Purpose: Microvascular invasion (MVI) is a well-known pathological prognostic factor in hepatocellular carcinoma (HCC).This study aimed to predict MVI and to assess post-resection prognosis using the ADV (multiplication of AFP, des-γcarboxyprothrombin—also known as proteins induced by vitamin K absence or antagonist-II [PIVKA-II], and tumor volume), AP (multiplication of AFP and PIVKA-II), and MoRAL (model to predict tumor recurrence [TR] after liver transplantation) scores. Methods: This international multicenter study included 9,061 patients who underwent hepatic resection for solitary HCC measuring 1.0–10 cm from 2010 to 2017 at ten Korean centers and 73 Japanese centers, and were followed up until 2020. Results: The receiver operating characteristic (ROC) area under the curve (AUC) for diagnosis of MVI was 0.734 for the ADV score at 4.7log, 0.684 for the AP score at 3.7log, and 0.705 for the MoRAL score at 162.0. The ADV score exhibited the strongest predictive ability for MVI. The ROC AUC for actuarial 5-year TR was 0.586 for the ADV score, 0.583 for the AP score, and 0.586 for the MoRAL score, demonstrating similar prognostication efficacy. The hazard ratios for TR and overall survival demonstrated strong, stepwise positive correlations with increases in both the ADV and AP scores, but not the MoRAL score. Conclusions The ADV score is a superior integrated biomarker for predicting post-resection prognosis in patients with HCC, outperforming both the AP and MoRAL scores. The AP score appears to be a simplified alternative to the ADV score, particularly in cases of small HCC.

Objective: The economic hardship brought by the coronavirus disease-2019 (COVID-2019) pandemic has caused mental health problems among people of different socioeconomic status (SES). As social support helps to buffer these problems, we investigated the association between job loss related to COVID-19 and depression, anxiety, and suicidal thoughts; the differences in the effects according to SES; and the mediating effects of social support. Methods: The effects of COVID-19-related job loss on depression, anxiety, and suicidal thoughts among 1,364 people were investigated through semi-structured and self-administered questionnaires: Patient Health Questionnaire–9, General Anxiety Disorder–7, and the Functional Social Support Questionnaire. Logistic regression and subgroup analyses were performed to assess the association between job loss and mental health status, and the moderating effects of income and educational levels. Moreover, the mediating effects of perceived social support on the association between job loss and depression, anxiety, and suicidal thoughts were analyzed. Results: COVID-19-related job loss increased the risk of depression and suicidal thoughts. Adults with lower income and education level were at higher risk of depression, anxiety, and suicidal thoughts; perceived social support level had significant mediating effects on the association between job loss and depression/anxiety; and income level had significant moderating effects on this mediating pathway. Conclusion COVID-19-related job loss were likely to be significantly associated with negative mental health outcomes, especially among individuals with low income and education levels. As social support had buffering effects on such outcomes, related government policies in cooperation with the governance of communities and stakeholders must be prepared.

Objectives: Deliberate self-poisoning (DSP) is the most common suicide method and can be life-threatening. The purpose of this study was to investigate the factors related to the lethality of DSP and the characteristics of the adolescent group. Methods: A retrospective study was conducted on patients who had visited an academic hospital’s regional emergency medical center between 2015 and 2018. The data reviewed through their medical records included sociodemographic factors, clinical variables, and psychiatric treatment. Four groups (Q1–Q4) were categorized by descriptive analysis using the risk-rescue rating scale. Results: A total of 491 patients were enrolled in this study. This study showed that high lethality had statistically significant associations with male sex, older age, admitting suicidal intentions, and the use of herbicides for suicide. Logistic regression analyses showed a significant association between high-lethality and female [odds ratio (OR)=0.50, 95% confidence interval (CI)=0.30–0.81, p=0.01], non-psychiatric drugs (over-the-counter drug: OR=2.49, 95% CI=1.08–5.74, p=0.03; herbicide: OR=8.65, 95% CI=3.91–19.13, p<0.01), and denial of suicide intent (OR=0.28, 95% CI=0.15–0.55, p<0.01). Conclusion This study showed the clinical factors associated with the high lethality of DSP and suggested that efforts were needed to care for and thoroughly examine patients with DSP.

