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Ying-Fei Yang,1 Yi-Jun Lin,2 Shu-Han You,3 Tien-Hsuan Lu,4 Chi-Yun Chen,5,6 Wei-Min Wang,1 Min-Pei Ling,7 Szu-Chieh Chen,8,9 Chung-Min Liao1 1Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 10617, Taiwan; 2Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Taipei, 11230, Taiwan; 3Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung City, 20224, Taiwan; 4Department of Science Education and Application, National Taichung University of Education, Taichung, 403514, Taiwan; 5Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, 32610, USA; 6Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32608, USA; 7Department of Food Science, National Taiwan Ocean University, Keelung City, 20224, Taiwan; 8Department of Public Health, Chung Shan Medical University, Taichung, 40201, Taiwan; 9Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, 40201, TaiwanCorrespondence: Chung-Min Liao, Department of Bioenvironmental Systems Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan, Email cmliao@ntu.edu.twBackground: The emergence and progression of highly divergent SARS-CoV-2 variants have posed increased risks to global public health, triggering the significant impacts on countermeasures since 2020. However, in addition to vaccination, the effectiveness of non-pharmaceutical interventions, such as social distancing, masking, or hand washing, on different variants of concern (VOC) remains largely unknown.Objective: This study provides a mechanistic approach by implementing a control measure model and a risk assessment framework to quantify the impacts of control measure combinations on the transmissions of five VOC (Alpha, Beta, Delta, Gamma, and Omicron), along with a different perspective of risk assessment application.Materials and Methods: We applied uncontrollable ratios as an indicator by adopting basic reproduction number (R0) data collected from a regional-scale survey. A risk assessment strategy was established by constructing VOC-specific dose-response profiles to implicate practical uses in risk characterization when exposure data are available.Results: We found that social distancing alone was ineffective without vaccination in almost all countries and VOC when the median R0 was greater than two. Our results indicated that Omicron could not be contained, even when all control measure combinations were applied, due to its low threshold of infectivity (~3× 10− 4 plague-forming unit (PFU) mL− 1).Conclusion: To facilitate better decision-making in future interventions, we provide a comprehensive evaluation of how combined control measures impact on different countries and various VOC. Our findings indicate the potential application of threshold estimates of infectivity in the context of risk communication and policymaking for controlling future emerging SARS-CoV-2 variant infections.Keywords: SARS-CoV-2, variants of concern, basic reproduction number, modeling, non-pharmaceutical interventions, infection risk

Tsen-Pei Chen,1,2 Ying-Jia Lin,3 Yu-Lin Wang,4,5 Li-Min Wu,2,6 Chung-Han Ho3,7,8 1Department of Nursing, Chi Mei Medical Center, Tainan City, Taiwan; 2School of Nursing, Kaohsiung Medical University, Kaohsiung City, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan; 4Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan City, Taiwan; 5Department of Biomedical Engineering, National Cheng Kung University, Tainan,Taiwan; 6Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan; 7Department of Information Management, Southern Taiwan University of Science and Technology, Tainan City, Taiwan; 8Cancer Center, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Li-Min Wu, School of Nursing, Department of Medical Research, Kaohsiung Medical University Hospital, No. 100, Shin-Chuan 1st Road., Sanmin District, Kaohsiung City, 807378, Taiwan, Email painting@kmu.edu.tw Chung-Han Ho, Department of Medical Research, Chi Mei Medical Center, No. 901, Chung Hwa Road, Yongkang Dist, Tainan City, 710, Taiwan, Email ho.c.hank@gmail.comBackground: Stroke survivors in post-acute care frequently experience physiological dysfunction and reduced quality of life. This study aims to assess the impact of the Post-Acute Care Interprofessional Collaborative Practice (PAC-IPCP) program across different care settings, and to identify sensitive tools for assessing physiological functions among post-acute stroke survivors.Methods: This retrospective study involved 210 stroke survivors in Taiwan. Participants who self-selection for their preferred between hospital care setting and home care setting under PAC-IPCP. Multiple assessment tools were utilized, including the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment (MNA), EQ-5D-3L, and Instrumental Activities of Daily Living (IADL). The logistic regression was used to estimate the odds ratios of various functional assessment tools between hospital and home care settings. Additionally, the area under the ROC curves was used to determine which functional assessment tools had higher accuracy in measuring the association between care settings.Results: Of the study population, 138 stroke survivors (65.71%) selection hospital care setting and 72 stroke survivors (34.29%) selection home care setting. The PAC-IPCP program was equally effective in both care settings for physical function status and quality of life improvements. Specifically, the BI emerged as the most sensitive tool for assessing care settings, with an adjusted OR of 1.04 (95% CI:1.02– 1.07, p < 0.0001; AUC = 0.7557). IPCP-based hospital and home care models are equally effective in facilitating improved functional outcomes in post-acute stroke survivors.Conclusion: The PAC-IPCP program is versatile and effective across care settings. The BI stands out as a robust assessment tool for physiological functions, endorsing its broader clinical application. Future studies should also consider swallowing and nutritional status for a more holistic approach to rehabilitation.Keywords: stroke, neurology, subacute care, recovery of function, health care

