Patient-perceived symptomatic benefits of olanzapine treatment for nausea and vomiting in patients with advanced cancer who received palliative care through consultation teams: a multicenter prospective observational study.

PURPOSE: To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer. METHODS: We conducted a multicenter prospective observational study in a tertiary care setting (Trial registration number: UMIN000020493, date of registration: 2016/1/12). We measured the following: average nausea in the last 24 h using a Numeric Rating Scale (NRS: range 0-10) at baseline and day 2, patient-perceived treatment benefit (based on a 5-point verbal scale), and adverse events (AEs; using the Common Terminology Criteria for Adverse Events version 4). RESULTS: The 85 participants (45% men) had a mean age of 58.7±15.8 years. Major causes of N/V were opioids (44%) and chemotherapy (34%). All patients received a daily dose of olanzapine of 5 mg or less as first-line treatment (N=35) or second- or later-line treatment (N=50). Nausea NRS decreased from 6.1±2.2 to 1.8±2.0 (differences: -4.3, 95% CI -3.7 to -4.9, p<0.001). The proportion of patients who did not experience vomiting episodes in the last 24 h increased from 40-89%. Mean decrease in nausea NRS by patient-perceived treatment benefit were as follows: -0.8 for "none" (n=4, 5%); -2.8 for "slight" (n=17, 20%); -3.3 for "moderate" (n=14, 16%); -4.7 for "lots" (n=25, 29%); and -6.1 for "complete" (n=25, 29%; p-for-trend<0.001). The most prevalent AE was somnolence (n=15, 18%). CONCLUSION: Short-term and relatively low-dose olanzapine treatment was effective for multifactorial N/V. Confirmatory studies with longer observation periods are needed to clarify the duration of the effect and adverse events.

A survey of practice in management of malignancy-related ascites in Japan.

Although ascites is a distressing complication observed commonly in the course of advanced cancer, there is no effective treatment established for malignancy-related ascites. We conducted a nationwide survey of cancer physicians in Japan who treat malignancy-related ascites in order to determine what kind of therapeutic approach is thought to be significant and what kind of diuretic prescriptions are thought to be standard for malignancy-related ascites. From 2017 to 2018, we sent a one-page memo to oncologists in Japan asking them to participate in a questionnaire-style survey that they could complete online. The significance of each of the nine representative interventions was measured on a 5-stage Likert scale. At the same time, participants were asked about what type and dosage of diuretics they thought to be standard as a treatment for malignancy-related ascites. Ultimately, 187 oncologists responded to our invitation. The interventions that were particularly significant were reducing hydration volume, paracentesis, and symptom management with analgesics. The respondents indicated that the importance of diuretics was significantly lower than that of these three interventions. Furthermore, 86.2% of the respondents in Japan regarded the use of loop diuretics ± aldosterone antagonists as the standard of diuretic therapy for malignancy-related ascites, and the most common regimen was 20 mg of oral furosemide ± 25 mg of spironolactone daily at the start, and 30-40 mg ± 50 mg daily at the time of initial escalation. Although our study revealed that the attitude of oncologists in Japan toward therapeutic options for malignancy-related ascites was nearly consistent with that of previous reports from other countries, it was newly found that they seemed to commonly be concerned with preventing overhydration of terminally ill cancer patients and that analgesics were also thought to be a significant form of intervention.

Views on life and death of physicians, nurses, cancer patients and general population in Japan.

This study aimed to investigate views on life and death among physicians, nurses, cancer patients, and the general population in Japan and examine factors affecting these views. We targeted 3,140 physicians, 470 nurses, 450 cancer patients, and 3,000 individuals from the general population. We used the Death Attitudes Inventory (DAI) to measure attitudes toward life and death. The collection rates were 35% (1,093/3,140), 78% (366/470), 69% (310/450), and 39% (1,180/3,000) for physicians, nurses, patients, and the general population, respectively. We found that age, sex, social role (i.e., physician, nurse, cancer patient, and general population) were significantly correlated with DAI subscales. Compared with general population, attitudes toward death of physicians, nurses and cancer patients differed significantly even after adjusted their age and sex. Our study is the first to analyze differences in views on life and death among physicians, nurses, cancer patients, and the general population in Japan.

The influence of childhood abuse, adult life events, and affective temperaments on the well-being of the general, nonclinical adult population.

BACKGROUND: Previous studies have shown the effects of childhood abuse, life events, and temperaments on well-being (positive affect) and ill-being (negative affect). We hypothesized that childhood abuse, affective temperaments, and adult life events interact with one another and influence positive and negative affects in the general adult population and tested this hypothesis using structural equation modeling. METHODS: A total of 415 participants from the general, nonclinical adult population were studied using the following self-administered questionnaires: the Subjective Well-Being Inventory (SUBI); Life Experiences Survey (LES); Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A); and the Child Abuse and Trauma Scale (CATS). The data were analyzed with single and multiple regression analyses and structural equation modeling (Mplus). RESULTS: Childhood abuse indirectly predicted the worsening of positive and negative affects through cyclothymic, anxious, and irritable temperaments as measured by the TEMPS-A in the structural equation model. The cyclothymic, anxious, and irritable temperaments directly worsened the positive and negative affects and the negative appraisal of life events that occurred during the past year, while the hyperthymic temperament had the opposite effects. LIMITATIONS: The subjects of this study were nonclinical volunteers. The findings might not be generalizable to psychiatric patients. CONCLUSION: This study demonstrated that childhood abuse, particularly neglect, indirectly worsened the well-being of individuals through cyclothymic, anxious, and irritable affective temperaments. An important "mediator" role of affective temperaments in the effect of childhood abuse on well-being was suggested.

Assessment of Cancer-Related Fatigue, Pain, and Quality of Life in Cancer Patients at Palliative Care Team Referral: A Multicenter Observational Study (JORTC PAL-09).

INTRODUCTION: Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams. MATERIALS AND METHODS: Patients who were referred to palliative care teams at three institutions and met the inclusion criteria were invited to complete the Brief Fatigue Inventory, Brief Pain Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative. RESULTS: Of 183 patients recruited, the majority (85.8%) were diagnosed with recurrence or metastasis. The largest group (42.6%) comprised lung cancer patients, of whom 67.2% had an Eastern Cooperative Oncology Group Performance Status of 0-1. The mean value for global health status/quality of life was 41.4, and the highest mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative symptom item score was for pain (51.0). The mean global fatigue score was 4.1, and 9.8%, 30.6%, 38.7%, and 20.8% of patients' fatigue severity was classified as none (score 0), mild (1-3), moderate (4-6), and severe (7-10), respectively. DISCUSSION: Cancer-related fatigue, considered to occur more frequently in cancer patients, was successfully assessed using patient-reported outcomes with the Brief Fatigue Inventory for the first time in Japan. Results suggested that fatigue is potentially as problematic as pain, which is the main reason for palliative care.

Oral nutritional support can shorten the duration of parenteral hydration in end-of-life cancer patients: a randomized controlled trial.

Tube feeding or hydration is often considered for end-of-life cancer patients despite the negative effects on quality of life. The efficacy of oral nutritional support in this setting is unknown. We conducted a randomized trial to compare the efficacies of an amino acid jelly, Inner Power® (IP), and a liquid enteral product, Ensure Liquid® (EL), in terminally ill cancer patients. We randomly assigned patients to 3 arms: EL, IP, and EL+IP. The primary endpoint was drip infusion in vein (DIV)-free survival, which was defined as the duration from nutritional support initiation to administration of parenteral hydration. Twenty-seven patients were enrolled in the study, of whom 21 were included in the intention-to-treat analysis. The median age of the subjects was 69 yr. There were significant differences between the arms with regard to the median DIV-free survival (0.5, 6.0, and 4.5 days in the EL, IP, and EL + IP arms, respectively; P = 0.05). The median overall survival was 7, 9, and 8 days in the EL, IP, and EL + IP arms, respectively. IP may shorten the duration of parenteral hydration in terminally ill cancer patients and does not affect their survival.

Views on death with regard to end-of-life care preferences among cancer patients at a Japanese university hospital.

OBJECTIVE: This study investigates the views on death among cancer patients in Japan and examines how these views are related to age, sex, and physical condition. We also investigate how these views are related to where patients would like to spend their final days and whether or not they would like to be told how long they have left to live. METHOD: We targeted 450 cancer patients receiving outpatient treatment in the radiology department at the University of Tokyo Hospital. We used the Death Attitudes Inventory (DAI) developed by Hirai to measure attitudes about death. RESULTS: Of the 450 patients approached, we received responses from 310 (69% collection rate). The results of the t test and one-way ANOVA showed that, in terms of "death anxiety/fear," the under-65 group (17.73 ± 6.69) scored significantly higher than the 65-and-over group (15.43 ± 7.69, t = 2.685, df = 280, p < 0.01); the group with KPS scores 70 or above (16.88 ± 7.21) scored higher than the group with KPS scores below 70 (12.73 ± 7.09, t = 2.168, df = 280, p = 0.03); and no significant difference was found for sex, metastasis, or treatment stage. SIGNIFICANCE OF RESULTS: Our results demonstrate that, although views on death among cancer patients may differ according to sex, age, and physical condition, taking these factors into account when understanding such views can be useful in predicting where patients may wish to spend their final days.

Assessment of reasons for referral and activities of hospital palliative care teams using a standard format: a multicenter 1000 case description.

CONTEXT: The many benefits of hospital palliative care teams (PCTs) are well known. However, their specific activities have not been fully clarified, and no standardized methods for reporting PCT activities are available. OBJECTIVES: The aim of this study was to investigate, through the use of a standard format, the activities performed by hospital PCTs in Japan. METHODS: This was a prospective observational study. A total of 21 hospital PCTs were included in this study, and each recruited approximately 50 consecutively referred patients. Participating PCTs filled in a standard form for reporting activities. RESULTS: We obtained data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005 patients (95%) had cancer. The median number of reasons for referral and problems identified by PCTs was two (0-22) and four (0-18), respectively. The two major reasons for referral were pain (63%) and anxiety/depression/grief/emotional burden (22%). The major recommendations were pharmacological treatment (74%), care for the patient's physical symptoms (49%), and support for patient's decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patient's physical symptoms (77%), and pharmacological treatment (74%). CONCLUSION: The components of hospital PCT activities were successfully measured using the Standard Format for Reporting Hospital PCT Activity. The results of this study and the format for reporting hospital PCT activity could be effective in improving hospital PCT practice and for the education of new hospital PCT members.

Melinjo (Gnetum gnemon L.) Seed Extract Decreases Serum Uric Acid Levels in Nonobese Japanese Males: A Randomized Controlled Study.

Melinjo (Gnetum gnemon L.) seed extract (MSE) containing trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) and other derivatives exerts various beneficial effects. However, its mechanism of action in humans remains unknown. In this study, we aimed to investigate beneficial effects of MSE in healthy adult males. In this double-blind, randomized controlled study, 30 males aged 35-70 years with ≤10% flow-mediated dilatation received placebo or 750 mg MSE powder for 8 weeks, and twenty-nine males (45.1 ± 8.8 years old) completed the trial. There was a significant difference in the melinjo and placebo groups. Compared with the placebo control, MSE significantly reduced serum uric acid at 4 weeks and 8 weeks (n = 14 and 15, resp.). HDL cholesterol was significantly increased in the melinjo group. To clarify the mechanism of MSE for reducing uric acid, we investigated xanthine oxidase inhibitory activity, angiotensin II type 1 (AT1) receptor binding inhibition rate, and agonistic activities for PPAR α and PPAR γ . MSE, trans-resveratrol, and a resveratrol dimer, gnetin C (GC), significantly inhibit AT1 receptor binding and exhibit mild agonistic activities for PPAR α and PPAR γ . In conclusion, MSE may decrease serum uric acid regardless of insulin resistance and may improve lipid metabolism by increasing HDL cholesterol.

Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer.

CONTEXT: Although an evidence-based clinical guideline for parenteral hydration therapy was established in Japan, the efficacy of the guideline has not been assessed. OBJECTIVES: Our purpose was to explore the effect of parenteral hydration therapy based on this clinical guideline on quality of life (QoL), discomfort, symptoms, and fluid retention signs in patients with advanced cancer. METHODS: This multicenter, prospective, observational study included 161 patients with advanced abdominal cancer who received guideline-based hydration therapy. We evaluated the longitudinal changes of the global QoL (Item 30 of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30); the Discomfort Scale; the intensity of seven physical symptoms; and the severity of fluid retention signs. We also evaluated patient satisfaction and the feeling of benefit from hydration one week after the study commenced, and bronchial secretions, hyperactive delirium, communication capacity, and agitation 48 hours before a patient's death. RESULTS: The global QoL, the Discomfort Scale, and the intensities of all physical symptoms, except for vomiting and drowsiness, were stable throughout the study period. More than 80% of patients maintained all fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling of benefit was 5.43 (range 0-7). CONCLUSION: Guideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer.