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Background: We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT)., Materials and Methods: Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups., Results: Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D 50  = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D 50  = 30 Gy) compared to the low-comorbidity group (D 50  = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively., Conclusion: Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment., Methods: Hospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m 2 ) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis., Results: A total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment., Conclusions: Remdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Patients with atrial fibrillation (AF) may be at higher risk for cancer, possibly due to the presence of coexisting risk factors. In this study, we investigate the magnitude and predictors of this potential risk within a population-based study., Methods and Results: The study cohort included 332,555 AF patients aged ≥20 years without past history of cancer. Standardized incidence ratio (SIR) was used as a measure of relative risk, comparing observed cancer incidence among patients with AF with that expected based on cancer incidence in the Taiwanese population. During the observation period, 22,911 incident cancers occurred with an incidence of 1.65%/year. Compared with the general population, AF patients had a significantly higher cancer risk with a SIR of 1.37 (95%CI = 1.36-1.39). Patients with new-onset AF had an elevated cancer risk which was highest within 1 year (SIR = 2.30; 95%CI, 2.25-2.36) and persisted beyond 10 years after AF was diagnosed (SIR = 1.18; 95%CI, 1.11-1.25). Age ≥ 65 years, male gender, hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and liver cirrhosis were significantly associated with development of cancers among AF patients. The hazard ratio of cancers increased from 1.40 (95%CI = 1.28-1.53) for patients having 1 risk factor to 5.14 (95%CI = 4.03-6.06) for patients with 6 risk factors, in comparison to those without any risk factors., Conclusion: In the nationwide cohort study, we show that AF patients had a higher risk of cancer. Age, male gender, hypertension, diabetes, COPD and liver cirrhosis are important risk factors of cancer among AF patients. Prompt and detailed examinations may be considered for incident AF patients with multiple risk factors to early detect the occult malignancy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Several cardiovascular diseases exhibit seasonal variations, but data about cold temperature and risk of ischemic stroke in patients with atrial fibrillation (AF) are limited., Objective: The purpose of this study was to investigate the risk of ischemic stroke in different seasons, testing the hypothesis that the cold weather season would increase the risk of stroke in AF., Methods: This study used the National Health Insurance Research Database in Taiwan. From 2000 to 2012, a total of 289,559 AF patients were enrolled, and 34,991 experienced ischemic stroke after mean follow-up of 3 years. The relationship between risk of ischemic stroke and temperatures was analyzed., Results: The highest incidence of ischemic stroke was observed in winter, which was the coldest season, with an incidence rate of 0.33 per 100 person-months. Compared with the summer period, the risk of ischemic stroke increased by 10% in spring (incidence rate ratio [IRR] 1.10; 95% confidence interval [CI] 1.07-1.13) and by 19% in winter (IRR 1.19; 95% CI 1.15-1.22) but did not differ significantly between summer and autumn (IRR 1.00; 95% CI 0.97-1.03). Compared with the days with an average temperature of 30°C, the risk of ischemic stroke for days with an average temperature <20°C significantly increased. Lower 7-, 10-, or 14-day average temperatures were significantly associated with an increased risk of ischemic stroke in the case-crossover analysis., Conclusion: In this nationwide study, a seasonal variation of incidence of ischemic stroke in AF patients was observed, with an increased risk of stroke on days with an average temperature <20°C. AF-related stroke may be influenced by environmental interactions., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Most data on the clinical epidemiology of atrial fibrillation (AF) come from Western populations, and data for Asians are limited. We investigated the lifetime risk and projected number of AF among Asians. The annual risks of adverse events among patients with AF, time trends, and the risks compared with patients without AF were analyzed., Methods: Between 2000 and 2011, 289,559 patients aged ≥ 20 years experienced new-onset AF in Taiwan. The incidence, prevalence, and lifetime risk of AF were calculated. The risk of adverse events among patients with AF were analyzed and compared with that of age- and sex-matched patients without AF., Results: The incidence of AF in year 2011 was 