Validity of the Korean Version of the Brief Irritability Test in Psychiatric Patients.

OBJECTIVE: This study aimed to investigate the validity and reliability of the Korean version of the Brief Irritability Test (BITe) and adapt it for Korean patients with psychiatric disorders. METHODS: A total of 296 patients at the Department of Psychiatry of Hanyang University Guri Hospital completed the BITe, Korean Beck Depression Inventory-II, Korean Beck Anxiety Inventory, the Korean version of the State-Trait Anger Expression Inventory, and Barratt Impulsiveness Scale-11. Construct validity was confirmed through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Reliability testing included assessments of internal consistency (Cronbach's α) and item-total correlations. Convergent validity was examined through correlational analyses with variables such as anxiety, depression, anger, and impulsivity. RESULTS: First, the scale had good internal consistency with a Cronbach's α of 0.88. Second, EFA indicated a single dimensionality of the BITe, and CFA demonstrated a reasonable fit for the single-factor model (comparative fit index=0.97, Tucker-Lewis Index=0.95, normed fit index=0.97, goodness-of-fit index=0.96, root mean square error of approximation=0.12, standardized root mean residual=0.03). Finally, the convergent validity analysis revealed a significant positive correlation with depression, anxiety, and anger, except for anger control, which is a sub-variable of anger. CONCLUSION: The results showed that the Korean version of the BITe had good psychometric properties, and might serve as a valuable tool for assessing irritability in Korean patients with psychiatric disorders.

Clinical and financial impact of immune checkpoint inhibitors following platinum chemotherapy in patients with advanced or metastatic non-small cell lung cancer: a nationwide population-based study.

Background: Although various studies have demonstrated that the clinical efficacy of immune checkpoint inhibitors (ICIs) improves the prognosis of patients with non-small cell lung cancer (NSCLC), studies on the financial aspects based on large population-based data are needed. This study aimed to analyze the differences in medical expenses and the effect of ICIs on the prognosis of patients with advanced or metastatic NSCLC. Methods: Patients newly diagnosed with stage IIIB or IV NSCLC who received palliative chemotherapy between 2013 and 2020 were selected from the nationwide database of the population covered by the Korean National Health Insurance Service. Interrupted time-series analysis was performed to evaluate the effects of subsequent ICI use after platinum-based cytotoxic chemotherapy (CC) on overall mortality. Progression-free survival and medical expenditure were also assessed. Results: In the final study population, 2,485 and 4,812 patients were included in the ICI and non-ICI groups, respectively. ICI treatment significantly lowered the risk of death [adjusted hazard ratio, 0.79; 95% confidence interval (CI): 0.75-0.84]. And the ICI-treated patients were less likely to experience disease progression (adjusted odds ratios, 0.92; 95% CI: 0.85-0.99). Furthermore, after the introduction of ICIs, both total and cancer-related medical expenses per capita showed an increasing trend [ß: $4.56K, standard error (SE): $0.27K, P<0.0001 and ß: $4.54K, SE: $0.27K, P<0.0001, respectively]. Conclusions: Subsequent ICI use after platinum-based CC improved the overall survival rate of patients with advanced NSCLC. With the increasing burden of individual medical expenses, further research is required to identify patients for whom ICI treatment may be effective.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Data-mining analysis of media frame effects on social perception of schizophrenia renaming in Korea.

BACKGROUND: In 2011, Korean Neuropsychiatric Association renamed schizophrenia from 'mind split disorder' ('Jungshinbunyeolbyung' in Korean) to 'attunement disorder' ('Johyeonbyung' in Korean), in a strategic way to reduce social stigma toward people with schizophrenia. However, there remains an elusive consensus that how the renaming effort has contributed to changes in the social perception of schizophrenia in Korea. METHODS: With this regard, we explored whether media frames alter the social perception, in ways of respecting or disrespecting schizophrenia patients before and after the renaming. This study extensively investigated media keywords related to schizophrenia across the time by applying both language and epidemiologic analyses. RESULTS: In results, the media keywords have been negatively described for schizophrenia patients both before and after the renaming. Further, from an analysis using the regression model, a significant correlation was observed between the frequency of negative keywords and the hospitalization frequency of schizophrenia patients. CONCLUSIONS: These findings suggest that the social perception of schizophrenia has been scarcely changed, but rather remained negatively biased against schizophrenia patients, in spite of the renaming effort. Notably, the biased media frames have been demonstrated to negatively impact on the social perception, and even on the medical use patterns of general schizophrenia patients. In conclusion, we suggest that the unbiased media frames along with the renaming effort may collectively help reduce the negative social perception of schizophrenia. TRIAL REGISTRATION: This study was approved from the Institute of Review Board (IRB) of the Yoing-In Mental Hospital (IRB No. YIMH-IRB-2019-02).