Yuan-Kai Fu,1 Chi-chin Sun,2,3 Kuan-Jen Chen,1,3 Yu-Jr Lin,4 Chee-Jen Chang,4– 6 Shu-Chen Chang,4 Ming-Hui Sun1,3 1Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 3College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan; 5Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan; 6Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, TaiwanCorrespondence: Ming-Hui Sun, Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, No. 5, Fuxing Street, Guishan District, Taoyuan, 333, Taiwan, Tel +886-3-3281200 ext 8666, Fax +886-3-3287798, Email minghui0215@gmail.comStudy Objectives: To evaluate the association between obstructive sleep apnea (OSA) and dry eye disease (DED) and analyze the impact of Continuous Positive Airway Pressure (CPAP) on DED.Methods: This is a retrospective population-based case-control study. Patients who underwent polysomnography in Taiwan from March 1, 2009, to March 1, 2020, were identified from the database of a sleep center. Patients who were diagnosed with keratoconjunctivitis sicca or tear film insufficiency were included. Patients without data from Schirmer’s test, lacking tear break-up time values, or with a history of refractive surgery, Sjögren’s syndrome, ocular injuries, or a disability in eyelid closure were excluded. All patients with DED enrolled had DED in both eyes. OSA severity between patients with and without DED was compared.Results: In total, 86 patients with DED and 86 age-matched patients without DED were enrolled. Significant differences in apnea-hypopnea index values (patients with DED: 29.1 ± 23.4, patients without DED: 17.9 ± 20.2, P < 0.001), OSA severity (P < 0.001), and lowest oxygen saturation (P = 0.040) between patients with and without DED were observed. A multivariate logistic regression model indicated that the use of CPAP was independently associated with DED after adjustments for OSA severity. Patients undergoing CPAP were at greater risk of developing DED than those not undergoing CPAP (Odds ratio: 3.93, 95% confidence interval: 1.47– 10.49, P = 0.006).Conclusion: OSA severity is associated with DED and might be attributed to the use of CPAP.Keywords: dry eye disease, obstructive sleep apnea, continuous positive airway pressure

Yi-Chun Liu,1 Shuh-Kuan Liau,1 Cheng-Chieh Hung,1 Chao-Yu Chen,1 Yueh-An Lu,1 Yu-Jr Lin,2 Ya-Chung Tian,1 Yung-Chang Chen,1 Fan-Gang Tseng,3,4 Hsiang-Hao Hsu1 1Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Research Services Center for Health Information, from Chang Gung University, Taoyuan, Taiwan; 3Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan; 4Institute of Nano Engineering and Microsystems, National Tsing Hua University, Hsinchu, TaiwanCorrespondence: Hsiang-Hao Hsu, Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, No. 5 Fu-Shin Street, Guishan, Taoyuan, 333, Taiwan, Tel +886-3-328-1200 ext. 8181, Fax +886-3-3282173, Email hsianghao@gmail.comBackground: Listeriosis is caused by the facultative anaerobic bacterium Listeria monocytogenes. Infection from Listeria-contaminated food or water is the main etiology. If Listeria travels outside the intestines, it can cause invasive listeriosis, such as sepsis, meningitis, and meningoencephalitis. Invasive illness is especially dangerous for pregnant women and their newborns, elderly people, and people with compromised immune systems or medical conditions such as end-stage kidney disease (ESKD) patients receiving long-term dialysis.Purpose: Describe the manifestations and hospital outcomes of invasive listeriosis and identify the risk factors for in-hospital and one-year mortality in ESKD patients receiving long-term dialysis.Patients and Methods: This retrospective observational study examined hospitalized patient records at a Taiwanese tertiary medical center from August 1, 2000, to August 31, 2021. ESKD patients on chronic dialysis were identified with invasive listeriosis by blood culture and discharge diagnosis. Over 21 years, we accurately recorded 26 cases.Results: ESKD patients on chronic dialysis with invasive listeriosis have a poor prognosis. Only 53.8% of chronic dialysis patients with invasive listeriosis survived their first hospital episode. 42.3% of hospitalized ESKD patients with invasive listeriosis survived one year later. In univariate analysis, shock, tachypnea (RR ≥ 22), respiratory failure, qSOFA score ≥ 2, and lower initial platelet count were linked to greater in-hospital mortality rates.Conclusion: ESKD patients with invasive listeriosis have a grave prognosis. Our research reveals that an early blood sample for a bacterial culture may identify invasive listeriosis in chronic dialysis patients with fever, nausea or vomiting, confusion, and respiratory distress. This study is the first to identify a lower platelet count and qSOFA score ≥ 2 as markers of high-risk invasive listeriosis in ESKD patients.Keywords: chronic dialysis, ESKD, invasive listeriosis, qSOFA, outcome

