Structural variability of the cerebral cortex in schizophrenia and its association with clinical symptoms.

BACKGROUND: Substantial evidence indicates structural abnormalities in the cerebral cortex of patients with schizophrenia (SCZ), although their clinical implications remain unclear. Previous case-control studies have investigated group-level differences in structural abnormalities, although the study design cannot account for interindividual differences. Recent research has focused on the association between the heterogeneity of the cerebral cortex morphometric features and clinical heterogeneity. METHODS: We used neuroimaging data from 420 healthy controls and 695 patients with SCZ from seven studies. Four cerebral cortex measures were obtained: surface area, gray matter volume, thickness, and local gyrification index. We calculated the coefficient of variation (CV) and person-based similarity index (PBSI) scores and performed group comparisons. Associations between the PBSI scores and cognitive functions were evaluated using Spearman's rho test and normative modeling. RESULTS: Patients with SCZ had a greater CV of surface area and cortical thickness than those of healthy controls. All PBSI scores across cortical measures were lower in patients with SCZ than in HCs. In the patient group, the PBSI scores for gray matter volume and all cortical measures taken together positively correlated with the full-scale IQ scores. Patients with deviant PBSI scores for gray matter volume and all cortical measures taken together had lower full-scale IQ scores than those of other patients. CONCLUSIONS: The cerebral cortex in patients with SCZ showed greater regional and global structural variability than that in healthy controls. Patients with deviant similarity of cortical structural profiles exhibited a lower general intelligence than those exhibited by the other patients.

Characterization of the extracellular free water signal in schizophrenia using multi-site diffusion MRI harmonization.

Studies applying Free Water Imaging have consistently reported significant global increases in extracellular free water (FW) in populations of individuals with early psychosis. However, these published studies focused on homogenous clinical participant groups (e.g., only first episode or chronic), thereby limiting our understanding of the time course of free water elevations across illness stages. Moreover, the relationship between FW and duration of illness has yet to be directly tested. Leveraging our multi-site diffusion magnetic resonance imaging(dMRI) harmonization approach, we analyzed dMRI scans collected by 12 international sites from 441 healthy controls and 434 individuals diagnosed with schizophrenia-spectrum disorders at different illness stages and ages (15-58 years). We characterized the pattern of age-related FW changes by assessing whole brain white matter in individuals with schizophrenia and healthy controls. In individuals with schizophrenia, average whole brain FW was higher than in controls across all ages, with the greatest FW values observed from 15 to 23 years (effect size range = [0.70-0.87]). Following this peak, FW exhibited a monotonic decrease until reaching a minima at the age of 39 years. After 39 years, an attenuated monotonic increase in FW was observed, but with markedly smaller effect sizes when compared to younger patients (effect size range = [0.32-0.43]). Importantly, FW was found to be negatively associated with duration of illness in schizophrenia (p = 0.006), independent of the effects of other clinical and demographic data. In summary, our study finds in a large, age-diverse sample that participants with schizophrenia with a shorter duration of illness showed higher FW values compared to participants with more prolonged illness. Our findings provide further evidence that elevations in the FW are present in individuals with schizophrenia, with the greatest differences in the FW being observed in those at the early stages of the disorder, which might suggest acute extracellular processes.

White matter tract alterations in schizophrenia identified by DTI-based probabilistic tractography: a multisite harmonisation study.

INTRODUCTION: It has been suggested that schizophrenia involves dysconnectivity between functional brain regions and also the white matter structural disorganisation. Thus, diffusion tensor imaging (DTI) has widely been used for studying schizophrenia. However, most previous studies have used the region of interest (ROI) based approach. We, therefore, performed the probabilistic tractography method in this study to reveal the alterations of white matter tracts in the schizophrenia brain. METHODS: A total of four different datasets consisted of 189 patients with schizophrenia and 213 healthy controls were investigated. We performed retrospective harmonisation of raw diffusion MRI data by dMRIharmonisation and used the FMRIB Software Library (FSL) for probabilistic tractography. The connectivities between different ROIs were then compared between patients and controls. Furthermore, we evaluated the relationship between the connection probabilities and the symptoms and cognitive measures in patients with schizophrenia. RESULTS: After applying Bonferroni correction for multiple comparisons, 11 different tracts showed significant differences between patients with schizophrenia and healthy controls. Many of these tracts were associated with the basal ganglia or cortico-striatal structures, which aligns with the current literature highlighting striatal dysfunction. Moreover, we found that these tracts demonstrated statistically significant relationships with few cognitive measures related to language, executive function, or processing speed. CONCLUSION: We performed probabilistic tractography using a large, harmonised dataset of diffusion MRI data, which enhanced the statistical power of our study. It is important to note that most of the tracts identified in this study, particularly callosal and cortico-striatal streamlines, have been previously implicated in schizophrenia within the current literature. Further research with harmonised data focusing specifically on these brain regions could be recommended.

