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Objectives: Early pharmacologic intervention is considered necessary for improving the prognosis in patients with first-episode schizophrenia (FES). However, few nationwide population-based studies have focused on early medication adherence. We investigated the status of early adherence to antipsychotics and the effect of early adherence on later clinical outcomes in FES.Methods: We used data from the South Korean Health Insurance Review Agency database (2009-2021). We selected 28,931 patients with FES who had a prescription record of at least one antipsychotic medication within 180 days after their diagnosis. We measured early medication adherence using the medication possession ratio (MPR) and compared demographic characteristics and results of psychiatric hospitalization between the adherence group (0.6≤MPR

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.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.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.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.

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia (TRS). However, it remains uncertain whether antipsychotic augmentation to clozapine has the superior effectiveness over clozapine alone and the effect size of clozapine compared to other antipsychotic drugs in TRS. Therefore, we examined the comparative effectiveness of antipsychotic monotherapy and polypharmacy on the risk of psychiatric admission and treatment discontinuation in TRS. Data were collected from the Health Insurance Review Agency database between January 2010 and December 2019 in South Korea. Among prevalent patients with schizophrenia, we defined 22,327 patients with TRS as those who had been prescribed with clozapine at least once during the entire observation period. Stratified Cox proportional hazards regressions were performed using data on all antipsychotic prescriptions of patients with TRS to investigate the risk of psychiatric hospitalization and treatment discontinuation associated with antipsychotic treatment. In individual comparisons, clozapine monotherapy was the most effective for the risk of psychiatric hospitalization compared to no use (hazard ratio [HR] = 0.23, 95% confidence interval [CI] = 0.22-0.25). In group comparisons, clozapine with long-acting injectable (LAI) second-generation antipsychotics (SGA) was superior to clozapine monotherapy for the risk of psychiatric hospitalization (HR = 0.60, 95%CI = 0.41-0.88). Clozapine monotherapy was associated with the lowest risk of treatment discontinuation in the individual and group comparisons. This retrospective observational population-based study reports that clozapine with LAI SGA is more effective in lowering the risk of psychiatric hospitalization in antipsychotic group comparison with the reference of clozapine monotherapy.

Purpose: The purpose of this study was to identify the associations of chronic physical disease between patients with severe mental illness and the general population of South Korea. Methods: This study was conducted with National Health Insurance Corporation (NHIC) data from 2014 to 2019. A total of 842,459 people were diagnosed with severe mental illness (SMI) in this period, and the same number of controls were established by matching by sex and age. A descriptive analysis was conducted on the sociodemographic characteristics of patients with SMI. Conditional logistic regression analysis was performed to identify the associations between comorbid physical disease in patients with SMI and those of the general population. SAS Enterprise Guide 7.1 (SAS, Inc, Cary, NC) were used to perform all statistical tests. Result: The analysis revealed significant differences in medical insurance, income level, and Charlson Comorbidity Index (CCI) weighted by chronic physical disease, between patients with severe mental illness and the general population. Conditional logistic regression analysis between the two groups also revealed significant differences in all nine chronic physical diseases. Conclusions: The study found that people with severe mental illness had more chronic comorbid physical diseases than the general population. Therefore, people with severe mental illness have a reduced quality of life and a higher risk of excess mortality.

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).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).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]; and20 mg/day: HR =1.62, 95% CI =1.37-1.91 [P 0.01]). In the subgroup taking10 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 taking10 mg/day (HR =1.48, 95% CI =1.21-1.80; P 0.01).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.

It is essential to clinically distinguish bipolar affective disorder from unipolar affective disorders. However, patients previously diagnosed with unipolar affective disorder are sometimes later diagnosed with bipolar affective disorder, known as diagnostic conversion. Here we investigated diagnostic conversion using data from a nationwide population-based register.We obtained claims data from 2007 to 2020 in Korea's Health Insurance Review Agency database and identified a cohort of patients who were diagnosed with unipolar depression in 2009 without prior psychiatric diseases within the previous 2 years. We studied the rate of diagnostic conversion and risk factors, especially antidepressants.About 6.5% of patients underwent diagnostic conversion during the observation period. Younger age at disease onset and usage of antidepressants increased the relative risk for diagnostic conversion. Patients using serotonin-norepinephrine reuptake inhibitors (SNRI) showed more than twice the risk compared to no usage of antidepressant.First, this study was based on the population-based register data. Thus, we defined the patient cohort diagnosed with unipolar depression with strict inclusion criteria. Second, the exposure time differed between different antidepressants. Third, we estimated the relative risk for diagnostic conversion compared to no use of antidepressants. Moreover, we could not rule out the potential influence of antidepressant polypharmacy.We confirmed diagnostic conversion in some patients and identified younger age or usage of antidepressants, especially SNRI, as risk factors. Because unipolar and bipolar affective disorders show different disease courses or prognoses and have different treatment strategies, clinicians should be mindful of diagnostic conversion.

Background: Mammographic Breast Density (MBD) was known as a risk of breast cancer in either pre or postmenopausal women. The underlined mechanism remain unclear. Aldehyde dehydrogenase 1 (ALDH-1) and CD44+CD24− are the most consistently used biomarkers to identify and characterize breast cancer stem cells (CSCs). However, correlation between expression of CSCs and MBD remains unclear. We aimed to clarify the association between CD44, CD24 or ALDH-1 and the clinical factors including MBD for investigating their effects on overall survival (OS). Method: 159 operable breast cancers were finally included for double immune-histochemical staining of CD44, CD24 and single expression of ALDH-1. MBD was categorized according to the American College of Radiology Breast Imaging Reporting and Data System. Positive expression of CSC was defined when both Aldehyde dehydrogenase 1 (ALDH-1) and CD44+CD24− were expressed. Clinical values were age, co-morbidity (hypertension, hyperlipidemia, Diabetes Mellitus), body mass index, menopausal status. We also examined overall survival (OS) with the log-rank test. Result: Positive expression of BCSC was 33.3% (53/159 patients). It correlated with premenopausal status, high histologic grade, high Ki-67 expression, and low expression of ER or PR (Table 1). During mean 74 months, High BMD was correlated with worse OS in either pre- or postmenopausal patients (p=0.04) and worse OS in patients with co-morbidity (p=0.08). Expression of CSC was not associated with overall survival. In a group with CSC expression, patients of higher MBD(≥ 51%) was worse OS (p=0.046) compared with a group with non-CSC expression. Co-morbidity was significantly correlated with poor DFS in non-expressed group compared with CSC expressed group (p=0.01). In Cox-regression analysis, co-morbidity (HR=0.05, 95% CI: 0.006-0.44, p=0.007) and MBD ( HR= 0.14, 95% CI: 0.02-1.16, p=0.06) increased risk of OS. Conclusion: High MBD could be a prognostic factor in operable breast cancer. Each risk factor of survival was important, but host factors including comorbidity and MBD might be considered. Table 1.The correlation between BCSC and clinical variables in patient with operable breast cancerCSC(-)CSC(+)Number(%)Number(%)BMINormal68(65.4)36(34.6)0.63Obesity38(69.1)17(30.9)ComorbidityNo57(62.6)34(37.4)0.21Yes49(72.1)19(27.9)MBD≤ 50 %28(77.8)8(22.2)0.13≥ 51 %60(63.8)34(36.2)Age( year) Citation Format: JungSun Lee, Woo-Gyeong Kim. High Mammographic Breast density was correlated with overall survival of operable breast cancer which expressed CD44+CD24-/ALDH-1+ [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-24.

