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Introduction: In real-world practice, most non-small cell lung cancer (NSCLC) patients receiving combined immunochemotherapy are exposed to short-course corticosteroids following immune checkpoint inhibitor (ICI) infusion to prevent chemotherapy-related adverse events. However, whether this early short-course corticosteroid use prevents immune-related adverse events (irAEs) remains unknown. Methods: Between January 1st, 2015, and December 31st, 2020, NSCLC patients who received at least one cycle of ICI with or without chemotherapy were enrolled. Early short-course corticosteroids were defined as corticosteroids administered following ICI injection and before chemotherapy on the same day and no longer than 3 days afterward. The patients were categorized as either "corticosteroid group" or "non-corticosteroid group" depending on their exposure to early short-course corticosteroid. The frequencies of irAEs requiring systemic corticosteroid use and irAEs leading to ICI discontinuation were compared between the two groups, and exploratory survival analyses were performed. Results: Among 252 eligible patients, 137 patients were categorized as "corticosteroid group" and 115 patients as "non-corticosteroid group." The corticosteroid group enriched patients in the first-line setting (n = 75, 54.7%), compared to the non-corticosteroid group (n = 28, 24.3%). Thirty patients (21.9%) in the corticosteroid group and 35 patients (30.4%) in the non-corticosteroid group developed irAEs requiring systemic corticosteroid use (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.35–1.18; p = 0.15). Eight patients (5.8%) in the corticosteroid group, as compared with 18 patients (15.7%) in the non-corticosteroid group, permanently discontinued ICI due to irAEs (OR, 0.34; 95% CI, 0.12–0.85; p = 0.013). Conclusion: Early short-course corticosteroids following each ICI injection may reduce the rate of irAEs that lead to ICIs discontinuation, warranting further investigation of its prophylactic use to mitigate clinically significant irAEs. [ABSTRACT FROM AUTHOR]

PURPOSE: The Blood First Assay Screening Trial (BFAST) is a prospective study using next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) in treatment-naïve advanced/metastatic non–small-cell lung cancer (NSCLC). We compared liquid biopsy to tissue testing and analyzed genomic alterations in Taiwanese patients with NSCLC using the BFAST database. MATERIALS AND METHODS: A total of 269 patients underwent FoundationOne Liquid Companion Diagnostic (F1LCDx) assay at the National Taiwan University Hospital, of whom 264 underwent tissue-based genetic testing also. We analyzed the actionable mutations and the concordance between tissue-based genetic testing, which was limited to EGFR , ALK , ROS1 , and BRAF , in a real-life clinical setting and blood-based NGS in the clinical trial. Additionally, we analyzed the co-occurring genomic alterations from the blood-based ctDNA assay. RESULTS: A total of 76.2% patients showed actionable mutations. Standard tissue testing did not detect known driver alterations in about 22.7% of the patients (sensitivity, 70.24%). Liquid NGS detected additional mutations (RET , KRAS , MET , and ErbB2) in 14% of the patients, which went undetected by the standard-of-care testing. The complementary use of ctDNA NGS increased the detection rate by 42%. The F1LCDx assay had a sensitivity of 83.41%. Lower tumor and metastasis stages predicted nondetected blood-based NGS ctDNA results. Common co-occurring mutations in the blood-based NGS ctDNA assay were TP53 , DNMT3A , TET2 , PIK3CA , CTNNB1 , and RB1. Among the patients with EGFR-mutated NSCLC, TET2 co-occurring alterations correlated with shorter progression-free survival of EGFR tyrosine kinase inhibitor treatment. CONCLUSION: NGS ctDNA analysis in comprehensive genetic testing improves actionable mutation identification, vital for treating Asian NSCLC cases with high actionable mutation rates. Lower stages correlated with undetected blood-based NGS ctDNA assay results. Genomic analysis using a blood-based ctDNA assay enhances actionable mutation detection. [ABSTRACT FROM AUTHOR]

Background: The occurrence of postoperative complications within 30 days (PC1M) of a craniotomy for the removal of a primary malignant brain tumor has been associated with a poor prognosis. However, it is still unclear to early predict the occurrence of PC1M. This study aimed to identify the potential perioperative predictors of PC1M from its preoperative, intraoperative, and 24-h postoperative parameters. Methods: Patients who had undergone craniotomy for primary malignant brain tumor (World Health Organization grades III and IV) from January 2011 to December 2020 were enrolled from a databank of Kaohsiung Veterans General Hospital, Taiwan. The patients were classified into PC1M and nonPC1M groups. PC1M was defined according to the classification by Landriel et al. as any deviation from an uneventful 30-day postoperative course. In both groups, data regarding the baseline characteristics and perioperative parameters of the patients, including a new marker-kinetic estimated glomerular filtration rate, were collected. Logistic regression was used to analyze the predictability of the perioperative parameters. Results: The PC1M group included 41 of 95 patients. An American Society of Anesthesiologists score of > 2 (aOR, 3.17; 95% confidence interval [CI], 1.19–8.45; p = 0.021), longer anesthesia duration (aOR, 1.16; 95% CI, 0.69–0.88; p < 0.001), 24-h postoperative change in hematocrit by > − 4.8% (aOR, 3.45; 95% CI, 1.22–9.73; p = 0.0019), and 24-h postoperative change in kinetic estimated glomerular filtration rate of < 0 mL/min (aOR, 3.99; 95% CI, 1.52–10.53; p = 0.005) were identified as independent risk factors for PC1M via stepwise logistic regression analysis. When stratified according to the age of ≥ 65 years (OR, 11.55; 95% CI, 1.30–102.79; p = 0.028), the reduction of kinetic estimated glomerular filtration rate was more robustly associated with a higher risk of PC1M. Conclusions: Four parameters were demonstrated to significantly influence the risk of PC1M in patients undergoing primary malignant brain tumor removal. Measuring and verifying these markers, especially kinetic estimated glomerular filtration rate, would help early recognition of PC1M risk in clinical care. [ABSTRACT FROM AUTHOR]

Background: Studies comparing the effectiveness of either adjuvant oral uracil‐tegafur (UFT) or intravenous chemotherapy on early‐stage (stage I and II) non‐small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited. Methods: From January 2011 to December 2017, patients with early‐stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse‐free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders. Results: A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49–0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61–0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score‐matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48–1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72–1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non‐drinker (HR: 0.66, 95% CI: 0.34–0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42–0.97, p = 0.0341). Conclusions: This population‐based study in the real‐world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early‐stage NSCLC patients after surgery. [ABSTRACT FROM AUTHOR]

The emergency room (ER) digital bedside card is a simple and important invention. It can be directly connected to the hospital information system to display important patient information in real time, reduce the workload of ER staff, improve their satisfaction, and provide useful information for patients and their families. We conducted a prospective study of ER staff using questionnaires and conducted Wilcoxon signed-rank test to compare before and after ER digital bedside card implementation in the Tamsui MacKay Memorial Hospital. Sixty participants of the ER staff joined the study before and after digital card implementation. After the ER digital bedside card was set up, the number of round trips from the nursing station to the ER bedside and the number of common questions asked by patients and their family members were significantly reduced. The cards reduced the response time for frequently asked questions by patients and their family members and significantly improved the satisfaction of ER staff. Our study showed that ER digital bedside cards reduced the workload of ER staff, provided patients and their families with useful information, and greatly improved ER staff satisfaction. This marks an important milestone in the future development of smart ER. [ABSTRACT FROM AUTHOR]

Switched-mode power supplies (SMPS) are becoming an essential part of many electronic systems as the industry drives toward miniaturization and energy efficiency. However, practical SMPS design courses are seldom offered. In this paper, a generalized MATLAB/SIMULINK modeling technique is first presented. A proposed practical SMPS design course at Lunghua University, Taiwan, which incorporates this technique, is then described. In order to validate the correctness of the proposed modeling technique, four prototype SMPS are provided in this paper. These prototype circuits also serve as the laboratory section of the proposed course. The main objective of the course is to teach final-year undergraduate students and first-year Master's students how to design an SMPS in real life. The positive response from students indicates that the proposed technique is useful for SMPS design courses. (Contains 3 tables and 28 figures.)

