Publications by authors named "Tzu-Ting Chen"

93 Publications

Influenza vaccination reduces incidence of peripheral arterial occlusive disease in elderly patients with chronic kidney disease.

Sci Rep 2021 Mar 1;11(1):4847. Epub 2021 Mar 1.

Department of Primary Care Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

An influenza vaccination might reduce the risk of incident peripheral arterial occlusive disease (PAOD) in patients with chronic kidney disease (CKD), but supporting evidence is limited. This case-crossover study analyzed data from Taiwan's real-world National Health Insurance Research Database. This study included elderly (≥ 67 years old) patients with CKD having incident PAOD from January 1, 2006, to June 30, 2015. We defined 1 year before PAOD onset as the index date for the self-control group. A conditional logistic regression model was used to investigate exposure to an influenza vaccination for estimating the risk for incident PAOD following vaccination. In total, this study included 46,782 elderly patients with CKD having incident PAOD. The odds ratios for incident PAOD were 0.85 (95% confidence interval 0.77-0.94), 0.85 (0.79-0.92), 0.84 (0.79-0.90), and 0.85 (0.81-0.90) at 1, 2, 3, and 4 months after an influenza vaccination, respectively. We observed consistent results for the subgroups of patients with CKD and concomitant diabetes. However, we did not observe any beneficial effects of influenza vaccination in patients with advanced CKD or end-stage renal disease. This study demonstrated that influenza vaccination may be associated with a reduced risk of incident PAOD among patients with early-stage CKD.
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http://dx.doi.org/10.1038/s41598-021-84285-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921588PMC
March 2021

Long-term Clinical Outcome of Major Adverse Vascular Events After Hypertensive Disorders of Pregnancy.

Obstet Gynecol 2021 02;137(2):285-293

Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, the Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, the Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung City, the Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, the Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, the Emergency Department, Shuang Ho Hospital, Taipei Medical University, New Taipei City, the Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, the Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, the Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, and the Department of Dentistry and Department of Medical Research, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

Objective: To assess the association between hypertensive disorders of pregnancy and adverse events after pregnancy, including chronic kidney disease and major adverse cardiovascular events (cerebrovascular accident, coronary artery disease, or death).

Methods: A nationwide, population-based cohort study was conducted analyzing women with hypertensive disorders of pregnancy identified from Taiwan National Health Insurance Research Database from 2004 to 2015. Hypertensive disorders of pregnancy were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The study cohort was comprised of women aged 20-40 years diagnosed with hypertensive disorders of pregnancy from 2006 to 2013. The comparison group comprised of four randomly selected women without hypertensive disorders of pregnancy, matched for age and index date for each woman with hypertensive disorders of pregnancy. All the women were followed from the date of cohort entry until they developed chronic kidney disease or major adverse cardiovascular events or until the end of 2015, whichever occurred first. A Cox proportional hazard model was used to estimate the risk of chronic kidney disease and major adverse cardiovascular events.

Results: We identified 29,852 women with a diagnosis of hypertensive disorders of pregnancy and 119,408 matched women without hypertensive disorders of pregnancy who fit the inclusion criteria. The crude hazard ratios (HRs) were 5.22 (95% CI 4.67-5.83) and 2.26 (95% CI 1.99-2.57) for chronic kidney disease and major adverse cardiovascular events. After adjusting for potential confounders, hypertensive disorders of pregnancy was associated with a higher risk of chronic kidney disease (adjusted HR, 4.26; 95% CI 3.80-4.78), and major adverse cardiovascular events (adjusted HR, 2.15; 95% CI 1.89-2.45).

Conclusion: This population-based cohort study indicated that women with hypertensive disorders of pregnancy are at a higher risk of chronic kidney disease and major adverse cardiovascular events than women without hypertensive disorders of pregnancy. Further studies are required to clarify the nature of these associations and to improve public health interventions.
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http://dx.doi.org/10.1097/AOG.0000000000004277DOI Listing
February 2021

Impact of dialysis modality on major adverse cardiovascular events and all-cause mortality: a national population-based study.

Nephrol Dial Transplant 2020 Dec 12. Epub 2020 Dec 12.

Department of Internal Medicine, Division of Nephrology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

Background: Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) modalities render objective assessment of survival benefits a greater challenge.

Methods: Data were retrieved from Taiwan's National Health Insurance Database from 1 January 2006 to 31 December 2015. We included 13 662 and 41 047 long-term dialysis patients in a propensity score matching study design and a time-varying study design, respectively, to compare major adverse cardiovascular events (MACEs) between patients receiving PD and HD. We also included 109 256 dialysis patients to compare the all-cause mortality among different RRT modalities.

