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Purpose: In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects. Methods: Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2 mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24 h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events. Results: A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14 years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3–4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24 h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4–77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed. Conclusion: Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings. Trial registration number: UMIN000031381, registered 20/02/2018. [ABSTRACT FROM AUTHOR]

Purpose: Recent guidelines for prognostic evaluation recommend clinicians’ prediction of survival (CPS) for survival prediction in patients with advanced cancer. However, CPS is often inaccurate and optimistic. Studies on factors associated with overestimation or underestimation of CPS are limited. We aimed to investigate the factors associated with the overestimation and underestimation of CPS in patients with far-advanced cancer. Methods: The current study was a secondary analysis of an international multicenter prospective cohort study, which enrolled newly admitted patients with advanced cancer in palliative care units (PCUs) in Japan, Korea, and Taiwan from 2017 to 2018. We obtained the temporal CPS at enrollment and performed multivariate logistic regression analysis to identify the factors associated with “underestimation (less than 33% of actual survival)” and “overestimation (more than 33% of actual survival).” Results: A total of 2571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. Older age (adjusted odds ratio [aOR] 1.01; 95% confidence interval [CI] 1.01–1.02; P < 0.01) and reduced oral intake (aOR 0.68; 95% CI 0.51–0.89; P < 0.01) were identified as significant factors associated with underestimation. Dyspnea (aOR 1.28; 95% CI 1.06–1.54; P = 0.01) and hyperactive delirium (aOR 1.34; 95% CI 1.05–1.72; P = 0.02) were identified as significant factors associated with overestimation. Conclusion: Older age was related to underestimation, while dyspnea and hyperactive delirium were related to overestimation of CPS for patients with weeks of survival. However, reduced oral intake was less likely to lead to underestimation. [ABSTRACT FROM AUTHOR]

Purpose: Delirium is a common and serious comorbidity in patients with advanced cancer, necessitating effective management. Nonetheless, effective drugs for managing agitated delirium in patients with advanced cancer remain unclear in real-world settings. Thus, the present study aimed to explore an effective pharmacotherapy for this condition. Methods: We conducted a secondary analysis of a multicenter prospective observational study in Japan. The analysis included patients with advanced cancer who presented with agitated delirium and received pharmacotherapy. Agitation was defined as a score of the Richmond Agitation-Sedation Scale for palliative care (RASS-PAL) of ≥ 1. The outcome was defined as -2 ≤ RASS-PAL ≤ 0 at 72 h after the initiation of pharmacotherapy. Multiple propensity scores were quantified using a multinomial logistic regression model, and adjusted odds ratios (ORs) were calculated for haloperidol, chlorpromazine, olanzapine, quetiapine, and risperidone. Results: The analysis included 271 patients with agitated delirium, and 87 (32%) showed -2 ≤ RASS-PAL ≤ 0 on day 3. The propensity score-adjusted OR of olanzapine was statistically significant (OR, 2.91; 95% confidence interval, 1.12 to 7.80; P = 0.030). Conclusions: The findings suggest that olanzapine may effectively improve delirium agitation in patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Purpose: It is important for palliative care providers to identify what factors are associated with a "good death" for patients with advanced cancer. We aimed to identify factors associated with a "good death" evaluated by the Good Death Scale (GDS) score among inpatients with advanced cancer in palliative care units (PCUs) in Japan. Methods: The study is a sub-analysis of a multicenter prospective cohort study conducted in Japan. All variables were recorded on a structured data collecting sheet designed for the study. We classified each patient into better GDS group or worse GDS group, and examined factors associated with better GDS using multivariate analysis. Results: Between January and December 2017, 1896 patients were enrolled across 22 PCUs in Japan. Among them, a total of 1157 patients were evaluated. Five variables were significantly associated with a better GDS score in multivariate analysis: preferred place of death at PCU (odds ratio [OR] 2.85; 95% confidence interval [CI] 1.72–4.71; p < 0.01), longer survival time (OR 1.02; 95% CI 1.00–1.03; p < 0.01), not sudden death (OR 1.96; 95% CI 1.27–3.04; p < 0.01), better spiritual well-being in the last 3 days in life (OR 0.53; 95% CI 0.42–0.68; p < 0.01), and better communication between patient and family (OR 0.81; 95% CI 0.66–0.98; p = 0.03). Conclusions: We identified factors associated with a "good death" using GDS among advanced cancer patients in Japanese PCUs. Recognition of factors associated with GDS could help to improve the quality of end-of-life care. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to explore the association between impending death and continual changes in respiratory and heart rates measured using a non-wearable monitor every minute for the final 2 weeks of life in dying cancer patients.Methods: In this longitudinal study, we enrolled patients in a palliative care unit and continuously measured their respiratory and heart rates via a monitor and additionally captured their other vital signs and clinical status from medical records.Result: A dataset was created comprising every 24-h data collected from every-minute raw data, including information from 240 days prior to death from 24 patients (345,600 data); each patient's data were measured for 3-14 days until death. After confirming the associations between the respiratory and heat rate values on the day of death (n = 24) or other days (2-14 days before death, n = 216) and the mean, maximum, minimum, and variance of respiratory and heart rates every 24 h by univariate analyses, we conducted a repeated-measures logistic regression analysis using a generalized estimating equation. Finally, the maximum respiratory rate and mean heart rate were significantly associated with death occurring within the following 3 days (0-24 h, 0-48 h, and 0-72 h), except for the maximum respiratory rate that occurs within 0-24 h.Conclusion: The maximum respiratory rate and mean heart rate measured every minute using a monitor can warn family caregivers and care staff, with the support of palliative care professionals, of imminent death among dying patients at home or other facilities. [ABSTRACT FROM AUTHOR]