Xin-Mei Hu,1,&ast; Can-Can Wang,1,&ast; Yu Xiao,1 Yu Liu,1 Hong-Ri Huang,2 Peng Jiang,1 Ying-Kai Wang,1 Yun-Jin Lin,1 Liang-Cheng Li,3 Zhong-Quan Qi1 1Medical College, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Research and Development, Guangxi Taimei Rensheng Biotechnology Co., Ltd, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong-Quan Qi, Guangxi University, Da-Xue-Dong Road No. 100, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region, 530004, People’s Republic of China, Tel +8613806001271, Email yxyyz@gxu.edu.cn Liang-Cheng Li, Xiamen University, No. 4221-115, Rm 355, Xiang’an District, Xiang’an, Xiamen Fujian Province, 361102, People’s Republic of China, Tel +8618359206906, Email lchli2013@xmu.edu.cnPurpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future.Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection.Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group.Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.Keywords: exosomes, cynomolgus monkeys, safety, immunotoxicity

Sheng-Kai Wang,1 Jia-Wei Cai,2 Yu Zhang,3 Ya-Jing Lin,4 Yi-Hui Yang2 1Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, People’s Republic of China; 2Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Pathology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Clinical Laboratory, the First People’s Hospital of Wenling, Affiliated to Wenzhou Medical University, Taizhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yi-Hui Yang, Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No. 365, Renmin East Road, Jinhua, 321000, People’s Republic of China, Tel/Fax +86 139 5848 5323, Email aoliao0211@163.comAbstract: Squamous cell carcinoma (SCC) in situ can occur on any skin or mucus surface and is more commonly found in elderly patients on areas of skin that have been sunburnt. Most previous case reports are from dermatologists, with few published reports from pathologists. In this study, three patients underwent pathological routine and auxiliary immunohistochemical (IHC) examination and were ultimately diagnosed with pagetoid SCC in situ – a different diagnosis from the initial clinical assessment. All three patients received a complete resection of the skin mass. After follow-up, as of June 2023, the patients had no tumour recurrence or metastasis. Pagetoid SCC in situ is a particular type of SCC in situ that has no specific features in clinical manifestations, gross diagnosis or histopathological sections. The final diagnosis depends on IHC staining. Pagetoid SCC in situ expresses EMA, CK5/6 and p63 but not CEA, CK8 or S-100, which are expressed in extramammary Paget’s disease. Pagetoid SCC in situ is usually only locally invasive, and the main treatment is complete surgical resection. The prognosis is related to human papillomavirus infection, surgical margin closure, disease location, tumour thickness and other factors.Keywords: pagetoid, pagetoid squamous cell carcinoma in situ

Gui-Qin Zhong,1,&ast; Bi-Hua Lin,1,&ast; Yu-Xuan Chen,2 Yan-Juan Lin,1 Chun-Mei Chen3 1Department of Neurosurgery Nursing, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 2College of Nursing, Fujian Medical University, Fuzhou, 350108, People’s Republic of China; 3Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan-Juan Lin, Department of Neurosurgery Nursing, Fujian Medical University Union Hospital, No. 29, Xin Quan Road, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +8613365910562, Email linyanjuanlyj9k@126.com Chun-Mei Chen, Department of Neurosurgery, Fujian Medical University Union Hospital, No. 29, Xin Quan Road, Fuzhou City, Fujian Province, 350001, People’s Republic of China, Tel +8613365910678, Email chenchumeiccm0@126.comObjective: To investigate the prevalence of postoperative kinesiophobia in patients with cervical spondylotic myelopathy (CSM) and factors influencing the occurrence of kinesiophobia, to provide relevant basis for making clinical decisions for targeted interventions.Methods: We enrolled a total of 85 patients who underwent CSM surgery at two grade-A general public hospitals in Fujian Province between September 2021 and May 2022. We conducted a questionnaire survey using the Tampa Scale for Kinesiophobia (TSK) and the Zung Self-Rating Anxiety Scale (SAS). Patients evaluated pain using a visual analogue scale. We used one-way ANOVA and logistic multiple regression analysis to identify the relevant influencing factors.Results: The TSK score was (41.88± 4.46) in 85 postoperative CSM patients, 65 males and 20 females, and there were 31 patients under 40 years old, 54 patients over 40 years old, 58 patients below high school education and 27 patients above high school education, and among them, 81.17% were diagnosed with kinesiophobia. Age was positively correlated with TSK score (r = 0.379, P < 0.05) and therefore a risk factor for kinesiophobia (OR = 1.941, 95% CI = 1.021– 3.690). Additionally, the duration of the disease was a protective factor for kinesiophobia (OR = 0.179, 95% CI = 0.053– 0.605).Conclusion: Patients with CSM were at high risk of developing kinesiophobia postoperatively. Age and duration of the disease were factors influencing the occurrence of kinesiophobia in this group.Keywords: cervical spondylotic myelopathy, influencing factors, kinesiophobia, postoperative

