Association of the First Antipsychotic Treatment Duration With the Re-Initiation of Treatment in Schizophrenia: A National Health Insurance Data-Based Study / 대한정신분열병학회지

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 <2 years of the first antipsychotic treatment. In patients who discontinued treatment (n=23,030), the rate of treatment re-initiation was 74.2% (n=17,086). As the duration of the first antipsychotic treatment increased, the time to re-initiation of treatment decreased (β=-0.146, p<0.001); however, the rate of treatment re-initiation was relatively constant (hazard ratio=1.001, p<0.001). @*Conclusion@#Long-term antipsychotic treatment was not significantly associated with the rate of treatment re-initiation but showed a negative association with the time to re-initiation of treatment. Further research is needed to better understand the optimal treatment duration for FES.

Effectiveness and Safety of Liraglutide Treatment in Patients with a Psychiatric Disorder / 신경정신의학

Objectives@#Liraglutide is a glucagon-like-peptide-1 receptor agonist which has been used as an anti-obesity drug. It was reported that patients might develop or worsen suicidal ideas and/or depression during liraglutide treatment, especially when it comes to patients with a psychiatric disorder. The purpose of this study was to evaluate the effectiveness and safety of liraglutide, especially in terms of the psychiatric adverse effects. @*Methods@#A retrospective chart review study was conducted on psychiatric patients prescribed liraglutide for more than one month from September 2018 to September 2020. Based on their medical records, we investigated the change in the weight and body mass index (BMI) of patients from the baseline to 6 months of receiving liraglutide treatment. Information on the adverse effects was also obtained, including psychiatric adverse effects such as insomnia, anxiety, depression, and suicidal ideation. A mixed linear model was used for assessing the time effect on change in weight and BMI. @*Results@#A total of 24 patients were included in the current study, and the most common psychiatric diagnosis included major depressive disorder (n=13, 54.2%). There was a significant change in weight (F=6.127, p=0.001) and BMI (F=6.749, p<0.001) during the liraglutide treatment. Worsening of depression and anxiety occurred in one patient but improved after the adjustment of psychiatric medications. @*Conclusion@#The current study found that liraglutide treatment in patients with a psychiatric disorder can be a safe and effective intervention for weight reduction.

Effectiveness and Safety of Liraglutide Treatment in Patients with a Psychiatric Disorder / 신경정신의학

Objectives@#Liraglutide is a glucagon-like-peptide-1 receptor agonist which has been used as an anti-obesity drug. It was reported that patients might develop or worsen suicidal ideas and/or depression during liraglutide treatment, especially when it comes to patients with a psychiatric disorder. The purpose of this study was to evaluate the effectiveness and safety of liraglutide, especially in terms of the psychiatric adverse effects. @*Methods@#A retrospective chart review study was conducted on psychiatric patients prescribed liraglutide for more than one month from September 2018 to September 2020. Based on their medical records, we investigated the change in the weight and body mass index (BMI) of patients from the baseline to 6 months of receiving liraglutide treatment. Information on the adverse effects was also obtained, including psychiatric adverse effects such as insomnia, anxiety, depression, and suicidal ideation. A mixed linear model was used for assessing the time effect on change in weight and BMI. @*Results@#A total of 24 patients were included in the current study, and the most common psychiatric diagnosis included major depressive disorder (n=13, 54.2%). There was a significant change in weight (F=6.127, p=0.001) and BMI (F=6.749, p<0.001) during the liraglutide treatment. Worsening of depression and anxiety occurred in one patient but improved after the adjustment of psychiatric medications. @*Conclusion@#The current study found that liraglutide treatment in patients with a psychiatric disorder can be a safe and effective intervention for weight reduction.

