Search

Chun-Hao Chen,1 Ming-Chyi Huang,2 Yi-Hang Chiu,3 I-Ming Chen,1,4 Chun-Hsin Chen,3,5 Mong-Liang Lu,3,5 Tsung-Yang Wang,1 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 3Department of Psychiatry, Wan-Fang Hospital, Taipei, Taiwan; 4Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 5Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen, Department of Psychiatry, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, 10002, Taiwan, Tel +886-2-2312-3456 ext. 66787, Fax +886-2-2381-3208, Email hsichungchen@ntu.edu.twObjective: This study aimed to investigate the relationship between eveningness preference and poor sleep quality and eventually examine the moderation effect of stress susceptibility.Methods: Individuals with non-acute major depressive disorder or bipolar affective disorder and healthy participants were recruited. The Composite Scale of Morningness (CSM) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate chronotype and sleep quality, respectively. Eysenck Personality Questionnaire, Tridimensional Personality Questionnaire, Perceived Stress Scale, and Beck Anxiety Inventory were used to formulate stress susceptibility and as indicator variables for empirical clustering by latent class analysis (LCA). Linear regression models were used to examine the relationship between chronotype preference and sleep quality. The interaction terms of CSM and stress susceptibility were examined for the moderation effect.Results: A total of 887 individuals were enrolled in this study, with 68.2% female and 44.1% healthy participants. Three subgroups were derived from LCA and designated as low stresssusceptibility (40.2%), moderate stress susceptibility (40.9%), and high stress susceptibility (18.8%) groups. After controlling for covariates, the CSM scores inversely correlated with PSQI scores [b (se)=− 0.02 (0.01), p=0.01], suggesting that individuals with eveningness preferences tend to have poor sleep quality. Moreover, stress susceptibility moderated the relationship between CSM and PSQI scores (p for interaction term = 0.04). Specifically, the inverse association between CSM and PSQI was more robust in the high stress susceptibility group than that in the low stress susceptibility group.Conclusion: Eveningness preference was associated with poor sleep quality, and this relationship was moderated by stress susceptibility.Keywords: chronotype, empirical clustering, moderation effect, stress susceptibility, sleep quality

Meng-Jer Hsieh,1 Ning-Hung Chen,2 Shih-Lung Cheng,3,4 Chi-Wei Tao,5 Yu-Feng Wei,6,7 Yao-Kuang Wu,8 Ming-Cheng Chan,9,10 Shih-Feng Liu,11– 13 Wu-Huei Hsu,14 Tsung-Ming Yang,15 Ming-Shian Lin,16,17 Ching-Lung Liu,18 Ping-Hung Kuo,19 Ying-Huang Tsai1,20 1Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital and School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 4Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli, Taoyuan, Taiwan; 5Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 6School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 9Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 10National Chung Hsing University, Taichung, Taiwan; 11Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 13College of Medicine, Chang Gung University, Taoyuan, Taiwan; 14Critical Medical Center, China Medical University Hospital, Taichung, Taiwan; 15Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 16Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan; 17Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 18Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 19Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 20Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, People’s Republic of ChinaCorrespondence: Ying-Huang Tsai, Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, No. 5 Fu-Xin St, Kweishan District, Taoyuan, Taiwan, Email chestmed@cgmh.org.twBackground: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan.Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics.Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period.Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.Keywords: tiotropium/olodaterol, umeclidinium/vilanterol, indacaterol/glycopyrronium, LABA/LAMA therapy, Taiwan, cohort study, propensity score matching, chronic obstructive pulmonary disease, moderate-to-severe exacerbation

Hsi-Chung Chen,1,2 Nai-Wei Hsu,3– 5 Po-Jung Pan,6 Po-Hsiu Kuo,1,7 Meng-Yueh Chien,8 Pesus Chou9 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 3Division of Cardiology, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan; 4Department of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 5Public Health Bureau of Yilan County, Yilan, Taiwan; 6Department of Physical Medicine and Rehabilitation & Community Medicine Center, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan; 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 8College of Medicine, National Taiwan University and the Physical Therapy Center of National Taiwan University Hospital, Taipei, Taiwan; 9Community Medicine Research Center & Institute of Public Health, National Yang-Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Hsi-Chung ChenDepartment of Psychiatry, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, 10002, TaiwanTel +886-2-2312-3456 ext. 66787Fax +886-2-2381-320Email hsichungchen@ntu.edu.twObjective: Poor sleep quality is prevailing, deleterious, but heterogeneous in older adults. This study aimed to develop a simplified instrument to screen and classify poor sleep quality in community-dwelling older adults, by which stepped care with needs-based interventions could be implemented.Methods: Cohorts of adults aged 65 years and older were used to develop the Rapid Classification Scale for Sleep Quality (RCSSQ). Poor sleep quality was defined with the Pittsburgh Sleep Quality Index (PSQI). Established subgroups of poor sleep quality in the development dataset (n = 2622) were used as the criterion standard. Two independent validation datasets (n = 964 and 193, respectively) were used to examine the external validity. Questions in the PSQI were examined by the stepwise multinomial logistic regressions to determine the optimal numbers of items in the RCSSQ. On the premise of item parsimony and instrument validity, the optimal combination of reduced items was determined.Results: In the development dataset, the 4-item RCSSQ (RCSSQ-4) was the optimal predictive model. In terms of internal validity, the accuracy rates to identify PSQI-defined poor sleep quality and its subgroups in the developmental dataset by the RCSSQ-4 were 89.0% and 79.9%, respectively. Meanwhile, the RCSSQ-4 also had good external validity in the validation datasets to detect PSQI-defined poor sleep quality (accuracy rates: 89.1– 90.7%). Furthermore, the profiles of PSQI component scores and comorbid conditions for the predicted subgroups in the validation dataset were comparable with the criterion standard.Conclusion: The RCSSQ-4 is a valid instrument for screening and subgrouping poor sleep quality in community-dwelling older adults. The RCSSQ-4 may help guide tailored interventions under the context of stepped care in the community.Keywords: older adults, screen, sleep quality, subgroup, scale, the Yilan study