Antipsychotic treatment and risk of discontinuation and hospitalization in first-episode schizophrenia: a nationwide population-based study.

BACKGROUND: Current evidence on antipsychotic treatment and risk of psychiatric hospitalization in first-episode schizophrenia (FES) is largely based on the findings from randomized clinical trials (RCTs). However, the generalization of the findings to real-world patients is limited due to inherent caveats of the RCT. We aimed to investigate the treatment discontinuation and risk of psychiatric hospitalization using a nationwide population database. METHODS: The Health Insurance Review Agency database in South Korea was obtained, and the observation period started from 1 January 2009 to 31 December 2016. We defined the maintenance period as the period from 6-month after the diagnosis of schizophrenia, which is utilized for the main results. For a total of 44 396 patients with FES, a within-individual Cox regression model was used to compare the risk of the treatment discontinuation and psychiatric hospitalization. RESULTS: In group comparison, a long-acting injectable (LAI) antipsychotic group was associated with the lowest risk of the treatment discontinuation (0.64, 0.55-0.75) and psychiatric hospitalization (0.29, 0.22-0.38) in comparison with a typical antipsychotic group and no use, respectively. Among individual antipsychotics, the lowest risk of the treatment discontinuation was observed in LAI paliperidone (0.46, 0.37-0.66) compared to olanzapine. Clozapine was found to be the most effective antipsychotic in lowering the risk of psychiatric hospitalization as monotherapy compared to no use (0.23, 0.18-0.31). CONCLUSIONS: In real-world patients with FES, LAI paliperidone and clozapine were associated with low treatment discontinuation and better effectiveness in lowering the risk of psychiatric hospitalization.

Cognitive deficits, clinical variables, and white matter microstructure in schizophrenia: a multisite harmonization study.

Cognitive deficits are among the best predictors of real-world functioning in schizophrenia. However, our understanding of how cognitive deficits relate to neuropathology and clinical presentation over the disease lifespan is limited. Here, we combine multi-site, harmonized cognitive, imaging, demographic, and clinical data from over 900 individuals to characterize a) cognitive deficits across the schizophrenia lifespan and b) the association between cognitive deficits, clinical presentation, and white matter (WM) microstructure. Multimodal harmonization was accomplished using T-scores for cognitive data, previously reported standardization methods for demographic and clinical data, and an established harmonization method for imaging data. We applied t-tests and correlation analysis to describe cognitive deficits in individuals with schizophrenia. We then calculated whole-brain WM fractional anisotropy (FA) and utilized regression-mediation analyses to model the association between diagnosis, FA, and cognitive deficits. We observed pronounced cognitive deficits in individuals with schizophrenia (p < 0.006), associated with more positive symptoms and medication dosage. Regression-mediation analyses showed that WM microstructure mediated the association between schizophrenia and language/processing speed/working memory/non-verbal memory. In addition, processing speed mediated the influence of diagnosis and WM microstructure on the other cognitive domains. Our study highlights the critical role of cognitive deficits in schizophrenia. We further show that WM is crucial when trying to understand the role of cognitive deficits, given that it explains the association between schizophrenia and cognitive deficits (directly and via processing speed).

