 km nearly a petrochemical complex was recruited in central Taiwan. First-morning urine and blood samples were collected from each subject, and urinary TDGA level was analyzed through liquid chromatography-tandem mass spectrometry. Liver function was determined by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hepatic fibrosis was assessed using the AST to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). Risk of hepatotoxicity induced by TDGA exposure was estimated using multivariate logistic regression. The median (range, subclinically abnormal %) AST and ALT levels of all subjects were 26.0 (17.0-99.0, 25.7%) and 15.0 (7.0-211.0, 5.9%) IU/L, respectively. Children in the highest urinary TDGA quartile (≥160.0 μg/g creatinine) exhibited significantly elevated median AST levels compared with those in the lowest quartiles (<35.4 μg/g creatinine, p = 0.033). After adjustment for potential confounding factors, children in the highest quartiles (Q 4 ) of TDGA level had significantly increased odds ratio (OR) of subclinically abnormal AST (OR = 3.86; 95% confidence interval: 1.54-9.67) compared with those in the lowest quartile. A dose-response trend (p = 0.004) was observed. Our findings support the hypothesis that elevated urinary TDGA level in children living near petrochemical complex is associated with susceptibility to hepatotoxicity., (Copyright © 2018 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.)