Prevention of delirium with agitation by yokukansan in older adults after cancer surgery.

OBJECTIVE: Preventing postoperative delirium with agitation is vital in the older population. We examined the preventive effect of yokukansan on postoperative delirium with agitation in older adult patients undergoing highly invasive cancer resection. METHODS: We performed a secondary per-protocol analysis of 149 patients' data from a previous clinical trial. Patients underwent scheduled yokukansan or placebo intervention 4-8 days presurgery and delirium assessment postoperatively. Delirium with agitation in patients aged ≥75 years was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the Japanese version of the Delirium Rating Scale-Revised-98. We assessed odds ratios for yokukansan (TJ-54) compared with placebo for the manifestation of postoperative delirium with agitation across patients of all ages (n = 149) and those aged ≥65 years (n = 82) and ≥ 75 years (n = 21) using logistic regression. RESULTS: Delirium with agitation manifested in 3/14 and 5/7 patients in the TJ-54 and placebo groups, respectively, among those aged ≥75 years. The odds ratio for yokukansan vs. placebo was 0.11 (95% confidence interval: 0.01-0.87). An age and TJ-54 interaction effect was detected in patients with delirium with agitation. No intergroup differences were observed in patients aged ≥65 years or across all ages for delirium with agitation. CONCLUSIONS: This is the first study investigating the preventive effect of yokukansan on postoperative delirium with agitation in older adults. Yokukansan may alleviate workforce burdens in older adults caused by postoperative delirium with agitation following highly invasive cancer resection.

Yokukansan for Treatment of Preoperative Anxiety and Prevention of Postoperative Delirium in Cancer Patients Undergoing Highly Invasive Surgery. J-SUPPORT 1605 (ProD Study): A Randomized, Double-Blind, Placebo-Controlled Trial.

CONTEXT: No standard preventive or therapeutic methods have been established for preoperative anxiety and postoperative delirium in patients with cancer. OBJECTIVES: To clarify the therapeutic effect of yokukansan for perioperative psychiatric symptoms in patients with cancer as well as to confirm its safety profile. METHODS: This is a randomized, double-blind, and placebo-controlled trial conducted at a single center in Tokyo, Japan. About 195 patients with cancer scheduled to undergo tumor resection took one packet of the study drug, which was administered orally. Coprimary outcomes were change in preoperative anxiety assessed with the Hospital Anxiety and Depression Scale-Anxiety and incidence of postoperative delirium assessed with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Interim analysis was performed with one-third (n = 74) of the target number of registered patients. RESULTS: Because this trial was canceled based on the results of the interim analysis and the protocol treatment was discontinued in patients who were already registered, conclusions were based on the full analysis set of 160 participants. There were no significant differences between groups in the change of mean Hospital Anxiety and Depression Scale-Anxiety score (intervention group [SD] 0.4 [3.0] vs. placebo group 0.5 [3.0]; P = 0.796) or the incidence of postoperative delirium (32% vs. 30%; P = 0.798). There were no serious adverse events in either group. CONCLUSION: In patients with cancer undergoing highly invasive surgeries, yokukansan demonstrated no significant efficacy for the treatment of preoperative anxiety or the prevention of postoperative delirium. Yokukansan is already used in daily practice in Japan, but we should be careful with its future use.

Integrated communication support program for oncologists, caregivers and patients with rapidly progressing advanced cancer to promote patient-centered communication: J-SUPPORT 1904 study protocol for a randomised controlled trial.