1.51 per 1,000 person-years, with a lifetime risk of AF being appropriately 1 in 7 for subjects aged > 20 years. The prevalence of AF is estimated to be 4.01% in 2050. Compared with patients without AF, AF was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 2.61), heart failure (aHR, 3.31), ischemic stroke (aHR, 3.34), dementia (aHR, 1.56), sudden cardiac death (aHR, 1.83), and myocardial infarction (aHR, 1.62); all P < .01. The risks of ischemic stroke, heart failure, and mortality were especially higher compared with patients without AF in the initial period (approximately 6 months) after AF was first diagnosed., Conclusions: The burden of AF among Asian patients is increasing, with a lifetime risk of AF being 1 in 7. Optimized management of any associated comorbidities should be part of the holistic management approach for AF., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Exosomes, secreted by several cell types, including cancer cells, can be isolated from the peripheral blood and have been shown to be powerful markers of disease progression in cancer. In this study, we examined the prognostic significance of circulating exosomal microRNAs (miRNAs) in multiple myeloma (MM). A cohort of 156 patients with newly diagnosed MM, uniformly treated and followed, was studied. Circulating exosomal miRNAs were isolated and used to perform a small RNA sequencing analysis on 10 samples and a quantitative reverse transcription polymerase chain reaction (qRT-PCR) array on 156 samples. We studied the relationship between miRNA levels and patient outcomes, including progression-free survival (PFS) and overall survival (OS). We identified miRNAs as the most predominant small RNAs present in exosomes isolated from the serum of patients with MM and healthy controls by small RNA sequencing of circulating exosomes. We then analyzed exosomes isolated from serum samples of 156 patients using a qRT-PCR array for 22 miRNAs. Two of these miRNAs, let-7b and miR-18a, were significantly associated with both PFS and OS in the univariate analysis and were still statistically significant after adjusting for the International Staging System and adverse cytogenetics in the multivariate analysis. Our findings support the use of circulating exosomal miRNAs to improve the identification of patients with newly diagnosed MM with poor outcomes. The results require further validation in other independent prospective MM cohorts., (© 2017 by The American Society of Hematology.)

Background: Influenza infection could activate systemic inflammatory responses and increase the sympathetic tone that plays an important role in the pathogenesis of atrial fibrillation (AF)., Objectives: The goal of the present study was to investigate whether influenza infection was a risk factor for AF. We also aimed to study whether influenza vaccination could decrease the risk of AF., Methods: From 2000 to 2010, a total of 11,374 patients with newly diagnosed AF were identified from the Taiwan National Health Insurance Research Database. On the same date of enrollment, 4 control patients (without AF) with matched age and sex were selected to be the control group for each study patient. The relationship between AF and influenza infection or vaccination 1 year before the enrollment was analyzed., Results: Compared with patients without influenza infection or vaccination (reference group; n = 38,353), patients with influenza infection without vaccination (n = 1369) were associated with a significantly higher risk of AF with an odds ratio of 1.182 (P = .032) after adjustment for baseline differences. The risk of AF was lower in patients receiving influenza vaccination without influenza infection (n = 16,452) with an odds ratio of 0.881 (P < .001). In patients who have received influenza vaccination and experienced influenza infection (n = 696), the risk of AF was similar to that in the reference group (odds ratio 1.136; P = .214). The lower risk of AF with vaccination was consistently observed in subgroup analyses., Conclusion: Influenza infection was significantly associated with the development of AF, with an 18% increase in the risk, which could be reduced through influenza vaccination., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Both U.S. and European guidelines recommend use of the CHA2DS2-VASc rather than CHADS2 score for stroke risk stratification in atrial fibrillation (AF). However, the CHA2DS2-VASc score has not been proved to be better than CHADS2 score for Asians in a large-scale study., Objective: The purpose of this study was to compare the accuracies of CHADS2 and CHA2DS2-VASc scores in predicting ischemic stroke in Chinese patients., Methods: This study used the National Health Insurance Research Database in Taiwan. A total of 186,570 AF patients without antithrombotic therapies were selected as the study cohort. The clinical end-point was occurrence of ischemic stroke., Results: During follow-up of 3.4 ± 3.7 years, 23,723 patients (12.7%) experienced ischemic stroke. The CHA2DS2-VASc