Patients with hematologic malignancies (HMs) have a significantly elevated risk of mortality compared to other cancer patients treated in the intensive care unit (ICU). The prognostic impact of numerous poor outcome indicators has changed, and research has yielded conflicting results. This study aims to determine the ICU and hospital outcomes and risk factors that predict the prognosis of critically ill patients with HMs. In this retrospective study, conducted at a referral hospital in Taiwan, 213 adult patients with HMs who were admitted to the medical ICU were evaluated. We collected clinical data upon hospital and ICU admission. Using a multivariate regression analysis, the predictors of ICU and hospital mortality were assessed. Then, a scoring system (Hospital outcome of critically ill patients with Hematological Malignancies (HHM)) was built to predict hospital outcomes. Most HMs (76.1%) were classified as high grade, and more than one-third of patients experienced a relapsed or refractory disease. The ICU and hospital mortality rates were 55.9% and 71.8%, respectively. Moreover, the disease severity was high (median Sequential Organ Failure Assessment (SOFA) score: 11 and Acute Physiology and Chronic Health Evaluation (APACHE II) score: 28). The multivariate analysis revealed that high-grade HMs, invasive mechanical ventilation requirement, renal replacement therapy initiation in the ICU, and a high SOFA score correlated with ICU mortality. Furthermore, a higher HHM score predicted hospital mortality. This study demonstrates that ICU mortality primarily correlates with the severity of organ dysfunction, whereas the disease status markedly influences hospital outcomes. Furthermore, the HHM score significantly predicts hospital mortality. [ABSTRACT FROM AUTHOR]

Background: CT is the major detection tool for pancreatic cancer (PC). However, approximately 40% of PCs < 2 cm are missed on CT, underscoring a pressing need for tools to supplement radiologist interpretation. Methods: Contrast-enhanced CT studies of 546 patients with pancreatic adenocarcinoma diagnosed by histology/cytology between January 2005 and December 2019 and 733 CT studies of controls with normal pancreas obtained between the same period in a tertiary referral center were retrospectively collected for developing an automatic end-to-end computer-aided detection (CAD) tool for PC using two-dimensional (2D) and three-dimensional (3D) radiomic analysis with machine learning. The CAD tool was tested in a nationwide dataset comprising 1,477 CT studies (671 PCs, 806 controls) obtained from institutions throughout Taiwan. Results: The CAD tool achieved 0.918 (95% CI, 0.895–0.938) sensitivity and 0.822 (95% CI, 0.794–0.848) specificity in differentiating between studies with and without PC (area under curve 0.947, 95% CI, 0.936–0.958), with 0.707 (95% CI, 0.602–0.797) sensitivity for tumors < 2 cm. The positive and negative likelihood ratios of PC were 5.17 (95% CI, 4.45–6.01) and 0.10 (95% CI, 0.08–0.13), respectively. Where high specificity is needed, using 2D and 3D analyses in series yielded 0.952 (95% CI, 0.934–0.965) specificity with a sensitivity of 0.742 (95% CI, 0.707–0.775), whereas using 2D and 3D analyses in parallel to maximize sensitivity yielded 0.915 (95% CI, 0.891–0.935) sensitivity at a specificity of 0.791 (95% CI, 0.762–0.819). Conclusions: The high accuracy and robustness of the CAD tool supported its potential for enhancing the detection of PC. [ABSTRACT FROM AUTHOR]

Statins exert cholesterol-independent beneficial effects, including immunomodulatory effects. In this study, we attempted to investigate the association between statin therapy and the risk of viral infection. We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. We identified patients with hyperlipidemia and divided them into two cohorts: statin users and statin nonusers. A 1:1 propensity score matching was conducted between the two cohorts, and a Cox proportional hazards model was used to evaluate the risk of viral infection. Overall, a total of 20,202 patients were included in each cohort. The median follow-up durations were 4.41 and 6.90 years for statin nonusers and users, respectively. The risk of viral infection was 0.40-fold (95% confidence interval = 0.38–0.41) in statin users than in statin nonusers after adjustment for potential confounders. Statin treatment was associated with a significantly lower risk of viral infection in all age groups older than 18 years in both men and women. Moreover, the risk of viral infection substantially reduced as the duration of statin treatment increased. Our findings suggest that statin therapy is associated with a significantly lower risk of viral infection in patients with hyperlipidemia. [ABSTRACT FROM AUTHOR]

Background: The treatment options for epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR‐tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole‐brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial. Methods: A total of 150 EGFR‐mutant NSCLC patients with BMs who received first‐ or second‐generation EGFR‐TKIs as first‐line treatment between January 2012 and October 2019 were included in this analysis. Results: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung‐mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35–0.83), who received afatinib or erlotinib as first‐line treatment (HR: 0.521, 95% CI: 0.33–0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32–0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23–0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR‐TKI provided more OS benefits in patients with Lung‐mol GPA ≥3 compared with EGFR‐TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227). Conclusions: The study demonstrated that EGFR‐mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung‐mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status. [ABSTRACT FROM AUTHOR]

Background: Patients in remission after first-episode psychosis are inclined to discontinue antipsychotic treatment, which may lead to higher risk of relapse and unfavorable outcomes. Paradoxically, also there are evidences suggesting that certain patients may stay well in drug-free condition. Psychiatrists' views towards this dilemma might affect their approaches to these patients, and discrepant attitudes are noted between Western and Asian clinicians. This study aimed to examine psychiatrists' attitudes about discontinuing antipsychotic medications after remission from first-episode psychosis. Methods: Psychiatrists were recruited for this study using convenience sampling. A cross-sectional survey was conducted using a set of questionnaires comprising nine items for attitudes toward medication discontinuation, six vignettes for probing psychiatrists' practice in designated clinical scenarios, and a list of criteria that may affect their responses. Results: Responses were provided by 118 psychiatrists, two-thirds men, mean age 39.8 ± 10.1 years and mean experience 12.7 ± 9.7 years. Half of the participants endorsed that fewer than 20% of the remitted patients should stop medication completely; the majority advised that an observation period of 1 year or longer is necessary while discontinuing medication. The majority would not initiate discussion with patients about discontinuing medication. Responding to two case vignettes, those who endorsed that more patients could stop antipsychotics were also more inclined to discuss it with patients, but not consistently in response to the other four case vignettes. Taiwan psychiatrists expressed a wide range of decision-making considerations for discontinuing antipsychotics. Conclusion: The majority of Taiwan psychiatrists thought it was not feasible to stop medications completely but were willing to consider this option. Once being presented with actual clinical scenarios, many participants hesitated to discontinue antipsychotic medications for various reasons. The proactive attitude of psychiatrists towards conducting clinical trials to test the feasibility of medication discontinuation may help to provide better reference for this clinical dilemma. [ABSTRACT FROM AUTHOR]

Non-adherence to medication among patients with schizophrenia is an important clinical issue with very complex reasons. Since medication administration is an essential nursing responsibility, improving strategies for patient medication compliance must be fully understood. This study aimed to explore the strategies mental health nurses (MHNs) implement in clinically improving patients with schizophrenia and to describe the nurses' tacit knowledge of application strategies. A qualitative study with purposeful sampling was used. Twenty-five experienced MHNs in a psychiatric hospital in central Taiwan were given an in-depth interview. The texts were content-analyzed using NVivo 12 Pro software. MHNs promote medication adherence among patients with schizophrenia using the following strategies: establishing a conversational relationship, overall assessment of non-adherence to medication, understanding the disease and adjusting the concept of medication, incorporating interpersonal connection feedback, and building supportive resources. This study explored the strategies of MHNs that incorporated knowledge in managing treatment adherence in patients with schizophrenia. The findings add knowledge to clinical nursing practice about medication adherence among patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH.Methods: This study retrospectively enrolled patients in the Taiwan cohort - Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline.Results: From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone.Conclusion: To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population. [ABSTRACT FROM AUTHOR]

