Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

PURPOSE: Opioid-induced constipation is the most frequent and non-self-limiting adverse effect of opioid analgesia, reducing adherence and interfering with pain relief. This clinical trial aimed to clarify the preventive effect of naldemedine versus placebo for constipation in patients with cancer starting regularly dosed strong opioids therapy. METHODS: This multicenter, double-blinded, randomized, placebo-controlled, confirmatory trial was conducted between July 2021 and May 2023 at four academic hospitals in Japan (ClinicalTrials.gov identifier: jRCTs031200397). Patients with cancer starting a first-time regularly dosed strong opioid for cancer pain and age 20+ years were included. Eligible patients were randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio for 14 days with protocol treatment. The primary end point was the proportion of patients with a Bowel Function Index (BFI) of <28.8 on day 14. The secondary end points included frequency of spontaneous bowel movements (SBM), quality of life (QOL), and frequency of opioid-induced nausea and vomiting (OINV). RESULTS: Of the 103 patients assessed for eligibility, 99 received either naldemedine (n = 49) or placebo (n = 50). A BFI of <28.8 on day 14 was significantly more likely to occur in the naldemedine group (64.6%; 95% CI, 51.1 to 78.1) versus placebo (17.0%; 95% CI, 6.3 to 27.8), and the difference between groups was 47.6% (95% CI, 30.3 to 64.8; P < .0001). The frequency of SBM, QOL, and the severity of OINV were nominally significant in the naldemedine group than in the control group. CONCLUSION: Naldemedine prevented constipation and improved constipation-related QOL, with possible preventive effect on OINV in patients with cancer starting regularly dosed opioids therapy.

Culturally Adapted RN-MD Collaborative SICP-Based ACP: Feasibility RCT in Advanced Cancer Patients.

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.

Prognostic Impact of Malignant Wounds in Patients With Head and Neck Cancer: Secondary Analysis of a Prospective Cohort Study.

INTRODUCTION: Malignant wounds are lesions caused by metastasis from distant primary cancers or by direct invasion of the cutaneous structures of a primary cancer, and are most common in patients with breast or head and neck cancers. Malignant wounds not only cause physical symptoms, but also affect survival. Recognizing prognosis in terminal-stage cancer patients is necessary for both patients and health care providers. The prognostic impact of malignant wounds in patients with head and neck cancer has been poorly investigated. METHODS: This is a secondary analysis of the results of a prospective cohort study that investigated the dying process in patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prognostic impact of malignant wounds in patients with head and neck cancer. The difference in survival between patients with head and neck cancer who had malignant wounds and those who did not was compared using the log-rank test. RESULTS: Of 1896 patients admitted to palliative care units, 68 had head and neck cancer, and 29 of these had malignant wounds. Overall survival was significantly shorter in patients with malignant wounds than that in those without (median: 19.0 days vs 32.0 days, P = 0.046). CONCLUSION: Patients with head and neck cancer who had malignant wounds had worse overall survival than those who did not.

The needs of patients with noncancer diseases and their families from hospital-based specialized palliative care teams in Japan.

BACKGROUND: Hospital-based specialized palliative care teams (HSPC) are important for symptom management and ethics support, especially during complex decision-making, but the needs of patients with noncancer diseases and their families from the HSPC are unclear. This study aimed to (I) compare the prevalence of symptom between patients with and without cancer and explore changes in symptom intensity after HSPC consultation in patients with noncancer; (II) determine factors related to ethics support; and (III) compare the percentage of request contents from patients and their families when a certified nurse specialist in gerontological nursing (geriatric care nurse below) is present in the HSPC to that when a certified nurse specialist in palliative care (palliative care nurse below) is present in the HSPC. METHODS: We utilized a retrospective cohort study to analyze 761 patients (360 with noncancer and 401 with cancer) referred to our HSPC at the National Center for Geriatrics and Gerontology using 10-year data (since 2011) available in an electronic medical record database. (I) Symptom scores of the Support Team Assessment Schedule were compared between noncancer and cancer groups and between initial and 1-week assessments for noncancer patients. (II) Ethics support was compared between noncancer (including dementia) and cancer. The presence or absence of ethics support requests, which was set as the objective variable, was examined using logistic regression analysis. (III) The percentage of request contents selected from nine items defaulted on the electronic medical record when a geriatric care nurse was present in our HSPC were compared to those when a palliative care nurse was present in our HSPC. RESULTS: Compared to those with cancer, patients with noncancer suffered more from dyspnea and sputum accumulation. More than 10% of patients with noncancer had suffered from pain, dyspnea, sputum accumulation, and anorexia that required treatment, with symptom scores showing improvement after 1 week of HSPC involvement, except for the sputum accumulation. Moreover, for anorexia, symptom scores improved, but >10% of these patients continued to suffer. Patients with noncancer diseases, including dementia, received ethics support than those with cancer without dementia. More requests for ethics support were received when a geriatric care nurse was in the HSPC than when a palliative care nurse was in the HSPC. Logistic regression analysis revealed that requests for ethics support were more frequent from patients or families with impaired decision-making capacity or when the patient lacked an advocate. CONCLUSIONS: The needs of patients with noncancer diseases and families from the HSPC in Japan included (I) symptom management for intractable conditions, such as sputum accumulation; (II) ethics support for patients with noncancer diseases, including dementia, with impaired decision-making capacity, and without advocates; and (III) advice on ethics issues from a geriatric care nurse.

Good Death and Quality of End-of-Life Care in Patients with Coexisting Cancer and Dementia: Perspective of Bereaved Families.

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.

Factors related to accurate clinicians' prediction of survival: an international multicenter study in East Asia.

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.

Associations of nutrition impact symptoms with depression in patients with advanced cancer.

PURPOSE: Advanced cancer patients have nutrition impact symptoms (NISs), while many of them have depressive moods. This study aimed to determine the associations of NISs with depression. METHODS: This study was a secondary analysis. The dietary intake and 19 NISs in patients receiving palliative care were evaluated using 10-point scales, and the patients were categorized into two groups (non-depression and depression groups) using the cutoff based on the Patient Health Questionnaire-9 (PHQ-9). To determine associations between depression and the number of NISs with a score of ≥ 4, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. RESULTS: A total of 225 participants were divided into the non-depression group (n = 148) and the depression group (n = 77). The prevalence of depression was 34.2%. Dietary intake was lower, and the number of NISs with a score of ≥ 4 was higher in the depression group (both p < 0.001). All NISs were more severe in the depression group. Significant differences were observed in 15 of the 19 NISs. In the logistic regression model, significantly higher adjusted ORs were observed in the groups with 4-6 NISs and 7 or more NISs with a score of ≥ 4 (10.76 [95% CI, 2.07-55.91], p = 0.016; 17.02 [95% CI, 3.08-94.22], p < 0.001) than in the group with no NISs with a score of ≥ 4. CONCLUSION: Having four or more NISs with a score ≥ 4 was associated with depression.

Dying Patients' Quality of Care for Five Common Causes of Death: A Nationwide Mortality Follow-Back Survey.

Background: The importance of high-quality care for terminal patients is being increasingly recognized; however, quality of care (QOC) and quality of death and dying (QOD) for noncancer patients remain unclear. Objectives: To clarify QOC and QOD according to places and causes of death. Design, Subjects: A nationwide mortality follow-back survey was conducted using death certificate data for cancer, heart disease, stroke syndrome, pneumonia, and kidney failure in Japan. The questionnaire was distributed to 115,816 bereaved family members between February 2019 and February 2020. Measurements included QOC, QOD, and symptoms during the last week of life. Analyses used generalized estimating equations adjusting for age, sex, and region. Results: Valid responses were returned by 62,576 (54.0%). Family-reported QOC and QOD by the place of death were significantly higher at home than in other places across all causes of death (for all combinations with hospital p < 0.01). In stroke syndrome and pneumonia, QOD significantly differed between hospital and home (stroke syndrome: 57.1 vs. 72.4, p < 0.001, effect size 0.77; pneumonia: 57.3 vs. 71.1, p < 0.001, effect size 0.78). No significant differences were observed in QOC and QOD between cancer and noncancer. The prevalence of symptoms was higher for cancer than for other causes of death. Conclusions: QOC and QOD were higher at home than in other places of death across all causes of death. The further expansion of end-of-life care options is crucial for improving QOC and QOD for all terminal patients.