Wen-Yin Chen,1,2 Hsing-Cheng Liu,1,3 Ying-Chih Cheng,2,4 Hua Li,2 Chi-Chieh Huang,2 Yu-Wei Ding,2 Ming-Chyi Huang,1,3 Chih-Chiang Chiu,1,3 Yu-Kang Tu,2,5 Po-Hsiu Kuo2,5,6 1Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; 2Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 3Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Psychiatry, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 5Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan; 6Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Yu-Kang Tu; Po-Hsiu KuoDepartment of Public Health, College of Public Health, National Taiwan University, Room 521, No. 17, Xuzhou Road, Taipei City, 100, TaiwanEmail yukangtu@ntu.edu.tw; phkuo@ntu.edu.twIntroduction: The priority of interventions to alleviate cognitive deficits in patients with bipolar disorder (BD) is inconclusive. We systematically evaluate the efficacy of pharmacological or neurostimulation interventions for cognitive function in BD through a network meta-analysis.Methods: The PubMed, PsycINFO, Embase, and Cochrane Library databases were searched from database inception to September 30, 2021. Following PRISMA guidelines, all eligible studies were randomized controlled trials of adult bipolar patients that provided detailed cognitive outcomes. Studies were excluded if participants limited to comorbid substance use disorder or the intervention was a psychotherapy. Network meta-analysis comparing different interventions was conducted for 8 cognitive domains. Partially ordered set with Hasse diagram was used to resolve conflicting rankings between outcomes. The study was preregistered on PROSPERO database (CRD42020152044).Results: Total 21 RCTs including 42 tests for assessing intervention effects on cognition were retrieved. Adjunctive erythropoietin (SMD = 0.61, 95% CI = 0.00– 1.23), Withania somnifera (SMD = 0.58, 95% CI = 0.03– 1.13), and galantamine (SMD = 1.22, 95% CI = 0.10– 2.35) was more beneficial for attention, working memory, and verbal learning in euthymic BD patients than treatment as usual, respectively. Hasse diagram suggested ranking of choice when multiple domains were combined.Conclusion: Considerable variability in measurements of cognitive domains in BD was observed, and no intervention resulted in superior benefits across all domains. We suggested interventions priority can be tailored according to individual patients’ cognitive deficits. As current findings from relatively small and heterogeneous dataset, future trials with consensus should be applied for building further evidence.Keywords: cognitive function, systematic review, network meta-analysis, Hasse diagram, partially ordered set

Sze-Yu Chen,1 Chun-Hao Chen,1 Chen Lo,1 Mong-Liang Lu,2 Cheng-Dien Hsu,3 Yi-Hang Chiu,2 Chun-Hsin Chen,2 Shih-Ku Lin,4,5 Ming-Chyi Huang,5 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Wan-Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Psychosomatic Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; 4Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen Email hsichungchen@ntu.edu.twPurpose: This study aimed to elucidate the various co-occurring patterns of depressive symptomatology and sleep-wake-related disturbances (SWRDs) in patients with mood disorders.Patients and Methods: Individuals in non-acute states of major depressive disorder or bipolar disorder were recruited. The Beck Depression Inventory II (BDI-II) was utilized to evaluate depressive symptoms. BDI-II items were classified into three domains: cognitive, affective, and somatic. Between-domain differences with various SWRDs were examined. Latent class analysis was used to empirically classify participants using BDI-II items as indicator variables. Co-occurring patterns between domains of BDI-II items and SWRDs were re-examined in each subgroup to elucidate inter-individual differences.Results: In total, 657 participants were enrolled. Of participants, 66.8% were female, and 52.4% were diagnosed with major depressive disorder. Each BDI-II domain exhibited different co-occurring patterns. The somatic domain was most likely to co-occur with various SWRDs. Three subgroups were derived from latent class analysis and were designated as poor sleep quality and high insomnia (n=150), poor sleep quality and moderate insomnia (n=248), and poor sleep quality and low insomnia (n=159). The group with more severe insomnia presented with more severe depressive and anxiety symptoms. The three subgroups further differed in co-occurring patterns. From the low insomnia to high insomnia group, the associations with various SWRDs appeared in the sequence of somatic, affective, and cognitive domains.Conclusion: Co-occurring patterns between domains of depressive symptomatology with various SWRDs differ and may vary among individuals.Keywords: co-occurring, latent class analysis, mood disorders, sleep-wake-related disturbance, depression

Meng-Jer Hsieh,1,2 Shu-Yi Huang,1 Tsung-Ming Yang,1 Chi-Wei Tao,3 Shih-Lung Cheng,4 Chao-Hsien Lee,5 Ping-Hung Kuo,6 Yao-Kuang Wu,7,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Ming-Shian Lin,12 Chin-Chou Wang,13 Yu-Feng Wei,14 Ying-Huang Tsai1,2 1Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang-Gung Medical foundation, Chiayi, Taiwan; 2Department of Respiratory Therapy, School of Medicine, Chang-Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 8School of Medicine, Tzu Chi University, Hualien, Taiwan; 9Department of pulmonary and critical care medicine, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 11Division of Chest Medicine, Taichung Veterans General Hospital, Taiwan; 12Dpartment of Internal Medicine, Ditmanson Medical Foundation, Chia-Yi Cristian Hospital, Chia-Yi, Taiwan; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang-Gung Medical Foundation, Kaohsiung, Taiwan; 14Department of Internal Medicine E-Da Hospital, I-Shou University, Kaohsiung, Taiwan Background: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.Subjects and methods: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.Results: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.Conclusion: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. Keywords: chronic obstructive pulmonary disease, GOLD guidelines, inhaled corticosteroids, long-acting bronchodilators