Results: For MACE, the hazard ratio (HR) for PD patients compared to HD patients was 0.95 [95% confidence interval (CI) 0.89-1.02] in the propensity score study design and 1.06 (95% CI 1.01-1.12) in the time-varying study design. For all-cause mortality, the HR for PD patients compared to HD patients was 1.09 (95% CI 1.05-1.13) in the propensity score study design and 1.13 (95% CI 1.09-1.17) in the time-varying study design. The HR for death was higher at a level of statistical significance for females (1.21, 95% CI 1.15-1.28), patients ≥65 years old (1.30, 95% CI 1.24-1.36) and diabetes mellitus (DM; 1.28, 95% CI 1.22-1.34).

Conclusions: The HR for MACE is significantly higher among PD patients in time-varying design analysis. In addition, all-cause mortality was higher in PD patients compared to patients with HD, especially in those who were aged ≥65 years, female or DM.
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http://dx.doi.org/10.1093/ndt/gfaa282DOI Listing
December 2020

Radio-contrast medium exposure and dialysis risk in patients with chronic kidney disease and congestive heart failure: A case-only study.

Int J Cardiol 2021 Feb 12;324:199-204. Epub 2020 Sep 12.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. Electronic address:

Background: Dialysis for end stage renal disease is considered a major public health challenge. Pre-existing chronic kidney disease (CKD) and congestive heart failure (CHF) may be independent risk factors for contrast-induced acute kidney injury. The aim of this study is to investigate dialysis risk in patients with CKD and CHF after radio-contrast medium exposure or coronary catheterization.

Method: This case-crossover design used the Health Insurance Database to identify incident dialysis patients with CKD and CHF. Patients themselves in 6 months ago serve as their own controls. This prevents selection bias in the control group, such as healthy volunteer bias and confounding bias. Conditional logistic regression model was used to estimate the risk of dialysis shortly after radio-contrast medium exposure.

Results: In total, 36,709 patients with CKD and CHF underwent dialysis after radio-contrast medium exposure. At 1 week, the odds ratio (OR) for dialysis was 4.49 (95% Confidence Interval: 3.99-5.05). The ORs for acute-temporary (N = 23,418) and chronic dialysis (N = 13,291) were 5.57 (4.83-6.42) and 2.37 (1.90-2.95) after radio-contrast medium exposure, respectively. The ORs for dialysis after radio-contrast medium exposure in advanced CKD patients (N = 12,030) were 3.25 (2.53-4.19) and 4.85 (4.24-5.54) in early CKD patients (N = 24,679). The ORs for dialysis after coronary catheterization in patients with CKD and CHF was 3.75 (2.57-5.48).

Conclusions: In this study, the clinical risk for acute-temporary or chronic dialysis was significantly high when the bias was fully considered. We need strategies to reduce the subsequent risk of dialysis after radio-contrast medium exposure, especially in patients with CKD and CHF.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.014DOI Listing
February 2021

The autonomic features of somatization diagnoses: Somatic symptom disorder and persistent somatization.

Asian J Psychiatr 2020 Oct 18;53:102356. Epub 2020 Aug 18.

Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.

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http://dx.doi.org/10.1016/j.ajp.2020.102356DOI Listing
October 2020

Venetoclax plus cytochrome P450 inhibitors without ramp-up strategy led to low risk of tumor lysis syndrome in acute myeloid leukemia.

Ann Hematol 2020 Sep 3;99(9):2193-2195. Epub 2020 Jul 3.

Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, 2 Yude Rd, North District, Taichung, 404, Taiwan.

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http://dx.doi.org/10.1007/s00277-020-04168-2DOI Listing
September 2020

Prognostic Effect of Comorbid Disease and Immune Gene Expression on Mortality in Kidney Cancer-A Population Based Study.

Cancers (Basel) 2020 Jun 22;12(6). Epub 2020 Jun 22.

Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei City 110, Taiwan.