A Novel Objective Measure for Terminal Delirium: Activity Scores Measured by a Sheet-Type Sensor.

CONTEXT: Delirium is a significant concern in end-of-life care. Continuous monitoring of agitation levels using objective methods may have advantages over existing measurement scales. OBJECTIVES: To examine whether an objective measure of activity scores measured using a sheet-type non-wearable sensor (Nemuri SCAN [NSCAN]) was correlated with agitation levels measured using the modified Richmond Agitation-Sedation Scale (RASS) in terminally ill patients with cancer. METHODS: We conducted a single-center, prospective, observational study in a palliative care unit using the NSCAN to measure activity scores and the RASS to assess agitation levels. RASS scores were prospectively measured by ward nurses blinded to the NSCAN variables. A database was created to pair the RASS scores and activity scores at night on the same day. RESULTS: During the observation period, 1209 patients were hospitalized, and 3028 pairs of assessments of 971 patients were analyzed. The NSCAN activity scores significantly increased with increasing RASS scores (Jonckheere-Terpstra test, p < 0.001). The mean values of the activity scores for each RASS score were RASS -5, 28.9; RASS -4, 36.4; RASS -3, 41.7; RASS -2, 57.4; RASS -1, 58.8; RASS 0, 62.6; RASS 1, 79.6; RASS 2, 106.5; and RASS 3, 118.7. CONCLUSION: The NSCAN activity significantly correlated with modified RASS agitation scores. Real-time NSCAN data on agitation may aid timely interventions for optimal symptom control. To improve outcomes for patients suffering from terminal delirium, more research on monitoring tools is warranted.

Enhancing end-of-life care quality and achieving a good death for the elderly in Japan.

BACKGROUND: In the context of an aging populations, there is an escalating need for palliative care tailored to the needs of the elderly. This study aimed to assess differences in symptoms and good death among the elderly, along with the structures and processes involved in end-of life care, and to explore the impact of age on achieving a good death. METHODS: We conducted a questionnaire survey for bereaved family members of patients with cancer, heart disease, stroke, pneumonia, and kidney failure in 2019 and 2020. The study population was categorized into the following age groups: ≤64, 65-74, 75-84, and ≥85. The outcomes included symptom intensity, achievement of a good death, and receipt of quality care. RESULTS: In total, 62,576 bereaved family members agreed to participate in the survey (response rate; 54.0 %). The weighted percentages of 'severe' and 'very severe' symptoms decreased with age. These trends were observed across age groups, even among the elderly. The strongest effect of age on achieving a good death was found for 'feeling that life is complete' with reference to those aged ≤64 years: 65-74 years (odds ratio [OR]; 2.09, 95 % CI; 1.94 to 2.25), 75-84 years (OR; 4.86, 95 % CI; 4.52 to 5.22) and ≥85 years (OR; 12.8, 95 % CI; 11.9 to 13.8). CONCLUSION: Age-specific differences were observed in quality of death, quality of care, and symptom intensity. It is important to provide individualized consideration for each age group rather than categorizing them broadly as the elderly when caring for them.

Preferences of bereaved family members on communication with physicians when discontinuing anticancer treatment: referring to the concept of nudges.

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 (ß = 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.' (ß = 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.

Associations of nutrition impact symptoms with dietary intake and eating-related distress in patients with advanced cancer.

