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Li-Ting Kao,1 Shian-Chin Ko,2 Ping-Jen Chen,3,4 Yu-Cih Wu,5 Kuang-Ming Liao,6 Yi-Shan Liang,1 Chung-Han Ho,5,7,8 Fu-Wen Liang9– 11 1Department of Respiratory Therapy, Chi Mei Medical Center, Tainan, Taiwan; 2Center for Palliative Care, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Family Medicine and Division of Geriatrics and Gerontology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan; 6Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan; 7Department of Information Management, Southern Taiwan University of Science and Technology, Tainan City, Taiwan; 8Cancer Center, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 9Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center for Big Data Research, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Chung-Han Ho, Department of Medical Research, Chi Mei Medical Center, No. 901, Zhonghua Road Yongkang District, Tainan City, 71004, Taiwan, Tel +886-6-281-2811, Email ho.c.hank@gmail.com Fu-Wen Liang, Department of Public Health, College of Health Sciences, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung, 807, Taiwan, Tel +886-7-312-1101 Ext 2786, Fax +886-7-311-0811, Email fwliang@kmu.edu.twPurpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD.Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan’s National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization.Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions—especially cancer—and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1– 2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1– 2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years.Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization.Keywords: cancer comorbidity, inpatient care, joinpoint regression, Taiwan’s health insurance database

Shun-Hua Chen,1 Po-Jen Chen,2 Chiu-Hsiang Lee,3,4 Yu-Ping Wu,3,4 Daniel Kwasi Ahorsu,5,6 Mark D Griffiths,7 Chung-Ying Lin8 1School of Nursing, Fooyin University, Kaohsiung, 83102, Taiwan; 2Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, 824005, Taiwan; 3Department of Nursing, Chung Shan Medical University, Taichung, Taiwan; 4Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan; 5Mental Health Research Centre, the Hong Kong Polytechnic University, Hung Hom, Hong Kong; 6Department of Special Education and Counselling, the Education University of Hong Kong, Tai Po, Hong Kong; 7International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 8Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanCorrespondence: Chiu-Hsiang Lee, Department of Nursing, Chung Shan Medical University, Department of Nursing, Chung Shan Medical University Hospital, 1253F, Jengshin Hall, Taichung, 402, Taiwan, Tel +886-4-24730022 ext. 12216, Email csha528@gmail.com Daniel Kwasi Ahorsu, Department of Special Education and Counselling, The Education University of Hong Kong, B4-1/F-13, Tai Po, Hong Kong, Email daniel.ahorsu@connect.polyu.hkPurpose: Resilience continues to be an important concept in the nursing profession due to its significant role in personal healthcare, patients’ healthcare, and leadership. The present study examined the mediating role of perceived stress in the association between mindfulness and resilience among registered nurses in order to understand their importance among those in the Taiwanese nursing profession.Materials and Methods: Between October and November 2021, a total of 816 registered nurses participated in a cross-sectional survey including psychometric measures assessing perceived stress (Chinese Perceived Stress Scale-10), mindfulness (Chinese Mindful Attention Awareness Scale), and resilience (Chinese Questionnaire of Resilience).Results: Results indicated that perceived stress mediated the association between mindfulness and resilience (standardized coefficient = 0.251, p< 0.001), although there was no significant association between mindfulness and resilience (standardized coefficient = 0.042, p=0.16). This suggests that perceived stress may function as both distress and eustress because mindfulness was not directly associated with resilience but indirectly via perceived stress.Conclusion: Nurses and their administrators should focus on different ways of coping with stress so that they become more resilient in facing other stressors. Future studies may be conducted to examine the mediating role of perceived stress in the association between other coping strategies and resilience among registered nurses.Keywords: coping, healthcare, Taiwan, cross-sectional survey, mediation analysis, mindfulness, resilience