The effect of comorbidities and the immune profiles of the kidney cancer microenvironment play a major role in patients' prognosis and survival. Using the National Health Insurance Research Database (Taiwan), we identified patients aged >20 years with a first diagnosis of kidney cancer between 2005 and 2014. Differences in demographic characteristics and comorbidities were examined using the Pearson chi-squared test or the t test. The Cox regression model was used to construct the nomogram. RNA-seq data were applied from The Cancer Genome Atlas database, and correlations between immune metagenes and clinical characteristics were determined using a linear regression model. In this nationwide cohort study, including 5090 patients with kidney cancer, predictors in our prediction models included age, sex, chronic kidney disease, dialysis requirements, renal stones, cerebrovascular disease, and metastasis tumor. In the tumor tissue profiles, significant positive correlations between immune metagenes and clinical stage or overall survival were observed among Natural Killer (NK) cells (CD56-), CD4+ T-helper 2 (Th2) cells, and activated Dendritic Cell (aDC). A negative correlation was observed between expression level of Dendritic Cell (DC) and overall survival. Patients with kidney cancer exhibit high prevalence of comorbid disease, especially in older patients. Comorbid disease types exert unique effects, and a particular comorbidity can affect cancer mortality. Moreover, the expression of immune metagenes can be utilized as potentialbiomarkers especially for further study of molecular mechanisms as well as microenvironments in kidney cancer.
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http://dx.doi.org/10.3390/cancers12061654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352532PMC
June 2020

Parasympathetic activity as a potential biomarker of negative symptoms in patients with schizophrenia.

Asia Pac Psychiatry 2020 Sep 26;12(3):e12392. Epub 2020 May 26.

Department of Psychiatry, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan.

Introduction: Autonomic dysfunction in patients with schizophrenia has raised concern considering the higher cardiovascular mortality and morbidity rate. This phenomenon has been demonstrated using various measurements and is inferred to be associated with demographics, medical treatment, and psychopathology. However, few have targeted the role of negative symptoms within schizophrenia.

Methods: Schizophrenia patients with stationary psychopathology were recruited from a chronic ward, a daycare center, and a nonintensive case management program. Demographic data, medication history, the Positive and Negative Syndrome Scale (PANSS) score, the Personal and Social Performance Scale (PSP) score, and the five-minute resting-state heart rate variability (HRV) were collected at trial initiation (Time 1) and a year later (Time 2). The relationships between variables and HRV indices were evaluated using correlation and regression analyses.

Results: A total of 63 participants were recruited at Time 1, with 29 participants remaining at Time 2. Correlation analyses showed a negative correlation between the PANSS negative score (PANSS-N) and total power (TP), low-frequency power (LF), and high-frequency power (HF) at Time 1. The results were further examined with multiple linear regression analysis and remained significant between the PANSS-N score and HF (β = -0.306, P = .012). A generalized estimating equation model revealed the above negative association to be significant considering both timepoints.

Discussion: The negative association between negative symptom severity and parasympathetic activity was significant, which may inspire further research into the corresponding treatment, the mechanisms, and the use of HRV as an applicable biomarker for treatment response.
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http://dx.doi.org/10.1111/appy.12392DOI Listing
September 2020

Lethal mushroom: Volvariella volvacea infective endocarditis in a patient after allogeneic peripheral blood stem cell transplantation.

J Formos Med Assoc 2020 02 19;119(2):664-666. Epub 2019 Oct 19.

Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jfma.2019.09.008DOI Listing
February 2020

Effects and Safety of an Oral Adsorbent on Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis.

J Clin Med 2019 Oct 17;8(10). Epub 2019 Oct 17.

Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.

Background: AST-120 (Kremezin), which is an oral spherical carbon adsorbent, has been reported to have the potential for retarding disease progression in patients with chronic kidney disease. We aimed to evaluate its efficacy and safety in this study.

Methods: We systematically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases. The primary outcomes were the renal outcome and all-cause mortality, and the change in serum indoxyl sulfate (IS) levels. The safety outcome was also evaluated in terms of reported major adverse events. A random-effects model was used when heterogeneity was expected.

Results: Eight studies providing data for 3349 patients were included in the meta-analysis. The risk ratio of renal outcome and all-cause mortality were 0.97 (95% CI: 0.88-1.07; 6 trials) and 0.94 (0.73-1.20; 5 trials), respectively. Furthermore, the weighted mean change in IS levels from baseline to the end of the study was -0.28 mg/dL (95% CI: -0.46 to -0.11; 4 trials).

Conclusions: This study provides evidence that AST-120 can effectively lower IS levels but still controversial in terms of slowing disease progression and all-cause mortality. Except for dermatological events, the incidence of adverse events did not differ significantly between the AST-120 and placebo groups.
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http://dx.doi.org/10.3390/jcm8101718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832608PMC
October 2019

Specific personality traits and associated psychosocial distresses among individuals with heroin or methamphetamine use disorder in Taiwan.

J Formos Med Assoc 2020 Mar 7;119(3):735-742. Epub 2019 Sep 7.

Department of Psychiatry, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan; Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Previous studies showed the association between substance use disorders (SUDs) and borderline and antisocial personality disorders. Substance abusers may have emotional, somatic and interpersonal distresses. This study aimed to investigate the associations between substance, personality and psychosocial distresses.

