Factors associated with self-perceived treatment-resistance in bipolar disorder.

Patients with bipolar disorder often report self-perceived treatment resistance. However, it is not known to what extent it is due to actual treatment resistance. The Juntendo University provides "Bipolar Disorder Treatment Rebuilding Program," in which patients with self-reported treatment resistant bipolar disorder are hospitalized for 2 weeks and undergo detailed examinations. In this study, we report our experience with the initial 43 patients hospitalized during the one and half years after the launch of the program. Among the patients who underwent full assessment, only one was regarded as having genuine treatment-resistant bipolar disorder without comorbidity. In other cases, ten were not diagnosed with bipolar disorder, 3 had organic brain diseases, 12 had comorbid mental disorders and its symptoms were regarded as treatment-resistant bipolar symptoms by the patients, and 18 did not receive adequate treatment because attendant physicians did not adhere to the treatment guidelines or patients did not adhere to the treatment because of lack of insight. The number of participants was not large, and selection bias hampered the generalization of the findings. Insight and adherence were assessed without the use of validated tools. We could not verify recovery after adequate treatment because of the limited hospitalization period. The findings suggest that most patients with self-perceived treatment-resistant bipolar disorder may not have genuine treatment-resistant bipolar disorder. These results shed light on the difficulties of public education of bipolar disorder and importance of providing appropriate services for diagnosis and treatment of bipolar disorder in the community.

Identification of risk factors for the onset of delirium associated with COVID-19 by mining nursing records.

COVID-19 has a range of complications, from no symptoms to severe pneumonia. It can also affect multiple organs including the nervous system. COVID-19 affects the brain, leading to neurological symptoms such as delirium. Delirium, a sudden change in consciousness, can increase the risk of death and prolong the hospital stay. However, research on delirium prediction in patients with COVID-19 is insufficient. This study aimed to identify new risk factors that could predict the onset of delirium in patients with COVID-19 using machine learning (ML) applied to nursing records. This retrospective cohort study used natural language processing and ML to develop a model for classifying the nursing records of patients with delirium. We extracted the features of each word from the model and grouped similar words. To evaluate the usefulness of word groups in predicting the occurrence of delirium in patients with COVID-19, we analyzed the temporal changes in the frequency of occurrence of these word groups before and after the onset of delirium. Moreover, the sensitivity, specificity, and odds ratios were calculated. We identified (1) elimination-related behaviors and conditions and (2) abnormal patient behavior and conditions as risk factors for delirium. Group 1 had the highest sensitivity (0.603), whereas group 2 had the highest specificity and odds ratio (0.938 and 6.903, respectively). These results suggest that these parameters may be useful in predicting delirium in these patients. The risk factors for COVID-19-associated delirium identified in this study were more specific but less sensitive than the ICDSC (Intensive Care Delirium Screening Checklist) and CAM-ICU (Confusion Assessment Method for the Intensive Care Unit). However, they are superior to the ICDSC and CAM-ICU because they can predict delirium without medical staff and at no cost.

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia.

Aim: To investigate the real-world effectiveness and safety of lemborexan for treating comorbid insomnia associated with other psychiatric disorders, and whether lemborexant helps reduce the dose of benzodiazepines (BZs). Methods: This retrospective observational study was conducted on outpatients and inpatients treated by physicians of Juntendo University Hospital Mental Clinic between April 2020 and December 2021. Results: Data of 649 patients who were treated with lemborexant were eventually enrolled. About 64.5% of patients were classified as the responder group. Response rates of ≥60% were recorded for most psychiatric disorders. Upon administration of lemborexant, diazepam-equivalent dose of BZs had been significantly reduced in participants (3.7 ± 8.2 vs. 2.9 ± 7.9, p < 0.001). The results of logistic regression analysis showed that outpatient (odds ratios: 2.310; 95% confidence interval [CI]: 1.32-4.05), shorter duration of BZ use (<1 year) (odds ratios: 1.512; 95% CI: 1.02-2.25), no adverse events (odds ratios: 10.369; 95% CI: 6.13-17.54), larger reduction of diazepam-equivalent dose of BZs upon introducing lemborexant prescription (odds ratios: 1.150; 95% CI: 1.04-1.27), and suvorexant was the replacement drug (odds ratios: 2.983; 95% CI: 1.44-6.19), which were significant predictors of good response. Conclusion: Although this is a retrospective and observational study with many limitations, our study results suggest that lemborexant is effective and safe.

Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study.

BACKGROUND/AIMS: Interaction of receptor for advanced glycation end products (RAGE) with amyloid-ß increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs. METHODS: Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls. RESULTS: Linkage disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an increased risk of AD. Although there were no statistical associations for the other three SNPs, haplotypic analyses detected genetic associations between AD and the RAGE gene. Although relatively few cases were studied, results from the SNPs showed that they did not modify the risk of developing LBDs in the Japanese population. CONCLUSION: Our findings suggested that polymorphisms in the RAGE gene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.

Genetic Association between Presenilin 2 Polymorphisms and Alzheimer's Disease and Dementia of Lewy Body Type in a Japanese Population.

BACKGROUND/AIMS: Mutations in the presenilin 2 (PSEN2) gene cause familial Alzheimer's disease (AD). Common polymorphisms affect gene activity and increase the risk of AD. Nonsynonymous polymorphisms in the PSEN2 gene showed Lewy body dementia (LBD) phenotypes clinically. Therefore, we aimed to investigate whether PSEN2 gene polymorphisms were associated with AD or LBD. METHODS: Seven single nucleotide polymorphisms (SNPs) of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBD patients, and 105 age-matched controls. RESULTS: Linkage disequilibrium (LD) examination showed strong LD from rs1295645 to rs8383 on the gene in our cases from Japan. There were no associations between the SNPs studied here and AD onset, and haplotypic analyses did not detect genetic associations between AD and the PSEN2 gene. Although the number of the cases was small, the SNPs studied did not modify the risk of developing LBD in a Japanese population. CONCLUSION: The common SNPs of the PSEN2 gene did not affect the risk of AD or LBD in a Japanese population. Because genetic variability of the PSEN2 gene is associated with behavioral and psychological symptoms of dementia (BPSD) in AD and LBD, further detailed analyses considering BPSD of both diseases would be required.