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Satoshi Inoue,1 Yoji Saito,2 Satoru Tsuneto,3 Etsuko Aruga,4 Azusa Ide,1 Yasuyuki Kakurai5 1Clinical Development Department, R&D Division, Daiichi Sankyo, Tokyo,2Department of Anesthesiology, Faculty of Medicine, Shimane University, Shimane, 3Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 4Department of Palliative Medicine, School of Medicine, Teikyo University, Tokyo, 5Biostatistics and Data Management Department, R&D Division, Daiichi Sankyo, Tokyo, Japan Background: In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b) extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics.Subjects and methods: This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88) or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93) orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone). The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS) score from baseline to completion of treatment.Results: The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was −0.4 mm (95% CI −5.9 to 5 mm) by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets relative to oxycodone tablets. The incidence of adverse events was 80.7% (71 of 88) in the hydromorphone group and 83.7% (77 of 93) in the oxycodone group. The most common adverse events were nausea, vomiting, somnolence, diarrhea, and constipation, most of which are commonly observed with opioid analgesics.Conclusion: The efficacy and safety of hydromorphone extended-release tablets were equivalent to those of the oxycodone extended-release formulation. Keywords: hydromorphone, oxycodone, cancer pain, palliative medicine, double-blind study

Purpose: The aim of this study was to clarify factors related to the preference of place for end-of-life cancer care and death, from the perspective of the bereaved family.Methods: In June 2007, in Japan, a cross-sectional anonymous questionnaire, which included a well-validated scale of component factors of hospice outcome, was administered to the bereaved family members (N = 294) of cancer patients who had died at home at least 6 months ago. Participants were recruited from 14 home hospices across the nation. We asked the preference of place for end-of-life care and death.Results: Fifty-eight percent of participants preferred home settings for end-of-life care and 68% preferred to die at home. Multivariate logistic regression identified: (1) males, participant who had other caregivers, a higher-good death concept, and those who experienced mastery as a consequence of caregiving were more likely to prefer home for end-of-life cancer care and (2) males, participant who had other caregivers, and experienced reprioritization as a consequence of caregiving and those who were enrolled in home hospice services for more than 60 days were more likely to prefer to die at home.Conclusions: Home hospice services need to be developed in Japan so that family support programs can be initiated early enough to support the family burden of household maintenance and caring for the patient. Quality improvement of home hospice services will support patients and families through end-of-life care and facilitate a good death at home. [ABSTRACT FROM AUTHOR]

In palliative care, steroids are often used to alleviate symptoms such as pain, fatigue, anorexia, nausea, and vomiting. Steroids occasionally induce psychiatric adverse effects. It has been reported that treatment of the steroid-induced psychiatric symptoms involves dosage reduction or discontinuation of steroid, and concomitant administration of psychotropics. There were few reports on effectiveness of treatment of steroid-induced psychiatric symptoms by switching from one steroid to the other. We experienced the case of 67-year-old man with malignant pleural mesothelioma and pulmonary emphysema who developed psychiatric symptoms after switching from oral prednisolone 10 mg/day to intravenous betamethasone 2 mg/day. He began to complain that 'time repeats cycles of going and coming' and that he was 'unable to distinguish between daytime and night,' and his face became expressionless. He gazed at familiar healthcare professionals as if seeing them for the first time, complaining: 'I feel something obscure or strange in my head.' He was unable to remember events on the same or the previous day at all, and made no verbal response to questions by healthcare professionals. He did not know how to eat or use the toilet, and thus required assistance in daily life activities. He did not respond even when talked to by his family members. He continued gazing at them, sometimes saying: 'Where am I now? Am I sick?' He behaved restlessly, repeating cycles of lying and sitting. The symptoms disappeared gradually after re-switching from intravenous betamethasone 2 mg/day to oral prednisolone 10mg/day. 'Steroid switching' may serve as a valid alternative treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: In order to improve the quality of palliative care, we can learn from bereaved families who were dissatisfied with the care they received. The primary aim of this study was to explore why bereaved families were dissatisfied with specialized inpatient palliative care. METHODS: This qualitative study formed part of a nationwide questionnaire survey administered to 1225 bereaved family members of cancer patients who died in certified palliative care units in Japan. The participants were 22 consecutive family members who reported a greater need for improvement in care. Data were analysed by the content analysis. RESULTS: The reasons that the bereaved families listed are classified into 27 categories and seven themes: (1) lack of perceived support for maintaining hope; (2) lack of perceived respect of individuality, especially in attitudes toward death; (3) perceived poor quality of care, especially psychological care, not being treated with dignity and inadequate explanation from physicians; (4) inadequate staffing and equipment, especially physician availability; (5) unavailability of timely administration; (6) lack of accurate information about palliative care units; and (7) family's practical and economic burden. CONCLUSIONS: This study identified the multiple sources of dissatisfaction with specialized inpatient palliative care for bereaved families. These findings could be useful in developing a more desirable system of specialised inpatient palliative care. [ABSTRACT FROM AUTHOR]