Objectives: The optimal duration of maintenance treatment for patients with first-episode schizophrenia (FES) remains unclear. We examined the first antipsychotic treatment duration and its association with re-initiation of treatment using a nationwide claim database.Methods: Data from the Health Insurance Review and Assessment Service database in South Korea for 2007–2016 were used. Linear regression analysis and Cox proportional hazard models were used to evaluate the associations between the duration of the first antipsychotic treatment, time to re-initiation of treatment, and occurrence of treatment re-initiation.Results: Of 30,143 patients with FES, 80.4% (n=24,231) received

In terms of thought disorder, the language of patients with schizophrenia itself could be a valuable resource. Some valuable studies on the language of patients with schizophrenia have been performed. However, most such studies have been confined to English-speaking countries, or at least those where Indo-European languages are spoken. Therefore, we investigated linguistic anomalies in the language of Korean patients with schizophrenia. Short texts written by 69 patients with schizophrenia from a single mental hospital and matched normal control participants were analyzed. We evaluated these texts in terms of semantic and syntactic errors. Then, we compared the error rates adjusted for text length between patients and normal control participants. We also divided the patients with schizophrenia into two groups by their duration of illness and compared these two groups to investigate the relationship between the duration of illness and linguistic anomalies. The patients with schizophrenia committed a total of 1.86 (2.52) semantic errors and 1.37 (1.79) syntactic errors per 100 characters, which were significantly more frequent than errors committed by normal control participants. Furthermore, there was a notably high number of semantic errors relative to syntactic errors in the language of patients with schizophrenia. Our study results are consistent with previous studies from English-speaking countries, implying that the linguistic anomalies of patients with schizophrenia are not confined to a single language. Because language is essential in mental function, further research on linguistic anomalies in patients with schizophrenia is recommended.

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.

Background/aims Because ankylosing spondylitis (AS) mainly affects sacroiliac joints, special attention should be given to normal labour and pregnancy outcomes. Here, we investigate pregnancy outcomes in Korean women with AS. Methods Based on data from the Korean Health Insurance Review and Assessment Service claims database since July 2007, maternal complications were compared between women with AS and 1:10 matched general population by maternal age and year of delivery. Additionally, the 27 deliveries from 21 patients with AS who were seen at a tertiary hospital were retrospectively evaluated using 1:4 matched control group by maternal and gestational age. Results In the population-based cohort, there were 1,293 deliveries in 996 patients with AS. Higher maternal age and more comorbidities were reported than in the general population. However, compared to age and delivery-year matched population, only the rate of Caesarean section (CS) was higher in women with AS (odds ratio, 1.52; 95% confidence interval, 1.36 to 1.70). Incidence of other maternal complications was comparable between women with AS and control subjects. In the hospital-based cohort, the CS rate was higher in women with AS (44.4% vs. 20.4%, p = 0.002). Causes of CS was not different in both groups, including previous uterine surgery. There were no significant differences in foetal outcomes, including growth restriction, foetal malformations and Apgar score. Conclusion CS deliveries were performed more often in women with AS. However, other maternal complications and offspring complications were similar between women with AS and healthy control subjects.

Surgeons are often reluctant to offer further intervention to patients with medically intractable facial blushing. This is mainly because of the relatively high failure rate of blushing resolution and a high incidence of compensatory hyperhidrosis. In this study, we sought to identify the type of blushing that would benefit from surgery and minimize compensatory hyperhidrosis by applying diffuse sympathicotomy (DS). This study was a retrospective review of 62 patients who underwent R2 endoscopic thoracic sympathicotomy (ETS) and preemptive DS for facial blushing. Facial blushing was classified as autonomic-mediated blushing (thermoregulatory, emotional) and vasodilator-mediated blushing (constant) based on the history and precipitating factors for blushing. DS was performed at lower-thoracic levels in the form of limited DS (right R5/7/9/11, left R5/6/8/10) or extended DS (bilateral R5-11). Resolution of blushing (described as "almost disappeared") was achieved in 48% of patients with a median follow-up of 19.6 months. There was a significant difference in resolution among 3 types of blushing (emotional: 55%, thermoregulatory: 28%, constant: 15%, P = .03). Multivariate analysis confirmed thermoregulatory and constant type blushing as a potential independent predictor of blushing resolution. Even though there was no difference between the DS procedures with respect to compensatory hyperhidrosis, intolerable compensatory hyperhidrosis (Hyperhidrosis Disease Severity Scale = 4) occurred in only 11% of patients. DS redistributed sweating area, being predominantly on the chest and mid-back (89%), also seen on the abdomen-waist-groin-buttocks-thighs (63%). Overall, 77% of patients experienced satisfactory results. Emotional blushing proved to be an established indication of ETS where good long-term results can be expected. Expansion of surgical indication to thermoregulatory or constant type blushing needs to be validated in future studies. Additionally, compensatory hyperhidrosis, another hurdle for ETS, can be minimized by preemptive DS, resulting in redistribution and decrease of sweating.