Cai-Feng Lan,1,&ast; Bi-Hua Lin,2,&ast; Cai-Ling Nie,1 Xiu-Ling Guo,1 Dan-Hong Zhou,1 Yan-Juan Lin3 1Department of Gynecology and Obstetrics, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 2Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 3Nursing Department, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan-Juan LinNursing Department, Fujian Medical University Union Hospital, No. 29 of Xinquan Road, Gulou District, Fuzhou, 350001, Fujian, People’s Republic of ChinaTel +86 591 86218332Email yjlin689@163.comObjective: To investigate the occurrence and influencing factors of moderate to severe pain in patients with cesarean scar pregnancy (CSP) after uterine artery embolization (UAE).Methods: Ninety-eight patients with CSP who underwent UAE in gynecology department of the Fujian Medical University Union Hospital from January 2017 to December 2020 were enrolled, and the specialty data in patients were collected for pain assessment with the adoption of the numerical rating scale (NRS).Results: Moderate to severe pain occurred in 36 patients after surgery, and the interquartile of time to the first onset of postoperative pain in patients was 3.04 (1.75, 7.40) hours. The number of pregnancies, number of miscarriages, human chorionic gonadotropin (HCG) before curettage, duration of medication before UAE, and hemorrhage after UAE were not significantly correlated with the occurrence of moderate to severe pain after UAE (P > 0.05). The volume of gestational sac and days of gestation were responsible for the occurrence of moderate to severe pain after UAE (P < 0.05), with the former being the main influencing factor, and these explained 8.3% of the total variance.Conclusion: Moderate to severe pain occurred commonly in patients with CSP undergoing UAE. In clinical care of patients with CSP who are going to undergo UAE, data concerning the volume of gestational sac and days of gestation should be considered for anticipatory pain assessment, and interventions should be implemented as early as possible to reduce the pain and improve the experience of care.Keywords: cesarean scar pregnancy, uterine artery embolization, moderate to severe pain, research

Shuh-Kuan Liau,1 George Kuo,1 Chao-Yu Chen,1 Yu-Cheng Chen,2 Yueh-An Lu,1 Yu-Jr Lin,3 Cheng-Chieh Hung,1 Ya-Chung Tian,1 Hsiang-Hao Hsu1 1Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; 3Research Services Center for Health Information from Chang Gung University, Taoyuan, TaiwanCorrespondence: Hsiang-Hao HsuDepartment of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, No. 5 Fu-Shin Street, Kweishan, Taoyuan, 333, TaiwanTel +886-3-328-1200 ext. 8181Fax +886-3-3282173Email hsianghao@gmail.comPurpose: To elucidate the in-hospital and long-term outcomes of infective endocarditis (IE) in end-stage kidney disease (ESKD) patients on chronic dialysis and to analyze the risk factors of mortality.Patients and Methods: The case files of 1,817 patients who were hospitalized for IE over a 14-year period were retrospectively reviewed. Of these, 116 ESKD patients on chronic dialysis were enrolled in this study. Cox’s proportional hazard model was used to evaluate the risk factors of mortality and long-term outcomes.Results: The in-hospital mortality rate of the 116 enrolled patients was as high as 43.1%. Patients who survived the index admission had a three-year mortality rate of 33%. Univariate analysis was used to compare survivors and non-survivors; poor in-hospital outcomes were associated with the use of a tunneled cuffed catheter for dialysis access, a shorter duration hospitalization, shock or respiratory failure during hospitalization, a higher white blood count, a higher percentage of polymorphonuclear leukocytes, a higher C-reactive protein level, a lower serum albumin level, and a higher total bilirubin level. Following multivariate adjustment, shock (odds ratio, 9.29, with a 95% confidence interval [CI] of 2.78 to 34.24; p< 0.001) or respiratory failure (odds ratio, 25.16, with a 95% CI of 5.63 to 153.54; p< 0.001) during hospitalization was strongly associated with increased in-hospital mortality. Patients who underwent cardiac operations (odds ratio, 0.22, with a 95% CI of 0.052 to 0.86; p=0.031) had better in-hospital outcomes. Heart failure reduced ejection fraction (HFrEF) at the time of initial hospitalization was an independent risk factor for 3-year mortality (hazard ratio, 3.48, with a 95% CI of 1.09 to 11.09; p=0.035).Conclusion: The outcomes of IE for ESKD patients on chronic dialysis were poor. Only 56.9% of these patients survived the index admission and their mortality rate over three years was 33%. Shock or respiratory failure during hospitalization was associated with increased in-hospital mortality. Patients who underwent cardiac operations had better in-hospital outcomes. HFrEF at the time of initial hospitalization was an independent risk factor for three-year mortality.Keywords: infective endocarditis, chronic dialysis, end-stage kidney disease, blood-stream infection, infectious disease, sepsis