Po-Jui Chen,1 I-Huang Lin,1 Yi-Chun Chi,2 Chun-Chieh Lai,1 Jia-Horung Hung,1 Sung-Huei Tseng,1 Yi-Hsun Huang1 1Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Yi-Hsun Huang, Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Email jackhyh@gmail.comAbstract: Purpose: This study aimed to evaluate the therapeutic efficacy and long-term outcomes of treatment with topical 2% ganciclovir solution in immunocompetent patients with aqueous humor polymerase chain reaction (PCR)-proven cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis.Methods: We retrospectively reviewed the findings for immunocompetent patients diagnosed with CMV uveitis or endotheliitis based on clinical manifestations and polymerase chain reaction (PCR) examination results and treated with topical 2% ganciclovir solution at National Cheng Kung University Hospital. Clinical outcome measurements included evaluations of the response rate, relapses, resolution of anterior chamber inflammation, visual acuity, and intraocular pressure.Results: The study included 38 eyes of 32 patients. Long-term administration of topical 2% ganciclovir significantly decreased keratic precipitates (p = 0.001), anterior chamber cells (p = 0.001), and reduced intraocular pressure (p < 0.001). Only one eye was unresponsive to topical ganciclovir treatment, and the recurrence decreased to 0.13 relapses per year. The presence of keratic precipitates and higher intraocular pressure at the initial presentation were significantly associated with recurrence (p = 0.036 and p = 0.001, respectively).Conclusions:: Long-term use of topical 2% ganciclovir solution is effective, safe, and applicable when commercialized ganciclovir gel is not available.Keywords: cytomegalovirus, endotheliitis, ganciclovir, uveitis

Ching-Chun Li,1 Tsung-Kun Chang,1,2 Yen-Cheng Chen,1,3 Hsiang-Lin Tsai,1,2 Ching-Wen Huang,1,2 Wei-Chih Su,1,3 Cheng-Jen Ma,1,3 Tzu-Chieh Yin,1,4,5 Po-Jung Chen,1 Jaw-Yuan Wang1– 3,6– 8 1Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Surgery, Kaohsiung Municipal Tatung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Surgery, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, TaiwanCorrespondence: Jaw-Yuan Wang, Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan, Tel +886-7-3122805, Email cy614112@ms14.hinet.net; jawyuanwang@gmail.comBackground: The prognosis of metastatic colorectal cancer (mCRC) depends on the metastatic site and systemic therapy regimen. Peritoneal metastases are associated with a relatively unfavorable prognosis among patients with mCRC. In this article, we present the treatment outcomes of patients with peritoneal carcinomatosis (PC)-only, liver metastasis (LiM)-only, and lung metastasis (LuM)-only CRC.Methods: Overall, 206 mCRC patients with single-site metastasis and who had received treatment from January 2014 to December 2018 were recruited. Among 206 patients with mCRC, 15 had PC-only mCRC, 145 had LiM-only mCRC, and 46 had LuM-only mCRC. They attended regular follow-ups until November 2020, and the median follow-up period was 24.7 months (5.1– 41.3 months). Patients’ characteristics, including clinical data, gene mutation profiles, and clinical outcomes, were evaluated. All patients with PC-only CRC were treated with first-line bevacizumab and FOLFIRI, and the irinotecan dose escalation depended on UGT1A1 polymorphism.Results: Of the 206 patients, no statistical difference was observed between the PC-only, LiM-only, and LuM-only groups in terms of age, primary tumor location, RAS mutation status, BRAF mutation status, and epidermal growth factor receptor overexpression (all P > 0.05). Patients with PC-only CRC had a median progression-free survival (mPFS) of 18.0 months and a median overall survival (mOS) of 24.6 months. Patients with LiM-only or LuM-only CRC had mPFS of 18.2 and 26.6 months and mOS of 25.0 and 44.5 months, respectively. No significant differences regarding PFS and OS (both P > 0.05) between the three groups of patients with mCRC were observed.Conclusion: Our study revealed that in patients with PC-only mCRC treatment of first-line bevacizumab and FOLFIRI through irinotecan dose escalation according to UGT1A1 polymorphism could confer such patients with comparable outcomes to that of patients with LiM-only and LuM-only mCRC.Keywords: prognosis, metastatic colorectal cancer, peritoneal carcinomatosis-only, UGT1A1, irinotecan dose escalation