score performed better than CHADS2 score in predicting ischemic stroke assessed by c-indexes (0.698 vs 0.659, P <.0001). Among 25,286 patients with a CHADS2 score of 0, the CHA2DS2-VASc score ranged from 0 to 3, and the annual stroke rate ranged from 1.15% to 4.47%. Compared to patients with a CHA2DS2-VASc score of 0, the hazard ratio of ischemic stroke for patients with a CHA2DS2-VASc score of 3 was 3.998., Conclusion: Patients with a CHADS2 score of 0 were not necessarily "low risk," and the annual stroke rate can be as high as 4.47% when patients were further stratified by the CHA2DS2-VASc score. In contrast, patients with a CHA2DS2-VASc score of 0 had a truly low risk of ischemic stroke, with an annual stroke rate around 1.15%. As with Caucasians, the CHA2DS2-VASc score should be used for stroke risk stratification in Asians., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of our study was to evaluate the overall cancer risk among patients with the irritable bowel syndrome (IBS) by using a nationwide population-based data set., Methods: We obtained data on newly diagnosed IBS patients (age ≥ 20 years) without antecedent cancer from the Taiwan National Health Insurance Research Database for the period between 2000 and 2010. Standardized incidence ratios (SIRs) were calculated for various types of cancer in the IBS patients., Results: A total of 1,043 people among the 29,838 IBS patients had developed cancer, and the follow-up was 139,185 person-years (median, 4.56 years), leading to a significantly increased SIR (1.18; 95% confidence interval [CI]) = 1.11-1.26) among all cancer types. However, after excluding cancer that developed within the first year after IBS diagnosis, the increased SIR of overall cancer was nonsignificant. In particular, the IBS patients exhibited an increased risk of cancers of the colon and rectum (SIR = 1.51; 95% CI = 1.31-1.73), liver and biliary tract (SIR = 1.40; 95% CI = 1.21-1.62), pancreas (SIR = 1.56; 95% CI = 1.02-2.28), and kidney (SIR = 1.56; 95% CI = 1.10-2.15)., Conclusions: An increased SIR in IBS patients was observed only within the first year of IBS diagnosis. The findings of this study might have resulted from detection bias, localized symptoms, or paraneoplastic syndromes associated with IBS-like symptoms. Additional prospective studies are necessary to confirm these findings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is associated with an increased risk of cognitive impairment and functional decline, and may contribute to development of dementia., Objectives: Data from a nationwide large-scale population-based cohort study are lacking. Besides, how best to predict the occurrence of incident dementia among AF subjects remains uncertain., Methods: A total of 332,665 AF subjects without dementia were identified as the study group from the "National Health Insurance Research Database" in Taiwan. For each study patient, one age- and sex-matched subject without AF and dementia was selected as the control group. The study end point was occurrence of dementia, and the usefulness of CHADS2 and CHA2DS2-VASc scores in predicting dementia was analyzed., Results: During the follow-up, 29,012 AF patients experienced dementia with an annual incidence of 2.12%, higher than non-AF subjects (1.50%). Patients with AF possessed a higher risk of dementia with a hazard ratio (HR) of 1.420 after adjustments for age, gender, baseline differences and medication use. Among AF patients, the CHADS2 and CHA2DS2-VASc scores were significant predictors of dementia with an adjusted HR of 1.520 and 1.497 per 1 increment of the CHADS2 and CHA2DS2-VASc scores, respectively. The c-index for CHA2DS2-VASc in predicting dementia (0.611, 95% confidence interval [CI]=0.608-0.614) was significantly higher than the CHADS2 score (0.589, 95% CI=0.586-0.592) (DeLong test p<0.001)., Conclusions: In this nationwide cohort study, AF was independently associated with a higher risk of dementia. The CHA2DS2-VASc score can be used to estimate the risk of dementia in AF patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Atrial fibrillation (AF) is associated with cognitive decline and may contribute to an increased risk of dementia. The goal of the present study was to investigate whether statin use prevented non-vascular dementia in subjects with AF., Methods: Data from the National Health Insurance Research Database of Taiwan were used in this study. The study group comprised 51,253 AF subjects aged ≥ 60 years who had received statin treatment. For each study patient, four age- and sex-matched AF subjects without statin exposure were selected as the control group (n=205,012). The risk of non-vascular dementia was compared between the statin and control groups., Results: During the follow-up period, 17,201 patients experienced non-vascular dementia. The annual incidence of non-vascular dementia was lower in the statin group than in the control group (1.89% vs. 2.20%; p<0.001). Statin use exhibited a protective effect on the occurrence of