Yu-Feng Wei,1,2 Ying-Huang Tsai,3 Chin-Chou Wang,4 Ping-Hung Kuo5 On behalf of the TOLD Study Group 1Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 2Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 4Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China Purpose: A low body mass index (BMI) is a poor prognostic marker of acute exacerbations and mortality in patients with COPD. However, the impact of overweight and obesity on COPD-related outcomes is uncertain. The aim of this study was to examine whether a high BMI is associated with the frequent exacerbator phenotype (≥2/year) in Taiwanese patients with COPD. Patients and methods: Data were obtained from the Taiwan Obstructive Lung Disease study, a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals in Taiwan. Multivariate logistic regression models were used to explore the association between BMI and other factors with the frequency of COPD exacerbations in these patients. Results: Among the whole study cohort (n=1,096), 735 (67.1%) had no exacerbations and 148 (13.5%) were frequent exacerbators in the previous year. The BMI values of the patients with 0, 1, and ≥2 exacerbations were 23.6, 23.5, and 22.6 kg/m2, respectively. In all, 256 (23.4%) and 196 (17.9%) patients were overweight (27 kg/m2 > BMI ≥24 kg/m2) and obese (BMI ≥27 kg/m2), respectively. Even after adjusting for multiple factors, overweight and obesity were associated with the frequency of exacerbations (odds ratio [95% confidence interval] 0.49 [0.28–0.87, P=0.015] and 0.49 [0.26–0.94, P=0.033], respectively). Conclusion: Our results suggest that overweight and obesity are associated with a lower frequency of COPD exacerbations in Taiwan. Keywords: acute exacerbation, COPD, obesity, overweight

Wan-Chun Huang,1 Ying-Huang Tsai,2 Yu-Feng Wei,3 Ping-Hung Kuo,4 Chi-Wei Tao,5 Shih-Lung Cheng,6 Chao-Hsien Lee,7 Yao-Kuang Wu,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Chin-Chou Wang,12 Ming-Shian Lin1,131Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 2Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 3Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, 4Department of Internal Medicine, National Taiwan University Hospital, 5Department of Internal Medicine, Cheng-Hsin General Hospital, 6Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, 7Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, 9Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 11Division of Chest Medicine, Taichung Veterans Genera Hospital, Taichung, 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 13Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan, Republic of ChinaBackground: COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.Methods: The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40 years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.Results: Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P

Yu-Feng Wei,1 Ping-Hung Kuo,2 Ying-Huang Tsai,3 Chi-Wei Tao,4 Shih-Lung Cheng,5,13 Chao-Hsien Lee,6 Yao-Kuang Wu,7 Ning-Hung Chen,8 Wu-Huei Hsu,9 Jeng-Yuan Hsu,10 Ming-Shian Lin,11 Chin-Chou Wang12 1Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 4Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 5Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan; 8Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University and China Medical University Hospital, Taichung, Taiwan; 10Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 11Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 13Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taoyuan, Taiwan Background and objective: The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice. The aim of this study was to explore the factors associated with the use of ICS in these patients. Methods: The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan. Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients. Results: Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively). The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients. Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14–4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24–2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40–2.96; P

Previous studies on acetaldehyde dehydrogenase 2 (ALDH2) focused on drinking behavior or alcoholism because the ALDH2*2 allele protects against the risk of developing alcoholism. The mechanism provides that the ALDH2 gene's protective effect is also involved in dopamine metabolism. The interaction of the ALDH2 gene with neurotransmitters, such as dopamine, is suggested to be related to alcoholism. Because alcoholism is often co-morbid with antisocial personality disorder (ASPD), previous association studies on antisocial alcoholism cannot differentiate whether those genes relate to ASPD with alcoholism or ASPD only. This study examined the influence of the interaction effect of the ALDH2*1*1, *1*2 or *2*2 polymorphisms with the dopamine 2 receptor (DRD2) Taq I polymorphism on ASPD. Our 541 Han Chinese male participants were classified into three groups: antisocial alcoholism (ASPD co-morbid with alcohol dependence, antisocial ALC; n = 133), ASPD without alcoholism (ASPD not co-morbid with alcohol dependence, antisocial non-ALC; n = 164) and community controls (healthy volunteers from the community; n = 244). Compared with healthy controls, individuals with the DRD2 A1/A1 and the ALDH2*1/*1 genotypes were at a 5.39 times greater risk for antisocial non-ALC than were those with other genotypes. Our results suggest that the DRD2/ANKK1 and ALDH2 genes interacted in the antisocial non-ALC group; a connection neglected in previous studies caused by not separating antisocial ALC from ASPD. Our study made this distinction and showed that these two genes may be associated ASPD without co-morbid alcoholism. [ABSTRACT FROM AUTHOR]

Background. Although alcohol dependence (AD) and major depression (MD) are highly co-morbid, their causal relationship is unclear. In this longitudinal study, we used a genetically informative population-based twin sample to examine the age-at-onset distributions and the temporal relationship of AD and MD.Method. Our sample included 7477 twins, whose diagnoses of AD and MD and age-at-onset information were obtained from structured interviews. Individual-level survival analyses were conducted based on 2603 monozygotic (MZ) twins, and co-twin diagnosis was included in models as an index of familiar liability to AD and MD.Results. The age-at-onset distributions of AD and MD differed substantially. Most onsets of AD were in young adulthood, whereas MD had a flatter distribution across age. Most subjects, especially women, had an onset of MD preceding AD. Prior MD significantly affected risk for developing AD, and this risk decreased over time. By contrast, preceding AD had negligible effects on the risk for future MD. Familial risk was transmitted within disorders but there was little evidence of additional familial liability shared across disorders.Conclusions. Risk for developing AD was substantially increased by a prior episode of MD. The association was only partially accounted for by familial factors, providing support for a direct causal effect such as self-medication. The etiologic path from AD to MD was insignificant. [ABSTRACT FROM AUTHOR]

