Abstract
Background
Clinical guidelines recommend antipsychotics for the treatment of delirium; however, there has been no confirmed recommendation regarding their administrating patterns. This study ...aims to investigate whether different dosing patterns of antipsychotics (single or multiple administrations) influence the outcomes of delirium treatment.
Methods
This is a secondary analysis of a prospective observational study involving patients with advanced cancer and delirium receiving antipsychotics. The Delirium Rating Scale Revised-98 was administered at baseline and after 72 h of starting pharmacotherapy. Patients were classified into single administration group (received a single dosage within 24 h before the assessment) and multiple administration group (received more than one dosage).
Results
A total of 555 patients (single administration 492 (88.6%); multiple administration 63 (11.4%)) were subjected to analyses. The patients in the multiple administration group were more likely to be male, in psycho-oncology consulting settings, with lower performance status, with hyperactive delirium and with severer delirium symptoms. In the multivariate analysis, single administration was significantly associated with better improvement of delirium (p < 0.01, 95% confidence interval: 1.83–5.87) even after controlling covariates. There were no significant differences in the mean dosages of antipsychotics per day in chlorpromazine equivalent (single administration 116.8 mg/day, multiple administration 123.5 mg/day) and the incidence of adverse events between the two groups.
Conclusions
In this observational study sample, Delirium Rating Scale severity score improvement in single administration was higher than that seen in multiple administration. There was no difference in adverse events between the two groups.
Administration of antipsychotics in a single dosage was associated with larger degree of improvement of delirium than multiple administrations without increased risk of adverse events in patients with advanced cancer.
TDP-43 is an RNA-binding protein important for many aspects of RNA metabolism. Abnormal accumulation of TDP-43 in the cytoplasm of affected neurons is a pathological hallmark of the neurodegenerative ...diseases frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Several transgenic mouse models have been generated that recapitulate defects in TDP-43 accumulation, thus causing neurodegeneration and behavioural impairments. While aging is the key risk factor for neurodegenerative diseases, the specific effect of aging on phenotypes in TDP-43 transgenic mice has not been investigated. Here, we analyse age-dependent changes in TDP-43 transgenic mice that displayed impaired memory. We found the accumulation of abundant poly-ubiquitinated protein aggregates in the hippocampus of aged TDP-43 transgenic mice. Intriguingly, the aggregates contained some interneuron-specific proteins such as parvalbumin and calretinin, suggesting that GABAergic interneurons were degenerated in these mice. The abundance of aggregates significantly increased with age and with the overexpression of TDP-43. Gene array analyses in the hippocampus and other brain areas revealed dysregulation in genes linked to oxidative stress and neuronal function in TDP-43 transgenic mice. Our results indicate that the interneuron degeneration occurs upon aging, and TDP-43 accelerates age-dependent neuronal degeneration, which may be related to the impaired memory of TDP-43 transgenic mice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Feasibility and favorable pre-post changes in psychological outcomes were observed in this first pilot study of mindfulness-based cognitive therapy for Japanese breast cancer patients.
Abstract
...Objectives
Mindfulness-based intervention has been receiving growing attention in cancer care. This study aimed to examine feasibility and to preliminary explore effectiveness of mindfulness-based cognitive therapy (MBCT) in Japanese breast cancer patients, and to explore possible modification of the program so that it fits better with this population.
Methods
Twelve participants with diagnosis of Stage I–III breast cancer received an eight session, weekly MBCT intervention in a group therapy format. The participants were followed up until 3 months after the completion of the program.
Results
All the participants completed the program with high attendance rate (mean number of attended sessions = 7.7). Significant improvement in anxiety (Hospital Anxiety and Depression Scale (HADS) – anxiety subscale; effect size Cohen’s d = 0.88, P < 0.05), trauma-related psychological symptoms (Impact of Event Scale-revised; d = 0.64, P < 0.01) and quality of life (Functional Assessment of Cancer Therapy-Breast Cancer: FACT-B; d = 0.72, P < 0.01), and trend-level improvement in depression (HADS – depression subscale; d = 0.53, P = 0.054) were observed. Qualitative analyses suggested the program may be beneficial for alleviating fear of cancer recurrence and for increasing spiritual well-being. Some recommended modification of the program was indicated from the post-intervention interviews.
Conclusions
Mindfulness-based cognitive therapy was well accepted by Japanese breast cancer patients and yielded favorable effect on their psychological status and quality of life. Further effectiveness study in a randomized-control design is warranted.
Patient participation is a key foundation of advance care planning (ACP). However, a patient himself/herself may be left out from sensitive conversations such as end-of-life (EOL) care discussions. ...The objectives of this study were to investigate patients' participation rate in the discussion of Cardiopulmonary Resuscitation (CPR) / Do-Not-Attempt-Resuscitation (DNAR) order, and in the discussion that the patient is at his/her EOL stage (EOL disclosure), and to explore their associated factors.
This is a retrospective chart review study. The participants were all the patients who were hospitalized and died in a university-affiliated teaching hospital (tertiary medical facility) in central Tokyo, Japan during the period from April 2018 to March 2019. The following patients were excluded: (1) cardiopulmonary arrest on arrival; (2) stillbirth; (3) under 18 years old at the time of death; and (4) refusal by their bereaved family. Presence or absence of CPR/DNAR discussion and EOL disclosure, patients' involvement in those discussions, and their associated factors were investigated.
