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Background Gamma-glutamyl transferase (GGT) has been associated with coronary heart disease, diabetes mellitus, and hypertension, but its association with psoriasis has not yet been elucidated. Aims We conducted this study to determine the association between the risk of psoriasis and the serum GGT. Methods We conducted a nationwide population-based study. A total of 9,939,350 people met the enrolment criteria. The study population was classified into four groups based on GGT levels and the risk of psoriasis was calculated for each group. Results The incidence rates of psoriasis per 1,000 person-years were 2.96105 and 3.68577 in the lowest and highest GGT groups, respectively. After adjusting for age, sex, income, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol intake, exercise, and body mass index, the highest GGT group showed a significantly increased risk of developing psoriasis (hazard ratio: 1.057, 95% confidence interval: 1.044-1.07). This risk of psoriasis was significantly higher among the old age group (hazard ratio: 1.162, 95% confidence interval: 1.128-1.197) and women (hazard ratio: 1.14, 95% confidence interval: 1.117-1.164). Limitations The limitations of this study included the retrospective design, International Classification of Diseases code-based diagnosis, small hazard ratio, and non-availability of data on covariates. Conclusion The GGT level was found to be an independent risk factor for developing psoriasis.

Background: A nonlinear association between serum hepatitis B virus (HBV) DNA levels and hepatocellular carcinoma (HCC) risk has been suggested in patients with chronic hepatitis B (CHB)., Objective: To develop and externally validate a prognostic model for HCC risk in noncirrhotic adult patients with CHB and no notable alanine aminotransferase (ALT) elevation., Design: Multinational cohort study., Setting: A community-based cohort in Taiwan (REVEAL-HBV [Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus]; REACH-B [Risk Estimation for HCC in CHB] model cohort) and 8 hospital-based cohorts from Korea and Hong Kong (GAG-HCC [Guide with Age, Gender, HBV DNA-HCC] and CU-HCC [Chinese University-HCC] cohorts)., Participants: Model development: 6949 patients with CHB from a Korean hospital-based cohort. External validation: 7429 patients with CHB combined from the Taiwanese cohort and 7 cohorts from Korea and Hong Kong., Measurements: Incidence of HCC., Results: Over median follow-up periods of 10.0 and 12.2 years, the derivation and validation cohorts identified 435 and 467 incident HCC cases, respectively. Baseline HBV DNA level was one of the strongest predictors of HCC development, demonstrating a nonlinear parabolic association in both cohorts, with moderate viral loads (around 6 log 10 IU/mL) showing the highest HCC risk. Additional predictors included in the new model (Revised REACH-B) were age, sex, platelet count, ALT levels, and positive hepatitis B e antigen result. The model exhibited satisfactory discrimination and calibration, with c-statistics of 0.844 and 0.813 in the derivation and validation cohorts with multiple imputation, respectively. The model yielded a greater positive net benefit compared with other strategies in the 0% to 18% threshold., Limitation: Validation in cohorts of other races and receiving antiviral treatment was lacking., Conclusion: Our new prognostic model, based on the nonlinear association between HBV viral loads and HCC risk, provides a valuable tool for predicting and stratifying HCC risk in noncirrhotic patients with CHB who are not currently indicated for antiviral treatment., Primary Funding Source: Korean government., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0384.

Background: While all-cause mortality is reportedly increased in preserved ratio impaired spirometry (PRISm), no remedial efforts have been suggested., Aim: To study the ability of physical activity (PA) on reducing the morality increased in PRISm patients., Design: We prospectively enrolled a cohort of Taiwanese adults from 1994 to 2018 in a health surveillance program., Methods: Mortality risks of those who were inactive were compared against those meeting the current recommendation of 150 min/week of PA. Cox proportional hazards models were used for hazard ratios and life table method was for estimating loss of life expectancy., Results: A total of 461 183 adults were enrolled. Among them, one-seventh of the cohort (65 832 or 14.3%) had PRISm, and 53.1% were inactive. Those who were inactive with PRISm had 28% increased mortality from all-cause, 45% from cardiovascular diseases (CVDs) and 67% from respiratory disease, with a 3-year reduction in life expectancy (males, 3.72 and females, 2.93). In PRISm patients who met the exercise recommendation, excess mortality was reduced by two-third, both all-cause (from 28% to 9%) and CVD (from 45% to 15%)., Conclusion: PRISm involves a large portion of general population (14.3%) and shortens life expectancy by 3 years. More than half of the subjects were physically inactive, and adherence to 150 min/week of PA was associated with a two-third reduction of excess mortality from all cause and from CVD. Recommending PA among those with PRISm might be highly beneficial, although exercise alone may not eliminate all risks associated with PRISm., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/purpose: Patients with advanced cancer sometimes travel to locations that have the treatment that they need. We explored the prognostic factors of survival in patients with advanced lung cancer who travel long distances in Taiwan., Methods: We obtained data from the National Taiwan University Hospital (NTUH) Integrated Medical Database. Patients who received a diagnosis of stage IV lung cancer from 2010 to 2019 and were treated in NTUH and its Hsinchu and Yunlin branches were enrolled. Factors associated with survival were analyzed using a Cox hazard regression model., Results: In total, 6178 patients with stage IV lung cancer were enrolled. Young age, female sex, smaller primary tumor size, better performance, and non-squamous cell non-small cell histology were independently associated with longer survival. Treatment in medical centers and long travel distances (>50 km) were associated with longer survival in the univariate analysis but not in the multivariate analysis (hazard ratio [HR]: 1.04, p = 0.361; HR: 0.99, p = 0.775, respectively). Participation in clinical trials was associated with longer survival in the univariate (HR: 0.53, p < 0.001) and multivariate analyses (HR: 0.62, p < 0.001). For the 1144 patients in the Hsinchu area, enrolment in clinical trials was an independent prognostic factor (HR: 0.72, p = 0.040), whereas treatment in medical centers was not (HR: 0.95, p = 0.635)., Conclusion: Long travel distances and treatment in medical centers were not independently associated with survival for patients with advanced lung cancer. Enrolment in clinical trials was an independent prognostic factor., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by defective neutrophil killing of microbial pathogens and recurrent infections. We aimed to investigate the clinical, genetic features, treatment, and outcomes in patients with CGD., Methods: Pediatric patients diagnosed with CGD from a medical center in Taiwan were enrolled from January 1999 to Oct 2021., Results: Nine pediatric patients with CGD were enrolled: six X-linked (XL) CGD with CYBB gene mutations, three autosomal recessive (AR) CGD with two NCF1 and one CYBA gene mutations. The median age of onset and age of diagnosis was 0.92 and 2.64 years, respectively. Patients with XL-CGD had a younger age of onset (4.6 months vs. 1.83 years, P = 0.06) and age of diagnosis (1.71 vs. 8.86 years, P = 0.024) than AR-CGD patients. The most common sites of infections were skin and soft tissue abscesses. The most common pathogens were Staphylococcus, Serratia, and Salmonella spp. Prophylactic antibiotics, anti-fungal agents, and interferon-gamma (IFN-γ) were given in 9 (100%), 7 (77.8%), and 8 (88.9%) patients, respectively. The mean duration of IFN-γ usage was 5.15 years. One male patient with XL-CGD was successfully treated with hematopoietic stem cell transplantation at 2.2 years. The mortality rate was 11.1%, and the estimated overall survival at 20 years was 66.7%., Conclusion: Staphylococcus aureus, Serratia marcescens, and Salmonella infections are important in Taiwanese CGD patients. Patients with XL-CGD have early disease onset. IFN-γ prophylaxis and prophylactic anti-microbial agents might have an effect on alleviating the infection episodes in CGD patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Since the 24-hr PM 2.5 (particle aerodynamic diameter less than 2.5 μm) concentration standard was regulated in Taiwan in 2012, the PM 2.5 concentration has been decreasing year by year, but the ozone (O 3 ) concentration remains almost the same. In particular, the daily maximum 8-hr average O 3 (MDA8 O 3 ) concentration frequently exceeds the standard. The goal of this study is to find a solution for reducing PM 2.5 and O 3 simultaneously by numerical modeling. After the Volatile Organic Compounds (VOC S )-limited and nitrogen oxides (NO X )-limited areas were defined in Taiwan, then, in total, 50 scenarios are simulated in this study. In terms of the average in Taiwan, the effect of VOC S emission reduction is better than that of NO X on the decrease in PM 2.5 concentration, when the same reduction proportion (20%, 40%) is implemented. While the effect of further NO X emission reduction (60%) will exceed that of VOC S . The decrease in PM 2.5 is proportional to the reduction in precursor emissions such as NO X , VOC S , sulfur dioxides (SO 2 ), and ammonia (NH 3 ). The lower reduction of NO X emission for whole Taiwan caused O 3 increases on average but higher reduction can ease the increase, which suggests the implement of NO X emission reductions must be cautious. When comparing administrative jurisdictions in terms of grids, districts/towns, and cities/counties, it was found that controlling NO X and VOC S at a finer spatial resolution of control units did not benefit the decrease in PM 2.5 but did benefit the decrease in O 3 . The enhanced O 3 control strategies obviously cause a higher decrease of O 3 throughout Taiwan due to NO X and VOC S emission changes when they are implemented in the right places. Finally, three sets of short-term and long-term goals of controlling PM 2.5 and O 3 simultaneously are drawn from the comprehensive rankings for all simulated scenarios, depending on whether PM 2.5 or O 3 control is more urgent. In principle, the short-term scenarios could be ordinary or enhanced version of O 3 decrease with lower NO X /VOC S emissions, while the long-term scenario is enhanced version of O 3 decrease plus high emission reductions for all precursors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