Studies applying Free Water Imaging have consistently reported significant global increases in extracellular 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 (FW) 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 who represent 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. Quadratic and non-parametric curves were used to model between-group FW differences in averaged whole brain white matter. In individuals with schizophrenia, whole brain FW was higher than in controls across all ages, with the greatest FW values observed from 15 to 23 years of age (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 of age, an attenuated monotonic increase in FW was observed, but with markedly lower 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 age. 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 indicate that FW might be a reliable imaging marker of acute, extracellular processes which appear to occur predominantly in the early stages of schizophrenia.

Sung Woo Joo,1 Harin Kim,1 Young Tak Jo,1 Soojin Ahn,1 Young Jae Choi,1 Woohyeok Choi,1 Soyeon Park,2 Jungsun Lee1 1Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Department of Psychiatry, Medical Foundation Yongin Mental Hospital, Yongin, Republic of KoreaCorrespondence: Jungsun Lee, Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3422, Fax +82-2-485-8381, Email js_lee@amc.seoul.krBackground: Although the use of electroconvulsive therapy (ECT) in the treatment of schizophrenia has decreased since the advent of antipsychotic drugs, ECT is still implemented in several clinical indications. However, a few population-based studies have examined its real-world effectiveness in schizophrenia.Methods: We used data from 2010 to 2019 from the Health Insurance Review and Assessment Service database in the Republic of Korea. We selected 380 schizophrenia patients having more than six ECT sessions and 1140 patient controls matched for age, sex, calendar year at entry, and the number of psychiatric hospitalizations before the time point of start of psychiatric hospitalization for ECT. Antipsychotic treatment discontinuation, psychiatric hospitalization, and direct medical costs were used as measures of clinical outcomes. Multiple regression analysis was used for any group-by-time interaction effect, and 1-year pre- and post-ECT periods were compared within and between the groups.Results: We found a significantly lower number of antipsychotic treatment discontinuations in the ECT group during the 1-year post-ECT period (t=2.195, p=0.028). A larger decrease was found in the number of psychiatric hospitalizations in the ECT group, with a group-by-time interaction effect (p=0.043). The direct medical costs in the 1-year pre- (t=− 8.782, p< 0.001) and post-ECT periods (t=− 9.107, p< 0.001) were higher in the ECT group than in the control group, with no significant change across both periods.Conclusion: We found that the ECT group had a larger decrease in the number of psychiatric hospitalizations in the 1-year post-ECT period than the control group.Keywords: schizophrenia, electroconvulsive therapy, population-based

Connective tissue disease (CTD) might occur during the course of idiopathic pulmonary fibrosis (IPF). Clinical factors associated with CTD development in IPF patients have still not been identified. We investigated which antibodies have a significant association with the development of CTD during the clinical course of IPF.We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014 and investigated the time to CTD development after IPF diagnosis in these patients.CTD developed in 15 patients at a median of 2.1 years (range 1.2-4.8) after IPF diagnosis. All patients had anti-neutrophil cytoplasmic antibodies (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonia with autoimmune features (IPAF). Survival duration for IPF patients with progression to CTD was 5.3 (3.8, 6.7) years, which was significantly longer than for IPF patients without progression to CTD [2.9 (1.7, 4.8), p = 0.001]. Independent risk factors for CTD development in IPF patients included female gender [adjusted hazard ratio (HR) 5.319, p = 0.0082], titer of rheumatoid factor (RF; adjusted HR, 1.006; p = 0.022), titer of anti-citrullinated protein antibody (ACPA; adjusted HR, 1.009; p = 0.0011), and titer of myeloperoxidase (MPO)-ANCA (adjusted HR, 1.02; p0.0001).Progression to CTD is uncommon in IPF patients. However, a significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. RF, ACPA, and MPO-ANCA might be significantly associated with CTD development in IPF patients. Key Points • A significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. • IPF/UIP with high titers of RF, ACPA, or MPO-ANCA might be the initial clinical manifestation of CTD. • RF, ACPA, and MPO-ANCA may be significantly associated with the development of pulmonary fibrosis in patients with CTD.