Methods: This cross-sectional, questionnaire-based study recruited 39 individuals with heroin use disorder (HUD), 111 with methamphetamine use disorder (MUD) and 101 as the control group in a rural area of Taiwan. The Tridimensional Personality Questionnaire (TPQ) and Opiate Treatment Index were used to assess the association between personality and psychosocial conditions. Deviations of the three personality dimensions of TPQ (novelty seeking, harm avoidance, and reward dependence) could reflect eight personality patterns.

Results: We found SUD was associated with high novelty seeking and harm avoidance traits and explosive (borderline) personality pattern, whereas HUD was also linked with sensitive (narcissistic) pattern. Subjects with HUD tended to have more deviant personality traits than subjects with MUD. For subjects with SUDs, all three personality dimensions and sensitive (narcissistic) personality patterns were associated with emotional and somatic distresses, and those with explosive (borderline) and sensitive (narcissistic) patterns had poor social functioning.

Conclusion: Our results indicate substance abusers with high novelty seeking and harm avoidance, corresponding to explosive (borderline) or sensitive (narcissistic) patterns, to have a higher tendency to suffer from somatic and psychosocial distresses.
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http://dx.doi.org/10.1016/j.jfma.2019.08.026DOI Listing
March 2020

Randomized, double-blind, placebo, and risperidone-controlled study of lurasidone in the treatment of schizophrenia: Results of an inconclusive 6-week trial.

Asia Pac Psychiatry 2019 Sep 25;11(3):e12354. Epub 2019 Mar 25.

Institute of CNS Pharmacology, Tokyo, Japan.

Objective: The efficacy and safety of lurasidone in schizophrenia has been demonstrated in multiple controlled trials, primarily in US and European populations. The aim of the current study was To evaluate lurasidone for the treatment of schizophrenia among patients in Japan, Korea, and Taiwan.

Methods: Hospitalized patients (N = 460) with schizophrenia were randomized to 6 weeks of fixed-dose lurasidone 40 mg/d, lurasidone 80 mg/d, risperidone 4 mg/d, or placebo. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S).

Results: No significant endpoint differences in PANSS total score were found for lurasidone or risperidone vs placebo. Lurasidone was safe and well tolerated, with minimal effects on weight and metabolic parameters.

Discussion: The current study was inconclusive regarding the efficacy of lurasidone in schizophrenia but further confirmed its safety and tolerability.
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http://dx.doi.org/10.1111/appy.12354DOI Listing
September 2019

Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population.

Sci Rep 2019 02 25;9(1):2694. Epub 2019 Feb 25.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

It remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1-5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63-0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.
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http://dx.doi.org/10.1038/s41598-019-38991-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389886PMC
February 2019

Response by Chen and Tu to Letter Regarding Article, "Risk of Infective Endocarditis After Invasive Dental Treatment: A Case-Only Study".

Circulation 2019 01;139(1):142-143

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei (T.-T.C., Y.-K.T.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038024DOI Listing
January 2019

Effect of Statins on Renal Function in Chronic Kidney Disease Patients.

Sci Rep 2018 11 2;8(1):16276. Epub 2018 Nov 2.

Department of Nephrology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.

Dyslipidemia is associated with glomerular injury. However, the effect of statins on chronic kidney disease (CKD) progression remains controversial. We aimed to investigate the efficacy of statins for renal protection in patients with CKD. The retrospective cohort study comprised 3441 patients diagnosed with CKD in multiple medical centers. We divided the patients into two cohorts based on statin prescription, and compared proportions and risks of CKD progression events between the two groups. CKD progression event was defined as an average annual decline of eGFR >5 mL/min/1.73 m or advancement to the dialysis stage. The result revealed that among all incident patients with CKD, 28.7% and 30.3% of the users and nonusers demonstrated CKD progression, respectively. The crude odds ratio (OR) of CKD progression was 0.93 [95% confidence interval (CI) 0.78-1.10]. After adjustment for baseline characteristics, the adjusted OR was 0.80 (95% CI 0.63-1.01). The sensitivity analysis results showed consistent OR for CKD progression, stratification by age, sex, Charlson score, and statins use within 1 year before index date. The effect of statins was significant in patients with CKD stage 3B-5 (OR 0.68, 95% CI 0.48-0.95), but not statistically significant in those with CKD stage 1-3A (OR 0.97, 95% CI 0.68-1.38). The effect of statins was significant in patients with proteinuria ≥1000 mg/day (OR 0.63, 95% CI 0.43-0.92), but not statistically significant in those with proteinuria <1000 mg/day (OR 1.02, 95% CI 0.74-1.41).
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http://dx.doi.org/10.1038/s41598-018-34632-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215008PMC
November 2018

Responsiveness and predictive validity of the computerized digit vigilance test in patients with stroke.

