Beyond Legal Boundaries: Public and Clinician Perspectives on Treatment Withdrawal in Infants With Poor Neurological Prognosis.

BACKGROUND: Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. METHODS: We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. RESULTS: Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. CONCLUSION: The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.

Investigating the association of opioid prescription with the incidence of psychiatric disorders: nationwide cohort study in South Korea.

BACKGROUND: The relationship between opioid use and the incidence of psychiatric disorders remains unidentified. AIMS: This study examined the association between the incidence of psychiatric disorders and opioid use. METHOD: Data for this population-based cohort study were obtained from the National Health Insurance Service of South Korea. The study included all adult patients who received opioids in 2016. The control group comprised individuals who did not receive opioids in 2016, and were selected using a 1:1 stratified random sampling procedure. Patients with a history of psychiatric disorders diagnosed in 2016 were excluded. The primary end-point was the diagnosis of psychiatric disorders, evaluated from 1 January 2017 to 31 December 2021. Psychiatric disorders included schizophrenia, mood disorders, anxiety and others. RESULTS: The analysis included 3 505 982 participants. Opioids were prescribed to 1 455 829 (41.5%) of these participants in 2016. Specifically, 1 187 453 (33.9%) individuals received opioids for 1-89 days, whereas 268 376 (7.7%) received opioids for ≥90 days. In the multivariable Cox regression model, those who received opioids had a 13% higher incidence of psychiatric disorder than those who did not (hazard ratio 1.13; 95% CI 1.13-1.14). Furthermore, both those prescribed opioids for 1-89 days and for ≥90 days had 13% (hazard ratio 1.13, 95% CI 1.12-1.14) and 17% (hazard ratio 1.17, 95% CI 1.16-1.18) higher incidences of psychiatric disorders, respectively, compared with those who did not receive opioids. CONCLUSIONS: This study revealed that increased psychiatric disorders were associated with opioid medication use. The association was significant among both short- and long-term opioid use.

Optogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions.

Biomolecular condensates, often assembled through phase transition mechanisms, play key roles in organizing diverse cellular activities. The material properties of condensates, ranging from liquid droplets to solid-like glasses or gels, are key features impacting the way resident components associate with one another. However, it remains unclear whether and how different material properties would influence specific cellular functions of condensates. Here, we combine optogenetic control of phase separation with single-molecule mRNA imaging to study relations between phase behaviors and functional performance of condensates. Using light-activated condensation, we show that sequestering target mRNAs into condensates causes translation inhibition. Orthogonal mRNA imaging reveals highly transient nature of interactions between individual mRNAs and condensates. Tuning condensate composition and material property towards more solid-like states leads to stronger translational repression, concomitant with a decrease in molecular mobility. We further demonstrate that ß-actin mRNA sequestration in neurons suppresses spine enlargement during chemically induced long-term potentiation. Our work highlights how the material properties of condensates can modulate functions, a mechanism that may play a role in fine-tuning the output of condensate-driven cellular activities.

Association of hair cortisol concentration with brain-derived neurotrophic factor gene methylation: The role of sex as a moderator.

Hair cortisol concentration (HCC) reflects the long-term activity of the hypothalamus-pituitary-adrenal (HPA) axis in response to stress. Brain-derived neurotrophic factor DNA methylation (BDNF DNAM) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain-derived neurotrophic factor (BDNF) DNAM, and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNAM and Val66Met genotypes. We analyzed the effects of BDNF DNAM, sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNAM and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNAM with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNAM was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNAM and HCC. Therefore, BDNF DNAM was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNAM with long-term HPA axis activity.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Thermodynamic modulation of gephyrin condensation by inhibitory synapse components.

Phase separation drives compartmentalization of intracellular contents into various biomolecular condensates. Individual condensate components are thought to differentially contribute to the organization and function of condensates. However, how intermolecular interactions among constituent biomolecules modulate the phase behaviors of multicomponent condensates remains unclear. Here, we used core components of the inhibitory postsynaptic density (iPSD) as a model system to quantitatively probe how the network of intra- and intermolecular interactions defines the composition and cellular distribution of biomolecular condensates. We found that oligomerization-driven phase separation of gephyrin, an iPSD-specific scaffold, is critically modulated by an intrinsically disordered linker region exhibiting minimal homotypic attractions. Other iPSD components, such as neurotransmitter receptors, differentially promote gephyrin condensation through distinct binding modes and affinities. We further demonstrated that the local accumulation of scaffold-binding proteins at the cell membrane promotes the nucleation of gephyrin condensates in neurons. These results suggest that in multicomponent systems, the extent of scaffold condensation can be fine-tuned by scaffold-binding factors, a potential regulatory mechanism for self-organized compartmentalization in cells.

New-onset mental illness and long-term survival in survivors of critical illness: population-based cohort study in South Korea.