non-vascular dementia, with an adjusted hazard ratio (HR) of 0.832 (95% confidence interval=0.801-0.864). Among statin types, the use of rosuvastatin was associated with the largest risk reduction (adjusted HR=0.661). Statin exposure duration was related inversely to the risk of non-vascular dementia., Conclusions: In this large-scale nationwide cohort study, statin use was associated with a lower risk of non-vascular dementia in AF. Use of more potent statin and longer exposure time may be associated with greater benefits., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Orthostatic hypotension (OH) is a common condition encountered in the elderly. The present study aimed to examine the relationship between OH and adverse events in Asians., Methods: We used the "National Health Insurance Research Database" in Taiwan. A total of 1226 patients with OH and without previous history of ischemic stroke and myocardial infarction were identified as the study group. For each study patient, ten age-, sex- and comorbidity-matched subjects without OH were selected to constitute the control group (n = 12,260). The clinical endpoints were ischemic stroke, myocardial infarction and all-cause mortality., Results: The mean age of the study population was 54.8 ± 19.0 years and males accounted for 47% of the patients. During the follow-up of 4.5 ± 2.9 years, 704 (5.2%) patients developed ischemic stroke, 190 (1.4%) patients developed myocardial infarction, and 733 (5.4%) patients died. In the multivariable Cox regression analyses which were adjusted for age, gender and differences in medication usages, OH was significantly associated with an increased risk of ischemic stroke (hazard ratio [HR] = 1.40, 95% confidence interval (CI) = 1.09-1.81, p = 0.009), all-cause mortality (HR = 1.35; 95% CI = 1.05-1.73, p = 0.018) and adverse events (ischemic stroke, myocardial infarction or mortality) (HR = 1.41; 95% CI = 1.18-1.68, p < 0.001)., Conclusion: OH is an independent factor associated with ischemic stroke and mortality in Asians. Whether aggressive managements for stroke prevention could improve the outcome for OH patients deserves further study., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Atrial fibrillation (AF) is prevalent in end-stage renal disease (ESRD) patients and negatively impacts patient outcomes. We explored the incidence and risk factors for new-onset AF among patients with ESRD undergoing renal replacement therapy, without a prior history of AF, retrieved from Taiwan's National Health Insurance Research Database (NHIRD). For each of 134,901 patients with ESRD, one age- and gender-matched control and one similarly matched patient with chronic kidney disease (CKD), a total of 404,703 patients, were selected from the NHIRD. The study endpoint was the occurrence of new-onset AF and patients were followed an average of 5.1 years. The incidence rates of AF were 12.1, 7.3, and 5.0 per 1000 person-years for ESRD, CKD, and control patients, respectively. Among patients with ESRD, age, hypertension, heart failure, coronary artery disease, peripheral arterial occlusive disease, and chronic obstructive pulmonary disease were significant risk factors for new-onset AF. Thus, patients with ESRD had a significantly higher risk of new-onset AF. The presence of multiple risk factors was associated with a higher possibility of AF occurrence.

Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with <20 ng of DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues], coupled with an informatics pipeline to specifically identify relevant predefined variants and created a knowledge base of related potential treatments, current practice guidelines, and open clinical trials. We validated OCP using molecular standards and more than 300 FFPE tumor samples, achieving >95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Saxagliptin was associated with an increased risk of hospitalization for heart failure (HHF) in diabetic patients with high cardiovascular risk. This study assessed the risk of HHF during an exposure to sitagliptin in general diabetic patients., Methods: In Taiwan National Health Insurance research database, a study of the beneficiaries aged ≥ 45 years with diabetes treated with or without sitagliptin between March 2009 and July 2011 was conducted. Patients treated with sitagliptin were matched to patients never exposed to a dipeptidyl peptidase-4 (DPP-4) inhibitor by the propensity score methodology. The outcome measures were the first and the total number of HHF, and mortality for heart failure or all causes., Results: A total of 8288 matched pairs of patients were analyzed. During a median of 1.5 years, the first event of HHF occurred in 339 patients with sitagliptin and 275 patients never exposed to a DPP-4 inhibitor (hazard ratio: 1.21, 95% confidence interval: 1.04-1.42, P = 0.017); all-cause mortality was similar (hazard ratio: 0.87, 95% confidence interval: 0.74-1.03, P = 0.109). The risk for HHF was proportional to exposure (hazard ratio: 1.09, 95% confidence interval: 1.06-1.11, P < 0.001 for every 10% increase in adherence to sitagliptin). Overall, there were 935 events of HHF, in which the association between the number of HHF and the adherence to sitagliptin was linear. The greatest total number of HHF occurred in the patients with the highest adherence., Conclusions: The use of sitagliptin was associated with a higher risk of HHF but no excessive risk for mortality was observed., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The risk of acute myocardial infarction (AMI) in patients with atrial fibrillation (AF) with a CHA2DS2-VASc score of 0 (for men) or 1 (for women) has not been previously investigated., Objective: The objective of the present study was to compare the risk of AMI in AF and non-AF subjects with a low (0 or 1) CHA2DS2-VASc score., Methods: By using the National Health Insurance Research Database in Taiwan, we identified 7254 men with AF (with a CHA2DS2-VASc score of 0) and 4860 women with AF (with a CHA2DS2-VASc score of 1). For each study patient, 1 age-, sex-, and CHA2DS2-VASc score-matched subject without AF was randomly selected to constitute the control group (n = 12,114). The clinical end point was the occurrence of AMI., Results: During a mean follow-up period of 5.7 ± 3.6 years, 258 patients (1.1%) suffered an AMI, with an annual incidence of 0.29% and 0.10% for patients with and without AF. AF was an independent risk factor of AMI, with an adjusted hazard ratio (HR) of 2.93 (95% confidence interval 2.21-3.87; P < .001). The risk of AMI was higher in men with AF than in women with AF, with a hazard ratio of 2.24 (95% confidence interval 1.61-3.11; P < .001) after adjustment for age and other comorbidities., Conclusion: In patients with a CHA2DS2-VASc score of 0 or 1, AF was an independent risk factor of AMI. The risk of AMI was higher in men with AF than in women with AF. Cardiovascular risk prevention should be performed as part of the holistic management of AF to minimize the risks of AMI associated with AF., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The implantation of a permanent pacemaker (PPM) is life-saving for patients with life-threatening bradycardia. However, the effectiveness and prognosis of PPM implantations for extremely old patients (≥ 90 years old) have not been investigated., Methods: From 2001-2012, a total of 108 patients older than 90 years were identified from 2630 consecutive patients receiving PPM implantations in our hospital as the study group. For each study patient, 4 age-, sex-, and comorbidity-matched subjects who did not have the diagnoses of bradyarrhythmias indicated for PPM implantations were selected from the "Taiwan National Health Research Database" to constitute the control group (n = 432). The study end point was all-cause mortality., Results: The median age of the study population was 91 (interquartile range, 90-93) years. Among the PPM group, 45 patients died during the follow-up with an annual mortality rate of 18.7%. The risk of mortality did not differ significantly between the study and control groups with a hazard ratio of 1.020 (95% confidence interval, 0.724-1.437; P = 0.912) after the adjustment for age and sex. Procedure-related complications occurred in 7.4% of the patients receiving PPM implants, and pocket hematoma was the most common. The preimplantation history of heart failure and cerebrovascular accident, rather than age, were significant predictors of mortality among PPM recipients., Conclusions: Nonagenarians with severe bradyarrhythmias could retain the same life expectancies as those without bradyarrhythmias through PPM implantations. Extremely old age (≥90 years) should not be a barrier for PPM implants when indications are present., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Renal dysfunction is a significant risk factor for ischemic stroke in atrial fibrillation (AF). However, the incidence of ischemic stroke and how to predict its occurrence among AF patients with end-stage renal disease (ESRD) are unclear., Objective: The purpose of this study was to compare the CHADS2 and CHA2DS2-VASc scores for stroke risk stratification in AF patients with ESRD., Methods: A total of 10,999 AF patients with ESRD undergoing renal replacement therapy who were not receiving oral anticoagulants or antiplatelet agents were identified from Taiwan's National Health Insurance Research Database. The study end-point was occurrence of ischemic stroke., Results: The median (interquartile) CHADS2 and CHA2DS2-VASc scores for the study cohort were 3 (2-5) and 5 (4-7), respectively. During follow-up, 1217 patients (11.7%) experienced ischemic stroke, with an incidence rate of 6.9 per 100 person-years. In Cox regression models, the CHADS2 and CHA2DS2-VASc scores both were significant predictors of ischemic stroke. C-indexes for CHADS2 and CHA2DS2-VASc were 0.608 and 0.682, respectively (P < .001). CHA2DS2-VASc improved the net reclassification index by 4.8% compared with CHADS2 (P < .0001). Among 1409 patients with a