Impact of the early phase of the COVID-19 pandemic on the use of mental health services in South Korea: a nationwide, health insurance data-based study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the utilization of mental health services. Existing evidence investigating this issue at the nationwide level is lacking, and it is uncertain whether the effects of the COVID-19 pandemic on the use of psychiatric services differs based on psychiatric diagnosis. METHODS: Data from the claims database between October 2015 and August 2020 was obtained from the Health Insurance Review and Assessment agency in South Korea. Based on the main diagnostic codes, psychiatric patients were identified and categorized into diagnostic groups (anxiety disorders, bipolar and related disorders, depressive disorders, and schizophrenia spectrum disorders). We calculated the number of psychiatric inpatients and outpatients and the medication adherence of patients for each month. We compared the actual and predicted values of outcomes during the COVID-19 pandemic and performed interrupted time-series analyses to test the statistical significance of the impact of the pandemic. RESULTS: During the COVID-19 pandemic, the number of inpatients and admissions to psychiatric hospitals decreased for bipolar and related disorders and depressive disorders. In addition, the number of patients admitted to psychiatric hospitals for schizophrenia spectrum disorders decreased. The number of psychiatric outpatients showed no significant change in all diagnostic groups. Increased medication adherence was observed for depressive, schizophrenia spectrum, and bipolar and related disorders. CONCLUSIONS: In the early phase of the COVID-19 pandemic, there was a trend of a decreasing number of psychiatric inpatients and increasing medication adherence; however, the number of psychiatric outpatients remained unaltered.

Linguistic anomalies observed in the Sentence Completion Test in patients with schizophrenia.

BACKGROUND: Schizophrenia is a chronic, debilitating disorder characterised by distorted thinking, perceptions, behaviours, and even language impairments. We investigated the linguistic anomalies in Korean schizophrenia patients compared to non-psychotic psychiatric controls to determine whether the linguistic anomalies in English speakers with schizophrenia were replicated in Korean speakers. METHODS: Thirty-four schizophrenia patients and 70 non-psychotic psychiatric controls were included in this study. The SCT was utilised as the text data for analysis. For linguistic analysis, we evaluated texts regarding semantics and syntax. We separately counted the number of semantic or syntactic errors in the written texts of study participants and compared them between patients and controls. RESULTS: Schizophrenia patients showed significantly more semantic errors (p < .001) and syntactic errors (p < .001) per 1,000 characters than non-psychotic psychiatric controls. Specifically, inappropriate word or syntactic component selection is noticeable in schizophrenia patients. These differences were still significant after adjusting for general intelligence measured by the K-WAIS-IV. CONCLUSION: Schizophrenia patients showed both semantic and syntactic errors in written language. Moreover, these errors seemed to be partly independent of general intelligence. Notably, patients showed a noticeable number of syntactic errors. Further investigation into the language of patients with schizophrenia and schizophrenia-spectrum disorders is required.

Structural impairment in superficial and deep white matter in schizophrenia.

OBJECTIVE: Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects. METHODS: We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman's rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing. RESULTS: Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial-occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing. CONCLUSION: We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.

Elucidating the relationship between white matter structure, demographic, and clinical variables in schizophrenia-a multicenter harmonized diffusion tensor imaging study.

White matter (WM) abnormalities are repeatedly demonstrated across the schizophrenia time-course. However, our understanding of how demographic and clinical variables interact, influence, or are dependent on WM pathologies is limited. The most well-known barriers to progress are heterogeneous findings due to small sample sizes and the confounding influence of age on WM. The present study leverages access to the harmonized diffusion magnetic-resonance-imaging data and standardized clinical data from 13 international sites (597 schizophrenia patients (SCZ)). Fractional anisotropy (FA) values for all major WM structures in patients were predicted based on FA models estimated from a healthy population (n = 492). We utilized the deviations between predicted and real FA values to answer three essential questions. (1) "Which clinical variables explain WM abnormalities?". (2) "Does the degree of WM abnormalities predict symptom severity?". (3) "Does sex influence any of those relationships?". Regression and mediator analyses revealed that a longer duration-of-illness is associated with more severe WM abnormalities in several tracts. In addition, they demonstrated that a higher antipsychotic medication dose is related to more severe corpus callosum abnormalities. A structural equation model revealed that patients with more WM abnormalities display higher symptom severity. Last, the results exhibited sex-specificity. Males showed a stronger association between duration-of-illness and WM abnormalities. Females presented a stronger association between WM abnormalities and symptom severity, with IQ impacting this relationship. Our findings provide clear evidence for the interaction of demographic, clinical, and behavioral variables with WM pathology in SCZ. Our results also point to the need for longitudinal studies, directly investigating the casualty and sex-specificity of these relationships, as well as the impact of cognitive resiliency on structure-function relationships.

