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Background Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Few studies focused on the relationship between septicemia and MS. Aim To evaluate the potential impact of septicemia on risk for MS. Design Two cohorts of patients with septicemia and without septicemia were followed up for the occurrence of MS. Methods Patients of 482 790 with septicemia was enrolled from the National Health Insurance Research Database between 2001 and 2011 as the study group to match the 1 892 820 individuals, as the control group, by age and gender. Incidence of MS in both groups was calculated. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR) for MS between groups. Results Septicemia patients had a 3.06-fold (95% CI: 2.16-4.32, P

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Background Evidence regarding the association between asthma and endometriosis is limited and inconsistent. The goal of the study was to investigate whether women diagnosed as having asthma were at a greater risk of endometriosis than age-matched unaffected women. Methods We conducted a nationwide population-based retrospective study by using data retrieved from the Taiwan National Health Insurance Research Database during the period of 2000–2005 with follow-up through 2013. The current analysis included 7337 women aged 12–50 years with newly diagnosed asthma and using asthma-related medications and 29,348 age-matched women without asthma. A Cox proportional hazards regression model was used to estimate the risks of endometriosis in women with asthma as compared with those without asthma. Results The overall risk of endometriosis in the asthma group was 1.50-fold higher (95% confidence interval = 1.33–1.70) than that in the nonasthma group. A stratified analysis by age further revealed that patients with asthma were associated with a higher risk of endometriosis in age groups of 21–50 years. Conclusion Compared with women without asthma, women with asthma of reproductive age are at a higher risk of endometriosis. Additional studies are warranted to elucidate the mechanism(s) underlying the association between asthma and a higher risk of endometriosis.

// Chung-Hsing Chou 1, 2 , Jiunn-Tay Lee 1, 2 , Chun-Chieh Lin 1 , Yueh-Feng Sung 1 , Che-Chen Lin 3 , Chih-Hsin Muo 3 , Fu-Chi Yang 1 , Chi-Pang Wen 4 , I-Kuan Wang 5, 6, 7 , Chia-Hung Kao 5, 8 , Chung Y. Hsu 5 and Chun-Hung Tseng 9 1 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China 2 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China 3 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, Republic of China 4 Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan, Republic of China 5 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, Republic of China 6 Department of Internal Medicine, College of Medicine, China Medical University, Taichung, Taiwan, Republic of China 7 Division of Kidney Disease, China Medical University Hospital, Taichung, Taiwan, Republic of China 8 Department of Nuclear Medicine, PET Center, China Medical University Hospital, Taichung, Taiwan, Republic of China 9 Department of Neurology, China Medical University Hospital, Taichung, Taiwan, Republic of China Correspondence to: Jiunn-Tay Lee, email: jiunntay@gmail.com Keywords: septicemia, infection, dementia, Alzheimer’s disease, non-Alzheimer dementias Received: May 17, 2017 Accepted: August 04, 2017 Published: September 15, 2017 ABSTRACT Background: Systemic infection has been linked to cognitive impairment. We hypothesized that patients with septicemia are predisposed to increased risks for developing dementia in a long-term setting. Methods: This observational, retrospective, longitudinal, nation-wide population-based study was conducted using the data deduced from Longitudinal Health Insurance Database (LHID) in Taiwan. All patients with septicemia hospitalized for the first time from 2001 to 2011 without prior dementia were included. The development of Alzheimer’s disease (AD) or non-Alzheimer dementias (NAD) in relation to the development of septicemia for each patient was recorded. An age- and sex-matched cohort without septicemia and without prior dementia served as the control. Septicemia, dementia, and other confounding factors were defined according to International Classification of Diseases Clinical Modification Codes. Cox proportional-hazards regressions were utilized to analyze adjusted hazard ratios. Results: Patients with septicemia had a higher risk for developing dementia based on hazard ratios (HRs) ( p 0.05). Furthermore, higher severity of septicemia was associated with increased risk of developing dementia. Conclusions: Our findings suggest that septicemia is associated with an increased risk in developing NAD but not AD. A likely causal role of septicemia in increasing the risk of NAD is suggested, according to the findings that patients with higher severity of septicemia carried greater risk of sustaining dementia.

The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance. A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%. A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Inflammatory processes have a detrimental role in the pathophysiology of ischemic stroke. However, little is known about the endogenous anti-inflammatory mechanisms in ischemic brain. Here, we identify CXCL14 as a critical mediator of these mechanisms. CXCL14 levels were upregulated in the ischemic brains of humans and rodents. Moreover, hypoxia inducible factor-1α (HIF-1α) drives hypoxia- or cerebral ischemia (CI)-dependent CXCL14 expression via directly binding to the CXCL14 promoter. Depletion of CXCL14 inhibited the accumulation of immature dendritic cells (iDC) or regulatory T cells (Treg) and increased the infarct volume, whereas the supplementation of CXCL14 had the opposite effects. CXCL14 promoted the adhesion, migration, and homing of circulating CD11c+ iDC to the ischemic tissue via the upregulation of the cellular prion protein (PrPC), PECAM-1, and MMPs. The accumulation of Treg in ischemic areas of the brain was mediated through a cooperative effect of CXCL14 and iDC-secreted IL-2-induced Treg differentiation. Interestingly, CXCL14 largely promoted IL-2-induced Treg differentiation. These findings indicate that CXCL14 is a critical immunomodulator involved in the stroke-induced inflammatory reaction. Passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation.

Until now, the surface markers of multipotent mesenchymal stem cells (MSCs) had not been fully identified. Here, we found that the IGF1 receptor (IGF1R), regarded as a pluripotent marker of embryonic stem cells (ESCs), was also expressed in human dental pulp derived-mesenchymal stem cells (hDSCs), which displayed a potential for both self-renewal and multipotency. hDSC-secreted IGF1 interacted with IGF1R through an autocrine signaling pathway to maintain this self-renewal and proliferation potential. Stereotaxic implantation of immunosorted IGF1R+ hDSCs in rats with neonatal hypoxia-ischemia (NHI) promoted neuroplasticity, improving the neurological outcome by increasing expression of the anti-apoptotic protein Bcl-2, which enhanced both neurogenesis and angiogenesis. In addition, treatment with IGF1R+ hDSCs significantly modulated neurite regeneration and anti-inflammation in vivo in NHI rats and in vitro in primary cortical cultures under oxygen/glucose deprivation. Autocrine regulatory expression of IGF1R contributed to maintaining the self-renewal capacity of hDSCs. Furthermore, implantation of IGF1R+ hDSCs increased neuroplasticity with neurite regeneration and immunomodulation in and the NHI rat model.

