Prediabetes as a risk factor for new-onset atrial fibrillation: the propensity-score matching cohort analyzed using the Cox regression model coupled with the random survival forest.

BACKGROUND: The glycemic continuum often indicates a gradual decline in insulin sensitivity leading to an increase in glucose levels. Although prediabetes is an established risk factor for both macrovascular and microvascular diseases, whether prediabetes is independently associated with the risk of developing atrial fibrillation (AF), particularly the occurrence time, has not been well studied using a high-quality research design in combination with statistical machine-learning algorithms. METHODS: Using data available from electronic medical records collected from the National Taiwan University Hospital, a tertiary medical center in Taiwan, we conducted a retrospective cohort study consisting 174,835 adult patients between 2014 and 2019 to investigate the relationship between prediabetes and AF. To render patients with prediabetes as comparable to those with normal glucose test, a propensity-score matching design was used to select the matched pairs of two groups with a 1:1 ratio. The Kaplan-Meier method was used to compare the cumulative risk of AF between prediabetes and normal glucose test using log-rank test. The multivariable Cox regression model was employed to estimate adjusted hazard ratio (HR) for prediabetes versus normal glucose test by stratifying three levels of glycosylated hemoglobin (HbA1c). The machine-learning algorithm using the random survival forest (RSF) method was further used to identify the importance of clinical factors associated with AF in patients with prediabetes. RESULTS: A sample of 14,309 pairs of patients with prediabetes and normal glucose test result were selected. The incidence of AF was 11.6 cases per 1000 person-years during a median follow-up period of 47.1 months. The Kaplan-Meier analysis revealed that the risk of AF was significantly higher in patients with prediabetes (log-rank p < 0.001). The multivariable Cox regression model indicated that prediabetes was independently associated with a significant increased risk of AF (HR 1.24, 95% confidence interval 1.11-1.39, p < 0.001), particularly for patients with HbA1c above 5.5%. The RSF method identified elevated N-terminal natriuretic peptide and altered left heart structure as the two most important risk factors for AF among patients with prediabetes. CONCLUSIONS: Our study found that prediabetes is independently associated with a higher risk of AF. Furthermore, alterations in left heart structure make a significant contribution to this elevated risk, and these structural changes may begin during the prediabetes stage.

Prediabetes increases the risk of major limb and cardiovascular events.

BACKGROUND: Prediabetes, an intermediate stage between normal blood sugar levels and a diabetes mellitus diagnosis, is increasing in prevalence. Severe prediabetes is associated with a similar risk of complications as diabetes, but its relationship with peripheral arterial disease remains underexplored. METHODS: We conducted a retrospective cohort study involving 36,950 adult patients, utilizing electronic medical records from the National Taiwan University Hospital between 2014 and 2019. We employed multivariable Cox regression and Kaplan-Meier analysis with the log-rank test to analyze major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in relation to normal glucose regulation (NGR) and prediabetes. RESULTS: During the 131,783 person-years follow-up, 17,754 cases of prediabetes and 19,196 individuals with normal glucose regulation (NGR) were identified. Kaplan-Meier analysis revealed an increased incidence of both MALE and MACE in individuals with prediabetes. (log-rank p = 0.024 and < 0.001). Prediabetes exhibited a significant association with an elevated risk of MALE (adjusted hazard ratio (aHR) 1.26 [95% CI 1.10-1.46], p = 0.001) and MACE (aHR 1.46 [1.27-1.67], p < 0.001). Furthermore, in individuals with prediabetes, the elevation in the risk of MALE commenced before HbA1c levels surpassed 5.0% (for HbA1c 5.0-5.5%: aHR 1.78 (1.04-3.04), p = 0.036; HbA1c 5.5-6.0%: aHR 1.29 [1.06-1.58], p = 0.012; aHbA1c 6.0-6.5%: aHR 1.39 [1.14-1.70], p < 0.001). Similarly, the onset of increased MACE risk was observed when HbA1c levels exceeded 5.5% (for HbA1c 5.5-6.0%: aHR 1.67 [1.39-2.01], p < 0.001; HbA1c 6.0-6.5%: HR 2.10 [1.76-2.51], p < 0.001). Factors associated with both MALE and MACE in prediabetes include advanced age, male gender, higher body mass index, and a history of heart failure or atrial fibrillation. CONCLUSION: We demonstrated higher susceptibility to MALE and MACE in prediabetes compared to normoglycemic counterparts, notwithstanding lower HbA1c levels. Complications may manifest at an earlier prediabetes trajectory. Intensive lifestyle modification may improve the prognosis of severe prediabetes.