Background: Selective deep biliary cannulation is the first and the most important step before further biliary therapy. Transpancreatic sphincterotomy (TPS), and needle knife fistulotomy (NKF) were commonly used in patients with difficult cannulation, but few studies compare the outcome between TPS and NKF.Methods: A total of 78 patients who met the criteria of difficult cannulation in the National Taiwan University hospital from October 2015 to October 2017 were retrospectively reviewed. Their baseline demographics, success rate of biliary cannulation, and the rate of adverse events were assessed.Results: 31 patients and 47 patients underwent TPS and NKF for difficult biliary access, respectively. The characteristics of the 2 groups were similar, but patients in TPS group had more frequent pancreatic duct cannulation. Bile duct cannulation was successful in 23 patients (74.2%) in the TPS group and 39 (83.0%) in the NKF group (P = 0.34). There was no difference between the TPS and NKF in the rate of adverse events, including post-ERCP pancreatitis (PEP) (16.1% vs. 6.4%, p = 0.17), and hemorrhage (3.2% vs. 8.5%, p = 0.35). No perforation occurred.Conclusions: Both TPS and NKF have good biliary access rate in patient with difficult cannulation. TPS has acceptable successful rate and similar complication rate, compared with NKF. [ABSTRACT FROM AUTHOR]

Distal biliary strictures (DBS) are common and may be caused by both malignant and benign pathologies. While endoscopic procedures play a major role in their management, a comprehensive review of the subject is still lacking. Our consensus statements were formulated by a group of expert Asian pancreatico‐biliary interventional endoscopists, following a proposal from the Digestive Endoscopy Society of Taiwan, the Thai Association for Gastrointestinal Endoscopy, and the Tokyo Conference of Asian Pancreato‐biliary Interventional Endoscopy. Based on a literature review utilizing Medline, Cochrane library, and Embase databases, a total of 19 consensus statements on DBS were made on diagnosis, endoscopic drainage, benign biliary stricture, malignant biliary stricture, and management of recurrent biliary obstruction and other complications. Our consensus statements provide comprehensive guidance for the endoscopic management of DBS. [ABSTRACT FROM AUTHOR]

Rationale: Accumulating evidence has linked prolonged exposure to heavy metals to cancer occurrence in the urinary system. However, the specific biological mechanisms responsible for the association of heavy metals with the unusually high incidence of upper tract urothelial carcinoma in Taiwan are complex and incompletely understood. Methods: To elucidate the specific biological mechanism and identify molecular indicators of the unusually high association of upper tract urothelial carcinoma with heavy metal exposure, protein expression following the treatment of T24 human bladder carcinoma and RT4 human bladder papilloma cell line models with arsenic (As) and cadmium (Cd) was studied. Proteomic changes in these cell models were integrated with data from a human bladder cancer (BLCA) tissue proteome to identify possible protein indicators of heavy metal exposure. Results: After mass spectrometry based proteomic analysis and verification by Western blotting procedures, we identified 66 proteins that were up‐regulated and 92 proteins that were down‐regulated in RT4 cell extracts after treatment with As or Cd. Some 52 proteins were up‐regulated and 136 proteins were down‐regulated in T24 cell extracts after treatment with Cd. We further confirmed that down‐expression of the PML (promyelocytic leukemia) protein was sustained for at least 75 days after exposure of bladder cells to As. Dysregulation of these cellular proteins by As was associated with three biological pathways. Immunohistochemical analyses of paraffin‐embedded BLCA tissue slides confirmed that PML protein expression was decreased in BLCA tumor cells compared with adjacent noncancerous epithelial cells. Conclusions: These data suggest that PML may play an important role in the pathogenesis of BLCA and may be an indicator of heavy metal exposure in bladder cells. [ABSTRACT FROM AUTHOR]

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure. [ABSTRACT FROM AUTHOR]

Background: It has been unclear whether diabetes mellitus (DM) is positively associated with a risk of venous thromboembolism (VTE). In addition, whether the risk of VTE is altered in patients with type 1 diabetes (T1DM) has rarely been explored. Aim: We investigated whether patients with T1DM are at a relatively high risk of VTE development. Methods: We retrieved data from the National Health Insurance Research Database of Taiwan to conduct this retrospective cohort study. The T1DM group consisted of 4967 patients diagnosed as having T1DM before 2003. The non-T1DM group comprised 19 868 age- and sex-matched enrollees without T1DM. Cox proportional hazard regression analysis was used to investigate the hazard ratio of VTE in patients with T1DM relative to those without T1DM. Results: During a mean follow-up period of 8.61 years, the risk of VTE in the T1DM group was 5.33-fold higher than in the non-T1DM group after adjusting for dyslipidemia, hypertension, stroke, lower leg fracture or surgery, and obesity. Further stratified analysis revealed that the risk of VTE was significantly high in both sexes and in all age groups below the age of 60. Conclusion: T1DM appears to be an independent risk factor for VTE development. [ABSTRACT FROM AUTHOR]

Very-low-birth-weight (VLBW) infants have a high risk of postdischarge growth retardation (GR). Continued GR might exert negative long-term effects on their health. This study examined the prevalence and the risk factors for postdischarge GR among VLBW infants in Taiwan. Nationwide data from the Taiwan Premature Infant Follow-up Network between 2007 and 2011 were analyzed. Infants with a gestational age (GA) < 37 weeks and birth body weight (BBW) < 1500 g were enrolled. They were followed up after discharge at the corrected ages of 6, 12, and 24 months. Associations between postdischarge GR at the follow-ups and possible risk factors were analyzed. The prevalence of postdischarge GR among 2124 VLBW infants was 17.3%, 19.4%, and 13.8% at the corrected age (CA) of 6, 12, and 24 months, respectively. The significant perinatal factors of postdischarge GR were being small for gestational age (SGA) and extremely low birth weight (ELBW). ELBW infant with extra-uterine growth retardation (EUGR) at discharge or longer length of hospital stay (LOS) had poorer growth outcomes. Among non-ELBW infants, EUGR at discharge and surgical necrotizing enterocolitis (NEC) were the main influencing factors of unfavorable growth outcomes. RDS with surfactant therapy had a positive effect of postdischarge growth outcomes in ELBW infants. Postdischarge GR is still a serious problem in Taiwan. Being SGA and ELBW and EUGR were significant risk factors for postdischarge GR throughout the first two years of life in VLBW infants. An integrated and organized team for postdischarge care as well as scheduled follow-ups, detailed nutritional education, and thorough inspection are necessary. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to (1) identify the changes of 5 domains of family caregiver (FC) burden, overall burden, and its subtrajectories when caring for newly diagnosed advanced lung cancer patients during the first 6 months following cancer diagnosis; and (2) identify the FC-related and patient-related factors most associated with the overall FC burden and each of its subtrajectories.Methods: A total of 150 newly diagnosed advanced lung cancer patient-FC dyads were recruited from a Taiwanese medical center. The overall FC burden was evaluated 4 times: before treatment, and 1, 3, and 6 months after treatment. The potential subtrajectory of the caregiver burden was investigated by latent class growth analysis. The FC-related and patient-related factors having the greatest effect on the overall FC burden and its subtrajectories over time were identified by generalized estimating equations.Results: The highest level of burden domain was "Impact on daily schedule" over time. Generally, most of the FC reported a moderate level of overall burden over the investigation period. Three subtrajectories of the overall FC burden over time (% caregivers) were identified: high burden (34.7%), moderate burden (56.0%), and low burden (9.3%), respectively. The self-efficacy of FC was the strongest factor related to the changes of the FC's burden and burden in each subtrajectory.Conclusion: The results support the existing and different types of subtrajectories of the FC's burden. Health care professionals should provide care based on those differences. Further research to test interventions which integrate those important factors related to FC's burden, particularly FC's self-efficacy, is strongly suggested. [ABSTRACT FROM AUTHOR]