Background: Purposeless physiological monitoring at the end-of-life is not recommended. However, studies on how families feel regarding the death of patients with terminal cancer without continuous electrocardiographic monitoring (CEM) are lacking., Objectives: To explore the impact on the quality of care and the feelings and psychological distress experienced by families when CEM is not used during the 24 hours preceding a patient's death., Methods: In this multicenter cross-sectional, self-report questionnaires were distributed to 1087 bereaved families at Japanese specialized palliative care units in 2018., Results: Out of 671 responses, 394 valid responses were analyzed. Families of nonmonitored patients (NM-group) accounted for 79.2%, while those with bedside electrocardiogram monitoring (MB-group) and remote nurse station monitoring (MC-group) comprised 11.9% and 8.9%, respectively. In the NM-group, 85.5% expressed satisfaction without CEM, which was more than 10% lower than other groups. While 14% in the NM-group desired patient monitoring, families who received adequate explanations about CEM had lower proportions compared to the MB-group ( P = .021). Univariate analyses showed no significant differences in evaluations of the quality of care and families' psychological distress (mean scores of Overall Care Satisfaction, Care Evaluation Scale, Good Death Inventory, Brief Grief Questionnaires) across all groups., Conclusion: While the majority of NM-group were satisfied with their patient's care without CEM, the proportion of dissatisfied families was higher than in other groups. Although not using CEM is not a major hindrance to end-of-life care for patients with terminal cancer, providing sufficient explanations may be important for satisfactory care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Modified versions of the Objective Prognostic Score (mOPS) needs to be validated to reflect practical palliative care circumstances in Taiwan., Objectives: We compared the abilities of an mOPS score of 1.5 or higher versus a Karnofsky Performance Status (KPS) score of 30 or lower to predict 2-week mortality in patients with advanced cancer in Taiwan., Design: Observational study., Setting/subjects: We performed a secondary analysis of an international multicenter cohort study of patients in East Asia. Participants were inpatients with advanced cancer in palliative care units (PCUs) in Taiwan., Measurements: We compared the mOPS-B model, which does not require laboratory tests, with the KPS in a 2-week survival timeframe. We compared the accuracy of the prognostic models using sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Calibration plots and net reclassification indices (NRI) for 2-week survival were compared between the two models. Differences in survival between the higher- and lower-scoring groups of each model were identified using the log-rank test., Results: We included 317 patients, with a median survival of 14.0 days. The mOPS-B had a high sensitivity (0.82) and high AUROC value (0.69). By contrast, the KPS demonstrated good sensitivity (0.77) and an acceptable AUROC value (0.65) for predicting 2-week survival. The calibration plot did not demonstrate satisfactory agreement between the actual and predicted survival times in either the mOPS-B or the KPS groups. Our NRI was positive (absolute value: 22%), indicating that mOPS-B predicted 2-week survival better than KPS., Conclusions: The mOPS-B may serve better than the KPS as a screening tool for admission to PCUs in Taiwan because it was more accurate at predicting 2-week survival., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Context: Cultural adaptation is essential for optimizing programs centered around autonomy, such as the Serious Illness Care Program (SICP), especially for populations valuing family-involved decision-making., Objectives: We aimed to evaluate the feasibility and efficacy of a culturally adapted SICP-based nurse-physician collaborative Advance Care Planning (ACP) intervention tailored for patients with advanced cancer who prefer family-involved decision-making., Methods: Oncology nurses, extensively trained and closely collaborating with physicians, conducted structured discussions with patients in the intervention group. The culturally adapted SICP-based ACP intervention was supplemented with trust-building, family involvement, and understanding of patient values. Primary inclusion criteria included patients within six weeks of initiating first-line palliative chemotherapy. Primary endpoints were achieving a 70% completion rate and assessing spiritual well-being (FACIT-Sp) at six months. Secondary endpoints included anxiety (GAD-7), depression (PHQ-9), quality of life (QOL) (CoQoLo), and ACP progress (ACP Engagement Scale) at the same interval., Results: Forty-one patients (67.2%) completed the six-month follow-up, falling short of the targeted completion rate. The least-squares mean change from baseline in spiritual well-being at six months was 3.00 in the intervention group and -2.22 in the standard care group (difference, 5.22 points; 95% confidence interval, 1.38-9.06; P = 0.009). Similar superiority of the intervention was observed in QOL and ACP progress., Conclusion: Despite not meeting the targeted completion rate, the intervention group demonstrated enhanced spiritual well-being, QOL, and ACP progress. Our findings suggest revisions to the intervention manual to improve feasibility and to progress to an efficacy-focused randomized controlled trial., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with coexisting cancer and dementia often have complex health care needs and face challenges in achieving a good death., Objectives: To evaluate good death achievement and end-of-life (EOL) care in patients with coexisting cancer and dementia from the perspective of bereaved families., Design: Cross-sectional nationwide postal survey., Setting/subjects: Bereaved families of patients with cancer who died in hospice and palliative care units across Japan., Measurements: Bereaved families completed an anonymous, self-reported questionnaire. Their perspective on achieving a good death was assessed using the Good Death Inventory (GDI) (total score: 18-126). The Revised Care Evaluation Scale-short version (CES2) was used to assess EOL care (total score: 10-60). We examined the Brief Grief Questionnaire (BGQ) (total score: 0-10) and Patient Health Questionnaire 9 (PHQ9) (total score: 0-27)., Results: Data from 670 participants were analyzed, including 83 (12.4%) bereaved families of patients with coexisting cancer and dementia. No statistical differences were observed in the total GDI score for 18 items (dementia comorbidity vs. nondementia comorbidity groups, mean ± standard deviation, respectively, 78.4 ± 17.7 vs. 80.0 ± 15.5, adjusted [adj] P = 0.186), CES2 score (49.70 ± 9.22 vs. 48.82 ± 8.40, adj P = 0.316), BGQ score (3.40 ± 2.41 vs. 4.36 ± 2.28, adj P = 0.060), and PHQ9 score (4.67 ± 4.71 vs. 5.50 ± 5.37, adj P = 0.788)., Conclusions: GDI, CES2, BGQ, and PHQ9 scores did not differ significantly between groups, regardless of the presence of dementia in hospice and palliative care units. Patients with coexisting cancer and dementia can achieve a good death by high-quality EOL care., (© Ayumi Takao et al., 2024; Published by Mary Ann Liebert, Inc.)