Purpose: The benefits of parenteral nutrition and hydration (PNH) in patients with advanced cancer remain unknown. Therefore, we conducted a prospective multicenter cohort study to assess the effects of PNH on survival in patients with malignant bowel obstruction (MBO). Methods: The present study was a secondary analysis. Data on primary nutritional administration routes during the first week of admission to palliative care units, i.e., parenteral nutrition and parenteral hydration, were obtained. Data on the averaged calorie sufficiency rate/total calorie intake (75% ≤ or 750 kcal/day ≤ , 50–75% or 500–750 kcal/day, 25–50% or 250–500 kcal/day, and < 25% or < 250 kcal/day) were also obtained. Participants with MBO were included and divided into two groups: PNH-high (25% ≤ or 250 kcal/day ≤) and PNH-low (< 25% or < 250 kcal/day). We performed time-to-event analyses using the Kaplan–Meier method, log-rank test, and univariate and multivariate Cox regression analyses. Results: Patients were divided into the PNH-high (n = 68) and PNH-low (n = 76) groups. A significant difference was observed in survival rates between the two groups (log-rank P < 0.001). Median survival times were 35.5 (95% CI 27–44) and 17.5 (95% CI 13–21) days, respectively. In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the PNH-high group (HR 0.55 (95% CI 0.36–0.83), P = 0.005) than in the PNH-low group. Conclusion: The present results indicated the beneficial effects of PNH for prolonging survival in advanced cancer patients with MBO in palliative care units. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Spiritual well-being is very important in patients undergoing palliative care. Although psychosocial factors have been suggested to be associated with spiritual well-being, the relationship between physical signs and spiritual well-being has not been fully elucidated. The aim of this study was to explore diverse factors associated with spiritual well-being among palliative care patients in Japan. Methods: This study is a secondary analysis of a multicenter prospective cohort study involving patients admitted to palliative care units in Japan. Physicians recorded all data prospectively on a structured sheet designed for the study. The spiritual well-being score was measured using the Integrated Palliative Outcome Scale after patients' death in regard to symptoms over the previous 3 days. We classified each patient into "better" score (0–1) and "worse" score (2–4) groups and examined diverse factors associated with spiritual well-being. Results: Among the 1896 patients enrolled, 1313 were evaluated. In the multivariate analysis, seven variables were significantly associated with "worse" score: worse spiritual well-being on admission (2–4) (p < 0.0001), younger age (< 80) (p = 0.0001), hyperactive delirium over 3 days before death (mild/moderate/severe) (p = 0.0001), expressed wish for hastened death (yes) (p = 0.0006), worse communication among patients and families (Support Team Assessment Schedule score 2–4) (p = 0.0008), pleural effusion (present) (p = 0.037), and marital status (unmarried) (p = 0.0408). Conclusion: Recognizing factors associated with spiritual well-being is potentially useful for identifying high-risk groups with lower spiritual well-being at the end of life. Further study is required to investigate factors associated with patient-reported spiritual well-being. [ABSTRACT FROM AUTHOR]

Purpose: For appropriate advance care planning, functional prognostication is necessary. However, there are no studies of functional prognostication in patients with cancer. The aim of this study was to develop a functional prognostic scoring system for patients with advanced cancer. Methods: In this multicenter prospective observational study, 1896 patients were enrolled. First, Cox regression analysis and the combination of forward and backward variable selection were used to identify the best subset of predictors. Second, the prognostic score value was defined from each regression coefficient of a significant prognostic factor. The Functional Palliative Prognostic Index (FPPI) was calculated by summing the prognostic scores. Results: Patients were classified into three groups by the FPPI. For walking, the 14-day functional survival probability was > 72.8% for group A (score 0), 28.4–72.8% for group B (score 1), and < 28.4% for group C (score 2–3). For eating, the 14-day functional survival probability was > 71.8% for group A (score 0–3), 29.6–71.8% for group B (score 3.5–5.5), and < 29.6% for group C (score 6–9). For communicating, the 14-day functional survival probability was > 76.6% for group A (score 0–6.5), 22.6–76.6% for group B (score 7–10), and < 22.6% for group C (score 10.5–16). Regarding each item, group B functionally survived significantly longer than group C, and group A functionally survived significantly longer than either of the others. Conclusion: We firstly developed a functional prognostic scoring system for patients with advanced cancer. This FPPI system promises to be helpful in advance care planning. [ABSTRACT FROM AUTHOR]