Background: Premature ejaculation (PE) is one of the most common male sexual dysfunctions with prominent psychological consequences. Type D personality (TDP) is also associated with multiple psychological disorders, such as depression and anxiety. However, the correlation between PE and TDP remains unknown. Aim: The study sought to investigate the relationships between depressive symptoms, TDP, and PE. Methods: Adult males in Taiwan who were 20 to 40 years of age and who had sexual intercourse in the past 6 months were recruited to complete online questionnaires composed of general demographics, the Premature Ejaculation Diagnostic Tool (PEDT), 5-item International Index of Erectile Function (IIEF-5), Type D Scale-14, and Depression and Somatic Symptom Scale (DSSS). Chi-square test and independent Student's t test were used to compare the parameters between the TDP and non-TDP groups. Univariate and multivariate logistic regression analyses were conducted to evaluate factors related to PE. Outcomes: Outcomes were the prevalence of PE and TDP in young Taiwanese men, the associations between depressive symptoms and PE and TDP, and the predictive factors of PE. Results: In total, 2558 men with a mean age of 31.3 ± 5.3 years were included in the present study. Among them, 315 (12.3%) and 767 (30.1%) participants were classified as having PE and moderate-to-severe erectile dysfunction (ED), respectively. In total, 1249 (48.8%) participants met the criteria for TDP. The PEDT, IIEF-5, and DSSS, including the total scores and depression and somatic subscales, were significantly higher in men with TDP (all P <.001). PE prevalence was significantly greater in men with TDP than in those without TDP (16.2% vs 8.6%; P <.001). Most parameters, including age, moderate-to-severe ED, the Type D Scale-14 subscales, and the DSSS somatic and depressive subscales, were significantly associated with PE in the univariate analysis. Only the depressive subscale of the DSSS and moderate-to-severe ED (IIEF-5 ≤16) were the independent predictors of PE in the multivariate analysis. Clinical Implications: The results suggest that it is important to consider the psychological effects of PE in young men, and the study has provided a biopsychosocial aspect to manage patients with PE. Strengths and Limitations: This is the first study to evaluate the association between PE, TDP, and depression in a large population of young adult males. However, the cross-sectional design may have limited the investigation of causality, and selection bias may be present. Conclusion: Men with TDP tended to have higher PEDT scores and a prevalence of PE and ED. Moderate-to-severe ED and depressive symptoms are the independent predictive factors of PE. [ABSTRACT FROM AUTHOR]

Volatile organic chemical exposure resulting from surgical operations is common in operating room personnel. The potential risk of long-term exposure to these low-level chemicals is always a concern. This study was conducted in an area hospital located in northern Taiwan to investigate the internal exposure scenario for operating room personnel. Breath samples were collected before and after surgery, whereas area samples were collected during the surgeries in process. There were 18 volatile organic compounds identified in the samples with gas chromatography-mass spectrometry. The average concentrations of sevoflurane (P = 0.0082), dimethyl sulfide (P = 0.0550), and methyl methacrylate (P = 0.0606) in breath samples collected after surgical operations were significantly higher compared to those obtained before surgical operations, whereas only slight elevations were present for benzene and hexamethyldisiloxane (P < 0.100). In addition, electrosurgical smoke-related chemicals, such as benzene, toluene, ethylbenzene, and m / p -xylene, also presented higher levels in operating room samples compared to the control area. Specifically, the findings in this preliminary study suggested the associations of elevated exposure to sevoflurane across various surgeries to methyl methacrylate with orthopedic surgery and to hexamethyldisiloxane with conventional electrosurgical units. Future study is warranted to explore the short-term high-level chemical exposure in operating rooms and to propose effective preventive measures accordingly to keep any exposure to chemicals at the lowest practical level. [ABSTRACT FROM AUTHOR]

Temperature measurements carried out on 9 hydrocarbon exploration boreholes together with Bottom Simulating Reflectors (BSRs) from reflection seismic images are used in this study to derive geothermal gradients and heat flows in the northern margin of the South China Sea near Taiwan. The method of Horner plot is applied to obtain true formation temperatures from measured borehole temperatures, which are disturbed by drilling processes. Sub-seafloor depths of BSRs are used to calculate sub-bottom temperatures using theoretical pressure/temperature phase boundary that marks the base of gas hydrate stability zone. Our results show that the geothermal gradients and heat flows in the study area range from 28 to 128°C/km and 40 to 159mW/m2, respectively. There is a marked difference in geothermal gradients and heat flow beneath the shelf and slope regions. It is cooler beneath the shelf with an average geothermal gradient of 34.5°C/km, and 62.7mW/m2 heat flow. The continental slope shows a higher average geothermal gradient of 56.4°C/km, and 70.9mW/m2 heat flow. Lower heat flow on the shelf is most likely caused by thicker sediments that have accumulated there compared to the sediment thickness beneath the slope. In addition, the continental crust is highly extended beneath the continental slope, yielding higher heat flow in this region. A half graben exists beneath the continental slope with a north-dipping graben-bounding fault. A high heat-flow anomaly coincides at the location of this graben-bounding fault at the Jiulong Ridge, indicating vigorous vertical fluid convection which may take place along this fault. [ABSTRACT FROM AUTHOR]

Propionyl-CoA carboxylase (PCC) is involved in the catabolism of branched chain amino acids, odd-numbered fatty acids, cholesterol, and other metabolites. PCC consists of two subunits, α and β, encoded by the PCCA and PCCB genes, respectively. Mutations in the PCCA or PCCB subunit gene may lead to propionic acidemia. In this study, we performed mutation analysis on ten propionic acidemia patients from eight unrelated and nonconsanguineous families in Taiwan. Two PCCA mutations, c.229C→T (p.R77W) and c.1262A→C (p.Q421P), were identified in a PCCA-deficient patient. Six mutations in the PCCB gene, including c.-4156_183+3713del, c.580T→C (p.S194P), c.838dup (p.L280Pfs*11), c.1301C→T (p.A434V), c.1316A→G (P.Y439C), and c.1534C→T (p.R512C), were identified in seven PCCB-deficient families. The c.-4156_183+3713del mutation is the first known large deletion that affects the PCCB gene functions. Furthermore, the c.1301C→T and c.-4156_183+3713del mutations in the PCCB gene have not been reported previously. Clinical features demonstrated that these two frequent mutations are associated with low enzyme activity and a classic propionic acidemia phenotype. [ABSTRACT FROM AUTHOR]

Background: Although endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) has been shown to increase the diagnostic yield over conventional bronchoscopic techniques, an important issue regarding the optimal number of biopsy specimens required has not been thoroughly investigated. Objectives: We sought to examine whether the number of biopsy specimens taken was associated with the diagnostic yield of EBUS-guided TBB and, if this was the case, to determine the optimal number of specimens required for the maximum diagnostic yield in peripheral pulmonary lesions. Methods: The medical records of patients undergoing EBUS-guided TBB for the diagnosis of peripheral pulmonary lesions from 2008 to 2010 were retrospectively reviewed. The association of clinical and radiological features, including the number of biopsy specimens, with the diagnostic yield was analysed. Results: A total of 384 patients were included for analysis. The overall diagnostic yield of EBUS-guided TBB was 73%, and the only factor influencing the diagnostic yield was the position of the probe. Patients in which the EBUS probe was placed within the lesions had a significantly higher yield (85%) than those in which the probe was adjacent to or outside the lesions (38%; p < 0.001). When the number of biopsy specimens was determined based on their adequacy, it was an insignificant factor in predicting the diagnostic yield. Conclusions: Probe position independently predicts the diagnostic yield of EBUS-guided TBB. In real-world practice, the optimal number of biopsy specimens should be decided on a case-by-case basis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Dissemination of multidrug-resistant, particularly tigecycline-resistant, Acinetobacter baumannii is of critical importance, as tigecycline is considered a last-line antibiotic. Acquisition of tet(X), a tigecycline-inactivating enzyme mostly found in strains of animal origin, imparts tigecycline resistance to A. baumannii. Herein, we investigated the presence of tet(X) variants among 228 tigecycline-non-susceptible A. baumannii isolates from patients at a Taiwanese hospital via polymerase chain reaction using a newly designed universal primer pair. Seven strains (3%) carrying tet(X)-like genes were subjected to whole genome sequencing, revealing high DNA identity. Phylogenetic analysis based on the PFGE profile clustered the seven strains in a clade, which were thus considered outbreak strains. These strains, which were found to co-harbor the chromosome-encoded tet(X6) and the plasmid-encoded blaOXA-72 genes, showed a distinct genotype with an uncommon sequence type (Oxford ST793/Pasteur ST723) and a new capsular type (KL129). In conclusion, we identified an outbreak clone co-carrying tet(X6) and blaOXA-72 among a group of clinical A. baumannii isolates in Taiwan. To the best of our knowledge, this is the first description of tet(X6) in humans and the first report of a tet(X)-like gene in Taiwan. These findings identify the risk for the spread of tet(X6)-carrying tigecycline- and carbapenem-resistant A. baumannii in human healthcare settings. [ABSTRACT FROM AUTHOR]

