Search

Tissue injury in peripheral sites can result in long-term potentiation in nociceptive neurons and surrounding glial cells, potentially resulting in the development of chronic inflammatory pain (CIP). Acupoint injection (AI) is similar to Western phototherapy, which injects solutions at specific sites to mitigate chronic pain. AI has shown greater benefits compared with acupuncture. In this study, we examined the therapeutic effect and explored the underlying mechanisms of AI in mice CIP model.We injected thrice complete Freund's adjuvant (CFA) into the mouse's hind paw to induce CIP.We found that, after two weeks, CFA injection significantly induced mechanical and thermal hyperalgesia which were attenuated by AI treatment. Transient receptor potential V1 (TRPV1) channels and associated molecules were all increased in CIP in mice dorsal root ganglion (DRG), spinal cord (SC), thalamus, and somatosensory cortex (SSC). The aforementioned molecules were mitigated in AI and Trpv1 knockout mice. Furthermore, Iba1-positive cells (microglial marker) were also potentiated and shared a similar tendency with TRPV1.These findings suggest that AI can alleviate chronic pain by reducing TRPV1 overexpression in both neuronal and microglial cells. Our results suggest new potential therapeutic targets for AI in chronic pain.

This study takes advantage of abundant data from the Economics Department at National Tsing Hua University to empirically evaluate whether there exist academic performance differentials between undergraduate students from two entrance channels (exam-based and application-based methods) across courses and grades. We first evaluate the academic performance between the students based on two entrance channels, and then incorporate the General Scholastic Ability Test (GSAT) score (including five subjects of Chinese Literature, Mathematics, English, Science, and Society) into the independent variables to control for the students' ability. Our empirical results exhibit the students recruited through the application-based method outperform those admitted from the exam-based method in required courses after controlling for the students' individual characteristics. Nevertheless, we found that the advantage disappears for the elective courses. Furthermore, the academic gaps between the two groups of students tend to decline or disappear when students are seniors. The findings indicate that entrance exam scores (e.g., the Scholastic Assessment Test (SAT) scores in the United States) are good indicators for predict college academic performance, making the potential function of entrance exam in Taiwan relatively comparable to that in the United States. The findings also detail that individual GSAT scores on English, Math, and Society are positively and significantly associated with his/her performance on the core courses in Economics, supporting a significant learning progression from the curricula of senior high school to the undergraduate college education.

This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R2 = 0.74, p &lt, 0.005). The hyperintensity of either 250 ± 50 mm3 (larger) or 100 ± 50 mm3 (smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study.

This study validates the measure, research-abstract writing assessment (RAWA), with two rating scales of global move of rhetorical purpose and local pattern of language use in applied linguistics (the scale level/score ranging from 0 to 5). The study adopted the embedded design of mixed-methods research that included both the quantitative latent regression model (LRM) for testing how the examinees’ (30 EFL doctoral students, 30 EFL master’s students) RAWA responses can be explained by examinee-group competence, scale-by-level difficulty of two scales, and rater expertise (5 raters); and the qualitative interviews on five raters’ perceptions. The LRM results revealed the scale-level difficulty effect, namely across the scales level 1 and level 5 of the global move being the easiest and the most difficult. The expert raters rated with lower scores. They also adopted the advanced subscales (i.e., content elements, brevity) as criteria and conducted self-monitoring while rating. The findings reveal the sub-competences of research-abstract writing, namely the global move sub-competence of move and content elements and the local pattern sub-competence of language use and brevity. Pedagogically, EFL graduate students should further develop the sub-competences of content element and brevity, once mastering those of move and language use as the basics.

Background: Neuroinflammatory processes initiated by injury, infection, and other insults induce long-term alterations in the signaling characteristics of nociceptive neurons and associated non-neuronal cells, resulting in chronic inflammatory pain (CIP). Prolotherapy, also termed acupoint injection (AI) therapy, utilizes anatomically based meridians derived from Chinese Medicinal Theory to attenuate chronic pain. In fact, AI has demonstrated superior results compared to traditional acupuncture methods without significant side effects. Methods: In this study, we explored the efficacy and underlying mechanisms of AI on CIP in mice. The mouse hindpaw was injected with complete Freund’s adjuvant (CFA) to induce CIP, followed AI treatment. Results: After two weeks, indices of mechanical and thermal hyperalgesia were significantly reduced by AI treatment. CIP was associated with elevated expression levels of transient receptor potential V1 (TRPV1) channels, various downstream kinases and transcription factors, and nociception-associated voltage-gated sodium channels (Navs) in dorsal root ganglion (DRG), spinal cord, thalamus, and somatosensory cortex, while AI-induced analgesia was associated with reversal of these expression changes. Further, upregulation of TRPV1-associated signaling factors was not observed in Trpv1 knockout mice following CFA injection. In addition, the activated microglial markers Iba-1 and S100B demonstrated similar expression changes and were colocalized with TRPV1. Conclusions: These findings suggest that AI can mitigate chronic pain (and sequel such as comorbid depression) by suppressing TRPV1 overexpression in neuronal or microglial cells.

Single photon emission computed tomography (SPECT) has been employed to detect Parkinson&rsquo, s disease (PD). However, analysis of the SPECT PD images was mostly based on the region of interest (ROI) approach. Due to limited size of the ROI, especially in the multi-stage classification of PD, this study utilizes deep learning methods to establish a multiple stages classification model of PD. In the retrospective study, the 99mTc-TRODAT-1 was used for brain SPECT imaging. A total of 202 cases were collected, and five slices were selected for analysis from each subject. The total number of images was thus 1010. According to the Hoehn and Yahr Scale standards, all the cases were divided into healthy, early, middle, late four stages, and HYS I~V six stages. Deep learning is compared with five convolutional neural networks (CNNs). The input images included grayscale and pseudo color of two types. The training and validation sets were 70% and 30%. The accuracy, recall, precision, F-score, and Kappa values were used to evaluate the models&rsquo, performance. The best accuracy of the models based on grayscale and color images in four and six stages were 0.83 (AlexNet), 0.85 (VGG), 0.78 (DenseNet) and 0.78 (DenseNet).

Purpose The purpose of this paper is twofold: to develop the college-attendance value scale (CAVS) in the Taiwan context to understand undergraduates’ reasons for or benefits from college education, and to examine how the value relates to additional motivational goals, academic performance, and expected terminal degree. Design/methodology/approach Data analyses involved sophomores (n=729) who completed a learning-experience survey that included CAVS of the personal value and collective value subscales, expected terminal degree, Achievement Goal Questionnaire, and cumulative grade point average (CGPA). Construct validity evidence was substantiated by the results of exploratory factor analysis (n=364) for two-factor identification, and by the results of confirmatory factor analysis (n=365) for a good model-fit. Findings The interrelations between variables in regression analysis supported the predictive validity; achievement goals were predictors of CGPA, while personal value was a sole predictor of expected terminal degree. Findings suggest that CAVS is a predictive measure for Taiwanese undergraduates’ academic performance and choices. Practical implications In terms of policy implications, college students’ values of college attendance should not only be regularly investigated by institutional research, but should be widely applied by university students, educators and administrators to facilitate the optimal learning development for each undergraduate. Originality/value The study develops a short but effective scale of college-attendance value for the Taiwanese students who usually attend college after graduating from high school. The CAVS is useful in manifesting the students’ major reasons for pursuing college education.

Osteoporosis has been associated with cancer development. We conducted a nationwide population-based cohort study in Taiwan to evaluate this possible association of osteoporosis with subsequent cancer development.A total of 35,979 patients diagnosed with osteoporosis between 2000 and 2010 identified from the National Health Insurance Research Database comprised the osteoporosis cohort, and each patient was randomly frequency matched with one individual from the general population (without osteoporosis) based on age, sex, and year of osteoporosis diagnosis to form the non-osteoporosis (control) cohort. Cox proportional hazard regression analysis was used to calculate adjusted hazard ratios and 95% confidence intervals and determine the effect of osteoporosis on cancer risk.Patients with osteoporosis showed a significantly higher risk of developing liver and thyroid cancers and lower risk of colorectal cancer than did individuals without osteoporosis. Male patients with osteoporosis had a significantly increased risk for liver cancer, whereas female patients with osteoporosis had a significantly increased risk for thyroid cancer, but a significantly decreased risk for overall and colorectal cancers. In addition, more significant findings were observed when age ≤64 years or the follow-up duration was ≤5 years; however, a significantly lower risk for colorectal cancer was observed when follow-up duration was5 years. Study limits including lack of data for some health-related behaviors, inclusion criteria of osteoporosis and potential selection bias have been discussed.Patients with osteoporosis showed a higher risk for liver and thyroid cancers and a lower risk for colorectal cancer than did control individuals. Stratified analyses by sex, age, and follow-up duration showed various patterns in different cancers.

SummaryThe spleen is a crucial organ in humans. However, little is known about the association of venous thromboembolism (VTE) with splenic injury and splenectomy in trauma patients. The aim of this study was to determine the subsequent risk of VTE following splenic injury and splenectomy. A nationwide retrospective cohort study was conducted by analysing data from the National Health Insurance Research Database in Taiwan. We included 6,162 splenic injury patients (3,033 splenectomised and 3,129 nonsplenectomised patients) and 24,648 comparison patients who were selected by frequency match based on sex, age, and the index year during 2000–2006. All patients were followed until the occurrence of VTE, 31 December, 2011, death, or withdrawal from the insurance program. The age of patients with splenic injury was 41.93 ± 16.44 years. The incidence rates of VTE were 11.81, 8.46, and 5.21 per 10,000 person-years in the splenic injury patients with splen -ectomy, splenic injury patients without splenectomy, and comparison patients, respectively. Compared with the comparison cohort, splenic injury patients with splenectomy exhibited a 2.21-fold risk of VTE (95 % confidence interval [CI], 1.43–3.43), whereas those without splenectomy exhibited a 1.71-fold risk of VTE (95 % CI, 1.05–2.80). The overall incidence rate of VTE was 1.97-fold higher in the splenic injury cohort than the comparison cohort (95 % CI, 1.38–2.81). Although splenectomy increased the risk of VTE 1.35-fold compared with no splenectomy, the difference was not statistically significant (95 % CI, 0.74–2.45). These results may alert physicians and patients to the complications of splenic injury and splenectomy.