Nadine Abi-Jaoudeh,1 Farshid Dayyani,2 Pei Jer Chen,3 Dayantha Fernando,1 Nicholas Fidelman,4 Hanna Javan,1 Po-Chin Liang,5 Jen-I Hwang,6 David K Imagawa7 1Department of Radiological Sciences, University of California Irvine, Orange, CA, USA; 2Chao Comprehensive Digestive Disease, University of California Irvine, Orange, CA, USA; 3Hepatitis Research Center, National Taiwan University, Taipei City, Taiwan; 4Department of Radiology, University of California San Francisco, San Francisco, CA, USA; 5Department of Medical Imaging, National Taiwan University, Taipei City, Taiwan; 6Department of Radiology, Taichung Veteran General Hospital, Taichung, Taiwan; 7Surgery Services, University of California Irvine, Orange, CA, USACorrespondence: Nadine Abi-JaoudehUniversity of California Irvine, Department of Radiological Sciences, 101 The City Drive South Route, 140 Rm 115, Orange, CA, 92868, USATel +1-540-292-6567Email nadine@hs.uci.eduBackground: Tirapazamine (TPZ) is a hypoxia activated drug that may be synergistic with transarterial embolization (TAE). The primary objective was to evaluate the safety of combining TPZ and TAE in patients with unresectable HCC and determine the optimal dose for Phase II.Methods: This was a Phase 1 multicenter, open-label, non-randomized trial with a classic 3+3 dose escalation and an expansion cohort in patients with unresectable HCC, Child Pugh A, ECOG 0 or 1. Two initial cohorts consisted of I.V. administration of Tirapazamine followed by superselective TAE while the remaining three cohorts underwent intraarterial administration of Tirapazamine with superselective TAE. Safety and tolerability were assessed using NCI CTCAE 4.0 with clinical, imaging and laboratory examinations including pharmacokinetic (PK) analysis and an electrocardiogram 1 day pre-dose, at 1, 2, 4, 6, 10, and 24 hours post-TPZ infusion and an additional PK at 15- and 30-minutes post-TPZ. Tumor responses were evaluated using mRECIST criteria.Results: Twenty-seven patients (mean [range] age of 66.4 [37– 79] years) with unresectable HCC were enrolled between July 2015 and January 2018. Two patients were lost to follow-up. Mean tumor size was 6.53 cm ± 2.60 cm with a median of two lesions per patient. Dose limiting toxicity and maximum tolerated dose were not reached. The maximal TPZ dose was 10 mg/m2 I.V. and 20 mg/m2 I.A. One adverse event (AE) was reported in all patients with fatigue, decreased appetite or pain being most common. Grade 3– 5 AE were hypertension and transient elevation of AST/ALT in 70.4% of patients. No serious AE were drug related. Sixty percent (95% CI=38.7– 78.9) achieved complete response (CR), and 84% (95% CI=63.9– 95.5) had complete and partial response per mRECIST for target lesions.Discussion: TAE with TPZ was safe and tolerable with encouraging results justifying pursuit of a Phase II trial.Keywords: phase I trial, hypoxia activated agent, hepatocellular carcinoma, image guided locoregional therapies, transarterial chemoembolization

Hsuan-Wei Chen,1 Yi-Lin Chiu,2 Tsai-Yuan Hsieh,1 Peng-Jen Chen,1 Tien-Yu Huang,1 Hsuan-Hwai Lin,1 Yu-Lueng Shih,1 Jung-Chun Lin1 1Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Biochemistry, National Defense Medical Center, Taipei, TaiwanCorrespondence: Jung-Chun LinDivision of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Sec 2, Cheng-Kung Road, Neihu 114, Taipei, TaiwanTel +886-2- 87927409Fax +886-2- 87927139Email doc10506@gmail.comBackground: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans.Methods: A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25[OH]D) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus.Findings: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders.Conclusion: In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.Keywords: cytokines, interferon-α, PBMCs, VDR signaling, vitamin D

Pei-Ju Chen,1 Kuang-Yao Yang,2,3 Wann-Cherng Perng,4 Kuan-Chia Lin,5,6 Kwua-Yun Wang7 1School of Nursing, National Yang-Ming University, Taipei, Taiwan, Republic of China; 2Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 3Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 4Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 5Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, Republic of China; 6Communty Medicine Research Center, Preventive Medicine Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China; 7Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China Purpose: Chronic obstructive pulmonary disease (COPD) impacts health-related quality of life in men more than in women. In patients with dyspnea, frailty is more likely to develop and aggravate disability. Despite this, few studies have addressed frailty in men with COPD. The present study investigated the effects of dyspnea and its related factors on frailty in men with COPD. Patients and methods: This cross-sectional observational study selected 125 participants by voluntary sampling at the thoracic outpatient clinics of two medical centers in Taiwan. The modified Medical Research Council questionnaire was used as the basis to classify dyspnea. Data were collected using questionnaires and analyzed using IBM SPSS Statistics for Windows, version 24.0 (IBM Corporation., Armonk, NY, USA). Results: There were 85.90% and 26.70% patients with COPD assessed in the unfit stage among the dyspnea and non-dyspnea groups, respectively. Additionally, the number of medication use and the COPD Assessment Test (CAT) scores were correlated with the period from fitness to unfitness among the dyspnea group and non-dyspnea group. Conclusion: COPD with dyspnea was more common in the unfit stages. The total number of medication use and CAT scores were significantly related to frailty. Keywords: chronic obstructive, dyspnea, frail elderly, men, pulmonary disease