CPR/DNAR discussions were observed in 336 out of the 358 patients (93.9%). However, 224 of these discussions were carried out without a patient (patient participation rate 33.3%). Male gender (odds ratio (OR) = 2.37 95% confidence interval (CI) 1.32-4.25), living alone (OR = 2.51 1.34-4.71), and 1 year or more from the date of diagnosis (OR = 1.78 1.03-3.10) were associated with higher patient's participation in CPR/DNAR discussions. The EOL disclosure was observed in 341 out of the 358 patients (95.3%). However, 170 of the discussions were carried out without the patient (patient participation rate 50.1%). Patients who died of cancer (OR = 2.411.45-4.03) and patients without mental illness (OR=2.41 1.11-5.25) were more likely to participate in EOL disclosure.
In this clinical sample, only up to half of the patients participated in CPR/DNAR discussions and EOL disclosure. Female, living with family, a shorter period from the diagnosis, non-cancer, and mental illness presence are risk factors for lack of patients' participation in CPR/DNAR or EOL discussions. Further attempts to facilitate patients' participation, based on their preference, are warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Japanese Psycho-Oncology Society and Japanese Association of Supportive Care in Cancer recently launched the clinical practice guidelines for delirium in adult cancer patients. The aim of the ...guidelines was to provide evidence-based recommendations for the clinical assessment and management of delirium in cancer patients. This article reports the process of developing the guideline and summarizes the recommendations made.
The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multidisciplinary members, formulated nine clinical questions. A systematic literature search was conducted to identify relevant articles published prior to through 31 May 2016. Each article was reviewed by two independent reviewers. The level of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development and Evaluation system. The modified Delphi method was used to validate the recommendation statements.
This article provides a summary of the recommendations with rationales for each, as well as a short summary.
These guidelines will support the clinical assessment and management of delirium in cancer patients. However, additional clinical studies are warranted to further improve the management of delirium.
Postoperative delirium is a common and serious complication after extensive surgery. This study aimed to investigate the incidence and risk factors for postoperative delirium after major head and ...neck cancer surgery.
A retrospective analysis was performed for 293 patients who underwent major head and neck cancer surgery lasting >6 h at our institution between January 2012 and November 2015. All data were assessed by two psychiatrists. Univariate and multivariate analyses were performed.
Postoperative delirium developed in 50 (17.1%) patients; most cases (84.0%) of postoperative delirium were observed between postoperative day (POD) 1 and POD 3. Multivariate analysis revealed that an age >70 years was the significant risk factor for postoperative delirium incidence after major head and neck cancer surgery; the multivariate hazard ratio was 3.935 (95% confidence interval 1.873–8.265, p < 0.001).
Most cases of postoperative delirium after major head and neck cancer surgery were observed between POD 1 and POD 3, and a multivariate analysis revealed that an age >70 years was a significant risk factor for postoperative delirium incidence. Clinicians should pay particular attention to the possibility of delirium incidence during the first 3 days after surgery for patients aged >70 years.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The Reelin-Dab1 pathway plays important roles in the development of central nervous system. In the autosomal recessive mutant mouse yotari, there is a replacement of a part of Dab1 gene with a long ...interspersed nuclear element fragment, and it was previously suggested that no protein derived from this gene was present. We here show that an aberrant fragment of Dab1 protein (p64/60) is present in the brain of yotari mouse. The amount of p64/60 is relatively abundant in the embryonic stages and decreased in the postnatal ones. Unlike wild-type Dab1 protein, p64/60 is not phosphorylated by Fyn kinase and localizes considerably to the nucleus. These data suggested that some phenotypes of yotari may be attributable to the presence of p64/60. It also raises a caveat that a tissue from yotari is not a perfect control for immunostaining of Dab1 protein.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
Postoperative delirium is common after extensive surgery, and is known to be associated with sleeping medications. In this study, we aimed to investigate the relationships between sleeping ...medications and postoperative delirium after pharyngolaryngectomy with esophagectomy.
Methods
We performed a retrospective analysis of 65 patients who underwent pharyngolaryngectomy with esophagectomy at Shizuoka Cancer Center Hospital between January 2012 and March 2016. All data were assessed by two psychiatrists, and univariate and multivariate analyses were performed.
Results
Postoperative delirium developed in 9 (13.8%) patients, with most cases (77.8%) occurring between postoperative day (POD) 1 and POD 3. Of the 24 patients taking a minor tranquilizer after surgery, 8 (33.3%) became delirious, but, of the remaining 41 patients taking ramelteon with or without suvorexant, only one (2.4%) became delirious after surgery. Moreover, of the 16 patients taking both ramelteon and suvorexant, no postoperative delirium was observed. Ramelteon with or without suvorexant was significantly associated with a decreased rate of postoperative delirium compared with minor tranquilizer use (
p
= 0.001). Multivariate analysis confirmed that the use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium (odds ratio 0.060,
p
= 0.013).
Conclusion
The use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium after pharyngolaryngectomy with esophagectomy. However, using minor tranquilizers was associated with postoperative delirium. We recommend ramelteon with or without suvorexant for preventing postoperative delirium after pharyngolaryngectomy with esophagectomy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We present an improvement of energy density analysis (EDA), which partitions the total energy obtained by Hartree–Fock and/or density functional theory calculations, with the use of the natural ...atomic orbital (NAO) A.E. Reed et al., J. Chem. Phys. 83 (1985) 735 and Löwdin’s symmetric-orthogonal orbital (LSO). The present NAO- and LSO-EDA schemes are applied to analyses of CO
2 and
Li
9
+
with various basis sets. Numerical results confirm that NAO-EDA exhibits less basis-set dependence, while the conventional results are very sensitive to the adopted basis sets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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