The purpose of this study is twofold, testing how hierarchical motivation modeling explains college students’ academic performances over subsequent semesters; extending the motivation modeling on the university graduate attributes of another sample at a certain time point, by the regular, contextualized institutional-research (IR) practices. The hierarchical motivation modeling denotes that college-attendance values explain achievement goals, eliminating the effect of prior academic performance (i.e., the covariate). Participants were two cohorts of college sophomores with a 1-year gap in Taiwan who voluntarily responded to regular university-wide surveys. The path analysis results of Study 1 (N = 652, 39% female, 61% male) confirmed that the modeling explains the subsequent academic performance, and study hours. Those of Study 2 (N = 681, 43% female, 57% male) further confirmed that achievement goals mediate the values and the attributes. These IR findings indicate directions for college education innovation in boosting the motivated trajectory and the desired learning outcomes worldwide.

Background & Aims Pyogenic liver abscess (PLA) is a rare and severe extraintestinal complication in patients with inflammatory bowel disease (IBD). However, the incidence of PLA in patients with IBD remains unknown. Methods A nationwide cohort study was conducted by analysing data from the National Health Insurance Research Database in Taiwan. Patients with IBD (N = 11 504) from 2000 to 2010 and control participants without IBD (N = 46 016) were included in this study. We analysed the risks of PLA by using competing-risks (death) regression models. Results The incidence of PLA was higher in the IBD cohort than in the control cohort (6.72 vs 4.06 per 10 000 person-years), with an adjusted subhazard ratio (SHR) of 1.46 (95% confidence interval [CI], 1.01–2.12). Patients with IBD who required two or more hospitalizations per year and underwent laparotomy had an increased risk of PLA. Patients with ulcerative colitis were more likely to develop PLA than were those with Crohn's disease (incidence, 8.56 vs 5.45 per 10 000 person-years; adjusted SHR, 1.65 vs 1.32). Among the IBD cohort, age and gender did not affect PLA risk. Patients with diabetes mellitus or percutaneous aspiration of the gallbladder and biliary tract and who underwent endoscopic insertion of a biliary drainage tube exhibited a significantly increased risk of PLA. Conclusions Patients with IBD exhibited an increased risk of developing PLA, particularly those with ulcerative colitis. Knowledge of the expected frequency and potential risk for this severe extraintestinal infection may minimize the serious consequences.

Background This study evaluated the relationship between sleep disorders (SDs) and osteoporosis risk in Taiwan. Methods From the Taiwan National Health Insurance data, we identified 44,690 newly diagnosed SD patients (846 with apnea and 43,844 without) from 1998 to 2001 and 89,380 comparisons without SD in the same period frequency matched by sex, age and diagnosis year. Incident osteoporosis was measured by the end of 2010. Result Patients with apnea-SD and nonapnea SD exhibited a higher osteoporosis incidence rate than did the comparisons (9.97 and 13.3 vs. 6.77 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratio (HR) of osteoporosis was 2.98 (95% confidence interval [CI] = 2.36–3.74) in apnea-SD patients, compared with 2.76 (95% CI = 2.64–2.88) in nonapnea-SD patients after controlling for sex, age, comorbidities, and treatment. Greater HRs of osteoporosis were observed for female patients (4.00, 95% CI = 3.72–4.29) and those aged >64 years (42.0, 95% CI = 33.5–52.7) in the apnea SD sub-cohort. Apnea SD was associated with the highest risk of osteoporosis without fracture compared with both the nonapnea SD sub-cohort and comparisons. Conclusion Patients with sleep disorders have an elevated risk of osteoporosis, especially for women and the elderly.

Background context Previous studies on the risk and prevalence of diabetes among spinal cord injury (SCI) patients are limited and controversial. Purpose To compare the risk and incidence rate (IR) of Type 2 diabetes in SCI and non-SCI patients. Study design This is a population-based retrospective cohort study. Patient sample Data from Taiwan's National Health Insurance Research Database for the period 1997 to 2010 were analyzed. Patients aged 20 years and older newly identified with SCIs during this period were included in the SCI cohort. A non-SCI comparison cohort was randomly selected from National Health Insurance beneficiaries and matched with the SCI cohort based on age, sex, and index date. Outcome measures Both cohorts were followed until the first of the following occurred: the diagnosis of Type 2 diabetes (International Classification of Disease, Ninth Revision, Clinical Modification codes 250), withdrawal from the insurance system, the end of 2010, or death. Methods A Cox proportional hazards regression analysis was used to estimate the risk of developing diabetes. Results Taiwan possesses an older SCI population, with a mean age of 51.6 years. The IR for diabetes in patients with and without SCIs was 22.1 per 10,000 person-years and 17.2 per 10,000 person-years, respectively. The adjusted hazard ratio (HR) for diabetes was 1.33 times higher in patients with SCIs than in those without SCIs. In patients with SCIs, men (adjusted HR=1.23, 95% confidence interval (CI)=1.04–1.44), older people (adjusted HR=4.26 in patients older than 65 years, 95% CI=3.16–5.74), patients with comorbidity (adjusted HR=1.36, 95% CI=1.14–1.62), and patients with a complete thoracic SCI (T-spine injury) (adjusted HR=2.13, 95% CI=0.95–4.79) were more likely to be diagnosed with diabetes than other patient subgroups. Conclusions Our findings may facilitate the prioritizing of preventive health strategies and planning of long-term care for SCI patients.

