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    [[alternative]]Antimicrobial resistance among imipenem-non-susceptible Escherichia coli and Klebsiella pneumoniae isolates, with an emphasis on novel β-lactam/β-lactamase inhibitor combinations and tetracycline derivatives: The Taiwan surveillance of antimicrobial resis

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    [[abstract]]Background: To determine susceptibility of imipenem-non-susceptible Escherichia coli (INS-EC) and Klebsiella pneumoniae (INS-KP) isolates collected during 2020–2022 through a national surveillance program in Taiwan to novel antibiotics, and to compare the results with those obtained during 2012–2018. Methods: Minimum inhibitory concentrations were determined by broth microdilution methods. Genes encoding carbapenemases including blaKPC, metallo-β-lactamase (MBL) genes, and blaOXA-48 were detected via multiplex PCR. Data retrieved from our 2012–2018 study were used for comparison. Results: Of 3260 E. coli and 1457 K. pneumoniae isolates collected during 2020–2022, 0.9 % and 9.5 %, were INS-EC and INS-KP, respectively. Cefepime-zidebactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam were active against 100 %, 75.9 %, 65.5 %, and 79.3 % of 29 INS-EC isolates respectively; and against 100 %, 90.6 %, 64.5 %, and 67.4 % of 138 INS- KP isolates, respectively. Susceptibility was contingent upon carbapenemase types. Susceptibility rates of cefepime-zidebactam and ceftazidime-avibactam remained constant from 2012 to 2018 through 2020–2022 but those of imipenem-relebactam and meropenem-vaborbactam decreased significantly, which may be partially attributable to the increasing prevalence of blaOXA-48. Eighteen MBL-gene-positive isolates and two blaKPC-positive isolates were resistant to ceftazidime-avibactam, whereas all were susceptible to cefepime-zidebactam. Tigecycline had a higher susceptibility rate than eravacycline and omadacycline for K. pneumoniae isolates. Lascufloxacin and delafloxacin were effective against fewer than 10 % of INS isolates. Susceptibilities to novel tetracyclines and fluoroquinolones remained similar from 2012 to 2018 through 2020–2022. Conclusions: This study highlights significant resistance patterns of INS-EC and INS-KP isolates in Taiwan. The declining susceptibility rates and the rising prevalence of genetic resistance determinants highlight the importance of ongoing surveillance and antimicrobial stewardship

    [[alternative]]公衛學會五十周年紀念專文二:台灣「公共衛生核心課程基本能力測驗」的發展歷史與回顧分析

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    [[abstract]]Objectives: The Credential Examination on Public Health Core Course Competencies (or the Core Competency Exam) was conducted annually in Taiwan for 12 years, from 2009 to 2020. This study aims to analyze the initiation and development of the exam, encompassing the creation of the questions database and evaluation of pass rates, item difficulty, and the discrimination index, and provide directions for enhancing core course competencies. Methods: This study sought to understand the history of the exam, its development, and its annual conduction by reviewing documents provided by the Taiwan Public Health Association. Additionally, the exam questions on five subjects (Biostatistics, Epidemiology, Social and Behavioral Sciences, Environmental and Occupational Health, and Public Health Policy and Administration) were analyzed to determine their accuracy, difficulty, and discrimination ability. The statistical analyses included calculation of frequencies, percentages, and Pearson’s correlation coefficients, analysis of variance, nonparametric analysis of variance, and chi-square tests. Results: A total of 4,225 individuals registered for the exam between 2009 and 2020, and 2,183 of them passed, which was approximately 60.4% of the nonabsentees. From 2010, only multiple-choice questions were used for all five subjects. Therefore, item difficulty and the discrimination index were analyzed for the data collected from 2010 to 2020. The average pass rate was approximately 60% (range: 55.6%–71.5%). The participants scored lower in Biostatistics (average accuracy and standard error across problems: 0.54 ± 0.01) and Environmental and Occupational Health (0.51 ± 0.01) than in Epidemiology (0.56 ± 0.01), Social and Behavioral Sciences (0.67 ± 0.01), and Public Health Policy and Administration (0.58 ± 0.01). However, the discrimination index for Biostatistics (0.39 ± 0.01) was significantly higher (p < 0.001) than that for the other four subjects (range: 0.14–0.31). The before-test problem difficulty (easy, fair, or difficult) and the after-test problem accuracy (high, medium, or low) were significantly similar (p < 0.001) for all subjects except Biostatistics. Conclusions: The pass rate of the Core Competency Exam was found to have been stable. However, the difficulty level and item discrimination index varied among the five subjects. Focusing on specific topics and developing reference textbooks for these subjects may be necessary. © 2024, Taiwan Public Health Association. All rights reserved

    Exploring the causal relationship between metabolomics and thyroid cancer risk using genetic instrumental variables