INTRODUCTION: Communication is an essential aspect of care for patients with progressive serious illnesses. This study aims to evaluate the efficacy of a new, integrated communication support program for oncologists, patients with rapidly progressing advanced cancer and their caregivers. METHODS AND ANALYSIS: The proposed integrated communication support programme is in the randomised control trial stage. It comprises a cluster of oncologists from comprehensive cancer centre hospitals in a metropolitan area in Japan. A total of 20 oncologists, 200 patients with advanced pancreatic cancer and the patients' caregivers are enrolled in this study as of the writing of this protocol report. Oncologists are randomly assigned to the intervention group (IG) or control group (CG). Patients and caregivers are allocated to the same group as their oncologists. The IG oncologists receive a 2.5-hour individual communication skills training, and patients and caregivers receive a half-hour coaching intervention to facilitate prioritising and discussing questions and concerns; the CG participants do not receive any training. Follow-up data will be collected quarterly for 6 months for a year and then annually for up to 3 years. The primary endpoint is the intergroup difference between before-intervention and after-intervention patient-centred communication behaviours during oncology visits. ETHICS AND DISSEMINATION: This study is conducted in accordance with the ethical guidelines for clinical studies published by Japan's Ministry of Education, Cultural, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the ethical principles established for research on humans stipulated in the Declaration of Helsinki and further amendments thereto. The protocol was approved by the Institutional Review Board of National Cancer Center, Japan on 4 July 2018 (ID: 2017-474). TRIAL STATUS: This study is currently enrolling participants. Enrolment period ends 31 July 2020; estimated follow-up date is 31 March 2023. TRIAL REGISTRATION NUMBER: UMIN Clinical Trial Registry (UMIN000033612); pre-results.

Developing the structure of Japan's cancer survivorship guidelines using an expert panel and modified Delphi method.

PURPOSE: To develop consensus-based components used in the first evidence-based cancer survivorship guidelines in Japan. METHODS: Purposive sampling was used to recruit a panel of experts in oncology clinical practice, nursing, health science, epidemiology, and patient advocacy. The panel engaged in a modified Delphi process to (1) generate consensus related to the definition of survivorship, (2) determine the aim and target users of the guideline, and (3) identify clinical issues for inclusion. A Web-based survey and panel meeting were conducted to obtain the panelists' feedback on the initial draft proposed by the secretariat. Multiple online votes were then completed until all elements of the proposed guidelines reached an approval rate of 80% or higher. Following each round, iterative refinements were made based on all panelists' feedback. RESULTS: Twenty-two experts were enrolled in the panel and participated in four rounds of online voting and two face-to-face meetings. Ultimately, the panel reached consensus on the definition of survivorship, the aim of the guidelines, and target users. Moreover, 11 of the original 17 clinical issues were retained. Finally, the panel selected two priority areas to implement immediately. CONCLUSION: The panel's consensus on the definition of survivorship, aim and target users of the guideline, and 11 clinical issues will serve as a compass for the development of comprehensive cancer survivorship guidelines in Japan. IMPLICATIONS FOR CANCER SURVIVORS: A culturally sensitive consensus approach was developed to improve the long term health and well- being of cancer survivors in Japan.

Yokukansan for perioperative psychiatric symptoms in cancer patients undergoing high invasive surgery. J-SUPPORT 1605 (ProD Study): study protocol for a randomized controlled trial.

BACKGROUND: Preoperative anxiety and postoperative delirium affect both short- and long-term prognoses in patients with cancer; therefore, these conditions require early prevention and treatment. However, no standard preventive or therapeutic methods have been established for them. Yokukansan, a Japanese herbal medicine for the treatment of insomnia and anxiety, causes relatively few adverse drug reactions and effectively improves the behavioral and psychological symptoms of dementia. Thus, it is expected to be useful for treating and/or preventing perioperative psychiatric symptoms in patients with cancer. The objective of this study is to clarify the therapeutic effect of Yokukansan for preoperative anxiety and its preventive effect on postoperative delirium in cancer patients, as well as to confirm its safety profile. METHODS: This study is a randomized, double-blind, placebo-controlled study in cancer patients scheduled to undergo tumor resection. Patients who provide consent are randomly allocated to receive oral administration of Yokukansan or placebo, and study drug administration is continued for 4 days or longer prior to surgery. We defined two primary endpoints, change in preoperative anxiety and incidence of postoperative delirium. Secondary endpoints are severity score of postoperative delirium, duration of postoperative delirium, amount of benzodiazepines used prior to surgery, amount of antipsychotic agents used after surgery, and number of postoperative hospitalization days. We plan to complete the analysis on March 31, 2021. The target number of registered patients is 110 per group, or 220 in total. DISCUSSION: This study is the first randomized, double-blind, placebo-controlled study intended to clarify the effects of a Japanese herbal medicine, Yokukansan, in the prevention and treatment of perioperative psychiatric symptoms in patients with cancer. The trial was initiated on August 14, 2017, with 195 subjects randomized by October 5, 2018. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000027561 . Registered on 31 May 2017.

Yokukansan for the treatment of preoperative anxiety and postoperative delirium in colorectal cancer patients: a retrospective study.

BACKGROUND: Yokukansan (YKS), a Japanese traditional herbal medicine for neurosis and insomnia, is speculated to be useful for perioperative psychiatric symptoms in cancer patients, but there exists little empirical evidence. This study provides preliminary data about the efficacy, feasibility, and side effects of YKS for the treatment of preoperative anxiety and postoperative delirium in cancer patients. METHODS: We retrospectively reviewed the medical records of colorectal cancer patients who took YKS for preoperative anxiety, evaluating the following: (1) patient characteristics, (2) feasibility of taking YKS, (3) changes in preoperative anxiety based on the Clinical Global Impression (CGI) scale and Edmonton Symptom Assessment System-revised (ESAS-r-anxiety), (4) incidence of postoperative delirium and (5) YKS-related side effects. RESULTS: We reviewed 19 medical records. There was a significant difference between ESAS-r-anxiety scores (P = 0.028) before and after taking YKS, but no difference between CGI scores (P = 0.056). The incidence of postoperative delirium was 5.2% (95% CI = 0.0-14.5). One patient could not complete the course of YKS during the perioperative administration period, but there were no side effects of Grade 2 or worse according to the Common Terminology Criteria for Adverse Events v4. CONCLUSIONS: Cancer patients could safely take YKS before surgery. There was a significant improvement in preoperative anxiety after taking YKS, and the incident rate of postoperative delirium was lower than in previous studies. These results suggest that YKS may be useful for perioperative psychiatric symptoms in cancer patients. Further well-designed studies are needed to substantiate our results.

Subjective depressive mood and regional cerebral blood flow in mild Alzheimer's disease.

BACKGROUND: Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of subjective depressive symptoms in AD. METHODS: Seventy-six consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. Subjective depressive symptoms were evaluated using the short version of the Geriatric Depression Scale (GDS). All patients underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by the Statistical Parametric Mapping 8 program. RESULTS: No significant differences between groups with high and low GDS scores were found with respect to age, sex, years of education, and revised Addenbrooke's Cognitive Examination scores. Compared to patients with low scores on GDS, patients with high scores showed significant hypoperfusion in the left inferior frontal region. CONCLUSIONS: The left inferior frontal region may be significantly involved in the pathogenesis of subjective depressive symptoms in AD. Subjective and objective depressive symptoms may have somewhat different neural substrates in AD.

Depressive symptoms and regional cerebral blood flow in Alzheimer's disease.

Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of depressive symptoms in AD, excluding the effect of apathy and anxiety. Seventy-nine consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. The level of depressive symptoms was evaluated using the depression domain of the Neuropsychiatric Inventory (NPI). The patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. After removing the effects of age, anxiety and apathy scores of NPI, and five subscales of Addenbrooke's Cognitive Examination-revised (ACE-R), correlation analysis of NPI depression scores showed a significant cluster of voxels in the left middle frontal gyrus (Brodmann area 9), similar to the areas in the simple correlation analysis. The dorsolateral prefrontal area is significantly involved in the pathogenesis of depressive symptoms in AD, and the area on the left side especially may be closely related to the depressive symptoms revealed by NPI.

A case of adult-onset adrenoleukodystrophy with frontal lobe dysfunction: a novel point mutation in the ABCD1 gene.

We report the case of a 48-year-old man with adult-onset adrenoleukodystrophy (ALD) who developed dementia with subacute onset. He was abulic, indifferent to his surroundings, and without insight with regards to his own disease. An elevated plasma very long chain fatty acid level and a novel point mutation IVS3+2t>g in the ABCD1 gene confirmed the diagnosis of ALD. Diffusion-weighted MRI revealed a high intensity area in the white matter of the frontal lobes. Severe brain hypoperfusion in the frontal lobes was revealed. We believe that this is a rare case of adult-onset adrenoleukodystrophy with predominant frontal lobe dysfunction.

Availability of psychiatric consultation-liaison services as an integral component of palliative care programs at Japanese cancer hospitals.

OBJECTIVE: Collaboration between psychiatry and palliative medicine has the potential to enhance the quality of medical practice. The integration between palliative care and psychiatry has been attempted only in discrete medical settings and is not yet firmly established as an institution. Our objective was to determine the availability and degree of integration between psychiatric consultation-liaison services and palliative care in Japan. METHODS: A survey questionnaire was mailed to consultation-liaison psychiatrists at 375 government-designated cancer hospitals regarding their consultation-liaison services. RESULTS: A total of 375 survey questionnaires were sent to consultation-liaison psychiatrists, with a response rate of 64.8%. Designated cancer hospitals with approved palliative care teams were significantly more likely to have a consultation-liaison psychiatrist in the palliative care team than those in non-approved palliative care teams [80/80 (100%) versus 110/153 (73%); P= 0.008]. Approved palliative care teams had double the number of referrals, conducted rounds more frequently and held conferences more frequently. Psychiatrists of the approved palliative care teams spent more of their time on palliative care consultations, adhered more closely to consultation processes and contributed more actively to the integration of developmental perspectives in treatment plans. CONCLUSIONS: In Japan, most designated cancer hospitals with approved palliative care teams were more likely to integrate psychiatric consultation-liaison services into their palliative care programs. Systematic strategies for integration between palliative care and consultation-liaison psychiatry would contribute to the provision of appropriate psychosocial care for cancer patients and families at all stages.

Involvement of a psychiatric consultation service in a palliative care team at the Japanese cancer center hospital.

OBJECTIVE: Close collaboration between the cancer care team service and the psychiatric consultation service is recommended to provide adequate comprehensive care to cancer patients. In Japan, specialized palliative care teams work in conjunction with consultation-liaison psychiatrists as an essential members. There are, however, few studies reporting on these services. METHODS: We obtained the characteristics, physical and psychiatric symptoms and outcomes of cancer patients by analyzing the database of patients referred to the palliative care team at the National Cancer Center Hospital East, Japan. RESULTS: Among consecutive 2000 referrals, most patients referred to the palliative care team present both physical and psychiatric symptoms. Psychiatric diagnoses were provided for ∼70% of these patients. Consultation-liaison psychiatrists provided medical care to 80% of all the referrals. The main symptoms for psychiatric consultation were delirium (28%), adjustment disorder (18%), major depression (7.6%) and dementia (6.6%). CONCLUSIONS: Psychiatric problems are common in cancer patients of the palliative care team. The palliative care team should assess the psychiatric problems in cancer patients, and the involvement of the consultation-liaison psychiatrists in the palliative care teams may be one of the strategies to establish the psychosocial support for cancer patients in the acute hospital settings.

[Psycho-oncology: human side of cancer medicine].

Psycho-oncology has been struggling to explore human side of cancer, which is a multidisciplinary area of oncology, epidemiology, immunology, endocrinology, sociology and bioethics, as well as psychiatry and psychology. This subspecialty addresses the two major goals; improving all aspects of quality of life, and cancer morbidity and mortality. Psycho-oncology in the 21 century addresses the needs at all stage of cancer, including prevention, diagnosis, treatment, rehabilitation, recurrence, ending active cancer treatment and palliative care. This paper focused and described current topics of psycho-oncology.

[Scientific background of psycho-oncology].

UNLABELLED: We discussed the future direction of studies on psycho-oncology by reviewing relevant previous findings regarding treatment, early detection, and prevention of psychiatric disorders experienced by cancer patients. PSYCHIATRIC DISORDERS IN CANCER PATIENTS: It is reported that the common psychiatric disorders among cancer patients are adjustment disorder, major depression, and delirium. In addition, prevalence of adjustment disorder and major depression is higher among advanced cancer patients than that among patients with early stage cancer, and that delirium is the most common disorder among patients with terminally ill cancer. TREATMENT: Some meta-analytical studies reveal an effectiveness of psychotherapy for anxiety and depression among cancer patients however, several systematic reviews do not. Three randomized clinical trials indicate the efficacy of pharmacological treatments, anti-depressants, for major depression in cancer patients. It is suggested that delirium in advanced/terminally ill cancer patients can be ameliorated by detection and management of underlying causes of delirium and concurrent symptomatic treatment such as pharmacotherapy. EARLY DETECTION: Several brief screening instruments have been developed to detect adjustment disorder, major depression, and delirium among cancer patients. PREVENTION: One randomized clinical trial indicates the efficacy of SSRI for preventing depression occurring after interferon therapy among patients with malignant melanoma. No other effective strategy for prevention of psychiatric disorders among cancer patients has been clarified. CONCLUSION: There are not enough findings for effective treatments for ameliorating the common psychiatric disorders experienced by cancer patients, and very few studies for prevention while there are several available findings regarding early detection of their psychiatric disorders. Thus future studies on developing novel treatments including prevention and studies on mechanism should be encouraged. Psycho-oncology group in National Cancer Center are now conducting several clinical studies such as biological studies (neuro-imaging studies), studies to establish novel treatment strategy (n-3 poly unsaturated fatty acid), and multi-faceted intervention study (screening and individually tailored psychotherapy and pharmacotherapy).

Predictive factors for suicidal ideation in patients with unresectable lung carcinoma.

BACKGROUND: Despite serious concern over the suicidality of cancer patients in clinical oncology practice, few studies have addressed this issue. The purpose of the current study was to investigate the prevalence and predictive factors of suicidal ideation in patients with unresectable lung carcinoma in a follow-up setting. METHODS: Patients with newly diagnosed unresectable nonsmall cell lung carcinoma participated in this study. Their suicidal ideation was assessed 6 months after disclosure of the cancer diagnosis. Predictive factors for suicidal ideation were investigated by assessing a broad range of biomedical and psychosocial factors between the time of disclosure and start of cancer therapy (baseline) and 6 months after disclosure of the cancer diagnosis (follow-up). RESULTS: Although strong suicidal ideation was rare in this population, 13 (15%) of the 89 subjects who completed the baseline and follow-up ratings had some degree of suicidal ideation 6 months after disclosure of the cancer diagnosis. Univariate analysis revealed that significant predictive factors for suicidal ideation were pain at baseline, declining physical function, and the development of a depressive disorder. Multivariate analysis indicated that pain at baseline (odds ratio [OR] = 3.72, 95% confidence interval [CI] = 1.12-14.69, P = 0.04) and the development of a depressive disorder (OR =27.97, 95% CI = 5.18-214.14, P = 0.0003) were the final significant predictive factors. CONCLUSIONS: Suicidal ideation among unresectable lung carcinoma patients should not be neglected because it is not rare. Comprehensive care consisting of at least earlier pain management and appropriate psychiatric intervention is indispensable to prevent subsequent suicidal ideation.

Clinical factors associated with suicidality in cancer patients.

BACKGROUND: Previous epidemiological studies have indicated that the risk of suicide in cancer patients is higher than that of the general population. In addition, euthanasia and physician-assisted suicide (PAS) have recently become controversial medical, ethical and legal issues all over the world. Although suicide in cancer patients and appropriate management of cancer patients with suicidality are critical issues in clinical oncology practice, there have been very few studies to understand suicidality in cancer patients. The purpose of this study was to explore the clinical factors associated with suicidality in Japanese patients with cancer. METHODS: We investigated the clinical factors associated with suicidality in cancer patients by analyzing the consultation data of patients referred to the Psychiatry Division, National Cancer Centre Hospital and Hospital East, Japan. RESULTS: Of 1713 psychiatric referrals, 62 (3.6%) were related to suicidality, including 44 cases with suicidal ideation, 10 suicide attempts and eight cases who had requested euthanasia and/or continuous sedation. Most of the patients suffered from physical distress and/or psychiatric disorders. The results of a multivariate analysis comparing cancer patients with a psychiatric referral related to suicidality and those referred for other reasons indicated that impaired physical functioning and major depression were significant associated factors. CONCLUSIONS: Our findings suggest that early detection and appropriate management of major depression and comprehensive care improving physical functioning may help to prevent suicide and manage suicidality in Japanese cancer patients.