Search

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.

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.

Cadmium-induced toxicity can affect fish embryo development, ion homeostasis regulation, energy metabolism, maturation and growth, stress response, and immunity. However, studies on the toxic effects of cadmium exposure to aquatic animals, particularly olive flounder (Paralichthys olivaceus), are limited. In this study, juvenile P. olivaceus (mean length, 12.9 ± 1.3 cm; mean weight, 23.1 ± 3.2 g) was exposed to waterborne cadmium (0, 50, 100, 200, and 400 μg/L) for 10 d. Hematological parameters, including hematocrit value and hemoglobin level, in P. olivaceus were significantly decreased after waterborne cadmium exposure. Plasma components such as calcium, glucose, cholesterol, glutamic-oxaloacetic transaminase, and glutamic-pyruvic transaminase were significantly altered via cadmium exposure. The activities of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione S-transferase, were significantly altered in P. olivaceus after cadmium exposure. Acetylcholinesterase activity was significantly inhibited upon waterborne cadmium exposure. Hepatic heat shock protein 70 was significantly upregulated in P. olivaceus after waterborne cadmium exposure. Therefore, waterborne cadmium at concentrations of100 or 200 μg/L can induce physiological toxicity in P. olivaceus via changes in hematological parameters, antioxidant enzymes, neurotransmitters, and stress indicators.

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.

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

The phonon angular momentum (PAM) may exhibit exotic temperature dependence as it is sensitive to the phonon lifetime. Constant phonon-lifetime approximation fails to depict such behavior. Here, we study the PAM of AlN, GaN, and graphene-like boron nitride (g-BN) monolayer with full consideration of phonon lifetime using first-principles calculations. We show that wurtzite AlN and GaN acquire divergent PAM at low temperatures from their lowest-lying phonon branches. The g-BN monolayer, on the other hand, does not have finite PAM at equilibrium structure. Rather it shows intriguing strain-dependence in PAM; the compressive strain greater than the critical size generates divergent PAM at low temperatures due to the divergent lifetime of TA phonons. As PAM couples with rotational excitations in solids associated with charge, spin, or electromagnetic fields, our study demonstrates a possibility of mechanical and thermal engineering of such excitations., Comment: 37 pages, 16 figures, to be published in Physical Review B

A total of 150 21-day-old weaned piglets [(Yorkshire × Landrace) × Duroc] were randomly assigned to 3 groups based on average initial body weight (6.96 ± 0.21 kg) to evaluate the effects of dietary supplementation of probiotic, paraprobiotic, and hydrolyzed yeast mixture (PPY) on growth performance, nutrient digestibility, fecal bacteria counts, fecal calprotectin contents, and diarrhea rate in a 42-day experiment (phase 1: days 1-14; phase 2: days 15-42). There were 10 replicate pens per treatment with 5 pigs per pen (three gilts and two barrows). The experimental diets were a basal diet, without additive (CON), a basal diet supplemented with pharmacological levels of zinc oxide (ZnO; TRT1), and an experimental treatment including PPY (TRT2). Pigs in TRT1 were provided with a basal diet + 3000 mg/kg (as fed) ZnO during phase 1, and a basal diet during phase 2. Pigs in TRT2 were provided with a basal diet + 200 mg/kg (as fed) probiotic for a final concentration of 2 × 109 colony forming units (CFU)/kg diet + 800 mg/kg (as fed) paraprobiotic + 10 g/kg (as fed) hydrolyzed yeast mixture during phase 1, and a basal diet +100 mg/kg (as fed) probiotic + 400 mg/kg (as fed) paraprobiotic mixture during phase 2. Pigs in TRT1 and TRT2 tended to be heavier at day 14 and were significantly heavier at day 42 than CON pigs. Growth rate during days 1-14, 15-42, and 1-42 was similarly affected by treatment while feed efficiency was unaffected by treatment in the first 14 days but was significantly higher for TRT 1 pigs between 15-42 and 1-42 days with TRT2 being intermediate. Apparent nitrogen and energy digestibility were both significantly higher for pigs on TRT1 and TRT2 compared with the CON. There were no significant differences in any parameters measured between TRT1 and TRT2. Therefore, we demonstrated that PPY supplementation had comparable effects as ZnO on nutrient digestibility and the performance of weaned piglets.

Background. Although the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR- TKI) therapy has been proven in non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs presents a serious clinical problem. Hence, the identification of new therapeutic strategy is needed to treat EGFR-TKI-resistant NSCLC. Methods. Acquired EGFR-TKI-resistant lung cancer cell lines (HCC827, H1993, and H292 cells with acquired resistance to gefitinib or erlotinib) were used for cell-based studies. IncuCyte live cell analysis system and XFp analyzer were used for the determination of cell proliferation and energy metabolism, respectively. In vivo anticancer effect of phenformin was assessed in xenografts implanting HCC827 and gefitinib-resistant HCC827 (HCC827 GR) cells. Results. HCC827 GR and erlotinib-resistant H1993 (H1993 ER) cells exhibited different metabolic properties compared with their respective parental cells, HCC827, and H1993. In EGFR-TKI-resistant NSCLC cells, glycolysis markers including the glucose consumption rate, intracellular lactate level, and extracellular acidification rate were decreased; however, mitochondrial oxidative phosphorylation (OXPHOS) markers including mitochondria-driven ATP production, mitochondrial membrane potential, and maximal OXPHOS capacity were increased. Cell proliferation and tumor growth were strongly inhibited by biguanide phenformin via targeting of mitochondrial OXPHOS complex 1 in EGFR-TKI-resistant NSCLC cells. Inhibition of OXPHOS resulted in a reduced NAD+/NADH ratio and intracellular aspartate levels. Recovery of glycolysis by hexokinase 2 overexpression in erlotinib-resistant H292 (H292 ER) cells significantly reduced the anticancer effects of phenformin. Conclusion. Long-term treatment with EGFR-TKIs causes reactivation of mitochondrial metabolism, resulting in vulnerability to OXPHOS inhibitor such as phenformin. We propose a new therapeutic option for NSCLC with acquired EGFR-TKI resistance that focuses on cancer metabolism.

Purpose: This study aimed at developing an adaptive control algorithm using ANN based on chilled water mass flow control to provide the optimal indoor thermal environment of the data center and save cooling energy. Method: The predictive model inherent in the control algorithm uses the model developed in preliminary research. The control algorithm including the predictive model was developed using three techniques with relearning function. To verify the adaptability of the finally selected ANN prediction-based adaptive control algorithm, it is compared and evaluated through simulations with the existing widely applied ON-OFF and PID controllers. Result: Among the three relearning techniques, the RMSE of the control algorithm to which the sliding window was applied is 0.04 (℃), which has the highest prediction accuracy. Thus, was selected as the final control algorithm model. To verify the adaptability and scalability of the selected ANN control algorithm, the containment size and the set-temperature scenario were changed into two and compared and analyzed with ON-OFF, PID controller using simulation. As a result, the ANN controller showed the highest accuracy with RMSE 0.23℃ and 0.24℃, respectively, in both control scenarios. Also, It showed the best performance in terms of maximum temperature difference and energy consumption. That is, the adaptability and scalability of the ANN-based control algorithm to the new environment have been reasonably verified.

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.