Background: Drug reference apps promote self-management and improve the efficiency and quality of work for physicians, nurses, pharmacists, and patients. This study aimed to describe a systematic and stepwise process to identify drug reference apps in Taiwan, assess the quality of these apps, and analyze the influential factors for user ratings. Methods: A two-step algorithm (KESS) consisting of keyword growing and systematic search was proposed. Seven independent reviewers were trained to evaluate these apps using Mobile App Rating Scale (MARS). A logistic regression model was fitted and average marginal effects (AME) were calculated to identify the effects of factors for higher user ratings. Results: A total of 23 drug reference apps in Taiwan were identified and analyzed. Generally, these drug reference apps were evaluated as acceptable quality with an average MARS score of 3.23. Higher user engagement, more functionality, better aesthetics, and more information associated with higher user ratings. Navigation is the most influential factor on higher user ratings (AME: 13.15%) followed by performance (AME: 11.03%), visual appeal (AME: 10.87%), credibility (AME: 10.67%), and quantity of information (AME: 10.42%). Conclusions: User experience and information clearly affect user ratings of drug reference apps. Five key factors should be considered when designing drug reference apps. [ABSTRACT FROM AUTHOR]

An editorial is presented which addresses the authors' views about the protection of universal health coverage in non-United Nations member states such as Taiwan, and it mentions the World Health Organization (WHO) and the Taiwanese government's Act to Implement the International Covenant on Civil and Political Rights. The International Covenant on Economic, Social and Cultural Rights (ICESCR) and a right to health in Taiwan are examined, along with human rights and global health policy.

The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB) and Pseudomonas aeruginosa. Antimicrobial agents are critical for treating the nosocomial infections caused by NFGNB. The aim of this study was to assess antimicrobial resistance and the use of antimicrobial agents. The bacterial isolates of 638,152 specimens from both inpatients and outpatients, retrieved from 2001 to 2008 at a medical center in central Taiwan, were examined for their susceptibility to various antimicrobial agents, including cefepime, imipenem, ciprofloxacin, gentamicin, amikacin, meropenem, and levofloxacin. Administrated prescriptions of the monitored antibiotics were analyzed using the Taiwan National Health Insurance Research Database (NHIRD). Our results show that the defined daily doses (DDDs) for cefepime, imipenem, and ciprofloxacin increased with time, and a trend toward reduced antimicrobial sensitivities of both ACB and P. aeruginosa was noticeable. In conclusion, the antimicrobial sensitivities of ACB and P. aeruginosa were reduced with the increased use of antibiotics. Continuous surveillance of antibiotic prescriptions and the prevalence of emerging resistance in nosocomial infections is warranted. [ABSTRACT FROM AUTHOR]

Raw milk production in Taiwan has increased year after year, which means that the environmental impact might also be intensified in certain regions. To balance both consumer demand and environmental sustainability, evaluating the potential impact and understanding the causal relationship between production and environment is imperative. This study applied the life cycle assessment (LCA) protocol to explore water consumption for raw milk production from cradle to farm gate of five dairy farms in Hsinchu County and evaluate the stress-weighted water scarcity footprint (WSF) as well as the water scarcity productivity (WSP) of the 16 Taiwanese counties and cities. Results indicated that the highest stress-weighted WSF of the dairy farms for raw milk production was located in northern and central Taiwan and was around 44.8 H2Oeq/kg fat- and protein-corrected milk (FPCM). On the other hand, both the smallest stress-weighted WSF (about 2.2 H2Oeq/kg FPCM) and the highest WSP (0.749 kg FPCM/m3 water) of the dairy farms were located in Nantou and Chiayi Counties, because these two counties were the least water-stressed regions in Taiwan. The achievement of this study could be the first and important reference for the sustainable production of raw milk and optimizing the industrial policy of dairy farming by policy makers. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) of plasma cell-free DNA identifies driver mutations in advanced non-small cell lung cancer (NSCLC) and may complement routine molecular evaluation. The utility of liquid NGS at the start of tumour workup is undetermined. This is a randomised study of patients with suspected advanced NSCLC. All patients received blood liquid NGS testing at their first clinic visit and underwent standard histological diagnosis and tissue genotyping, encompassing polymerase chain reaction based methods for EGFR mutation, immunohistochemical (IHC) staining for ALK fusion and BRAF V600E mutation, and an IHC screening followed by confirmation using fluorescence in situ hybridization confirmation for ROS1 fusion. They were then randomly assigned to receive NGS results either after tissue genotyping (Group A) or as soon as possible after histological diagnosis of advanced NSCLC (Group B). The study measured time to start of systemic treatment as the primary endpoint and secondary endpoints included biomarker discovery rate, objective response rate (ORR), and progression-free survival (PFS). This study enroled 180 patients with suspected advanced NSCLC, randomised into two groups. 63 patients in Group A and 59 in Group B with advanced NSCLC were confirmed as advanced NSCLC and analysed. Most had adenocarcinoma (Group A: 77.8%, Group B: 79.7%). The prevalence of EGFR mutations in the two groups was similar (Group A: 57.1%; Group B: 56.6%). Other driver alterations were rare. The median time to treatment was shorter in Group B (20 days) than in Group A (28 days). ORR and PFS did not differ between groups significantly. Liquid NGS had high concordance with tissue testing and identified driver mutations in 42.6% (20/47) of tissue-negative cases. Performing liquid NGS at the initial clinic visit for suspected advanced NSCLC identifies more patients suitable for targeted therapies and shortens time to the start of treatment. • Liquid NGS finds treatable mutations in over 60% of East Asian NSCLC patients. • Upfront liquid NGS shortens the time to treatment by 8 days in advanced NSCLC. • Liquid NGS detects 42.6% of cases missed by four-gene tissue testing. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To examine the changes in quality of life (QOL), symptoms, self-efficacy for coping with cancer, and factors related to those changes in patients with newly diagnosed advanced lung cancer.Design: Longitudinal and correlational.Setting: Oncology inpatient wards and outpatient departments of a medical center in northern Taiwan.Sample: 101 patients newly diagnosed with stage IIIB or IV lung cancer.Methods: Questionnaires were used to assess patients' QOL, symptoms, and self-efficacy before treatment and at one and three months following treatment. Factors related to the changes in global QOL and five functional dimensions were analyzed using six generalized estimating equation models.Main Research Variables: QOL, symptoms, and self-efficacy for coping with cancer.Findings: Patients reported moderate levels of global QOL, symptom severity, and self-efficacy for coping with cancer. They also reported high physical and cognitive functions, but relatively low role and social functions. Factors were significantly related to the most functional dimensions, including self-efficacy, fatigue, pain, sleep difficulties, and demographic- and disease-related factors. Self-efficacy was the most robust factor for predicting QOL.Conclusions: Patients with advanced lung cancer experience a compromised global QOL and relatively low social and role functioning during the first three months following cancer diagnosis. Levels of self-efficacy and symptoms significantly affected changes in QOL and functioning.Implications for Nursing: Applying a systematic assessment of changes in QOL and developing comprehensive interventions with self-efficacy training and symptom management are strongly recommended for clinical care to improve the QOL of patients with advanced lung cancer. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders (SD) and erectile dysfunction (ED) both play crucial roles in quality of life and have received increasing attention in the general population and among physicians.Methods: This study investigated the risk of ED in people diagnosed with SD compared with that in age- and sex-matched unaffected people. This longitudinal, nationwide, population-based cohort study was conducted using data in the Taiwan National Health Insurance Research Database (NHIRD) from January 1998 to December 2011. The sample consisted of 603 people with sleep apnea, 17,182 people with non-apnea SD, and 35,570 matched comparisons as controls. A Cox proportional hazard regression was used to compute the risk of ED in people with SD relative to that in people without SD.Results: The ED incidences were 9.44-fold higher (95% CI 6.49-13.7) in the sleep apnea cohort and 3.72-fold higher (95% CI 3.13-4.41) in the non-apnea SD cohort than in the control cohort, respectively, after age, sex, and comorbidities were adjusted for. The incidence of ED was higher in younger adults (adjusted hazard ratio (HR), 10.4 (95% CI 5.93-18.4) in the sleep apnea cohort and adjusted HR, 4.20 (95% CI 3.07-5.76) in non-apnea SD cohort) and those using benzodiazepine (adjusted HR, 9.69 (95% CI 5.48-10.6) in the sleep apnea cohort and adjusted HR, and 3.83 (95% CI 3.20-4.59) in the non-apnea SD cohort).Conclusion: This nationwide population-based cohort study provides evidence that people with SD, particularly those with sleep apnea, exhibit an increased risk of subsequent ED. [ABSTRACT FROM AUTHOR]