Background: This study aimed to clarify the situation and evaluate the communication on anticancer treatment discontinuation from the viewpoint of a bereaved family, in reference to the concept of nudges., Methods: A multi-center questionnaire survey was conducted involving 350 bereaved families of patients with cancer admitted to palliative care units in Japan., Results: The following explanations were rated as essential or very useful: (i) treatment would be a physical burden to the patient (42.9%), (ii) providing anticancer treatment was impossible (40.5%), (iii) specific disadvantages of receiving treatment (40.5%), (iv) not receiving treatment would be better for the patient (39.9%) and (v) specific advantages of not receiving treatment (39.6%). The factors associated with a high need for improvement of the physician's explanation included lack of explanation on specific advantages of not receiving treatment (β = 0.228, P = 0.001), and lack of explanation of 'If the patient's condition improves, you may consider receiving the treatment again at that time.' (β = 0.189, P = 0.008)., Conclusions: Explaining the disadvantages of receiving treatment and the advantages of not receiving treatment, and presenting treatment discontinuation as the default option were effective in helping patients' families in making the decision to discontinue treatment. In particular, explanation regarding specific advantages of not receiving treatment was considered useful, as they caused a lower need for improvement of the physicians' explanation., (© The Author(s) 2024. Published by Oxford University Press.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Symptom burdens tend to increase for patients with cancer and their families over the disease trajectory. There is still a lack of evidence on the associations between symptom changes and the quality of dying and death. In this context, this research investigated how symptom changes influence the quality of dying and death., Methods: This international prospective cohort study (the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED), 2017-2019) included 22, 11, and 4 palliative care units across Japan, South Korea, and Taiwan. Eligible participants were adults (Japan and Korea, ≥18 years; Taiwan, ≥20 years) with locally advanced or metastatic cancer. Physical and psychological symptoms were assessed by physicians upon admission and within 3 days before death. Death quality was assessed using the Good Death Scale (GDS), developed in Taiwan. Univariate and multivariate regression analyses were used to identify correlations between symptom severity changes and GDS scores., Results: Among 998 patients (542 [54.3%] men and 456 [45.7%] women; mean [SD] age = 70.1 [± 12.5] years), persistent dyspnea was associated with lower GDS scores when compared to stable dyspnea (β = -0.427, 95% CI = -0.783 to -0.071). Worsened (-1.381, -1.932 to -0.831) and persistent (-1.680, -2.701 to -0.659) delirium were also significantly associated with lower GDS scores., Conclusions: Better quality of dying and death was associated with improved symptom control, especially for dyspnea and delirium. Integrating an outcome measurement for the quality of dying and death is important in the management of symptoms across the disease trajectory in a goal-concordant manner., (© The Author(s) 2023. Published by Oxford University Press.)

Objectives: Insufficient preparedness for bereavement can affect a family's psychological health status after bereavement. However, factors associated with preparedness remain unclear. This study aimed to identify factors associated with preparedness for bereavement in families of patients with cancer., Methods: We conducted a secondary analysis of a nationwide bereaved family survey in Japan, analyzing data from 9123 family members of patients with cancer. Logistic regression analysis was conducted to explore how sociodemographic factors, health status, and perceived care for patients and families were associated with preparedness for bereavement., Results: Of the 9123 families, 1338 (15.1%) were not prepared for bereavement. Factors associated with insufficient preparedness for bereavement (all p < 0.001) were found as follows: patients' spouses (OR = 2.54), receiving care in acute hospitals (OR = 1.83), worse psychological health status during caregiving (OR = 2.13), lower social support for family members (OR = 1.90), wrong patients' awareness of medical condition from family's perspective (OR = 1.75-2.12), family preference of more aggressive treatment rather than palliative care (OR = 1.71) or not sure (OR = 2.31), not wanting to know information about the patient's prognosis (OR = 1.64-1.77), end-of-life discussion with physician 1 month before patient's death (OR = 1.45), and late or early end-of-life discussions with physician and family (OR = 1.78-1.95)., Conclusions: This study's results might assist clinicians in assessing and identifying families who are not prepared for bereavement; however, preparedness for bereavement may have been associated with other factors., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Background: No standardized method has been established for evaluating the accuracy of a clinicians' prediction of survival (CPS). Till now, no study has compared the accuracy of CPS according to the evaluation methods using the same dataset. We aimed to examine the accuracy of CPS by different statistical approaches in patients with far-advanced cancer., Methods: The current study was a secondary analysis of an international multicenter prospective cohort study. Newly admitted patients with advanced cancer were enrolled in palliative care units (PCUs) in Japan, Korea, and Taiwan. We obtained the temporal CPS at enrollment. The patients were classified into groups of days (≤7 days) and weeks (≤30 days) based on CPS and actual survival (AS). We evaluated the accuracy of CPS by the distribution, area under the receiver operating characteristics curve (AUROCs), and an estimate ±33% of AS., Results: A total of 2,571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. As for the "days" category, the distribution of AS is larger than that of CPS, however, the results are reversed in the "weeks" category. The AUROCs showed over 80% discrimination for both the "days" and "weeks" categories. Accurate CPS within ±33% of AS was approximately 30% in both "days" and "weeks" categories., Conclusions: We showed a discrepancy of approximately 30-80% in the accuracy of CPS among three different analysis methods: distribution, AUROC, and AS comparison. Considering the low accuracy of AS comparisons, clinicians should provide a wide range of survival time. CPS was able to effectively discriminate and may be useful for risk stratification.

