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Aim: Evidence suggests an association between maternal hypothyroidism and risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in offspring. We examined the risk of ASD and ADHD in individuals with congenital hypothyroidism (CHT)., Methods: A nationwide population-based cohort study enrolled a total of 1260 children younger than 12 years with a confirmed diagnosis of CHT and no prior diagnosis of any neurodevelopmental disorders, selected from the National Health Insurance Research Database of Taiwan between 1998 to 2013. In addition, 12,600 controls matched for sex, age, and residence were selected. Cox proportional hazards analysis was used to investigate the association among CHT, ASD, and ADHD., Results: Children with CHT were associated with a higher incidence of ASD (7.1‰ vs 1.3‰, P < 0.001) and ADHD (39.7‰ vs 18.7‰, P < 0.001) than the control group. Cox regression analyses demonstrated that children with CHT were associated with elevated risks of ASD (hazard ratio [HR], 4.72 [95% confidence interval (CI), 2.08-10.70]) and ADHD (HR, 2.03 [95% CI, 1.49-2.77]), after adjusting for demographic data and family history of major psychiatric disorders, compared with the control group., Conclusion: Children with CHT were associated with approximately a two-fold increased risk of ADHD and a four-fold increased risk of ASD than the control group. Our study highlights the need for future research to elucidate the potential pathophysiology among CHD, ASD, and ADHD., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Background: Pre-cluster symptoms (PCSs) are symptoms preceding cluster bouts and might have implications for the treatment of cluster headache (CH). This study investigated the prevalence of PCSs, and their utility in predicting upcoming bouts as well as the associations with therapeutic efficacy., Methods: We prospectively collected data from patients with CH. Each patient received a structured interview and completed questionnaire surveys during CH bouts. In sub-study 1, we cross-sectionally analyzed the prevalence, symptomatology, and predictability of upcoming bouts. Overall, 34 PCSs, divided into seven categories, were queried, including head and neck pain, cranial autonomic symptoms, restlessness, fatigue or mood changes, sleep alterations, constitutional symptoms, and generalized pain. In sub-study 2, we recorded the weekly frequency of CH attacks after the initiation of verapamil concurrently with a 14-day transitional therapy based on the patients' headache diary. A responder to verapamil was defined as a patient who have a reduction from baseline of at least 50% in the weekly frequency of CH attacks 4 weeks after the initiation of verapamil., Results: A total of 168 CH patients (women/men: 39/129) completed the study. In sub-study 1, we found 149 (88.7%) experienced PCSs, with a median of 24 (IQR 18 to 72) hours before the bouts. Up to 57.7% of patients with PCS reported that they could predict upcoming bouts. Among the seven categories of PCSs, head and neck pain was the most common (81.0%) and was associated with a higher predictability of upcoming bouts (odds ratio [OR] = 4.0; 95% confidence interval [CI] 1.7-9.6). In sub-study 2, we found two categories of PCSs were associated with the response to verapamil: sleep alteration (OR = 2.5 [95% CI = 1.3-4.8], p = 0.004) and ≥ 1 cranial autonomic symptoms (OR = 2.7 [95% CI = 1.4-5.1], p = 0.003)., Conclusion: PCSs were very common in CH and could be used to predict upcoming bouts. Different symptom categories of PCSs may have different clinical implications., (© 2024. The Author(s).)

Background: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations., Methods: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected., Results: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m 2 increase), but was not associated with HIV serostatus., Conclusion: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus., Competing Interests: Declaration of competing interest CCH has received honoraria for speaking at educational events or consulting from Gilead Sciences, and research funding from Gilead Sciences. HYS has received research funding from Gilead Sciences. The remaining authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: The inconsistent relationship between chemical exposure and estimated glomerular filtration rate (eGFR) has been examined in only a few studies. We investigated the association between paraben exposure and indicators of renal function in a total of 361 individuals recruiting from a representative study., Method: The levels of urinary parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were measured using UPLC-MS/MS. The association between paraben exposure and indices of renal function was assessed using multiple logistic regression and Bayesian Kernel Machine Regression (BKMR)., Results: The median levels of urinary parabens in the adult group were significantly higher than those in the minor group, that is, 397 vs. 148 ng/mL for MeP, 38.8 vs. 13.6 ng/mL for EtP, 117 vs. 57.7 ng/mL for PrP, and 6.61 vs. 2.79 ng/mL for BuP (all P < 0.001). In the adult group, multivariate regression models confirmed a positive association between the albumin-to-creatinine ratio and urinary MeP (β = 0.580) and a positive association of BUN (β = 0.061) and a negative association of eGFR (β = -0.051) with urinary EtP (all P < 0.001). In the adult group, compared with the lowest tertile group, the adjusted odds ratio in the third tertile (T 3 ) of urinary EtP levels indicated a 3.08 times increased risk of eGFR abnormalities, followed by the second tertile (T 2 ) with a 2.63 times increased risk. The generalized additive model (GAM) and BKMR models showed a non-linear correlation between urinary EtP levels and early CKD, as well as reduced eGFR. We observed a significant positive cumulative effect of urinary paraben on eGFR, and a significant positive single exposure effect of urinary EtP with eGFR abnormality., Conclusion: We found a significant association between exposure to EtP and an increased risk of high BUN levels and decreased eGFR., 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. Published by Elsevier Inc.)

Background: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied., Objectives: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates., Methods: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed., Results: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes., Conclusion: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes., (© 2024. The Author(s).)

Background: Frailty epitomizes the most complex consequence of an aging population. This study aimed to evaluate the impact of frailty, measured using the Clinical Frailty Scale (CFS), on outcomes of older people in an emergency department (ED)., Methods: We conducted a prospective observational study enrolling patients aged 65 years and older in a medical center of Taiwan between March 8, 2021, and November 30, 2021. The primary outcome was 90-day mortality rate. Individuals were categorized into three groups based on the CFS scores. Logistic regression was employed to examine the influence of frailty on clinical outcomes following covariate adjustment. Survival analysis was conducted using Kaplan-Meier curves and Log rank tests., Results: A total of 473 individuals were included in the study, with a mean age of 82.1 years, and 60.5% of them were males. The 90-day mortality rate was 10.6%. Among these groups, the CFS score 7-9 group had the highest 90-day mortality rate (15.9%), followed by the CFS score 4-6 group (8.0%) and the CFS score 1-3 group (7.1%). The multiple logistic regression analyses demonstrated a significant impact of CFS score on prognosis, with adjusted odd ratios of 1.24 (95% CI 1.06-1.47) for 90-day mortality, 1.18 (95% CI 1.06-1.31) for hospitalization, and 1.30 (95% CI 1.12-1.52) for 180-day mortality. The Kaplan-Meier curves revealed a significantly higher 90-day mortality rate for patients with high CFS scores (Log rank tests, p = 0.019)., Conclusion: In the older ED population, the severity of frailty assessed by the CFS emerged as a significant and important prognostic factor for hospitalization, 90-day mortality, and 180-day mortality., Competing Interests: The authors declare no conflict of interest., (© 2024 Lin et al.)

Introduction: Ever since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute's exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure., Methods: Urine samples ( N  = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography-tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated., Results: Our study found that the median level of BPA was significantly higher in adults (9.63 μg/g creatinine) than in minors (6.63 μg/g creatinine) ( p  < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA., Discussion: Our study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Chen, Chang, Huang, Chang and Huang.)