Fu-Chi Kang,1 Pei-Jung Chen,2 Bo-Syong Pan,2,3 Meng-Shao Lai,2,3 Yung-Chia Chen,4 Bu-Miin Huang2,31Department of Anesthesia, Chi Mei Medical Center, Chiali, 2Department of Cell Biology and Anatomy, 3Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 4Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Background: Chemotherapy is not limited to a single treatment, and the evidence demonstrates that different drug combinations can have positive results in patients. In this study, we sought to determine whether cordycepin combined with cisplatin and/or paclitaxel would have an additive effective on inducing apoptosis in mouse Leydig tumor cells, and the mechanisms were also briefly examined.Methods: The additive effects of cordycepin combined with cisplatin and/or paclitaxel on apoptosis in MA-10 cells were investigated by monitoring changes in morphological characteristics and examining cell viability, flow cytometry assays, and Western blot analyses.Results: Combination of cordycepin plus cisplatin and/or paclitaxel for 12 and 24 hours induced apoptotic features in MA-10 cells. The MTT assay showed that the combination treatment reduced the viability of MA-10 cells in a dose-dependent manner, with additive effects. Cell cycle analysis showed that combination treatment significantly increased subG1 phase cell numbers in MA-10 cells, indicating apoptosis. Moreover, cordycepin plus cisplatin and/or paclitaxel significantly induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase, and phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, p38, and p53 proteins in MA-10 cells.Conclusion: Cordycepin plus cisplatin and/or paclitaxel can have an additive effect on apoptosis in MA-10 cells, with activation of caspase, mitogen-activated protein kinase, and p53 signal pathways. Keywords: cordycepin, cisplatin, paclitaxel, apoptosis, drug combination, additive effect, MA-10 cells, Leydig tumor cells

Chih-Chang Yeh,1,2 Yu-Han Su,3 Yu-Jhe Lin,3 Pin-Jyun Chen,3 Chung-Sheng Shi,1 Cheng-Nan Chen,3,* Hsin-I Chang3,* 1Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China; 2Orthopaedic Department, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan, Republic of China; 3Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression. Keywords: liposome, osteoarthritis, curcuminoid, OPG/RANKL ratio, bone turnover

Background: Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a 'next-step'. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted. Method: The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored. Results: Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to 'next-step' treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI. Conclusion: SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI. [ABSTRACT FROM AUTHOR]

Background. It is unclear whether hepatitis B e antigen (HBeAg) seroconversion induced by nucleos(t)ide analogues (NUC) has a prognosis that is similar to that of spontaneous HBeAg seroconversion. Methods. A total of 148 noncirrhotic NUC-induced HBeAg seroconverters were consecutively enrolled. A historical control of 407 noncirrhotic spontaneous HBeAg seroconverters was also recruited. We compared the rates of HBeAg seroreversion and HBV reactivation between these 2 cohorts. Results. There were 1652.8 and 465.2 person-years of follow-up for spontaneous and NUC-induced HBeAg seroconverters, respectively. Compared with NUC-induced seroconverters, spontaneous seroconverters were younger when achieving HBeAg seroconversion. We thus compared these 2 cohorts according to their age at HBeAg seroconversion. In patients achieving HBeAg seroconversion before 30 years of age, NUC-induced seroconverters had a higher 2-year HBeAg seroreversion rate than spontaneous seroconverters (12.0% vs 2.9%; P = .004) and were at a higher risk of HBV reactivation (hazard ratio, 4.6; 95% confidence interval, 1.5-14.4). Using multivariate analysis, NUC-induced HBeAg seroconversion remained a risk factor of both endpoints in young HBeAg seroconverters. Conclusion. NUC-induced HBeAg seroconverters may not have durable response after stopping therapy. For patients achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg seroreversion and HBV reactivation is higher in NUC-induced seroconverters than spontaneous HBeAg seroconverters. [ABSTRACT FROM AUTHOR]

This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming. [ABSTRACT FROM AUTHOR]