Background: Death pronouncement is an important moment that can impact a family's bereavement process; however, necessary improvements in physicians' behavior during death pronouncement remain unclear., Objectives: To explore whether the lack of certain behaviors by the physician was associated with a perceived need for improving death pronouncement for advanced cancer patients in palliative care units (PCUs)., Methods: This study was a secondary analysis of a nationwide multicenter questionnaire survey conducted in 2018 that targeted bereaved family members of cancer patients who died in PCUs. We performed univariate analysis to investigate the need to improve behavior toward death pronouncement. We performed bivariate analysis to investigate the relationship among the need for improvement in behavior toward death pronouncement, physician attribution (primary responsible physician, a member of the same team, and another physician), and nine specific behaviors., Results: Four hundred twenty-two questionnaires (64.2%) were returned. We analyzed 356 responses and found that 32.5% perceived the need to improve death pronouncement. Lack of certain behaviors at death pronouncement, especially not explicitly explaining the cause of death to family members (odds ratio: 11.89, p  < 0.001), were positively associated with the need for improvement. There were significant differences among the types of physician attribution regarding the need for improvement (primary responsible physician vs. a member of the same team vs. another physician [15.1% vs. 42.6% vs. 45.7%, p  < 0.001])., Conclusion: There was a significant positive association between the lack of certain behaviors toward death pronouncement and the need for improvement. The major lack of behavior toward death pronouncement was not explicitly explaining the cause of death to family members and not calling out to the patient before beginning the patient's examination., Competing Interests: The author(s) declared no potential conflicts of interest regarding the research, authorship, and/or publication of this article., (© Jun Hamano et al., 2023; Published by Mary Ann Liebert, Inc.)

Background: This study aimed to investigate the effectiveness of anticholinergics (AC) for death rattle in dying patients with cancer., Methods: This is a prospective cohort study enrolled Terminally ill adult (20 years or older) patients with cancer who developed substantial death rattle (Back score ≥2) from 23 palliative care units in Japan. AC treatment for death rattle was prescribed according to primary physician's decision. The primary outcome was the proportion of patients whose death rattle improved, which was defined as a Back score of ≤1. We compared the proportion of improved cases in patients treated with (AC group) and without (non-AC group) AC, controlling potential confounders by employing propensity score weighting., Results: Of the 1896 patients enrolled, we included 196 who developed a substantial death rattle. Of these, 81 received AC. 56.8% in the AC group and 35.4% in the non-AC group had an improved death rattle at 8 hours after baseline. In the weighted analysis, AC group showed significant improvements in death rattle, with an adjusted OR of 4.47 (95% CI 2.04 to 9.78; p=0.0024). All sensitivity analyses achieved essentially the same results. In the subgroup analysis, ACs were strongly associated with death rattle improvement in men, patients with lung cancer, and type 1 death rattle (adjusted OR 5.81, 8.38 and 9.32, respectively)., Conclusions: In this propensity score-weighted analysis, ACs were associated with death rattle improvement in terminally ill patients with cancer who developed substantial death rattle., Trial Registration Number: UMIN-CTR (UMIN00002545)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is ongoing debate on whether continuous deep sedation (CDS) for psycho-existential suffering is appropriate. Objective: We aimed to (1) clarify clinical practice of CDS for psycho-existential suffering and (2) assess its impact on patients' survival. Methods: Advanced cancer patients admitted to 23 palliative care units in 2017 were consecutively enrolled. We compared patients' characteristics, CDS practices, and survival between those receiving CDS for psycho-existential suffering ± physical symptoms and only for physical symptoms. Results: Of 164 patients analyzed, 14 (8.5%) received CDS for psycho-existential suffering ± physical symptoms and only one of them (0.6%) solely for psycho-existential suffering. Patients receiving CDS for psycho-existential suffering, compared with those only for physical symptoms, were likely to have no specific religion ( p  = 0.025), and desired (78.6% vs. 22.0%, respectively; p  < 0.001) and requested a hastened death more frequently (57.1% vs. 10.0%, respectively; p  < 0.001). All of them had a poor physical condition with limited estimated survival, and mostly (71%) received intermittent sedation before CDS. CDS for psycho-existential suffering caused greater physicians' discomfort ( p  = 0.037), and lasted for longer ( p  = 0.029). Dependency, loss of autonomy, and hopelessness were common reasons for psycho-existential suffering that required CDS. The survival time after CDS initiation was longer in patients receiving it for psycho-existential suffering (log-rank, p  = 0.021). Conclusion: CDS was applied to patients who suffered from psycho-existential suffering, which often associated with desire or request for a hastened death. Further studies and debate are warranted to develop feasible treatment strategies for psycho-existential suffering.