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    [[abstract]]Purpose: This study investigates potential causal links between circulating metabolites and thyroid cancer risk using genetic instrumental variables. Methods: Summary data from a genome-wide association study (GWAS) on circulating metabolites (N=7,824)and thyroid cancer GWAS summary data, including 1,054 cases and 490,920 controls, were analyzed. Using genetic variants and the inverse variance weighted method, the study assessed the causal impact of metabolites on thyroid cancer risk and identified affected metabolite levels. Results: Isovalerylcarnitine and but yrylcarnitine demonstrated significant positive associations with the risk of thyroid cancer, exhibiting odds ratios of 6.11 (95% CI: 1.26 to 29.71) and 1.77 (95% CI: 1.05 to 2.96), respectively. The research uncovered a nuanced relationship between thyroid cancer and seven metabolites: glutamine, citrulline, ornithine, 4-hydroxyhippurate, stearamide, N1-methyl-3-pyridone-4-carboxamide, and taurolithocholate 3-sulfate.Conclusion: Our research reveals potential links between various metabolites and thyroid cancer risk, enhancing our understanding of the role circulating metabolites play in the etiology of thyroid cancer.[Disclosure of COI by Responsible researcher] Lead presenter is not the Responsible researcher.[Lead presenter] We have no financial relationships to disclose

    Acute kidney disease staging based on estimated glomerular filtration rate predicts outcomes better than staging based on serum creatinine in patients with dialysis-requiring AKI

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    [[abstract]]Background: The comparative performance of two staging systems for acute kidney disease (AKD), designated AKDeGFR and AKDsCr, remains uncertain. Our objective is to assess the predictive ability of these staging systems concerning outcomes. Methods: This population-based retrospective observational cohort study identified 71,289 hospitalized patients with acute kidney injury requiring dialysis between July 1, 2015, and June 30, 2022, in the Taiwan National Health Insurance Research Database. AKD stages were defined according to the ADQI 16 Workgroup (AKDsCr) and 2021 KDIGO Consensus (AKDeGFR). Cox proportional hazard models were constructed to examine associations between AKD stages and outcomes including mortality and sustained renal recovery. Results: The AKDeGFR staging system predicted both outcomes better than the AKDsCr staging system (Figure 1). Hazard ratios and 95% confidence intervals for mortality across increasing AKDeGFR stages were 1.27 (1.18 - 1.36), 1.70 (1.59 - 1.82), 2.49 (2.35 - 2.64), 2.96 (2.78 - 3.15), and 5.22 (5.02 - 5.43). Conversely, within the AKDsCr staging system, hazard ratios and 95% confidence intervals for mortality across ascending stages were 1.00 (0.93 - 1.07), 1.00 (0.91 - 1.10), 0.93 (0.81 - 1.07), and 3.37 (3.27 - 3.46). Subgroup and sensitivity analyses yielded consistent results. Conclusion: The AKDeGFR staging system performs better than the AKDsCr staging system in patients with acute kidney injury requiring dialysis regarding all-cause mortality and kidney recovery

    Population structure of the invasive Asian tiger mosquito, aedes albopictus, in Europe

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    [[abstract]]The Asian tiger mosquito, Aedes albopictus, is currently the most widespread invasive mosquito species in the world. It poses a significant threat to human health, as it is a vector for several arboviruses. We used a SNP chip to genotype 748 Ae. albopictus mosquitoes from 41 localities across Europe, 28 localities in the native range in Asia, and 4 in the Americas. Using multiple algorithms, we examined population genetic structure and differentiation within Europe and across our global dataset to gain insight into the origin of the invasive European populations. We also compared results from our SNP data to those obtained using genotypes from 11 microsatellite loci (N = 637 mosquitoes from 25 European localities) to explore how sampling effort and the type of genetic marker used may influence conclusions about Ae. albopictus population structure. While some analyses detected more than 20 clusters worldwide, we found mosquitoes could be grouped into 7 distinct genetic clusters, with most European populations originating in East Asia (Japan or China). Interestingly, some populations in Eastern Europe did not share genetic ancestry with any populations from the native range or Americas, indicating that these populations originated from areas not sampled in this study. The SNP and microsatellite datasets found similar patterns of genetic differentiation in Europe, but the microsatellite dataset could not detect the more subtle genetic structure revealed using SNPs. Overall, data from the SNP chip offered a higher resolution for detecting the genetic structure and the potential origins of invasions

    Real-world use and treatment outcomes of ceftazidime-avibactam in gram-negative bacterial infection in Taiwan: A multicenter retrospective study