Background: Air pollutants cause endocrine disorders and hormone disruption. The relationship between air pollutants and polycystic ovary syndrome (PCOS) must be carefully investigated using a nationwide cohort. Methods: Data were extracted from two nationwide databases, namely Longitudinal Health Insurance Database and Taiwan Air Quality Monitoring Database, and analyzed. The study considered a range of data that began on 1 January 2000 and ended on 31 December 2013. Women diagnosed with PCOS were excluded. From the residential data, the study assessed the daily concentrations of sulfur dioxide (SO2), nitrogen oxides (NOx), nitrogen monoxide (NO), nitrogen dioxide (NO2), and PM2.5 the women were exposed to. A Cox proportional hazard regression model was applied to assess PCOS risk. Results: In total, 91,803 women were enrolled in this study, of those women, 2072 developed PCOS after 12 years of follow-up. The mean daily concentrations of SO2, NOx, NO, NO2, and PM2.5 women were exposed to were 4.25 (&plusmn, 1.44) ppb, 20.41 (&plusmn, 6.65) ppb, 9.25 (&plusmn, 4.36) ppb, 20.99 (&plusmn, 3.33) ppb, and 30.85 (&plusmn, 6.16) &mu, g/m3, respectively. Compared with the first-quartile levels of exposure, the fourth-quartile levels of exposure to SO2, NOx, NO, NO2, and PM2.5 increased PCOS risk by 10.31 times (95% CI = 8.35&ndash, 12.7), 3.37 times (95% CI = 2.86&ndash, 3.96), 4.18 times (95% CI = 3.57&ndash, 4.89), 7.46 times (95% CI = 6.38&ndash, 8.71), and 3.56 times (95% CI = 3.05&ndash, 4.15), respectively. Conclusion: Women exposed to a high concentrations of air pollutants, namely SO2, NO, NO2, NOx, and PM2.5, had a high PCOS risk.

Objective: Early reports indicate that individuals with type 2 diabetes mellitus (T2DM) may have a greater incidence of breast malignancy than patients without T2DM. The aim of this study was to investigate the effectiveness of three different models for predicting risk of breast cancer in patients with T2DM of different characteristics. Study design and methodology: From 2000 to 2012, data on 636,111 newly diagnosed female T2DM patients were available in the Taiwan&rsquo, s National Health Insurance Research Database. By applying their data, a risk prediction model of breast cancer in patients with T2DM was created. We also collected data on potential predictors of breast cancer so that adjustments for their effect could be made in the analysis. Synthetic Minority Oversampling Technology (SMOTE) was utilized to increase data for small population samples. Each datum was randomly assigned based on a ratio of about 39:1 into the training and test sets. Logistic Regression (LR), Artificial Neural Network (ANN) and Random Forest (RF) models were determined using recall, accuracy, F1 score and area under the receiver operating characteristic curve (AUC). Results: The AUC of the LR (0.834), ANN (0.865), and RF (0.959) models were found. The largest AUC among the three models was seen in the RF model. Conclusions: Although the LR, ANN, and RF models all showed high accuracy predicting the risk of breast cancer in Taiwanese with T2DM, the RF model performed best.

Background Aspirin lowered some cancer occurrence rate, through the inhibition of the cyclooxygenase enzyme. The association of aspirin-use and hepatocellular carcinoma (HCC) occurrence rate in hepatitis B virus (HBV) carriers is well known. However, the association in hepatitis C virus (HCV) carriers is not known. Our purpose is comparing the HCC occurrence rate in HCV carriers with or without Aspirin treatment. Methods In this retrospective cohort study, the participants were ones newly-diagnosed with HCV from 2000 to 2012 in Taiwan. These HCV carriers with aspirin treatment were defined as the control group, whereas those without aspirin were defined as a compared cohort. We used a 1:1 propensity score matching by age, sex, comorbidities, drugs, diagnosis year and index year with covariate assessment. Results Our study sample consisted of 2980 aspirin-treated HCV carriers and 7771 non-aspirin-treated HCV carriers. After propensity score matching, each cohort consisted of 1911 HCV carriers. The adjusted hazard ratio (aHR) of HCC incidence in aspirin users (aHR=0.56, 95% CI=0.43-0.72, p < 0.001 ) was significantly lower than that in non-aspirin users. The Kaplan-Meier curves show that among the HCV carriers, aspirin users had a lower cumulative incidence rate of HCC in the first 10-year aspirin treatment course ( p < 0.0001 ). Conclusions The HCC incidence rate was lower in the aspirin users than non- aspirin users among HCV carriers, supporting the aspirin effect may be acting through inhibition of the cyclooxygenase enzyme pathway. Moreover, the patients got HCC protection by aspirin within 1-year treatment course and had best HCC prevention during 1- to 2-year aspirin treatment course. We encourage aspirin treatment to prevent HCC in HCV carriers.

Background Identifying colorectal cancer associated risks is important for conducting a program for the survey and prevention of colorectal cancer. Aim To investigate the association between use of insulin or metformin with colorectal cancer (CRC) in type 2 diabetes (T2DM). Design Population-based cohort study. Methods Through analysis of National Health Insurance (NHI) database between 1998 and 2010 in Taiwan, we identified 66 324 T2DM patients aged ≥ 20 years and selected subjects without diabetes by 1: 1 randomly matching with the study cohort based on age, sex and index date. We followed up the participants until 31 December 2011 or when they withdrew from the NHI program. Results Compared with non-diabetic subjects, the T2DM patients exhibited an increased risk of CRC [adjusted HR (aHR) = 1.56, 95% confidence interval (CI) = 1.39–1.75], after adjustment for age, sex, urbanization level, comorbidities and examinations of colonoscopy, sigmoidoscopy, or stool occult blood test. Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58–0–2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54–0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations. Compared with the non-insulin cohort, the risk of CRC tended to increase with the incremental dosage of insulin exposure. Conclusion Our population-based cohort study demonstrated an association between T2DM and CRC. Among the T2DM patients, insulin use was associated with an increased risk of CRC and metformin use was associated with a decreased risk of CRC. Inability to obtain information on several potential confounding factors, such as lifestyle and dietary habits, is the major limitation of the study.

Background: Alzheimer’s disease, the most common cause of dementia among the elderly, is a progressive and irreversible neurodegenerative disease. Exposure to air pollutants is known to have adverse effects on human health, however, little is known about hydrocarbons in the air that can trigger a dementia event. Objective: We aimed to investigate whether long-term exposure to airborne hydrocarbons increases the risk of developing dementia. Method: The present cohort study included 178,085 people aged 50 years and older in Taiwan. Cox proportional hazards regression analysis was used to fit the multiple pollutant models for two targeted pollutants, including total hydrocarbons and non-methane hydrocarbons, and estimated the risk of dementia. Results: Before controlling for multiple pollutants, hazard ratios with 95% confidence intervals for the overall population were 7.63 (7.28-7.99, p Conclusion: Our findings suggest that total hydrocarbons and non-methane hydrocarbons may be contributing to dementia development.