Additive Burden of Abnormal Diffusivity in the Brainwith Schizophrenia: A Diffusion Tensor Imaging Studywith Public Neuroimaging Data

Objective@#Diffusion tensor imaging has been extensively applied to schizophrenia research. In this study, we counted the number ofabnormal brain regions with altered diffusion measures in patients with schizophrenia to enumerate the burden of abnormal diffusivityin the brain. @*Methods@#The public neuroimaging data of the COBRE project from SchizConnect were used for the study. The studied dataset consistedof data from 57 patients with schizophrenia and 71 healthy participants. FreeSurfer and FSL were applied for image processingand analysis. After verifying 161 regions of interest (ROIs), mean diffusion measures in every single ROI in all study participants weremeasured and normalized into Z-scores. Each ROI was then defined as normal or abnormal on the basis of a cutoff absolute Z-score of1.96. 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 inhealthy participants. @*Conclusion@#Thus, the patient group showed a significant increase in abnormal ROIs, strongly indicating that schizophrenia is notcaused by the pathology of a single brain region, but is instead attributable to the additive burden of structural alterations within multiplebrain regions. Psychiatry Investig 2020;17(4):341-349

Characteristics of Delirium in Patients with Hearing Disturbances / 신경정신의학

OBJECTIVES: Several studies have delineated the relationship between hearing disturbances and the prevalence or characteristics of psychotic symptoms; however, most of those studies focused on psychiatric patients and not general inpatients. Delirium has a high incidence among general inpatients, and patients with delirium are easily affected by psychotic symptoms that lead to irritable behaviors. This study examined the relationship between hearing disturbance and psychotic symptoms among patients with delirium. METHODS: At the Asan Medical Center in Seoul, South Korea, this study examined 27 inpatients who had both delirium and hearing disturbances between January 1, 2009 and December 31, 2018, and 146 inpatients at the Asan Medical Center who had delirium but no hearing disturbances between July 1, 2018 and December 31, 2018. This study investigated whether the two groups showed differences in the prevalence and characteristics of delirium symptoms, particularly psychotic symptoms. In addition, the correlation between clinical characteristics of delirium and the recommended dosage of antipsychotics was analyzed in patients who had been diagnosed with delirium and had hearing disturbances. RESULTS: Compared to inpatients who only had delirium, those who had both delirium and hearing disturbances had a significantly higher prevalence of hallucination and delusion. CONCLUSION: The prevalence of psychotic symptoms, such as hallucination and delusion, was higher in patients who had both delirium and hearing disturbances, which is in line with the results from previous studies on psychiatric patients. Physicians should focus on improving communication with such patients by employing non-verbal communication methods.

Gray Matter Microstructural Abnormalities and Working Memory Deficits in Individuals with Schizophrenia

OBJECTIVE: Working memory impairments serve as prognostic factors for patients with schizophrenia. Working memory deficits are mainly associated with gray matter (GM) thickness and volume. We investigated the association between GM diffusivity and working memory in controls and individuals with schizophrenia. METHODS: T1 and diffusion tensor images of the brain, working memory task (letter number sequencing) scores, and the demographic data of 90 individuals with schizophrenia and 97 controls were collected from the SchizConnect database. T1 images were parcellated into the 68 GM Regions of Interest (ROI). Axial Diffusivity (AD), Fractional Anisotropy (FA), Radial Diffusivity (RD), and Trace (TR) were calculated for each of the ROIs. RESULTS: Compared to the controls, schizophrenia group showed significantly increased AD, RD, and TR in specific regions on the frontal, temporal, and anterior cingulate area. Moreover, working memory was negatively correlated with AD, RD, and TR in the lateral orbitofrontal, superior temporal, inferior temporal, and rostral anterior cingulate area on left hemisphere in the individuals with schizophrenia. CONCLUSION: These results demonstrated GM microstructural abnormalities in the frontal, temporal, and anterior cingulate regions of individuals with schizophrenia. Furthermore, these regional GM microstructural abnormalities suggest a neuropathological basis for the working memory deficits observed clinically in individuals with schizophrenia.