Raman spectrum preprocessing method for automatic denoising and suppression of the fluorescent background. In this method, noise is reduced using wavelet transform, and a modified polynomial curve fitting method is implemented such that an algorithm can independently identify the optimal curve parameters for fluorescent background suppression. To address the problem of imbalanced datasets, the present study employed a synthetic minority oversampling technique to increase the volume of data in minority classes. This technique enables the prediction of pesticides that are otherwise difficult to detect, and the prediction accuracy is comparable to that of detection with large data volumes. The proposed convolutional neural network model was verified to accurately identify the type of single pesticides and composition of mixed pesticides. The prediction accuracy for mixed pesticides reached 99.1%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We review the epidemiology, policies, and control programs of HIV infection in Taiwan in the past 40 years since the first case of HIV infection was diagnosed in 1984. With the introduction of combination antiretroviral therapy (ART) in Taiwan in 1997, the incidences of HIV-related opportunistic illnesses and mortality have significantly declined. However, despite improved access to HIV testing and treatment, late presentation of HIV infection remains common. Unprotected sex, particularly among men who have sex with men, continues to be the leading risk for HIV transmission after implementation of harm reduction program to control an outbreak of HIV infection among people who inject drugs that occurred in 2003-2007. The sequential introduction of well-tolerated, effective, single-tablet antiretroviral regimens has facilitated the implementation of "treat-all" policy in 2016, rapid ART initiation within 7 days of diagnosis in 2018, and same-day ART initiation in 2021 when immunochromatography was used for rapid confirmation of HIV infection. Government-funded pilot program of pre-exposure prophylaxis for HIV infection, which was launched in 2016 followed by wider enrollment of people at high risk for HIV acquisition in 2018, have contributed to sustained declines of the incidence of HIV infection since 2018, along with high rates of linkage to HIV care, ART initiation, viral suppression, and retention in care in Taiwan. Challenges remain to achieve HIV elimination and long-term successful management of HIV infection, which include stigma and discrimination, late presentation of HIV infection, and accelerated ageing with increasing rates of co-morbidities among people with HIV., (Copyright © 2024. Published by Elsevier B.V.)

Bipolar disorder is a leading contributor to the global burden of disease 1 . Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown 2 . We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings 3 , and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder 4 , highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder., Competing Interests: Competing interests: T.E.T., H. Stefansson and K.S. are employed by deCODE Genetics/Amgen. E.A.S. is an employee of Regeneron Genetics Center and owns stocks of Regeneron Pharmaceutical. K.-H.L. and X.W. are employed by 23andMe. Multiple additional authors work for pharmaceutical or biotechnology companies in a manner directly analogous to academic co-authors and collaborators. A.H.Y. has given paid lectures and served on advisory boards relating to drugs used in affective and related disorders for several companies (AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allergan, Bionomics and Sumitomo Dainippon Pharma), was Lead Investigator for the Embolden study (AstraZeneca), BCI Neuroplasticity study and Aripiprazole Mania study, and is an investigator for Janssen, Lundbeck, Livanova and Compass. J.I.N. is an investigator for Janssen. P.F.S. is on the advisory committee and a shareholder of Neumora Therapeutics. G.B. reports consultancy and speaker fees from Eli Lilly and Illumina, and grant funding from Eli Lilly. M. Landén has received speaker fees from Lundbeck. O.A.A. has served as a speaker for Janssen, Lundbeck and Sunovion, and as a consultant for Cortechs.ai. A.M.D. is a founder of and holds equity interest in CorTechs Labs and serves on its scientific advisory board; is a member of the scientific advisory board of Human Longevity and the Mohn Medical Imaging and Visualization Center; and has received research funding from General Electric Healthcare. E.V. has received grants and served as a consultant, advisor or CME speaker for the following entities: AB-Biotics, Abbott, Allergan, Angelini, AstraZeneca, Bristol Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, GlaxoSmithKline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Catalan Government (AGAUR and PERIS), the Spanish Ministry of Science, Innovation, and Universities (AES and CIBERSAM), the Seventh European Framework Programme and Horizon 2020 and the Stanley Medical Research Institute. S.K.-S. received author’s, speaker’s and consultant honoraria from Janssen, Medice Arzneimittel Pütter GmbH and Takeda outside of the current work. A. Serretti is or has been a consultant and/or speaker for: Abbott, AbbVie, Angelini, AstraZeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi and Servier. J.R.D. has served as an unpaid consultant to Myriad-Neuroscience (formerly Assurex Health) in 2017 and 2019, and owns stock in CVS Health. B.M.N. is a member of the scientific advisory board at Deep Genomics, and consultant for Camp4 Therapeutics, Takeda Pharmaceutical and Biogen. B.-C.L., J.-W.K., Y.K.L., J.H.K., M. J. Cheon and D.J.K. are employed by Genoplan. I.B.H. is the Co-Director of Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to Headspace. I.B.H. is also the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M (AUD) Australian Government-funded Project Synergy (2017–2020; a 3-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. M.J.O. and M.C.O. have received funding from Takeda Pharmaceuticals and Akrivia Health outside the scope of the current work. P. B. Mitchell. has received remuneration from Janssen (Australia) and Sanofi (Hangzhou) for lectures or advisory board membership. J.A.R.-Q. was on the speakers’ bureau and/or acted as consultant for Biogen, Idorsia, Casen-Recordati, Janssen-Cilag, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the past 3 years; has also received travel awards (airplane tickets and hotel) for taking part in psychiatric meetings from Idorsia, Janssen-Cilag, Rubió, Takeda, Bial and Medice; and the Department of Psychiatry chaired by J.A.R.-Q. received unrestricted educational and research support from the following companies in the past 3 years: Exeltis, Idorsia, Janssen-Cilag, Neuraxpharm, Oryzon, Roche, Probitas and Rubió. All other authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Reports on the efficacy of omega-3 fatty acids (n-3 PUFAs) for the treatment of late-life depression (LLD) are mixed, and most studies focus on the modification of depressive symptoms rather than depression prevention. The aim of the present study was to investigate the efficacy of n-3 PUFAs in preventing depressive recurrence in patients with late-life depression. In addition, we investigated the effects of n-3 PUFAs on changes in depressive and anxiety symptoms and inflammatory markers in LLD., Methods: A 52-week, double-blind, randomized, controlled trial was conducted. We enrolled a total of 39 euthymic patients with LLD. They were randomized to receive either n-3 PUFAs (1.2 g per day of eicosapentaenoic acid and 1 g of docosahexaenoic acid) or placebo for 52 weeks. Recurrence of depression and severity of depression symptoms were assessed at baseline and weeks 4, 8, 16, 24, 32, 40, and 52., Results: A total of 39 patients completed the trial with 19 in the n-3 PUFAs group and 20 in the placebo group. Cox proportional hazard regression indicated that n-3 PUFAs had significant protective effect on depression recurrence (Hazard Ratio: 0.295, 95 % Confidence Interval: 0.093-0.931, p value =0.037). But n-3 PUFAs intervention had no significant effect in reducing depressive or anxiety symptoms, inflammatory markers over the placebo group., Limitation: The results should be interpreted with consideration of the modest sample size., Conclusion: These findings suggest that n-3 PUFAs may have a prophylactic effect in currently euthymic patients with LLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Suicide is among the severe outcomes of mental illness and has been reported to be associated with neurodegeneration and cognitive impairment. The blood neurofilament light chain (NfL) level is a biomarker of neuronal damage in neuropsychiatric disorders. This study investigated whether the NfL levels are associated with lifetime suicidal behaviors and whether this level is higher in patients with major depressive disorder (MDD) compared with healthy controls., Methods: In this cross-sectional study, we included 73 patients with MDD and 40 age- and sex-matched controls. The blood NfL levels were measured using an enzyme-linked immunosorbent assay. We compared the NfL levels between patients with MDD and controls and performed regression analysis to evaluate the association between the NfL levels and suicidal behaviors., Results: Nearly half of the patients with MDD (43.80%) reported lifetime suicide attempts. Those with MDD had higher blood NfL levels, but their levels did not significantly differ from those of the healthy controls. Logistic regression results revealed higher risks of lifetime suicide planning (Odds ratio (OR) = 1.64) and suicide attempts (OR = 1.94) with every 10 pg/mL increase in the NfL levels., Conclusions: Our results demonstrate that higher serum NfL levels were associated with lifetime suicidal behavior., (© The Author(s) 2025. Published by Oxford University Press on behalf of CINP.)