Background There is some evidence that the prevalence of depression in patients with tuberculosis (TB) is higher than those in the general population. However, the incidence of depression after Mycobacterium tuberculosis infection remains unknown. Our aim was to assess the association between TB and the subsequent risk of depression. Methods We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The TB cohort included 9020 patients who were newly diagnosed and recruited between 2000 and 2010. Each patient was randomly frequency-matched for age, sex and the year of index date with four people without TB from the general population. The newly diagnosed depression was followed up until the end of 2011. The relative risks of depression were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. Results The overall incidence rate of depression was 1.54-fold higher in the TB cohort as compared with the controlled cohort (8.15 vs. 5.29 per 1000 person-years, 95% confidence interval [CI] = 1.45–1.64). Stratified analyses by gender, age group, monthly income and comorbidities revealed that the adjusted hazard ratio (HR) of depression was higher in males as well as individuals older than 65 years with a low monthly income and comorbidities. Conclusion People who have been diagnosed with TB have a significantly higher risk of developing depression compared with those in the general population. We should pay more attention to this group of individuals and ensure that they are offered appropriate support. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is the main cause of nosocomial infections, which are increasingly difficult to treat due to the emergence of carbapenem resistance. This study focused on major carbapenemase genes and explored the association between carbapenemase genes, sequence types (ST types), and capsular types (K types). A total of 98 carbapenem-resistant A. baumannii (CRAB) strains were collected from two hospitals, the Chang Gung Memorial Hospital-Lin Kou branch (LCGMH) in northern Taiwan and the CGMH-Kaohsiung branch (KCGMH) in southern Taiwan, from 2015 to 2017. Major carbapenemase genes of class A, B, and D β-lactamases were detected by polymerase chain reaction. All strains except 1 were positive for bla OXA-51-like , 76 strains (77.6%) carried bla OXA-23-like , and 25 strains (25.5%) carried bla OXA-24-like. The regional distribution showed that bla OXA-23-like was more common than bla OXA-24-like in both hospitals (85.3% and 60% in LCGMH and KCGMH, respectively); however, the percentage of bla OXA-24-like was much higher in KCGMH (46.7%) than in LCGMH (16.2%). Oxford multilocus sequence typing and global optimal eBURST analysis were conducted for 59 strains. The results of this study showed the association between bla OXA gene patterns, ST types, and K types and demonstrated that four major K types, KL2, KL10, KL22, and KL52, which were associated with specific ST types, were mainly clustered into clonal complexes CC208 and CC549 (a unique clonal complex found in Taiwan). These findings provide important information for monitoring the epidemiology and dissemination of this pathogen. [ABSTRACT FROM AUTHOR]

Abstract: Bottom simulating reflectors (BSRs) observed on seismic sections are often considered as indicators for the existence of free gas, delineating the base of the gas hydrate stability zone. Abundant BSRs seen on seismic sections acquired off the SW coast of Taiwan indicate the likely and prevalent existence of gas hydrates in the study area. This study aims to characterize the occurrence of BSRs off SW Taiwan and to understand their relationship to topography, tectonic activity, and possible migration paths of gas-bearing fluids in this area. The tectonic setting off SW Taiwan is during the initial stage of arc-continent collision between the Luzon arc and the northeastern continental margin of the South China Sea. A series of west-vergent, imbricated folds and emergent thrusts develop in the accretionary wedge. Each fold-and-thrust sequence corresponds to an elongated submarine ridge if its crest is not buried by flat-lying sediments. By contrast, normal faulting prevails in the northeastern margin of the South China Sea. A correlation between distribution of BSRs, topography, and tectonic features can be observed. Four major occurrences of BSR types of ridge type, basin type, submarine-canyon type, and continental slope type, are recognized on the basis of the relationship of BSRs to topographic and structural features. Main characteristics of BSRs in the study area can be described as: (1) they occur mostly beneath topographic highs; (2) a discordant relationship between surfaces of the seafloor and underlying strata where BSRs are present; (3) BSRs are prevalent especially beneath the crest and flank of the upthrusting, large and inclined slope basins; and (4) in general, a series of high-amplitude dipping reflectors beneath BSRs can be found. These features indicate that gas hydrate may accumulate preferably beneath topographic ridges especially underneath four-way-dip topographic closures. This effect may exist because the buoyancy-driven, gas-bearing fluids tend to migrate upward and laterally toward structural highs and their corresponding topographic ridges. The distribution of BSRs indicates that gas hydrates occur more commonly in the accretionary wedge than in the South China continental margin. We suggest that the more widespread occurrence of gas hydrates in the accretionary wedge is due to the existence of multiple fault zones, which may help to tap more deep-seated gas-bearing fluids, in addition to the shallow biogenic gas, in this region. [Copyright &y& Elsevier]

Abstract: Off southwest Taiwan, a west-advancing orogenic wedge has obliquely impinged on the northern continental slope of the South China Sea (SCS) margin. We analyzed a dense grid of multi-channel seismic profiles to reveal the tectonic features in this oblique collision setting. In the upper SCS slope and adjacent to the accretionary wedge, the rifted continental margin is characterized by a deep-seated, oceanward-dipping, listric and active normal fault with rotated hangingwall strata beneath the slope. To the west of this slope segment, the mid-Oligocene to Recent post-breakup sediments show prograding and aggrading shelf-margin clinoforms that cover a series of small, possibly Paleogene, rift basins. In the submarine accretionary wedge, a series of west-vergent, NNW-striking fold-and-thrust structures characterizes the lower wedge, which can be further divided into frontal and rear segments with distinct structural features. The frontal segment is characterized by four west-vergent blind thrusts with gently folded limbs. In contrast, the rear, arcward segment is characterized by west-vergent, emergent and imbricate thrusts with tilted beds truncated at the hangingwalls. Strata within slope basins are tilted arcward, with dips that increase with depth, indicating continued relative uplift along thrust planes during sedimentation. Pulsed thrust activity is further evidenced by an array of arcward-dipping unconformable surfaces with westward onlapping strata in the basins. Longitudinal sedimentary tapering of pre-orogenic sediments correlates strongly with curvature of the submarine frontal accretionary belt, suggesting that pre-orogenic sediment thickness is the major control on the geometry of frontal structures. The preexisting SCS slope that lies obliquely in front of the advancing accretionary wedge has impeded the advancing of frontal folds resulting in a successive termination of folds against and along strike of the SCS slope. The existence of the SCS slope also leads the strike of impinging folds with NNW-trend to turn more sharply to a NE-strike, parallel to strike of the SCS slope. Our analysis shows that the pre-orogenic mechanical/crustal heterogeneities and seafloor morphology exert strong controls on the thrust-belt development in the incipient Taiwan arc-continent collision zone. [Copyright &y& Elsevier]