BACKGROUND AND PURPOSE Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. METHODS From the Taiwan Stroke Registry data, 39 174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re-stroke incidence and 1-year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60-89 and

Background: Prognosis of the aged population requiring maintenance dialysis has been reportedly poor. We aimed to develop prediction models for one-year cost and one-year mortality in aged individuals requiring dialysis to assist decision-making for deciding whether aged people should receive dialysis or not. Methods: We used data from the National Health Insurance Research Database (NHIRD). We identified patients first enrolled in the NHIRD from 2000&ndash, 2011 for end-stage renal disease (ESRD) who underwent regular dialysis. A total of 48,153 Patients with ESRD aged &ge, 65 years with complete age and sex information were included in the ESRD cohort. The total medical cost per patient (measured in US dollars) within one year after ESRD diagnosis was our study&rsquo, s main outcome variable. We were also concerned with mortality as another outcome. In this study, we compared the performance of the random forest prediction model and of the artificial neural network prediction model for predicting patient cost and mortality. Results: In the cost regression model, the random forest model outperforms the artificial neural network according to the mean squared error and mean absolute error. In the mortality classification model, the receiver operating characteristic (ROC) curves of both models were significantly better than the null hypothesis area of 0.5, and random forest model outperformed the artificial neural network. Random forest model outperforms the artificial neural network models achieved similar performance in the test set across all data. Conclusions: Applying artificial intelligence modeling could help to provide reliable information about one-year outcomes following dialysis in the aged and super-aged populations, those with cancer, alcohol-related disease, stroke, chronic obstructive pulmonary disease (COPD), previous hip fracture, osteoporosis, dementia, and previous respiratory failure had higher medical costs and a high mortality rate.

There have not been any longitudinal studies reported that chronic low back pain (CLBP) patients are at risk for stroke. Thus, in this study, we explored the association between CLBP and strokes.Data (2000∼2010) from the Taiwan National Health Insurance database were analyzed. We matched 10,308 CLBP patients with 20,616 propensity score-matched non-low back pain (NLBP) patients according to age, gender, index year and comorbidities. Covariates of age, gender, comorbidities, and usage of non-steroidal anti-inflammatory drugs (NSAIDs) were adjusted and analyzed.The mean follow-up duration was 8 years. CLBP patients had higher risks of all stroke, hemorrhagic stroke, and ischemic stroke. The adjusted hazard ratios (aHRs) were 2.35 (95 % confidence interval (CI): 2.14-2.57, p0.001), 1.55 (95 % CI: 1.16-2.06, p = 0.003), and 2.41 (95 % CI: 2.18-2.66, p0.001), respectively. After adjusting and analyzing the NSAIDs used for the varied duration in the CLBP patients, we did not observe any impacts of such NSAIDs used on the association of CLBP with strokes. The association between CLBP and ischemic stroke was most prominent in the patients less than 50 years old with aHR: 3.56 (CI: 2.74∼4.61, p0.001).CLBP was associated with increased risk of strokes, especially ischemic stroke, and the association was most prominent in patients less than 50 years old. Further large prospective studies on detailed lifestyle-related factors and qualitative pain assessment are needed to clarify the causal relationship between CLBP and stroke.

The management of perforated peptic ulcer (PPU) has shifted from vagotomy/drainage to simple closure, followed by postoperative proton pump inhibitors (PPIs) and Helicobacter pylori (HP) eradication. Few studies have focused on the long-term impacts of this trend shift. We hypothesize that simple closure with PPIs is sufficient and does not carry an elevated rate of repeated surgery in non-HP-infected PPU patients. Hospitalized PPU patients who underwent simple closure or truncal vagotomy/pyloroplasty (TVP) in the National Health Insurance Research Database (NHIRD) from 2000 to 2008 were collected. The index date was defined as the date of ulcer admission. Patients who underwent other ulcer surgeries (e.g., gastrectomy, highly or selective vagotomy), who had a history of HP infection, or who were 100 years old were excluded. Additionally, the distributions of postoperative nonsteroidal anti-inflammatory drug (NSAID) and PPI use were calculated using the Longitudinal Health Insurance Database (LHID). After exclusion, a total of 66,413 patients were enrolled. There were 7232 (10.9%) patients who underwent TVP and 59,181 (89.1%) patients who underwent simple closure. The incidences of repeated ulcer-associated surgery were 5.10 and 23.05 versus 5.11 and 15.77 per 1000 person-years in the TVP cohort vs. the simple closure cohort before and after propensity score matching, respectively. When adjusted for age, sex, comorbidity, and Charlson comorbidity index score, the TVP cohort had a 68% (HR) and 66% (sHR) decreased risk compared with the simple closure cohort before propensity score matching, with a 67% decreased risk after propensity score matching in Cox proportional subdistribution hazard analysis and a 66% decreased risk in Fine-Gray proportional subdistribution hazard analysis. The LHID analysis showed a lower rate of postoperative NSAID use and a higher rate of postoperative PPI use in simple closure patients. Our findings suggest that in the Asian population, simple closure increases the risk of repeated ulcer-associated surgery in non-HP-infected PPU patients compared with TVP patients. However, further studies are warranted.

Aim Under-management of diabetes can lead to a hyperglycaemic episode (HCE), which could be further strengthened in the presence of schizophrenia and the use of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with schizophrenia. Additionally, the duration of antipsychotic use on the risk of HCE is examined. Materials and methods A total of 13858 diabetic patients with schizophrenia and 55407 controls (without schizophrenia) matched by gender, age, index year, and Charlson Comorbidity Index score were included between 1999 and 2010 and followed to the end of 2013 using from the Taiwan National Health Insurance Research Database. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (95% CI) of the HCE incidence rate between the two groups studied. Results Diabetic patients with schizophrenia were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic use (4.73 versus 2.43 per 1,000 person-years, HR: 2.16, 95% CI: 1.85-2.51). Also, in diabetic patients with schizophrenia, a longer duration of antipsychotic use was associated with a lower risk of HCE after adjustment for the above-mentioned variables, suggesting a protective effect of antipsychotics against HCE during prolonged use. Conclusion This study highlights the need to pay more attention to the risk of HCE in diabetic patients with schizophrenia and the importance of proper use of antipsychotics may reduce the risk of HCE.

Background The effects of statins on anxiety and depression in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) have not been reported. This population-based study investigated these effects. Methods Taiwan's National Health Insurance Research Database between 2000 and 2010. We enrolled two ACOS cohorts, one of statin users ( n = 1252) and one of nonstatin users matched by age, sex, and index date ( n = 7887). The cumulative incidence of anxiety and depression was analyzed using time-dependent Cox proportional regression analysis. Results After adjustment for multiple confounding factors, including age, sex, comorbidities, and medications—statins, inhaled corticosteroids (ICSs), and oral steroids (OSs)—the ACOS cohort with statin use had significantly lower risks of anxiety and depression (anxiety: adjusted hazard ratio [aHR] = 0.34, 95% confidence interval [CI] = 0.28–0.42; depression: aHR = 0.36, 95% CI = 0.25–0.53). The aHRs (95% CIs) for statin use with ICSs or OSs were 0.32 (0.13–0.78) and 0.37 (0.24–0.57), respectively. Conclusion The ACOS cohort with statin use had lower risks of anxiety and depression, regardless of age, sex, commodities, or ICSs and OSs. The incidences of anxiety and depression were relatively low among users of statins with ICSs or OSs in the ACOS cohort.