Incidence, Prevalence, and Mortality of People with Psoriasis and Psoriatic Arthritis in Taiwan: A Nationwide Cohort Study.

There is a recognized need to better understand changes in the epidemiology of psoriasis and psoriatic arthritis (PsA) over time in Asia. Using the Taiwan National Health Insurance claim records this population-based study examined changes in the prevalence, incidence, and mortality rates in patients with psoriasis or psoriatic arthritis in Taiwan over 12 years. Patients with ≥1 diagnosis code for psoriasis or psoriatic arthritis, recorded either by dermatologists or rheumatologists, were identified. Annual age- and sex-standardized prevalence and incidence rates were calculated using the Taiwan general population as reference. To investigate mortality, each patient in the incident cohort was matched to 10 comparators from the general population by sex and age (at diagnosis). The risk of mortality between study cohorts and comparators was analysed by Cox proportional hazard regression. The prevalence of psoriasis (0.18-0.86%) and psoriatic arthritis (0.01-0.08%) increased steadily between 2006 and 2017. The incidence rates, however, remained stable (psoriasis: 62-65 per 100,000 person-years; psoriatic arthritis: 6-5 per 100,000 person-years). The risk of all-cause mortality for patients with psoriasis (hazard ratio 1.16; 95% confidence interval: 1.13-1.19) was higher than the general population, despite a decreasing trend over time in the all-cause mortality rates for both groups. The steady increase in the prevalence of psoriasis despite stable incidence rates suggests that improvements in life expectancy may be the key determinant of this increase.

Quality assurance of integrative big data for medical research within a multihospital system.

BACKGROUND: The need is growing to create medical big data based on the electronic health records collected from different hospitals. Errors for sure occur and how to correct them should be explored. METHODS: Electronic health records of 9,197,817 patients and 53,081,148 visits, totaling about 500 million records for 2006-2016, were transmitted from eight hospitals into an integrated database. We randomly selected 10% of patients, accumulated the primary keys for their tabulated data, and compared the key numbers in the transmitted data with those of the raw data. Errors were identified based on statistical testing and clinical reasoning. RESULTS: Data were recorded in 1573 tables. Among these, 58 (3.7%) had different key numbers, with the maximum of 16.34/1000. Statistical differences (P < 0.05) were found in 34 (58.6%), of which 15 were caused by changes in diagnostic codes, wrong accounts, or modified orders. For the rest, the differences were related to accumulation of hospital visits over time. In the remaining 24 tables (41.4%) without significant differences, three were revised because of incorrect computer programming or wrong accounts. For the rest, the programming was correct and absolute differences were negligible. The applicability was confirmed using the data of 2,730,883 patients and 15,647,468 patient-visits transmitted during 2017-2018, in which 10 (3.5%) tables were corrected. CONCLUSION: Significant magnitude of inconsistent data does exist during the transmission of big data from diverse sources. Systematic validation is essential. Comparing the number of data tabulated using the primary keys allow us to rapidly identify and correct these scattered errors.

Higher long-term visit-to-visit glycemic variability predicts new-onset atrial fibrillation in patients with diabetes mellitus.