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    [[abstract]]Objectives: Ceftazidime-avibactam (CAZ-AVI) has been launched in Asian countries for five years, but local real-world data about patient characteristics, efficacy, and safety of CAZ-AVI is limited. We conducted a multicenter, retrospective study to investigate the clinical characteristics, microbiology, and outcomes of patients treated with CAZ-AVI for Gram-negative bacterial infection in Taiwan. Methods: This investigation was conducted as a multicenter retrospective cohort study involving five medical centers in Taiwan. Adult patients with documented/suspected Gram-negative bacterial infection and received >= 24 hours of CAZ-AVI were eligible for study cohort enrollment. In-hospital mortality was defined as the primary outcome, while symptom resolution or significant improvement, considered the secondary outcome, was defined as clinical success. Results: Among the 472 patients treated by CAZ-AVI, 46.2 % (218/472) had respiratory tract infections, 22.0 % (104/472) had complicated urinary tract infections, 14.0 % (66/472) had complicated intra-abdominal infections, and 10.0 % (47/472) had primary bacteremia. Most patients receiving ceftazidime/avibactam in Taiwan are old (mean: 70.6 years old), have a high SOFA score (mean 8.4), and have a high Charlson Comorbidity Index score (345/472, 73.1 %>= 4). 90 % of CAZ-AVI were used as targeted therapy for pathogens, including Klebsiella pneumoniae (64.4 %, 304/472), Pseudomonas aeruginosa (17.8 %, 84/472), Escherichia coli (8.3 %, 39/472), and Enterobacter spp. (2.3 %, 11/472). The overall clinical success rate is 58.1 % (274/472). The in-hospital mortality rate is 41.1 % (194/472). Conclusions: Most patients receiving CAZ-AVI as targeted therapy in Taiwan with characteristics of older age, high SOFA scores, and high CCI scores. Receiving immunomodulators, higher SOFA score, and Enterobacter spp. infections were the significant factors associated with in-hospital mortality, whereas early initiating CAZ-AVI treatment and CAZ-AVI monotherapy are associated with better outcome

    Role of neoadjuvant chemoradiation therapy for resectable and borderline resectable pancreatic adenocarcinoma-A systematic review and meta-analysis

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    [[abstract]]BACKGROUND: Randomized trials and meta-analyses have indicated longer survival with neoadjuvant than with adjuvant therapy in patients with resectable or borderline resectable (R/BR) pancreatic adenocarcinoma. Despite the efficacy of chemotherapy, the role of radiation therapy as an adjuvant or neoadjuvant treatment for patients with R/BR pancreatic adenocarcinoma remains unclear. In this systematic review and meta-analysis, we compared the benefits of additional chemoradiation therapy (CRT) to neoadjuvant chemotherapy (NAC) with NAC alone for R/BR pancreatic adenocarcinoma. METHODS AND MATERIALS: A systematic literature search was conducted on Embase, Web of Science, PubMed, Cochrane, and Google Scholar. Median overall survival (OS) was the primary endpoint. Secondary endpoints included disease-free survival (DFS), resection rate, and R0 resection rate. RESULTS: This review and meta-analysis included 31 prospective studies, of which 9 were randomized trials. In these studies, 658 patients from 14 study arms received NAC alone and 912 patients from 19 study arms received both NAC and CRT (NAC-CRT). The pooled median OS was 25.55 months (95% CI, 21.59-30.24 months) for NAC alone and 17.55 months (95% CI, 16.47-18.70 months; P < .0001) for NAC-CRT. The pooled R0 resection rate was higher with NAC-CRT (83.43%) than with NAC (69.97%; P < .0001). No significant difference was observed in DFS or resection rate between the 2 groups. In patients who received 5 or more cycles of initial chemotherapy, NAC-CRT was associated with longer OS than NAC (23.30 vs 21.85 months; P = .856). CONCLUSIONS: NAC provides significantly longer OS than NAC-CRT to R/BR pancreatic adenocarcinoma. NAC-CRT is associated with a significantly improved R0 resection rate. This positive local effect of CRT can be translated to extended survival when 5 cycles or more of NAC are prescribed

    On estimation of overall treatment effects in multiregional clinical trials under a discrete random effects model

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    [[abstract]]Multiregional clinical trials (MRCTs) have become a standard strategy for pharmaceutical product development worldwide. The heterogeneity of regional treatment effects is anticipated in an MRCT. For a two-group comparative study in an MRCT, patient assignments, including regional weights and treatment allocation ratios, are predetermined under the same protocol. In practice, the observed patient assignments at the final analysis stage are often not equal to the predetermined patient assignments, which may impact the accuracy of estimating the overall treatment effect and may lead to a biased estimator. In this study, we use a discrete random effects model (DREM) to account for the heterogeneous treatment effect across regions in an MRCT and propose a bias-adjusted estimator of the overall treatment effect through a naïve estimator conditioned on ancillary statistics based on the observed patient assignments at the final analysis stage in the trial. We also perform power analysis for the overall treatment effect and determine the overall sample size for the bias-adjusted estimator with the DREM. Results of simulation studies are given to illustrate applications of the proposed approach. Finally, we provide an example to demonstrate the implementation of the proposed approach

    [[alternative]]Primers, snp markers and method for genotyping mycobacterium tuberculosis

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    [[abstract]]本發明係提供一種用於結核分枝桿菌(M.tuberculosis)之基因型鑑定之引子組,其係選自由引子組1至25(SEQ ID Nos.1至50)所成群組之一種或多種;亦提供一種用於結核分枝桿菌之基因型鑑定之延伸引子,其係選自由SEQ ID Nos.51至75所成群組之一種或多種。本發明亦提供結核分枝桿菌之單核苷酸多態性標記之組合。本發明進一步提供一種基因型鑑定結核分枝桿菌之方法及套組

    免疫抑制细胞及其制造和使用方法

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    [[abstract]]本发明涉及一种免疫抑制细胞及其制造和使用方法。所述免疫抑制细胞通过将一前驱细胞培养于含有GRO趋化激素之培养基中而得到

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