Objective: Smokers with stroke were reported to have a better survival than nonsmokers, and this phenomenon was labeled as “smoking paradox”. This study is to assess its validity from a national stroke registry data. Methods: A total of 88,925 cases of stroke registered in the nationwide stroke registry system of Taiwan between 2006 and 2016, with 4,169 deaths, were analyzed. Age-specific mortality rate for current, ex- and non-smokers were calculated. NIHSS score (National Institutes of Health Stroke Scale) was measured at 3 months and 6 months Cox model was used to compare complications, mortality and outcomes between smoker and non-smoker ground. Results: Smokers constituted more than half of the men (55%) but only 5% of the women. The median age for current smokers was 60.2, for nonsmokers, 71.6, and for ex-smokers, 72.5. Smokers, with nearly 12 years younger than nonsmokers, had smaller mortality rate at younger age groups with fewer deaths, but much larger mortality after age 60, and doubled the mortality rate at the largest group after age 70. Smokers, who quit early, had similar outcome as nonsmokers. When age was controlled, current smokers had worse functional outcome (NIHSS) even at 3 months (adjusted OR, 1.08; 95% CI, 1.02-1.14). Conclusion: Smokers, but not ex-smokers, developed stroke 12 years younger than nonsmokers, an ominous sign for smokers. They had higher age-specific mortality rate and poorer outcome than nonsmokers. Quitting early nearly reversed the harms. Smoking paradox does not exist.

Background Suboptimal management of diabetes can lead to a hyperglycemic crisis episode (HCE), which could be further enhanced in the presence of bipolar disorder (BD) and the prescription of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with BD. Additionally, the duration of antipsychotic prescription on HCE risk is examined. Methods Using the Taiwan National Health Insurance Research Database, 6099 diabetic patients with BD and 24,378 diabetic patients without BD matched by gender, age, index year, and Charlson Comorbidity Index score were enrolled between 1999 and 2010 and followed to the end of 2013. Participants who developed HCE during the follow-up period were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between two groups studied. Results Diabetic patients with BD were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic prescription (3.84 versus 2.71 per 1,000 person-years, HR: 1.41, 95% CI: 1.15–1.71). Also, this study revealed that male gender, more comorbidities, and a longer duration of antipsychotic prescription were potential risk factors for developing HCE. Limitations This study only deals with data on the duration of antipsychotic prescription, without showing the effects of different antipsychotics on HCE risk. Conclusion This study highlights the need to pay attention to the risk of HCE in diabetic patients with BD and the importance of careful prescription of antipsychotics to reduce the HCE incident.

Aims This study investigated whether patients with alcoholic cirrhosis have a high risk of hemorrhagic stroke. Methods In this study, 17,094 patients diagnosed with cirrhosis between 2000 and 2010 were identified using the Taiwan National Health Insurance claims data. Identified patients were randomly selected and propensity score matched with individuals without cirrhosis according to age, sex, comorbidities and index year. Results The overall incidence rate of stroke was 4.41 and 12.1 per 1000 person-years in the chronic liver disease and cirrhosis (CLDC) with hepatitis B virus (HBV) or hepatitis C virus (HCV) cohort and the alcoholic CLDC cohort, respectively. The alcoholic CLDC cohort exhibited a 4.53-fold higher risk of hemorrhagic stroke (adjusted subhazard ratio [aSHR] = 4.53, 95% confidence interval [CI] = 3.05-6.71) than did the non-CLDC cohort, and the CLDC with HBV or HCV cohort exhibited a 1.40-fold higher risk of hemorrhagic stroke (aSHR = 1.40, 95% CI = 1.10-1.78) than did the non-CLDC cohort. The alcoholic CLDC cohort and the CLDC with HBV or HCV cohort showed an aSHR of 1.80 (95% CI = 1.36-2.40) and 0.95 (95% CI = 0.83-1.07) for ischemic stroke, respectively, compared with the non-CLDC cohort. Conclusion Alcoholic patients with CLDC had a higher risk of hemorrhagic stroke compared with non-alcoholic patients with CLDC and patients without CLDC.

Background: Air pollution has been associated with autoimmune diseases. Nephrotic syndrome is a clinical manifestation of immune-mediated glomerulopathy. However, the association between nephrotic syndrome and air pollution constituents remains unknown. We conducted this nationwide retrospective study to investigate the association between PM2.5 and nephrotic syndrome. Methods: We used the Longitudinal Health Insurance Database (LHID) and the Taiwan Air Quality-Monitoring Database (TAQMD). We combined and stratified the LHID and the TAQMD data by residential areas of insurants linked to nearby air quality-monitoring stations. Air pollutant concentrations were grouped into four levels based on quartile. Univariable and multivariable Cox proportional hazard regression models were applied. Findings: Relative to Q1-level SO2, subjects exposed to the Q4 level were associated with a 2.00-fold higher risk of nephrotic syndrome (adjusted HR = 2.00, 95% CI = 1.66&ndash, 2.41). In NOx, relative to Q1 NOx concentrations, the adjusted HRs of nephrotic syndrome risk were 1.53 (95% CI = 1.23&ndash, 1.91), 1.30 (95% CI = 1.03&ndash, 1.65), and 2.08 (95% CI = 1.69&ndash, 2.56) for Q2, Q3, and Q4 levels, respectively. The results revealed an increasing trend for nephrotic syndrome risk correlating with increasing levels of NO, NO2, and PM2.5 concentrations. Interpretation: High concentrations of PM2.5, NO, NO2, and SO2 are associated with increased risk of nephrotic syndrome.

Importance Intravenous alteplase reduces disability after ischemic stroke in patients 4.5 to 9 hours after onset and with wake-up onset stroke selected using perfusion imaging mismatch. However, whether the benefit is consistent across the 4.5- to 6-hours, 6- to 9-hours, and wake-up stroke epochs is uncertain. Objective To examine the association of reperfusion with reduced disability, including by onset-to-randomization time strata in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) randomized clinical trials. Design, Setting, and Participants Individual patient meta-analysis of randomized clinical trials performed from August 2001 to June 2018 with 3-month follow-up. Patients had acute ischemic stroke with 4.5-to 9-hours poststroke onset or with wake-up stroke were randomized to alteplase or placebo after perfusion mismatch imaging. Analysis began July 2019 and ended May 2020. Exposures Reperfusion was defined as more than 90% reduction in time to maximum of more than 6 seconds’ lesion volume at 24- to 72-hour follow-up. Main Outcomes and Measures Ordinal logistic regression adjusted for baseline age and National Institutes of Health Stroke Scale score was used to analyze functional improvement in day 90 modified Rankin Scale score overall, including a reperfusion × time-to-randomization multiplicative interaction term, and in the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata. Symptomatic hemorrhage was defined as large parenchymal hematoma with a National Institutes of Health Stroke Scale score increase of 4 points or more. Results Reperfusion was assessable in 270 of 295 patients (92%), 68 of 133 (51%) in the alteplase group, and 38 of 137 (28%) in the placebo reperfused group (P