Fever as a Side Effect after Electroconvulsive Therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is the most important and safe nonpharmacological treatment for psychiatric disorders. Some patients experience unexplained fever after ECT, but only a few studies have reported on this. METHOD: We investigated fever after ECT by retrospectively reviewing the medical records of patients. Patients treated at the ECT unit of the Department of Psychiatry at Asan Medical Center, Seoul, South Korea, between 30 June 2004 and 30 June 2019, were included. Differences in variables were compared between groups with or without fever after ECT sessions. RESULT: There were 28 patients (8.8%) in the fever group. Forty-three ECT sessions (1.5%) resulted in fever after treatment. The female-to-male ratio was higher in the fever group than in the control group, and the mean number of total ECT sessions was also higher in the fever group than in the control group, but there were no other differences between the 2 groups. CONCLUSION: Comparing fever and control sessions, fever sessions relatively preceded control sessions and had a longer seizure duration. Postictal delirium occurred more often in the fever sessions than in control sessions. Fever sessions had a higher white blood cell count and lower concomitant quetiapine dosage than control sessions. Because 8.8% of patients who received ECT experienced fever after treatment more than once, fever after ECT is considered to be a common side effect.

Investigating Sexual Dimorphism of Human White Matter in a Harmonized, Multisite Diffusion Magnetic Resonance Imaging Study.

Axonal myelination and repair, critical processes for brain development, maturation, and aging, remain controlled by sexual hormones. Whether this influence is reflected in structural brain differences between sexes, and whether it can be quantified by neuroimaging, remains controversial. Diffusion-weighted magnetic resonance imaging (dMRI) is an in vivo method that can track myelination changes throughout the lifespan. We utilize a large, multisite sample of harmonized dMRI data (n = 551, age = 9-65 years, 46% females/54% males) to investigate the influence of sex on white matter (WM) structure. We model lifespan trajectories of WM using the most common dMRI measure fractional anisotropy (FA). Next, we examine the influence of both age and sex on FA variability. We estimate the overlap between male and female FA and test whether it is possible to label individual brains as male or female. Our results demonstrate regionally and spatially specific effects of sex. Sex differences are limited to limbic structures and young ages. Additionally, not only do sex differences diminish with age, but tracts within each subject become more similar to one another. Last, we show the high overlap in FA between sexes, which implies that determining sex based on WM remains open.

Delay in psychiatric hospitalization from the diagnosis of first-episode schizophrenia and its association with clinical outcomes and direct medical costs: a nationwide, health insurance data-based study.

BACKGROUND: Early intervention is essential for improving the prognosis in patients with first-episode schizophrenia (FES). The Mental Health Act limits involuntary hospitalization in South Korea to cases where an individual exhibits both a mental disorder and a potential for harming themselves or others, which could result in a delay in the required treatment in FES. We investigated the effect of delay in the first psychiatric hospitalization on clinical outcomes in FES. METHODS: The South Korean Health Insurance Review Agency database (2012-2019) was used. We identified 15,994 patients with FES who had a record of at least one psychiatric hospitalization within 1 year from their diagnosis. A multivariate linear regression model and a generalized linear model with a gamma distribution and log link were used to examine associations between the duration from the diagnosis to the first psychiatric admission and clinical outcomes as well as direct medical costs after 2 and 5 years. RESULTS: Within both the 2-year and the 5-year period, longer durations from the diagnosis to the first psychiatric admission were associated with an increase in the number of psychiatric hospitalizations (2-y: B = 0.003, p = 0.003, 5-y: B = 0.007, p = 0.001) and an increase in direct medical costs (total: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.005; inpatient care: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.017). CONCLUSIONS: Earlier psychiatric admission from the diagnosis is associated with a decrease in the number of psychiatric admissions as well as in direct medical costs in patients with FES.

Risk of treatment discontinuation and psychiatric hospitalization associated with early dose reduction of antipsychotic treatment in first-episode schizophrenia: A nationwide, health insurance data-based study.