CHADS2 score of 0 or 1, the CHA2DS2-VASc score ranged from 1 to 4, with event rates ranging from 2.1 to 4.7 per 100 person-years., Conclusion: The CHA2DS2-VASc score was useful in predicting ischemic stroke in AF patients with ESRD undergoing dialysis and was superior to the CHADS2 score. The net clinical benefit balancing stroke reduction against major bleeding with anticoagulation in these high-risk patients remains to be defined., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Digoxin and related cardiac glycosides have been used for almost 100 years in atrial fibrillation (AF). However, 2 recent analyses of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial showed inconsistent results regarding the risk of mortality associated with digoxin use. The goal of the present study was to investigate the relationship between digoxin and the risk of ischemic stroke and mortality in Asians., Methods: This study used the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 4781 patients with AF who did not receive any antithrombotic therapy were selected as the study population. Among the study population, 829 participants (17.3%) received the digoxin treatment. The risk of ischemic stroke and mortality in patients who received digoxin and those who did not was compared., Results: The use of digoxin was associated with an increased risk of clinical events, with an adjusted hazard ratio of 1.41 (95% confidence interval [CI], 1.17-1.70) for ischemic stroke and 1.21 (95% CI, 1.01-1.44) for all-cause mortality. In the subgroup analysis based on coexistence with heart failure or not, digoxin was a risk factor for adverse events in patients without heart failure but not in those with heart failure (interaction P < 0.001 for either end point). Among patients with AF without heart failure, the use of β-blockers was associated with better survival, with an adjusted hazard ratio of 0.48 (95% CI, 0.34-0.68)., Conclusions: Digoxin should be avoided for patients with AF without heart failure because it was associated with an increased risk of clinical events. β-Blockers may be a better choice for controlling ventricular rate in these patients., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Although hyperuricemia has been reported to be a risk factor of stroke, the relationship between hyperuricemia and stroke in patients with atrial fibrillation (AF) remains uncertain. The goal of the present study was to investigate whether hyperuricemia could potentially refine clinical risk stratification in AF., Methods: This study used the "National Health Insurance Research Database" in Taiwan. A total of 7601 AF patients who did not receive antiplatelet agents or oral anticoagulants were identified as the study population. Hyperuricemia was defined as having at least one episode of gout attack necessitating long-term treatment with uric acid-lowering agents. The association between hyperuricemia and ischemic stroke was analyzed., Results: During the follow up of 3.0±2.7 years, 1116 patients (14.7%) experienced ischemic stroke with an annual rate of around 4.9%. Hyperuricemia significantly predicts stroke, with a hazard ratio (HR) of 1.280 after adjusting for CHA2DS2-VASc score and other comorbidities. Among the 376 patients with a CHA2DS2VASc score of 0, hyperuricemia can further stratify them into 2 groups with different stroke rates (7.1% versus 1.3%, p=0.020). The adjusted HR of hyperuricemia in predicting ischemic stroke diminished from 7.491 for patients with a CHA2DS2-VASc score of 0 to 1.659 for those with a score of 3, and became insignificant for patients with a score ≥4., Conclusions: Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF. It deserves a prospective trial to investigate whether it would change the current strategy for stroke preventions using oral anticoagulants., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate the risk of cancer among patients with nonapnea sleep disorders (SDs)., Methods: We included newly diagnosed SD patients aged 20 years and older without antecedent cancer between 2000 and 2010 from the National Health Insurance Research Database. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of patients with SD with that of the general population., Results: During the 10-year study period, 2062 cancers developed among 63,381 SD patients, who were observed for 382,826 person-years (median follow-up of 6.23 years). The SIR for all cancers was 1.19 (95% confidence interval [CI], 1.14e1.24). For specific cancer types, SD patients exhibited an increased SIR for liver and lung cancers (1.44; 95% CI, 1.28e1.61 and 1.34; 95% CI, 1.18e1.51, respectively)., Conclusions: We observed that overall cancer risk is increased among Asian SD patients. In terms of individual cancers, the risks of liver and lung cancers were elevated. Clinicians should be aware of the possibility of increased liver and lung cancers among SD patients in Taiwan. A prospective study is necessary to confirm these findings., (2013 Elsevier Inc. All rights reserved.)

