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Background/Aims@#The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. @*Methods@#We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. @*Results@#A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85–1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77–1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59–0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. @*Conclusions@#In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.
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Background@#The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group. @*Methods@#We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality. @*Results@#Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m 2 or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043–1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584–14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042–8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691–98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294–10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison. @*Conclusion@#Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.
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Background/Aims@#To identify changes in symptoms and pulmonary sequelae in patients with coronavirus disease 2019 (COVID-19). @*Methods@#Patients with COVID-19 hospitalized at seven university hospitals in Korea between February 2020 and February 2021 were enrolled, provided they had ≥ 1 outpatient follow-up visit. Between January 11 and March 9, 2021 (study period), residual symptom investigations, chest computed tomography (CT) scans, pulmonary function tests (PFT), and neutralizing antibody tests (NAb) were performed at the outpatient visit (cross-sectional design). Additionally, data from patients who already had follow-up outpatient visits before the study period were collected retrospectively. @*Results@#Investigation of residual symptoms, chest CT scans, PFT, and NAb were performed in 84, 35, 31, and 27 patients, respectively. After 6 months, chest discomfort and dyspnea persisted in 26.7% (4/15) and 33.3% (5/15) patients, respectively, and 40.0% (6/15) and 26.7% (4/15) patients experienced financial loss and emotional distress, respectively. When the ratio of later CT score to previous ones was calculated for each patient between three different time intervals (1–14, 15–60, and 61–365 days), the median values were 0.65 (the second interval to the first), 0.39 (the third to the second), and 0.20 (the third to the first), indicating that CT score decreases with time. In the high-severity group, the ratio was lower than in the low-severity group. @*Conclusions@#In COVID-19 survivors, chest CT score recovers over time, but recovery is slower in severely ill patients. Subjects complained of various ongoing symptoms and socioeconomic problems for several months after recovery.
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Modern electroconvulsive therapy (ECT) is a non-pharmacological and biological treatment that is clinically effective and safe. ECT is used in the treatment of many psychiatric disorders, some neurological diseases, and psychiatric emergencies requiring a rapid and life-saving clinical response. Generalized seizures of the central nervous system induced by the electrical stimulation of ECT are an essential component of the therapeutic effects, which are attributed to the various neuronal responses of the brain. Modern ECT is conducted under general anesthesia, given to the extent of loss of consciousness, followed by administration of a muscle relaxant, and ECT with minimally appropriate electrical stimulation. ECT optimization has the main objective of ensuring maximum clinical efficacy and safety with minimal adverse events through adequate generalized seizures. Since its first introduction in clinical practice in 1938, many studies have been carried out and advances made to enhance the therapeutic effects of ECT and address the adverse events associated with it. As a result, there have been developments such as the use of a square wave instead of a sine wave, various electrode placements, dose titration methods, seizure thresholds, general anesthesia with muscle relaxation, session scheduling, monitoring of electroencephalograms (EEG) and electromyograms, etc. and these have been applied to actual clinical practice. Research on the clinical characteristics and the optimal ECT parameters to increase the efficacy of seizures is still ongoing. In this review, various factors associated with ECT such as EEG monitoring, motor seizures, electrode placements, stimulation dose and titration, seizure evaluation and adequacy, and the ECT algorithms are discussed to improve the efficacy of modern ECT as a useful treatment for psychiatric disorders.
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“Breakthrough” of psychosis despite good compliance of antipsychotics medication for a long time is a major obstacle to the treatment of schizophrenia, whether the mechanism is caused by dopamine hypersensitivity or insufficient dose of antipsychotics. Researchers advocating “Dopamine Supersensitivity Psychosis” (DSP) emphasize to avoid excessive inhibition of dopamine 2 receptors from the beginning of treatment. On the other hand, researchers advocating “Breakthrough psychosis on Antipsychotic Maintenance Medication” (BAMM) in which psychosis recurs due to insufficient medication despite continuous administration of antipsychotics without non-adherence argue that dose of antipsychotics should be increased to enhance therapeutic effect. In patients using long-acting antipsychotics injection (LAI), non-compliance can be ruled out. We believe that in treating non-affective psychosis, it is necessary to continuously maintain the lowest dose possible using the optimal dose considering the side effects of second-generation antipsychotics and the cycle and stage of psychosis, and the optimal formulation such as LAI.