Background: The objective prognostic score (OPS) needs to be modified to reflect practical palliative care circumstances. Objectives: We aimed to validate modified models of OPS with few or no laboratory tests for patients with advanced cancer. Design: An observational study was performed. Setting/Subjects: A secondary analysis of an international, multicenter cohort study of patients in East Asia was performed. The subjects were inpatients with advanced cancer in the palliative care unit. Measurements: We developed two modified OPS (mOPS) models to predict two-week survival: mOPS-A consisted of two symptoms, two objective signs, and three laboratory results, while mOPS-B consisted of three symptoms, two signs, and no laboratory data. We compared the accuracy of the prognostic models using sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Calibration plots for two-week survival and net reclassification indices (NRIs) were compared for the two models. Survival differences between higher and lower score groups of each model were identified by the log-rank test. Results: We included a total of 1796 subjects having median survival of 19.0 days. We found that mOPS-A had higher specificity (0.805-0.836) and higher AUROCs (0.791-0.797). In contrast, mOPS-B showed higher sensitivity (0.721-0.725) and acceptable AUROCs (0.740-0.751) for prediction of two-week survival. Two mOPSs showed good concordance in calibration plots. Considering NRIs, replacing the original OPS with mOPSs improved overall reclassification (absolute NRI: 0.47-4.15%). Higher score groups of mOPS-A and mOPS-B showed poorer survival than those of lower score groups ( p  < 0.001). Conclusions: mOPSs used reduced laboratory data and had relatively good accuracy for predicting survival in advanced cancer patients receiving palliative care.

Objective: Cultural, social, and legal factors have been known to affect physicians' practice of continuous deep sedation. There have been few quantitative studies to compare continuous deep sedation practice in Asian countries. We aimed to describe and compare clinical characteristics of continuous deep sedation in Japan, Korea and Taiwan., Methods: Patients with advanced cancer admitted to participating palliative care units were enrolled from January 2017 to September 2018. We evaluated and compared (i) the prevalence of continuous deep sedation, (ii) the characteristics of sedated and non-sedated groups in each country, and (iii) continuous deep sedation administration patterns among the three countries., Results: A total of 2158 participants were included in our analysis, and 264 received continuous deep sedation. The continuous deep sedation prevalence was 10, 16 and 22% in Japan, Korea and Taiwan, respectively. Delirium was the most frequent target symptom in all countries, along with dyspnoea (in Japan) and psychological symptoms (in Korea). Midazolam was most frequently used in Japan and Taiwan, but not in Korea (P < 0.001). Among the patients receiving continuous deep sedation, the hydration amount on the final day was significantly different, with median volumes of 200, 500 and 0 mL in Japan, Korea and Taiwan, respectively (P < 0.001). In Korea, 33% of the continuous deep sedation administration caused a high degree of physicians' discomfort, but 3% in Japan and 5% in Taiwan (P < 0.001)., Conclusions: Clinical practices of continuous deep sedation and physicians' discomfort related to continuous deep sedation initiation highly varied across countries. We need to develop optimal decision-making models of continuous deep sedation and hydration during continuous deep sedation in each country., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

End-of-life patients with cancer may find expressing their symptoms difficult if they can no longer communicate verbally because of deteriorating health. In this study, we assessed these symptoms using machine learning, which has excellent predictive capabilities and has recently been applied in healthcare. We performed a retrospective clinical survey involving 213 patients with cancer from August 2015 to August 2016. We divided the reported symptoms into two groups-visible and nonvisible symptoms. We used decision tree analysis, an analytical machine learning method that organizes and analyzes information in the form of a tree diagram to visually represent the information structure. Our machine learning model used patient background data and visible symptoms to predict nonvisible symptoms: pain, dyspnea, fatigue, drowsiness, anxiety, delirium, inadequate informed consent, and spiritual issues. The highest and/or lowest values for prediction accuracy, sensitivity, and specificity were 88.0%/55.5%, 84.9%/3.3%, and 96.7%/24.1%, respectively. This work will facilitate better assessment and management of symptoms in patients with cancer. This study was the first to predict nonvisible symptoms using decision tree analyses for patients with cancer receiving palliative care. Notably, applications based on our results may assess symptoms to the same extent as healthcare professionals., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: The prevalence of dementia and cancer has increased in recent years. The presence of dementia complicates the care of terminal cancer patients and affects their family caregivers. However, palliative care research seldom focuses on the family caregivers of patients with terminal cancer and dementia. This study aimed to evaluate the degree and factors of caregiver burden in cancer patients with dementia who died in hospice palliative care units. Methods: A nationwide cross-sectional survey was conducted among bereaved family members of patients with cancer who died in palliative care units. An anonymous self-report questionnaire was sent to bereaved family members, and they were asked if they were aware of the diagnosis of dementia. The short version of the Caregiver Consequence Inventory was used to measure caregiver burden. Results: The analysis included 670 bereaved family members. Of these, 83 (12.4%) were bereaved family members of terminal cancer patients with dementia. The caregiver burden was statistically significantly higher (3.61 ± 1.58 vs 3.22 ± 1.47; p < 0.036) among family caregivers of terminal cancer patients with dementia. Longer anti-cancer treatment duration (odd ratio, 4.63), poor mental and physical health of family caregivers (odds ratio, 2.05 and 2.20, respectively), pain (odd ratio, 1.72), and dyspnea (odds ratio, 1.67) were contributing factors for caregiver burden. Conclusions: Family caregivers of terminal cancer patients with dementia require care that considers the characteristics of the two serious diseases. Considering the goal of anti-cancer treatment and symptom relief may be a useful strategy for reducing caregiver burden.

Background: Little is known about accuracy and confidence of clinicians' prediction of survival (CPS) in East-Asian countries. Objective: We aimed to examine accuracy of CPS for 7-, 21-, and 42-day survival in palliative inpatients and its association with prognostic confidence. Design: An international prospective cohort study in Japan (JP), Korea (KR), and Taiwan (TW). Setting/Subjects: Subjects were inpatients with advanced cancer admitted to 37 palliative care units in three countries. Measurements: Discrimination of CPS was investigated through sensitivity, specificity, overall accuracy, and area under the receiver operating characteristics curves (AUROCs) according to 7-, 21-, and 42-day survival. The accuracies of CPS were compared with those of Performance Status-based Palliative Prognostic Index (PS-PPI). Clinicians were instructed to rate confidence level on a 0-10-point scale. Results: A total of 2571 patients were analyzed. The specificity was highest at 93.2-100.0% for the 7-day CPS, and sensitivity was highest at 71.5-86.8% for the 42-day CPS. The AUROCs of the seven-day CPS were 0.88, 0.94, and 0.89, while those of PS-PPI were 0.77, 0.69, and 0.69 for JP, KR, and TW, respectively. As for 42-day prediction, sensitivities of PS-PPI were higher than those of CPS. Clinicians' confidence was strongly associated with the accuracy of prediction in all three countries (all p -values <0.01). Conclusions: CPS accuracies were highest (0.88-0.94) for the seven-day survival prediction. CPS was more accurate than PS-PPI in all timeframe prediction except 42-day prediction in KR. Prognostic confidence was significantly associated with the accuracy of CPS.

Objectives: It has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries., Methods: This international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors., Results: A total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5-19.5) in Japan, 23.0 days (95% CI 19.9-26.1) in Korea, and 15.0 days (95% CI 13.0-17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01-1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00-1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77-1.35; p = 0.89)., Significance of Results: SWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer.

Context: Bereaved family members sometimes experience distress due to stressful life events. However, the effects of this distress on depression and grief remain unclear., Objectives: To clarify the degree of distress due to postbereavement stressful life events, its associated factors, especially social isolation, and its effects on major depressive disorder (MDD) and complicated grief (CG) risks among bereaved family members of patients with cancer., Methods: This cross-sectional questionnaire survey was conducted in 2018 as part of the J-HOPE4 study. We recruited 1740 bereaved family members of patients with cancer who died from July to August of 2018. We assessed distress due to postbereavement stressful life events with the Bereavement Secondary Stressor Scale, social isolation with the Lubben Social Network Scale Short-Form, and the MDD and CG risk with the Patient Health Questionnaire-9 and Brief Grief Questionnaire, respectively., Results: Among the 913 (52.5%) respondents, 88%, 57%, 46%, 28%, and 19% experienced distress due to incidental tasks, daily life difficulties, financial problems, problems with other people, and deterioration of family relationships, respectively. More distress was associated with higher risks of MDD (odds ratio [OR] = 2.5, P < 0.01) and CG (OR = 2.5, P < 0.01). Social isolation and specific backgrounds were associated with more distress in response to stressful life events., Conclusion: Most family members experienced distress due to stressful life events, which were risk factors for MDD and CG. Assessing risk factors for maladaptation to post-bereavement life changes and enhancing readiness to adapt to them is important., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Bereaved family members are known to have a higher risk of suicide, although relevant research is lacking. We aimed to clarify the percentage of bereaved family members of patients with cancer who experience suicidal ideation and the associated factors., Methods: We conducted a secondary analysis of two cross-sectional nationwide bereavement surveys in Japan, analyzing data from a total of 17,237 bereaved family members of patients with cancer. The Patient Health Questionnaire 8 (PHQ-8) and Item 9 of the PHQ-9 were used to assess depression (PHQ-8 score ≥10) and suicidal ideation, respectively. We assessed items such as socio-demographic data, complicated grief (CG), preparedness for bereavement, and perceived social support. Logistic regression analysis was used to reveal factors related to suicidal ideation., Results: Overall, 11 % of subjects reported some amount of suicidal ideation in the previous two weeks, with a suicidal ideation rate as high as 42 % among those with a higher risk of depression. Significant associations (all p < 0.0001) were found between suicidal ideation and the family member's depressive state (OR: 10.01), poor physical health status during caregiving (OR: 1.24), poor psychological health status during caregiving (OR: 1.38) pre-existing mental illness (OR: 1.38), insufficient preparedness for bereavement (OR: 0.59), and poor perceived social support (OR: 1.42)., Limitations: The respondents were limited to family members of patients with cancer in Japan, and the study involved cross-sectional self-reported data., Conclusions: Clinicians should identify bereaved family members at a high risk of suicide by carefully assessing these risk factors identified in the present study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: End-of-life experiences (ELEs), such as deathbed visions (DBVs), have been reported worldwide. However, ELEs have rarely been discussed in clinical practice, possibly because of the different perceptions of ELEs among clinicians and families. Therefore, this study aimed to investigate the differences in perception regarding ELEs, especially DBVs, between clinicians and families., Methods: We conducted a multicentre, prospective and observational study with patients with cancer. After the patients' death, clinicians recorded their perceptions of patients' ELEs during the palliative care unit admission, and bereaved families responded to a questionnaire about ELEs. The primary outcome was the frequency and concordance of DBVs from the perspective of bereaved family members and clinicians. The second outcome was each group's frequency of terminal lucidity and terminal coincidence., Results: The study included 443 patients. DBVs were reported more frequently by family members than clinicians (14.0% vs 2.7%, p<0.001). Among family members, terminal lucidity and terminal coincidence were observed at 7% and 7.9%, respectively, while only one case each was reported by clinicians., Conclusions: Clinicians and family members may perceive ELEs differently. Enabling patients and their families to talk about ELEs would assist in optimising grief care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Accurate prognostication is important for patients and their families to prepare for the end of life. Objective Prognostic Score (OPS) is an easy-to-use tool that does not require the clinicians' prediction of survival (CPS), whereas Palliative Prognostic Score (PaP) needs CPS. Thus, inexperienced clinicians may hesitate to use PaP. We aimed to evaluate the accuracy of OPS compared with PaP in inpatients in palliative care units (PCUs) in three East Asian countries., Method: This study was a secondary analysis of a cross-cultural, multicenter cohort study. We enrolled inpatients with far-advanced cancer in PCUs in Japan, Korea, and Taiwan from 2017 to 2018. We calculated the area under the receiver operating characteristics (AUROC) curve to compare the accuracy of OPS and PaP., Results: A total of 1,628 inpatients in 33 PCUs in Japan and Korea were analyzed. OPS and PaP were calculated in 71.7% of the Japanese patients and 80.0% of the Korean patients. In Taiwan, PaP was calculated for 81.6% of the patients. The AUROC for 3-week survival was 0.74 for OPS in Japan, 0.68 for OPS in Korea, 0.80 for PaP in Japan, and 0.73 for PaP in Korea. The AUROC for 30-day survival was 0.70 for OPS in Japan, 0.71 for OPS in Korea, 0.79 for PaP in Japan, and 0.74 for PaP in Korea., Significance of Results: Both OPS and PaP showed good performance in Japan and Korea. Compared with PaP, OPS could be more useful for inexperienced physicians who hesitate to estimate CPS.