For chronic obstructive pulmonary disease (COPD), the role of physical activity in reducing COPD mortality and heart loading and in extending life expectancy remains unclear. Participants in comprehensive medical screening were recruited with spirometry on everyone. We analyzed physical activity volume calculated from intensity, duration and frequency of self-reported exercise history. Deaths were identified from the National Death File. The impacts of physical activity on mortality, heart rate and life expectancy were analyzed. Among the cohort of 483,603 adults, 32,535 had spirometry-determined COPD, indicating an adjusted national prevalence of 11.4% (male) and 9.8% (female). On the average, COPD increased all-cause mortality with a hazard ratio of 1.44 and loss of 6.0 years in life expectancy. Almost two thirds (65%) of the causes of deaths were extra-pulmonary, such as cardiovascular disease, diabetes, cancer and kidney diseases. In addition, COPD was associated with increases in heart rate proportionate to its severity, which led to higher mortality. Participants with COPD who were fully active physically could reduce mortality and have improved heart rates as compared with those without physical activity. In addition, their life expectancy could be extended close to those of the no COPD but inactive cohort. Fully active physical activity can help patients with COPD overcome most of the mortality risks, decrease heart rate, and achieve a life expectancy close to that of patients without COPD. The effectiveness of physical activity on COPD is facilitated by its systemic nature beyond lung disease., (© 2021. The Author(s).)

Background: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC., Methods: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status., Results: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26)., Conclusions: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background : Health literacy has become the best predictor of healthcare status. However, two-thirds of health providers are unaware of patients' health literacy. Thus, the aim of the study is to investigate factors related to Chinese-speaking nurses' knowledge and experience of health literacy. Methods : This cross-sectional study used a web-based survey. A total of 430 nurses were recruited by stratified sampling from different levels of hospitals and community health centers in Taiwan. Primary outcome measure by Health Literacy Knowledge and Experience. Results : The participants' overall health literacy knowledge was limited; the correct responses were 51%. The education level of the participants, job category, working years, and having attended in-service patient education programs were the predictors of knowledge of health literacy ( p < 0.05); Institute, job category, and having attended in-service patient education programs were the predictors of experience of health literacy ( p < 0.01). Conclusions : Participants' education levels and In-service patient education programs are beneficial factors to improve nurses' knowledge of health literacy. Furthermore, nursing education should emphasize on how to identify individuals' health literacy and using readable healthcare materials to improve health education.

Adverse health effects have been observed in nearby residents due to exposure to petrochemical-derived chemicals. The objective of this study was to examine associations of soluble metals with lung and liver toxicity in fine particulate matter (PM 2.5 ) in the vicinity of a petrochemical complex. PM 2.5 was collected in the vicinity of a petrochemical complex of Mailiao Township (Yunlin County, Taiwan) to investigate lung and liver toxicity in BALB/c mice. The PM 2.5 concentration was 30.2 ± 11.2 μg/m 3 , and the PM 2.5 was clustered in major local emissions (19.1 μg/m 3 ) and minor local emissions (14.1 μg/m 3 ) using a k-means clustering model. The PM 2.5 (50 and 150 μg/kg) and PM 2.5 -equivalent soluble nickel (Ni), vanadium (V), and lead (Pb) concentrations were intratracheally instilled into BALB/c mice. PM 2.5 and V significantly decreased the tidal volume after exposure (p < 0.05). The peak expiratory flow (PEF) and peak inspiratory flow (PIF)/PEF ratio were significantly altered by 150 μg/kg V (p < 0.05). V and Pb significantly increased total protein and lactate dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF) (p < 0.05). Interleukin (IL)-6 in BALF significantly increased after exposure to Pb (p < 0.05) accompanied by lung inflammatory infiltration. PM 2.5 and Pb significantly increased levels of 8-isoprostane (p < 0.05). The level of caspase-3 activity significantly increased after exposure to Pb (p < 0.05). LDH in the liver was significantly increased by PM 2.5 (p < 0.05). 8-Isoprostane in the liver was significantly increased by PM 2.5 and Pb (p < 0.05). IL-6 in the liver was significantly increased by PM 2.5 , Ni, V, and Pb after exposure (p < 0.05), accompanied by liver inflammatory infiltration. Our results demonstrated that V in PM 2.5 was associated with an increase in 8-isoprostane for all emissions and major local petrochemical emissions. In conclusion, V contributes to in vivo liver toxicity induced by PM 2.5 in the vicinity of a petrochemical complex.

Backgrounds: Behçet's disease (BD) is a rare vasculitic disorder affecting all sizes of vessels. Among BD patients, 4 to 25% of patients with diagnosed age younger than 16 years old are defined as juvenile BD (JBD). This study aimed to evaluate the clinical manifestations and treatments of patients with JBD, with a particular focus on the effectiveness and safety of anti-tumor necrosis factor (TNF)-alpha therapy., Methods: We retrospectively reviewed data of all patients diagnosed with JBD at age of 16 years or younger in a tertiary hospital in Taiwan. The clinical manifestations, laboratory data, treatments, disease courses, and clinical outcomes were evaluated. The effectiveness of anti-TNF-alpha therapy was measured based on changes in Behçet's Disease Current Activity Form (BDCAF) scores, prednisolone dosages and the immunosuppression load scores., Results: Fifty-five patients were included in the study. The median age at disease onset was 11 years. The most common clinical presentation was recurrent oral aphthous ulcers (100%), followed by genital ulceration (69.1%), skin lesions (36.4%), gastrointestinal symptoms (29.1%), ocular involvement (27.3%), and arthralgia (27.3%). Ninety-one percent of the patients fulfilled the International Criteria for Behçet's Disease, and 36.4% met the Paediatric Behçet's Disease criteria. The most frequently used medications were prednisolone (74.5%) and colchicine (54.5%). Six patients with refractory or severe JBD received anti-TNF-alpha therapy. These patients were diagnosed at a younger age compared with those who did not receive anti-TNF-alpha therapy (7.5 vs 13 years; P = 0.012), the BDCAF scores reduced significantly at the 1st month, the 6th month and 1 year after the treatment. They did not use steroids after the first year of treatment, and, after treatment for 6 months, their immunosuppression load scores reduced significantly. Due to the limited case numbers, literature reviews of anti-TNF-alpha therapy for refractory JBD were conducted, which had a total 18 JBD patients receiving anti-TNF-alpha therapy, of which fifteen patients had favorable outcomes after treatment with minimal side effects., Conclusions: Anti-TNF-alpha therapy may be necessary for JBD patients with refractory disease courses. Anti-TNF-alpha therapy was effective and safe in these patients, especially regarding its corticosteroid- and immunosuppressive drug-sparing effects.

Background/aim: Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC., Materials and Methods: This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method., Results: Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype., Conclusion: We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Gefitinib, erlotinib and afatinib are approved for first-line treatment of advanced non-small cell lung cancer (NSCLC) bearing an activating epidermal growth factor receptor (EGFR) mutation. However, the clinical outcomes among the three EGFR tyrosine kinase inhibitors (TKIs) are still controversial. We aimed to evaluate clinical outcomes and secondary EGFR T790M mutation among the three EGFR TKIs. From May 2014 to January 2016, a total of 301 patients received treatment with gefitinib, erlotinib or afatinib, for first-line treatment of advanced NSCLC with an activating EGFR mutation, based on their clinicians' choice. The median overall survival (OS) was 37.0 months. Although the baseline characteristics of patients were unequal, progression-free survival and OS did not differ among the 3 groups. Multivariate analysis found that gefitinib (adjusted odds ratio [aOR] 3.29, 95% confidence interval [CI], 1.15-9.46, p = 0.027), EGFR TKI treatment duration more than 13 months (aOR 3.16, 95% CI, 1.20-8.33, p = 0.020), male (aOR 3.25, 95% CI, 1.10-9.66, p = 0.034), initial liver metastasis (aOR 4.97, 95% CI 1.18-20.96, p = 0.029) and uncommon EGFR mutation (aOR 0.14, 95% CI, 0.02-0.97, compared to EGFR deletion 19, p = 0.047) were independent factors for secondary T790M mutation. In real-world practice, choosing first line EGFR TKI based on the patients' clinical characteristics yielded good clinical outcomes. First-line gefitinib, longer EGFR TKI treatment duration, male, initial liver metastasis and uncommon EGFR mutations may be independent factors for secondary EGFR T790M mutation., (© 2018 UICC.)

Background: Childhood asthma comprises different phenotypes with complex pathophysiology. Different asthma phenotypes evoke various clinical symptoms and vary in their responses to treatments., Methods: We applied k-means clustering algorithm of twelve objective laboratory tests among 351 asthmatic children enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We constructed gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with different asthma phenotypes., Results: Five distinct phenotypes of childhood asthma were identified and can be characterized by either eosinophil-predominant or neutrophil-predominant inflammatory characteristics. In the gene expression profile analysis, significant differences were noted for neutrophil-predominant asthma, compared with samples from all the other asthma phenotypes. The vast majority of the differentially expressed genes in neutrophil-predominant asthma was associated with corticosteroid response. From an independent inhaled corticosteroid (ICS) response cohort, we also found neutrophils could be activated in this severe asthma phenotype and neutrophil-predominant asthma may be associated with corticosteroid nonresponsiveness., Conclusion: Phenotype clustering of childhood asthma can be helpful to identify clinically relevant patients and reveal different inflammatory characteristics in asthmatic children. Neutrophil-predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Gene expression profile of different asthma phenotypes not only improve our knowledge of childhood asthma, but also can guide asthma precision medicine., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background and Aims: We aimed at developing a novel risk prediction model for death from cardiovascular disease (CVD) for Chinese individuals, based upon a large cohort from Taiwan., Methods: This Chinese cohort came from Taiwan, with 381,963 individuals free from CVD, recruited from a private health surveillance program. With a median follow-up of 8.8 years, 1894 CVD deaths out of a total of 10,829 deaths were identified by linking cohort ID with the National Death File., Results: A novel CVD death risk prediction model for Chinese individuals was established from this cohort. An increase in the resting heart rate was the statistically independent predictor in this model. The discriminatory accuracy was measured by generating the receiver operating characteristic (ROC) curve, and the area under the ROC curve was 0.913 (95% CI = 0.907 to 0.920)., Conclusions: A novel cardiovascular death prediction model with high predictability for Chinese individuals was demonstrated in the present study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Dental radiography plays an important role in clinical diagnosis, treatment and surgery. In recent years, efforts have been made on developing computerized dental X-ray image analysis systems for clinical usages. A novel framework for objective evaluation of automatic dental radiography analysis algorithms has been established under the auspices of the IEEE International Symposium on Biomedical Imaging 2015 Bitewing Radiography Caries Detection Challenge and Cephalometric X-ray Image Analysis Challenge. In this article, we present the datasets, methods and results of the challenge and lay down the principles for future uses of this benchmark. The main contributions of the challenge include the creation of the dental anatomy data repository of bitewing radiographs, the creation of the anatomical abnormality classification data repository of cephalometric radiographs, and the definition of objective quantitative evaluation for comparison and ranking of the algorithms. With this benchmark, seven automatic methods for analysing cephalometric X-ray image and two automatic methods for detecting bitewing radiography caries have been compared, and detailed quantitative evaluation results are presented in this paper. Based on the quantitative evaluation results, we believe automatic dental radiography analysis is still a challenging and unsolved problem. The datasets and the evaluation software will be made available to the research community, further encouraging future developments in this field. (http://www-o.ntust.edu.tw/~cweiwang/ISBI2015/)., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing., Methods: The study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5-15 quids of BQ a day. Physical activity of each individual, based on "MET-hour/week", was classified as "inactive" or "active", where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated., Results: Nearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing., Conclusions: Chewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan.