The aim of this study is to determine whether patients with a non-apnea sleep disorder (NA-SD) and comorbidity have an increased risk of periodontal disease.Patients newly diagnosed with NA-SDs in 1997 to 2010 were identified as the study cohort from the Taiwan National Health Insurance database. For each patient with NA-SD, two matched controls without sleep disorders were randomly selected for comparison.The overall incidence rate ratio of severe periodontal diseases was 39% higher in the NA-SD cohort than in the comparison cohort (7.93 versus 5.69 per 1,000 person-years), with an adjusted hazard ratio (HR) of 1.36 (95% confidence interval [CI]: 1.30 to 1.43). The effect of NA-SD on the risk of severe periodontal diseases was higher in young and middle-aged patients compared with patients65 years of age (35 years of age, HR: 1.13, 95% CI: 1.04 to 1.24; 35 to 49 years of age, HR: 1.73, 95% CI: 1.61 to 1.86; 50 to 64 years of age, HR: 1.69, 95% CI: 1.58 to 1.81; ≥65, HR: [reference] 1.0).NA-SD might increase the risk of periodontal disease.

When using cardiac nuclear medicine images for diagnosis, the filtered back-projection (FBP) algorithm can reconstruct positron emission tomography (PET) images under low count rates. However, background strike artifacts in PET images are affected by diagnostic judgment. Hence, this study developed a robust method of removing background strike artifacts from FBP images without reducing image quality. A Jaszczak anthropomorphic torso phantom and a laboratory rabbit were used for performance tests of the proposed method. Parallel computing was applied to optimize the mask size of morphological structure operator (MSO) by minimizing the background standard deviation (Std). The optimal MSO mask size for the evaluated Jaszczak phantom was 3×3. The FBP images processed by MSO had significantly reduced strike artifacts measured by background Std ( P =1E-5). After MSO processing, the time activity curve (TAC) of FBP images was stable and resembled the original FBP images ( P =0.5). The proposed approach is highly stable and reduces noise by 13.08±2.32 in FBP images after MSO processing with 3×3 mask.

The association between periodontal disease treatment and end-stage renal disease (ESRD) remains unclear. This study aims to determine whether surgical periodontal treatment reduces ESRD risk.From the insurance claims data of patients with periodontal disease who were free of ESRD from 1997 to 2009, 35,496 patients were identified who underwent surgery for subgingival curettage and/or periodontal flap and are considered the treatment cohort. For comparison, 141,824 patients who did not undergo these treatments were considered the no-treatment cohort. Follow-ups were performed until the end of 2009 to estimate the incidence and risk of ESRD in these two cohorts. Cox proportional hazard regression was used to estimate the related hazard ratio (HR) and 95% confidence interval (CI) of ESRD.The incidence of ESRD was lower in the treatment cohort than in the no-treatment cohort (4.66 versus 7.38 per 10,000 person-years), with an adjusted HR of 0.59 (95% CI = 0.46 to 0.75). Sex- and age-specific analysis showed that the incidence rate ratio of the treatment cohort to the no-treatment cohort was higher for women than for men and declined with age. The risks of ESRD were consistently lower in the treatment cohort even when compared by comorbidity.Patients with periodontal disease who undergo procedures for subgingival curettage and/or periodontal flap have a remarkably decreased risk of ESRD.

Purpose We conducted a nested case-control study to evaluate the association between risk of cancer and mirtazapine use in depression patients in Taiwan. Methods We obtained data from the Taiwan National Health Insurance Research Database to conduct a population-based nested case-control study. The study cohort included 16 897 patients diagnosed with depression between January 1, 2000 and December 31, 2008. We identified 530 cancer patients as the study group and matched 4 non-cancer subjects with each cancer patient by incident density, age, and sex. Odds ratios and 95% confidence intervals were estimated using multivariate conditional logistic regression analysis. Results Use of mirtazapine for depression did not have significant effect on overall cancer incidence (odds ratio: 1.03, 95% confidence interval: 0.72–1.48). Further analysis of annual mirtazapine dosages and the duration of mirtazapine use revealed no significant effect on cancer risk. Conclusion The findings of this population-based nested case-control study suggest that mirtazapine use may not provide a tumor suppression effect in humans such as that seen in the animal model. Future large-scale and in-depth investigations in this area are warranted. Copyright © 2013 John Wiley & Sons, Ltd.

