Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

OBJECTIVES: There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. METHODS: This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. RESULTS: Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. SIGNIFICANCE OF RESULTS: This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

A multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of ramelteon for the prevention of postoperative delirium in elderly cancer patients: a study protocol for JORTC-PON2/J-SUPPORT2103/NCCH2103.

Postoperative delirium is an important issue in cancer patients, affecting surgical outcomes and the quality of life. Ramelteon is a melatonin receptor agonist with high affinity for MT1 and MT2 receptors. Clinical trials and observational studies in Japan, including in surgical cancer patients, have shown efficacy of ramelteon in delirium prevention, with no serious safety concerns. However, clinical trials from the USA have reported conflicting results. A Japanese phase II study investigated the efficacy and safety of ramelteon for delirium prevention following gastrectomy in patients aged ≥75 years, with findings suggesting the feasibility of a phase III trial. The aim of this multi-centre, double-blind, randomized placebo-controlled phase III trial is to evaluate the effectiveness and safety of oral ramelteon for postoperative delirium prevention in cancer patients aged ≥65 years as advanced medical care. The trial protocol is described here.

A decision tree prediction model for a short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions: A secondary analysis of a multicenter and prospective observational study (Phase-R).

OBJECTIVE: There is no widely used prognostic model for delirium in patients with advanced cancer. The present study aimed to develop a decision tree prediction model for a short-term outcome. METHOD: This is a secondary analysis of a multicenter and prospective observational study conducted at 9 psycho-oncology consultation services and 14 inpatient palliative care units in Japan. We used records of patients with advanced cancer receiving pharmacological interventions with a baseline Delirium Rating Scale Revised-98 (DRS-R98) severity score of ≥10. A DRS-R98 severity score of <10 on day 3 was defined as the study outcome. The dataset was randomly split into the training and test dataset. A decision tree model was developed using the training dataset and potential predictors. The area under the curve (AUC) of the receiver operating characteristic curve was measured both in 5-fold cross-validation and in the independent test dataset. Finally, the model was visualized using the whole dataset. RESULTS: Altogether, 668 records were included, of which 141 had a DRS-R98 severity score of <10 on day 3. The model achieved an average AUC of 0.698 in 5-fold cross-validation and 0.718 (95% confidence interval, 0.627-0.810) in the test dataset. The baseline DRS-R98 severity score (cutoff of 15), hypoxia, and dehydration were the important predictors, in this order. SIGNIFICANCE OF RESULTS: We developed an easy-to-use prediction model for the short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions. The baseline severity of delirium and precipitating factors of delirium were important for prediction.

Stress and coping strategies among allogeneic haematopoietic stem cell transplantation survivors: A qualitative study.

OBJECTIVE: The aim of this qualitative study was to explore allogeneic haematopoietic stem cell transplantation (allo-HSCT) survivors' perspectives of stresses and their coping strategies, in order to attain a deeper understanding of their experience. METHODS: We conducted semi-structured interviews with 20 Japanese allo-HSCT survivors about the stresses they experienced and how they coped. We then conducted a content-driven thematic analysis of the interview results. The interview questions probed stresses and coping strategies related to allo-HSCT. RESULTS: We identified 74 stresses across 7 domains: symptoms after transplantation, limitations in daily life, appearance changes, relationship anxieties, work impairment and financial issues, uncertainty and disappointed expectations. In addition, 21 coping strategies were identified across 3 domains: direct efforts to manage problems, adaptive attitude, and seeking and using social support. CONCLUSION: By identifying a broad range of stressors associated with allo-HSCT, insight was gained as to the impact of allo-HSCT on survivors' lives. These results provide a foundation for the future development of resources for survivors, their significant others and clinicians. Stressors and coping strategies among allo-HSCT survivors were comprehensively characterised, which will provide useful information for patients and enable healthcare practitioners to provide better care.

Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase-R).

BACKGROUND: Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy. SUBJECTS, MATERIALS, AND METHODS: We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data-recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2). RESULTS: Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy. CONCLUSION: Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure. IMPLICATIONS FOR PRACTICE: Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.

Japanese physicians' attitudes toward end-of-life discussion with pediatric patients with cancer.