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

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.

Purpose Despite a large number of resting-state functional MRI (rsfMRI) studies in schizophrenia, current evidence on the abnormalities of functional connectivity (FC) of resting-state networks shows high variability, and the findings on recent-onset schizophrenia are insufficient compared to those on chronic schizophrenia. Patients and methods We performed a rsfMRI in 46 patients with recent-onset schizophrenia and 22 healthy controls. Group independent component brainmap and dual regression were performed for voxel-wise comparisons between the groups. Correlation of the symptom severity, cognitive function, duration of illness, and a total antipsychotics dose with FC was evaluated with Spearman's rho correlation. Results The patient group had areas with a significantly decreased FC compared to that of the control group in which it existed in the left supplementary motor cortex and supramarginal gyrus (the executive control network) and the right postcentral gyrus (the auditory network). The patient group had a significant correlation of the total antipsychotics dose with the FC of the cluster in the left supplementary motor cortex in the executive control network. Conclusion Patients with recent-onset schizophrenia have decreased FC of the executive control and auditory networks compared to healthy controls.

Objective Diffusion tensor imaging has been extensively applied to schizophrenia research. In this study, we counted the number of abnormal brain regions with altered diffusion measures in patients with schizophrenia to enumerate the burden of abnormal diffusivity in the brain.Methods The public neuroimaging data of the COBRE project from SchizConnect were used for the study. The studied dataset consisted of data from 57 patients with schizophrenia and 71 healthy participants. FreeSurfer and FSL were applied for image processing and analysis. After verifying 161 regions of interest (ROIs), mean diffusion measures in every single ROI in all study participants were measured and normalized into Z-scores. Each ROI was then defined as normal or abnormal on the basis of a cutoff absolute Z-score of 1.96. The number of abnormal ROIs was obtained by each diffusion measure.Results The numbers of ROIs with increased radial diffusivity and increased trace were significantly larger in the patient group than in healthy participants.Conclusion Thus, the patient group showed a significant increase in abnormal ROIs, strongly indicating that schizophrenia is not caused by the pathology of a single brain region, but is instead attributable to the additive burden of structural alterations within multiple brain regions.

Background/Aims: A substantial portion of gout patients have normal serum urate levels during an acute attack but data on the clinical characteristics and risk of recurrence compared with hyperuricemic patients are limited. Methods: In this retrospective cohort study, clinical features of normouricemic and hyperuricemic patients were compared. Multivariate analysis was performed to determine whether normouricemic patients were less likely to have a recurrent attack. Results: Among a total of 221 gout patients, 88 (39.8%) had normouricemia during an acute attack. Postsurgical gout (22.7% vs. 6.0%, p < 0.001), hemodialysis initiation (9.1% vs. 2.3%, p = 0.029) and inflammatory activity were higher in normouricemic patients than in hyperuricemic patients. The frequency of renal insufficiency was lower in normouricemic patients (25.0% vs. 53.4%, p < 0.001). However, the recurrence rate of gout attack was not different between the two groups (24.7% vs. 33.0%, p = 0.220). In multivariate analysis, female sex, history of urinary stone, presence of tophi, and use of thiazide were associated with increase of recurrent gout attack, but not with serum urate status during an acute attack (hazard ratio, 1.075; 95% confidence interval, 0.972 to 1.190; p = 0.159). Conclusions: Normouricemia during an acute gout attack was more frequently observed in postsurgical episodes, hemodialysis initiation and patients with preserved renal function. While higher inflammatory activity was observed in normouricemic patients, recurrent attack was not associated with serum urate levels during an acute attack. Thus, careful follow-up should be considered in gout patients regardless of serum urate levels during an acute attack.