Objective: The anti-inflammatory and cardiovascular protective effects of statin for patients with systemic lupus erythematosus (SLE) are not clear. We tested the hypothesis that statin use is associated with reduced mortality and morbidity in SLE patients with hyperlipidemia., Methods: We included 4095 patients with SLE and hyperlipidemia from the entire population using the Taiwan National Health Insurance Research Database between 1997 and 2008. A total of 935 matching sets (1:2) of patients who had never used lipid-lowering medications and statin users were included in the nested matched cohort. Cox proportional hazards regression was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between statin and all-cause mortality, coronary artery disease (CAD), cerebrovascular disease (CVD) and end-stage renal disease (ESRD), conditional for matching sets in the matched cohort., Results: The multivariate adjusted hazard ratios (HR) for statin users, as compared with patients had never used lipid-lowering medications, were 0.67 (95% CI, 0.54 to 0.83) for death from any cause. High-dose statins (>365 cumulative defined daily dose) significantly reduced risk of all-cause mortality (HR 0.44, 95% CI 0.32 to 0.60); CAD (HR 0.20, 95% CI 0.13 to 0.31); CVD (HR 0.14, 95% CI 0.08 to 0.25); and ESRD (HR 0.22, 95% CI, 0.16 to 0.29), with similar results in the nested matched study., Conclusion: Statin therapy in SLE patients with hyperlipidemia may reduce the risk of mortality, cardiovascular disease and ESRD. The effect of statins needs to be demonstrated in large prospective studies with long-term follow-up., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: Limited information is available regarding long-term effects of air pollution on blood pressure (BP) and hypertension., Objective: We studied whether 1-year exposures to particulate matter (PM) and nitrogen oxides (NOx) were correlated with BP and hypertension in the elderly., Methods: We analyzed cross-sectional data from 27,752 Taipei City residents > 65 years of age who participated in a health examination program in 2009. Land-use regression models were used to estimate participants' 1-year exposures to particulate matter with aerodynamic diameter ≤ 10 μm (PM10), coarse particles (PM2.5-10), fine particles (≤ 2.5 μm; PM2.5), PM2.5 absorbance, NOx, and nitrogen dioxide (NO2). Generalized linear regressions and logistic regressions were used to examine the association between air pollution and BP and hypertension, respectively., Results: Diastolic BP was associated with 1-year exposures to air pollution, with estimates of 0.73 [95% confidence interval (CI): 0.44, 1.03], 0.46 (95% CI: 0.30, 0.63), 0.62 (95% CI: 0.24, 0.99), 0.34 (95% CI: 0.19, 0.50), and 0.65 (95% CI: 0.44, 0.85) mmHg for PM10 (10 μg/m3), PM2.5-10 (5 μg/m3), PM2.5 absorbance (10-5/m), NOx (20 μg/m3), and NO2 (10 μg/m3), respectively. PM2.5 was not associated with diastolic BP, and none of the air pollutants was associated with systolic BP. Associations of diastolic BP with PM10 and PM2.5 absorbance were stronger among participants with hypertension, diabetes, or a body mass index ≥ 25 kg/m2 than among participants without these conditions. One-year air pollution exposures were not associated with hypertension., Conclusions: One-year exposures to PM10, PM2.5-10, PM2.5 absorbance, and NOx were associated with higher diastolic BP in elderly residents of Taipei.

Objectives: Differential diagnosis is essential, since secondary headache due to paranasal sinus lesions are similar in headache characteristics to primary headache. However, since patients visiting the emergency department due to acute severe headache are primarily treated by neurologists, paranasal sinuses lesions and anatomical variations of the nasal cavity causing the headache are commonly overlooked because of the clinician's lack of knowledge about rhinosinugenic headache. This study investigated the prevalence of paranasal sinus lesions and anatomical variations that may cause secondary headaches in patients who were diagnosed as primary headache and treated by neurologists in the emergency room., Methods: A retrospective study was done involving 1235 patients who visited the emergency department from January 2008 to December 2012 and who were diagnosed with primary headache. From the axial view of brain computed tomography, examination of sinusitis, mucosal contact points, concha bullosa, isolated sphenoid lesion, and osteoma were done, and location and morphology was analyzed., Methods: Three hundred fifty-five of 1235 (28.7%) patients had sinusitis, mucosal contact points, concha bullosa, isolated sphenoid lesion, and osteoma as possible causes for secondary headaches., Conclusion: Differential diagnosis of primary headaches requires knowledge of paranasal sinus lesions including rhinosinusitis or anatomical variations. Also, interdisciplinary evaluation of acute headache presenting to the emergency room is necessary for accurate diagnosis and proper management.

Background/purpose: Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis in children. It is considered to be an IgA-containing immune complex-mediated disease. Chemokines are small secreted proteins that attract leukocytes during inflammation. Our aim was to determine the serum levels of chemokines and investigate the association of chemokine gene polymorphisms with childhood HSP., Methods: Serum levels of chemokines (interleukin-8/CXCL8, MCP-1/CCL2, RANTES/CCL5, MIG/CXCL9, and IP-10/CXCL10) were determined using cytometric beads arrays. We investigated the association of three single-nucleotide polymorphisms (SNPs) MCP1/CCL2 -2518C/T, RANTES/CCL5 -403C/T, and RANTES/CCL5 -28C/G with HSP in 85 HSP patients and 136 healthy controls., Results: Five serum chemokine levels were significantly elevated in patients with the acute stage of HSP compared to the normal controls (p < 0.05). MCP1/CCL2 -2518 TT genotype and T allele were associated with the risk for HSP with OR (95% CI) 3.32 (1.45-7.59) and 1.78 (1.20-2.64), respectively. The RANTES/CCL5 -28 GG genotype was associated with a significantly lower percentage of corticosteroid usage and lower corticosteroid accumulative dose in HSP patients. RANTES/CCL5 -403 TC and TT genotype were significantly associated with renal manifestations with an OR (95% CI) of 4.33 (1.44-12.99), adjusted for sex and age and the other two SNP genotypes., Conclusion: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis., (Copyright © 2013. Published by Elsevier B.V.)

Background: Juvenile dermatomyositis is a rare childhood multisystem autoimmune disease involving primarily the skin and muscles, and it may lead to long-term disability. This study aimed to describe the clinical course of juvenile dermatomyositis and determine if any early clinical or laboratory features could predict outcome., Methods: Medical charts of patients aged ≤18 years and diagnosed with juvenile dermatomyositis (according to the criteria of Bohan and Peter) at the Pediatric Department, National Taiwan University Hospital, between 1989 and 2009 were reviewed. The endpoints for disease assessment were complete clinical response and complete clinical remission. Cox's proportional hazards model was fitted to identify important predictors of complete clinical remission., Results: A total of 39 patients with juvenile dermatomyositis were reviewed. Two-thirds were females, and the mean age at disease onset was 81.97 ± 46.63 months. The most common initial presentations were Gottron's papule (82.1%) and muscle weakness (82.1%). After excluding one patient with an incomplete record, the remaining 31 patients who had muscle weakness were analyzed; among them, 22 (70.97%) achieved complete clinical response, but only six (19.4%) achieved complete clinical remission. Multivariate analysis showed that female sex, negative Gowers' sign at disease onset, and positive photosensitivity at disease onset were favorable factors to achieve complete clinical remission. Moreover, covariate-adjusted survival curves were drawn for making predictions of complete clinical remission. Only 13 (33.33%) patients were symptom free at the end of follow up, whereas the other 26 suffered from different kinds of complications. None of them developed malignancy, but two (5.13%) patients died during the follow-up period., Conclusion: Factors such as male sex and Gowers' sign were unlikely to favor the achievement of complete clinical remission in juvenile dermatomyositis. Certain complications cannot be avoided, and thus more effective treatments and monitoring strategies are needed for better control of juvenile dermatomyositis., (Copyright © 2014. Published by Elsevier B.V.)

Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by elevated or normal serum IgM and decreased IgG, IgA, and IgE due to defective immunoglobulin class switching. X-linked HIGM (XHIGM, HIGM1) is the most frequent type, is caused by mutations in the CD40 ligand gene, and is regarded as a combined T and B immunodeficiency. We report an 18-year-old male who was diagnosed initially with hypogammaglobulinemia in infancy, but developed repeated pneumonia, sepsis, cellulitis, perianal abscess, pericarditis, and bronchiectasis despite regular intravenous immunoglobulin replacement therapy. The patient died at age 18 years due to pneumonia and tension pneumothorax. Mutation analysis revealed CD40L gene mutation within Exon 5 at nucleotide position 476 (cDNA 476G > A). This nonsense mutation predicted a tryptophan codon (TGG) change to a stop codon (TGA) at position 140 (W140X), preventing CD40L protein expression. Sequence analysis in the family confirmed a de novo mutation. The second case of 6-month-old male infant presented as Pneumocystis jiroveci pneumonia and acute respiratory distress syndrome. Gene analysis of the CD40L gene revealed G to C substitution in Intron 4 (c.409 + 5G > C) and mother was a carrier. Hematopoietic stem cell transplantation, the only cure for XHIGM, was arranged in the second case., (Copyright © 2012. Published by Elsevier B.V.)

This study aimed to characterize the manifestations of clinical symptoms and signs, primary rheumatic diseases, and other autoantibodies in pediatric patients with positive anti-SSA and/or anti-SSB antibodies. Subjects under age 18 with positive anti-SSA and/or anti-SSB antibodies were screened and enrolled in a tertiary hospital in Taiwan. Data were collected via medical records,including age, gender, onset of the primary rheumatic disease, clinical symptoms and signs, and the medication used. Schirmer test for Sjögren's syndrome (SS) screening was performed in all enrolled patients. Among twenty enrolled subjects, seventeen of them had systemic lupus erythematosus; four of them were diagnosed as SS with positive Schirmer test. In addition to antinuclear antibodies and anti-DNA antibodies, other common autoantibodies were anti-RNP antibodies (50 %) and anti-Sm antibodies(30 %). The most common symptoms were arthritis (60 %)followed by malar rash (40 %). In conclusion, we observed that a low proportion of childhood SS (4/20) exists in our patients with positive SSA and/or anti-SSB antibodies. It is suggested that clinicians should focus more on the clinical symptoms in these patients, rather than undertaking invasive diagnostic interventions to rule out Sjögren's syndrome.

Background: Cow's milk allergy is the first manifestation of the allergic march, because cow's milk proteins are the first foreign proteins consumed in large quantities by infants. The aim of this study was to determine which of these proteins causes the greatest sensitization in Taiwanese individuals, and its correlation with atopic patients., Methods: We retrospectively reviewed the medical records of atopic patients who were treated at the National Taiwan University Hospital from January 2009 to March 2011. A total of 190 patients were enrolled and tested for isolated cow's milk protein (α-lactalbumin, β-lactoglobulin, and casein) sensitization. These patients were further divided into atopic dermatitis and non-atopic dermatitis subgroups, and also grouped by age. Differences in sensitization to cow's milk proteins between groups were analyzed using the non-parametric Mann-Whitney U-test., Results: The sensitization rate to α-lactalbumin-specific IgE was 60%, followed by β-lactoglobulin (46.84%) and casein (40.53%). The levels of specific IgE antibodies against α-lactalbumin, β-lactoglobulin, and casein were higher in patients with atopic dermatitis (1.8, 1.19, 0.95 vs. 0.77, 0.55, 0.40 kUA/L). The younger age group had higher mean specific IgE antibodies against cow's milk proteins than the older age groups., Conclusion: There was a different distribution of cow's milk protein sensitization in Taiwanese patients in our study, with α-lactalbumin being most common as compared to casein in Western countries. Among the patients with cow's milk sensitization, the atopic dermatitis group had significantly higher cow's milk protein-specific IgE antibodies as compared to the non-atopic dermatitis group., (Copyright © 2012. Published by Elsevier B.V.)

This study is conducted to characterize the intra-urban distribution of NOx and NO2; develop land use regression (LUR) models to assess outdoor NOx and NO2 concentrations, using the ESCAPE modeling approach with locally specific land use data; and compare NOx and NO2 exposures for children in the Taipei Metropolis by the LUR models, the nearest monitoring station, and kriging methods based on data collected at the measurement sites. NOx and NO2 were measured for 2 weeks during 3 seasons at 40 sampling sites by Ogawa passive badges to represent their concentrations at urban backgrounds and streets from October 2009 to September 2010. Land use data and traffic-related information in different buffer zones were combined with measured concentrations to derive LUR models using supervised forward stepwise multiple regressions. The annual average concentrations of NOx and NO2 in Taipei were 72.4 ± 22.5 and 48.9 ± 12.2 μg/m(3), respectively, which were at the high end of all 36 European areas in the ESCAPE project. Spatial contrasts in Taipei were lower than those of the European areas in the ESCAPE project. The NOx LUR model included 6 land use variables, which were lengths of major roads within 25 m, 25-50 m, and 50-500 m, urban green areas within 300 m and 300-5,000 m, and semi-natural and forested areas within 500 m, with R(2)=0.81. The NO2 LUR model included 4 land use variables, which were lengths of major roads within 25 m, urban green areas within 100 m, semi-natural and forested areas within 500 m, and low-density residential area within 500 m, with R(2)=0.74. The LUR models gave a wider variation in estimating NOx and NO2 exposures than either the ordinary kriging method or the nearest measurement site did for the children of Taiwan Birth Cohort Study (TBCS) in Taipei., (Copyright © 2013. Published by Elsevier B.V.)

Objective: The incidence and prevalence of juvenile idiopathic arthritis (JIA) vary widely across the world but data in East Asia is lacking. Uveitis is a serious cause of morbidity in JIA. This study aimed to analyze the incidence and prevalence of JIA, and the characteristics of JIA-associated uveitis in Taiwan., Methods: A population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. Each patient was individually tracked from 1999 to 2009 to identify the diagnosis of JIA and uveitis using the International Classification of Diseases diagnostic codes. Multivariate logistic regression was used to determine the risk factors and complications of uveitis in patients with JIA., Results: The study cohort had 2636 cases of JIA and included juvenile rheumatoid arthritis (57.7%), enthesitis-related arthritis (ERA) (39.2%), and psoriatic arthritis (3.1%). The average annual incidence of JIA and JIA-associated uveitis were 4.93 (range, 3.93-6.23) and 0.25 (range, 0.12-0.37) cases per 100,000 population, respectively. The average period prevalence of JIA was 33.8 cases per 100,000 population. Uveitis occurred in 4.7% of patients with JIA, while JIA-associated uveitis was complicated by cataract (11.2%) and glaucoma (24.8%). Enthesitis-related arthritis was significantly associated with uveitis (OR: 3.47; 95% CI: 2.24-5.37) (p<0.0001). Uveitis diagnosed before JIA was the most significant risk factor for complications of glaucoma or cataract (OR: 3.54; 95% CI: 1.44-8.72) (p = 0.006)., Conclusions: The incidence of JIA is low but that of JIA-associated uveitis is increasing. Higher percentage of males in patients with ERA and the strong association between ERA and uveitis are unique for children with JIA in Taiwan. Uveitis diagnosed before arthritis is an important risk factor for complications. Continuous ophthalmologic follow-up is needed for children with JIA or uveitis of unknown etiology.

Objective: To clarify the epidemiology of asthma admission in a nationwide survey, we analyze the characteristics of hospitalized patients in Taiwan., Methods: Data regarding asthma-associated hospitalizations were obtained from the National Health Insurance Research Database of Taiwan from January 2001 to December 2002. Patient characteristics in terms of severity, mortality, and cost were stratified by age, gender, and presence of comorbidities., Results: A total of 59,983 hospitalizations with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 493.xx and asthma-related treatment were included in the current analysis. When stratified by age, the number and duration of hospitalizations were distributed in J-shape distribution, with the nadir located in the range of 8-18 years of age. The severity of asthma was found to increase with age (p < 0.001) and was more severe in men compared with women (p < 0.001). The severity of in-hospital patients was significantly greater in subjects with underlying respiratory disease compared to patients with other comorbidities, such as cardiovascular disease and infectious disease. The mortality rates of all hospitalized asthma patients and pediatric hospitalized asthma patients were 0.77% and 0.02%, respectively. The risk factor for mortality of asthma was older age and male gender in multiple regression., Conclusion: The severity of asthma increased after 18 years of age. Increased comorbidities in elderly patients might contribute to asthma severity. The mortality rate was low in pediatric patients and significantly increased in males and the elderly. The above findings suggest that additional effort is required in the treatment of elderly and male asthmatic patients., (Copyright © 2013. Published by Elsevier B.V.)

Objective: Gastrointestinal (GI) involvement in childhood Behçet disease (BD) is not well understood. We aimed to clarify the intestinal presentation in children with BD., Methods: Medical records of 85 children with recurrent oral ulcers between 1990 and 2010 at the National Taiwan University Hospital were reviewed retrospectively. Twenty of them who fulfilled the Mason and Barnes criteria for the diagnosis of childhood BD were enrolled. The clinical and laboratory characteristics were analyzed., Results: Among 20 patients, the median age at diagnosis was 13.2 years. The common presentations included oral ulcers (100%), genital ulcers (70%), skin lesions (65%), and GI symptoms (50%). Five of 10 patients with GI symptoms received endoscopic examinations and all had ulcers. Divided by the age of 10, patients younger than 10 years tended to have higher rates of GI symptoms initially and intestinal ulcers (P = 0.002 and 0.015, respectively). Platelet count was significantly lower in young patients (P = 0.0151). Patients without GI symptoms had higher rates of skin involvement than patients with GI symptoms (P = 0.019)., Conclusions: Young children with BD tended to have more GI presentations. For children with BD younger than 10 years having GI symptoms, endoscopic examinations may be considered.

The aim of the present study was to estimate the wall effect of the self-made spherical graphite-walled cavity chamber with the Monte Carlo method for establishing the air-kerma primary standard of high-dose-rate (HDR) ¹⁹²Ir brachytherapy sources at the Institute of Nuclear Energy Research (INER, Taiwan). The Monte Carlo method established in this paper was also employed to respectively simulate wall correction factors of the ¹⁹²Ir air-kerma standard chambers used at the National Institute of Standards and Technology (NIST, USA) and the National Physical Laboratory (NPL, UK) for comparisons and verification. The chamber wall correction calculation results will be incorporated into INER's HDR ¹⁹²Ir primary standard in the future. For the brachytherapy treatment in the esophagus or in the bronchi, the position of the isotope may have displacement in the cavity. Thus the delivered dose would differ from the prescribed dose in the treatment plan. We also tried assessing dose distribution due to the position displacement of HDR ¹⁹²Ir brachytherapy source in a phantom with a central cavity by the Monte Carlo method. The calculated results could offer a clinical reference for the brachytherapy within the human organs with cavity.

Background/purpose: Single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) gene are associated with allergic diseases in different populations. This study aimed to determine the distribution of two SNPs at -1082A/G and -592A/C (rs1800896 and rs1800872, respectively) in the IL-10 gene promoter of Taiwanese food allergy (FA) patients, and also to compare the serum IL-10 levels between patients with (FA) and controls., Methods: Thirty-seven patients with FA and 52 controls were enrolled, and their peripheral blood was collected for IL-10 SNP genotyping and the corresponding serum IL-10 level of each genotype., Results: The thirty-seven FA patients had positive food-specific IgE (≥ 0.75kU/L) to more than one food, and the most frequent allergens wereshrimp and crab (56.8% and 35.1%, respectively). The genotype distributions in the FA patients compared to the control group were AA and AG at -1082A/G (86.5% and 13.5% vs. 86.6% and 13.4%, respectively), and AA, AC, and CC at -592A/C (45.9%, 43.3% and 10.8% vs. 38.5%, 48.1% and 13.4%, respectively). Serum IL-10 levels were significantly lower in the FA group than in the control group (p=0.0187), and the IL-10 level of -592A/C of genotype AA was significantly lower than that of the other genotypes (AC+CC) (p=0.007). Patients with AA/AA haplotype homozygotes (10 of 24) had significantly lower serum IL-10 levels than those with other haplotypes., Conclusions: The two SNPs at -1082A/G and -592A/C of IL-10 were associated with FA in our Taiwanese population, and FA patients with the genotype AA/AA haplotype homozygotes had lower serum IL-10 levels. This suggests that IL-10 might play a critical role in the pathogenesis of FA. We suggest that it may be practicable to evaluate the serum IL-10 levels of FA patients and to predict the possibility of FA if genotypes and haplotypes are checked regularly., (Copyright © 2012. Published by Elsevier B.V.)

Background/purpose: The diagnosis of systemic onset juvenile idiopathic arthritis (SoJIA) on disease onset is challenging and made mainly by exclusion. This study aimed to investigate the initial clinical and laboratory features of children with SoJIA in Taiwan., Methods: Patients diagnosed with SoJIA at the National Taiwan University Hospital between 1997 and 2007 were evaluated and data were collected by retrospective chart review. Inferential statistics were used to compare features of patients with steroid use for <6 months or >6 months., Results: Twenty-eight (28) patients (13 boys and 15 girls) were included in this study. The mean age of onset was 8.7 years old. The most common presentations were fever (100%), arthritis (89.3%), and skin rash (67.9%). The patterns of arthritis in affected patients were 50% oligoarticular type and 39% polyarticular type. The most common joints involved were the knee (76% of patients with arthritis), ankle (56%), and elbow and proximal interphalangeal joints (28%). The most common pattern of fever during first week was intermittent (53%). Prolonged use of steroid was associated with leukocytosis (17.63±7.71 vs. 11.93±4.43×10(9) leukocytes/L, p<0.05) and higher aspartate aminotransferase (89.4 vs. 31.2 U/L, p<0.05) on initial presentation., Conclusion: In SoJIA, extra-articular features such as fever, rash, and lymphadenopathy are most prominent. Leukocytosis and polyarticular pattern on presentation may indicate a refractory clinical course., (Copyright © 2012. Published by Elsevier B.V.)

Background: The PEARL study showed that the proportion of psoriasis patients achieving the primary endpoint (at least 75% improvement from baseline to week 12 in the Psoriasis Area and Severity Index) was significantly higher in ustekinumab-treated patients compared with placebo. There is a paucity of data regarding the impact of psoriasis and its treatment on health-related quality of life (HRQoL) in Asian patients., Objectives: To evaluate the effect of ustekinumab on HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis enrolled in the phase III, randomized, double-blind, placebo-controlled PEARL study., Methods: In the PEARL study, 121 patients were randomized to receive ustekinumab 45 mg at weeks 0, 4, and 16 (n=61) or placebo at weeks 0 and 4 with crossover to ustekinumab at weeks 12 and 16 (n=60). A major secondary endpoint was the change in Dermatology Life Quality Index (DLQI) from baseline at week 12. Other endpoints included the change in individual DLQI domains, proportion of patients achieving DLQI ≤ 1 (no negative effect), and proportion of patients achieving ≥ 5-point reduction in DLQI (clinically meaningful improvement) at week 12., Results: At baseline, psoriasis had a very large effect on HRQoL (average DLQI, 15.7). At week 12, patients treated with ustekinumab 45 mg had significantly greater improvement from baseline in DLQI scores compared with placebo (mean decrease, 11.2 vs 0.5 (P<0.001). Likewise, 32.2% and 1.7% of patients receiving ustekinumab 45 mg and placebo, respectively, achieved a DLQI ≤ 1, and 81.4% and 18.3% achieved ≥ 5-point reduction (both P<0.001 vs placebo). Individual DLQI domains in the ustekinumab group were significantly improved compared with placebo (P<0.001). For ustekinumab-randomized patients, HRQoL improvements were sustained through week 28. Placebo patients who crossed over to ustekinumab experienced similar improvements compared with those randomized to ustekinumab., Conclusions: Ustekinumab significantly improves HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis.

Background/purpose: To investigate the clinical manifestations, disease activity and prognosis in different types of vasculitis., Methods: The charts of pediatric patients with vasculitis diagnosed from December 1997 to December 2007 were retrospectively reviewed. The first clinical manifestations and laboratory results were recorded at the time of diagnosis, and outcome evaluations with history of flare-ups were analyzed., Results: A total of 508 vasculitis patients were included in this study, of whom 124 had Henoch-Schönlein purpura (HSP), and 351 had Kawasaki disease (KD). Hematuria was observed in 79% of recurrent HSP patients at the time of diagnosis, and was associated with an increased risk of relapse (p = 0.000). In Kawasaki disease, the clinical symptoms with erythematous changes in Bacille Calmette-Guérin scars and coronary artery dilatation were more prominent in patients younger than 1 year old, and lymphadenopathy was more common in patients older than 1 year old (p = 0.001). The risk of coronary dilatation was significant in the patients with an initial presentation of thrombocytosis, and greater in patients younger than 1 year old (p = 0.027). Thrombocytopenia was more prominent in vasculitis-associated autoimmune diseases. Marked lymphocytosis with increased C-reactive protein levels was significantly noted in urticarial vasculitis patients compared with HSP patients in multivariate logistic regression analysis., Conclusion: Vasculitis disease activity and prognosis were associated with initial laboratory results and clinical manifestations. Further large-scale clinical trials are warranted to validate these findings., (Copyright © 2011. Published by Elsevier B.V.)

This paper describes the establishment by the Institute of Nuclear Energy Research (INER, Taiwan) of the reference air kerma rate (RAKR) calibration standard for measurement of high-dose rate (HDR) (192)Ir brachytherapy source strength. A bilateral comparison has been made in the RAKR standards for HDR (192)Ir brachytherapy sources at the INER and Physikalisch-Technische Bundesanstalt (PTB, Germany) and the measurement difference was within the overall standard uncertainty and showed good agreement between the two calibration standard systems established at the INER and the PTB. Besides, INER also worked with 20 domestic hospitals to organise an on-site measurement comparison programme to explore the status of HDR (192)Ir brachytherapy source strength determination in Taiwan. The comparison results presented the ratios of RAKR with vendor values, as determined by INER and hospitals from the programme. The ratios fall in all cases within the ± 3 % guaranteed by the vendors for a coverage factor of k = 2 or at 95 % confidence level.

Background: The antinuclear antibody (ANA) test is the most commonly used test to screen for autoimmune diseases. However, only a limited numbers of studies have addressed the characteristics of patients positive for ANA. In this study, we aimed to clarify the relationship between initial presentations, ANA titer, and final diagnoses., Methods: Patients who visited National Taiwan University Hospital and received a first ANA test were enrolled and then followed for a further 6 months. The symptoms and signs at the time of ANA testing, ANA titers, and the final diagnoses were recorded and analyzed., Results: A total of 355 patients were positive for ANA. Joint pain was the most common initial presentation at the time of ANA testing. Compared with the patients with low ANA titers (<1:640), those with high ANA titers (≥ 1:640) were more susceptible to autoimmune diseases. More importantly, of the patients with initial presentations of joint pain, fever, abnormal urinalysis, or skin rash/skin tightness, autoimmune diseases were more frequently diagnosed in those with high ANA titers than with low ANA titers (p<0.05). In addition, both anti-double strand DNA antibodies and anti-extractable nuclear antibodies were more commonly detected in patients with high ANA titers., Conclusions: A high ANA titer seems to be a useful biomarker for the diagnosis of autoimmune diseases, especially for patients presenting with joint pain, fever, abnormal urinalysis, or skin rash/skin tightness., (Copyright © 2011. Published by Elsevier B.V.)

Background/purpose: The aim of the study was to investigate the clinical characteristics and nutritional status of juvenile rheumatoid arthritis (JRA) in Taiwanese children., Methods: Fifty-three patients were included in this study. The disease subtype and patient characteristics were recorded. Body mass index (BMI) was determined. Seventy-five healthy age-matched children served as a control group., Results: The inflammation parameters, including white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate, were elevated in the systemic group. The BMI level of the JRA group was significantly lower than the control group (p = 0.006), especially in the male patients (p = 0.016) and when the patient age was greater than 4 (p = 0.011). The patients with oligoarticular onset JRA had significantly lower BMI compared with the healthy control group (p = 0.012)., Conclusion: Nutritional status is often impaired in patients with JRA. The BMI of the JRA patients was lower than that of age-matched healthy children, especially in the male group, and when disease onset age was greater than 4. In our unselected sample, the most affected disease subtype was oligoarticular onset JRA., (Copyright 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to investigate the initial clinical manifestations, laboratory data, complications, and outcomes of patients with pediatric-onset mixed connective tissue disease (MCTD) in Taiwan. We reviewed medical charts of patients younger than 18 years with a diagnosis of mixed connective tissue disease based on the criteria of Kasukawa (1) at the pediatric department of National Taiwan University Hospital from 1993 to 2008. A total of 12 patients were included. All of the patients were female. The mean age at disease onset was 10.7 years (range 6.5 to 14 years). The most common symptoms at disease onset were polyarthritis (7/12 patients) and Raynaud's phenomenon (7/12 patients). The clinical symptoms changed with time, and other symptoms encompassing the criteria for MCTD developed sequentially. Inflammatory manifestations (arthritis, fever, and skin rash) improved following treatment, whereas sclerodermatous features (sclerodactyly, esophageal disease, and vasculopathy) persisted and were often unresponsive to therapy. The organ involvement-free rates at 2 years, 5 years, and 10 years were 91.7%, 78.6%, and 52.4%, respectively. In this retrospective study, sclerodermatous changes of internal organs were a poor prognostic factor in our population, and we emphasize that long-term follow-up is necessary, and appropriate treatment should be applied to improve the outcomes.

Background and Purpose: The purpose of this study was to analyze the clinical course and outcomes of children with status asthmaticus treated in a pediatric intensive care unit (PICU) in Taiwan., Methods: The medical charts of all patients aged from 2 to 18 years with status asthmaticus who were admitted to the PICU National Taiwan University Hospital, Taipei, Taiwan, from 1990 to 2006 were reviewed retrospectively., Results: Twenty eight children were admitted on 33 occasions; 4 patients had more than 1 admission. The mean age was 6.23 years (range, 2-17 years). No control medication was regularly used prior to admission for 81.8% of the episodes. The mean PICU stay was 2.55 days (range, 1-13 days) and, for 78.8% of episodes, the patients were discharged from the ICU within 2 days. For 11 episodes (33.3%), the patients required mechanical ventilation for a mean duration of 3.6 days. The mortality rate was 3.3% (n = 1). Complications included bronchopneumonia (57.6%), hemodynamic compromise (9.1%), neurologic symptoms (6.1%), and air leak (3.3%). Patients requiring mechanical ventilation had significantly lower initial pulse oximeter oxygen saturation (<90%), lower blood gas pH (<7.25), higher partial pressure of carbon dioxide, and longer duration of PICU and hospital stay (p < 0.05) when compared with patients not requiring mechanical ventilation. For patients with a history of repeated PICU admissions for asthma, the intubation rate was 77.7%., Conclusions: The prognosis for childhood status asthmaticus is favorable. The most common trigger factors were respiratory tract infection and poor asthma control.