Yi-Jun Lin,1 Hsing-Chieh Lin,2 Ying-Fei Yang,2 Chi-Yun Chen,2 Min-Pei Ling,3 Szu-Chieh Chen,4,5 Wei-Yu Chen,6,7 Shu-Han You,8 Tien-Hsuan Lu,2 Chung-Min Liao2 1Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei, Taiwan; 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan; 3Department of Food Science, National Taiwan Ocean University, Keelung City, Taiwan; 4Department of Public Health, Chung Shan Medical University, Taichung, Taiwan; 5Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung City, TaiwanCorrespondence: Chung-Min LiaoDepartment of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan, ROCTel +886 2 3366 3475Email cmliao@ntu.edu.twBackground: Broad-scale evidence has shown the significant association between ambient air pollutants and the development of tuberculosis (TB). However, the impact of air quality on the risk of TB in Taiwan is still poorly understood.Objective: To develop a probabilistic integrated population-level risk assessment approach for evaluating the contribution of ambient air pollution exposure to the risk of TB development among different regions of Taiwan.Materials and methods: A Bayesian-based probabilistic risk assessment model was implemented to link exposure concentrations of various air pollutants quantified in a probabilistic manner with the population-based exposure-response models developed by using an epidemiological investigation.Results: The increment of the risk of TB occurred in a region with a higher level of air pollution, indicating a strong relationship between ambient air pollution exposures and TB incidences. Carbon monoxide (CO) exposure showed the highest population attributable fraction (PAF), followed by nitrogen oxides (NOX) and nitrogen dioxide (NO2) exposures. In a region with higher ambient air pollution, it is most likely (80% risk probability) that the contributions of CO exposure to development of TB were 1.6–12.2% (range of median PAFs), whereas NOX and NO2 exposures contributed 1.2–9.8% to developing TB.Conclusion: Our findings provide strong empirical support for the hypothesis and observations from the literature that poor air quality is highly likely to link aetiologically to the risk of TB. Therefore, substantial reductions in CO, NOX, and NO2 exposures are predicted to have health benefits to susceptible and latently infected individuals that provide complementary mitigation efforts in reducing the burden of TB. Considering that people continue to be exposed to both TB bacilli and ambient air pollutants, our approach can be applied for different countries/regions to identify which air pollutants contribute to a higher risk of TB in order to develop potential mitigation programs.Keywords: tuberculosis, ambient air pollution, exposure-response function, probabilistic risk assessment, population attributable fraction

Yi-Hsien Cheng,1 Yi-Jun Lin,2 Szu-Chieh Chen,3,4 Shu-Han You,5 Wei-Yu Chen,6,7 Nan-Hung Hsieh,8 Ying-Fei Yang,9 Chung-Min Liao9 1Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; 2Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3Department of Public Health, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 4Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China; 5Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung, Taiwan, Republic of China; 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 7Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 8Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA; 9Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan, Republic of China Background: The high prevalence of dengue in Taiwan and the consecutive large dengue outbreaks in the period 2014–2015 suggest that current control interventions are suboptimal. Understanding the effect of control effort is crucial to inform future control strategies. Objectives: We developed a framework to measure season-based health burden risk from 2001 to 2014. We reconstructed various intervention coverage to assess the attributable effect of dengue infection control efforts. Materials and methods: A dengue–mosquito–human transmission dynamic was used to quantify the vector–host interactions and to estimate the disease epidemics. We used disability-adjusted life years (DALYs) to assess health burden risk. A temperature-basic reproduction number (R0)–DALYs relationship was constructed to examine the potential impacts of temperature on health burden. Finally, a health burden risk model linked a control measure model to evaluate the effect of dengue control interventions. Results: We showed that R0 and DALYs peaked at 25°C with estimates of 2.37 and 1387, respectively. Results indicated that most dengue cases occurred in fall with estimated DALYs of 323 (267–379, 95% CI) at 50% risk probability. We found that repellent spray had by far the largest control effect with an effectiveness of ~71% in all seasons. Pesticide spray and container clean-up have both made important contributions to reducing prevalence/incidence. Repellent, pesticide spray, container clean-up together with Wolbachia infection suppress dengue outbreak by ~90%. Conclusion: Our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on dengue infection prevalence and disease incidence in the southern region of Taiwan. Keywords: dengue, DALYs, modeling, infection, control intervention

Yi-Ju Lin,1 Chin-Yuan Wang,2 Elizabeth H Chang,1,3,4 Ssu-Wei Cheng,5 Yu Ko1,4 1Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 2Department of Internal Medicine, Division of Endocrinology and Metabolism, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4Research Center for Pharmacoeconomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 5Department of Pharmacy, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Objective: The aim of this study was to translate, adapt, and validate the Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS) in type 2 diabetes mellitus (DM) patients taking oral antidiabetic drugs (OADs) in Taiwan. Patients and methods: The SOADAS was translated to Chinese and was modified based on reviews of two physicians, five diabetes educators, and two patient focus groups. A cross-sectional interviewer-administered survey was conducted in adult patients with type 2 DM who were taking OADs. The Chinese version of the SOADAS (C-SOADAS), the EuroQol 5 dimensions 3-level (EQ-5D-3L) questionnaire, and a demographic questionnaire were administered to participants. Instrument structure, internal consistency, convergent validity, and known-group validity were assessed. Results: A total of 260 DM patients were recruited. The mean score of an individual item ranged from 3.6 to 3.9, while the mean total score (out of 25 possible points) was 18.7 points. Overall, floor and ceiling effects were negligible. The Cronbach’s α value was 0.81. All the four predetermined hypotheses for known-group validity assessment were fulfilled. In convergent validity testing, the C-SOADAS total scores were found to be correlated with EuroQol-Visual Analog Scale (EQ-VAS) scores (r = 0.2; p < 0.01) but not with EuroQol 5 dimensions (EQ-5D) index scores (r = 0.02; p = 0.81). Conclusion: The 5-item C-SOADAS appears to be a psychometrically acceptable measure of OAD treatment satisfaction among type 2 DM patients in Taiwan. The tool may be incorporated into clinical practice to quickly assess treatment outcomes from patients’ perspectives. Keywords: diabetes mellitus, oral antidiabetic agent, satisfaction, validation, reliability, C-SOADAS, Taiwan