Disc degeneration and muscle dysfunction are common spinal degenerations in the elderly. This in vitro study was carried out to investigate the effects of these two degenerative changes on spinal stability. The stability of nine porcine cervical spines (C2-T1) with mechanically simulated cervical muscles (sternocleidomastoid (SCM), splenius capitis (SPL), semispinalis capitis (SSC)) was tested before and after experiment-induced disc degeneration. The patterns of muscle recruitments included: no muscle recruitment, normal recruitment of SCM/SPL/SSC, and SCM/SPL/SSC muscle dysfunctions. The neutral zone (NZ) and the range of motion (ROM) in the sagittal plane were measured to determine spinal stability. The results showed that the NZ and the ROM of a degenerative spine were larger than those of an intact spine under no muscle recruitment, but not under muscle recruitments. For both intact and degenerative spines, the NZ and the ROM were greatest under no muscle recruitment, followed by SSC dysfunction, SCM dysfunction, and SPL dysfunction, and smallest under normal muscle recruitment. In conclusion, muscle recruitments stabilize both intact and degenerative cervical spines, while dysfunctional muscles do not maintain stability efficiently as normal muscles do. Thus, spinal stability is more significantly affected by muscle dysfunction than by disc degeneration. Muscle training is suggested for the elderly with spinal degeneration to improve stability. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To develop a cost-effective and robust genetic diagnostic tool for patients with idiopathic nonsyndromic sensorineural hearing impairment.Study Design: Development of a diagnostic tool and validation in a prospective cohort.Methods: Twenty common sequence variants in GJB2, SLC26A4, and the mitochondrial 12S rRNA gene were selected based on our previous epidemiological study. These variants were analyzed using the SNaPshot technique. The efficacies of the SNaPshot multiplex assays were determined by using a prospective cohort composed of 214 unrelated Taiwanese patients with idiopathic sensorineural hearing impairment. The results of the assays were compared to the results obtained by direct sequencing.Results: We developed a diagnostic technique consisting of two consecutive panels of SNaPshot multiplex assays, with each panel screening 10 common sequence variants. Theoretically, this design can detect more than 98% of the known deafness-associated sequence variants in Taiwanese individuals. A total of 126 (58.9%) patients were diagnosed as having at least one sequence variant using the SNaPshot multiplex assays. In total, the SNaPshot assays yielded an accuracy of more than 99%.Conclusions: The strengths of SNaPshot multiplex assays include high accuracy, high sensitivity, high flexibility (the examination panel can be easily expanded for additional mutations), low cost (less than US $10 per patient), and easy implementation for any institute with a DNA sequencer. Although only 20 to 30 mutations can be examined in two to three runs of the SNaPshot assay, this technology may be suitable for first-pass screening of deafness-associated mutations in populations with a relatively homogeneous ethnic background. [ABSTRACT FROM AUTHOR]

Accurate epidemiological data on common deafness genes are essential to improve the efficiency and to reduce the cost of molecular diagnosis. They may depend on several factors, including a clear delineation of the source of patients being studied. In the present study, we hypothesize that patients with idiopathic sensorineural hearing loss recruited from different sources might reveal discrepancies in the epidemiological results of genetic screening, because patients from different sources might demonstrate distinct clinical or audiologic features and thus result in biased selection of subjects. To elucidate the relative importance of common deafness genes in Taiwanese and to verify our hypothesis, we conducted a prospective project screening mutations in GJB2, SLC26A4 and mitochondrial 12S rRNA gene in a total of 420 Taiwanese families with idiopathic bilateral sensorineural hearing loss, of which 325 families were recruited from hospitals and 95 from hearing rehabilitation facilities. Allele frequencies of common mutations in these three genes and distributions of the corresponding genotypes were then compared between the two groups. The allele frequencies of mutations in SLC26A4, GJB2 and mitochondrial 12S rRNA in the probands of the 420 families were 14.4, 21.7 and 3.8%, respectively. The allele frequency of SLC26A4 mutations in the hospital group was significantly higher than that in the rehabilitation facility group (16.2 vs. 8.4%, chi(2)-test, p < 0.05), whereas no difference in the frequencies of GJB2 mutations and mitochondrial 12S rRNA mutations was found between the two groups. Distributions of probands classified by SLC26A4 genotypes were also different between the two groups (chi(2)-test, p < 0.05). Accordingly, a discrepancy in the genetic screening results might exist between different sources of idiopathic hearing-impaired patients. Further analysis of audiological results and construction of a logistic regression model showed that different audiological features, namely hearing levels and hearing loss patterns, might be responsible for the unequal distributions of mutations and probands between the hospital and rehabilitation facility groups. [ABSTRACT FROM AUTHOR]

BACKGROUND: EMR techniques have high success rates for treating small lesions of the upper-GI tract; however, tumors larger than 15 mm are frequently removed by piecemeal resection, which is associated with an increased rate of disease recurrence and difficulty in histologically evaluating the specimen. OBJECTIVE: To describe a simple technique of using internal traction to facilitate endoscopic submucosal dissection (ESD) procedures in the excision of large, early gastric cancers. DESIGN: Case series. SETTING: A tertiary medical center in Taiwan. PATIENTS AND METHODS: Eight patients with early gastric cancers larger than 20 mm underwent ESD. INTERVENTIONS: A standard hemoclip modified with surgical suture was used to provide traction to improve visualization of the dissection plane during ESD. MAIN OUTCOME MEASUREMENTS: Proportion with complete en bloc resection. RESULTS: En bloc resection of the lesion was achieved in 8 patients. One patient underwent additional surgery because an adequate safe margin was not obtained by ESD. LIMITATIONS: One endoscopist performed all procedures, and only 8 patients were studied in an uncontrolled manner. CONCLUSIONS: The internal traction method appears to facilitate en bloc ESD of early gastric cancers larger than 20 mm. [ABSTRACT FROM AUTHOR]

PURPOSE: Acute respiratory failure requiring mechanical ventilation in severe community-acquired pneumonia has been shown to be a significant negative prognostic factor. We analyzed the early evolution of the Pao(2)/Fio(2) ratio and evaluated its clinical value as an outcome predictor. MATERIALS AND METHODS: This is a prospective study conducted in a tertiary referral hospital. In 62 adult patients requiring early mechanical ventilation due to severe community-acquired pneumonia, we measured serial changes in Pao(2)/Fio(2) ratio and other clinical variables within the first 48 hours of mechanical ventilation and compared the difference between survivors and nonsurvivors. RESULTS: The initial Pao(2)/Fio(2) ratio was lower in nonsurvivors (n = 27) than in survivors (n = 35) (158.0 +/- 55.8 vs 117.9 +/- 50.6, P = .025). Over the next 48 hours, the ratio increased significantly in survivors but not in nonsurvivors (analysis of variance, P < .001). An increase in Pao(2)/Fio(2) ratio greater than 56 mm Hg had a sensitivity of 75% and a specificity of 81% of survival. A definite causative pathogen was identified in 36 patients (58%) and the 3 most commonly isolated pathogens were Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae. Ten patients received inadequate initial empirical antimicrobial therapy, in which the Pao(2)/Fio(2) ratio change was significantly less than those who were adequately treated (analysis of variance, P < .001). Mortality was much higher (86% [6/7]) in patients who received inadequate antibiotics and where Pao(2)/Fio(2) ratio change was less than 56 mm Hg. On multivariate analysis, trend changes in Pao(2)/Fio(2) ratio over 48 hours, shock, and Acute Physiology and Chronic Health Evaluation II score were documented to be independent predictors of mortality. CONCLUSIONS: A progressive improvement of Pao(2)/Fio(2) ratio during the first 48 hours of mechanical ventilation indicates favorable outcome. Serial measurement of this ratio should be considered in decision making for therapeutic strategy.Copyright © 2007 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the study was to describe the outcome of patients after 1 year's implementation of an integrated delivery system for respiratory care mandated by the National Health Insurance Bureau in Taiwan. DESIGN: A retrospective observational study was conducted in a step-down respiratory care center (RCC). PATIENTS: Patients included adults receiving prolonged mechanical ventilation (>/=21 days). MEASUREMENTS AND MAIN RESULTS: A total of 224 cases were available for review; 108 (48.2%) patients were successfully weaned. Those who failed weaning had a longer stay in the intensive care unit and RCC (25.1 vs 20.9 and 31.4 vs 18.6 days, P < .05), but there were no differences in the patients' ages (74.3 vs 70.4 years, P = .17) or the Simplified Acute Physiology Score II (52 vs 46.9, P = .18) before admission to the RCC. After discharge from the RCC, only 4.9% of the patients still on a ventilator were weaned within 1 year. Patients who failed weaning in the RCC had a shorter overall survival (5.2 vs 10.4 months, P < .05) and a