Objective: Approximately 30-50% of sudden sensorineural hearing loss (SSNHL) patients show poor response to systemic steroid therapy. Additionally, the most appropriate treatment for patients with refractory sudden sensorineural hearing loss (RSSNHL) is unknown. This study aimed to explore the best treatment for RSSNHL., Design: Using a frequentist contrast-based model and PRISMA guidelines, this study compared five salvage regimes: intratympanic injection of steroids (ITS), hyperbaric oxygen (HBO) therapy, post auricle steroid injection (PSI), ITS combined with HBO therapy, and continued systemic steroids., Study Sample: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomised controlled trials and cohort studies comparing treatment regimens for RSSNHL., Results: Compared with the control group (no additional treatment), PSI and ITS demonstrated significant improvements. The mean hearing gain was greater after PSI (11.1 dB [95% CI, 4.4-17.9]) than after ITS (7.7 dB [95% CI, 4.8-10.7]). When a restricted definition of RSSNHL was used, the ITS + HBO therapy showed the largest difference in improvement for pure tone average compared with the control group (14.5 dB [95% CI, 4.2-25.0])., Conclusions: The administration of either PSI or ITS leads to the greatest therapeutic effect in patients with RSSNHL. However, a consensus on the definition of RSSNHL is needed.

Introduction: The Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened a multidisciplinary workgroup to update appropriate use criteria (AUC) for amyloid positron emission tomography (PET) and to develop AUC for tau PET., Methods: The workgroup identified key research questions that guided a systematic literature review on clinical amyloid/tau PET. Building on this review, the workgroup developed 17 clinical scenarios in which amyloid or tau PET may be considered. A modified Delphi approach was used to rate each scenario by consensus as "rarely appropriate," "uncertain," or "appropriate." Ratings were performed separately for amyloid and tau PET as stand-alone modalities., Results: For amyloid PET, seven scenarios were rated as appropriate, two as uncertain, and eight as rarely appropriate. For tau PET, five scenarios were rated as appropriate, six as uncertain, and six as rarely appropriate., Discussion: AUC for amyloid and tau PET provide expert recommendations for clinical use of these technologies in the evolving landscape of diagnostics and therapeutics for Alzheimer's disease., Highlights: A multidisciplinary workgroup convened by the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging updated the appropriate use criteria (AUC) for amyloid positron emission tomography (PET) and to develop AUC for tau PET. The goal of these updated AUC is to assist clinicians in identifying clinical scenarios in which amyloid or tau PET may be useful for guiding the diagnosis and management of patients who have, or are at risk for, cognitive decline These updated AUC are intended for dementia specialists who spend a significant proportion of their clinical effort caring for patients with cognitive complaints, as well as serve as a general reference for a broader audience interested in implementation of amyloid and tau PET in clinical practice., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: REMIT is the first real-world study of mepolizumab effectiveness in patients with severe asthma (SA) in Taiwan., Objectives: The primary objective evaluated changes in clinically significant exacerbations (CSEs; defined as use of oral corticosteroids (OCS) or emergency department (ED) visits and/or hospitalizations) in the 12 months pre- and post-mepolizumab treatment. Secondary objectives assessed changes in the number of CSEs requiring ED visits/hospitalizations and daily maintenance OCS (mOCS) dosage 12 months pre- and post-mepolizumab treatment. Three- and four-component clinical remissions were analyzed based on OCS-free, exacerbation-free, and asthma control (± stability in lung function)., Design: REMIT was a retrospective, observational, self-controlled study analyzing patients in Taiwan with SA who were newly prescribed subcutaneous mepolizumab 100 mg Q4W., Methods: Data were extracted from records of 15 medical centers in Taiwan for patients indexed between November 1, 2018 and October 31, 2020., Results: A total of 170 patients were included: mean age at index date, 58.7 years; 53.5% female; 100% Chinese; 7.1% with chronic rhinosinusitis with nasal polyps, 1.8% with eosinophilic granulomatosis with polyangiitis, 1.2% with hypereosinophilic syndrome; and 55.7% with blood eosinophil count >300/µL. Pre-treatment, 71.2% had ⩾2 exacerbations, and 28.7% were on mOCS; 75.3% had no prior biologic treatment, and 24.7% had switched from other biologics. Most patients (80.0%) completed ⩾10 mepolizumab doses. Following the first mepolizumab administration (index date), CSEs reduced by 46.0% (rate ratio (RR): 0.545, 95% confidence interval (CI): 0.418-0.710; p  < 0.0001) in the 12 months post-index. Exacerbations requiring ED visits/hospitalization reduced by 46.9% (RR: 0.531, 95% CI: 0.349-0.808; p  = 0.0031). Median mOCS dose reduced by 100% by end of study and 81.8% of patients discontinued mOCS post-treatment. After 1 year of mepolizumab treatment, 28% and 23% patients achieved three- and four-component clinical remission, respectively., Conclusion: Mepolizumab use in a patient population in Taiwan with SA significantly reduced CSEs and mOCS use in routine clinical practice.