Objective We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[ 18 F]fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC). Methods Among the 127 male HCC patients who underwent 18 F-FDG PET/CT scan, the 18 FDG uptakes at the bilateral breasts in 9 patients with gynecomastia were recorded as standard uptake value (SUVmax) and the visual interpretation in both early and delayed images. Results The mean early SUVmax was 1.58/1.57 (right/left breast) in nine gynecomastia patients. The three patients with early visual score of 3 had higher early SUVmaxs. Conclusion Gynecomastia is a possible cause of false-positive uptake on 18 F-FDG PET/CT images.

This study examines the utilization patterns of myocardial perfusion imaging (MPI) and cardiac catheterization (CC) under Taiwan’s national health insurance program. This study used the longitudinal health insurance database with 1,000,000 people were randomly selected from the national health insurance research database. This study obtained data from these patients with coronary artery disease (CAD) and comparison with the utilization of MPI or CC between 2005 and 2009. The incidence of CAD did not significantly change, while the prevalence of CAD, utilization of MPI, and the utilization of CC for the CAD patients increased annually. There were the most CAD patients in Northern Taiwan (43.5 %), followed by Southern, Central, and Eastern Taiwan. The utilizations of both of MPI (12.7 per 100 CAD patients) and CC (10.6 per 100 CAD patients) were most frequent in Northern Taiwan followed by Southern, Central, and Eastern Taiwan. However, the MPI/CC ratio was 1.20 in Northern Taiwan, followed by Southern, Central, and Eastern Taiwan (0.88, 0.64, and 0.52, respectively, P = 0.0008). The use of MPI was higher than CC only in Northern Taiwan. MPI may be underutilized to serve the role of gatekeeper for CC in the other regions.

Background The purpose of the study was to explore the possible association between the use of insulin sensitizers (thiazolidinediones, TZDs) and the risk of cancer in Taiwanese diabetic patients. Patients and Methods From the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22 910 diabetic patients newly diagnosed from 2001 to 2009 and 91 636 non-diabetic comparisons frequency matched with age, sex, and calendar year, excluding those with cancer at the baseline. Among the diabetics, 4159 patients were treated with TZDs and the rest of 18 752 patients were on other anti-diabetic medications (non-TZDs). Results In comparison to the non-diabetes group, the non-TZDs group had an increased risk of developing cancer [the adjusted hazard ratio (HR): 1.20 and 95% confidence interval (CI) = 1.11–1.30]. The TZDs group had a HR of 1.18 (95% CI = 0.98–1.42). Analysis of site-specific cancer risks showed that both TZDs and non-TZDs groups with elevated risks of colorectal and pancreatic cancer. However, the non-TZDs group had an increased risk of liver cancer when comparing with TZD and non-diabetes groups. Conclusion This study suggests that patients with diabetes are at an elevated risk of cancer (especially in colorectal and pancreatic cancers), and the use of TZDs might decrease the liver cancer risk in diabetic patients. Further investigation using large samples and rigorous methodology is warranted.

Objective: Migraines are one of the most common neurological disorders. Dementia is a neurodegenerative disease characterized by slow progressive memory loss and cognitive dysfunction. This retrospective cohort study investigates the association between migraines and dementia using a nationwide population-based database in Taiwan. Methods: We retrieved the data analyzed in this study from the National Health Insurance Research database (NHIRD) in Taiwan. We used multivariate Cox proportion-hazards regression models to assess the effects of migraines on the risk of dementia after adjusting for sociodemographic characteristics and comorbidities. Results: The migraine cohort had a higher prevalence of diabetes, hypertension, coronary artery disease, head injury and depression at baseline (p < 0.0001). After adjusting the covariates, migraine patients had a 1.33-fold higher risk of developing dementia [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.22-1.46]. The sex-specific incidence rate of dementia was higher in men than in women in both cohorts, with an HR of 1.09 (95% CI 1.00-1.18) for men compared to women. Kaplan-Meier analysis shows that the cumulative incidence of dementia was 1.48% greater in the migraine cohort than in the nonmigraine cohort (log-rank test, p < 0.0001). Conclusions: This study shows that migraines are associated with a future higher risk of dementia after adjusting for comorbidities. Specifically, the association between migraine and dementia is greater in young adults than in older adults.