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Background@#Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea. @*Methods@#We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics. @*Results@#During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m 2 .Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092;95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients.Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group.The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m 2 ), and the one remaining patient died from a secondary infection. @*Conclusion@#About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m2 ) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.
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Background@#Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. @*Methods@#This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. @*Results@#Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). @*Conclusion@#Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.
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Despite the coronavirus disease 2019 (COVID-19) vaccination roll-out, variant-related outbreaks have occurred repeatedly in Korea. Although public hospitals played a major role in COVID-19 patients’ care, difficulty incorporating evolving COVID-19 treatment guidelines called for a clinical pathway (CP). Eighteen public hospitals volunteered, and a professional review board was created. CPs were formulated containing inclusion/exclusion criteria, application flow charts, and standardized order sets. After CP roll-out, key parameters improved, such as increased patient/staff five-point satisfaction scores (0.41/0.57) and decreased hospital stays (1.78 days)/medical expenses (17.5%). The CPs were updated consistently after roll-out as new therapeutics drugs were introduced and quarantine policies changed.
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Objective@#Telomere shortening has been seen in major psychiatric disorders, including major depressive disorder.However, only a few small studies have examined this in bipolar disorder (BD). We compared the telomere length in patients with BD1 or BD2 with that in matched healthy controls. @*Methods@#We included 215 patients with BD (128 BD1, 87 BD2) and 204 age- and sex-matched healthy controls. Relative telomere length was determined by quantitative polymerase chain reaction. The patients and controls were compared separately for age groups, sex, and BD subgroups (BD1 and BD2). @*Results@#We found significant telomere shortening in patients with BD1 (p ＜ 0.001), but not in patients with BD2.In male patients with BD1, the 30−39 year age group had significant shortening of telomere length than controls (p = 0.01). Female patients with BD1 in the 19−29-year age group had significantly shortened telomeres compared to the controls (p ＜ 0.01). @*Conclusion@#Our results suggest a significant reduction in telomere length in BD1. Telomere shortening would be a potential biomarker for BD.
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Background@#Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. @*Methods@#A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. @*Results@#A total of 86 severe COVID-19 patients were evaluated including 48 remdesivirtreated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1–5 to 11–15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). @*Conclusion@#The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.
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Objectives@#This study examined the satisfaction of patients who had undergone electroconvulsive therapy to provide important information for improving the social misunderstanding about electroconvulsive therapy, to increase the effectiveness of treatment, and make a decision of effective treatment. @*Methods@#A questionnaire survey was conducted to determine the satisfaction, adverse effects, attitudes, and experiences toward electroconvulsive therapy in patients at 2 to 4 weeks after finishing an acute course of electroconvulsive therapy in three psychiatric hospitals. @*Results@#There were 85 respondents (38 males), whose average age was 42.0±13.6 years and average illness duration was 12.8±8.9 years. Fifty-two patients (61.2%), 19 (22.4%), 8 (9.4%), and 6 (7.1%) were diagnosed with schizophrenia, major depressive disorder, bipolar disorder, and other mental disorders, respectively. The average session number for acute electroconvulsive therapy was 12.6±6.0 sessions, and 61 patients (71.8%) had received maintenance electroconvulsive therapy. Among the respondents, 60.0% reported that they were satisfied with the electroconvulsive therapy. Satisfaction was similar according to sex, age, diagnosis, electrode placement, and use of anesthetic agents. Forty-three (53.8%) patients experienced memory impairment during acute electroconvulsive therapy. @*Conclusion@#This study showed that patients who received electroconvulsive therapy were generally satisfied with the treatment and that memory impairment should be detected early and managed promptly. Follow-up studies with a large number of subjects and variables will be needed to determine the predictive factors affecting satisfaction toward electroconvulsive therapy.
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Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.
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Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.
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Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.
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Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.