Aim: The ability to predict outcomes can help clinicians to better triage and treat stroke patients. We aimed to build prediction models using clinical data at admission and discharge to assess predictors highly relevant to stroke outcomes. Methods: A total of 37,094 patients from the Taiwan Stroke Registry (TSR) were enrolled to ascertain clinical variables and predict their mRS outcomes at 90 days. The performances (i.e., the area under the curves (AUCs)) of these independent predictors identified by logistic regression (LR) based on clinical variables were compared. Results: Several outcome prediction models based on different patient subgroups were evaluated, and their AUCs based on all clinical variables at admission and discharge were 0.85-0.88 and 0.92-0.96, respectively. After feature selections, the input features decreased from 140 to 2-18 (including age of onset and NIHSS at admission) and from 262 to 2-8 (including NIHSS at discharge and mRS at discharge) at admission and discharge, respectively. With only a few selected key clinical features, our models can provide better performance than those previously reported in the literature. Conclusion: This study proposed high performance prognostics outcome prediction models derived from a population-based nationwide stroke registry even with reduced LR-selected clinical features. These key clinical features can help physicians to better focus on stroke patients to triage for best outcome in acute settings.

Objective: Rheumatoid arthritis (RA) has been associated with inhaled pollutants in several studies, and it is a disease of chronic inflammation. The association between air pollution and the risk of RA remains unclear. Therefore, we conducted this nationwide, retrospective, sex-stratification study to evaluate this association. Methods: We collected data from the Longitudinal Health Insurance Database (LHID), maintained by the Taiwan Bureau of National Health Insurance, and the Taiwan Air Quality-Monitoring Database (TAQMD), released by the Taiwan Environmental Protection Agency. The TAQMD provides the daily concentrations of particulate matter with the aerodynamic diameter

Background Chronic idiopathic urticaria (CIU) is defined as urticaria that is not caused by external triggers. The pathogenesis of CIU remains unknown. A previous study investigated whether hypertension is associated with extended duration of CIU. Objective To investigate the possible association between CIU and hypertension. Methods We performed a population-based retrospective cohort study of 2,460 patients with CIU and 9,840 age-, sex-, and index year–matched comparison patients, using the National Health Insurance of Taiwan database. The median follow-up periods were 7.13 years for the CIU cohort and 7.20 years for the non-CIU cohort. The distributions by sex and age were similar for both cohorts. Results The CIU cohort had a 1.37-fold (95% CI, 1.22–1.53) greater risk of developing subsequent hypertension than the non-CIU cohort after adjusting for sex, age, comorbidities, and nonsedating antihistamine use. Conclusion This nationwide retrospective cohort study found that CIU is associated with a higher future risk of hypertension after adjusting for sex, age, comorbidities, and nonsedating antihistamine use. The detailed pathophysiologic mechanisms require further clarification in prospective studies.

Bipolar disorder (BD) is a systemic inflammatory disease, and disrupted bone metabolism due to the inflammatory process can cause fracture. Despite evidence of an association between lower bone mineral density and an increased risk of fracture among patients with depression, schizophrenia, and anorexia nervosa, whether BD is a risk factor for subsequent fracture is unknown. To determine the association between BD and fracture and to examine the risk factors for fracture among patients with BD. In this study, we enrolled patients diagnosed with BD from the Taiwan National Health Insurance Research Database. Patients newly diagnosed with BD (ICD-9-CM 296) from 2001 to 2008 were included in the BD cohort, and the date of the initial diagnosis of BD was used as the index date. The comparison cohort, comprising participants without BD, was frequency matched to the BD cohort by age, sex, and index year, and the occurrence of fracture was evaluated in both cohorts. The BD and comparison cohorts were comprised of 47,271 patients with BD and 1,89,084 frequency-matched participants without BD, respectively. The incidence of fracture was higher among patients with BD than among the controls. Cox models showed that BD was an independent risk factor for fracture irrespective of comorbidities [hazard ratio (HR) = 1.79, 95 % confidence interval (CI) = 1.73–1.84, p

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Aβ release via IκB kinase 2 (IKK2). Furthermore, L5+Aβ synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IκBα, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor-κB (NF-κB). Injecting L5+Aβ shortened tail-bleeding time by 50% (n = 12; P < .05 vs L1-injected mice), which was prevented by the IKK2 inhibitor. Our findings suggest that, through LOX-1, atherogenic L5 potentiates Aβ-mediated platelet activation, platelet aggregation, and hemostasis via IKK2/NF-κB signaling. L5 elevation may be a risk factor for cerebral atherothrombosis, and downregulating LOX-1 and inhibiting IKK2 may be novel antithrombotic strategies.

Herbs have been regarded as aphrodisiacs in treating impotence for many centuries despite little true scientific evidence. Our latest refined penile venous stripping (PVS) technique is effective in treating impotence, although this procedure remains controversial. A synergic effect of PVS and oral herbs was confirmed in our practice but lacked rigorous scientific proof. The objective of this report was to review our experience with this combination. From August 2010 to May 2014, 263 males underwent PVS. Among these, 67 unsatisfied men chose additional salvage therapy and were randomly assigned to oral herbs (n = 35) or placebo treatment (n = 32) which replaced herb eventually. All were evaluated with the international index of erectile function (IIEF-5) scoring and our dual pharmaco-cavernosography. The pre-op IIEF-5 score for the herb group was 9.7 ± 3.7, post-operative 13.9 ± 3.3 and post-herb 19.6 ± 3.4, while the control group scores were as follows: pre-op 9.3 ± 4.1, post-op 14.5 ± 3.6, post-placebo 15.1 ± 3.5 and post-herb 19.9 ± 3.2. Although there was no significant difference between the two groups pre-operatively, post-operatively and post-herb, a statistically significant difference was found post-salvage therapy (19.6 ± 3.4 versus 15.1 ± 3.6, P

Importance The safety and efficacy of intensive systolic blood pressure reduction in patients with intracerebral hemorrhage who present with systolic blood pressure greater than 220 mm Hg appears to be unknown. Objective To evaluate the differential outcomes of intensive (goal, 110-139 mm Hg) vs standard (goal, 140-179 mm Hg) systolic blood pressure reduction in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more vs less than 220 mm Hg. Design, Setting, and Participants This post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage-II trial was performed in November 2019 on data from the multicenter randomized clinical trial, which was conducted between May 2011 to September 2015. Patients with intracerebral hemorrhage and initial systolic blood pressure of 180 mm Hg or more, randomized within 4.5 hours after symptom onset, were included. Interventions Intravenous nicardipine infusion titrated to goals. Main Outcomes and Measures Neurological deterioration and hematoma expansion within 24 hours and death or severe disability at 90 days, plus kidney adverse events and serious adverse events until day 7 or hospital discharge. Results A total of 8532 patients were screened, and 999 individuals (mean [SD] age, 62.0 [13.1] years; 620 men [62.0%]) underwent randomization and had an initial SBP value. Among 228 participants with initial systolic blood pressures of 220 mm Hg or more, the rate of neurological deterioration within 24 hours was higher in those who underwent intensive (vs standard) systolic blood pressure reduction (15.5% vs 6.8%; relative risk, 2.28 [95% CI, 1.03-5.07];P = .04). The rate of death and severe disability (39.0% vs 38.4%; relative risk, 1.02 [95% CI, 0.73-1.78];P = .92) was not significantly different between the 2 groups. There was a significantly higher rate of kidney adverse events in participants randomized to intensive systolic blood pressure reduction (13.6% vs 4.2%; relative risk, 3.22 [95% CI, 1.21-8.56];P = .01), but no difference was observed in the rate of kidney serious adverse events. Conclusions and Relevance The higher rate of neurological deterioration within 24 hours associated with intensive treatment in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more, without any benefit in reducing hematoma expansion at 24 hours or death or severe disability at 90 days, warrants caution against generalization of recommendations for intensive systolic blood pressure reduction.