Background: This study aimed to explore (i) the consistency between physician-rated and bereaved family-perceived intensity of death rattle, (ii) the relationship between intensity of death rattle and the bereaved family's distress and (iii) the bereaved family's experience and feelings related to suctioning for death rattle., Methods: We used matched data for deceased patients from a prospective cohort study of cancer patients admitted to a palliative care unit, and their bereaved families from a nationwide questionnaire survey in Japan. The intensity of death rattle using Back's score was evaluated prospectively by physicians and retrospectively by bereaved families., Results: In total, 1122 bereaved families answered (response rate: 66.7%). Of these, 297 reported the development of death rattle. The maximum intensity of death rattle evaluated by physicians and perceived by bereaved families was poorly correlated (Spearman correlation coefficient 0.188, P = 0.082). The optimal cut-off point of Back's score for detecting high-level distress was 1/2, with a low accuracy of prediction (area under the curve 0.62). More than 70% of bereaved families indicated suctioning reduced the intensity of death rattle, made patients comfortable and themselves relieved, whereas a similar proportion felt patients were in distress during suctioning. Families who felt suctioning was gently performed and discussed well whether to do suctioning with health care providers felt less needs for improvement., Conclusions: Bereaved family-perceived intensity of death rattle did not correlate to physician-evaluated intensity, and the intensity of death rattle itself seemed to poorly correlate to family distress. Gently performed suctioning based on sufficient discussion with families can help reduce family-perceived patient discomfort., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To explore the unclear association between temporary discharge home from the palliative care unit and achievement of good death, in the background of increases in discharge from the palliative care unit. Association between experiences and circumstances of patient and family and duration of temporary discharge was also examined., Methods: This study was a secondary analysis of data from a nationwide post-bereavement survey., Results: Among 571 patients, 16% experienced temporary discharge home from the palliative care unit. The total good death inventory score (p < .05) and sum of 10 core attributes (p < .05) were significantly higher in the temporarily discharged and stayed home ≥2 weeks group. Among all attributes, "Independent in daily activities" (p < .001) was significantly better in the temporarily discharged and stayed home ≥2 weeks group. Regarding the experience and circumstance of patient and family, improvement of patient's appetite (p < .05), and sleep (p < .05) and peacefulness (p < .05) of family caregivers, compared to the patient being hospitalized, were associated with longer stay at home after discharge., Conclusions: Patient's achievement of good death was better in the temporarily discharged and stayed home longer group, but this seemed to be affected by high levels of independence of the patient. Temporary discharge from the palliative care unit and staying home longer was associated with improvement of appetite of patients and better sleep and mental health status of family caregivers. Discharging home from palliative care unit is worth being considered even if it is temporary., (© 2022 Japan Academy of Nursing Science.)