PURPOSE: We explored pediatricians' practices and attitudes concerning end-of-life discussions (EOLds) with pediatric patients with cancer, and identified the determinants of pediatricians' positive attitude toward having EOLds with pediatric patients. METHODS: A multicenter questionnaire survey was conducted with 127 pediatricians specializing in the treatment of pediatric cancer. RESULTS: Forty-two percent of participants reported that EOLds should be held with the young group of children (6-9 years old), 68% with the middle group (10-15 years old), and 93% with the old group (16-18 years old). Meanwhile, 6, 20, and 35% of participants answered that they "always" or "usually" discussed the incurability of the disease with the young, middle, and old groups, respectively; for the patient's imminent death, the rates were 2, 11, and 24%. Pediatricians' attitude that they "should have" EOLds with the young group was predicted by more clinical experience (odds ratio [OR] 1.077; p = 0.007), more confidence in addressing children's anxiety after EOLd (OR 1.756; p = 0.050), weaker belief in the demand for EOLd (OR 0.456; p = 0.015), weaker belief in the necessity of the EOLd for children to enjoy their time until death (OR, 0.506; p = 0.021), and weaker belief in the importance of maintaining a good relationship with the parents (OR 0.381; p = 0.025). CONCLUSIONS: While pediatricians nearly reached consensus on EOLds for the old group, EOLds with the young group remain a controversial subject. While pediatricians who supported EOLds believed in their effectiveness or necessity, those who were against EOLds tended to consider the benefits of not engaging in them.

Barriers of healthcare providers against end-of-life discussions with pediatric cancer patients.

OBJECTIVE: End-of-life discussions with patients can be one of the most difficult and stressful tasks for the oncologist. However, little is known about the discussions that healthcare providers have with patients in such situations and the difficulties they face. The primary end points of this study were to describe the contents of end-of-life discussion in the pediatric setting and the barriers to end-of-life discussion for pediatric patients, as perceived by pediatric healthcare providers. METHODS: Participants were 10 healthcare providers. Semi-structured interviews were conducted, and the KJ method was performed to analyze the data. RESULTS: We found 23 barriers against end-of-life discussion with pediatric cancer patients. These barriers were classified as follows: healthcare provider factors, patient factors, parent factors and institutional or cultural factors. In addition to barriers found in previous studies, some unique barriers were uncovered such as, 'Lack of confidence to face the patient after the discussion', 'Uncertain responsibility for treatment decision-making' and 'No compelling reason to discuss'. Healthcare providers actively discussed the purpose of treatment and the patients' wishes and concerns; however, they were reluctant to deal with the patients' own impending death and their estimated prognosis. CONCLUSIONS: End-of-life discussion with pediatric patients differs from that with adult patients. Further studies are required to analyze pediatric cases associated with end-of-life discussion and carefully discuss its adequacy, pros and cons.

Severe behavioral and psychological symptoms of dementia successfully treated at home with a blonanserin transdermal patch: A case report.

AIM: Behavioral psychological symptoms of dementia (BPSD) are sometimes difficult to treat due to severe psychiatric symptoms such as delusions of poisoning and violent behavior. Moreover, in cases of parental neglect, the management of these psychiatric symptoms becomes more difficult. Therefore, home-visiting doctors sometimes have to manage patients with BPSD and severe psychiatric symptoms, and a new approach is needed. In this case report, the effect of blonanserin transdermal patch on these patients is to be highlighted. METHODS: The patient is a 91-year-old woman diagnosed with Alzheimer's disease. She had severe BPSD such as delusion of robbery and violent behavior, and refused oral medications including memantine and yokukansan. Then she was treated with blonanserin transdermal patch (20 mg/day). The severity of psychiatric symptoms of BPSD was assessed over time using the Neuropsychiatric Inventory (NPI) score. Moreover, the patient's cognitive function was also assessed over time by Mini-Mental State Examination (MMSE). RESULTS: After the introduction of blonanserin patch, the patient's psychiatric symptoms were stabilized markedly, and both NPI and MMSE scores improved. The patient was able to stay at home calmly and was mentally well stabilized to the extent that she did not require hospitalization. No apparent side effects were admitted. CONCLUSIONS: The blonanserin transdermal patch may be able to manage BPSD at home and is effective in patients who refuse oral medications. Home-visiting doctors may consider the use of blonanserin patches at home for patients with severe BPSD, manifesting as delusions of poisoning and refusing oral drugs.

Delirium due to Trousseau syndrome treated with memantine and perospirone: A case report.

Background: Trousseau syndrome is a hypercoagulability syndrome associated with cancer. It is known that delirium occasionally occurs after the onset of Trousseau syndrome. However, there have been no detailed reports about treatment for psychiatric symptoms of delirium associated with Trousseau syndrome. Case Presentation: A 61-year-old man with lung cancer was hospitalized due to Trousseau syndrome. Delirium occurred after hospitalization and psychiatric symptoms worsened. Although haloperidol, risperidone, and chlorpromazine were used, severe insomnia persisted. After memantine (5 mg/day) was used with perospirone, the patient's psychiatric symptoms gradually decreased; he could sleep for 4-5 h at night. Due to psychiatric improvement, he was able to return home and resume immunotherapy for lung cancer as scheduled. Conclusion: We report the first case of Trousseau syndrome delirium treated by memantine used with perospirone. Although further studies are needed, memantine and perospirone might be candidates for the management of psychiatric symptoms associated with Trousseau syndrome.