Mycoplasma pneumoniae is currently the most commonly detected bacterial cause of childhood community-acquired pneumonia in several countries. Of note, clonal expansion of macrolide-resistant ST3 occurred in Japan and South Korea. An alarming surge in macrolide resistance complicates the treatment of pneumonia. We aimed to evaluate the clinical manifestation and clonal relatedness of M. pneumoniae circulating among children in Taiwan. We prospectively enrolled 626 children with radiologically confirmed pneumonia between 2017 and 2019. An M. pneumoniae infection was suspected on clinical grounds, and tested by real-time PCR and oropharyngeal swab cultures. We used multilocus sequence typing and whole-genome sequencing to characterize the genetic features of M. pneumoniae. A total of 226 children with M. pneumoniae pneumonia were enrolled. Macrolide resistance was found in 77% (174/226) of patients. Multi-locus sequence typing revealed that ST3 (n = 93) and its single-locus variant ST17 (n = 84) were the predominant clones among macrolide-resistant strains. ST17 presented clinical characteristics comparable to its ancestor ST3. On multivariate analysis, macrolide resistance (OR 3.5; 95% CI 1.4–8.5; p 0.007) was independently associated with fever >72 hours after macrolide treatment. By whole-genome sequencing, prediction analysis of recombination sites revealed one recombination site in ST3 and ST17 compared with M29 (a macrolide-sensitive ST3 strain isolated from China in 2005) containing cytadhesin MgpC-like protein, RepMP4 and RepMP5. ST17 had another recombination site containing an adhesin and RepMP2/3. In addition to macrolide resistance, ST3 and its ST17 variant might evolve through recombination between repetitive sequences and non-P1 cytadhesins for persistent circulation in Taiwan. [ABSTRACT FROM AUTHOR]

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain 9V -3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a , pbp2b , and pbp2x alleles into the β-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM , and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance. A clonal shift with a highly β-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain 9V -3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM , and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance., Competing Interests: The authors declare no conflict of interest.

Aims: We explored long-term employment status and income before and after depression diagnosis among men and women and at different working ages in Taiwan., Methods: Data from 2006 to 2019 were obtained from the National Health Insurance Research Database (NHIRD). Individuals with newly diagnosed depressive disorder aged 15 to 64 years during the study period were identified. An equal number of individuals without depression were matched for their demographic and clinical characteristics. Employment outcomes included employment status, which was categorized into employed or unemployed, and annual income. Based on the occupation categories and monthly insurance salary recorded in the Registry for Beneficiaries of the NHIRD, a subject was defined as unemployed if he or she differed from the income earner or the occupation category was unemployed. Monthly income was defined as zero for unemployed subjects and proxied as monthly insurance salary for others. Annual income was the sum of monthly income in each observation year., Results: A total of 420,935 individuals with depressive disorder were included in the study, and an equal number of individuals with not diagnosed depression served as controls. Employment rate and income were lower in the depression group than in the control group before the year of diagnosis, with a difference of 5.7% in employment rate and USD 1,173 in annual income. This gap increased considerably after the year of diagnosis (7.3% in employment rate and USD 1,573 in annual incomes) and further widened in the subsequent years (8.1% in employment rate and USD 2,006 in annual incomes in the 5th following year). The drops in the employment rate and income caused by depression were more evident in men and older age groups than in women and younger age groups, respectively. However, the reduction in employment rate and income in the following years after the diagnosis was more considerable among younger age groups., Conclusions: The effect of depression on employment status and income was significant during the year of diagnosis and continued afterwards. The effect on employment outcomes varied between genders and across all age groups.

Background: Nosocomial bloodstream infection (BSI) remains a significant cause of mortality and morbidity. We evaluate the trend of the pathogens of nosocomial BSI and investigate the distribution of the pathogens to demonstrate the risk factors of mortality., Methods: In this retrospective study, we collected data from a 2076-bed tertiary referral center that offers a full range of clinical services in central Taiwan during January, 2016 to December, 2017., Results: Five hundred and eighty-four patients were identified with nosocomial BSI. Among the comorbidities of nosocomial BSI patients with, the most frequent were hypertension, in 294 patients (50.3%), malignancy, in 279 patients (47.8%); diabetes, in 278 patients (47.6%); chronic kidney disease, in 171 patients (29.3%); and liver cirrhosis, in 132 patients (22.6%). Gram-positive organisms caused 22.9% of these nosocomial BSIs, gram-negative organisms caused 69.2%, and fungi caused 6.8%. The most common organism causing nosocomial BSIs were Klebsiella spp. (14%), E coli. (14%), and Enterococcus spp. (11%). Multivariate analysis of risk factors for mortality displayed that comorbidity with low body weight, liver cirrhosis, and malignancy, high CRP level, high Charlson Comorbidity Index and internal medicine and hematology/oncology distribution were strikingly associated with mortality (P = 0.0222, 0.0352, 0.0008, 0.0122, <0.001, and 0.041; [OR] = 1.8097, 1.9268, 2.7156, 2.7585, 3.5431, and 2.2449, respectively)., Conclusion: K. spp. and E coli. became the most common pathogens of nosocomial BSI in recent years. Comorbidities could be important roles to predictive the outcome of nosocomial BSI. The modifiable risk factors of nosocomial BSI may be investigated further to improve the outcome., Competing Interests: Declaration of competing interest No actual or potential conflicts of interest were associated with this study., (Copyright © 2021. Published by Elsevier B.V.)

Objective: The molecular pathogenesis of malignant gliomas, characterized by diverse tumor histology with differential prognosis, remains largely unelucidated. An APOBEC3 deletion polymorphism, with a deletion in APOBEC3B, has been correlated to risk and prognosis in several cancers, but its role in glioma is unclear. The authors aimed to examine the clinical relevance of the APOBEC3 deletion polymorphism to glioma risk and survival in a glioma patient cohort in Taiwan., Methods: The authors detected deletion genotypes in 403 glioma patients and 1365 healthy individuals in Taiwan and correlated the genotypes with glioma risk, clinicopathological factors, patient survival, and patient sex. APOBEC3 gene family expression was measured and correlated to the germline deletion. A nomogram model was constructed to predict patient survival in glioma., Results: The proportion of APOBEC3B-/- and APOBEC3B+/- genotypes was higher in glioblastoma (GBM) patients than healthy individuals and correlated with higher GBM risk in males. A higher percentage of cases with APOBEC3B- was observed in male than female glioma patients. The presence of APOBEC3B-/- was correlated with better overall survival (OS) in male astrocytic glioma patients. No significant correlation of the genotypes to glioma risk and survival was observed in the female patient cohort. Lower APOBEC3B expression was observed in astrocytic glioma patients with APOBEC3B-/- and was positively correlated with better OS. A 5-factor nomogram model was constructed based on male patients with astrocytic gliomas in the study cohort and worked efficiently for predicting patient OS., Conclusions: The germline APOBEC3 deletion was associated with increased GBM risk and better OS in astrocytic glioma patients in the Taiwan male population. The APOBEC3B deletion homozygote was a potential independent prognostic factor predicting better survival in male astrocytic glioma patients.