BACKGROUND: Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Glycemic variability (GV) is associated with risk of micro- and macrovascular diseases. However, whether the GV can increase the risk of AF remains unknown. METHODS: The cohort study used a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, a total of 27,246 adult patients with T2DM were enrolled for analysis. Each individual was assessed to determine the coefficients of variability of fasting glucose (FGCV) and HbA1c variability score (HVS). The GV parameters were categorized into quartiles. Multivariate Cox regression models were employed to estimate the relationship between the GV parameters and the risk of AF, transient ischemic accident (TIA)/ischemic stroke and mortality in patients with T2DM. RESULTS: The incidence rates of AF and TIA/ischemic stroke were 21.31 and 13.71 per 1000 person-year respectively. The medium follow-up period was 70.7 months. In Cox regression model with full adjustment, the highest quartile of FGCV was not associated with increased risk of AF [Hazard ratio (HR): 1.12, 95% confidence interval (CI) 0.96-1.29, p = 0.148] or TIA/ischemic stroke (HR: 1.04, 95% CI 0.83-1.31, p = 0.736), but was associated with increased risk of total mortality (HR: 1.33, 95% CI 1.12-1.58, p < 0.001) and non-cardiac mortality (HR: 1.41, 95% CI 1.15-1.71, p < 0.001). The highest HVS was significantly associated with increased risk of AF (HR: 1.29, 95% CI 1.12-1.50, p < 0.001), total mortality (HR: 2.43, 95% CI 2.03-2.90, p < 0.001), cardiac mortality (HR: 1.50, 95% CI 1.06-2.14, p = 0.024) and non-cardiac mortality (HR: 2.80, 95% CI 2.28-3.44, p < 0.001) but was not associated with TIA/ischemic stroke (HR: 0.98, 95% CI 0.78-1.23, p = 0.846). The Kaplan-Meier analysis showed significantly higher risk of AF, cardiac and non-cardiac mortality according to the magnitude of GV (log-rank test, p < 0.001). CONCLUSIONS: Our data demonstrate that high GV is independently associated with the development of new-onset AF in patients with T2DM. The benefit of maintaining stable glycemic levels to improve clinical outcomes warrants further studies.

Underweight is a major risk factor for atrial fibrillation in Asian people with type 2 diabetes mellitus.

BACKGROUND: Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Obesity commonly accompanies T2DM, and increases the risk of AF. However, the dose-relationship between body mass index (BMI) and AF risk has seldom been studied in patients with diabetes. METHODS: This cohort study utilized a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, 64,339 adult patients with T2DM were enrolled for analysis. BMI was measured and categorized as underweight (BMI < 18.5), normal (18.5 ≤ BMI < 24), overweight (24 ≤ BMI < 27), obesity class 1 (27 ≤ BMI < 30), obesity class 2 (30 ≤ BMI < 35), or obesity class 3 (BMI ≥ 35). Multivariate Cox regression and spline regression models were employed to estimate the relationship between BMI and the risk of AF in patients with T2DM. RESULTS: The incidence of AF was 1.97 per 1000 person-years (median follow-up, 70.7 months). In multivariate Cox regression, using normal BMI as the reference group, underweight (HR 1.52, 95% CI 1.25-1.87, p < 0.001) was associated with a significantly higher risk of AF, while overweight was associated with significantly reduced risk of AF (HR 0.82, 95% CI 0.73-0.89, p < 0.001). Kaplan-Meier analysis showed AF risk was highest in the underweight group, followed by obesity class 3, while the overweight group had the lowest incidence of AF (log-rank test, p < 0.001). The cubic restrictive spline model revealed a "J-shaped" or "L-shaped" relationship between BMI and AF risk. CONCLUSIONS: Underweight status confers the highest AF risk in Asian patients with T2DM.

Single and dual antiplatelet therapy in elderly patients of medically managed myocardial infarction.

BACKGROUNDS: To examine the comparative effectiveness between dual and single antiplatelet therapies in real-world, medically managed elderly patients with acute myocardial infarction (AMI). METHODS: This retrospective study identified very elderly (> 85 years) patients, who were medically managed, with their first AMI from the Taiwan National Health Insurance claims database from 2007 to 2010. Patients were classified as dual antiplatelet therapy (DAPT) group, aspirin only group and clopidogrel only group. Study outcomes included all-cause death, cardiovascular death and gastrointestinal bleeding. Treating DAPT group as the reference, we employed a multivariable Cox regression model to compare the relative risks of outcomes between 3 groups using pairwise comparison approach. RESULTS: Among 1469 patients with incident ST-elevation myocardial infarction (STEMI, 14%) or non-STEMI (86%), 390 patients were prescribed DAPT, 549 aspirin only, and 530 clopidogrel only. After 9 months of follow-up, aspirin only group had similar risks of all-cause death (adjusted HR 1.21, 95% CI 0.77-1.89, p = 0.41), cardiovascular death (adjusted HR 1.16, 95% CI 0.66-2.04, p = 0.60) and gastrointestinal bleeding (adjusted HR 1.66, 95% CI 0.77-3.57, p = 0.20) in comparison with DAPT group. Clopidogrel users had a higher risk of all-cause death (adjusted HR 1.50, 95% CI 1.00-2.25, p = 0.049) but similar risks of cardiovascular death and gastrointestinal bleeding when compared with DAPT. CONCLUSIONS: Among very elderly patients who were medically managed after AMI, single antiplatelet therapy had comparable protective effect as DAPT. But clopidogrel only strategy was associated with a higher risk of all-cause death.

Burden of asthma and COPD overlap (ACO) in Taiwan: a nationwide population-based study.

BACKGROUND: Patients with symptoms of both asthma and chronic obstructive pulmonary disease (COPD) may be classified with the term asthma-COPD overlap (ACO). ACO is of considerable interest as it is currently poorly characterised and has been associated with worse health outcomes and higher healthcare costs compared with COPD or asthma alone. Patients with ACO in Asia remain poorly described, and there is limited information regarding their resource utilisation compared with patients with asthma or COPD only. This study investigated the characteristics, disease burden and medical resource utilisation of patients with ACO in Taiwan. METHODS: This was a retrospective cohort study of patients identified from National Health Insurance (NHI) claims data in Taiwan in 2009-2011. Patients were classified into incident ACO, COPD or asthma cohorts according to International Classification of Disease, ninth revision, clinical modification codes in claims. Eligible patients were ≥40 years of age with 12 months' continuous enrolment in the NHI programme pre- and post-index date (date of the first relevant medical claim). RESULTS: Patients with ACO (N = 22,328) and COPD (N = 69,648) were older and more likely to be male than those with asthma (N = 50,293). Patients with ACO had more comorbidities and exacerbations, with higher medication use: short-acting ß2-agonist prescriptions ranged from 30.4% of patients (asthma cohort) to 43.6% (ACO cohort), and inhaled corticosteroid/long-acting ß2-agonist combination prescriptions ranged from 11.1% (COPD cohort) to 35.0% (ACO cohort) in the 12 months following index. Patients with ACO generally had the highest medication costs of any cohort (long-acting muscarinic antagonist costs ranged from $227/patient [asthma cohort] to $349/patient [ACO cohort]); they also experienced more respiratory-related hospital visits than patients with asthma or COPD (mean outpatient/inpatient visits per patient post-index: 9.1/1.9 [ACO cohort] vs 5.7/1.4 [asthma cohort] and 6.4/1.7 [COPD cohort]). CONCLUSIONS: Patients with ACO in Taiwan experience a greater disease burden with greater healthcare resource utilisation, and higher costs, than patients with asthma or COPD alone.

The Prognostic Impact of Type 2 Diabetes Mellitus on Early Cervical Cancer in Asia.

BACKGROUND: Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC. PATIENTS AND METHODS: We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I-IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality. RESULTS: A total of 2,946 patients had primary stage I-IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55). CONCLUSION: In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments. IMPLICATIONS FOR PRACTICE: Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during routine follow-up in this population is recommended.

Peri-onset non-steroidal anti-inflammatory drugs use and organ failure in acute pancreatitis: A multicenter retrospective analysis.

BACKGROUND: Organ failure (OF) of acute pancreatitis (AP) significantly contributes to AP-related mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced complications of AP. AIMS: We aimed to investigate whether NSAIDs ameliorates SIRS and OF in patients with AP. METHODS: Eligible patients with AP were retrospectively identified in 4 hospitals between January 2015 and December 2018. Associations between peri-onset NSAIDs use (day -3 to day 3) and OF, persistent OF (POF), and SIRS within the first week were analyzed. Propensity score-matched (PSM) analysis and inverse probability of treatment-weighted (IPTW) analysis were used to estimate risk ratios. RESULTS: Among 1,528 patients with AP (97 [6.3%] with NSAIDs use), 242 (15.8%) developed organ failure, 89 (5.8%) progressed to POF, and 27 (1.8%) died within 3 months. PSM analysis showed no association between peri-onset NSAIDs and OF (risk ratio [RR], 1.00; 95% confidence interval [CI], 0.46 to 2.15) and POF (RR, 0.80; 95% CI, 0.21 to 2.98). IPTW analysis yielded similar results. Patients with and without peri-onset NSAIDs use were comparable with respect to OF, POF, and SIRS across subgroups defined by COX-2 selectivity and dose. CONCLUSION: Peri-onset NSAIDs use was not significantly associated with reduced OF.

The effect of antiarrhythmic medications on the risk of cardiovascular outcomes in patients with atrial fibrillation and coronary artery disease.

BACKGROUND: While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was no comparative study of antiarrhythmic drugs (AADs) on the cardiovascular outcomes in general practice. METHODS: This study included patients with AF and CAD who received their first prescription of amiodarone, class Ic AADs (flecainide, propafenone), dronedarone or sotalol between January 2016 and December 2020. The primary outcome was a composite of hospitalization for heart failure (HHF), stroke, acute myocardial infarction (AMI), and cardiovascular death. We used Cox proportional regression models, including with inverse probability of treatment weighting (IPTW), to estimate the relationship between AADs and cardiovascular outcomes. RESULTS: Among the AF cohort consisting of 8752 patients, 1996 individuals had CAD, including 477 who took dronedarone and 1519 who took other AADs. After a median follow-up of 38 months, 46.3% of patients who took dronedarone and 54.4% of patients who took other AADs experienced cardiovascular events. Compared to dronedarone, the use of other AADs was associated with increased cardiovascular events after adjusting for covariates (hazard ratio [HR] 1.531, 95% confidence interval [CI] 1.112-2.141, p = 0.023) and IPTW (HR 1.491, 95% CI 1.174-1.992, p = 0.012). The secondary analysis showed that amiodarone and class Ic drugs were associated with an increased risk of HHF. The low number of subjects in the sotalol group limits data interpretation. CONCLUSION: For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs. Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly HHF.

Long-Term Visit-to-Visit Glycemic Variability as a Predictor of Major Adverse Limb and Cardiovascular Events in Patients With Diabetes.

Background Peripheral arterial disease (PAD) is a severe complication in patients with type 2 diabetes. Glycemic variability (GV) is associated with increased risks of developing microvascular and macrovascular diseases. However, few studies have focused on the association between GV and PAD. Methods and Results This cohort study used a database maintained by the National Taiwan University Hospital, a tertiary medical center in Taiwan. For each individual, GV parameters were calculated, including fasting glucose coefficient of variability (FGCV) and hemoglobin A1c variability score (HVS). Multivariate Cox regression models were constructed to estimate the relationships between GV parameters and composite scores for major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs). Between 2014 and 2019, a total of 45 436 adult patients with prevalent type 2 diabetes were enrolled for analysis, and GV was assessed during a median follow-up of 64.4 months. The average number of visits and time periods were 13.38 and 157.87 days for the HVS group and 14.27 and 146.59 days for the FGCV group, respectively. The incidence rates for cardiac mortality, PAD, and critical limb ischemia (CLI) were 5.38, 20.11, and 2.41 per 1000 person-years in the FGCV group and 5.35, 20.32, and 2.50 per 1000 person-years in HVS group, respectively. In the Cox regression model with full adjustment, the highest FGCV quartile was associated with significantly increased risks of MALEs (hazard ratio [HR], 1.57 [95% CI, 1.40-1.76]; P<0.001) and MACEs (HR, 1.40 [95% CI, 1.25-1.56]; P<0.001). Similarly, the highest HVS quartile was associated with significantly increased risks of MALEs (HR, 1.44 [95% CI, 1.28-1.62]; P<0.001) and MACEs (HR, 1.28 [95% CI, 1.14-1.43]; P<0.001). The highest FGCV and HVS quartiles were both associated with the development of PAD and CLI (FGCV: PAD [HR, 1.57; P<0.001], CLI [HR, 2.19; P<0.001]; HVS: PAD [HR, 1.44; P<0.001], CLI [HR, 1.67; P=0.003]). The Kaplan-Meier analysis showed significantly higher risks of MALEs and MACEs with increasing GV magnitude (log-rank P<0.001). Conclusions Among individuals with diabetes, increased GV is independently associated with the development of MALEs, including PAD and CLI, and MACEs. The benefit of maintaining stable glycemic levels for improving clinical outcomes warrants further studies.