BACKGROUND & AIMS: There is no definition of nutrition impact symptoms (NISs) in cancer care. Moreover, there is a lack of evidence on the associations of NISs with dietary intake and eating-related distress (ERD) in advanced cancer. Therefore, this study aimed to determine the associations of NISs with dietary intake and ERD in patients with advanced cancer. METHODS: This study entailed a secondary analysis of a multicenter self-reported questionnaire designed to develop measurements that assess ERD experienced by patients. Participants evaluated their dietary intake and 19 symptoms regarded as NISs using a 10-point scale. To determine the association between dietary intake and the number of NISs with a score ≥4, estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. Furthermore, to assess the association between ERD and the number of NISs with a score ≥4, multiple regression analysis was performed. RESULTS: A total of 302 patients were included in the analysis. The higher the number of NISs with a score ≥4, the lower the dietary intake tended to be. In the logistic regression model, significantly higher adjusted ORs than in the no NISs with a score ≥4 group were observed in the 4-6 NISs group, 7-9 NISs group, and 10 or more group (0.19 [95% CI, 0.07-0.52], p = 0.001; 0.11 [95% CI, 0.03-0.42], p = 0.001; 0.07 [95% CI, 0.01-0.36], p = 0.002, respectively). In the multiple regression analysis, the number of NISs with a score ≥4 was identified as one of the factors significantly associated with ERD. CONCLUSIONS: Having 4 or more NISs with a score ≥4 was shown to be predictive of the likelihood of reduced dietary intake. Furthermore, the higher the number of NISs with a score ≥4, the more likely the eating-related quality of life was impaired in advanced cancer.

Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia.

BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

Factors associated with multimodal care practices for cancer cachexia among registered dietitians.

PURPOSE: This study aimed to determine factors associated with multimodal care practices for cancer cachexia among registered dietitians (RDs) working in cancer care. METHODS: A secondary analysis was performed using RDs' data. Data on knowledge, skills, and confidence in multimodal care were obtained. Nine items regarding multimodal care practices were evaluated. Subjects were divided into two groups based on their answers associated with the nine items. Comparisons were obtained using the Mann-Whitney U test or chi-squared test. Multiple regression analysis was performed to identify the critical factors involved in practicing multimodal care by determining the variables with significant differences between the two groups. RESULTS: Two hundred thirty-two RDs were included in this study. Significant differences were observed in their primary area of practice (p = 0.023), the number of clinical guidelines used (p < 0.001), the number of items used in cancer cachexia assessment (p = 0.002), the number of symptoms used in cancer cachexia assessment (p = 0.039), training for cancer cachexia (p < 0.001), knowledge of cancer cachexia (p < 0.001), and confidence in cancer cachexia management (p < 0.001). The number of symptoms used in cancer cachexia assessment (B = 0.42, p = 0.019), knowledge of cancer cachexia (B = 6.60, p < 0.001), and confidence in cancer cachexia management (B = 4.31, p = 0.010) were identified as critical factors according to the multiple regression analysis. CONCLUSION: The RDs' knowledge and confidence in cancer cachexia management were associated with their multimodal care practices.

Successful Management of Terminal Delirium With Transdermal Blonanserin Patch in a Terminally Ill Cancer Patient.

Delirium is a distressing condition in terminally ill cancer patients, often treated with antipsychotics. Administering them orally, subcutaneously, or intravenously can be challenging in severely agitated patients. Transdermal antipsychotic patches offer an alternative, but their use for terminal delirium remains underexplored. We present the case of a 73-year-old man with advanced diffuse large B cell lymphoma who developed severe mixed delirium during third-line chemotherapy. Nonpharmacological interventions and oral risperidone plus intravenous haloperidol failed to improve his condition. Subsequently, a transdermal blonanserin patch was applied, resulting in the resolution of hallucinations on day 1 and agitation on day 3, allowing improved communication. The patch was easily applied daily without notable adverse events. However, he deteriorated a week later with an estimated survival of days, ultimately requiring continuous midazolam for refractory agitation. This case underscores the potential of transdermal blonanserin patches for delirium in terminally ill cancer patients, emphasizing the need for future prospective studies.

Extraction of Mucin from Rodent Feces and Determination of O-Linked Oligosaccharide Chain Equivalent Derived from Fecal Mucin.