Background: The addition of anti-angiogenesis drugs to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) or chemotherapy in patients with EGFR-mutant non-small cell lung cancer (NSCLC) can improve disease control. We conducted a study to evaluate the efficacy of combination therapeutic strategies and identify patients who could benefit from combination therapy., Methods: This study enrolled patients with stage IV EGFR-mutant NSCLC treated with first-line EGFR-TKIs between January 2014 and December 2020. We divided patients into three groups: patients who received an anti-angiogenesis drug as first-line combination therapy, those who received an anti-angiogenesis drug as further-line combination therapy, and those with no anti-angiogenesis therapy., Results: A total of 204 patients were enrolled in the final analysis. Progression-free survival (PFS) in patients receiving first-line anti-angiogenesis plus EGFR-TKI combination therapy was longer (18.2 months) than those treated with first-line EGFR-TKI monotherapy (10.0 months for both, p < 0.001). No difference in overall survival (OS) was observed among these three groups (30.5 vs. 42.6 vs. 33.7 months, p = 0.326). Multivariate Cox regression analysis revealed L858R mutation, pleural, liver, and bone metastasis as independent prognostic factors for poor OS. However, the addition of anti-angiogenesis therapy to patients with these poor prognostic factors improved OS to levels similar to those without these poor prognostic factors., Conclusion: First-line combination EGFR-TKI plus anti-angiogenesis therapy improves PFS in patients with stage IV EGFR-mutant NSCLC. Adding an anti-angiogenesis drug at any line to patients harboring L858R mutation with pleural, liver, or bone metastases can provide survival benefits., (© 2022. The Author(s).)

Background/aim: The tissue inhibitor of metalloproteinase-2 (TIMP-2) is a critical inhibitor of matrix metalloproteinases (MMPs). Along with MMPs, TIMP-2 regulates the breakdown and remodeling of the extracellular matrix (ECM) and basement membranes. This study investigated the role of genotypes of the TIMP-2 -418G/C (rs8179090) single nucleotide polymorphism on lung risk., Materials and Methods: A total of 358 lung cancer patients and 716 healthy subjects were recruited in this study. Genotypes were identified via the polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The distribution of alleles and genotype frequencies of TIMP-2 -418G/C genotypes between the two groups were compared and no statistically significant difference (p>0.05) was found. The heterozygous and homozygous variant genotypes showed no differential distribution between the control and case groups (p>0.05)., Conclusion: TIMP-2 -418G/C variants might not be associated with lung cancer susceptibility and could not serve as predictors., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Coronavirus Disease 2019 (COVID-19) is rapidly transmitted from person to person, causing global pandemic since December 2019. Instantly detecting COVID-19 is crucial for epidemic prevention. In this study, olfactory dysfunction is a significant symptom in mild to moderate COVID-19 patients but relatively rare in other respiratory viral infections. The Taiwan smell identification test (TWSIT) is a speedy and inexpensive option for accurately distinguishing anosmia that also quantifies the degree of anosmia. Using TWSIT in the outpatient clinic for early identifying the patients with mild to moderate COVID-19 can be promising., Methods: Nineteen patients confirmed COVID-19 in central Taiwan were collected and divided into two groups: olfactory dysfunction and non-olfactory dysfunction. Demographic characteristics, laboratory findings, and the results of the olfactory test were compared between these two groups., Findings: Thirteen (68.4%) of the 19 patients had olfactory dysfunction. The patients with olfactory dysfunction were younger than those without this symptom. The statistical difference in age distribution was significant between these two groups (IQR: 25.5-35.5 vs. IQR: 32.5-60.3; p-value: 0.012). There was no significant difference in gender, smoking history, comorbidities, travel history, respiratory tract infection symptoms, and laboratory findings between these two groups., Conclusion: This study demonstrated that young adults were prone to develop olfactory dysfunctions. In the flu season, olfactory dysfunction is considered a specific screening criterion for early detecting COVID-19 in the community. TWSIT can serve as a decent test for quantifying and qualifying olfactory dysfunction., (Copyright © 2021. Published by Elsevier B.V.)

Background: Tuberculosis (TB) is a serious opportunistic infection in liver transplant (LT) recipients with a high rate of morbidity and mortality. This study aims to clarify the frequency and risk factors for tuberculosis in LT recipients., Methods: A total of 884 LT recipients were investigated retrospectively at China Medical University Hospital, Taichung, Taiwan. We performed a case-control study (1:2) to investigate the potential risk factors and disease onset of TB after LT., Results: Among the 884 LT recipients, 25 of TB cases (2.8%) were reported from 2009 to 2016. The overall incidence of TB was 744 cases per 100,000 patient-year, which was 18-fold higher than the general population in Taiwan. The median time to develop TB after liver transplant was 20 months. Of the TB cases, 15 were pulmonary TB and 10 were extra-pulmonary TB. Five cases of those extra-pulmonary TB occurred in the first post-transplant year. Overall five-year survival rate was 63.3%. Multivariate analyses identified apical fibrotic change in pre-transplant computed tomographic (CT) finding and the exposure to mammalian target of rapamycin (mTOR) inhibitors before TB event as independent risk factors for TB development (Odd ratio (OR) 10.79, 95% confidence interval (CI), 1.73-67.49, p = 0.01; OR 3.847, 95% CI 0.80-18.51, P = 0.09, respectively)., Conclusion: TB incidence in LT recipients is high in this study. Among those post-transplant recipients with long-term immunosuppression, abnormal CT finding and exposure to mTOR inhibitors before liver transplant might be the risk factors for TB., (Copyright © 2019. Published by Elsevier B.V.)

The incidence of acute pancreatitis and related health care utilization are increasing. Acute pancreatitis may result in organ failure and various local complications with risks of morbidity and even mortality. Recent advances in research have provided novel insights into the assessment and management for acute pancreatitis. This consensus is developed by Taiwan Pancreas Society to provide an updated, evidence-based framework for managing acute pancreatitis., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to clarify the relationship between doctor-shopping behavior and clinical conditions, and to clearly outline the effects of both the number of clinic visits and the number of doctor changes on patients' health conditions. Data from January 1, 2000 to December 31, 2004 was collected from the National Health Insurance Research Database in Taiwan. After randomly selecting one million people, we extracted 5-year longitudinal data, about the number of clinic visits, number of doctor changes, and changes in self-health status for each patient with diabetes over the age of 18. We developed a relationship among the variables by using the generalized estimating equation. The results revealed that the number of clinic visits on the change of health status is a U curve, suggesting that health condition could be optimal with an appropriate number of clinic visits. The effect of the number of doctor changes is linearly correlated with health deterioration. The results suggest that disease conditions can only be controlled with an adequate number of clinic visits. Excessively frequent clinic visits are not only unfavorable to patients' health status but are also wasteful of limited medical resources. For diabetic mellitus patients, the more they change doctors, the worse their health status. All of these results are important for patients to stay healthy and to save medical resources.

Medication adherence plays an important role in disease management, especially for diabetes. The aim of this study was to examine the impacts of demographic characteristics on medication nonadherence and the impacts of nonadherence on both health status and medical expenses for diabetic patients in Taiwan.A total of 1 million diabetes mellitus patients were randomly selected from the National Health Insurance Research Database between January 1, 2000 and December 31, 2004. All records with missing values and those for participants under 18 years of age were then deleted. Because many patients had multiple clinical visit records, all records within the same calendar year were summarized into 1 single record for each person. This pre-processing resulted in 14,602 total patients with a combined 73,010 records over the course of 5 years. Generalized estimating equation models were then constructed to investigate the effects of demographic characteristics on medication nonadherence and the effects of nonadherence on patient health status and medical expenses. The demographic characteristics examined for each patient include gender, age, residential area, and socioeconomic status.Our analysis of how demographic variables impacted nonadherence revealed that elderly patients exhibited better overall medication adherence, but that male patients exhibited poorer medication adherence than female patients. Next, our analysis of how nonadherence impacted health status revealed that patients who exhibited medication nonadherence had poorer health status than patients with proper medication adherence. Finally, our analysis of how nonadherence impacted medical expenses revealed that patients who exhibited medication nonadherence incurred more medical expenses than those who exhibited proper medication adherence.This study's empirical results corroborate the general relationships expressed in the current literature regarding medication nonadherence. However, this study's results were statistically more reliable and revealed the precise impact on health status in terms of the Charlson comorbidity index and increased annual medical expenses. This indicates the need to improve patient attitudes toward medication adherence, which can have substantial effects both medically and economically.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital., Methods: Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections., Results: Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended., (Copyright © 2020. Published by Elsevier B.V.)