Although a growing number of studies have investigated the relationship between psychosocial factors and periodontitis, studies investigating the association between bipolar disorder (BD) and periodontitis are lacking. Using the Taiwan National Health Insurance Research Database, 4251 adolescents with BD and 17,004 age- and sex-matched controls were included. They were followed up from enrollment to the end of 2011 or death. Periodontitis was diagnosed during the follow-up. Cox regression analysis indicated that adolescents with BD had a higher risk of periodontitis (hazard ratio [HR]: 2.96, 95% confidence interval [CI] 2.77-3.17) than did controls. Subanalyses stratified by sex revealed a higher risk of periodontitis in male (HR: 2.83, 95% CI 2.56-3.14) and female (HR: 3.01, 95% CI 2.74-3.30) adolescents with BD than their respective controls. The long-term use of mood stabilizers was associated with a higher risk of periodontitis (HR: 1.19, 95% CI 1.06-1.35) in the BD cohort. Our study highlighted an increased risk of periodontitis in adolescents with BD compared with controls during the follow-up. We recommend that more attention should be paid to the prevention of periodontitis in adolescents with BD, especially those who are female or receiving mood stabilizers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: High-risk emergency department (ED) revisit is considered an important quality indicator that may reflect an increase in complications and medical burden. However, because of its multidimensional and highly complex nature, this factor has not been comprehensively investigated. This study aimed to predict high-risk ED revisit with a machine-learning (ML) approach., Methods: This 3-year retrospective cohort study assessed adult patients between January 2019 and December 2021 from National Taiwan University Hospital Hsin-Chu Branch with high-risk ED revisit, defined as hospital or intensive care unit admission after ED return within 72 hours. A total of 150 features were preliminarily screened, and 79 were used in the prediction model. Deep learning, random forest, extreme gradient boosting (XGBoost) and stacked ensemble algorithm were used. The stacked ensemble model combined multiple ML models and performed model stacking as a meta-level algorithm. Confusion matrix, accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) were used to evaluate performance., Results: Analysis was performed for 6282 eligible adult patients: 5025 (80.0%) in the training set and 1257 (20.0%) in the testing set. High-risk ED revisit occurred for 971 (19.3%) of training set patients vs 252 (20.1%) in the testing set. Leading predictors of high-risk ED revisit were age, systolic blood pressure and heart rate. The stacked ensemble model showed more favourable prediction performance (AUROC 0.82) than the other models: deep learning (0.69), random forest (0.78) and XGBoost (0.79). Also, the stacked ensemble model achieved favourable accuracy and specificity., Conclusion: The stacked ensemble algorithm exhibited better prediction performance in which the predictions were generated from different ML algorithms to optimally maximise the final set of results. Patients with older age and abnormal systolic blood pressure and heart rate at the index ED visit were vulnerable to high-risk ED revisit. Further studies should be conducted to externally validate the model., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Anaphylaxis is an acute and serious allergic reaction. Little is known about physician adherence to anaphylaxis guidelines among patients across different age groups., Objective: To investigate real-world physician adherence to anaphylaxis guidelines among children, adults, and older adults in emergency departments., Methods: This study retrospectively analyzed all consecutive patients with anaphylaxis who presented to 2 emergency departments at 2 branches of the largest tertiary hospital in Taiwan, between 2001 and 2020. Patients who met the diagnostic criteria for anaphylaxis were enrolled and grouped by age: children (<18 years), adults (18-64 years), and older adults (≥65 years)., Results: We enrolled 771 patients with anaphylaxis (159 children, 498 adults, and 114 older adults). Intramuscular epinephrine was administered in 294 cases (38.1%). There was a significant age-group difference in the rate of intramuscular epinephrine administration (46.5% in children, 37.3% in adults, and 29.8% in older adults; P trend = .004). When stratified by severity, 14.3% of older adults with moderate reactions received intramuscular epinephrine, whereas 35.2% of adults and 55.3% of children received intramuscular epinephrine (P trend < .001), whereas such difference was not found in patients with severe reactions. Upon discharge from emergency departments, 15.3% received allergist referral (52.2% in children, 6.6% in adults, and 1.8% in older adults; P trend < .001); 12.5% received education on avoidance of triggers (18.9%, 11.4%, and 7.9%; P trend = .01), and 16.1% received education on alarm symptoms (21.4%, 15.1%, and 13.2%; P trend = .05)., Conclusion: The real-world physician adherence to anaphylaxis guidelines remains suboptimal in emergency departments, particularly among older adults. Physician continuing education is needed to improve the gap between anaphylaxis guidelines and clinical practice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Several studies have suggested that some endocrine disruptors such as synthetic phenols, parabens and phthalates may disrupt thyroid hormone signaling and associated negative feed-backs with the central hypothalamic-pituitary-thyroid (HPT) axis. Therefore, we investigated urinary paraben and blood thyroid hormone levels in the Taiwanese population. Our sample comprised 264 adults (aged 18-97 years) and 75 minors (aged 7-17 years) from Taiwan Environmental Survey for Toxicants 2013. Urinary levels of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were assessed. Hormones of particular interest include: thyroid-stimulating hormone (TSH), triiodothyronine (T 3 ), and thyroxine (T 4 ). We sought integrated parameters to describe the transfer of thyroid hormones in homeostatic models. The geometric mean urinary paraben levels of the adults were higher than those of the minors (adults vs. minors; MeP: 383 vs. 62.4 ng/mL; PrP: 109 vs. 8.00 ng/mL; EtP: 39.5 vs. 2.38 ng/mL, and BuP: 6.36 vs. 2.13 ng/mL). In the male adults, we discovered that 0.253% (p = 0.032), 0.256% (p = 0.041) and 0.257% (p = 0.037) decreases in the TSH, TSH/T 4 and TSH/FreeT 4 ratio was associated with 1% EtP increases, respectively. In the female minors, 0.093% (p = 0.044), 0.072% (p = 0.047) and 0.156 (p = 0.004) increases in the TSH ratios were associated with a 1% MeP, EtP and BuP increase, respectively. Moreover, 0.151% (p = 0.008) and 0.177% (p = 0.001) increases in TSH/T 4 and TSH/free T 4 ratios were associated with a BuP 1% increase, respectively. Finally, EtP was positively associated with SPINA-GT (β: 15.66, p = 0.036) in the male adults. By contrast, EtP were positively associated with Jostel's TSH index and sTSHI (β: 0.072, p = 0.049; β: 0.107, p = 0.049) in the female minors. The Taiwanese population is commonly exposed to parabens, which can potentially lead to alteration of thyroid hormone homeostasis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The European System for Cardiac Operative Risk Evaluation (EuroSCORE II) is a well-established scoring system for predicting mortality in cardiac surgery. This system was derived predominantly from a European patient cohort; however, no validation of this system has been conducted in Taiwan. We sought to assess the performance of EuroSCORE II at a tertiary centre., Methods: The 2161 adult patients receiving cardiac surgery between 2017 and 2020 in our institution were included., Results: Overall, the in-hospital mortality rate was 7.89%. The performance of EuroSCORE II was assessed using the area under the receiver operator curve (AUC) for discrimination and the Hosmer-Lemeshow (H-L) test for calibration. Data were analysed for type of surgery, risk stratification, and status of the operation. EuroSCORE II had good discriminative power (AUC=0.854, 95% Confidence Interval (CI): 0.822-0.885) and good calibration (χ 2 =5.19, p=0.82) for all types of surgery except ventricular assist devices (AUC=0.618, 95% CI: 0.497-0.738). EuroSCORE II also showed good calibration for most types of surgery except coronary artery bypass surgery (CABG) combined procedure (P=0.033), heart transplantation (HT) (P=0.017), and urgent operation (P=0.041). EuroSCORE II significantly underestimated the risk for CABG combined procedure and urgent operations, and overestimated the risk for HT., Conclusion: EuroSCORE II had satisfactory discrimination and calibration power to predict surgical mortality in Taiwan. However, the model is poorly calibrated for CABG combined procedure, HT, urgent operation, and, likely, lower- and higher-risk patients., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed to investigate the infection statuses of dogs and cats, the animals with closer human interactions. Overall, the SFTSV RNA prevalence was 23% (170/735), with dogs showing a 25.9% (111/429) prevalence and cats at 19.3% (59/306) prevalence. Noticeably, the prevalence in stray animals (39.8% 77/193) was significantly higher than in domesticated ones (17.2%, 93/542). Among the four categories analyzed, the highest SFTSV prevalence was found in the stray dogs at 53.9% (120/193), significantly higher than the 24.2% prevalence noted in stray cats. In contrast, domesticated animals exhibited similar prevalence rates, with 17.1% for dogs and 17.2% for cats. It is noteworthy that in the domesticated animal groups, a significantly elevated prevalence (45%, 9/20) was observed among cats exhibiting thrombocytopenia compared to those platelet counts in the reference range (4.8%, 1/21). The high infection rate in stray animals, especially stray dogs, indicated that exposure to various outdoor environments influences the prevalence of infections. Given the higher human interaction with dogs and cats, there is a need for proactive measures to reduce the risk associated with the infection of SFTSV in both animals and humans.