Since the core protein of mucin in the digesta of the stomach and small intestine, which is less affected by bacteria, remains intact, mucin content can be measured by enzyme-linked immunosorbent assay (ELISA). However, the mucin core protein in bacteria-rich colon digesta and feces is partially hydrolyzed by bacterial enzymes and not fully recognized by mucin antibodies, so mucin cannot be accurately quantified by ELISA. This method quantifies the glycan content linked to the mucin core protein and expresses mucin content in the colon digesta and feces as the equivalent of O-linked oligosaccharide chain. Although mucin glycans are also hydrolyzed by colonic bacteria, this method is a more accurate and simple way to measure mucin content in the digesta of the large intestine and feces than the ELISA method.

Measurement of Mucinase Activity.

Mucinase consists of some proteases, glycosidases, sulfatases, and sialidases. It is not practical to measure individual enzyme activities when measuring mucinase activity. In this method, mucinase activity is measured using porcine gastric mucin as a substrate and feces as an enzyme source. This description includes fecal pellet preparation, reaction procedure of mucinase, measurement of reducing sugars liberated during the procedure, and determination of nitrogen content in the fecal preparations.

Effectiveness of antipsychotics for managing agitated delirium in patients with advanced cancer: a secondary analysis of a multicenter prospective observational study in Japan (Phase-R).

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.

Comparison of Pharmacological Treatments for Agitated Delirium in the Last Days of Life.

CONTEXT: Antipsychotics are often used in managing symptoms of terminal delirium, but evidence is limited. OBJECTIVES: To explore the comparative effectiveness of haloperidol with as-needed benzodiazepines (HPD) vs. chlorpromazine (CPZ) vs. levomepromazine (LPZ) for agitated delirium in the last days. METHODS: A prospective observational study was conducted in two palliative care units in Japan. Adult cancer patients who developed agitated delirium with a modified Richmond Agitation-Sedation Scale (RASS-PAL) of one or more were included; palliative care specialist physicians determined that the etiology was irreversible; and estimated survival was 3 weeks or less. Patients treated with HPD, CPZ, or LPZ were analyzed. We measured RASS, NuDESC, Agitation Distress Scale (ADS), and Communication Capacity Scale (CCS) on Days 1 and 3. RESULTS: A total of 277 patients were enrolled, and 214 were analyzed (112 in HPD, 50 in CPZ, and 52 in LPZ). In all groups, the mean RASS-PAL score significantly decreased on Day 3 (1.37 to -1.01, 1.87 to -1.04, 1.79 to -0.62, respectively; P < 0.001); the NuDESC and ADS scores also significantly decreased. The percentages of patients with moderate to severe agitation and those with full communication capacity on Day 3 were not significantly different. The treatments were well-tolerated. While one-fourth of HPD group changed antipsychotics, 88% or more of CPZ and LPZ groups continued the initial antipsychotics. CONCLUSION: Haloperidol with as-needed benzodiazepine, chlorpromazine, or levomepromazine may be effective and safe for terminal agitation. Chlorpromazine and levomepromazine may have an advantage of no need to change medications.

Fluid retention and weight loss in refractory cancer cachexia.

OBJECTIVES: It is unknown to what extent the fluid retention (FR) status disrupts the detection of weight loss rate (WLR) in adult patients with advanced cancer. This study aimed to determine the association of FR status with WLR. METHODS: This study was a secondary analysis of a prospective cohort study. FR was evaluated as follows: oedema (0, no; 1, yes), pleural effusion (0, no; 1, yes but asymptomatic; 2, symptomatic) and ascites (0, no; 1, yes but asymptomatic; 2, symptomatic). Patients were divided into three groups according to their FR scores: no-FR (0), moderate-FR (1-2) and high-FR (3-5). Multiple regression analysis was performed. RESULTS: Four hundred and twenty patients were categorised: no-FR group (n=164), moderate-FR group (n=158) and high-FR group (n=98). The prevalence of oedema, pleural effusion and ascites was 63.9%, 27.8% and 36.7% in the moderate-FR group, and 93.9%, 61.3% and 82.6% in high-FR group. The means of WLR were 9.2, 8.4 and 3.8 in the groups. The high-FR group and the FR score of 5 were correlated with WLR (estimate -4.71, 95% CI -7.84 to -1.58; estimate -10.29, 95% CI -17.84 to -2.74). CONCLUSIONS: The coexistence of FR was significantly correlated with WLR.