Nan-Hung Hsieh,1 Yi-Jun Lin,2 Ying-Fei Yang,2 Chung-Min Liao2 1Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA; 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan Background: Oseltamivir-resistant mutants with higher drug resistance rates and low transmission fitness costs have not accounted for influenza (sub)type viruses. Predicting the impacts of neuraminidase inhibitor therapy on infection rates and transmission of drug-resistant viral strains requires further investigation.Objectives: The purpose of this study was to assess the potential risk of oseltamivir-induced resistance for influenza A (H1N1) and A (H3N2) viruses.Materials and methods: An immune-response-based virus dynamic model was used to best fit the oseltamivir-resistant A (H1N1) and A (H3N2) infection data. A probabilistic risk assessment model was developed by incorporating branching process-derived probability distribution of resistance to estimate oseltamivir-induced resistance risk.Results: Mutation rate and sensitive strain number were key determinants in assessing resistance risk. By increasing immune response, antiviral efficacy, and fitness cost, the spread of resistant strains for A (H1N1) and A (H3N2) were greatly decreased. Probability of resistance depends most strongly on the sensitive strain number described by a Poisson model. Risk of oseltamivir-induced resistance increased with increasing the mutation rate for A (H1N1) only. The ≥50% of resistance risk induced by A (H1N1) and A (H3N2) sensitive infected cells were 0.4 (95% CI: 0.28–0.43) and 0.95 (95% CI 0.93–0.99) at a mutation rate of 10−6, respectively. Antiviral drugs must be administrated within 1–1.5 days for A (H1N1) and 2–2.5 days for A (H3N2) virus infections to limit viral production.Conclusion: Probabilistic risk assessment of antiviral drug-induced resistance is crucial in the decision-making process for preventing influenza virus infections. Keywords: influenza, resistance risk, oseltamivir, probabilistic risk assessment

Yi-Hsien Cheng,1 Shu-Han You,2 Yi-Jun Lin,3 Szu-Chieh Chen,4,5 Wei-Yu Chen,6 Wei-Chun Chou,2 Nan-Hung Hsieh,7 Chung-Min Liao3 1Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; 2National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, 3Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 4Department of Public Health, 5Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA Background: The interaction between influenza and pneumococcus is important for understanding how coinfection may exacerbate pneumonia. Secondary pneumococcal pneumonia associated with influenza infection is more likely to increase respiratory morbidity and mortality. This study aimed to assess exacerbated inflammatory effects posed by secondary pneumococcal pneumonia, given prior influenza infection. Materials and methods: A well-derived mathematical within-host dynamic model of coinfection with influenza A virus and Streptococcus pneumoniae (SP) integrated with dose–response relationships composed of previously published mouse experimental data and clinical studies was implemented to study potentially exacerbated inflammatory responses in pneumonia based on a probabilistic approach. Results: We found that TNFα is likely to be the most sensitive biomarker reflecting inflammatory response during coinfection among three explored cytokines. We showed that the worst inflammatory effects would occur at day 7 SP coinfection, with risk probability of 50% (likely) to develop severe inflammatory responses. Our model also showed that the day of secondary SP infection had much more impact on the severity of inflammatory responses in pneumonia compared to the effects caused by initial virus titers and bacteria loads. Conclusion: People and health care workers should be wary of secondary SP infection on day 7 post-influenza infection for prompt and proper control-measure implementation. Our quantitative risk-assessment framework can provide new insights into improvements in respiratory health especially, predominantly due to chronic obstructive pulmonary disease (COPD). Keywords: chronic obstructive pulmonary disease, pneumonia, influenza, coinfection, modeling, risk assessment

Ying-Fei Yang, Yi-Jun Lin, Chung-Min Liao Department of Bioenvironmental Systems Engineering, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan Abstract: Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK)/toxicodynamic (TD) properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe0) nanoparticles (NPs) are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe0NP application contributes to long-term environmental and human health impacts. The nematode Caenorhabditis elegans is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials. Here we present a TBTK/TD approach to appraise bioaccumulation and nanotoxicity of Fe0NPs in C. elegans. Built on a present C. elegans bioassay with estimated TBTK/TD parameters, we found that average bioconcentration factors in C. elegans exposed to waterborne and food-borne Fe0NPs were ~50 and ~5×10–3, respectively, whereas 10% inhibition concentrations for fertility, locomotion, and development, were 1.26 (95% CI 0.19–5.2), 3.84 (0.38–42), and 6.78 (2.58–21) µg·g–1, respectively, implicating that fertility is the most sensitive endpoint in C. elegans. Our results also showed that biomagnification effects were not observed in waterborne or food-borne Fe0NP-exposed worms. We suggest that the TBTK/TD assessment for predicting NP-induced toxicity at different concentrations and conditions in C. elegans could enable rapid selection of nanomaterials that are more likely to be nontoxic in larger animals. We conclude that the use of the TBTK/TD scheme manipulating C. elegans could be used for rapid evaluation of in vivo toxicity of NPs or for drug screening in the field of nanomedicine. Keywords: zerovalent iron nanoparticles, Caenorhabditis elegans, nanotoxicology, bioaccumulation, toxicity-based-toxicokinetic/toxicodynamic modeling