Treatment of Children and Adolescents with Attention Deficit Hyperactivity Disorder and/or Tourette's Disorder with Clonidine Extended Release

We aimed to assess the effectiveness and safety of clonidine extended release (ER) treatment in Korean youth with ADHD and/or Tourette's disorder. We retrospectively reviewed the medical records of 29 children and adolescents treated with clonidine ER. The effectiveness were retrospectively measured at baseline and after 4 and 12 weeks based on the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores. Safety was evaluated at each visit based on spontaneous reports from the subjects or from their parents/guardians. Significant decreases in the CGI-S scores for both ADHD (F=23.478, p < 0.001, partial η2=0.540) and tic symptoms (F=15.137, p < 0.001, partial η2=0.443) were noted over 12 weeks. The most common adverse event was somnolence (n=9, 31.0%) and life-threatening adverse effects were not observed. Our results provide preliminary evidence for the effectiveness and safety of clonidine ER.

Effectiveness and Safety of Electroconvulsive Therapy in Clinical Practice / 신경정신의학

OBJECTIVES: There is little research on the practice and effectiveness of electroconvulsive therapy (ECT) in Korea. This study investigated the practice pattern, effectiveness, and safety of ECT. METHODS: This chart review study included electronic medical records of 180 patients treated with ECT between January 2007 and December 2013 at the Asan Medical Center. Symptomatic improvement was assessed using Clinical Global Impression (CGI) scale. Treatment response was defined as CGI improvement scale score of 2 or less. Re-hospitalization was used as an indicator of recurrence. Safety was assessed by spontaneous reports from patients. RESULTS: One hundred and eighty patients underwent 1539 sessions of modified ECT. Their most frequent diagnosis was major depressive disorder (n=74, 41.1%). The most common indication for ECT was poor response to medication (n=177, 75.3%). Treatment response rate was 66.9% in acute phase group and 63.8% in the patients with poor response to medication. The recurrence rate at six months after the end of the course was 29.6%. Memory impairment or amnesia was the most common adverse effect. CONCLUSION: There was a remarkable improvement following ECT in patients who responded poorly to medications, and most adverse effects were tolerable and temporary. The present study suggests that ECT could be a useful treatment option.

The Intoxication of Beta Blocker with Psychiatric Drugs Focused on the Cardiovascular Adverse Effects

PURPOSE: Beta blocker (BB) has been prescribed for anxiety and panic disorder. Patients intoxicated by psychiatric drugs have often been exposed to BB. Moreover, BB overdose has adverse effects including cardiovascular effects, which can be life-threatening. This study was conducted to identify the characteristics of BB intoxication with psychiatric drugs and the adverse effects on the cardiovascular system. METHODS: A single center, retrospective study was performed from January 2010 to December 2015. A total of 4,192 patients visited the emergency department (ED) with intoxication, and 69 with BB intoxication were enrolled. RESULTS: Overall, 64 patients (92.8%) of enrolled patients were intoxicated with drugs prescribed for the purpose of psychiatric disorders. Propranolol was the most common BB (62 cases, 96.2%), and the median dose was 140.0 mg (25%-75% 80.0-260.0). Twenty-four patients (37.5%) had experienced cardiovascular events, and these patients tended to have decreased mentality, hypotension and coingestion with quetiapine. An initial mean arterial pressure (MAP) below 65 mmHg (odds ratio 10.069, 95% confidence interval 1.572-64.481, p=0.015) was identified as a factor of cardiovascular event upon multiple logistic regression analysis. CONCLUSION: Initial MAP below 65 mmHg was a factor of cardiovascular adverse effect in patients of BB intoxication with psychiatric drugs.