Both ischemic heart disease (IHD) and stroke are major causes of death worldwide. We investigated the effects of combined Traditional Chinese medicine (TCM) and western medicine (WM) on stroke risk in IHD patients.Taiwanese patients with IHD were enrolled in the TCM study during their outpatient visit. Stroke events after TCM or non-TCM treatment were examined. Chi-square tests and Student t-tests were used to examine differences between patients using and not using TCM. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs). Sex, age, and comorbidities were included in a multivariable Cox model to estimate the adjusted HR (aHR). The survival probability and the probability free of stroke were calculated by the Kaplan-Meier method.There were 733 IHD patients using TCM and 733 using non-TCM treatment, with the same proportion of sex and age within each cohort. Using single Chinese herb such as Dan Shen, San Qi, or Chuan Xiong would have lower stroke events and lower aHR than non-TCM in IHD patients. There was 0.3-fold lower stroke risk in IHD patients with combination TCM and non-TCM treatment (95% CI = 0.11-0.84, P = .02). Moreover, the survival rate was higher (P < .001) and the incidence of hemorrhagic stroke was significantly lower (P = .04) in IHD patients with TCM treatment.IHD patients using combined TCM and WM had a higher survival rate and lower risk of new onset stroke, especially hemorrhagic stroke than those who did not use TCM treatment.

[This corrects the article DOI: 10.1371/journal.pone.0221750.].

BACKGROUND: To evaluate the relation of head and neck cancer to chronic pancreatitis by analyzing Taiwan’s National Health Insurance Research Database. METHODS: We identified 11,237 patients with chronic pancreatitis as the case cohort, which was propensity score matched with another 11,237 patients without chronic pancreatitis by sex, age, index year, and comorbidities. We followed both cohorts between January 1, 2000, and December 31, 2011 to measure the incidence of head and neck cancer. RESULTS: Compared with patients without chronic pancreatitis, those with chronic pancreatitis were associated a greater risk of head and neck cancer [adjusted HR (aHR) =1.31, 95% confidence interval (CI): 1.07–1.60] and had a higher incidence of head and neck cancer (log-rank test, P

Aims This study aims to investigate the risk of hyperglycemic crisis episode (HCE) in diabetic patients with depression and to examine the relationship between the duration of antidepressants use and the risk of HCE. Methods In all, 26,746 diabetic patients with depression and 106,853 controls (without depression) matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were included between 1999 and 2010, then followed until the end of 2013. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between the two groups studied. Results Diabetic patients with depression had a significantly increased risk of HCE compared to unaffected controls after adjusted for gender, age, CCI score, and duration of antidepressants use (2.87 versus 2.50 per 1000 person-years, HR: 1.78, 95% CI: 1.56–2.03). Also, long-term use of antidepressants in diabetic patients with depression showed a significantly reduced risk of HCE compared to non-users after adjusting for the above-mentioned variables (HR: 0.44, 95% CI: 0.35–0.55). Conclusions This study shows diabetic patients with depression have an increased risk of HCE, and the use of antidepressants may reduce its risk.

Objective: To assess the association of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) with the subsequent development of gallbladder stone disease (GSD). Setting: Cohort Study. Participants: We identified two study cohort groups to evaluate the association of T1DM and T2DM with the development of GSD. The first group comprised a T1DM cohort of 7015 patients aged ≤ 40 years and a non-diabetes cohort randomly matched with the study cohort (4:1). The second group comprised a T2DM cohort of 51,689 patients aged ≥20 years and a non-diabetes cohort randomly matched with the study cohort (1:1). All patients were studied from 1996 to the end of 2011 or withdrawal from the National Health Insurance program to determine the incidence of GSD. Results: Compared with patients without diabetes, those with T1DM had a decreased risk of GSD [adjusted hazard ratios (aHR) = 0.48, 95% confidence interval (CI) = 0.25–0.92]. Those with T2DM had an increased risk of GSD (aHR = 1.55, 95% CI = 1.41–1.69), after adjustment for age, sex, comorbidities, and number of parity. The relative risk of GSD in the T2DM cohort was higher than that in the non-diabetes cohort in each group of age, sex, and patients with or without comorbidity. However, the relative risk of GSD in the T1DM cohort was lower than that in the non-diabetes cohort only in the age group of 20–40 years. Conclusion: Our population-based cohort study reveals a strong association between T2DM and GSD. However, an inverse relationship exists between T1DM and GSD in patients aged 20–40 years.

Meng Hsuen Hsieh,1,* Li-Min Sun,2,* Cheng-Li Lin,3,4 Meng-Ju Hsieh,5 Chung-Y Hsu,6 Chia-Hung Kao6–8 1Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA; 2Department of Radiation Oncology, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, Republic of China; 3Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, Republic of China; 4College of Medicine, China Medical University, Taichung, Taiwan, Republic of China; 5Department of Medicine, Poznan University of Medical Sciences, Poznan, Poland; 6Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, Republic of China; 7Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan, Republic of China; 8Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, Republic of China *These authors contributed equally to this work Objectives: Patients with type 2 diabetes (T2DM) are suggested to have a higher risk of developing pancreatic cancer. We used two models to predict pancreatic cancer risk among patients with T2DM. Methods: The original data used for this investigation were retrieved from the National Health Insurance Research Database of Taiwan. The prediction models included the available possible risk factors for pancreatic cancer. The data were split into training and test sets: 97.5% of the data were used as the training set and 2.5% of the data were used as the test set. Logistic regression (LR) and artificial neural network (ANN) models were implemented using Python (Version 3.7.0). The F1, precision, and recall were compared between the LR and the ANN models. The areas under the receiver operating characteristic (ROC) curves of the prediction models were also compared. Results: The metrics used in this study indicated that the LR model more accurately predicted pancreatic cancer than the ANN model. For the LR model, the area under the ROC curve in the prediction of pancreatic cancer was 0.727, indicating a good fit. Conclusion: Using this LR model, our results suggested that we could appropriately predict pancreatic cancer risk in patients with T2DM in Taiwan. Keywords: pancreatic cancer, type 2 diabetes, logistic regression, artificial neural network

Background and aims We aimed to determine whether patients with post-stroke dementia (PSD) have increased mortality risk in Taiwan. Methods We included ≥40-year-old patients who received a stroke diagnosis between 2000 and 2012 from a subset of the National Health Insurance Research Database of Taiwan. These patients were divided into PSD (International Classification of Diseases, Ninth Revision, Clinical Modification codes 290, 294.1, and 331.0) and post-stroke non-dementia (PSN) cohorts. Furthermore, we propensity score (PS) matched the PSD and PSN groups. PS was calculated through logistic regression to estimate the probability of stroke status assignment given the baseline variables, namely age, sex, and comorbidity. We calculated the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for death in the PSD and PSN cohorts after adjustments for age, sex, and comorbidities. Results Overall incidence density rates of death were 148.7 and 106.7 per 1,000 person-years in the PSD and PSN PS-matched cohorts, with the aHR of 1.42 (95% CI = 1.34–1.50). Average hospital days increased by 9.03 days and frequency of medical visits increased by 15.8 times per year in the PSD cohort compared with the PSN cohort. Conclusions The subsequent mortality rate in patients with PSD is increased compared with those without PSD. Moreover, the average hospital days and frequency of medical visit are increased in patients with PSD. Our findings provide crucial information for clinicians and the government to improve survival of patients after stroke.

Introduction Violent motor tics or severe self-harm behaviors have been reported in patients with Tourette's syndrome (TS) and leading to traumatic brain injury (TBI). The study aimed to determine the risk of TBI in TS patients, the effects associated with concurrent psychiatric disorders (attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or depressive disorder), and the effects of medication treatment (antipsychotics, antidepressants, or clonidine) on the risk of TBI. Methods Using the National Health Insurance Research Database of Taiwan, 2261 TS patients and 20349 non-TS controls matched by gender and age were enrolled between 2000 and 2012, and followed until the end of 2013. Participants who developed TBI during the follow-up period were identified. Cox regression analysis was performed to examine the risk of TBI between TS patients and non-TS controls. Results TS patients were associated with an increased risk of TBI compared to non-TS controls (hazard ratio (HR): 1.59, 95% confidence interval (95% CI): 1.37–1.85). Also, this study revealed TS patients with ADHD, OCD, or depressive disorder predicted a higher TBI incidence rate than those who did not, but the estimate was not statistically significant. Moreover, this study found that TS patients with frequent use of antipsychotics were associated with a lower risk of TBI than infrequent users (HR: 0.76, 95% CI: 0.57–0.99). Conclusions This study highlights the need to pay more attention to the risk of TBI in TS patients, and the importance of adequate antipsychotic medication may reduce the risk of TBI.

We investigated the effects of statins on tuberculosis (TB) and pneumonia risks in asthma&ndash, chronic pulmonary disease overlap syndrome (ACOS) patients. We extracted data of patients diagnosed as having ACOS during 2000&ndash, 2010 from the Taiwan National Health Insurance Research Database and divided them into statin users and nonusers. All study participants were followed up from the index date until death, withdrawal from insurance, or TB and pneumonia occurred (31 December 2011). The cumulative TB and pneumonia incidence was analyzed using Cox proportional regression analysis with time-dependent variables. After adjustments for multiple confounding factors including age, sex, comorbidities, and use of medications [statins, inhaled corticosteroids (ICSs), or oral steroids (OSs)], statin use was associated with significantly lower TB [adjusted hazard ratio (aHR) 0.49, 95% confidence interval (CI) 0.34&ndash, 0.70] and pneumonia (aHR 0.52, 95% CI 0.41&ndash, 0.65) risks. Moreover, aHRs (95% CIs) for statins combined with ICSs and OSs were respectively 0.60 (0.31&ndash, 1.16) and 0.58 (0.40&ndash, 0.85) for TB and 0.61 (0.39&ndash, 0.95) and 0.57 (0.45&ndash, 0.74) for pneumonia. Thus, statin users had lower TB and pneumonia risks than did nonusers, regardless of age, sex, comorbidities, and ICS or OS use. Pneumonia risk was lower among users of statins combined with ICSs or Oss and TB risk was lower among the users of statins combined with OSs.

Objective: Depression is a psychiatric disorder associated with poorer health outcomes. Inappropriate mechanical stress and aging are factors associated with developing cervical spondylosis. The connection between cervical spondylosis and depression is not developed. Methods: From the health insurance claims data of Taiwan, we identified 34,166 persons newly diagnosed with depression in 2000⁻2010 and 34,166 persons without the disorder frequency matched by sex, age and diagnosis year. Both cohorts were followed up to the end of 2013 to estimate incident cervical spondylosis. We further examined the risk of cervical spondylosis in depressed people taking antidepressants. Results: The incidence of cervical spondylosis was 1.8-fold greater in the depression cohort than in comparison cohort (9.46 vs. 5.36 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.79 (95% confidence interval (CI) = 1.66⁻1.92). The incidence of cervical spondylosis increased in patients who had taken medications of serotonin-specific reuptake inhibitors (SSRIs) or of non-SSRIs than in those without these medicines (9.13 or 11.5 vs. 6.54 per 1000 person-years, respectively). Conclusions: Patients with depression are at an increased risk of developing cervical spondylosis. Additional efforts in reducing the risk of cervical spondylosis might be required in depressed individuals undergoing anti-depressive therapy.

Background: Nurses are typically required to address patient emergencies, and they experience high stress levels in their work, which may expose them to a higher risk of stroke. This cohort study compared the risk of stroke between nurses and the general population. Methods: We used the Taiwan National Health Insurance database to conduct our retrospective cohort study, and we identified 83,641 individuals in the nurse group and 334,564 individuals in the control group. For the nurse group and the control group, we used the chi-square test in addition to applying Student&rsquo, s t-test, in order to compare the distribution differences for the continuous variables. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for ischemic stroke and hemorrhagic stroke through univariate and multivariate Cox proportional-hazards regression models, with stratification according to age, sex, and comorbidity. Results: The nurse group had a lower risk of ischemic stroke and hemorrhagic stroke in the crude model (HR = 0.66, 95% CI = 0.58&ndash, 0.75, HR = 0.58, 95% CI = 0.47&ndash, 0.72). After adjusting the prevalent variables, the nurse group still had a lower risk of stroke (HR = 0.68, 95% CI = 0.60&ndash, 0.77, HR = 0.59, 95% CI = 0.48&ndash, 0.73). Conclusion: The risks of both stroke types were lower in the nurse group than in the control. For stroke prevention, more frequent physical examinations are needed in order to enhance the health and well-being of people, including the nurses.

In most countries, the incidence of nasopharyngeal carcinoma (NPC) is no more than 1 per 100,000 for both men and women; however, it is much higher for men and women in Taiwan. The use of traditional Chinese medicine (TCM) as complementary and alternative medicine for the treatment of NPC and its treatment-related side effects has been increasing. The National Health Insurance (NHI) covers 99.6% of Taiwan’s residents. In the present population-based cohort study, we aimed to investigate the pattern of utilization of Chinese herbal products (CHPs) for NPC from 2001 through 2011 in Taiwan. We identified a total of 30294 patients with newly diagnosed NPC from the Registry for Catastrophic Illnesses Patient Database (RCIPD). Descriptive statistics and multiple logistic regression analysis were employed to estimate the adjusted odds ratios (aORs) for CHP utilization. From 2001 through 2011, 17816 patients aged ≥20 years were newly diagnosed with NPC. Of these, 4749 patients used TCM outpatient services for NPC treatment. TCM users were more likely to be women, young, residents of Central Taiwan, and white-collar workers. The most commonly prescribed formula CHP was Gan-Lu-Yin, followed by Xin-Yi-Qing Fei-Tang and Shan-Shen-Mai-Men-Dong-Tang. The most commonly prescribed single CHP was Hedyotis diffusa, followed by Radix Scrophulariae and Radix Ophiopogonis. These findings provide information regarding personalized therapies for NPC and can promote further clinical experiments and pharmacological research on CHPs for NPC treatment in Taiwan. Further well-designed randomized controlled studies and basic mechanistic studies should assess the safety and effectiveness of CHPs for NPC treatment.

Infection plays a major role in the development of autoimmune diseases. In this study, we investigated the relationship between scrub typhus and systemic autoimmune diseases. We enrolled 6,928 hospitalized patients with scrub typhus between 2000 and 2012 from the Taiwan National Health Insurance Research Database, and we compared them with 27,712 selected inpatients who had never been diagnosed with scrub typhus (1:4 ratio, matched by age, sex, and index year) in relation to the risk of developing autoimmune diseases. Cox proportional hazards regression analysis was used to analyze the risk of autoimmune diseases by sex, age, and comorbidities, with hazard ratios and 95% confidence intervals. The adjusted hazard ratio for autoimmune diseases for the scrub typhus group was 2.4 (95% confidence interval: 1.66, 3.48, P < 0.0001) compared with the control group. Subgroup analysis showed that women aged

Background Clopidogrel was thought to be superior to aspirin for secondary prevention of vascular diseases in clinical trials. In this study we assessed the safety and efficacy of clopidogrel versus aspirin in real‐world practice by using the Taiwan Stroke Registry. Methods and Results Patients with ischemic stroke (2006–2016) on aspirin or clopidogrel for secondary stroke prevention were identified in the Taiwan Stroke Registry. Stroke recurrence and mortality rates in patients receiving aspirin (N=34 679) were compared with those receiving clopidogrel (N=7611) during a 12‐month follow‐up period. Propensity score matching and conditional Cox proportional hazards regression model were applied to control confounding factors with 6443 patients in each group. After propensity score matching, stroke recurrence rates were comparable between groups, with 223 patients in the aspirin (3.46%) and 244 in the clopidogrel group (3.79%) (hazard ratio=1.13, 95% confidence interval=0.89–1.43, P =0.311). However, the mortality rate was significantly higher in the clopidogrel group (362 patients, 5.62%) than in the aspirin group (302 patients, 4.69%) (hazard ratio=1.30, 95% confidence interval=1.07–1.58, P =0.008). Results were consistent before and after propensity score matching. Conclusions Clopidogrel was as effective as aspirin for prevention of recurrent stroke in real‐world practice. However, the mortality rate was significantly higher in the clopidogrel than in the aspirin group.

Type 1 diabetes mellitus (T1DM) has been linked to many autoimmune problems. The association between T1DM and urticaria warrants investigation. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T1DM were recruited as the case group, and that group was matched by sex and age at a ratio of 1:4 to the control group comprising those without T1DM. The study period was 1998&ndash, 2011. All participants were followed up to the diagnosis of urticaria, withdrawal from the insurance program, death, or the end of the study. A multivariable Cox proportional hazard model was used to calculate the adjusted and crude hazard ratios for urticaria. A total of 5895 participants (1179 in the case group and 4716 in the control group) were followed up in the study. The total incidence rate of urticaria in patients with type 1 DM was 26.6 per 1000 person-years, and that in controls was 6.85 per 1000 person-years. Compared with the control group, the hazard ratio of urticaria in the case group was 2.84 (95% CI = 2.27&ndash, 3.56). Compared with age-matched participants without T1DM, patients with type 1 DM aged &lt, 18 years had a 3.62-fold higher risk of urticaria (95% CI = 2.85&ndash, 4.59). The hazard ratio in patients with an adjusted Diabetes Complications Severity Index (aDCSI) score of 1.01&ndash, 2.00 per year was 2.57 (95% CI = 1.18&ndash, 5.57), and that in patients with an aDCSI score of &gt, 2.00 per year was 4.47 (95% CI = 2.68&ndash, 7.47). T1DM patients aged &lt, 18 years had an increased risk of urticaria, but a similar phenomenon was not observed among T1DM patients older than 18 years.

Exposure to air pollutants is known to have adverse effects on human health; however, little is known about the association between hydrocarbons in air and an ischemic stroke (IS) event. We investigated whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increased IS risk. This retrospective cohort study included 283,666 people aged 40 years or older in Taiwan. Cox proportional hazards regression analysis was used to fit single- and multiple-pollutant models for two targeted pollutants, total hydrocarbons (THC) and nonmethane hydrocarbons (NMHC), and estimated the risk of IS. Before controlling for multiple pollutants, hazard ratios (HRs) of IS with 95% confidence intervals for the overall population were 2.69 (2.64-2.74) at 0.16-ppm increase in THC and 1.62 (1.59-1.66) at 0.11-ppm increase in NMHC. For the multiple-pollutant models controlling for PM2.5, the adjusted HR was 3.64 (3.56-3.72) for THC and 2.21 (2.16-2.26) for NMHC. Our findings suggest that long-term exposure to THC and NMHC may be a risk factor for IS development.

Background: A suitable multivariate predictor for predicting mortality following percutaneous coronary intervention (PCI) remains undetermined. We used a nationwide database to construct mortality prediction models to find the appropriate model. Methods: Data were analyzed from the Taiwan National Health Insurance Research Database (NHIRD) covering the period from 2004 to 2013. The study cohort was composed of 3,421 patients with acute myocardial infarction (AMI) diagnosis undergoing PCI. The dataset of enrolled patients was used to construct multivariate prediction models. Of these, 3,079 and 342 patients were included in the training and test groups, respectively. Each patient had 22 input features and 2 output features that represented mortality. This study implemented an artificial neural network model (ANN), a decision tree (DT), a linear discriminant analysis classifier (LDA), a logistic regression model (LR), a naive Bayes classifier (NB), and a support vector machine (SVM) to predict post-PCI patient mortality. Results: The DT model was found to be the most suitable in terms of performance and real-world applicability. The DT model achieved an area under receiving operating characteristic of 0.895 (95% confidence interval: 0.865–0.925), F1 of 0.969, precision of 0.971, and recall of 0.974. Conclusions: The DT model constructed using data from the NHIRD exhibited effective 30-day mortality prediction for patients with AMI following PCI.