Background: Improvement of oral hygiene through dental scaling was associated with a decreased risk of cardiovascular events. The goal of the present study was to investigate whether dental scaling can reduce the risk of atrial fibrillation (AF)., Methods: In year 2000, a total of 28,909 subjects who were age 60 or more without past history of cardiac arrhythmias were identified from the "National Health Insurance Research Database" in Taiwan. Among these subjects, those who have received dental scaling at least 1 time/year for 3 consecutive years (1998-2000) were selected to be the exposed group (n=3391). A total of 13,564 age, sex and underlying disease-matched subjects without receiving dental scaling were identified to be the non-exposed group. The study endpoint was the occurrence of new-onset AF., Results: During a follow-up of 4.6 ± 1.1 years, 478 participants (2.8%) developed AF. The exposed group had a lower AF occurrence rate than non-exposed group (2.2% versus 3.0%; p value=0.017). After an adjustment with age, gender, and comorbidities in the multivariate analysis, dental scaling was associated with a reduced risk of AF (hazard ratio=0.671, 95% CI=0.524-0.859; p value=0.002). Among the exposed group, the hazard ratio in developing AF was 0.340 (95% CI=0.247-0.489; p value <0.001) when subjects received 1 more dental scaling per year., Conclusions: The risk of AF was lower in subjects receiving dental scaling. Improvement of oral hygiene by dental scaling may be a simple and useful way to prevent AF., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The components of CHADS2 score were reported to be important risk factors for the development of atrial fibrillation (AF). The goal of the current study was to investigate whether the CHADS2 score was a useful scheme in predicting new-onset AF. Furthermore, we aimed to use the CHADS2 scoring system to estimate the individual risk in developing AF for patients with different comorbidities., Methods: From January 1, 2000 to December 31, 2001, a total of 702,502 patients older than 18 years old and who had no history of cardiac arrhythmias were identified from the "National Health Insurance Research Database" released by the Taiwan National Health Research Institutes. The CHADS2 score was calculated for every patient. Finally, 628,807 (score 0), 47,039 (score 1), 15,655 (score 2), 6843 (score 3), 3315 (score 4), 790 (score 5) and 53 (score 6) patients were studied and followed for the occurrences of AF., Results: During a follow-up of 9.0 ± 2.2 years, there were 9187 (1.3%) patients experiencing new-onset AF. The incidence of AF was 1.5 per 1000 patient-years. The incidence increased from 0.8 per 1000 patient-years for patients with a CHADS2 score of 0 to 34.6 per 1000 patient-years for those with a CHADS2 score of 6. After an adjustment for the gender and comorbidities, the hazard ratio (95% confidence interval) of each increment of the CHADS2 score in predicting AF was 2.342 (2.309-2.375; p<0.001)., Conclusions: The CHADS2 score, consisting of an age >75 and several clinical risk factors was useful in risk estimation and stratification of new-onset AF., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The goal of the present study was to investigate whether exposure to non-steroidal anti-inflammatory drugs (NSAIDs) was a risk factor for AF, and to discern which patients were at the highest risk for AF due to NSAID use., Methods: A total of 7280 patients with newly diagnosed AF from 2000 to 2009 were identified from the National Health Insurance Research Database. On the same date of enrollment, 10 patients without AF, who were matched for age, sex, and underlying disease for each study patient, were selected to be the control group. The relationship between NSAID exposure before enrollment and AF risk was analyzed., Results: The NSAID use was associated with an increased AF risk, especially for new users (odds ratio [OR]=1.651). Among new users, subgroup analysis revealed that patients with heart failure were at the highest risk for AF (OR=1.920). For patients who were only exposed to selective cyclooxygenase 2 (COX2) inhibitors, no significant associations were found between AF and selective COX2 inhibitor use, except for patients with chronic kidney or pulmonary disease (OR=1.656 and 1.707, respectively)., Conclusions: New NSAID use may predispose patients to AF, and the risk is almost doubled in heart failure patients. Use of selective COX2 inhibitors was not significantly related to AF occurrence, except in patients with chronic kidney or pulmonary disease., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Background: The risk of incident cancer after angiotensin II receptor blockers (ARBs) exposure was controversially reported by analyses of clinical trials and database. We assessed the occurrence of overall and site-specific cancers among ARB users and nonusers in the cohort with indications for ARB treatment., Methods: Data were obtained from the Taiwan National Health Insurance research database. Subjects exposed to ARBs ≥ 180 days with no cancer prior to the first year of ARB initiation were identified; age-, sex-, comorbidity- and time-matched nonusers without cancer before the index date plus 1 year were selected. Incidences of overall and the most common cancers between