AIM: We investigated the impact of early dose reduction of antipsychotic treatment on the risk of treatment discontinuation and psychiatric hospitalization in patients with first-episode schizophrenia (FES). METHODS: The Health Insurance Review Agency database in South Korea was used to include 16 153 patients with FES. At 6 months from their diagnosis, the patients were categorized by the magnitude of dose reduction (no reduction, 0%-50%, and >50%). With a reference of no reduction, the risk of treatment discontinuation and psychiatric hospitalization associated with dose reduction in the 1-year follow-up period after the first 6 months was examined with a Cox proportional hazard ratio model stratified by the mean daily olanzapine-equivalent dose in the first 3 months (<10, 10 to 20, >20 mg/day). RESULTS: A >50% dose reduction was associated with an increased risk of treatment discontinuation in all subgroups (<10 mg/day: hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.24-1.67 [P <0.01]; 10-20 mg/day: HR =1.60, 95% CI =1.37-1.86 [P <0.01]; and >20 mg/day: HR =1.62, 95% CI =1.37-1.91 [P <0.01]). In the subgroup taking <10 mg/day, an association of 0%-50% dose reduction with an increased risk of treatment discontinuation was observed (HR =1.20, 95% CI =1.09-1.31; P <0.01). A > 50% dose reduction was associated with increased risk of psychiatric hospitalization only in the subgroup taking <10 mg/day (HR =1.48, 95% CI =1.21-1.80; P <0.01). CONCLUSIONS: Our results suggest that an above certain dose of antipsychotic drugs is required to prevent psychiatric hospitalization, and extensive dose reduction of antipsychotic drugs could result in a higher risk of treatment discontinuation.

Improving the predictive potential of diffusion MRI in schizophrenia using normative models-Towards subject-level classification.

Diffusion MRI studies consistently report group differences in white matter between individuals diagnosed with schizophrenia and healthy controls. Nevertheless, the abnormalities found at the group-level are often not observed at the individual level. Among the different approaches aiming to study white matter abnormalities at the subject level, normative modeling analysis takes a step towards subject-level predictions by identifying affected brain locations in individual subjects based on extreme deviations from a normative range. Here, we leveraged a large harmonized diffusion MRI dataset from 512 healthy controls and 601 individuals diagnosed with schizophrenia, to study whether normative modeling can improve subject-level predictions from a binary classifier. To this aim, individual deviations from a normative model of standard (fractional anisotropy) and advanced (free-water) dMRI measures, were calculated by means of age and sex-adjusted z-scores relative to control data, in 18 white matter regions. Even though larger effect sizes are found when testing for group differences in z-scores than are found with raw values (p < .001), predictions based on summary z-score measures achieved low predictive power (AUC < 0.63). Instead, we find that combining information from the different white matter tracts, while using multiple imaging measures simultaneously, improves prediction performance (the best predictor achieved AUC = 0.726). Our findings suggest that extreme deviations from a normative model are not optimal features for prediction. However, including the complete distribution of deviations across multiple imaging measures improves prediction, and could aid in subject-level classification.

Clinical significance of HER2 status in T1bN0 breast cancer: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: The prognosis of patients with node-negative T1b tumors according to human epidermal growth factor receptor 2 (HER2) status is not known. This group of patients has not been studied in the available randomized trials. The objective of this study was to evaluate the survival of patients in a monoethnic group diagnosed with T1b lymph node-negative breast cancer depending on HER2 status. METHODS: We analyzed 3110 patients with T1bN0M0 breast cancer whose data were deposited into the Korean Breast Cancer Society Registry database between 2000 and 2009. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared according to HER2 status. RESULTS: Among all patients, 494 (15.9%) had HER2-positive breast cancer. At a mean follow-up of 93 months, 108 deaths and 86 breast cancer-specific deaths were noted among all patients. There was no significant difference in OS between the HER2-negative and HER2-positive groups (p = 0.103). The same result was observed for BCSS. However, in the subgroup of estrogen receptor (ER)-positive women, HER2-negative patients had a better BCSS prognosis than HER2-positive patients (p = 0.025). Multivariate analysis also indicated a significant difference in BCSS in the ER-positive subgroup (HR 2.60; 95% CI 1.15-5.87; p = 0.021). CONCLUSION: This study analyzed a large nationwide and monoethnic cohort and found a significant difference only in BCSS in the ER-positive subgroup according to HER2 status. Anti-HER2 therapy may be considered in HER2-positive and ER-positive patients with small, node-negative breast cancer.

White matter abnormalities across the lifespan of schizophrenia: a harmonized multi-site diffusion MRI study.