Three-Month Variability of Commonly Evaluated Biomarkers in Clinically Stable COPD.

Introduction: Clinical decisions in chronic obstructive pulmonary disease (COPD) treatment often utilize serially assessed physiologic parameters and biomarkers. To better understand the reliability of these tests, we evaluated changes in commonly assessed biomarkers over 3 months in patients with clinically stable COPD. Methods: We performed an observational prospective cohort study of 89 individuals with clinically stable COPD, defined as no exacerbation history within 3 months of enrollment. Biomarkers included lung function and functional performance status, patient-reported outcomes of symptoms and health status, and blood markers of inflammation. The correlation between testing at baseline and at 3-month follow-up was reported as the intraclass correlation coefficient (ICC). "Outliers" had significant variability between tests, defined as >1.645 standard deviations between the two measurements. Differences in clinical features between outliers and others were compared. Results: Participants with COPD (n = 89) were 70.5 ± 6.7 years old, 54 (61%) male, had a 40 pack-year smoking history with 24.7% being current smokers, and postbronchodilator forced expiratory volume in one second (FEV1) 62.3 ± 22.7% predicted. The biomarkers with excellent agreement between the initial and the follow-up measurements were FEV1 (ICC = 0.96), Saint George's Respiratory Questionnaire (SGRQ) (ICC = 0.98), COPD Assessment Test (CAT) (ICC = 0.93) and C-reactive protein (CRP) (ICC = 0.90). By contrast, parameters showing less robust agreement were 6-minute walking distance (ICC = 0.75), eosinophil count (ICC = 0.77), erythrocyte sedimentation rate (ICC = 0.75) and white blood cell count (ICC = 0.48). Individuals with greater variability in biomarkers reported chronic bronchitis more often and had higher baseline SGRQ and CAT scores. Conclusion: Our study evaluated the stability of commonly assessed biomarkers in clinically stable COPD and showed excellent agreement between baseline and three-month follow-up values for FEV1, SGRQ, CAT and CRP. Individuals with chronic bronchitis and more symptomatic disease at baseline demonstrated greater variability in 3-month interval biomarkers.

Clinical use of mood stabilizers beyond treatment for bipolar disorder: The REAP-MS study.

OBJECTIVE: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar. METHODS: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection. RESULTS: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication. CONCLUSIONS: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.

Clozapine Use for Bipolar Disorder: An Asian Psychotropic Prescription Patterns Consortium Study.

BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing. METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling. RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months. CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

Microbiota-Gut-Brain Axis in Major Depression: A New Therapeutic Approach.

Major depression is impacted by the disruption of gut microbiota. Defects in gut microbiota can lead to microbiota-gut-brain axis dysfunction and increased vulnerability to major depression. While traditional chemotherapeutic approaches, such as antidepressant use, produce an overall partial therapeutic effect on depression, the gut microbiome has emerged as an effective target for better therapeutic outcomes. Recent representative studies on the microbiota hypothesis to explore the association between gut pathophysiology and major depression have indicated that restoring gut microbiota and microbiota-gut-brain axis could alleviate depression. We reviewed studies that supported the gut microbiota hypothesis to better understand the pathophysiology of depression; we also explored reports suggesting that gut microbiota restoration is an effective approach for improving depression. These findings indicate that gut microbiota and microbiota-gut-brain axis are appropriate new therapeutic targets for major depression.

The factor structure of extrapyramidal symptoms evaluated using the Drug-Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP-4 study.

INTRODUCTION: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). METHODS: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis. RESULTS: The factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia). CONCLUSION: The results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute parkinsonism observed during action (F1), acute parkinsonism observed at rest (F2), and central dopaminergic mechanisms with pathophysiology other than acute parkinsonism (F3).

Risks of complicated acute appendicitis in patients with psychiatric disorders.

BACKGROUND: Acute appendicitis often presents with vague abdominal pain, which fosters diagnostic challenges to clinicians regarding early detection and proper intervention. This is even more problematic with individuals with severe psychiatric disorders who have reduced sensitivity to pain due to long-term or excessive medication use or disturbed bodily sensation perceptions. This study aimed to determine whether psychiatric disorder, psychotropic prescription, and treatment compliance increase the risks of complicated acute appendicitis. METHODS: The diagnosis records of acute appendicitis from four university hospitals in Korea were investigated from 2002 to 2020. A total of 47,500 acute appendicitis-affected participants were divided into groups with complicated and uncomplicated appendicitis to determine whether any of the groups had more cases of psychiatric disorder diagnoses. Further, the ratio of complicated compared to uncomplicated appendicitis in the mentally ill group was calculated regarding psychotropic dose, prescription duration, and treatment compliance. RESULTS: After adjusting for age and sex, presence of psychotic disorder (odds ratio [OR]: 1.951; 95% confidence interval [CI]: 1.218-3.125), and bipolar disorder (OR: 2.323; 95% CI: 1.194-4.520) was associated with a higher risk of having complicated appendicitis compared with absence of psychiatric disorders. Patients who are taking high-daily-dose antipsychotics, regardless of prescription duration, show high complicated appendicitis risks; High-dose antipsychotics for < 1 year (OR: 1.896, 95% CI: 1.077-3.338), high-dose antipsychotics for 1-5 years (OR: 1.930, 95% CI: 1.144-3.256). Poor psychiatric outpatient compliance was associated with a high risk of complicated appendicitis (OR: 1.664, 95% CI: 1.014-2.732). CONCLUSIONS: This study revealed a close relationship in the possibility of complicated appendicitis in patients with severe psychiatric disorders, including psychotic and bipolar disorders. The effect on complicated appendicitis was more remarkable by the psychiatric disease entity itself than by psychotropic prescription patterns. Good treatment compliance and regular visit may reduce the morbidity of complicated appendicitis in patients with psychiatric disorders.

Cardiovascular and cerebrovascular-associated mortality in patients with preceding bronchiectasis exacerbation.

BACKGROUND: Bronchiectasis is associated with an increased incidence of atherosclerotic cardiovascular disease (ASCaVD) and atherosclerotic cerebrovascular disease (ASCeVD). Its effect on associated mortality is unclear. OBJECTIVES: This study investigated the effects of bronchiectasis exacerbation prior to ASCaVD or ASCeVD events on mortality in patients with bronchiectasis using a large population-based database. METHODS: A retrospective cohort of patients with bronchiectasis who experienced ASCaVD (n = 1066) or ASCeVD (n = 825) was studied for the first time using a nationwide population-based database (National Health Insurance Service-National Sample Cohort, Korea, 2002-2015). We classified each cohort according to the presence of moderate bronchiectasis exacerbation within 1 year before the ASCaVD or ASCeVD event. We evaluated 90-day, 1-year, and all-cause mortalities risk. RESULTS: Within 1 year before the index ASCaVD or ASCeVD event, 149 (13.9%) and 112 (13.6%) patients with bronchiectasis experienced moderate exacerbation(s), respectively. Mild exacerbations did not different in frequency between the survivors and nonsurvivors. In both cohorts, more nonsurvivors experienced moderate exacerbations than survivors. The odds ratios of 90-day and 1-year mortalities and hazard ratios of all-cause mortalities on experiencing moderate exacerbations were 2.27 [95% confidence interval (CI) = 1.26-4.10], 3.30 (95% CI = 2.03-5.38), and 1.78 (95% CI = 1.35-2.34) in the bronchiectasis-ASCaVD cohort and 1.73 (95% CI = 0.94-3.19), 1.79 (95% CI = 1.07-3.00), and 1.47 (95% CI = 1.10-1.95), in the bronchiectasis-ASCeVD cohort. CONCLUSION: Hospitalization or emergency room visit for bronchiectasis exacerbation within 1 year before ASCaVD or ASCeVD is associated with an increased ASCaVD- or ASCeVD-associated mortality.

