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.

Objective: Previous studies have shown that certain severe mental illnesses (SMIs) increase the risk of dementia, but those that increase the risk to a greater degree in comparison with other SMIs are unknown. Furthermore, physical illnesses may alter the risk of developing dementia, but these cannot be well-controlled. Methods: Using the Taiwan National Health Insurance Research Database, patients with schizophrenia, bipolar disorder and major depressive disorder (MDD) were recruited. We also recruited normal healthy subjects as the control group.All subjects were aged over 60 years, and the duration of follow-up was from 2008 to 2015. Multiple confounders were adjusted, including physical illnesses and other variables. Use of medications, especially benzodiazepines, was analyzed in a sensitivity analysis. Results: 36,029 subjects (MDD: 23,371, bipolar disorder: 4,883, schizophrenia: 7,775) and 108,084 control subjects were recruited after matching according to age and sex. The results showed that bipolar disorder had the highest hazard ratio (HR) (HR: 2.14, 95% confidence interval [CI]: 1.99−2.30), followed by schizophrenia (HR: 2.06, 95% CI: 1.93−2.19) and MDD (HR: 1.60, 95% CI: 1.51−1.69). The results remained robust after adjusting for covariates, and sensitivity analysis showed similar results. Anxiolytics use did not increase the risk of dementia in any of the three groups of SMI patients. Conclusion SMIs increase the risk of dementia, and among them, bipolar disorder confers the greatest risk of developing dementia. Anxiolytics may not increase the risk of developing dementia in patients with an SMI, but still need to be used with caution in clinical practices.

Background/Aims:  Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods:  From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

Objective: The impact of serotonergic system on obsessive-compulsive disorder (OCD) is well studied. However, the correlation between OC presentations and autonomic nervous system (ANS) is still unclear. Furthermore, whether the correlation might be modulated by serotonin is also uncertain. Methods: We recruited eighty-nine healthy subjects. Serotonin transporter (SERT) availability by [ 123 I]ADAM and heart rate variability (HRV) tests were measured. Symptoms checklist-90 was measured for the OC presentations. The interaction between HRV and SERT availability were calculated and the correlation between HRV and OC symptoms were analyzed after stratified SERT level into two groups, split at medium. Results: The interactions were significant in the factors of low frequency (LF), high frequency (HF), and root mean square of successive differences (RMSSD). Furthermore, the significantly negative correlations between OC symptoms and the above HRV indexes existed only in subjects with higher SERT availability. Conclusion OC symptoms might be correlated with ANS regulations in subjects with higher SERT availability.

Objective: Weight gain is an important risk factor for morbidity and mortality among patients with schizophrenia. We speculated that positive symptoms, related to dopaminergic hyperactivity and altered mesolimbic function, are associated with weight gain. Methods: Twenty-two antipsychotic-naïve, first-episode patients with schizophrenia were enrolled. The Positive and Negative Syndrome Scale was completed at enrollment and follow-up. Body mass index (BMI) was also measured. Results: The increase in BMI, after 6.04 ± 2.16 years of follow-up, was associated with positive symptoms, but not negative symptoms, before treatment with antipsychotics in antipsychotic-naïve patients with schizophrenia. Conclusion This finding implied that dopaminergic hyperactivity could be an important factor to predict the treatment outcome. Body weight control is important for the health management of patients with schizophrenia with more severe positive symptoms.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform β and γ proteins significantly increased in the CSF 2–3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 β, γ, ɛ, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.
Angiostrongylus cantonensis ; Angiostrongylus ; Animals ; Brain ; Dexamethasone ; Eosinophils ; Humans ; Meninges ; Meningitis ; Mice ; Protein Isoforms ; Steroids

OBJECTIVE: Altered event-related potential (ERP) performances have been noted in attention deficit hyperactivity disorder (ADHD) patients and reflect neurocognitive dysfunction. Whether these ERP alterations and correlated dysfunctions exist in healthy parents with ADHD offspring is worth exploring. METHODS: Thirteen healthy parents with ADHD offspring and thirteen healthy controls matched for age, sex and years of education were recruited. The auditory oddball paradigm was used to evaluate the P300 wave complex of the ERP, and the Wechsler Adult Intelligence Scale-Revised, Wisconsin Card Sorting Test, and continuous performance test were used to measure neurocognitive performance. RESULTS: Healthy parents with ADHD offspring had significantly longer auditory P300 latency at Fz than control group. However, no significant differences were found in cognitive performance. CONCLUSION: The presence of a subtle alteration in electro-neurophysiological activity without explicit neurocognitive dysfunction suggests potential candidate of biological marker for parents with ADHD offspring.
Adult ; Attention Deficit Disorder with Hyperactivity ; Biomarkers ; Cognition ; Education ; Evoked Potentials ; Humans ; Intelligence ; Parents ; Wisconsin

OBJECTIVE: Hospitalization of patients with delirium after visiting the emergency department (ED) is often required. However, the readmission risk after discharge from the ED should also be considered. This study aimed to explore whether (i) immediate hospitalization influences the readmission risk of patients with delirium; (ii) the readmission risk is affected by various risk factors; and (iii) the healthcare cost differs between groups within 28 days of the first ED visit. METHODS: Using the National Health Insurance Research Database, the data of 2,780 subjects presenting with delirium at an ED visit from 2000 to 2008 were examined. The readmission risks of the groups of patients (i.e., patients who were and were not admitted within 24 hours of an ED visit) within 28 days were compared, and the effects of the severities of different comorbidities (using Charlson’s comorbidity index, CCI), age, gender, diagnosis and differences in medical healthcare cost were analyzed. RESULTS: Patients without immediate hospitalization had a higher risk of readmission within 3, 7, 14, or 28 days of discharge from the ED, especially subjects with more severe comorbidities (CCI≥3) or older patients (≥65 years). Subjects with more severe comorbidities or older subjects who were not admitted immediately also incurred a greater healthcare cost for re-hospitalization within the 28-day follow-up period. CONCLUSION: Patients with delirium with a higher CCI or of a greater age should be carefully considered for immediate hospitalization from ED for further examination in order to reduce the risk of re-hospitalization and cost of healthcare.
Comorbidity ; Delirium* ; Delivery of Health Care* ; Diagnosis ; Emergencies* ; Emergency Service, Hospital* ; Follow-Up Studies ; Health Care Costs* ; Hospitalization* ; Humans ; National Health Programs ; Risk Factors

Although several algorithms have been applied to treat patients with schizophrenia, their clinical use remains still limited, because most emphasize the prescription of antipsychotics. A new algorithm with a more holistic approach to treating patients with schizophrenia, to be used before applying traditional prescribing guidelines, was thus proposed by an expert team of Taiwanese psychiatrists. In this algorithm, several important treatment tasks/modalities are proposed, including long-acting injection anti-psychotics, shared decision-making, a case management system, compulsory treatment by law, community rehabilitation programs, the patients' feeling about their health care professionals (patients' behaviors) and their attitude/knowledge of their conditions/illness. This study proposes that evaluating the medication adherence of patients can be determined by two key domains, namely patients' behaviors and attitudes. Based on different levels of their behaviors (X-axis) and attitude/knowledge (Y-axis), it is possible to categorize patients with schizophrenia into six subgroups, for which various different interventions, including the use of antipsychotics, could be applied and integrated. Further research is needed to assess the applicability of this treatment algorithm in clinical settings.
Antipsychotic Agents ; Case Management ; Delivery of Health Care ; Holistic Health ; Humans ; Jurisprudence ; Medication Adherence* ; Prescriptions ; Psychiatry ; Rehabilitation ; Schizophrenia*

PURPOSE: The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. MATERIALS AND METHODS: We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). RESULTS: Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85+/-0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. CONCLUSION: Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Butanones/therapeutic use ; Chronic Pain/*drug therapy ; Diclofenac/therapeutic use ; Female ; Muscles/drug effects ; Naproxen/therapeutic use ; Pelvic Floor/*pathology ; Pelvic Pain/*drug therapy ; Piroxicam/therapeutic use ; Rats ; Rats, Wistar ; Thiazines/therapeutic use ; Thiazoles/therapeutic use