Disabil Rehabil 2019 11 28;41(22):2683-2687. Epub 2018 Jun 28.

School of Occupational Therapy, College of Medicine, National Taiwan University , Taipei , Taiwan.

To investigate the responsiveness and predictive validity of the computerized digit vigilance test (C-DVT) in inpatients receiving rehabilitation following stroke. Forty-nine patients completed the C-DVT and the Barthel Index (BI) after admission to and before discharge from the rehabilitation ward. The standardized response mean (SRM) was used to examine the responsiveness of the C-DVT. We used a paired -test to determine the statistical significance of the changes in scores on the C-DVT. We estimated the predictive validity of the C-DVT with the Pearson correlation coefficient () to investigate the association between the scores of the C-DVT at admission and the scores of the BI at discharge. Our data showed a small SRM (-0.31) and a significant difference (paired -test,  = 0.034) between the C-DVT scores at admission and discharge. These findings indicate that the C-DVT can appropriately detect changes in sustained attention. In addition, we found a moderate association ( = 0.48) between the scores of the C-DVT at admission and the scores of the BI at discharge, suggesting the sufficient predictive validity of the C-DVT. Our results showed that the C-DVT had adequate responsiveness and sufficient predictive validity in inpatients receiving rehabilitation following stroke. Implications for rehabilitation The computerized digit vigilance test (C-DVT) had adequate responsiveness to be an outcome measure for assessing the sustained attention in inpatients receiving rehabilitation after stroke. The C-DVT had sufficient predictive validity to predict daily function in inpatients receiving rehabilitation after stroke.
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http://dx.doi.org/10.1080/09638288.2018.1474953DOI Listing
November 2019

Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.

Sci Rep 2018 05 2;8(1):6908. Epub 2018 May 2.

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

This study investigated the characteristics of patients with different chronic kidney disease (CKD) stages according to various body mass index (BMI) categories and determined the influence of BMI in renal function deterioration. We conducted a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of CKD project (2008-2013) and National Health Insurance Research Database (2001-2013). A total of 7357 patients with CKD aged 20-85 years from 14 hospitals were included in the study. A higher male sex, diabetes mellitus (DM) and hypertension were noted among overweight and obese CKD patients, while more cancer prevalence was noted among underweight CKD patients. Charlson comorbidity index was significantly higher and correlated with BMI among late CKD patients. Patients with BMI < 18.5 kg/m exhibited non-significantly higher events of eGFR decline events in both early and late CKD stages than other BMI groups. BMI alone is not a determinant of CKD progression among our Taiwanese CKD patients. Obesity should be re-defined and body weight manipulation should be individualized in CKD patients.
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http://dx.doi.org/10.1038/s41598-018-24757-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932053PMC
May 2018

Risk of Infective Endocarditis After Invasive Dental Treatments: Case-Only Study.

Circulation 2018 07;138(4):356-363

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei (T.-T.C., Y.-C.Y., K.-L.C., M.-S.L., Y.-K.T.).

Background: Invasive dental treatments (IDTs) can yield temporary bacteremia and have therefore been considered a potential risk factor of infective endocarditis (IE). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves or damaged heart tissue, giving rise to IE. However, the association between IDTs and IE remains controversial. The aim of this study is to estimate the association between IDTs and IE.

Methods: The data in this study were obtained from the Health Insurance Database in Taiwan. We selected 2 case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors that do not vary with time are adjusted for implicitly. In the case-crossover design, a conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay, respectively. In the self-controlled case series design, a conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1 to 4, 5 to 8, 9 to 12, and 13 to 16 weeks following an IDT.

Results: In total, 9120 and 8181 patients with IE were included in case-crossover design and self-controlled case series design, respectively. In the case-crossover design, 277 cases and 249 controls received IDTs during the exposure period, and the odds ratio was 1.12 (95% confidence interval, 0.94-1.34) for 4 weeks. In the self-controlled case series design, we observed that 407 IEs occurred during the first 4 weeks after IDTs, and the age-adjusted incidence rate ratio was 1.14 (95% confidence interval, 1.02-1.26) for 1 to 4 weeks after IDTs.

Conclusions: In both study designs, we did not observe a clinically larger risk for IE in the short periods after IDTs. We also found no association between IDTs and IE among patients with a high risk of IE. Therefore, antibiotic prophylaxis for the prevention of IE is not required for the Taiwanese population.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.033131DOI Listing
July 2018

Reducing the time needed to administer a sustained attention test in patients with stroke.

PLoS One 2018 22;13(3):e0192922. Epub 2018 Mar 22.

School of Occupational Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan.

Administering a sustained attention test often takes a lengthy time, which can hamper routine assessments in clinical settings. Therefore, we first proposed a method to reduce the time needed for administering a sustained attention test (the Computerized Digit Vigilance Test, C-DVT). The method was to retrieve 5 segments from different trial positions of the original C-DVT testing. Then we compared the concurrent validity, convergent validity, and random measurement error of the examinees' performance on these segments to find the segment with better psychometric properties. The 5 segments were as follows: the first 50% of testing, the 21st~50th percentile of testing, the first 60% of testing, the 31st~60th percentile of testing, and the 36th~65th percentile of testing. Then we compared the validities and random measurement error of the examinees' performance on these segments. Ninety patients with stroke participated in the validity study, and 44 of them participated in the random measurement error study. The patients' scores on the 5 segments were highly correlated with those of the C-DVT (Pearson's r ≥ 0.98), indicating excellent concurrent validity. The patients' scores on the 5 segments were moderately correlated with those of the Tablet-based Symbol Digit Modalities Test (Pearson's r = -0.51~-0.48), indicating sufficient convergent validity. The amounts of random measurement error (percent standard error of measurement) were all limited: 5.1% for the C-DVT, 6.6% for the first 50% of testing, 6.0% for the 21st~50th percentile of testing, 6.1% for the first 60% of testing, 6.0% for the 31st~60th percentile of testing, and 6.1% for the 36th~65th percentile of testing. The patients needed on average 3~4 minutes to complete all the aforementioned testing. The patients' scores on the 5 segments showed excellent concurrent validity, sufficient convergent validity, and limited amounts of random measurement error in patients with stroke. We suggest the 31st~60th percentile of testing segment for users because it had the lowest amount of random measurement error and can reduce the time needed for formal testing by about 40%.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192922PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863955PMC
June 2018

Efficacy, tolerability, and safety of oral paliperidone extended release in the treatment of schizophrenia: a 24-week, open-label, prospective switch study in different settings in Taiwan.

Neuropsychiatr Dis Treat 2018 8;14:725-732. Epub 2018 Mar 8.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Purpose: Paliperidone extended release (ER) is an oral psychotropic treatment formulated to release paliperidone at a controlled, gradually ascending rate. We evaluated the efficacy and safety of switching to paliperidone ER in Taiwanese patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy.

Patients And Methods: This was a 24-week, open-label, single-arm, multicenter, Phase IV trial. Based on consulting psychiatrists' judgment, patients were deemed eligible for the switch to paliperidone ER; the switch was achieved by cross-tapering, using a recommended starting dose of 6 mg. Eligibility considerations included lack of efficacy, tolerability, and/or adherence to previous oral antipsychotic medication.

Results: Of the 297 enrolled patients, 178 (59.5%) completed the study. The main reasons for discontinuation included insufficient efficacy (8.7%), patient decision (8.4%), and adverse events (AEs; 6.4%). Improvements in the: Positive and Negative Syndrome Scale total score and Clinical Global Impression-Severity score were observed only in patients treated at medical centers and not in those treated at psychiatric hospitals. The most common AEs were insomnia, headache, constipation, and extrapyramidal syndrome. One or more serious AEs were reported in 11 (3.7%) patients; none resulted in death. No significant changes in body weight, plasma glucose, or lipid levels were observed.

Conclusion: Switching to paliperidone ER was effective and well tolerated for up to 24 weeks in patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy. The observed differences in treatment between psychiatric hospitals and medical centers with regard to dosage and titration of paliperidone ER warrant further investigation.
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http://dx.doi.org/10.2147/NDT.S161186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848663PMC
March 2018

An evaluation of the 25 by 25 goal for premature cardiovascular disease mortality in Taiwan: an age-period-cohort analysis, population attributable fraction and national population-based study.

Heart Asia 2017 7;9(2):e010905. Epub 2017 Aug 7.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Objectives: The aim of the 25 by 25 goal is to reduce mortality from premature non-communicable diseases by 25% before 2025. Studies have evaluated the 25 by 25 goal in many countries, but not in Taiwan. The aim of this study was to estimate the 25 by 25 goal for premature mortality from cardiovascular diseases in Taiwan.