Background: Bleeding and obstruction are common localized symptoms in patients with unresectable gastric cancer. Although there are several reports about surgical and endoscopic therapies for gastric cancer, there are few regarding palliative radiation therapy.Methods: We retrospectively analyzed data for 23 gastric cancer patients who underwent palliative radiation between April 2006 and March 2014, with either localized bleeding (n = 18) or upper gastric obstruction (n = 10).Results: The median (range) total dose and fraction (Fr) of radiotherapy (RT) were 42 (18-60) Gy and 20 (9-30) Fr, respectively. The response rates were 88.8% (bleeding) and 80% (obstruction). The median event-free survival times of the bleeding and obstruction groups from the start of radiation were 103 and 104 days, respectively. Adverse events with RT and chemo-radiotherapy (CRT) were grade 2 nausea (n = 4) and grade 2 esophagitis (n = 3) and grade 2 neutropenia (n = 3). In univariate analysis, the antrum as the gastric primary site (p = 0.063) and peritoneal metastasis (p = 0.054) occurred more frequently in the non-responders (n = 4) than the responders (n = 19). [ABSTRACT FROM AUTHOR]

Background: There is no consensus regarding whether cancer-induced hypercalcemia should be treated up until the patient's death. The primary aim of this study was to clarify physicians' attitude toward treating recurrent hypercalcemia in terminally ill cancer patients and associated factors. Methods: A nationwide, cross-sectional survey was performed involving 757 physicians of the Japanese Society for Palliative Medicine. Physicians' attitude toward treating hypercalcemia in terminally ill patients was assessed based on the response to the question: do you agree that you provide medical treatment for recurrent hypercalcemia up until a patient's death? As the potential determinants of physicians' attitudes, we examined their characteristics, beliefs about hypercalcemia, and beliefs about a good death. Results: We obtained a total of 380 (50.2 %) analyzable responses. A total of 163 physicians (43 %) agreed that hypercalcemia should be treated up until the patient's death, while the remaining 217 physicians (57 %) disagreed. The independent determinants of the attitude included the following: physicians' specialty, belief that hypercalcemia treatment improves pain, belief that hypercalcemia treatment improves nausea, belief that hypercalcemia treatment improves quality of life, belief that hypercalcemia treatment prolongs life, belief that the effect of hypercalcemia treatment reduces gradually, belief that death with hypercalcemia is less distressing, and the perception that being mentally clear is important for a good death. Conclusion: Japanese physicians had different attitudes toward treating hypercalcemia in terminally ill patients. Physicians' beliefs about the efficacy of medical treatment for hypercalcemia markedly influenced their attitudes. Clarifying evidence on the effect of hypercalcemia treatment on patients' symptoms and prognoses is strongly encouraged. [ABSTRACT FROM AUTHOR]

Nausea and vomiting are among the most common and distressing symptoms in patients with advanced cancer. Olanzapine, an antipsychotic agent, is known to have an affinity for multiple neurotransmitter receptors. Previous studies have reported olanzapine to be efficacious in the treatment of nausea and vomiting. Although it has been administered at a number of facilities, its applicability to treat nausea and vomiting in patients with advanced cancer is poorly understood. We investigated the use of olanzapine for nausea and vomiting in patients with advanced cancer at multiple centers. This retrospective study was carried out at seven palliative care units and three facilities with palliative care teams in Japan from 2013 to 2015. The dosage of olanzapine, treatment duration, and duration from initial use until death were collected from the medical records. One hundred and eight patients met our inclusion criteria. The average dose of olanzapine was 3.6 mg (2.5 mg, n = 61; 5 mg, n = 46; 10 mg, n = 1) and average treatment duration was 18.7 days. The average duration from initial use until death was 39.0 days. There were no differences in the duration of administration until death between olanzapine doses (2.5 and 5 mg). Our results suggest that olanzapine have been used in patients with poor prognoses for nausea and vomiting in patients with advanced cancer. Conducting a prospective trial would further yield promising results. [ABSTRACT FROM AUTHOR]

A 58-year-old man was admitted to our hospital complaining of fever and arthralgia. His clinical course and marked ciliary hyperemia led us to suspect tubulointestinal nephritis and uveitis (TINU) syndrome, which was confirmed ophthalmologically and by renal biopsy. Results of a drug-induced lymphocyte-stimulating test were positive for the Chinese herb “Goreisan.” This is the first case in which the use of “Goreisan” was causally related to TINU syndrome. [ABSTRACT FROM AUTHOR]