Background and Purpose: Primary hypogammaglobulinemia has been proposed to be associated with an increased incidence of allergic diseases, but the correlation between the clinical presentation and the serum immunoglobulin E (IgE) level has not been studied in this patient group. This study investigated the correlation of IgE levels and allergic condition in patients with primary hypogammaglobulinemia., Methods: Thirty five patients with primary hypogammaglobulinemia were enrolled from September 2004 to March 2005. Serum IgE levels were measured at clinic follow-up. Information regarding the patient's history of allergic diseases, including atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and asthma, were collected from chart review and clinic interviews., Results: Significantly lower mean +/- standard deviation serum IgE levels were found in allergic patients with primary hypogammaglobulinemia (123.9 +/- 148.8 IU/mL) than in the healthy control group (376.2 +/- 471.7 IU/mL) [p < 0.005] or in allergic patients without primary hypogammaglobulinemia (544.1 +/- 309.1 IU/mL) [p < 0.001]., Conclusions: Serum IgE level is not a suitable diagnostic criterion or treatment guide for allergy in patients with primary hypogammaglobulinemia.

Respiratory syncytial virus (RSV) bronchiolitis in early life is a risk factor for later development of asthma and atopy. Ribavirin is the only effective drug currently available against acute RSV bronchiolitis. However, the long-term effects of ribavirin remain unclear. We investigated a cohort of children hospitalized with RSV bronchiolitis from when they were under 2 yr old until they reached a mean age of 6.2 yr. In total, we enrolled 175 children in this study. Both the group treated with ribavirin and the group not treated with ribavirin included high-risk young children with congenital heart disease or chronic lung disease. Their respective age-matched controls, that we labeled groups A and B, both without ribavirin treatment, consisted of previously healthy subjects. Wheezing was either verified by physicians or estimated by a questionnaire. Allergen sensitization was judged by serum allergen-specific IgE levels. The cumulative incidence of physician-diagnosed asthma or recurrent wheezing in the ribavirin group (15%) was significantly lower than its incidence in the non-ribavirin-treated group (34%, p = 0.049), and in the control A group (43%, p = 0.005). Allergen sensitization was also least frequent in the ribavirin group. Ribavirin therapy was an independent factor in reducing the risk of developing asthma, asthma/recurrent wheezing, and sensitization to D. pteronyssinus/D. farinae. The long-term value of ribavirin for acute RSV bronchiolitis and its underlying mechanisms deserves further research.

Background: Cardiovascular diseases (CVDs) are the leading cause of death in most countries of the world. In this study, associations between CVDs and polymorphisms of angiotensin-converting enzyme (ACE), atrial natriuretic peptide (ANP), beta(2)-adrenal receptor (B2AR) and endothelial nitric oxide synthase (ENOS) genes were explored in a community-based setting., Methods: Between March and May 2001, 1740 subjects > or =35 years from the Matsu area in Taiwan were recruited to this study, representing 71.6% of the target population in Matsu. After informed consent was obtained during an interview, physical examination, resting ECG, serum biochemical profile and a questionnaire survey were used to obtain information. Genomic DNA was also collected and analyzed. Owing to technical limitations, 1186 samples were analyzed. Genetic polymorphisms of the genes in question were investigated using PCR and restriction fragment length polymorphism (RFLP). The distribution of allele frequencies for these genes was derived for stroke, coronary artery disease, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia and overweight subgroups., Results: The ENOS Glu298Asp polymorphism was associated with hypercholesterolemia (odds ratio 0.658, 95%CI 0.460-0.940; p=0.025) and the ACE D/I variant was associated with hypertriglyceridemia (odds ratio 0.722, 95%CI 0.536-0.973; p=0.033). Polymorphisms of the other genes were not associated with any of the disease groups., Conclusions: This community-based study reveals that genetic factors might play a role in the metabolism of lipids. The genetic risk for CVDs needs further investigation.

A case-control study was conducted to investigate the association between the consumption of local common foods that are rich in vitamin A and the risk of lung cancer in Taiwan. A total of 301 incident lung cancer cases, 602 hospital controls, and 602 neighborhood controls were recruited. The consumption of 13 food items and vitamin supplements was estimated by use of a food frequency questionnaire. The conditional logistic regression models were used to estimate the adjusted odds ratios (AOR) and 95% confidence intervals (CI) for lung cancer risk with each control group as reference by adjustment of covariates. A reduced risk for lung cancer was found to be associated with increased intakes of vitamin A, alpha-carotene, and beta-carotene from 13 food items. More servings of vegetables (AOR for the highest versus the lowest quartile = 0.67-0.70, 95% CI = 0.42-1.08, (plinear trend )= 0.04), garland chrysanthemum (AOR for the highest versus the lowest tertile = 0.58-0.74, 95% CI = 0.37-1.14, (plinear trend )<= 0.04) and sweet potato leaves (AOR for the highest versus the lowest tertile = 0.43-0.65, 95% CI = 0.28-0.96, (plinear trend )<= 0.03) were associated with the reduced risk for lung cancer. In conclusion, higher consumption of vitamin A-rich vegetables, especially garland chrysanthemum and sweet potato leaves might provide potential protection from lung cancer.

Eighty-eight patients' sera with allergen-specific IgE levels elevated only to food allergens were collected between October 1997 and March 2002 at the National Taiwan University Hospital. Thirty-three of the patients fulfilled the diagnostic criteria of asthma and were included. Most (72.7%) patients had elevated serum allergen-specific IgE levels only to one food allergen. The most common food allergens were milk and egg white. The patients with elevated soy bean-specific IgE levels had significantly higher levels of serum food allergen-specific IgE than those with either elevated milk or egg white-specific IgE levels. This study investigated some food allergen responses of asthmatic patients whose serum allergen-specific IgE levels were elevated only to food allergens. The results suggested that the allergic asthmatic response in our patients was most likely related to food rather than aeroallergens or fungal allergens.

Aims: To determine, by strain identification of Mycobacterium tuberculosis, whether transmission has occurred between individuals or whether new strains are present., Methods: A rapid protocol for random amplified polymorphic DNA (RAPD) analysis was developed. This protocol was applied to 64 strains of M tuberculosis that had been confirmed by culture and microbiological methods., Results: There are five groups of M tuberculosis prevalent in Taipei city, Taiwan. The major types are groups I and III. Groups I and II had been prevalent until the end of last year when, according to our group analysis, they had been eradicated. However, group III was continuously present from the middle of 1995 to the middle of 1996, and group IV was present at the end of both years, which indicated that both groups were transmitted continuously. These clustered strains had demographic characteristics consistent with a finding of transmission tuberculosis. Also, there were 13 of 64 strains with unique RAPD fingerprints that were inferred to be due primarily to the reactivation of infection. In the drug resistance analysis, the major type represented included group III and part of group IV., Conclusions: Our preliminary data imply, not only that the prevalence of M tuberculosis in Taipei city is due to transmission rather than reactivation, but that drug resistance also may play a role in tuberculosis transmission.