Psychological distress among healthcare providers in oncology during the COVID-19 pandemic in Japan: The mediating role of moral distress and resilience.

Objective: Even though vaccines have become widespread, there is an explosion of infection due to the emergence of new mutant strains, and support for healthcare providers' mental health is necessary. The aims of this study were to explore factors associated with the psychological distress, and to determine the degree of association between moral distress, resilience and psychological distress in order to consider intervention models for psychological distress of healthcare providers involved with cancer patients during the COVID-19 pandemic. Method: We conducted a cross-sectional survey among healthcare providers at the National Cancer Center, Japan. Psychological distress was assessed by the Hospital Anxiety and Depression Scale. We also assessed moral distress using the Moral Distress Thermometer and resilience using the Connor-Davidson Resilience Scale 10 in April and May 2020 which was the first surge of the epidemic period. Results: Five hundred sixty-six of 3,900 healthcare providers (14.5%) responded. Sixty-eight percent (385/566) responders were above the Hospital Anxiety and Depression Scale cutoff. Hierarchical regression analyses indicated that nurses, allied health professionals and office workers/engineers (odds ratio = 4.63; 95% confidence interval 1.90-11.29; p < 0.001, odds ratio = 3.88; 95% confidence interval 1.88-8.00; p < 0.001, odds ratio = 2.10; 95% confidence interval 1.06-4.18; p < 0.05) as well as healthcare providers with low resilience (odds ratio = 0.88; 95% confidence interval 0.85-0.91; p < 0.001) were at risk of psychological distress. Moral distress was not significantly associated with prevalence of psychological distress. Conclusion: During the first surge of the pandemic, a high prevalence of psychological distress was demonstrated among cancer center healthcare providers. The study suggests that mental health care should be available to cancer care providers. Since the COVID-19 pandemic is still going on, in addition to the efforts by our facilities, we should consider interventions that promote resilience and a feasibility study of these interventions.

Pilot Study of Lemborexant for Insomnia in Cancer Patients with Delirium.

Delirium occurs very frequently in cancer patients. Insomnia is a symptom of delirium. Lemborexant is a drug that regulates sleep-wake rhythms without causing extrapyramidal symptoms. Based on its ability to improve sleep, lemborexant is expected to have efficacy for insomnia with delirium. The purpose of this study was to determine the efficacy of lemborexant for insomnia in cancer patients with delirium. A retrospective observational study was conducted between July 2020 and February 2021. Fourteen patients (six females; mean age,69 years) were included. Lemborexant was effective in 11 of 14 (78.6%) patients. Of 14 patients, 10 had hyperactive delirium. Lemborexant might have similar efficacy for insomnia with and without delirium when compared with previous studies. The efficacy rate of lemborexant was 70% for patients with insomnia and hyperactive delirium. This study might lead to dose reductions of antipsychotic medications and fewer extrapyramidal symptoms in cancer patients with delirium.

Association of Antipsychotic Dose With Survival of Advanced Cancer Patients With Delirium.

CONTEXT: Delirium is common in patients with advanced cancer, and antipsychotics are widely used for its management. OBJECTIVES: We aimed to explore the association of the antipsychotic dose with survival of terminally ill cancer patients with delirium. METHODS: A secondary analysis of a multicenter prospective observational study was conducted. We enrolled adult advanced cancer patients who developed delirium and received antipsychotics at 14 palliative care units in Japan between September 2015 and May 2016. Hazard ratios of survival after starting antipsychotics between groups with different oral chlorpromazine equivalent doses: low: <100 mg, moderate: 100-200 mg, high: ≥200 mg, were calculated with adjustment for potential confounders using Cox regression. The antipsychotic dose-specific mortality risk was estimated with smooth splines. RESULTS: Of 453 patients enrolled, 422 patients were analyzed. The median antipsychotic dose was 92.6 mg: low-dose (N = 231), moderate-dose (122), and high-dose (69). The median survival of all patients was 11 days. Compared with the low-dose group, the high-dose group showed a significantly shorter survival (HR: 1.46, 95%CI: 1.08-1.98). Smooth splines demonstrated that HR continuously increased as the antipsychotic dose increased. In patients treated with atypical antipsychotics, the high-dose group showed a significantly shorter survival than the low-dose group (HR: 2.86), while in patients treated with typical antipsychotics, survival was not significantly different (0.99). CONCLUSIONS: Higher doses of antipsychotics were associated with increased mortality in terminally ill cancer patients with delirium. To minimize the potential mortality risk, antipsychotics should be started at low doses and titrated carefully.

Safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer: A large-scale multicenter prospective observational study in real-world palliative care settings.