We investigated the relationship between morphine treatment and the risk of atrial fibrillation (AF) in female patients with breast cancer. We identified a malignancy cohort of 73,917 female breast cancer patients without an AF history before the date of breast cancer diagnosis between 2000 and 2010 by using the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. This malignancy cohort was divided into morphine and comparison cohorts comprising 18,671 and 55,246 patients, respectively, and the incidences of newly diagnosed AF were calculated. We used the Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of AF. The effect of morphine was assessed through multivariable Cox proportional hazard regression controlling for age, the Charlson comorbidity index (CCI) score, and the use of bisphosphonates and paclitaxel. Compared with nonmorphine users, patients who received morphine exhibited a 4.37-fold (95% CI = 3.56–5.36) increase in the risk of developing AF. The risk of AF increased as the CCI score increased, but decreased in patients with tamoxifen treatment. This risk is especially significant in current morphine users of all ages and with low CCI score. AF risk increased as the duration of morphine use lengthened (P for trend

Nephrolithiasis is highly prevalent and has been associated with vascular diseases such as cardiovascular events. Few studies have comprehensively associated renal stones with stroke. This study explored whether patients with renal stones were at a higher stroke risk than those without renal stones. A national insurance claim dataset of 22 million enrollees in Taiwan was used to identify 53,659 patients with renal stones, and 214,107 were selected as age-, sex-, and comorbidity-matched controls for a 13-year follow-up. The relative stroke risk for the RS cohort was 1.06-fold higher than that for the non-RS group (95% confidence interval [CI] = 1.01–1.11). Age-specific analysis revealed that the adjusted stroke risk for the RS cohort increased as age decreased, with the highest risk of 1.47-fold (95% CI = 1.10–1.96) in patients aged 20 to 34 years, followed by a 1.12-fold risk (95% CI = 1.00–1.25) in patients aged 35 to 50 years. Sex-specific analysis clarified that women in the RS group had a 1.12-fold stroke risk compared with women in the non-RS group (95% CI = 1.03–1.21). Patients who had undergone >4 surgeries had up to 42.5-fold higher risk of stroke (95% CI = 33.8–53.4). The study utilized the national database and demonstrated that patients, particularly women and the younger population, with nephrolithiasis have an increased risk of ischemic stroke development. Patients treated with medication or through surgery for RSs showed steady and higher risks of stroke than those without surgical or medical intervention.

Neuropsychiatric diseases might enhance stroke development, possibly through inflammation and atherosclerosis. Approximately 25% to 40% of patients with stroke, largely younger patients, are not associated with any conventional stroke risk factors. In this research, we explored whether fibromyalgia (FM), a neuropsychosomatic disorder, increases stroke risk. From a claims dataset with one million enrollees sourced of the Taiwan National Health Insurance database, we selected 47,279 patients with FM and randomly selected 189,112 age- and sex-matched controls within a 3-year period from January 1, 2000 to December 31, 2002. Stroke risk was assessed using Cox proportional hazards regression. Comorbidities associated with increased stroke risk, such as hypertension, diabetes, hyperlipidemia, coronary heart disease, irritable bowel syndrome, and interstitial cystitis, were more prevalent in patients with FM and high stroke risk than in the controls. The overall stroke risk was 1.25-fold (95% confidence interval [CI]: 1.21–1.30) higher in the FM group than in the non-FM group. Even without comorbidities, stroke risk was higher in patients with FM than in the controls (adjusted hazard ratio [aHR] = 1.44, 95% CI: 1.35–1.53, P

This study examines whether pelvic inflammatory disease (PID) facilitates the development of intracerebral hemorrhage (ICH). By using outpatient claims data from the National Health Insurance Research Database (NHIRD) of Taiwan, we included the data of 25,508 patients who were newly diagnosed with PID between 1999 and 2004, and also from the Taiwan NHIRD, we randomly selected 102,032 women without PID, who were frequency-matched by age and entry-year and with 4 times the number of the PID patients, as the control cohort. We measured ICH risks associated with PID and comorbidities, including hyperlipidemia, diabetes, hypertension, ischemic heart disease, and atrial fibrillation, by the end of 2011. In comparison with the controls, the ICH hazard was less in the PID group with an adjusted hazard ratio (aHR) of 0.67 (95% confidence interval [CI]:0.50–0.90), which was noted by calculation with the Cox proportional regression model. The ICH risk in the PID patients reduced progressively with the advance of age, with aHRs of 0.75 (95% CI:0.41–1.39) and 0.50 (95% CI:0.29–0.88), respectively, in the age

Purpose Nephrotic syndrome is a common chronic illness encountered during childhood. Infections have been identified as a cause of nephrotic syndrome. The aim of this study was to evaluate the association between enteroviral infection and nephrotic syndrome. Methods A nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged

Learning Objectives After completing this course, the reader will be able to:Describe the effect of finasteride use on the incidence of prostate cancer and overall cancer.Describe the effect of dutasteride use on the incidence of renal cancer.Explain the relationship between finasteride dosage and risk of prostate cancer and overall cancer risk. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. 5α-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. Methods. We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. Results. Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00–3.59; overall cancer: OR = 1.51; 95% CI: 1.00–2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17–80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. Conclusions. This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride.