users and nonusers were compared., Results: There were 42,921 subjects enrolled in each group. During the mean follow-up of 4.8 ± 2.4 years, the cumulative incidence of cancer was 4% (ARB users) and 6% (ARB nonusers) (hazard ratio: 0.58, 95% confidence intervals 0.55-0.62; P<0.001). All ARBs significantly correlated with lower rates of cancer. Malignancies from the 7 most common sites were fewer in ARB users with the relative risk reduction of 28 to 49%. ARBs were associated with a decrease in incident cancer across subgroups including prior and concomitant exposure to angiotensin-converting enzyme inhibitors., Conclusions: In the cohort with indications for ARB treatment, exposure to ARBs was associated with lower risk of overall and site-specific cancers compared to nonusers. These findings reassure the safety of ARBs and support further investigations on ARBs and cancer prevention at the molecular level., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these patients. To identify any association between NSAID use and cancer risk in patients with end-stage renal disease on dialysis, we used Taiwan's National Health Insurance database to conduct a nationwide population-based, propensity score-matched cohort study. All cancers between groups were compared by Cox proportional hazards models. Compared to nonuse of NSAIDs, the use of non-COX-2-selective inhibitors (hazard ratio 0.81, 95% confidence interval 0.67-0.97) or COX-2-selective inhibitors (0.78, 0.62-0.98) was associated with a lower risk of developing cancer. NSAID use reduced the risk of respiratory (0.39, 0.19-0.79), breast (0.41, 0.19-0.89), kidney (0.58, 0.38-0.88), digestive tract (0.64, 0.49-0.85), and bladder cancers (0.73, 0.55-0.96). NSAID use, however, significantly increased risk for upper gastrointestinal bleeding (odds ratio, 1.15, 1.07-1.23) but not adverse cardiac or cerebrovascular events. Thus, NSAID use was associated with a lower risk of developing cancer in chronic dialysis patients; however, they should still be used with caution due to the side effects of gastrointestinal bleeding.

Background & Aims: Hepatic encephalopathy (HE) is a reversible neuropsychiatric disorder in cirrhotic patients. The cognitive dysfunction and increased accidental falls in HE and osteodystrophy in cirrhotic patients may contribute to orthopedic fractures. This study investigated the fracture incidence and risk factors in cirrhotic patients with HE., Methods: In total, 3764 cirrhotic patients with HE were identified from the Taiwan National Health Insurance database between 2000 and 2009. The fracture incidence of the HE patients was compared with that of 3764 age-, sex-, and comorbidity-matched cirrhotic patients without HE and non-cirrhotic controls. Cox proportional hazard models were used to estimate the risk of fracture in the HE patients., Results: Cirrhotic patients with and without HE had comparable increased risks of fracture (p <0.05) and cumulative incidences of fracture than controls (log-rank p <0.001). The estimated fracture rates were 7.09% for the HE group, 7.72% for the cirrhosis without HE group, and 4.05% for the controls, during the 18-month follow-up. The HE group had a higher incidence rate of skull fractures (IRR=2.61, 95% CI 1.04-6.57), but a lower rate of upper limb fractures (IRR=0.45, 95% CI 0.29-0.70) than the cirrhosis without HE group. Alcoholism, heart failure, and cerebrovascular disease were associated with increased risk of fracture in HE patients., Conclusions: Cirrhotic patients, with or without HE, are at an increased risk of orthopedic fractures. Skull fractures, rather than fractures in weight-bearing bones, are more frequently observed in HE patients, particularly those with comorbidities., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Infective endocarditis (IE) is an uncommon but potentially life-threatening disease. Poor oral hygiene has been assumed as an important risk factor for IE. We aimed to investigate whether the improvement of oral hygiene through dental scaling could reduce the risk of IE., Methods: From January 1, 2000 to December 31, 2009, a total of 736 patients with newly diagnosed IE were identified from the National Health Insurance Research Database. On the same date of enrollment, 10 patients (without IE) with matched age, sex, and underlying diseases were selected to be the control group for each study patient. The frequency of dental scaling before the enrollment was analyzed and compared between the study and the control groups., Results: The percentages of patients who ever received dental scaling before the enrollment were higher in the control group than that in the study group. For patients who received dental scaling once in 2 years, the risk of IE can be reduced by about 15% (odds ratio, 0.845; 95% confidence interval, 0.693-1.012) with a borderline P value (P = 0.058). Moreover, the risk of IE decreased significantly among patients who received dental scaling at least once per year, with an odds ratio of 0.696 (95% confidence interval, 0.542-0.894; P = 0.005)., Conclusions: Improvement of oral hygiene by dental scaling may reduce the risk of IE. More frequent and regular dental scaling (at least once per year) was associated with a significant decrease in IE., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)