Lower Energy to Make a Corneal Flap with a 60 kHz Femtosecond Laser Reduces Flap Inflammation and Corneal Stromal Cell Death But Weakens Flap Adhesion

PURPOSE: To compare corneal flaps created in rabbits with a 60 kHz femtosecond (FS) laser using different levels of raster energy and to measure early inflammation, corneal stromal cell death, and late postoperative adhesion strength. METHODS: Sixty rabbits were divided into three groups of 20 each. A flap 110 micrometer thick and 9.0 mm in diameter was made in one eye of each rabbit at raster energies of 0.7 microJ, 1.1 microJ, and 2.4 microJ. Histopathological evaluation for inflammation and apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed at 4 and 24 hours after flap creation. The adhesion strength of the flaps was measured with a tension meter at 1 and 3 months. RESULTS: Twenty four hours after flap creation, the 2.4 microJ group had more inflammatory and CD11b-positive cells than the 0.7 and 1.1 microJ groups. The number of TUNEL-positive cells increased with raster energy at 4 and 24 hours. The grams of force (gf) needed to detach the flaps at 3 months was significantly higher in 2.4 microJ group (170 gf) than in 0.7 microJ group (97.5 gf) and 1.1 microJ group (100 gf, p = 0.03). CONCLUSIONS: Using raster energy lower than 1.1 microJ to make a flap with a 60 kHz FS laser decreases inflammatory cell infiltration and corneal stromal cell death in the central cornea but may result in a weaker flap than using higher raster energy (2.4 microJ).

Lower Energy to Make a Corneal Flap with a 60 kHz Femtosecond Laser Reduces Flap Inflammation and Corneal Stromal Cell Death But Weakens Flap Adhesion

PURPOSE: To compare corneal flaps created in rabbits with a 60 kHz femtosecond (FS) laser using different levels of raster energy and to measure early inflammation, corneal stromal cell death, and late postoperative adhesion strength. METHODS: Sixty rabbits were divided into three groups of 20 each. A flap 110 micrometer thick and 9.0 mm in diameter was made in one eye of each rabbit at raster energies of 0.7 microJ, 1.1 microJ, and 2.4 microJ. Histopathological evaluation for inflammation and apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed at 4 and 24 hours after flap creation. The adhesion strength of the flaps was measured with a tension meter at 1 and 3 months. RESULTS: Twenty four hours after flap creation, the 2.4 microJ group had more inflammatory and CD11b-positive cells than the 0.7 and 1.1 microJ groups. The number of TUNEL-positive cells increased with raster energy at 4 and 24 hours. The grams of force (gf) needed to detach the flaps at 3 months was significantly higher in 2.4 microJ group (170 gf) than in 0.7 microJ group (97.5 gf) and 1.1 microJ group (100 gf, p = 0.03). CONCLUSIONS: Using raster energy lower than 1.1 microJ to make a flap with a 60 kHz FS laser decreases inflammatory cell infiltration and corneal stromal cell death in the central cornea but may result in a weaker flap than using higher raster energy (2.4 microJ).

Endocrinopathy in Hemochromatosis Patients Multi-Transfused for Aplastic Anemia / 대한소아혈액종양학회지

PURPOSE: Chronic blood transfusions result in excessive iron deposition leading to eventual tissue damage and impaired function of organs, such as the liver, spleen, pancreas, skin, thyroid, and heart. We evaluated the body iron status and endocrinopathy in repeatedly transfused patients with aplastic anemia (AA). METHODS: Fourteen patients with AA who were transfused with more than 10 Units of packed RBC since 1996 were evaluated. We evaluated the correlation of amount of blood transfused with status of iron stores (determined by serum iron, TIBC, ferritin and transferrin saturation) and organ damage. RESULTS: Patients received a median of 61 units (range 11~168 units) of PRC. Twelve patients (85.7%) had elevated serum ferritin levels, and 11 (78.6%) had elevated transferrin saturation. Serum ferritin (P<0.01; r=0.868), and transferrin saturation (P<0.05; r=0.569) were significantly correlated with the amount of PRC transfused, respectively. Five patients had clinically significant iron overload despite the use of deferoxamine. Organ damage caused by transfusion iron overload were skin pigmentation (N=3), hepatic (N=1) and endocrinologic abnormalities. Diabetes (N=3), hypothyroidism (N=3), and hyogonadotropic hypogonadism (N=1) were observed. No patient developed clinically significant arthropathy or cardiac disease. CONCLUSION: AA patients who received chronic blood transfusions develop iron overload which may lead to endocrinopathy. Iron status and organ dysfunction should be monitored and effective measures to prevent iron overload should be applied in patients who need chronic transfusions.