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Objective@#Telomere shortening has been seen in major psychiatric disorders, including major depressive disorder.However, only a few small studies have examined this in bipolar disorder (BD). We compared the telomere length in patients with BD1 or BD2 with that in matched healthy controls. @*Methods@#We included 215 patients with BD (128 BD1, 87 BD2) and 204 age- and sex-matched healthy controls. Relative telomere length was determined by quantitative polymerase chain reaction. The patients and controls were compared separately for age groups, sex, and BD subgroups (BD1 and BD2). @*Results@#We found significant telomere shortening in patients with BD1 (p ＜ 0.001), but not in patients with BD2.In male patients with BD1, the 30−39 year age group had significant shortening of telomere length than controls (p = 0.01). Female patients with BD1 in the 19−29-year age group had significantly shortened telomeres compared to the controls (p ＜ 0.01). @*Conclusion@#Our results suggest a significant reduction in telomere length in BD1. Telomere shortening would be a potential biomarker for BD.
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Background@#Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. @*Methods@#A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. @*Results@#A total of 86 severe COVID-19 patients were evaluated including 48 remdesivirtreated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1–5 to 11–15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). @*Conclusion@#The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.
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Objectives@#This study examined the satisfaction of patients who had undergone electroconvulsive therapy to provide important information for improving the social misunderstanding about electroconvulsive therapy, to increase the effectiveness of treatment, and make a decision of effective treatment. @*Methods@#A questionnaire survey was conducted to determine the satisfaction, adverse effects, attitudes, and experiences toward electroconvulsive therapy in patients at 2 to 4 weeks after finishing an acute course of electroconvulsive therapy in three psychiatric hospitals. @*Results@#There were 85 respondents (38 males), whose average age was 42.0±13.6 years and average illness duration was 12.8±8.9 years. Fifty-two patients (61.2%), 19 (22.4%), 8 (9.4%), and 6 (7.1%) were diagnosed with schizophrenia, major depressive disorder, bipolar disorder, and other mental disorders, respectively. The average session number for acute electroconvulsive therapy was 12.6±6.0 sessions, and 61 patients (71.8%) had received maintenance electroconvulsive therapy. Among the respondents, 60.0% reported that they were satisfied with the electroconvulsive therapy. Satisfaction was similar according to sex, age, diagnosis, electrode placement, and use of anesthetic agents. Forty-three (53.8%) patients experienced memory impairment during acute electroconvulsive therapy. @*Conclusion@#This study showed that patients who received electroconvulsive therapy were generally satisfied with the treatment and that memory impairment should be detected early and managed promptly. Follow-up studies with a large number of subjects and variables will be needed to determine the predictive factors affecting satisfaction toward electroconvulsive therapy.
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Chronotype is an important moderator of psychiatric illnesses, which seems to be controlled in some part by genetic factors. Clock genes are the most relevant genes for chronotype. In addition to the roles of individual genes, gene-gene interactions of clock genes substantially contribute to chronotype. We investigated genetic associations and gene-gene interactions of the clock genes BHLHB2, CLOCK, CSNK1E, NR1D1, PER1, PER2, PER3, and TIMELESS for chronotype in 1293 healthy Korean individuals. Regression analysis was conducted to find associations between single nucleotide polymorphism (SNP) and chronotype. For gene-gene interaction analyses, the quantitative multifactor dimensionality reduction (QMDR) method, a nonparametric model-free method for quantitative phenotypes, were performed. No individual SNP or haplotype showed a significant association with chronotype by both regression analysis and single-locus model of QMDR. QMDR analysis identified NR1D1 rs2314339 and TIMELESS rs4630333 as the best SNP pairs among two-locus interaction models associated with chronotype (cross-validation consistency [CVC] = 8/10, p = 0.041). For the three-locus interaction model, the SNP combination of NR1D1 rs2314339, TIMELESS rs4630333, and PER3 rs228669 showed the best results (CVC = 4/10, p < 0.001). However, because the mean differences between genotype combinations were minor, the clinical roles of clock gene interactions are unlikely to be critical.
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Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.