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.

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, We use a large (n = 1113) harmonized diffusion MRI dataset of individuals diagnosed with schizophrenia and healthy controls, in order to study the predictive performance of a normative modeling approach. This approach compares each individual with distribution derived from healthy controls to derive measures of deviation from the normal distribution. Our results show that combining deviation information from different white matter tracts, while using multiple imaging measures simultaneously, improves prediction performance, and could therefore aid in subject‐level classification.

Background Clozapine is generally considered as the treatment of choice for patients with treatment-resistant schizophrenia (TRS). However, its superiority has recently been questioned because olanzapine has been suggested as non-inferior to clozapine in its effectiveness. Aims We aimed to investigate the current status of clozapine prescriptions to identify any disparity between clinical guidelines and real-world practices. Method In this study, we utilised the Health Insurance Review Agency database in the Republic of Korea to investigate the real-world effectiveness of clozapine for patients with TRS. We compared differences in patient variables before and after clozapine administration, and we also performed survival analyses for both psychiatric admissions and emergency room visits among patients who used clozapine or olanzapine. Results This study investigated an incident cohort of 64 442 patients, and 2338 patients have been prescribed clozapine. Of these, 998 patients had TRS. In survival analysis, clozapine showed a worse survival rate for psychiatric admissions than olanzapine (hazard ratio 0.615). We also identified that clinicians tended to try a number of antipsychotics, as recommended, before starting patients on clozapine. Conclusions In conclusion, we found that olanzapine led to higher survival rates for psychiatric admissions than clozapine. Thus, considering the risk of serious adverse effects, clozapine may be used conservatively. Considering several studies advocating superior efficacy of clozapine, further studies with extensive data are recommended.

Objectives To investigate the frequency of monosodium urate (MSU) crystal deposits on dual-energy computed tomography (DECT) in patients with clinical diagnosis of gout and the factors associated MSU crystal positivity. Methods This study was conducted in patients with clinical diagnosis of gout who underwent DECT. Clinical features were compared between patients with positive and those with negative DECT results. A logistic regression analysis was performed to determine the factors associated with MSU crystal positivity on DECT. Results A total of 148 patients with clinical diagnosis of gout were included, and MSU crystal deposition on DECT was observed in 64 patients (43.3%). The patients with positive DECT results were more likely to have renal insufficiency, longer disease duration, and higher serum urate level than those with negative. In the multivariable analysis, first gout attack (odds ratio 0.462; 95% confidence interval 0.229–0.931, p = 0.031) was associated with a less likely MSU crystal deposit-positive DECT result. In the subgroup analysis of patients with first attack, serum urate level > 8 mg/dL was associated with DECT positivity. Conclusion Of the patients with clinical diagnosis of gout, those with renal insufficiency, longer disease duration, and high serum urate level were more likely to be positive of gout on DECT. First gout attack was associated with less likely to be positive for MSU crystal on DECT. Thus, performing DECT scan in the selected patients who had characteristics that highly probability of DECT positivity could increase positive predictive value.

We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis receiving bisphosphonate. A total of 199 RA patients, who were newly diagnosed with osteoporosis and receiving bisphosphonate between January 2005 and March 2017, were reviewed. Changes in BMD after 1 year were compared between patients treated with and without TNFi. The inverse probability of treatment weighting (IPTW) method using the propensity score was performed to minimize confounding factors, and logistic regression analysis was applied to identify any factors associated with significant BMD improvement (≥ 3%) at the lumbar spine and femur neck. Among patients receiving bisphosphonate, 29 were exposed to TNFi, and 170 patients were not exposed. The percentage change in BMD and the proportion of significant improvements at the lumbar spine and femur neck were similar between patients treated with and without TNFi, before and after IPTW adjustment. In addition, the disease activity score 28 (DAS28) with three variables [adjusted odds ratio (OR) 0.741, 95% confidence interval (CI) 0.592-0.927, p = 0.009] and cumulative steroid dose (adjusted OR 0.639, 95% CI 0.480-0.851, p = 0.002) were inversely associated with an improvement in BMD. Conversely, TNFi use was not associated with any improvement in BMD after adjustment by IPTW using the propensity score. TNFi did not influence BMD improvement in RA patients with osteoporosis receiving bisphosphonate, suggesting that TNFi cannot be considered as a preferred therapeutic option for increasing BMD.