Background: The symptom variability in major depressive disorder (MDD) complicates treatment assessment, necessitating a thorough understanding of MDD symptoms and potential biomarkers., Methods: In this prospective study, we enrolled 54 MDD patients and 39 controls. Over the course of weeks 1, 2, and 4 participants underwent evaluations, with electroencephalograms (EEG) recorded at baseline and week 1. Our investigation considered five previously identified syndromal factors derived from the 17-item Hamilton Depression Rating Scale (17-item HAMD) for assessing depression: core, insomnia, somatic anxiety, psychomotor-insight, and anorexia. We assessed treatment response and EEG characteristics across all syndromal factors and total scores, all of which are based on the 17-item HAMD. To analyze the topology of brain networks, we employed functional connectivity (FC) and a graph theory-based method across various frequency bands., Results: The healthy control group had notably higher values in delta band EEG FC compared to the MDD patient group. Similar distinctions were observed between the responder and non-responder patient groups. Further exploration of baseline FC values across distinct syndromal factors revealed significant variations among the core, psychomotor-insight, and anorexia subgroups when using a specific graph theory-based approach, focusing on global efficiency and average clustering coefficient., Limitations: Different antidepressants were included in this study. Therefore, the results should be interpreted with caution., Conclusions: Our findings suggest that delta band EEG FC holds promise as a valuable predictor of antidepressant efficacy. It demonstrates an ability to adapt to individual variations in depressive symptomatology, offering insights into personalized treatment for patients with depression., Competing Interests: Declaration of competing interest There were no conflicts of interest from funding sources. All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate factors associated with new-onset migraine (NOM) after transcatheter atrial septal defect (ASD) closure and predictors of unremitting NOM. The pathogenic role of migraine biomarkers such as calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) were also assessed., Background: New-onset migraine has been observed after transcatheter ASD closure. Neuropeptides like CGRP and NPY stored both in the brain and heart are implicated in migraine pathophysiology. The potential role of those migraine biomarkers in NOM, as well as the risk factors and long-term outcomes of NOM, remain largely unknown., Methods: We enrolled patients without previous migraine who underwent successful transcatheter ASD closure between 2001 and 2013. The parameters of transthoracic echocardiography, and plasma CGRP and NPY levels measured by enzyme-linked immunosorbent assay, were collected prospectively before and after ASD closure, and compared between patients with NOM and those without. Predictors of NOM were assessed. Telephone interviews were performed in 2022 to assess migraine status. Clinical and procedural characteristics were compared between patients with unremitting migraine and those with transient migraine that remitted within 1 year., Results: Of the 212 patients (median age, 21 years; 75.9% female), 43 (20.3%) had NOM. Potential predictors of NOM included a young age (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.96-0.99; p = 0.040), large ASD size (aOR 1.07, 95% CI 1.01-1.14; p = 0.022), and transient residual shunting after closure (aOR 2.78, 95% CI 1.05-7.36; p = 0.039). Post-closure plasma CGRP levels, but not NPY levels, were significantly higher than pre-closure levels (47.9 vs. 38.0 pg/mL, p = 0.023) among patients with NOM. Of the 27 patients with migraine who reported their migraine status at a median 14-year follow-up, 13 (48.1%) had unremitting migraine. Patients with unremitting migraine were more likely to have a smaller device-to-ASD size ratio (1.21 vs. 1.33, p = 0.039) and a larger pulmonary flow-to-systemic flow ratio (2.9 vs. 2.3, p = 0.012) than those with transient migraine., Conclusions: Calcitonin gene-related peptide may play a pathogenic role in NOM after transcatheter ASD closure. A young age, large ASD size, and transient residual shunting potentially predict migraine occurrence after ASD closure. NOM not reaching remission for years may result from a significant shunt before closure., (© 2024 American Headache Society.)