Metabolic abnormalities are common in patients with depressive disorders. However, the relationship between gout and depression is unclear. We explored the causal relationship among gout, antigout medication, and the associated risk of incidental depressive disorders. In this nationwide cohort study, we sampled data from the National Health Insurance Research Database to recruit 34,050 patients with gout as the gout cohort and 68,100 controls (without gout) as the nongout cohort. Our primary endpoint was the diagnosis of depressive disorders during follow-up. The overall study population was followed up until depression diagnosis, withdrawal from the NHI program, or the end of the study. The differences in demographic and clinical characteristics between both cohorts were determined using the Chi-square test for categorical variables and the t-test for continuous variables. Cox proportional hazard regression models were used to examine the effect of gout on the risk of depression, represented using the hazard ratio with the 95% confidence interval. Patients with gout exhibited a higher risk of depressive disorders than controls did. The risk of depressive disorders increased with age and was higher in female patients and those with hypertension, stroke, and coronary artery disease. Nonsteroidal antiinflammatory drug and prednisolone use was associated with a reduced risk of depression. Patients with gout who had received antigout medication exhibited a reduced risk of depressive disorders compared with nongout patients. Our findings support that gout increases the risk of depressive disorders, and that antigout medication use reduces the risk.

Diverticular disease and acute coronary syndrome (ACS) are common disorders that share several risk factors. Few researchers have evaluated the association between diverticular disease and ACS. We aimed to assess the risk of ACS in patients with diverticular disease. A nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. All patients aged ≥20 years with a diagnosis of diverticular disease from January 1, 2000, to December 31, 2011, were included in this study. For comparison, patients without diverticular disease were randomly selected and matched with the study cohort at a 4:1 ratio according to age, sex, and the year of the diagnosis of diverticular disease. Patients with incomplete age or sex information and a history of cardiovascular diseases were excluded from the study. All patients were followed until an ACS event, withdrawal from the insurance program, or December 31, 2011. In this study, 52,681 patients with diverticular disease and 210,724 patients without diverticular disease were included. Men accounted for 56.1% of patients and 57.8% of patients were ≥50 years old. The overall incidence density of ACS in patients with diverticular disease (45.5 per 10,000 person-years) was significantly higher than in those without diverticular disease (30.3 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.23 (95% confidence interval [CI], 1.14–1.32) after adjustment for age, sex, and comorbidities. The cumulative incidence of ACS in patients with diverticular disease was significantly higher than that in the control cohort (log-rank test, P

The spleen is a crucial organ in humans. Little is known about the association between stroke and splenic injury or splenectomy. The aim of this study was to determine the risk of stroke in patients with splenic injury and splenectomy. A nationwide cohort study was conducted by analyzing the National Health Insurance Research Database in Taiwan. For comparison, control patients were selected and matched with splenic injury patients in a ratio of 4:1 according to age, sex, and the year of hospitalization. We analyzed the risks of stroke using a Cox proportional-hazards regression analysis. A total of 11,273 splenic injury patients, including 5294 splenectomized and 5979 nonsplenectomized patients, and 45,092 control patients were included in this study. The incidence rates of stroke were 8.05, 6.53, and 4.25 per 1000 person-years in splenic injury patients with splenectomy, those without splenectomy, and the control cohort, respectively. Compared with the control cohort, splenic injury patients with splenectomy exhibited a 2.05-fold increased risk of stroke (95% confidence interval [CI] 1.8–2.34), whereas those without splenectomy exhibited a 1.74-fold increased risk (95% CI 1.51–2). Splenectomy entailed an additional 1.21-fold increased risk of stroke compared with nonsplenectomy in patients with splenic injury. This study revealed that splenic injury and splenectomy were significantly associated with an increased risk of hemorrhagic and ischemic strokes. The results of this study may alert physicians and patients to the complications of splenic injury and splenectomy.

Summary Background The association between enterovirus infections in children and risk of leukaemia is unclear. We aimed to assess the risk of leukaemia after enterovirus infection in children. Methods We did a nationwide retrospective cohort study by analysing data from the National Health Insurance Research Database (NHIRD) in Taiwan. Children with enterovirus infections aged younger than 18 years were identified. With use of computer-generated random numbers, children not infected with enterovirus were randomly selected and frequency matched (1:1) with children infected with enterovirus by sex, age, urbanisation level, parental occupation, and index year of enterovirus infection. We only included children with complete baseline data for age and sex and who had at least three clinic visits with the diagnosis of enterovirus infection. The diagnosis date of the first clinic visit for the enterovirus infection was defined as the index date for initiation of follow-up person-year measurement and participants. All study patients were followed up until they developed leukaemia, were lost to follow-up, withdrew from the NHI programme, or until the end of the study without leukaemia (censored). Our primary endpoint was a diagnosis of leukaemia during follow-up. Findings Insurance claims data for 3 054 336 children younger than 18 years were randomly selected from all insured children in the NHIRD. We identified 282 360 children infected with enterovirus and 282 355 children not infected with enterovirus between Jan 1, 2000, and Dec 31, 2007. The incidence density rates of leukaemia were 3·26 per 100 000 person-years for the enterovirus-infected and 5·84 per 100 000 person-years for the non-enterovirus-infected cohorts. The risk of leukaemia was significantly lower in the enterovirus-infected cohort than in the non-enterovirus-infected cohort (adjusted subhazard ratio [SHR] 0·44, 95% CI 0·31–0·60; p Interpretation The association between enterovirus infection and the reduced risk of developing leukaemia supports Greaves' delayed infection hypothesis for the cause of childhood leukaemia. Funding Taiwan Ministry of Health and Welfare, Academia Sinica, NRPB Stroke Clinical Trial Consortium, Tseng-Lien Lin Foundation, Taiwan Brain Disease Foundation, Katsuzo and Kiyo Aoshima Memorial Funds, China Medical University Hospital, and Taiwan Ministry of Education.