Several prominent theories of schizophrenia suggest that structural white matter pathologies may follow a developmental, maturational, and/or degenerative process. However, a lack of lifespan studies has precluded verification of these theories. Here, we analyze the largest sample of carefully harmonized diffusion MRI data to comprehensively characterize age-related white matter trajectories, as measured by fractional anisotropy (FA), across the course of schizophrenia. Our analysis comprises diffusion scans of 600 schizophrenia patients and 492 healthy controls at different illness stages and ages (14-65 years), which were gathered from 13 sites. We determined the pattern of age-related FA changes by cross-sectionally assessing the timing of the structural neuropathology associated with schizophrenia. Quadratic curves were used to model between-group FA differences across whole-brain white matter and fiber tracts at each age; fiber tracts were then clustered according to both the effect-sizes and pattern of lifespan white matter FA differences. In whole-brain white matter, FA was significantly lower across the lifespan (up to 7%; p < 0.0033) and reached peak maturation younger in patients (27 years) compared to controls (33 years). Additionally, three distinct patterns of neuropathology emerged when investigating white matter fiber tracts in patients: (1) developmental abnormalities in limbic fibers, (2) accelerated aging and abnormal maturation in long-range association fibers, (3) severe developmental abnormalities and accelerated aging in callosal fibers. Our findings strongly suggest that white matter in schizophrenia is affected across entire stages of the disease. Perhaps most strikingly, we show that white matter changes in schizophrenia involve dynamic interactions between neuropathological processes in a tract-specific manner.

Effects of comorbid alcohol use disorder on the clinical outcomes of first-episode schizophrenia: a nationwide population-based study.

BACKGROUND: Alcohol use disorder (AUD) is a common psychiatric comorbidity in schizophrenia, associated with poor clinical outcomes and medication noncompliance. Most previous studies on the effect of alcohol use in patients with schizophrenia had limitations of small sample size or a cross-sectional design. Therefore, we used a nationwide population database to investigate the impact of AUD on clinical outcomes of schizophrenia. METHODS: Data from the Health Insurance Review Agency database in South Korea from January 1, 2007 to December 31, 2016 were used. Among 64,442 patients with first-episode schizophrenia, 1598 patients with comorbid AUD were selected based on the diagnostic code F10. We performed between- and within-group analyses to compare the rates of psychiatric admissions and emergency room (ER) visits, and medication possession ratio (MPR) between the patients with comorbid AUD and control patients matched for the onset age, sex, and observation period. RESULTS: The rates of psychiatric admissions and ER visits in both groups decreased after the time point of diagnosis of AUD; however, the decrease was significantly greater in the patients with comorbid AUD compared to the control patients. While the comorbid AUD group showed an increase in MPR after the diagnosis of AUD, MPR decreased in the control group. The rates of psychiatric admissions, ER visits, and MPR were worse in the comorbid AUD group both before and after the diagnosis of AUD. CONCLUSIONS: The results emphasize an importance of psychiatric comorbidities, especially AUD, in first-episode schizophrenia and the necessity of further research for confirmative findings of the association of AUD with clinical outcomes of schizophrenia.

Educational needs and disaster response readiness: A cross-sectional study of clinical nurses.

AIM: To analyse clinical nurses' educational needs and disaster response readiness and the factors influencing their disaster response readiness. DESIGN: This was a cross-sectional study. METHODS: A convenience sample comprising 260 nurses with more than a year of working experience at a hospital in Korea was selected from 1-31 August 2019. Data on nurses' educational needs and disaster response readiness were collected from participants. A multiple regression model was used to examine the factors influencing disaster response readiness among nurses. RESULTS: Factors influencing personal readiness were number of years of clinical experience, being female, working in a medical ward, and educational needs for disaster response. Factors influencing self-protection were working in a medical ward and working in the emergency room. Factors influencing the emergency response were working in a medical ward and working in the emergency room. Factors influencing clinical management were a graduate-level education or higher, working in a medical ward, working in the emergency room, working in the paediatric ward, experience receiving disaster-related education, and educational needs for disaster response. CONCLUSION: It is essential to be aware of the educational needs and disaster readiness of hospital clinical nurses, to develop their capacity to respond such situations. In addition, to improve the disaster competency of nurses, it is necessary to develop an education programme that considers the factors influencing disaster response readiness in this study. IMPACT: Nurses must have the knowledge and skills to respond to a disaster. Nurse educators should help nurses strengthen their disaster-related knowledge, skills, and judgment. Hospital administrators should encourage nurse educators to provide disaster-related training and simulation-based education to increase nurses' disaster competency to act during disasters.

Discovery of Lactoferrin as a Stimulant for hADSC-Derived EV Secretion and Proof of Enhancement of Resulting EVs through Skin Model.

Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca2+, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca2+ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca2+, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs.