Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Objective: aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. Methods: aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. Results: aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. Conclusion aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

Background/Aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.