Purpose: Cancer of unknown primary site (CUP) is an aggressive disease with poor prognosis. As research on the experiences of CUP patients and their families is scarce, this study aimed to compare the family caregiver-perceived burden of CUP with that of common cancers (lung, colon, and stomach cancers). The association between family caregiver-perceived burden and CUP patients' quality of life (QOL) at end-of-life and family depression, respectively, was also explored., Methods: This was a pre-planned secondary analysis of nationwide cross-sectional survey data from the bereaved family caregivers of patients with cancer who died at 286 institutions. The major measurements were the eight-item family caregiver-perceived Burden scale (comprising specialist access, uncertainty, and prolonged diagnosis), Good Death Inventory, and Patient Health Questionnaire 9., Results: Of 27,591 survey responses, we analyzed 97 and 717 responses from family caregivers of patients with CUP and common cancer, respectively. The families of CUP patients scored significantly higher on all three burden subscales than those of common cancer patients (effect sizes: specialist access subscale, 0.3; uncertainty subscale, 0.66; and prolonged diagnosis subscale, 0.69; adjusted P < 0.01). Greater family burden was significantly associated with lower patient QOL and higher family depression. Burden was significantly associated with being a spouse, second opinion consultation, and diagnosis period of > 1 month., Conclusion: The family caregivers of CUP patients experience poor specialist access, greater uncertainty, and a prolonged diagnosis. They should be cared for from the initial stages to establish access to specialists, obtain an early diagnosis, and reduce uncertainty., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Research on the association between circumstances of death in advanced cancer patients and depression in their bereaved caregivers is limited., Methods: A longitudinal study was performed on patients admitted to 21 inpatient hospices/palliative care units (PCUs) in Japan. Patient symptoms were assessed at admission and in the last 3 days of life. Data on distressing events (unexpected death, bleeding) and received treatments (morphine prescriptions, continuous deep sedation, cardiopulmonary resuscitation) were also obtained. Bereaved caregiver depression was assessed 6 months or more after patient death via mail survey using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression analysis was used to explore variables predicting bereaved caregiver depression., Results: Of 1324 deceased patient-bereaved caregiver dyads, data were finally analyzed for 711 dyads. The proportion of probable depression (PHQ-9 scores ≥10) in bereaved caregivers was 13.6% (91/671; 95% confidence interval: 11.0-16.2). The multivariable logistic regression analysis showed that patient hyperactive delirium at PCU admission was significantly associated with the development of bereaved caregiver depression (odds ratio: 2.2, 95% CI: 1.2-3.8). Bereaved caregiver perceived low social support (OR: 4.7, 95% CI: 2.2-10.0) and low preparedness for death (OR: 4.5, 95% CI: 2.6-7.8) were also significantly associated with the development of depression. Other patient and bereaved caregiver variables had no association with depression., Conclusions: Hyperactive delirium in terminally ill cancer patients was associated with bereaved caregiver depression. The development of effective strategies to reduce delirium-related agitation and to provide educational interventions for caregivers may be needed., (© 2022 John Wiley & Sons Ltd.)

Purpose: Few large-scale studies have focused on the prevalence of symptoms and signs during the last days of patients diagnosed with advanced cancer. Identifying the patterns of specific symptoms according to cancer type is helpful to provide end-of-life care for patients with advanced cancer. We investigated the prevalence and severity of symptoms and signs associated with impending death in patients with advanced cancer., Methods: In this secondary analysis of an international multicenter cohort study conducted in three East Asian countries, we compared the severity of symptoms and signs among dying patients in the last 3 days of life according to the type of primary cancer using one-way analysis of variance (ANOVA). Post hoc analysis was conducted for multiple comparisons of each symptom according to the type of primary cancer., Results: We analyzed 2131 patients from Japan, Korea, and Taiwan. The prevalence of most symptoms and signs were relatively stable from 1 week after admission to the last 3 days of life. According to cancer type, edema of the lower extremities was the most common symptom and fatigue/ ascites were the most severe symptoms in digestive tract cancer. For lung cancer, respiratory secretion was the most prevalent and dyspnea/respiratory secretion were the most severe symptoms., Conclusion: We demonstrated the prevalence and severity of symptoms and signs associated with the impending death of patients with advanced cancer in East Asia. Our study can enable clinicians to recognize the specific symptoms and signs at the very end of life., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Some patients experience intense symptoms refractory to intensive palliative care, and palliative sedation is sometimes used. Palliative sedation may be classified into proportional and continuous deep sedation (CDS). The primary aim of this study was to compare family experience between families of patients who received proportional or CDS., Methods: A multicenter questionnaire survey was conducted involving bereaved families of cancer patients who received proportional or CDS based on a sedation protocol. Overall evaluation of sedation (satisfaction, family-perceived distress, appropriateness of timing, and patient distress) and 13-item family concerns, good death, satisfaction with care, depression, quality of care, unfinished business, and balance between symptom relief and maintaining communication were measured., Results: Among the 2120 patients who died, 222 patients received a continuous infusion of midazolam. A sedation protocol was used in 147 patients, and questionnaires were sent to 124 families. A total of 78 responses were finally returned (proportional, 58 vs. CDS, 20). There were no significant differences in the overall evaluation, family concerns, total score of good death, satisfaction, depression, or balance between symptom relief and maintaining communication. On the other hand, some quality of care items, i.e., relationship with medical staff (P < 0.01), physical care by nurses (P = 0.04), and coordination and consistency (P = 0.04), were significantly better in the CDS group than in the proportional sedation group. Family-reported unfinished business was also better in the CDS group, with marginal significance., Conclusions: Family experience of CDS was not less favorable than proportional sedation, and actually rated more favorably for some elements of quality of care and unfinished business., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: No studies have investigated the association between malignant brain tumor and the quality of dying, which is an important outcome in end-of-life care. This study aimed to clarify whether the quality of dying and related factors in patients with malignant brain tumor differ from those in patients with other malignant diseases., Methods: This was a secondary analysis of data collected by two nationwide, multicenter, bereavement surveys of palliative care units in Japan. This analysis included 14,171 bereaved family members (160 patients with malignant brain tumors). The quality of dying was examined using the good death inventory (GDI), a validated tool widely used in palliative care settings., Results: Patients with malignant brain tumors were younger (p < 0.0001) and had a longer palliative care unit stay during their end-of-life (p < 0.0001) than others. The total GDI score was significantly lower in patients with malignant brain tumors than others (p < 0.0001). Five GDI items were significantly lower in the malignant brain tumor group than other cancer group: "Being able to stay in one's favorite place" (p = 0.03); "Trusting the physician" (p = 0.003); "Not being a burden to others" (p = 0.01); "Being independent in daily activities" (p = 0.01); and "Feeling that one's life is worth living" (p = 0.001)., Conclusion: This study showed that the quality of dying of patients with malignant brain tumors was lower compared to other cancers, suggesting the need to review care for patients with malignant brain tumors based on their characteristics., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)