Background: Although significant research has explored the digital phenotype in mood disorders, the time-lagged and bidirectional relationship between mood and global positioning system (GPS) mobility remains relatively unexplored. Leveraging the widespread use of smartphones, we examined correlations between mood and behavioral changes, which could inform future scalable interventions and personalized mental health monitoring., Objective: This study aims to investigate the bidirectional time lag relationships between passive GPS data and active ecological momentary assessment (EMA) data collected via smartphone app technology., Methods: Between March 2020 and May 2022, we recruited 45 participants (mean age 42.3 years, SD 12.1 years) who were followed up for 6 months: 35 individuals diagnosed with mood disorders referred by psychiatrists and 10 healthy control participants. This resulted in a total of 5248 person-days of data. Over 6 months, we collected 2 types of smartphone data: passive data on movement patterns with nearly 100,000 GPS data points per individual and active data through EMA capturing daily mood levels, including fatigue, irritability, depressed, and manic mood. Our study is limited to Android users due to operating system constraints., Results: Our findings revealed a significant negative correlation between normalized entropy (r=-0.353; P=.04) and weekly depressed mood as well as between location variance (r=-0.364; P=.03) and depressed mood. In participants with mood disorders, we observed bidirectional time-lagged associations. Specifically, changes in homestay were positively associated with fatigue (β=0.256; P=.03), depressed mood (β=0.235; P=.01), and irritability (β=0.149; P=.03). A decrease in location variance was significantly associated with higher depressed mood the following day (β=-0.015; P=.009). Conversely, an increase in depressed mood was significantly associated with reduced location variance the next day (β=-0.869; P<.001). These findings suggest a dynamic interplay between mood symptoms and mobility patterns., Conclusions: This study demonstrates the potential of utilizing active EMA data to assess mood levels and passive GPS data to analyze mobility behaviors, with implications for managing disease progression in patients. Monitoring location variance and homestay can provide valuable insights into this process. The daily use of smartphones has proven to be a convenient method for monitoring patients' conditions. Interventions should prioritize promoting physical movement while discouraging prolonged periods of staying at home., (©Ting-Yi Lee, Ching-Hsuan Chen, I-Ming Chen, Hsi-Chung Chen, Chih-Min Liu, Shu-I Wu, Chuhsing Kate Hsiao, Po-Hsiu Kuo. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.12.2024.)

This study employed machine learning techniques to predict the rate of feline infectious peritonitis (FIP) diagnoses, with a specific focus on mutations in the spike protein gene of the feline coronavirus (FCoV). FIP is a fatal viral disease affecting the peritoneum of cats and is primarily caused by mutations in FCoV. Its diagnosis largely relies on evaluations of various biomarkers and clinical symptoms. The current analysis of FCoV spike protein gene mutations exhibits certain limitations. To address this problem, the present study employed a large dataset-comprising information on FCoV copy numbers, spike protein mutation outcomes, and related clinical data-and used machine learning models to analyze the association between spike protein gene mutations and FIP diagnosis. Various algorithms were used to establish highly accurate predictive models, namely logistic regression, random forest, decision tree, neural network, support vector machine, gradient boosting tree, and categorical boosting (CatBoost) algorithms. The model obtained using the CatBoost algorithm was discovered to have accuracy of 0.9541. Accordingly, a highly accurate predictive model was developed to enable early diagnosis of FIP and improve the rate of survival in cats. The application of machine learning technology in this study yielded research findings that provide veterinarians with effective tools for managing and preventing FIP, a painful and deadly disease for cats. This study is a pioneering work in the systematic application of multiple machine learning models to the prediction of FIP and comparison of performance results to improve diagnostic accuracy and efficiency. This study is the first of its kind in the field of FIP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pulmonary hypertension (PH) is a serious disease, however simple tools to predict outcomes are lacking. In our previous investigation, we found that heart rate variability (HRV) and heart rhythm complexity (HRC) were associated with the detection and severity of PH, however their association with PH mortality remains unclear. The aim of this study was to investigate these metrics as a tool for determining long-term outcomes in PH patients. We enrolled 74 Asian PH patients with WHO PH group 1 or 4 at a single hospital in Taiwan between March 2012 and June 2018. After a median follow-up duration of 58 months (to January 2023), 22 patients had died. The patients who died had a significantly lower lean body mass index (BMI), impaired renal function, higher N-terminal pro B-type natriuretic peptide (NT-proBNP) level, lower very low-frequency (VLF), lower short-term detrended fluctuation analysis α1 (DFAα1), and lower multiscale entropy scale 5 value. In multivariable analysis, BMI, VLF and multiscale entropy scale 5 were significantly associated with survival. The best cut-off VLF and scale 5 values were 115.13 and 0.738, respectively. We then categorized the study population into three groups: both elevated VLF/scale 5 (group 1), either depressed VLF or depressed scale 5 (group 2), and both depressed VLF/scale 5 (group 3). The results showed that group 1 had the best outcomes, whereas group 3 had the worst survival (P < 0.001). Combining HRV and HRC metrics appears to be a good non-invasive tool to predict the long-term outcomes of patients with PH., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Major depressive disorder (MDD) is a complex mental disorder, potentially linked to the gut-microbiota-brain axis. Probiotics like Lactobacillus plantarum PS128 (PS128) may improve depressive symptoms by modulating the gut microbiota based on our previous open trial. We conducted an 8-week double-blind, placebo-controlled trial to investigate the impact of PS128 on depression severity, markers of inflammation and gut permeability, and the gut microbiota composition in 32 patients with MDD with stable antidepressant treatment but moderate symptom severity. Following the 8-week intervention, both the Hamilton Depression Rating Scale-17 score (HAMD), and Depression and Somatic Symptoms Scale (DSSS) showed a significant decrease in both groups (p<0.001). However, there was no significant difference in the change of depression severity between groups (p=0.203). Moreover, alterations in serum levels of high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and intestinal fatty acid binding protein, as well as changes in the gut microbiota composition, did not exhibit significant differences before and after intervention or between the groups. In comparison to the placebo group, our study did not find significant effects of PS128 on depressive symptoms, biomarkers of inflammation and gut permeability, and the overall gut microbiota composition. Nonetheless, we observed a potential impact of PS128 on the symbiosis of specific taxa. To comprehensively understand the psychophysiological effects of PS128 in patients with MDD, further research with a larger sample size is imperative., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This work reports Ag(I)-catalyzed oxidative cyclizations of 1,4-diynamide-3-ols with 8-methylquinoline oxide to form 2-substituted furan-4-carboxamides. The reaction chemoselectivity is distinct from that reported in previous work by Hashmi. We performed density functional theory calculations to elucidate our proposed mechanism after evaluation of the energy profiles of two possible pathways. In this Ag(I) catalysis, the calculations suggest that the amide and alkyne groups of the 3,3-dicarbonyl-2-alkyne intermediates tend to chelate with the Ag(I) catalyst, further inducing a formyl attack at the Ag(I)-π-alkyne moiety to deliver the observed products.

Background: Dual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups., Methods: The TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed., Results: Data from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study., Conclusions: The three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is a serious, progressive lung disease for which treatments are scarce. Pirfenidone has been approved for the treatment of IPF in Taiwan since 2016. This study aimed to gain a better insight into pirfenidone's real-world safety and effectiveness in adult IPF patients in Taiwan., Methods: We conducted a prospective, multicenter, post-marketing surveillance study, and analyzed data from a small sample of 50 IPF patients treated with pirfenidone., Results: Most patients were men, with a mean age of 72.8 years (±10.3). They were in physiology stage I or II with a baseline mean forced vital capacity (FVC) of 2.236 L (73.8% of predicted value). After treatment with pirfenidone, the mean FVC decreased by 0.088 L at week 24 and 0.127 L at week 52. The mean 6 min walk test was 325.5 m at baseline, increased by 8.1 m at week 24, but then decreased by 23.0 m at week 52. These changes from baseline did not reach statistical significance. Pirfenidone prevented worsening of cough but did not stabilize dyspnea. During 52 weeks of treatment, the incidence of total adverse drug reactions was 62.0%, with decreased appetite (32.0%) and pruritis (10.0%) being the most common. The adverse events leading to treatment discontinuation were decreased appetite (8.0%), nausea (4.0%), and respiratory failure (4.0%). No safety concern was raised by the study. Treatment with pirfenidone stabilized both FVC and the subjective symptom of cough in most patients., Conclusions: This post-marketing surveillance study demonstrated that pirfenidone is an effective, safe, and well-tolerated treatment in patients with IPF in Taiwan.

Background: Quantitative thresholds are helpful to define an abnormal DaT SPECT in patients with suspected nigrostriatal degenerative diseases (NSDD). The optimal DaTQUANT threshold for diagnostic accuracy of DaT SPECT across combined movement and cognitive disorder populations has been previously described. Methods : We established optimal DaTQUANT thresholds that enhance the discrimination between dementia with Lewy bodies (DLB) and non-DLB dementia types, as well as between Parkinsonian syndromes (PS) and conditions not characterized by nigrostriatal degeneration (non-PS). Results: Data from a total of 303 patients were used in this retrospective analysis. Posterior putamen of the more affected hemisphere (MAH) was shown to be an accurate single-variable predictor for both DLB and PS and was comparable to the most accurate multi-variable models. Conclusions: Automated quantification with DaTQUANT can accurately aid in the differentiation of DLB from non-DLB dementias and PS from non-PS. Optimal thresholds for assisting a diagnosis of DLB are striatal binding ratio (SBR) ≤ 0.65, z-score ≤ -2.36, and a percent deviation ≤ -0.54 for the posterior putamen of the MAH. Optimal posterior putamen thresholds for assisting a diagnosis of PS are SBR ≤ 0.92, z-score ≤ -1.53, and a percent deviation ≤ -0.33, which are similar to our previously reported posterior putamen threshold values using a blended patient pool from multiple study populations.

Although guidelines for the use of 177 Lu-PSMA-617 published by various organizations are important, they do not include all the essential, practical points necessary for a complete institutional protocol. Therefore, a brief survey was performed to assess key components of the 177 Lu-PSMA-617 protocol before, during, and after delivery of therapy. This survey demonstrated the wide variability in many aspects of institutional protocols regarding determination of eligibility for and administration of 177 Lu-PSMA-617 therapy. The real-world protocol details provided here from a variety of institutions may help new and established theranostic programs., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Interreader and intrareader reproducibility of 18 F-flotufolastat PET/CT scans in newly diagnosed and recurrent prostate cancer patients was assessed from masked image evaluations from two phase 3 studies. Methods: 18 F-flotufolastat PET/CT images of newly diagnosed ( n = 352) or recurrent ( n = 389) patients were evaluated by 3 masked readers. Cohen κ was used to assess pairwise patient- and region-level interreader agreement. Agreement among all readers was assessed using Fleiss κ. Intrareader agreement between the first and repeat read (20% of images, ≥4 wk later) was assessed using Cohen κ. Results: Pairwise interreader agreement was 95% or better (newly diagnosed) and 75% or better (recurrent). The κ coefficients were impacted by the high-agreement-low-κ paradox: Cohen κ ranged from not estimable to 0.55, whereas Fleiss κ was 0.50 (newly diagnosed) and 0.41 (recurrent). Agreement was highest in the prostate of newly diagnosed patients (≥95%) and in the pelvic lymph nodes in recurrent patients (≥87%). Intrareader agreement was 86% or better across both populations. Conclusion: 18 F-flotufolastat PET/CT images can be reliably interpreted, with a high degree of inter- and intrareader agreement., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)