The Relationship between Stress, Inflammation, and Depression.

A narrative review about the relationship between stress, inflammation, and depression is made as follows: Chronic stress leads to various stress-related diseases such as depression. Although most human diseases are related to stress exposure, the common pathways between stress and pathophysiological processes of different disorders are still debatable. Chronic inflammation is a crucial component of chronic diseases, including depression. Both experimental and clinical studies have demonstrated that an increase in the levels of pro-inflammatory cytokines and stress hormones, such as glucocorticoids, substantially contributes to the behavioral alterations associated with depression. Evidence suggests that inflammation plays a key role in the pathology of stress-related diseases; however, this link has not yet been completely explored. In this study, we aimed to determine the role of inflammation in stress-induced diseases and whether a common pathway for depression exists. Recent studies support pharmacological and non-pharmacological treatment approaches significantly associated with ameliorating depression-related inflammation. In addition, major depression can be associated with an activated immune system, whereas antidepressants can exert immunomodulatory effects. Moreover, non-pharmacological treatments for major depression (i.e., exercise) may be mediated by anti-inflammatory actions. This narrative review highlights the mechanisms underlying inflammation and provides new insights into the prevention and treatment of stress-related diseases, particularly depression.

A Machine-Learning-Algorithm-Based Prediction Model for Psychotic Symptoms in Patients with Depressive Disorder.

Psychotic symptoms are rarely concurrent with the clinical manifestations of depression. Additionally, whether psychotic major depression is a subtype of major depression or a clinical syndrome distinct from non-psychotic major depression remains controversial. Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, we developed a machine-learning-algorithm-based prediction model for concurrent psychotic symptoms in patients with depressive disorders. The advantages of machine learning algorithms include the easy identification of trends and patterns, handling of multi-dimensional and multi-faceted data, and wide application. Among 1171 patients with depressive disorders, those with psychotic symptoms were characterized by significantly higher rates of depressed mood, loss of interest and enjoyment, reduced energy and diminished activity, reduced self-esteem and self-confidence, ideas of guilt and unworthiness, psychomotor agitation or retardation, disturbed sleep, diminished appetite, and greater proportions of moderate and severe degrees of depression compared to patients without psychotic symptoms. The area under the curve was 0.823. The overall accuracy was 0.931 (95% confidence interval: 0.897-0.956). Severe depression (degree of depression) was the most important variable in the prediction model, followed by diminished appetite, subthreshold (degree of depression), ideas or acts of self-harm or suicide, outpatient status, age, psychomotor retardation or agitation, and others. In conclusion, the machine-learning-based model predicted concurrent psychotic symptoms in patients with major depression in connection with the "severity psychosis" hypothesis.

Network analysis of psychiatric symptoms in schizophrenia: Findings from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP).

AIMS: Schizophrenia is a major mental disorder with a wide range of psychiatric symptoms. This study explored the structure of psychiatric symptoms of schizophrenia using network analysis in a large representative Asian sample based on a survey of clinical features and treatment used in schizophrenia patients across 15 countries/territories in Asia. METHODS: Data on the demographic characteristics and psychiatric symptoms in schizophrenia patients were extracted from the dataset of the fourth Research on Asia Psychotropic Prescription for Antipsychotics (REAP-AP) project. The presence of the following psychiatric symptoms including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms, social/occupational dysfunction, verbal aggression, physical aggression, and affective symptoms were analyzed. RESULTS: A total of 3681 patients were included. The network analysis revealed that verbal aggression, hallucinations, and social/occupational dysfunction were the most central symptoms, while the connections between social/occupational dysfunction and verbal aggression, and between hallucinations and disorganized speech were the two strongest edges. There were significant gender differences in the network structure based on the network structure invariance test (M=0.74, P = 0.03) and invariant edge strength test. The positive correlation between verbal aggression and hallucinations was significantly stronger in the female network than that in the male network (P = 0.03), while a negative correlation between affective symptoms and negative symptoms was found in the female, but not the male network (P < 0.01). CONCLUSION: Central symptoms including verbal aggression, hallucinations, and socio-occupational dysfunction should be addressed in developing targeted treatment strategy for schizophrenia patients.