Survival following surgery with or without adjuvant chemotherapy for stage I-IIIA non-small cell lung cancer: an east asian population-based study.

BACKGROUND: Asian ethnicity is associated with a distinct molecular etiology, treatment response, and survival outcome among patients with non-small cell lung cancer (NSCLC). This study examines the survival impact of platinum-based adjuvant chemotherapy for Asian patients with stage I-IIIA NSCLC. METHODS: This study recruited patients aged ≥18 years with histologically proven stage IA-IIIA NSCLC registered in the Taiwan Cancer Registry database in January 2004 to December 2007. Platinum-containing adjuvant chemotherapy had to be started within 90 days of the primary surgery. Kaplan-Meier survival curves, log-rank tests, and the Cox proportional hazards regression model were used to assess the influence of various risk factors on survival time. RESULTS: This study included 2,231 patients with stage IA-IIIA NSCLC who underwent primary surgery with a clear surgical margin. The percentages of all causes of death were significantly lower for the chemotherapy group for both stage II and stage IIIA patients. Multivariate analysis identified platinum-based adjuvant chemotherapy as an independent prognostic factor for the overall survival outcome of stage II (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.39-0.94; p = .024) and IIIA (HR, 0.71; 95% CI, 0.52-0.96; p = .029) patients. Among these patients, those who received adjuvant chemotherapy had a superior overall survival outcome for both genders, for the subgroup of patients aged ≥70 years, and for those with adenocarcinoma. CONCLUSION: Platinum-based adjuvant chemotherapy should be considered in the treatment plan for Asian patients with resected stage II and stage IIIA NSCLC.

Survival of patients with small cell lung carcinoma in Taiwan.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. The prognosis for SCLC patients remains unsatisfactory despite advances in chemotherapy. In this study, we sought to clarify the prognosis and treatment patterns of patients with SCLC. METHODS: A cohort comprising all patients diagnosed with SCLC between January 2004 and December 2006 was assembled from the Taiwan Cancer Database. Patients were followed up until December 31, 2009, to determine overall survival. Patient survival was estimated using the Kaplan-Meier method, and Cox's proportional hazard model was used to determine the relationship between prognostic factors and median survival time. RESULTS: Among the 1,684 patients diagnosed with SCLC, 1,215 (72%) were diagnosed with extensive-stage disease and 469 (28%) with limited-stage disease. Most of the patients were male (90%). The median survival duration of patients with limited-stage and extensive-stage SCLC was 10.3 months and 5.6 months, respectively. For limited-stage patients, surgery, chemotherapy, and combined chemotherapy and radiotherapy resulted in better survival than best supportive care (HR 0.20, p < 0.001; HR 0.61, p < 0.001, and HR 0.37, p < 0.001, respectively). For extensive-stage patients, male gender was significantly associated with a poor prognosis (HR 1.45, p < 0.001) and chemotherapy was shown to improve overall survival more effectively than best supportive care (HR 0.37, p < 0.001). CONCLUSION: For limited-stage SCLC patients, surgery, chemotherapy, and combined chemotherapy and radiotherapy improved survival compared to best supportive care. Extensive-stage SCLC patients benefited more from chemotherapy treatment than from best supportive care.

Incidence, risk factors and predictors of cardiovascular mortality for aortic stenosis among patients with diabetes mellitus.

AIMS: To find the incidence, risk factors and predictors of cardiovascular (CV) mortality for aortic stenosis (AS) in patients with type 2 diabetes mellitus (T2DM). METHODS: Between 2014 and 2019, 20,979 patients with T2DM who underwent echocardiography were enrolled for analysis. The mean follow-up period was 34 months. Multiple risk factors and outcomes for patients with and without AS were presented. RESULTS: AS was present in 776 (3.70%) patients. Age, female, chronic kidney disease, hyperlipidemia, and peripheral arterial disease statistically increased risk of AS. The CV mortality (adjusted hazard ratio [aHR] = 1.97; 95% confidence interval [CI] 1.336 - 2.906, p < 0.001) and risk of hospitalization for heart failure (HHF) (aHR = 1.73, 95% CI 1.442-2.082, p < 0.001) were significantly increased in patients with AS, without significant differences in acute myocardial infarction and stroke. Severity of AS, body mass index (<27 kg/m2), hypertension, hyperuricemia, left ventricular dysfunction (ejection fraction < 50%), and hematocrit (<38%) were significantly associated with increased CV mortality and HHF. CONCLUSIONS: AS was associated with an increased risk of CV mortality and HHF in patients with T2DM.

Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan.

Importance: The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels. Objective: To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Design, Setting, and Participants: This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019. Exposure: Use of Bcr-AbL TKIs. Main Outcomes and Measures: Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Results: Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex-matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81). Conclusions and Relevance: These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.

Intussusception and Kawasaki disease after rotavirus vaccination in Taiwanese infants.

BACKGROUND: Since 2006, two rotavirus vaccines have been licensed in Taiwan, either as a 2- (RV1) or 3-dose (RV5) schedule administered at ages 2, 4, and 6 months. This study assessed the risk of intussusception and Kawasaki disease (KD) associated with rotavirus vaccines among infants. METHODS: Cases of intussusception and KD in infants aged less than 365 days were identified from the National Health Insurance databases, from 1 January 2007 through 31 December 2014, using the first-ever ICD-9-CM diagnosis codes. Histories of rotavirus vaccination were obtained from the National Immunization Information System. The modified self-controlled case series design included vaccinated cases, and compared incidence rate ratios (IRRs) between the risk period (postvaccination days 1-21 [intussusception] or days 1-28 [KD]) and control period (ages 0-364 days outside the -14 to +21 [intussusception] or +28 [KD] days of vaccination) by each type and dose of vaccine. Conditional Poisson regression models were adjusted for age using age-in-week (7-day) categorization. RESULTS: Overall 2064 intussusception cases and 2079 KD cases were diagnosed in 567,726 recipients (5313 [0.9%] received both RV5 and RV1). An increase in intussusception risk was observed in the 1-7 days (IRR 12.59, 95% confidence interval [CI] 8.07-19.66) and 8-21 days (IRR 1.78, 95% CI 1.00-3.16) post dose 1 of RV1, but not RV5. Risk of KD was higher during the third week post dose 2 of RV5 (IRR 2.33, 95% CI 1.35-4.00), and fourth week post dose 1 of RV1 (IRR 1.98, 95% CI 1.16-3.40). CONCLUSION: Our finding of an increased risk of intussusception associated with RV1 in the first week after dose 1 is consistent with results of previous postlicensure studies. Further research should verify a potentially delayed risk of KD after rotavirus vaccination.

Late outcomes of off-pump versus on-pump coronary bypass in patients with diabetes: A nationwide study from Taiwan.

OBJECTIVES: Although the benefits and risks of on- and off-pump coronary artery bypass have been compared in several clinical trials, large-scale studies regarding long-term outcomes in patients with diabetes are lacking. We compared long-term outcomes after on- and off-pump coronary artery bypass in patients with diabetes. METHODS: We evaluated outcomes in 16,215 patients with diabetes who underwent isolated coronary artery bypass from 2000 to 2011. Clinical data validity was regulated by the single-payer, universal, and nationwide reimbursement systems. Long-term outcomes were compared using propensity score matched analyses. RESULTS: Off-pump surgery was associated with a greater incidence of repeat revascularization (P = .0036) in the long term. Propensity score matching identified 3796 patients in each group. There were no significant differences between on- and off-pump surgery regarding the long-term risks of mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87-1.02, P = .1667), stroke (HR, 0.97; 95% CI, 0.87-1.09, P = .6074), and myocardial infarction (HR, 1.05; 95% CI, 0.91-1.20, P = .5207). Off-pump surgery offered a survival benefit within 30 days (HR on vs off, 1.52, 95% CI, 1.24-1.85, P < .0001). In patients with diabetes and end-stage renal disease, on-pump surgery provided a significant long-term survival benefit (HR on vs off, 0.68, 95% CI, 0.51-0.91). CONCLUSIONS: In patients with diabetes undergoing isolated coronary artery bypass, off-pump surgery provided a 30-day benefit in mortality, but both groups had similar long-term survival. In off-pump surgery, repeat revascularization was a concern in the long term. In patients with diabetes and end-stage renal disease, on-pump surgery has long-term survival benefits.