The purpose of the study was to investigate the effects of research-article writing motivation and use of self-regulatory writing strategies in explaining second language (L2) research-article abstract writing ability, alongside the L2 literacy effect. Four measures were administered: a L2 literacy test, a research abstract performance assessment, and inventories of writing motivation and strategy. Participants were L2 graduate students in Taiwan ( N = 185; M age = 25.8yr., SD = 4.5, range = 22–53). Results of structural equation modeling showed a direct effect of motivation on research-article writing ability, but no direct effect of strategy or indirect effect of motivation via strategy on research-article writing ability, with L2 literacy controlled. The findings suggest research-article writing instruction should address writing motivation, besides L2 literacy.

We previously reported that intrathecal pro-opiomelanocortin gene electroporation could reduce pain sensitivity induced by chronic constriction injury (CCI) of the sciatic nerve. For optimal use of antinociceptive gene therapy, it might be important to control the expression of the transfected gene extrinsically. For this purpose, a doxycycline-controlled transrepressor system composed of two plasmids coding, respectively, for pro-opiomelanocortin gene (pTRE2-POMC) and the silencer (pTel-off) was employed. The regulation of beta-endorphin expression was first assessed in spinal neuronal culture, then we electrotranfected this plasmid into the spinal cord of mononeuropathic rats and evaluated the analgesic potential of this therapy in vivo by thermal and mechanical withdrawal latency. Intraperitoneal injections of various doses of doxycycline were made to elucidate the possible exogenous downregulation of transfected beta-endorphin gene expression in vivo. The levels of beta-endorphin were analyzed by intrathecal microdialysis and radioimmunoassay. Intrathecal pTRE2-POMC/pTel-off electroporation elevated spinal beta-endorphin levels, as manifested in a significantly elevated pain threshold for chronic constriction injury limbs. Intraperitoneal doxycycline decreased the antinociceptive effect and spinal beta-endorphin levels in a dose-dependent manner. We concluded that intrathecal pTRE2-POMC/pTel-off electroporation alleviates CCI-induced limb pain, and can be controlled by intraperitoneal doxycycline administration.

The concern regarding cancer risk has resulted in the recommendation to pull calcitonin nasal spray (CNS) from the market.We conducted a nested case-control study to evaluate the association between CNS use in osteoporosis patients in Taiwan and their subsequent risk of cancer.This was a population-based nested case-control study.Data were obtained from the Taiwan National Health Insurance Research Database.The study cohort consisted of 28 222 patients diagnosed with osteoporosis between January 1, 2000, and December 31, 2011. We identified 1925 cancer patients as the study group and 2 noncancer patients frequency matched according to age at index date, sex, comorbidity, index-year, and osteoporosis-year as the control group.Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis.Use of CNS in women with osteoporosis significantly increased the risk of liver cancer (OR = 1.94, 95% CI = 1.23-3.05) but decreased the risk of breast cancer (OR = 0.35, 95% CI = 0.15-0.80). Further analysis of monthly CNS dosages showed that the association between CNS and liver cancer is limited to higher-dose users.The findings of this population-based nested case-control study suggest that CNS use might increase the risk of liver cancer in female osteoporosis patients but decrease the risk of breast cancer. Our data do not completely support the decision to discontinue use of CNS in osteoporosis patients.

This study determined whether there is an increased risk of tinnitus in patients with temporomandibular joint (TMJ). We used information from health insurance claims obtained from Taiwan National Health Insurance (TNHI). Patients aged 20 years and older who were newly diagnosed with TMJ disorder served as the study cohort. The demographic factors and comorbidities that may be associated with tinnitus were also identified, including age, sex, and comorbidities of hearing loss, noise effects on the inner ear, and degenerative and vascular ear disorders. A higher proportion of TMJ disorder patients suffered from hearing loss (5.30 vs. 2.11 %), and degenerative and vascular ear disorders (0.20 vs. 0.08 %) compared with the control patients. The crude hazard ratio (HR) of tinnitus in the TMJ disorder cohort was 2.73-fold higher than that in the control patients, with an adjusted HR of 2.62 (95 % CI = 2.29–3.00). The comorbidity-specific TMJ disorder cohort to the control patients’ adjusted HR of tinnitus was higher for patients without comorbidity (adjusted HR = 2.75, 95 % CI = 2.39–3.17). We also observed a 3.22-fold significantly higher relative risk of developing tinnitus within the 3-year follow-up period (95 % CI = 2.67–3.89). Patients with TMJ disorder might be at increased risk of tinnitus.