Objective: This study aimed to develop a brief self-report measure of depressive and anxiety symptoms in victims of sexual violence. Methods: The sample, which consisted of 215 victims and 255 healthy controls, was recruited between December 2016 and November 2018 from eight Sunflower Centers. Eligible items were selected from existing scales of depression (CES-DC and CES-D) and anxiety (SAI-C and BAI) symptoms by item-total correlation coefficients and item response theory (IRT) analysis. Internal consistency coefficients were computed and the receiver operating characteristics curve was inspected to assess the validity of the brief scale and determine optimal cutoff scores. Results: The brief scales showed high internal consistency across all age groups. The optimal cutoff score of brief depression scale was 1.5 for children, 2.5 for adolescents, and 2.5 for the adults. That of brief anxiety scale was 8.5, 6.5, and 3.5, respectively. Conclusion The results underscore the need for age-appropriate screening measures of depressive and anxiety symptoms in victims of sexual violence.

The valproic acid (VPA)-induced animal model is one of the most widely utilized environmental risk factor models of autism. Autism spectrum disorder (ASD) remains an insurmountable challenge among neurodevelopmental disorders due to its heterogeneity, unresolved pathological pathways and lack of treatment. We previously reported that VPA-exposed rats and cultured rat primary neurons have increased Pax6 expression during post-midterm embryonic development which led to the sequential upregulation of glutamatergic neuronal markers. In this study, we provide experimental evidence that telomerase reverse transcriptase (TERT), a protein component of ribonucleoproteins complex of telomerase, is involved in the abnormal components caused by VPA in addition to Pax6 and its downstream signals. In embryonic rat brains and cultured rat primary neural progenitor cells (NPCs), VPA induced the increased expression of TERT as revealed by Western blot, RT-PCR, and immunostainings. The HDAC inhibitor property of VPA is responsible for the TERT upregulation. Chromatin immunoprecipitation revealed that VPA increased the histone acetylation but blocked the HDAC1 binding to both Pax6 and Tert genes. Interestingly, the VPA-induced TERT overexpression resulted to sequential upregulations of glutamatergic markers such as Ngn2 and NeuroD1, and inter-synaptic markers such as PSD-95, α-CaMKII, vGluT1 and synaptophysin. Transfection of Tert siRNA reversed the effects of VPA in cultured NPCs confirming the direct involvement of TERT in the expression of those markers. This study suggests the involvement of TERT in the VPA-induced autistic phenotypes and has important implications for the role of TERT as a modulator of balanced neuronal development and transmission in the brain.
Acetylation ; Animals ; Autism Spectrum Disorder ; Autistic Disorder ; Blotting, Western ; Brain ; Chromatin Immunoprecipitation ; Embryonic Development ; Female ; Histones ; Models, Animal ; Neurodevelopmental Disorders ; Neurons ; Phenotype ; Population Characteristics ; Pregnancy ; Rats ; Ribonucleoproteins ; Risk Factors ; RNA, Small Interfering ; Stem Cells ; Synaptophysin ; Telomerase* ; Transfection ; Up-Regulation ; Valproic Acid*

In the ‘Acknowledgements’ section on page 263 of the original article, the grant number was incorrectly stated.

OBJECTIVE: Several factors, such as male gender, older age, type of insurance, comorbid conditions, and medication type, have been associated with attention-deficit/hyperactivity disorder (ADHD) medication adherence rates, but the results have been inconsistent. We analyzed data to answer several questions: 1) How old were patients who first refilled their treatment medications used primarily for ADHD, regardless of the medication type? 2) What socio-demographic factors are associated with medication adherence? 3) What medical conditions, such as medication type and comorbid diagnosis, influence adherence? METHODS: We analyzed National Health Insurance data, which comprised continuously enrolled Korean National Medical Insurance children (6–18 years) with at least 2 ADHD prescription claims (January 2008–December 2011). The persistence of use regarding the days of continuous therapy without a 30-day gap were measured continuously and dichotomously. Adherence, using a medication possession ratio (MPR), was measured dichotomously (80% cut-off). RESULTS: The cumulative incidence of index cases that initiated medication refills for ADHD treatment during the 4 year period was 0.85%. The patients who exhibited a MPR greater than 80 comprised approximately 66%. The medication type, high school age groups, physician speciality, treatment at a private clinic, and comorbid conditions were associated with medication adherence during continuous treatment using a multivariate analysis. CONCLUSION: A better understanding of ADHD treatment patterns may lead to initiatives targeted at the improvement of treatment adherence and persistence. Other factors, including the severity, family history, costs, type of comorbidities, and switching patterns, will be analyzed in future studies.
Adolescent* ; Atomoxetine Hydrochloride ; Child* ; Cohort Studies* ; Comorbidity ; Compliance ; Diagnosis ; Humans ; Incidence ; Insurance ; Insurance, Health* ; Male ; Medication Adherence ; Multivariate Analysis ; National Health Programs ; Prescriptions ; Retrospective Studies*

We examined short- and long-term medication compliance among youth with attention-deficit hyperactivity disorder (ADHD), using data from the National Health Insurance database in Korea. Of the 5,699,202 6-14-year-old youth in 2008, we chose those with at least 1 medical claim containing an ICD-10 code for diagnosis of ADHD (F90.0) and no prescription for ADHD within the previous 365 days. We tracked the data every 6 months between 2008 and 2011, to determine treatment compliance among newly diagnosed, medicated patients. Further, we checked every 1 month of the 6 months after treatment commencement. Treatment continuity for each patient was calculated by sequentially counting the continuous prescriptions. For measuring compliance, we applied the medication possession ratio (MPR) as 0.6, 0.7, and 0.8, and the gap method as 15- and 30-days' intervals. There were 15,133 subjects; 11,934 (78.86%) were boys. Overall 6-month treatment compliance was 59.0%, 47.3%, 39.9%, 34.1%, 28.6%, and 23.1%. Monthly drop-out rates within the first 6 months were 20.6%, 6.5%, 4.7%, 3.7%, 3.0%, and 2.5%, respectively. When applying MPR more strictly or shorter gap days, treatment compliance lessened. This is the first nationwide report on 36-month treatment compliance of the whole population of 6-14-year-olds with ADHD. We found the beginning of the treatment, especially the first month, to be a critical period in pharmacotherapy. These results also suggest the importance of setting appropriate treatment adherence standards for patients with ADHD, considering the chronic course of ADHD.
Adolescent ; Attention Deficit Disorder with Hyperactivity/diagnosis/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Child ; Databases, Factual ; Female ; Humans ; Male ; *Medication Adherence ; Methylphenidate/*therapeutic use ; Republic of Korea ; Retrospective Studies

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.
Administration, Oral ; Adolescent ; Atomoxetine Hydrochloride/therapeutic use ; Attention Deficit Disorder with Hyperactivity/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Child ; Databases, Factual ; Drug Compounding ; Female ; Humans ; Insurance Claim Review ; Logistic Models ; Male ; Medication Adherence/*statistics & numerical data ; Methylphenidate/therapeutic use ; Odds Ratio ; Republic of Korea ; Retrospective Studies

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.
Administration, Oral ; Adolescent ; Atomoxetine Hydrochloride/therapeutic use ; Attention Deficit Disorder with Hyperactivity/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Child ; Databases, Factual ; Drug Compounding ; Female ; Humans ; Insurance Claim Review ; Logistic Models ; Male ; Medication Adherence/*statistics & numerical data ; Methylphenidate/therapeutic use ; Odds Ratio ; Republic of Korea ; Retrospective Studies