OBJECTIVE: To clarify the safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer receiving palliative care. METHODS: This was a prospective observational study involving consecutive patients with advanced cancer and delirium receiving antipsychotics in inpatient hospices or psycho-oncology settings. Adjusted mean scores of the Delirium Rating Scale Revised-98 (DRS; range: 0-39) were calculated at baseline and Day 3 using generalized estimating equations. Adverse events over 7 days were evaluated. RESULTS: Data from 756 patients were analyzed (Mage = 72 ± 11 years, 62% male, 48% bedridden). The adjusted mean DRS score significantly decreased after antipsychotics administration (21.5 [95% confidence interval 19.5 to 23.4] to 20.8 [18.9 to 22.8], p = 0.03, effect size [ES] = 0.02). Significant improvement was associated with age of 75 or older (ES = 0.07), better performance status (0.32), longer estimated prognosis (0.25), psycho-oncological consultation settings (0.20), hyperactive (0.14) or mix-motor subtypes (0.24) of delirium, and quetiapine administration (0.19); significant deterioration was observed in patients with "days" prognosis (0.18). Extrapyramidal symptoms (9.8%) and somnolence (8.5%) were the most prevalent adverse events. CONCLUSIONS: The use of antipsychotics as part of comprehensive delirium management was safe and may provide some symptomatic benefits for patients with terminal illness and delirium. Along with adequate non-pharmacological interventions, judicious use of antipsychotics is still recommended.

Electronic Cigarette Use and Smoking Abstinence in Japan: A Cross-Sectional Study of Quitting Methods.

The benefit of electronic cigarettes (e-cigarettes) in smoking cessation remains controversial. Recently, e-cigarettes have been gaining popularity in Japan, without evidence of efficacy on quitting cigarettes. We conducted an online survey to collect information on tobacco use, difficulties in smoking cessation, socio-demographic factors, and health-related factors in Japan. Among the total participants (n = 9055), 798 eligible persons aged 20-69 years who smoked within the previous five years were analyzed to assess the relationship between the outcome of smoking cessation and quitting methods used, including e-cigarettes, smoking cessation therapy, and unassisted. E-cigarette use was negatively associated with smoking cessation (odds ratio (OR) = 0.632; 95% confidence interval (CI) = 0.414-0.964) after adjusting for gender, age, health-related factors, and other quitting methods. Conversely, smoking cessation therapy (i.e., varenicline) was significantly associated with smoking cessation (OR = 1.885; 95% CI = 1.018-3.492) in the same model. For effective smoking cessation, e-cigarette use appears to have low efficacy among smokers in Japan. Allowing for the fact that this study is limited by its cross-sectional design, follow-up studies are needed to assess the prospective association between e-cigarette use and smoking cessation.

Universal scaling law in human behavioral organization.

We describe the nature of human behavioral organization, specifically how resting and active periods are interwoven throughout daily life. Active period durations with physical activity count successively above a predefined threshold, when rescaled with individual means, follow a universal stretched exponential (gamma-type) cumulative distribution with characteristic time, both in healthy individuals and in patients with major depressive disorder. On the other hand, resting period durations below the threshold for both groups obey a scale-free power-law cumulative distribution over two decades, with significantly lower scaling exponents in the patients. We thus find universal distribution laws governing human behavioral organization, with a parameter altered in depression.

Prospective study on influence of psychosocial factors on glycemic control in Japanese patients with type 2 diabetes.

The authors prospectively assessed the causal relationship between psychosocial factors and glycemic control in 256 Japanese outpatients with Type 2 diabetes. Using structural-equation modeling, they first developed a causal model in which glycosylated hemoglobin (HbA(1c)) at 6 months after assessment was influenced by the baseline psychosocial factors. Then, the reliability of the causal model was investigated with measurement of HbA(1c) at 12 months after baseline. Self-efficacy directly reinforced adherence, and adherence had a direct association with future HbA(1c). Other psychosocial factors, including social support, diabetes-related distress, daily burden, and emotion-focused coping prospectively influenced HbA(1c) indirectly through self-efficacy.

Yearlong physical activity and depressive symptoms in older Japanese adults: cross-sectional data from the Nakanojo study.

OBJECTIVE: The objective of this study was to investigate associations between accelerometer measurements of physical activity and psychosocial variables in older people. METHODS: Subjects were 184 Japanese aged 65-85 years. An accelerometer provided step count and physical activity intensity data throughout each 24-hour period for 1 year. At the end of the year, anxiety, depression, and cognitive function were assessed. RESULTS: Controlling for age, the daily number of steps, and the daily duration of moderate-intensity physical activity showed significant negative correlations with depressive mood. CONCLUSION: A depressive mood is associated with the quantity and quality of habitual physical activity.