Two Cases of Pichia Ohmeri Fungemia / 대한소아혈액종양학회지

Pichia ohmeri is an yeast-like fungus used in the food industry for fermentation. This organism has been implicated in human disease only in a few case reports. We describe herewith two cases of Pichia ohmeri fungemia in immunocompromised pediatric patients with central venous catheters. A 7-year-old patient with Burkitt's lymphoma undergoing chemotherapy and a newborn with low birth weight developed fungemia during hospitalizations. Both patients were receiving parenteral nutrition through central venous catheters. Both patients succumbed despite empiric treatment with amphotericin B in Case 1. A brief review of the literature ensues with the case reports.

Factors Influencing the Time to Full Enteral Feeding in Very Low Birth Weight Infants

PURPOSE: We investigated the factors influencing the time to reach full enteral feeding in very low birth weight infants. We compared the days of life to start tube or oral feeding, to regain birth weight, and to establish full enteral feeding in very low birth weight infants and determined the risk factors delaying full enteral feeding. METHODS: We reviewed the medical records of 214 newborn infants less than 1,500 g at birth, who were delivered at Chonnam National University Hospital from January 1, 1997 to May 31, 2000. These infants were divided into three groups by birth weight (less than 1,000 g, 1,000-1,249 g, and 1,250-1,499 g). Gestational age, birth weight, the days of life to start first tube or oral feeding, to regain bith weight and to reach full enteral feeding, and the possible risk factors delaying the progress of enteral feeding were analyzed. RESULTS: The gestational age was 29.69+/-2.33 weeks and the birth weight was 1,212+/-194.3 g. The time to start tube or oral feeding, to regain birth weight, and to establish full enteral feeding were significantly later and longer in the lower birth weight group. The time to reach full enteral feeding was related to the duration of mechanical ventilation and oxygen therapy, and was significantly longer in the infants with severe respiratory distress syndrome (RDS), chronic lung disease (CLD), apnea, intraventricular hemorrhage (IVH), cystic periventricular leukomalacia, sepsis/disseminated intravascular coagulopathy, ricketts, and total parenteral nutrition. CONCLUSION: The time to reach full enteral feeding was inversely related to the birth weight, and the risk factors for delayed full enteral feeding were the presence and/or the severity of diseases related to the prematurity such as the duration of mechanical ventilation and oxygen therapy, RDS, CLD, apnea, IVH, and sepsis.

Expression Pattern of Tumor Progression and Metastasis-related Gene Proteins - CD44H, CD44v6, erbB-2, and p53 -in Gastric Carcinoma

Immunohistochemical studies of the molecules associated with gastric tumor progression and metastasis were done to evaluate their relationship with known prognostic factors and their usefulness in assessment of the progression of gastric carcinoma in 127 gastric carcinoma tissues. The 4 antibodies used in this study were CD44H, CD44v6, erbB-2, and p53. The CD44H expression was detected in 76 (59.8%), CD44v6 in 63 (49.6%), erbB-2 in 18 (14.2%), and mutant p53 in 98 (77.2%) out of 127 cases of gastric carcinomas. There was no significant correlation between the expression rates of each four proteins. The expression rates of all 4 proteins were not significantly correlated with age and sex of the patients and lymph node metastasis, but the correlation between CD44v6 expression and the depth of tumor invasion and tumor stage was significant (p<0.05). These results suggest that CD44v6 is closely associated with tumor invasion, and high levels of CD44H, erbB-2 and p53 are associated with tumorigenesis of the stomach as they are highly expressed in early as well as in advanced gastric carcinomas. The findings also support the conclusion that the loss of control of alternative CD44 mRNA splicing resulted in production of CD44v6 splicing variant in tumor cell facilitates tissue invasion by increased adherence of the tumor cell to an extracellular matrix or by tumor cell migration. It can be expected that CD44v6 overexpression in tumor cells appears to be an important prognostic indicator for gastric tumor progression.