lower 1-year survival (23.6% vs 44.6%, P < .05). CONCLUSION: Patients admitted to the RCC were still critically ill. Patients who failed weaning in the RCC had had a longer intensive care unit and RCC stay and a worse outcome after leaving the RCC. Copyright © 2006 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Study Objectives: Severe acute respiratory syndrome (SARS) is a rapidly progressive disease caused by a novel coronavirus (CoV) infection. However, the disease presentation is nonspecific. The aim of this study was to define clearly the presentation, clinical progression, and laboratory data in a group of patients who had SARS.Design: Retrospective observational study.Setting: A tertiary care medical center with 51 negative-pressure isolation rooms in Taipei, Taiwan.Patients: Fifty-three patients with SARS seen between April 27 and June 16, 2003.Results: Fever (ie, temperature > 38 degrees C) was the most common symptom (98%) and the earliest. When admitted to the isolation unit of the hospital for observation, most patients reported nonspecific symptoms associated with their fever. Only two patients with preexisting illnesses had cough on the same day the fever began. Eventually, 39 patients (74%) developed cough, beginning at a mean (+/- SD) time of 4.5 +/- 1.9 days after fever onset, and 35 patients (66%) had diarrhea beginning at a mean time of 6.0 +/- 3.3 days after fever onset. Thirty-one patients (59%) had abnormal findings on chest radiographs on hospital admission, and all but 1 patient (98%) eventually developed lung infiltrates that were consistent with pneumonia. The majority of patients (63%) first developed unifocal infiltrates at a mean time of 4.5 +/- 2.1 days after fever onset, while in 37% of patients the initial infiltrates were multifocal, appearing at a mean time of 5.8 +/- 1.3 days after fever onset. Common laboratory findings included lymphopenia (on hospital admission, 70%; during hospitalization, 95%), thrombocytopenia (on hospital admission, 28%; during hospitalization, 40%), elevated lactate dehydrogenase (on hospital admission, 58%; during hospitalization, 88%), creatine kinase (on hospital admission, 18%; during hospitalization, 32%), and aspartate aminotransferase or alanine aminotransferase levels (on hospital admission, 27%; during hospitalization, 62%). Throat or nasopharyngeal swab for SARS-CoV by reverse transcriptase polymerase chain reaction (PCR) and real-time PCR was positive in 40 of the 47 patients (85%) in whom the test was performed.Conclusions: None of the presenting symptoms or laboratory findings are pathognomonic for SARS. Even though cough developed in a majority of patients, it did not occur until later in the disease course, suggesting that a cough preceding or concurrent with the onset of fever is less likely to indicate SARS. While PCR for SARS-CoV appears to be the best early diagnostic test currently available, it is clear that better methods are needed to differentiate between SARS and non-SARS illness on initial presentation. [ABSTRACT FROM AUTHOR]

Pre-treatment host and viral factors may affect serum ferritin levels in patients with hepatitis C virus (HCV) infection. We delineated pre-treatment factors associated with hyperferritinemia in these patients. 1682 eligible patients underwent pre-treatment assessment for serum ferritin and various host/viral factors. Univariate and multivariate logistic regression analyses were conducted to evaluate factors associated with hyperferritinemia. Multivariate logistic regression analyses revealed that age > 50 years (adjusted odds ratio [OR]: 1.38 (95% confidence interval [CI] 1.09-1.74), p = 0.008), fibrosis stage ≥ F3 (adjusted OR: 1.36 (95% CI 1.04-1.77), p = 0.02), fibrosis index based on four parameters (FIB-4) > 3.25 (adjusted OR: 1.46 (95% CI 1.11-1.92), p = 0.01), presence of metabolic dysfunction-associated steatotic liver disease (MASLD) (adjusted OR: 1.43 (95% CI 1.21-1.76), p = 0.001), and alanine transaminase (ALT) > 2 folds upper limit of normal (ULN) (adjusted OR: 2.87 (95% CI 2.20-3.75), p < 0.001) were associated hyperferritinemia. The log 10 value of HBV or HCV viral load was not associated with the log 10 value of ferritin level (Spearman's rank correlation coefficient: - 0.025, p = 0.81 and 0.002, p = 0.92). In conclusion, host factors, rather than viral factors, are associated with hyperferritinemia in patients with HCV., (© 2024. The Author(s).)