Background: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed., Methods: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry., Results: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively., Conclusions: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Estimating absolute risk of lung cancer for never-smoking individuals is important to inform lung cancer screening programs., Objectives: To integrate data on environmental tobacco smoke (ETS), a known lung cancer risk factor, with a polygenic risk score (PRS) that captures overall genetic susceptibility, to estimate the absolute risk of lung adenocarcinoma (LUAD) among never-smokers in Taiwan., Design, Setting, and Participants: The analyses were conducted in never-smoking women in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma, a case-control study. Participants were recruited between September 17, 2002, and March 30, 2011. Data analysis was performed from January 17 to July 15, 2022., Exposures: A PRS was derived using 25 genetic variants that achieved genome-wide significance (P < 5 × 10-8) in a recent genome-wide association study, and ETS was defined as never exposed, exposed at home or at work, and exposed at home and at work., Main Outcomes and Measures: The Individualized Coherent Absolute Risk Estimator software was used to estimate the lifetime absolute risk of LUAD in never-smoking women aged 40 years over a projected 40-year span among the controls by using the relative risk estimates for the PRS and ETS exposures, as well as age-specific lung cancer incidence rates for never-smokers in Taiwan. Likelihood ratio tests were conducted to assess an additive interaction between the PRS and ETS exposure., Results: Data were obtained on 1024 women with LUAD (mean [SD] age, 59.6 [11.4] years, 47.9% ever exposed to ETS at home, and 19.5% ever exposed to ETS at work) and 1024 controls (mean [SD] age, 58.9 [11.0] years, 37.0% ever exposed to ETS at home, and 14.3% ever exposed to ETS at work). The overall average lifetime 40-year absolute risk of LUAD estimated using PRS alone was 2.5% (range, 0.6%-10.3%) among women never exposed to ETS. When integrating both ETS and PRS data, the estimated absolute risk was 3.7% (range, 0.6%-14.5%) for women exposed to ETS at home or work and 5.3% (range, 1.2%-12.1%) for women exposed to ETS at home and work. A super-additive interaction between ETS and the PRS (P = 6.5 × 10-4 for interaction) was identified., Conclusions and Relevance: This study found differences in absolute risk of LUAD attributed to genetic susceptibility according to levels of ETS exposure in never-smoking women. Future studies are warranted to integrate these findings in expanded risk models for LUAD.

Due to the numerous industrial parks and high traffic density in Miaoli, Taiwan, large amounts of metals may be released into the atmosphere, accumulating in street dust. Therefore, this study aimed to collect street dust in Miaoli to quantify the metals and assess the accumulation degree, sources, and potential risks. The enrichment factor (EF), geological accumulation index (I geo ), ecological risk, and non-carcinogenic and lifetime carcinogenic risk were estimated to assess the accumulation degree and the potential environmental and health risks. Pearson correlation analysis, principal component analysis, and positive matrix factor model were used to clarify the relationship between levels of metals and identify possible sources. The levels of metals in street dust in order were Fe > Zn > Mn > Cu > Cr > Ni > Pb > Sr > Co > Sb. According to I geo , the level of Ni indicated moderately polluted. The levels of Zn, Cu, and Pb showed moderate to strong pollution, strong pollution, and very strong pollution, respectively. Results of average ecological risk analysis pointed out that Pb and Cu represent a very high risk, while other metals posed low-to moderate-level ecological risks. Excluding the Steel Enterprise area, based on the EF value and source identification, it might be concluded that Co, Sr, Fe, Mn, and Sb were mainly from natural sources, while Cu, Pb, and Zn come from anthropogenic pollution sources. Based on the results of the risk assessments, most metals pose no serious adverse health risk to humans. But, in comparison to Miaoli townships, the health risks of residents living in the Steel Enterprise area were higher. However, given that children and adolescents exposure to Co, Cr, Pb, and Ni together constitute a relatively higher carcinogenic risk (CR > 10 -6 ), more attention needs to be paid to the populations most susceptible., 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 Elsevier Ltd. All rights reserved.)

Background: Idiopathic mesenteric phlebosclerosis is a rare condition with unclear pathogenesis. This study aimed to investigate the clinical features, diagnostic modalities, treatments, and outcomes of idiopathic mesenteric phlebosclerosis patients in Taiwan., Methods: Idiopathic mesenteric phlebosclerosis patients diagnosed by the typical characteristic of tree-like mesenteric venous calcifications on plain abdominal radiography or computed tomography between January 1992 and July 2021 were retrospectively analyzed., Results: Totally, 36 idiopathic mesenteric phlebosclerosis patients were enrolled (50% females; mean age, 61.6 years). Among the included patients, 26 (72.2%) and 10 (27.7%) were symptomatic and asymptomatic, respectively. Abdominal pain (61.1%) accounted for the majority of all symptoms, followed by fever, diarrhea, and bloody stools. Our results showed that 83.3% of patients had at least 1 risk factor, whereas 16.6% of patients had none. Moreover, among the included patients, 36.1%, 44.4%, 50.0%, 38.8%, and 8.3% had cardiovascular disease, chronic renal disease, cancer, chronic liver disease, and diabetes mellitus, respectively. Our findings showed 94.4% of patients were diagnosed via abdominal computed tomography and plain abdominal radiography, whereas 5.6% of patients were diagnosed via plain abdominal radiography. The ascending colon was the most commonly involved site (100%). Our findings showed that 91.6% of patients experienced good recovery after conservative treatment, except for the 3 who died of sepsis and respiratory failure. By contrast, 8.3% of idiopathic mesenteric phlebosclerosis patients underwent colectomy. The average follow-up duration was 62.5 months., Conclusions: Idiopathic mesenteric phlebosclerosis remains a rare disease in Taiwan. Plain abdominal radiography and computed tomography can be utilized for establishing a definite diagnosis. Conservative treatment is usually adequate for most patients, with surgical treatment only indicated for severe cases.