The authors developed SOX-6, 9-transfected human adipose stem cells (SOX-6, 9ASCs) to treat osteoarthritis (OA) and tested their effectiveness in arresting OA progression when injected intra-articu...

Objective.Febuxostat has superior renal safety to allopurinol, but data on its hepatic safety are limited. Thus we compared the hepatotoxicity of febuxostat and allopurinol, and the clinical factors associated with hepatotoxicity, in patients with gout and fatty liver disease (FLD).Methods.We included gout patients treated with allopurinol or febuxostat who were diagnosed with fatty liver based on ultrasonography or computed tomography. Hepatotoxicity was defined as follows: (1) elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) at least 3× the upper limit of normal, when the baseline AST/ALT was normal; or (2) doubling of the baseline AST/ALT, when the baseline AST/ALT was elevated. The factors associated with hepatotoxicity were evaluated by Cox regression analysis.Results.Of 134 patients identified with gout and FLD, 32 (23.9%) received febuxostat and 102 (76.1%) received allopurinol. There were no significant differences in age, body mass index, comorbidity, or disease severity between the groups; however, the incidence of hepatotoxicity was significantly lower in the febuxostat group (3/32, 9.4%) than in the allopurinol group (36/102, 35.3%, p = 0.005). Diabetes (HR 3.549, 95% CI 1.374–9.165, p = 0.009) and colchicine use (HR 11.518, 95% CI 5.515–24.054, p < 0.001) were associated with a higher risk of hepatotoxicity, whereas febuxostat use was associated with a lower risk of hepatotoxicity (HR 0.282, 95% CI 0.086–0.926, p = 0.037).Conclusion.In the 32 patients studied, febuxostat was well tolerated in patients with gout and FLD. However, the presence of diabetes and colchicine use may increase the risk of hepatotoxicity.

Background Previous studies have reported functional and structural abnormalities in the thalamus and the pars triangularis of the inferior frontal gyrus in patients with insomnia disorder. However, no studies have been conducted on the white-matter tracts between these 2 brain regions. We aimed to compare the white-matter integrity and structure of the left thalamus–pars triangularis tracts between patients with insomnia and controls, and to characterize the relationship between white-matter integrity and clinical features in patients with insomnia. Methods In total, 22 participants with insomnia disorder and 27 controls underwent overnight polysomnography and brain magnetic resonance imaging, and then completed self-report clinical questionnaires and neurocognitive tests for spatial planning. Structural and diffusion measures such as fractional anisotropy, axial diffusivity, radial diffusivity and trace were analyzed in group comparison and correlation analyses. Results The insomnia group showed significantly lower fractional anisotropy (F = 8.647, p = 0.02) and axial diffusivity (F = 5.895, p = 0.038) in the left thalamus–pars triangularis tracts than controls. In patients with insomnia, fractional anisotropy in the tracts was correlated with the results of the Stockings of Cambridge test (r = 0.451, p = 0.034), and radial diffusivity was correlated with Epworth Sleepiness Scale score (r = 0.437, p = 0.042). Limitations Limitations included analyses of limited brain regions and the cross-sectional design. Conclusion The insomnia group showed decreased integrity in the left thalamus–pars triangularis tracts, and integrity was correlated with cognition and daytime sleepiness. These results may imply that insomnia is characterized by disintegration of the white-matter tract between the left thalamus and inferior frontal gyrus.