Yi-Chou Hou,1 Yen-Ju Lin,2 Kuo-Cheng Lu,1 Han-Sun Chiang,3 Chia-Chi Chang,4 Li-King Yang1 1Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, 2Department of Nursing, Taipei Medical University, 3Graduate Institute of Basic Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, 4School of Gerontology Health Management, College of Nursing, Taipei Medical University, Taipei, Taiwan, Republic of China Background: Music therapy has been applied in hemodialysis (HD) patients for relieving mental stress. Whether the stress-relieving effect by music therapy is predictive of clinical outcome in HD patients is still unclear.Methods: We recruited a convenience sample of 99 patients on maintenance HD and randomly assigned them to the experimental (n=49) or control (n=50) group. The experimental group received relaxing music therapy for 1 week, whereas the control group received no music therapy. In the experimental group, we compared cardiovascular mortality in the patients with and without cortisol changes.Results: The salivary cortisol level was lowered after 1 week of music therapy in the experimental group (−2.41±3.08 vs 1.66±2.11 pg/mL, P0.6 pg/mL (83.8% vs 63.6%, P

Chih-Chang Yeh,1,2 Yu-Han Su,3 Yu-Jhe Lin,3 Pin-Jyun Chen,3 Chung-Sheng Shi,1 Cheng-Nan Chen,3,* Hsin-I Chang3,* 1Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China; 2Orthopaedic Department, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan, Republic of China; 3Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression. Keywords: liposome, osteoarthritis, curcuminoid, OPG/RANKL ratio, bone turnover

Central giant cell granuloma is a relatively uncommon benign bony lesion of a variably aggressive nature. This paper presents the case of a 7-year-old boy with central giant cell granuloma in the anterior mandible. In children with mixed dentition, a pathologic lesion could be the underlying cause of regular tooth mobility and exfoliation of primary teeth and can easily be overlooked, especially in cases that are not accompanied by an obvious bony expansion. The clinician needs to be aware of possible oral pathology when tooth mobility and displacement are present, and central giant cell granuloma should be considered in the differential diagnosis for children with maligned and mobile teeth. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) presents high mortality and morbidity clinically and by far no effective preventive strategy has been established. Extract of Ginkgo biloba leaves, EGb 761, is a complex mixture that possesses several clinical beneficial effects such as anti-oxidation, anti-inflammation, anti-tumor, and cardioprotective property. With EGb 761 pretreatment, both lipopolysaccharide (LPS)-induced protein leakage and neutrophil infiltration, and LPS-induced inflammatory responses including increased myeloperoxidase (MPO) activity, lipid peroxidation, and metalloproteinase (MMP)-9 activity, were inhibited; LPS-suppressed activation of antioxidative enzymes (AOE) were reversed; and not only the phosphorylation of NF-κB but also the degradation of its inhibitor, IκB, were suppressed. These results suggested that the protection mechanism of EGb 761 is by inhibition of NFκB activation, possibly via the up-regulation of antioxidative enzymes. More studies are needed to further evaluate whether EGb 761 is a suitable candidate as an effective dietary strategy to reduce the incidence of endotoxin-induced ALI. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrosis plays a role in the development of a vulnerable substrate for atrial fibrillation (AF). Transforming growth factor (TGF)-β(1) is related to the degree of atrial fibrosis and the recurrence of AF after surgical maze procedures. Whether TGF-β(1) is associated with the outcome after catheter ablation for AF remains unclear. Objective: The purpose of this study was to investigate whether plasma TGF-β(1) was an independent predictor of AF recurrence after catheter ablation. Methods: Two hundred consecutive AF patients (154 with paroxysmal AF and 46 with nonparoxysmal AF) underwent catheter ablation. Their TGF-β(1) levels and clinical and echocardiographic data were collected before ablation. Results: Thirty patients (65%) with nonparoxysmal AF and 57 (37%) with paroxysmal AF had AF recurrence after catheter ablation. Among patients with nonparoxysmal AF, those experiencing recurrence had higher TGF-β(1) levels than did those who did not experience recurrence (34.63 ± 11.98 ng/mL vs 27.33 ± 9.81 ng/mL; P = .026). In patients with paroxysmal AF, recurrence was not associated with different TGF-β(1) levels. In patients with nonparoxysmal AF, TGF-β(1) levels and left atrial diameter (LAD) were independent predictors of AF recurrence after catheter ablation. Moreover, TGF-β(1) levels had an incremental value over LAD in predicting AF recurrence after catheter ablation (global χ(2) of LAD alone: 6.3; LAD and TGF-β(1) levels: 11.9; increment in global χ(2) = 5.6; P = .013). Patients with small LAD and low TGF-β(1) levels had the lowest AF recurrence rate at 11%. Conclusion: TGF-β(1) level is an independent predictor of AF recurrence in patients with nonparoxysmal AF and might be useful for identifying those patients likely to have better outcomes after catheter ablation. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction is recognized as an important risk factor for thromboembolic (TE) events in patients with atrial fibrillation (AF) under medical treatment.Objective: To investigate whether renal dysfunction is a useful predictor of TE events among patients receiving AF ablation. We also aimed to determine whether the diagnostic accuracy of the CHA(2)DS(2)-VASc score in predicting TE events could be improved by adding renal dysfunction into the scoring system.Methods: We enrolled a total of 547 patients with AF who underwent catheter ablation. Renal dysfunction was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m(2). The clinical end point was the occurrence of TE events (ischemic stroke, transient ischemic attack, or other systemic embolisms) during follow-up after catheter ablation.Results: During a follow-up of 38.9 ± 22.5 months, 16 patients (2.9%) experienced TE events. Both the CHA(2)DS(2)-VASc score and renal dysfunction were independent predictors of TE events in the multivariate analysis. Among patients with a CHA(2)DS(2)-VASc score of 0 or 1, renal dysfunction can further stratify them into 2 groups with different event rates (4.3% vs 0.3%; P = .046). A new scoring system derived by assigning 1 more point representing renal dysfunction to the CHA(2)DS(2)-VASc score could improve its predictive accuracy; the area under the receiver operating characteristic curve increased from 0.84 to 0.88 (P = .043).Conclusions: Renal dysfunction was a significant risk factor for TE events after catheter ablation of AF and may improve the diagnostic accuracy of the CHA(2)DS(2)-VASc score. [ABSTRACT FROM AUTHOR]

Background: Although four-dollar programs ($4 per 30-day supply for selected generic drugs) have become important options for seniors to obtain affordable medications, little is known about access to these programs and the characteristics of those who use them.Objectives: We quantify access to $4 programs based on driving distance; evaluate factors affecting the program use and potential cost-savings associated with switching to $4 programs in Medicare.Design: Observational study.Setting: US Medicare Part D data, 5% random sample, 2007Participants: 347,653 elderly beneficiaries without Medicaid coverage or low-income subsidies.Main Measures: We evaluated how use of $4 programs was affected by driving distance to the store and the beneficiary's demographic and socioeconomic status, insurance coverage, health status, comorbidities, and medication use. For those who did not use the $4 programs, we calculated potential savings from switching to $4 generics.Key Results: Eighty percent of seniors in Medicare Part D filled prescriptions for generic drugs that were commonly available at $4 programs. Among them, only 16.3% filled drugs through $4 programs. Beneficiaries who lived in poor areas, had less insurance, more co-morbidities, and used more drugs and lived closer to $4 generic retail pharmacies, were more likely to use these programs. Blacks were less likely to use the program relative to Whites (15.0% vs. 16.4%; OR=0.75, 95% CI 0.71-0.80). While 53.2% of nonusers would save by switching to $4 program after incorporating travelling costs, 58% of those who could save would have net annual out-of-pocket savings of less than $20.Conclusions: The take-up rate of $4 programs was low in 2007 among Medicare beneficiaries. As more stores offer $4 programs and increasing numbers of drugs become generic, more beneficiaries could potentially benefit, as could the Medicare program. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation of paroxysmal atrial fibrillation has been performed for more than 10 years. However, data about the long-term results were limited.Objectives: To evaluate the long-tem efficacy following paroxysmal atrial fibrillation ablation and to investigate whether there were different patterns of recurrences in patients with different CHADS(2) scores.Methods: A total of 238 patients with paroxysmal atrial fibrillation who received a catheter ablation from 2004 to 2007 were enrolled. Free of recurrence was defined as the absence of atrial arrhythmias without using any antiarrhythmic agents after ablation.Results: There were 121 patients (50.8%) suffering from recurrences after the first ablation procedure during a median follow-up period of 5 years. The CHADS(2) score and left atrial diameter were significant predictors of recurrences in the multivariate analysis. Different patterns of recurrence were observed in different groups of patients categorized on the base of CHADS(2) score. Among patients with a CHADS(2) score of ≥3 without recurrences at 2 years postablation, 63.6% experienced episodes of arrhythmias during the subsequent follow-up period. In contrast, in patients with a CHADS(2) score of 0 without recurrences at 2 years postablation, the future recurrence rate was only 2.7%.Conclusions: After a successful ablation, recurrences may continue to occur without reaching a plateau during the long-term follow-up, especially in patients with a high CHADS(2) score. The optimal follow-up strategy may differ and should be individualized for patients with different scores. [ABSTRACT FROM AUTHOR]