Immunocastration is an effective alternative to surgical castration for controlling the population of animals. As gonadotropin-releasing hormone (GnRH) regulates the reproductive endocrine system in mammals, it is a target antigen for vaccine formulation. Through this study, we evaluated the effectiveness of a recombinant subunit GnRH-1 vaccine for the immunocastration of the reproductive function of 16 mixed-breed dogs (Canis familiaris) provided voluntarily by different households. All the dogs were deemed clinically healthy prior to and during the experiment. A specific anti-GnRH immune response was detected at Week 4, which was maintained for at least 24 weeks after vaccination. Moreover, decreased levels of sexual hormones (testosterone as well as progesterone and estrogen, respectively) were observed in both male and female dogs. Estrous suppression was apparent in female dogs, and testicular atrophy and poor semen quality (concentration, abnormality, and viability) were observed in male dogs. In conclusion, the recombinant subunit GnRH-1 vaccine could successfully suppress fertility and delay the estrous cycle in canines. These results support the efficacy of the recombinant subunit GnRH-1 vaccine; thus, it is a suitable candidate for fertility control in dogs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jai-Wei Lee reports financial support was provided by Council of Agriculture in Taiwan., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years., Methods: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs., Results: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year., Conclusion: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study., Competing Interests: Declaration of competing interest All authors declared no conflict of interest., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement., Methods: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients <50 years, pathological fractures, missing data, and two AOMs prescribed were excluded. The real-world trends related to subsequent fragility fracture and death within 1 and 3 years were used to evaluate the potential effects due to revision of reimbursement policies., Results: Of 393,092 patients, among them, 336,229 patients met the criteria, whose mean age ranged from 73.3 to 74.4 years, and nearly 80% were female. Further analysis showed a steady increase of AOMs from 5567 (17.1%) and 8802 (27.0%) in 2008-6697 (18.3%) and 10,793 (29.5%) in 2018 for males and 80+ years respectively. The subsequent fragility fracture within one and three years post AOMs initiation was 5.81% and 11.80% in 2018., Conclusion: This study showed an immediate drop in AOMs prescription after the implementation of a new stricter reimbursement policy. It took 5 years to return the annual prescription number., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained., Methods: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed., Results: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (<25%) decreased from 38.8% in 2008 to 14.6% in 2018. In addition, the switchers increased from 5.9% in 2008 to 9.3% in 2018, indicating a more flexible choice of AOMs. The proportion of high adherence to AOMs was highest in high-urbanization areas, and the proportion increased about two times from 30% in 2008 to 60% in 2018., Conclusion: The implementation of new reimbursement criteria in 2011 was associated with increased adherence to AOMs and the increase was most apparent in high-urbanization areas., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Methods synthesizing multiple data sources without prospective datasets have been proposed for absolute risk model development. This study proposed methods for adapting risk models for another population without prospective cohorts, which would help alleviate the health disparities caused by advances in absolute risk models. To exemplify, we adapted the lung cancer risk model PLCOM2012, well studied in the west, for Taiwan., Methods: Using Taiwanese multiple data sources, we formed an age-matched case-control study of ever-smokers (AMCCSE), estimated the number of ever-smoking lung cancer patients in 2011-2016 (NESLP2011), and synthesized a dataset resembling the population of cancer-free ever-smokers in 2010 regarding the PLCOM2012 risk factors (SPES2010). The AMCCSE was used to estimate the overall calibration slope, and the requirement that NESLP2011 equals the estimated total risk of individuals in SPES2010 was used to handle the calibration-in-the-large problem., Results: The adapted model PLCOT-1 (PLCOT-2) had an AUC of 0.78 (0.75). They had high performance in calibration and clinical usefulness on subgroups of SPES2010 defined by age and smoking experience. Selecting the same number of individuals for low-dose computed tomography screening using PLCOT-1 (PLCOT-2) would have identified approximately 6% (8%) more lung cancers than the US Preventive Services Task Forces 2021 criteria. Smokers having 40+ pack-years had an average PLCOT-1 (PLCOT-2) risk of 3.8% (2.6%)., Conclusions: The adapted PLCOT models had high predictive performance., Impact: The PLCOT models could be used to design lung cancer screening programs in Taiwan. The methods could be applicable to other cancer models., (©2022 The Authors; Published by the American Association for Cancer Research.)

Objectives: To compare the clinical profiles between male and female cluster headache patients from a large cohort., Methods: This hospital-based study enrolled patients diagnosed with cluster headache between 1997 to 2021. Participants completed structured questionnaires collecting information on demographics, clinical profiles, and quality of life. Treatment regimens and effectiveness were determined through medical chart review. All variables were compared between the sexes., Results: In total, 798 patients (M/F:659/139) were enrolled. The male-to-female ratio was 4.7:1 for the full study period, but it declined from 5.2:1 to 4.3:1 for patients enrolled before and after 2010, respectively. The frequencies of chronic cluster headache (M:1.2%, F:1.4%) and aura (M:0.3%, F:0.7%) were low but similar between the sexes. Most headache features showed no difference between men and women. Female patients had significantly longer attack duration, shorter inter-bout duration, higher frequencies for eyelid edema, nausea and vomiting and lower frequencies for conjunctival injection and pacing. Sex difference did not influence headache-associated disability, anxiety, or depression, but poor sleep quality was significantly more common in women. Among menstruating women, 22/122 (18.0%) reported worsening headaches during menses. The effectiveness of treatment was similar between the sexes., Conclusions: Despite a decline of male-to-female ratio in the past two decades, most clinical profiles were similar between the sexes.

Background: The annual cut-off birthdate for entry into school in Taiwan is August 31. Thus, children and adolescents born in August are typically the youngest in their grades. The potential effect of relative age on the diagnosis of autism spectrum disorder (ASD) remains uncertain., Methods: A total of 9,548,393 individuals aged 3-17 years during the study period (from September 1, 2001, to August 31, 2011) identified from the Taiwan National Health Insurance Research Database were enrolled into our study. Logistic regression analysis was used to examine the likelihood of receiving ASD diagnosis for those who were born in August (the youngest) compared with those who were born in September (the oldest)., Results: Both boys and girls born in August had a higher likelihood of being diagnosed with ASD (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.16-1.32; OR: 1.23, 95% CI 1.06-1.42) than did those born in September. Sensitivity analysis conducted over different periods revealed consistent findings., Discussion: Relative age, as an indicator of neurocognitive maturity, is a crucial contributor to the risk of being diagnosed with ASD among children and adolescents. Our findings highlight the importance of considering the age of a child within a grade when diagnosing ASD., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A national 13-valent pneumococcal conjugate vaccine (PCV13) catch-up program among children aged 2-5 years in 2013, before routine infant immunization in 2015, successfully reduced serotype 19A-related invasive pneumococcal diseases in Taiwan. We aimed to investigate its impact on hospitalized childhood pneumonia., Methods: We analyzed the National Health Insurance Research Database, 2001-2017, for hospitalized children aged <18 years with the diagnoses of all-cause pneumonia, lobar/pneumococcal pneumonia, and pneumococcal parapneumonic diseases. The study period was divided into 2001-2005 (pre-PCV), 2006-2012 (private sectors), and 2013-2017 (universal PCV13 vaccination)., Results: On pneumococcal parapneumonic diseases, the national PCV13 vaccination program was associated with an immediate decline in 2-4-year-old children and significant decreasing trends in all ages. The incidence rate ratios of 2016-2017/2011-2012 were 0.16 (95% confidence interval [CI], 0.06-0.40) and 0.18 (95% CI, 0.13-0.23) in children aged < 2 and 2-4 years, respectively. We observed an increase of lobar/pneumococcal pneumonia cases after an early decline. The intensive/invasive medical needs and the fatality of all-cause pneumonia decreased significantly in children of all ages., Conclusions: Pneumococcal parapneumonic diseases and the disease burden of lobar/pneumococcal pneumonia and lower respiratory tract infections declined after the national PCV13 vaccination program., Impact: The impact study of the PCV13 immunization program on childhood pneumonia in Asian countries remained limited. The unique PCV13 immunization program in Taiwan, catch-up before primary infantile series, reduced severe childhood pneumococcal pneumonia at 5 years post PCV13. The intensive and invasive medical needs and fatality of all-cause pneumonia decreased significantly in children of all ages. We observed an increase in lobar/pneumococcal pneumonia after an early decline., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

Blue carbon ecosystems (BCEs) are a promising resource for the mitigation of global warming; however, climate spectrums and anthropogenic activities could influence the fragile balance of BCEs as carbon sinks or sources. We assess how oyster farming affects dissolved inorganic carbon (DIC) and total alkalinity (TA) on CO 2 fluxes in a mangrove-dominated lagoon. Water physical, chemical and biological parameters were recorded by in-situ buoys within the lagoon and at its inflow. Structural equation modeling was adopted to clarify the factors/processes controlling the partial pressure of CO 2 (pCO 2 ). A three-dimensional environmental model followed by a conceptual DIC model was used to quantify the spatiotemporal patterns of capture and release of DIC and TA by oyster production. The results showed that 49% of TA and DIC released from mangroves was depleted by oyster shell formation. DIC was reduced by algal photosynthesis and algal was served as a food source supporting oyster production. Annual oyster production through phytoplankton photosynthesis accounted for 11% of the atmosphere carbon inflows, suggesting that oyster production served as a significant atmospheric/terrestrial carbon sink in the lagoon. The results indicate that mangroves benefit local oyster production by acting as an important source of DIC and TA, and that the oyster aquaculture contributed to carbon capture in a mangrove-dominated lagoon ecosystem., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Due to excessive clinical blood usage and a rapidly aging population, an impending blood shortage in Taiwan is inevitable. This study aimed to determine the potential blood deficit in Taiwan in 2030. The numbers of units of whole blood (WB) donated and red blood cells (RBC) transfused will increase from 1,182,973 to 1,115,803 in 2018 to 1,230,500 and 1,250,760 in 2030, respectively. Considering the gap between donation and transfusion, we estimate a deficit of 97,633 units of WB in 2030. Blood collection will increasingly rely on donors over the age of 40. Moreover, we observed a large decline in units of WB donated among people less than 25 years old. A growing demand for RBC is attributed to the aging population and limited decreases in age-specific units of RBC transfused per capita. Scrutinizing and forecasting changes in blood collection and transfusion are necessary for generating strategies to mitigate blood shortages., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

To monitor trends in the distribution of yeast species and the susceptibilities of these species to commonly prescribed antifungal drugs, we conduct the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) every 4 years. We found that 25 of 294 Candida tropicalis isolates from TSARY 2014 and 31 of 314 C. tropicalis isolates from TSARY 2018 were resistant to fluconazole. We determined the genetic relatedness among fluconazole-resistant C. tropicalis isolates by multilocus sequence typing (MLST). Among 174 C. tropicalis isolates, including all 56 fluconazole-resistant, all 26 susceptible-dose dependent and 92 selected fluconazole-susceptible isolates, 59 diploid sequence types (DSTs) were identified. We found that 22 of the 25 fluconazole-resistant C. tropicalis from TSARY 2014 and 29 of the 31 fluconazole-resistant C. tropicalis from TSARY 2018 were genetically related and belonged to the same cluster (clade 4). A combination of mutation and overexpression of ERG11, encoding the target of azole drugs, was the major mechanism contributing to drug resistance. Approximately two-thirds of reviewed patients infected or colonised by fluconazole-resistant C. tropicalis were azole-naïve. Furthermore, there was no evidence of patient-to-patient transmission. Because the clade 4 fluconazole-resistant C. tropicalis strain persists in Taiwan, it is important to identify the source of azole-resistant C. tropicalis to prevent the spread of this resistant strain., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: To date, numerous cohort studies and meta-analyses have shown that childhood maltreatment is associated with a wide range of adverse physiological and psychological symptoms. Although childhood maltreatment has been linked to an increased risk of personality disorders, the direction and magnitude of the association remain uncertain. Therefore, this cohort study aimed to evaluate whether children who have suffered childhood maltreatment have a higher incidence of subsequent personality disorders, using a nationwide database in Taiwan., Methods: We conducted a large retrospective cohort study using data drawn from Taiwan's National Health Insurance Research Database between 2000 and 2015. A total of 10,345 children who experienced childhood maltreatment were identified using International Classification of Disease codes. They were then compared with 41,380 children who never experienced childhood maltreatment in terms of the prevalence rates of personality disorders., Results: Childhood maltreatment was associated with an increased risk of personality disorders (considering the control as reference: adjusted hazard ratio, 2.12; 95% confidence interval, 1.90-2.36; p < 0.001). The Kaplan-Meier analysis revealed a significantly higher 15-year cumulative incidence of personality disorders among childhood maltreatment victims than among controls (log-rank test, p < 0.001)., Conclusions: The present population-based study showed a positive association between prior childhood maltreatment and subsequent personality disorders in the general Taiwanese population. In order to reduce the risk of personality disorders, interventions should be implemented, identifying and supporting economically disadvantaged families and vulnerable children as early as possible., (Copyright © 2021. Published by Elsevier B.V.)

Background: Evidence for mitigation of transfusion-transmitted dengue informed by surveillance data is lacking. In this study, we evaluated the risk of positive dengue viral (DENV) ribonucleic acid (RNA) from blood transfusions during a large outbreak in Taiwan., Methods: Serum collected from blood donors living in districts experiencing the dengue epidemic were tested for DENV RNA using a qualitative transcription-mediated nucleic acid amplification assay (TMA). The TMA-reactive specimens were further tested for immunoglobulin (Ig)M and IgG antibodies, nonstructural protein 1 (NS1) antigen, and viral RNA by reverse-transcription polymerase chain reaction. We estimated DENV RNA prevalence and the number of DENV infections among blood donors., Results: A total of 4976 specimens were tested for DENV RNA, and 21 were TMA-reactive. The detection rate was 0.84 (95% confidence interval [CI], 0.15-4.73), 3.36 (95% CI, 1.31-8.60), and 6.19 (95% CI, 3.14-12.17) per 1000 donors in districts where the weekly dengue incidence was 5-50, 50-200, and 200 or more per 100 000 residents, respectively. Alanine aminotransferase screening only detected 4.4% of TMA-reactive donations. A total of 143 transfusion-transmitted DENV infections probably occurred during this outbreak, accounting for 9.2 in 10 000 dengue infections., Conclusions: Approximately 0.5%-1% of blood donations were DENV RNA positive in epidemic districts. The correlation of DENV RNA rates with dengue incidence may inform the design of effective control measures., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Rationale and Objective: Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified various bacterial drivers in different demographics, and compared them with dialysis patients to associate kidney disease progression with changes in gut microbiota., Study Design: This was a cross-sectional cohort study., Settings and Participants: Fecal samples were obtained from 119 healthy Taiwanese volunteers, and 16S rRNA sequencing was done on the V3-V4 regions to identify the bacterial enterotypes. Twenty-six samples from the above cohort were compared with fecal samples from 22 peritoneal dialysis and 16 hemodialysis patients to identify species-level bacterial biomarkers in the dysbiotic gut of chronic kidney disease (CKD) patients., Results: Specific bacterial species were identified pertaining to different demographics such as gender, age, BMI, physical activity, and sleeping habits. Dialysis patients had a significant difference in gut microbiome composition compared to healthy controls. The most abundant genus identified in CKD patients was Bacteroides , and at the species level hemodialysis patients showed significant abundance in B. ovatus , B. caccae, B. uniformis , and peritoneal dialysis patients showed higher abundance in Blautia producta (p ≤ 0.05) than the control group. Pathways pertaining to the production of uremic toxins were enriched in CKD patients. The abundance of the bacterial species depended on the type of dialysis treatment., Conclusion: This study characterizes the healthy gut microbiome of a Taiwanese population in terms of various demographics. In a case-control examination, the results showed the alteration in gut microbiota in CKD patients corresponding to different dialysis treatments. Also, this study identified the bacterial species abundant in CKD patients and their possible role in complicating the patients' condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shivani, Kao, Chattopadhyay, Chen, Lai, Lin, Lu, Huang, Tsai, Teng, Wu, Hsieh, Wang and Chuang.)

Background: Since 2011, Taiwan's National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures., Methods: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes., Results: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old., Conclusion: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population., (© 2022 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: The variations in ABO blood groups are reported to be associated with multiple disorders, including ulcerative colitis (UC). We aimed to investigate the distribution of ABO blood groups in UC patients and explore its impact on disease severity., Methods: We retrospectively collected 129 UC patients diagnosed at our hospital between January 2000 and November 2019. Clinical characteristics, ABO blood groups, and operation rates were analyzed., Results: The mean diagnostic age of patients was 38.97 years. Males accounted for the majority of all patients (62.8%). Of 129 patients, 43 (33.3%) were blood type O, 41 (31.8%) were blood type A, 38 (29.5%) were blood type B, and 7 (5.4%) were blood type AB. Although our patients had higher ratio of blood type A comparing our general population, there was no statistically significant association of ABO blood types distribution between these two groups (p = 0.1906). In the subgroup analysis, there were no significant difference of disease locations and operation rates between different ABO blood groups. Furthermore, blood type A patients had higher serum hemoglobin (Hb) levels compared to blood type O patients (13.31 g/dL vs. 12.30 g/dL, p = 0.0347). Blood type A patients had lower serum erythrocyte sedimentation rate (ESR) levels compared to blood type O patients (12.46 mm/hour vs. 21.5 mm/hour, p = 0.0288). Blood type O had higher serum ESR levels compared to non-O groups (p = 0.0228). In the ABO blood groups and mean diagnostic age (≤ 40 years or > 40 years), there were no statistically significant difference between these two age groups, p = 0.5515., Conclusions: Our results showed ABO blood groups are not associated with UC in spite of a higher ratio of blood type A in our patients. Blood type O patients had higher serum ESR levels; however, blood type A patients had higher Hb levels., Competing Interests: The authors have declared that no competing interests exist.

Background: Total knee replacement (TKR) surgery is a treatment option for advanced hemophilic arthropathy. Due to its rarity and complexity, previous reports could only demonstrate the results of single-site studies including few cases. This population-based study aimed to investigate the major epidemiological characteristics, mean consumption of coagulation factors, length of hospital stays, complications, and failure rate of primary TKR for severe hemophilia patients in Taiwan., Methods: A cohort of 996 hemophilia patients registered between 1995 and 2011 was included, and 103 primary TKRs were performed on 75 patients. Unilateral TKR was performed on 47 patients and bilateral TKRs on the remaining 28 patients, including 12 simultaneous and 16 staged surgeries. The mean age at surgery was 32.3 years (range, 17.3-55.7), and the mean follow-up duration was 77.9 months (range, 2.3-176.8)., Results: Failure was noted in 8 patients (8.5%) at mean 32.8 months (range, 2.3-95) after surgery. Four patients revealed aseptic loosening, whereas infection in 4. The 10-year prosthesis survivorship was 88.6%. For patients receiving unilateral TKR, the mean length of hospital stay was 15 days (range, 7-32). The mean cost of factor supplement was United States Dollar (USD) 43 543 with a mean 4-unit packed red blood cells transfusion (range, 0-38). The total admission cost was USD 48 326 (range, USD 4165-262 619)., Conclusion: The prevalence of TKA for hemophilia patients was 7.5% in Taiwan. The mean hospital stay was 14 days, and the 10-year prosthesis survivorship was 88.6%. The mean daily factor usage was decreased from 235.7 units preoperatively to 202.1 units postoperatively. In comparison with the staged-bilateral TKRs, the simultaneous procedures significantly reduced the mean total cost from USD 101 923 to USD 61 587 (p = 0.023). Therefore, in terms of cost-effectiveness, bilateral simultaneous TKR is more preferable than staged procedures., Competing Interests: Conflicts of interest: Dr. Hui-Chi Hsu, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background: The year 2013 marks a watershed in the history of medical education in Taiwan. Following Taiwan's Taskforce of Medical School Curriculum Reform recommendations, the medical school curriculum was reduced from 7 to 6 years. This study aimed to analyze the impact of medical school curriculum reform on medical students' performance in objective structured clinical examinations (OSCEs)., Methods: We retrospectively analyzed the OSCE records at Taipei Veterans General Hospital (Taipei VGH), one of Taiwan's largest tertiary medical centers, between November 2016 and July 2020. The eligibility criteria were medical students receiving a full one-year clinical sub-internship training at Taipei VGH and in their last year of medical school. All medical students received a mock OSCE-1 at the beginning of their sub-internship, a mock OSCE-2 after six months of training, and a national OSCE at the end of their sub-internship. The parameters for performance in OSCEs included "percentage of scores above the qualification standard" and "percentage of qualified stations.", Results: Between November 2016 and July 2020, 361 undergraduates underwent clinical sub-internship training at Taipei VGH. Among them, 218 were taught under the 7-year curriculum, and 143 were instructed under the 6-year curriculum. Based on baseline-adjusted ANCOVA results, medical students under the 7-year curriculum had a higher percentage of scores above the qualification standard than those under the 6-year curriculum at the mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 33.8% [95% CI 32.0-35.7] vs. 28.2% [95% CI 25.9-30.4], p < 0.001), and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001). Moreover, medical students in the 7-year curriculum had a higher percentage of qualified stations in mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001) and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 91.9% [95% CI 90.1-93.8] vs. 86.1% [95% CI 83.8-88.3], p = 0.001). After clinical sub-internship training, there were no differences in the percentage of scores above the qualification standard (7-year curriculum vs. 6-year curriculum: 33.5% [95% CI 32.2-34.9] vs. 34.6 [95% CI 32.9-36.3], p = 0.328) and percentage of qualified stations (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 88.1-90.7] vs. 90.2% [95% CI 88.6-91.8], p = 0.492)., Conclusions: At the beginning of the sub-internship, medical students under the 7-year curriculum had better OSCE performance than those under the 6-year curriculum. After the clinical sub-internship training in Taipei VGH, there was no difference in the national OSCE score between the 6- and 7-year curricula. Our study suggests that clinical sub-internship is crucial for the development of clinical skills and performance in the national OSCE., (© 2022. The Author(s).)

Background: Large-scale single nucleotide variation (SNV)-based blood group genotyping assays have been made available for over a decade. Due to differences in ethnic groups, there is much diversity in clinically important blood group antigens and genetic variants. Here, we developed a robust matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)-based blood group genotyping method on MassARRAY system., Study Design and Methods: A total of 1428 donors were enrolled into three groups: (a) reagent red cell donors; (b) rare donor or common antigen-negative donors; and (c) group O, R 1 R 1 /R 2 R 2 donors. Forty-two SNVs were designed for determining nine blood groups, with X/Y chromosome in two multiplex reactions, on MassARRAY 96-well format system. Further targeted sequence analyses were performed by Sanger sequencing., Results: WHO reference reagent (NIBSC code: 11/214) was tested for concordance with the provided genotype results. Among the donors, concordance rate was over 99%. Alleles of important phenotypes such as Mi(a+), Di(a+), and Asian-type DEL and alleles of rare blood groups such as Fy(a-), Jk(a-b-) and s- were screened. Three types of discrepancies were found. Serologically, the 'N' antigen was expressed on genetically MM with GYP*Mur red blood cells and caused genuine discrepancies (9.5%). Genetically, allele dropout (ADO) was caused by rare SNV in the primer for Ss genotype (2.1%) and partial insertion of RHD genes (0.9%) led to difficulties in predicting phenotypes., Conclusion: Hemo panel module and MassARRAY System in 96-well format showed good performance in terms of large-scale blood group genotyping and phenotype predictions. Implementation of this method is effective for routine blood group genotype screening of donors., (© 2021 International Society of Blood Transfusion.)

Background: The temporal association between type 1 diabetes mellitus (T1DM) and major psychiatric disorders, including schizophrenia, major affective disorder, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD), remains elusive., Methods: The specialized databases of catastrophic diseases and mental disorders and the longitudinal health insurance database of Taiwan National Health Insurance Research Database were used in current study. A total of 6,226 patients with T1DM and 62,260 age- and sex-matched controls were recruited between 2001 and 2010 and were followed until the end of 2011 for the identification of diagnoses of schizophrenia (International Classification of Clinical Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code: 295), bipolar disorder (ICD-9-CM codes: 296 except 296.2x, 296.3x, 296.9x, and 296.82), major depressive disorder (ICD-9-CM codes: 296.2x and 296.3x), ASD (ICD-9-CM code: 299), and ADHD (ICD-9-CM code: 314)., Results: Cox regression analysis revealed increased hazard ratios of schizophrenia (12.28), bipolar disorder (13.80), major depressive disorder (10.41), ASD (14.52), and ADHD (8.19) in patients with T1DM compared with controls., Discussion: Our findings indicate the importance of clinicians closely monitoring the mental health condition of children, adolescents, and adults with T1DM. Additional studies should be conducted to elucidate the definite pathomechanisms of comorbidities between T1DM and major psychiatric disorders., Competing Interests: Conflict of interest No conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

In Taiwan, freshwater clams (Corbicula fluminea) and hard clams (Meretrix lusoria) are the most frequently raised shellfish in land-based pond aquaculture, but research on the accumulation of organochlorine pesticides (OCPs) in these shellfish is limited. We detected the levels of 14 OCPs in 62 shellfish from Taiwanese aquafarms by performing gas chromatography-tandem mass spectrometry. OCP residues were detected in 4.84% of the samples including readings of 0.04 mg/kg chlordane (in a freshwater clam), 0.03 mg/g p,p'-DDE (in a freshwater clam), and 0.02 mg/g p,p'-DDE (in a hard clam). However, the associated estimated daily intake values were less than the acceptable daily intake levels of chlordane and p,p'-DDE Therefore, the consumption of these shellfish presents no immediate health risks. Our findings contribute to food safety and serve as a reference for OCP screenings for aquatic shellfish., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: More than 80% of patients who visited Emergency Department (ED) was not urgent in Taiwan in 2019. It causes insufficient medical services and a latent fiscal threat to the Nation Health Insurance (NHI). This study adopted simulation-based educating modules to explore the effect in teaching competence among primary and middle school teachers for efficient AEDRU (adequate emergency department resource usage) education in the future., Method: The subjects were 414 elementary and junior high school teachers in Taiwan. 214 participants attended the simulation-based workshop as the simulation-based group, whereas 200 participants took an online self-learning module as the self-learning group. The workshop was created by an expert panel for decreasing the unnecessary usage amount of ED medial resources. The materials are lecture, board games, miniature ED modules, and simulation-based scenarios. A teaching competence questionnaire including ED knowledge, teaching attitude, teaching skills, and teaching self-efficacy was conducted among participants before and after the intervention. Data were analyzed via McNemar, paired t test and the generalized estimating equations (GEE)., Results: The study showed that teachers who participated in the simulation-based workshop had improved more in teaching competence than those who received the online self-learning module. In addition, there were significant differences between the pre-test and post-test among the two groups in teaching competence., Conclusion: The simulation-based workshop is effective and it should be spread out. When students know how to use ED medical resources properly, they could affect their families. It can help the ED service to be used properly and benefits the finance of the NHI. The health care cost will be managed while also improving health., Competing Interests: Declaration of any potential financial and nonfinancial conflicts of interest: To the best of our knowledge, the named authors have no conflict of interest, financial or otherwise., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

To evaluate birth outcomes in women with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), we used insurance data of Taiwan to evaluate 11 adverse neonatal outcomes of infants born to women with HDP (N = 7775) and with both HDP and GDM (HDP/GDM) (N = 1946), comparing to women with neither disorder (N = 19,442), matched by age. The impacts of preeclampsia/eclampsia were also evaluated. Results showed that Caesarean section delivery was near 1.7-fold greater in the HDP/GDM and HDP groups than in comparisons. The preterm delivery rates were more than threefold greater in HDP/GDM group and HDP group than in comparisons with adjusted odds ratios (aORs) of 4.84 (95% confidence interval (CI) 4.34-5.40) and 3.92 (95% CI 3.65-4.21), respectively, followed by jaundice (aORs 2.95 (95% CI 2.63-3.33) and 1.90 (95% CI 1.76-2.06)), and small gestation age (SGA) (aORs 6.57 (95% CI 5.56-7.75) and 5.81 (95% CI 5.15-6.55)). Incidence rates of birth trauma, patent ductus arteriosus, atrial septal defect, respiratory distress syndrome, and neonatal hypoglycemia were also higher in the HDP/GDM and HDP groups than in the comparison group. Most adverse outcomes increased further in women with preeclampsia or eclampsia. In conclusion, women with HDP are at elevated risks of adverse neonatal outcomes. Risks of most adverse outcomes increase further for women with both HDP and GDM. Preeclampsia or eclampsia may also contribute to these outcomes to higher risk levels. Every pregnant woman with these conditions deserves specialized prenatal care., (© 2021. The Author(s).)

Four-hundred metric-ton chalazae are produced annually from the liquid-egg processing and always cause a heavy burden due to handling cost in Taiwan. After chalazae were hydrolyzed by protease A, the amounts of hydrophobic, aromatic, and branched-chain amino acids, as well as anserine were dramatically increased. This study was to understand the antifibrogenic effects of protease A-digested crude chalaza hydrolysates (CCH-As) on livers of thioacetamide (TAA) treated rats. CCH-As improved (P< 0.05) growth performance, serum liver damage indices, histopathological liver inflammation, and liver collagen deposition in TAA-treated rats. The antifibrogenic effects of CCH-As were due to decreased (P < 0.05) inflammatory/fibrogenic cytokine contents, α-smooth-muscle-actin (α-SMA) protein expression, and matrix metallopeptidase (MMP)-2 and -9 activities, as well as increased (P < 0.05) the antioxidant capacity in livers. CCH-As also increased (P < 0.05) cleaved caspase-3 and cleaved poly ADP-ribose polymerase protein levels in livers of TAA-treated rats which accelerating cell renewal. Thus, this study does not only reveal a novel nutraceutical ingredient, CCH-As, against liver fibrogenesis, but also offer an alternative way to expand the utilization of poultry byproducts., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The relationship between autoimmune rheumatic diseases, inflammatory bowel diseases, and carpal tunnel syndrome is unclear. We aimed to survey the occurrence and characteristics of carpal tunnel syndrome in autoimmune rheumatic diseases and inflammatory bowel diseases, compared with the general population., Methods: We used the Longitudinal Health Insurance Database 2015 from Taiwan's National Health Insurance Research Database. Patients diagnosed with autoimmune rheumatic diseases/inflammatory bowel diseases were identified. The incidence rates and surgical rates of carpal tunnel syndrome among individual diseases were calculated. The hazard ratios when compared with age and sex matched, and 1:1 ratio control groups were surveyed., Results: A total of 2591 women and 701 men were identified. The incidence rate of carpal tunnel syndrome was highest in Crohn disease (1001 per 100,000 person-years, 95% confidence interval = 0-2747), followed by scleroderma and Sjögren syndrome. The incidence rate in the control group was 571 per 100,000 person-years (95% confidence interval = 314-829). Significantly increased adjusted hazard ratios were seen in Sjögren syndrome (1.44, 95% confidence interval = 1.09-1.90) and rheumatic arthritis (1.33, 95% confidence interval = 1.05-1.70). The overall surgical rate was 0.2% in patients with autoimmune rheumatic diseases/inflammatory bowel diseases and 0.3% in the control group, without a significant difference (P = 0.85)., Conclusions: Patients with Sjögren syndrome and rheumatic arthritis are susceptible to carpal tunnel syndrome. Patients with autoimmune rheumatic diseases/inflammatory bowel diseases have similar surgical rates as general population., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The association between postpartum depression and postpartum psychosis and subsequent maternal and offspring mental disorders in Western countries has been established; however, whether the relationship can be generalized to the Asian population is unknown., Methods: Using the Taiwan National Health Insurance Research Database, this study enrolled 933,745 mother-infant pairs who delivered their first child and had no history of severe mental illness before childbirth from 2001 to 2010. Postpartum depression and postpartum psychosis were assessed in 3 periods between childbirth and 3, 6, or 12 months after childbirth. Subsequent maternal schizophrenia ( ICD-9-CM code: 295), bipolar disorder ( ICD-9-CM code: 296 except 296.2x, 296.3x, 296.9x, and 296.82), and depressive disorder ( ICD-9-CM codes: 296.2x, 296.3x, 300.4, and 311) and offspring autism spectrum disorder (ASD; ICD-9-CM code: 299) and attention-deficit/hyperactivity disorder (ADHD; ICD-9-CM code: 314) were identified during the follow-up period to the end of 2011., Results: Both postpartum depression and postpartum psychosis were found to be related to increased risks of schizophrenia, bipolar disorder, and depressive disorder in mothers, with hazard ratios (HRs) ranging between 8.80 (95% CI, 7.95-9.74) and 63.96 (95% CI, 50.39-81.18). Children exposed to maternal postpartum depression and psychosis were more likely to develop ADHD. Only postpartum depression was related to the likelihood of offspring ASD., Conclusions: Per these findings, we clinicians and health care providers should closely monitor the mental health condition of postpartum women and their children., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Background: Outbreaks of emerging infectious diseases, such as COVID-19, have negative impacts on bystander cardiopulmonary resuscitation (BCPR) for fear of transmission while breaking social distancing rules. The latest guidelines recommend hands-only cardiopulmonary resuscitation (CPR) and facemask use. However, public willingness in this setup remains unknown., Methods: A cross-sectional, unrestricted volunteer Internet survey was conducted to assess individuals' attitudes and behaviors toward performing BCPR, pre-existing CPR training, occupational identity, age group, and gender. The raking method for weights and a regression analysis for the predictors of willingness were performed., Results: Among 1,347 eligible respondents, 822 (61%) had negative attitudes toward performing BCPR. Healthcare providers (HCPs) and those with pre-existing CPR training had fewer negative attitudes (p < 0.001); HCPs and those with pre-existing CPR training and unchanged attitude showed more positive behaviors toward BCPR (p < 0.001). Further, 9.7% of the respondents would absolutely refuse to perform BCPR. In contrast, 16.9% would perform BCPR directly despite the outbreak. Approximately 9.9% would perform it if they were instructed, 23.5%, if they wore facemasks, and 40.1%, if they were to perform hands-only CPR. Interestingly, among the 822 respondents with negative attitudes, over 85% still tended to perform BCPR in the abovementioned situations. The weighted analysis showed similar results. The adjusted predictors for lower negative attitudes toward BCPR were younger age, being a man, and being an HCP; those for more positive behaviors were younger age and being an HCP., Conclusions: Outbreaks of emerging infectious diseases, such as COVID-19, have negative impacts on attitudes and behaviors toward BCPR. Younger individuals, men, HCPs, and those with pre-existing CPR training tended to show fewer negative attitudes and behaviors. Meanwhile, most individuals with negative attitudes still expressed positive behaviors under safer measures such as facemask protection, hands-only CPR, and available dispatch instructions., Competing Interests: The authors have declared that no competing interests exist.

Background: Identification and treatment for latent tuberculosis infection (LTBI) are of great epidemiological importance of controlling tuberculosis (TB) worldwide. Identification in high-risk population on dialysis and treatment with 12-week weekly rifapentine plus isoniazid (3HP) help improve prevention outcomes effectively., Methods: We conducted a single-center, nonrandomized follow-up study on end-stage renal disease patients on hemodialysis. The interferon-gamma release assay (IGRA) was used for the diagnosis of LTBI. Participants were treated with 3HP, and treatment responses were recorded and analyzed., Results: A total of 123 of the 641 patients showed positive IGRA results. The male sex, age >60 years, low serum albumin level (<4.0 g/dL), and hypercalcemia (serum calcium level > 10.2 mg/dL) were associated with IGRA positivity. Seventy-five patients were treated with 3HP, with a completion rate of 66.67%. The male sex, albumin level >4.0 g/dL, and absence of adverse drug reaction were associated with increased completion rates. Adverse drug reactions included dizziness, fatigue, nausea and vomiting, fever, and hypertension., Conclusion: Risk factors for LTBI in dialysis patients were identified to prioritize LTBI screening and initiate early treatment. The completion rate in dialysis patients were approximately 2 of 3 patients with mild adverse drug reaction, leading to discontinuation of the treatment., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Prescription-event monitoring studies have reported incident epilepsy or seizures in proton pump inhibitor (PPI) recipients. We examined the risk of epilepsy after prolonged PPI exposure and determine what age group was at higher risk of epilepsy., Methods: We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000). PPI users with subsequent epilepsy were selected as the case cohort. Controls were PPI users without subsequent epilepsy, matched for age, sex, PPI use indication, enrollment time, end point time, follow-up period, overall systemic health, and comorbidities. The total dose of PPI was defined as the cumulative defined daily dose (cDDD). Prolonged PPI use was defined as a cDDD > 365. A logistic regression analysis was performed. Population attributable risk was calculated., Results: Epilepsy occurred 4.13 years after the initiation of PPI use. PPI users with the highest risk of incident epilepsy received a cDDD > 365 [odds ratio = 1.63, 95% confidence interval = 1.37-1.95], followed by 121-365 cDDD (1.33, 1.18-1.51) and 31-120 cDDD (1.15, 1.02-1.29), compared to those receiving a cDDD ≤ 30, after adjusting for potential confounders. Prolonged PPI use increased the risk of epilepsy in all age groups, and the risk was highest for those older than 80 years (3.11, 1.67-5.79). The population attributable risk was 12.2% (> 365 cDDD vs ≤ 30 cDDD)., Discussion: Prolonged PPI therapy was associated with an increased risk of epilepsy, particularly in the elderly population., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: This study evaluated the predictors for delayed initiation and continuation of ADHD medication use in children and adolescents with ADHD in Taiwan. Methods: This longitudinal cohort study enrolled 188,061 children and adolescents with ADHD between 2001 and 2011. Delayed initiation of ADHD medications was defined as the interval >365 days between diagnosis and first prescription, and continuation of ADHD medications was defined as ≥365 defined daily doses of ADHD medications. Results: Of the included patients, 39.2% were never treated with ADHD medications. Delayed initiation and continuation of ADHD medication use were found in 11.9% and 19.9% of the ever-treated patients, respectively. Younger age at ADHD diagnosis, male sex, older mother's age at child's ADHD diagnosis, and higher family income were associated with more delayed initiation but were also associated with more continuation of ADHD medication use. Conclusions: The initiation and continuation of ADHD medication use might be underlined by different mechanisms and warrant different strategies.

Approximately 400 metric tons of egg chalazae, a byproduct in the liquid-egg processing plant, are produced yearly but always regarded as a waste in Taiwan. Our team successfully developed a crude egg chalaza hydrolysate by protease-A digestion (CCH-A). Free branched-chain amino acids, 3-aminoisobutyric acid, and β-alanine, and anserine were assayed in the CCH-A used in this study. Besides, the in vitro bile-acid binding ability and inhibitory lipase activity of CCH-As were demonstrated. Then, high-fat diet feeding for 10 wk caused hyperlipidemia, insulin resistance, and hepatosteatosis in hamsters (P < 0.05). However, CCH-A co-treatment decreased serum/liver triglyceride levels and lipid accumulation in livers by increasing daily fecal lipid/bile-acid outputs, upregulating fatty-acid β oxidation, and downregulating fatty-acid biosynthesis in livers (P < 0.05). CCH-A co-treatment also amended insulin resistance, augmented hepatic antioxidant capacity, and decreased liver damages and inflammatory responses (P < 0.05). Taken together, our results do not only demonstrate the hepatoprotective effects of CCH-As against a chronic high-fat dietary habit, achieving effects similar to Simvastatin, but also decrease the environmental burden of handling chalazae in the liquid-egg industry., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fine air pollutant particles have been reported to be associated with risk of preeclampsia. The association between air pollutant exposure and preeclampsia risk in heavily air polluted Taiwan warrants investigation. Methods: We combined data from Taiwan National Health Insurance (NHI) Research Database (NHIRD) and Taiwan Air Quality Monitoring Database. Women aged 16-55 years were followed from January 1, 2000, until appearance of ICD-9 coding of preeclampsia withdrawal from the NHI program, or December 31, 2013. Daily concentration of NOx, NO, NO 2 , and CO was calculated by Kriging method. The Cox proportional hazard regression model was used for risk assessment. Results: For NOx, Relative to Quartile [Q] 1 concentrations, the Q2 (adjusted hazard ratio adjusted = 2.20, 95% CI = 1.50-3.22), Q3 (aHR = 7.28, 95% CI = 4.78-11.0), and Q4 (aHR = 23.7, 95% CI = 13.7-41.1) concentrations were associated with a significantly higher preeclampsia or eclampsia risk. Similarly, for NO, relative to Q1 concentrations, the Q2 (aHR = 1.82, 95% CI = 1.26-2.63), Q3 (aHR = 7.53, 95% CI = 5.12-11.0), and Q4 (aHR = 11.1, 95% CI = 6.72-18.3) concentrations were correlated with significantly higher preeclampsia or eclampsia risk. Furthermore, for NO 2 , relative to Q1 concentration, the Q2 (aHR = 1.99, 95% CI = 1.37-2.90), Q3 (aHR = 6.15, 95% CI = 3.95-9.57), and Q4 (aHR = 32.7, 95% CI = 19.7-54.3) concentrations also associated with a significantly higher preeclampsia or eclampsia risk. Conclusion: Women exposed to higher NO X , NO, NO 2 , and CO concentrations demonstrated higher preeclampsia incidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Yang, Su, Wang, Jiang, Hsu and Kao.)