BACKGROUND: Critical care unit (CCU) survivors have a high risk of developing mental illness. AIMS: We aimed to examine the incidence and associated factors of newly developed mental illness among CCU survivors of critical illness. Moreover, we examined the association between newly developed mental illness and 2-year all-cause mortality. METHOD: All adult patients (≥20 years) who were admitted to the CCU during hospitalisation between 2010 and 2018 and survived for 1 year were defined as CCU survivors and were included in this nationwide population-based cohort study. CCU survivors with a history of mental illness before CCU admission were excluded from the study. RESULTS: A total of 1 353 722 CCU survivors were included in the analysis; of these, 33 743 survivors (2.5%) had newly developed mental illness within 1 year of CCU admission. Old age, longer CCU stay, hospital admission through the emergency room, increased total cost of hospitalisation, mechanical ventilatory support, extracorporeal membrane oxygenation support and continuous renal replacement therapy were associated with an increased incidence of newly developed mental illness. Moreover, the newly developed mental illness group showed a 2.36-fold higher 2-year all-cause mortality rate than the no mental illness group (hazard ratio: 2.36; 95% CI: 2.30-2.42; P < 0.001). CONCLUSIONS: In South Korea, 2.5% of CCU survivors had newly developed mental illness within 1 year of CCU admission. Moreover, newly developed mental illness was associated with an increased 2-year all-cause mortality.

Insomnia disorder and cancer mortality in South Korea: a secondary analysis of musculoskeletal disease cohort.

PURPOSE: The association between insomnia disorder and cancer-related mortality risk remains controversial. Therefore, this study aimed to investigate the correlation between insomnia disorder and cancer-related mortality. METHODS: Patients who were diagnosed with musculoskeletal disease (MSD) between 2010 and 2015 were included in this study as a secondary analysis of a patient cohort with MSD in South Korea. Cancer mortality was evaluated between January 1, 2016, and December 31, 2020, using multivariable Cox regression modeling. Patients with and without insomnia disorder constituted the ID and non-ID groups, respectively. RESULTS: The final analysis incorporated a total of 1,298,314 patients diagnosed with MSDs, of whom 11,714 (0.9%) died due to cancer. In the multivariable Cox regression model, the risk of total cancer-related mortality was 14% (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.10-1.19; P < 0.001) higher in the ID group than in the non-ID group. Moreover, the ID group had a higher risk of mortality due to esophageal (HR, 1.46; 95% CI, 1.08-1.96; P = 0.015), colorectal (HR, 1.20; 95% CI, 1.05-1.36; P = 0.007), head and neck (HR, 1.39; 95% CI, 1.01-1.94; P = 0.049), lung (HR, 1.17; 95% CI, 1.08-1.27; P < 0.001), and female genital organ (HR: 1.39, 95% CI: 1.09, 1.77; P = 0.008) cancers; leukemia; and lymphoma (HR, 1.30; 95% CI, 1.12-1.49; P < 0.001). CONCLUSION: Insomnia disorder was associated with elevated overall cancer mortality in patients with MSDs, which was more evident for cancer mortality due to esophageal, colorectal, head and neck, lung, and female genital organ cancers; leukemia; and lymphoma.

Predicting delirium and the effects of medications in hospitalized COVID-19 patients using machine learning: A retrospective study within the Korean Multidisciplinary Cohort for Delirium Prevention (KoMCoDe).

Objective: Delirium is commonly reported from the inpatients with Coronavirus disease 2019 (COVID-19) infection. As delirium is closely associated with adverse clinical outcomes, prediction and prevention of delirium is critical. We developed a machine learning (ML) model to predict delirium in hospitalized patients with COVID-19 and to identify modifiable factors to prevent delirium. Methods: The data set (n = 878) from four medical centers was constructed. Total of 78 predictors were included such as demographic characteristics, vital signs, laboratory results and medication, and the primary outcome was delirium occurrence during hospitalization. For analysis, the extreme gradient boosting (XGBoost) algorithm was applied, and the most influential factors were selected by recursive feature elimination. Among the indicators of performance for ML model, the area under the curve of the receiver operating characteristic (AUROC) curve was selected as the evaluation metric. Results: Regarding the performance of developed delirium prediction model, the accuracy, precision, recall, F1 score, and the AUROC were calculated (0.944, 0.581, 0.421, 0.485, 0.873, respectively). The influential factors of delirium in this model included were mechanical ventilation, medication (antipsychotics, sedatives, ambroxol, piperacillin/tazobactam, acetaminophen, ceftriaxone, and propacetamol), and sodium ion concentration (all p < 0.05). Conclusions: We developed and internally validated an ML model to predict delirium in COVID-19 inpatients. The model identified modifiable factors associated with the development of delirium and could be clinically useful for the prediction and prevention of delirium in COVID-19 inpatients.