Methods: We applied the age-period-cohort model to project the incidence of premature death from cardiovascular disease from 2015 to 2024 and used the population attributable fraction to estimate the contributions of targeted risk factors. The probability of death was used to estimate the percent change.

Results: The percent change in business-as-usual trend during 2010-2024 was only a 6% (range 1.7-10.7%) lower risk of premature mortality from cardiovascular disease among men. The greatest reduction in the risk of mortality occurred with a 30% reduction in the prevalence of smoking; however, there was only a 14.5% (10.6-18.3%) decrease in percent change and in the corresponding number of men (3706: range 3543-3868) who were prevented from dying. More than a 25% reduction in the percent change of premature cardiovascular disease mortality among women was achieved without control of any risk factor. To reach a 25% reduction in men before 2025, there needs to be a 70% reduction in the prevalence of smoking to reduce mortality by 26.2% (22.9-29.3%).

Conclusions: Cigarette smoking is the primary target in the prevention of cardiovascular disease. Through the stringent control of smoking, the goal of a 25% reduction in premature mortality from cardiovascular disease may be achieved before 2025 in Taiwan.
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http://dx.doi.org/10.1136/heartasia-2017-010905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818053PMC
August 2017

Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis.

PLoS One 2017 12;12(9):e0184380. Epub 2017 Sep 12.

Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Aims: Several studies reported treatment benefits of tolvaptan in patients with congestive heart failure (CHF). However, the optimal dosage remains unclear. We aimed to compare different dosage of tolvaptan to determine the optimal dosage in terms of the efficacy and safety.

Methods: We searched MEDLINE, PubMed, EMBASE, Cochrane CENTRAL and ClinicalTrials.gov through Aug 31, 2016. Randomized controlled trials (RCTs) comparing tolvaptan of different dosages or to placebo in patients with CHF were included. We used network meta-analysis to look for the optimal dosage in terms of effectiveness and safety. Urine output, body weight change and change in serum sodium were the main outcomes of efficacy. Adverse effects were the secondary outcomes. Quality was assessed by Cochrane risk-of-bias tool.

Results: Twelve RCTs reporting 14 articles with 5793 patients (mean age, 65.7 ± 11.9 years; 73.7% man) were included. Compared with placebo, the tolvaptan 30 mg had similar effects to tolvaptan 45-90 mg in terms of urine output (mean difference [MD] 2.03 liter; 95% confidence interval [CI] 1.3 to 2.71), body weight change (MD -1.12 kg; 95% CI -1.37 to -0.88) and change in serum sodium (MD 3.06 meq/L; 95% CI 2.43 to 3.68). Compared with placebo, tolvaptan of different dosage showed a non-significant higher risk of adverse effects.

Conclusions: These findings suggest that tolvaptan 30 mg and 45 mg may be the optimum dosage for CHF patients, because of its ability to provide favourable clinical results without greater adverse effects. However, tolvaptan is not beneficial for reducing all-cause mortality in CHF patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184380PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595312PMC
October 2017

Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study.

Schizophr Res 2018 03 6;193:126-133. Epub 2017 Jul 6.

Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Objective: Numerous studies have demonstrated that fluvoxamine has considerable pharmacokinetic and pharmacodynamic interactions with clozapine. We conducted a 12-week, randomized, double-blind, placebo-controlled study to evaluate the effects of fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia.

Methods: We recruited 85 patients who received a DSM-IV diagnosis of schizophrenia. Eligible patients were randomized to receive fluvoxamine 50mg/day plus clozapine 100mg/day or clozapine 300mg/day. We studied metabolic parameters, psychopathology, and drug levels at baseline and 4, 8, and 12weeks after the intervention. Plasma levels of clozapine, norclozapine, clozapine N-oxide, and fluvoxamine were determined using high-performance liquid chromatography with ultraviolet detection.

Results: No significant difference was observed in baseline characteristics between the two groups. Clozapine-fluvoxamine combined treatment significantly attenuated the increments in body weight, insulin resistance, and levels of insulin, glucose, and triglycerides compared with clozapine monotherapy. Both groups exhibited significant improvements in their Positive and Negative Syndrome Scale (PANSS) total and negative scores. The combined treatment group showed significant reduction in the PANSS general psychopathology scores compared with the monotherapy group. No difference was observed in the plasma clozapine level between the two groups. The monotherapy group showed higher levels of norclozapine and clozapine N-oxide than the combined group.

Conclusions: Compared with clozapine monotherapy, treatment with adjunctive fluvoxamine with clozapine for 12weeks can alleviate body weight gain and metabolic abnormalities in patients with schizophrenia, without sacrificing the clinical effect. Clinicians should interpret these findings cautiously considering the short duration of this study. The study was registered at www.clinicaltrials.gov (NCT01401491).
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http://dx.doi.org/10.1016/j.schres.2017.06.030DOI Listing
March 2018

Ag@Au nanoprism-metal organic framework-based paper for extending the glucose sensing range in human serum and urine.

Dalton Trans 2017 May;46(21):6985-6993

Department of Chemistry, Soochow University, Taipei 111, Taiwan.

In this work, we present a Ag@Au nanoprism-metal-organic framework-paper based glucose sensor for rapid, sensitive, single-use and quantitative glucose determination in human serum. To achieve painless measurement of glucose with a non-invasive detection methodology, this biosensor was further tested in human urine. In this approach, a new hybrid-Ag@Au nanoprism loaded in close proximity to micrometer sized coordination polymers as phosphorescent luminophores significantly enhanced the emission intensity due to metal-enhanced phosphorescence and worked as reaction sites to support more dissolved oxygen. Reports of enhanced phosphorescence intensity are relatively rare, especially at room temperature. The true enhancement factor of Ag@Au-phosphorescent metal-organic frameworks on paper was deduced to be 110-fold, making it a better optical type glucose meter. The results demonstrate the validity of the intensity enhancement effect of the excitation of the overlap of the emission band of a luminophore with the surface plasmon resonance band of Ag@Au nanoprisms. Ag@Au nanoprisms were used not only to improve the detection limit of glucose sensing but also to extend the glucose sensing range by enhancing the oxygen oxidation efficiency. The oxidation of glucose as glucose oxidase is accompanied by oxygen consumption, which increases the intensity of the phosphorescence emission. The turn-on type paper-based biosensor exhibits a rapid response (0.5 s), a low detection limit (0.038 mM), and a wide linear range (30 mM to 0.05 mM), as well as good anti-interference, long-term longevity and reproducibility. Finally, the biosensor was successfully applied to the determination of glucose in human serum and urine.
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http://dx.doi.org/10.1039/c7dt00875aDOI Listing
May 2017

Increased long-term risk of major adverse cardiovascular events in patients with carbon monoxide poisoning: A population-based study in Taiwan.

PLoS One 2017 25;12(4):e0176465. Epub 2017 Apr 25.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Background: Carbon monoxide (CO) poisoning may cause toxicity to the cardiovascular system. However, the association between CO poisoning and the risk of major adverse cardiovascular events (MACE) remains unestablished. We investigated the incidence of MACE after CO poisoning in Taiwan and evaluated whether CO-poisoned individuals had a higher risk of MACE than did the general population.

Methods: Using Taiwan's National Health Insurance Research Database (NHIRD) during 2005-2013, a nationwide population-based cohort study was conducted among patients who experienced CO poisoning between 2005 and 2013. CO poisoning was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The study cohort comprised patients with CO poisoning between 2005 and 2010 (N = 13,939). Each patient was matched according to age, sex and index date with four randomly selected controls from the comparison cohort (N = 55,756). All patients were followed from the study date until MACE development, death, or the end of 2013. The hazard ratios for MACE were compared between the two cohorts by using Cox proportional hazards regressions analyses.

Results: Incident cases of MACE were identified from the NHIRD. After adjustment for potential confounders, the study cohort was independently associated with a higher MACE risk (adjusted hazard ratio, 2.00; 95% confidence interval, 1.83-2.18).

Conclusion: This population-based cohort study indicated that patients with CO poisoning have a higher risk of MACE than do individuals without CO poisoning.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176465PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404866PMC
September 2017

A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice.

Cancer Med 2017 02 10;6(2):349-360. Epub 2017 Jan 10.

Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.

Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1 /FLT3- internal tandem duplication (ITD) were independent prognostic factors for the entire cohort. Among patients with intermediate-risk cytogenetics, patients with mutations in CEBPA , IDH2, and NPM1 in the absence of FLT3-ITD were associated with improved Overall survival (OS), similar to those with favorable-risk cytogenetics; patients with mutations in TET2, RUNX1, ASXL1, and DNMT3A were associated with reduced OS, similar to those with unfavorable-risk cytogenetics. We concluded that integration of cytogenetic and molecular profiling improves prognostic stratification of patients into three groups with more distinct prognoses (P < 0.001) and significantly reduces the number of patients classified as intermediate risk. In addition, our study demonstrates that next-generation sequencing (NGS)-based multi-gene sequencing is clinically applicable in establishing an accurate risk stratification system for guiding therapeutic decisions.
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http://dx.doi.org/10.1002/cam4.969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313641PMC
February 2017