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.

Psychological symptom burden associated with malignant wounds: Secondary analysis of a prospective cohort study.

OBJECTIVES: Patients with malignant wounds suffer from physical and psychological symptom burden. Despite psychological support being required, the impact of malignant wounds on patients' psychological distress is poorly investigated. We evaluated psychological distress associated with malignant wounds for patients at their end of life. METHODS: This study used the secondary analysis of the results of a large prospective cohort study, which investigated the dying process among patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prevalence of moderate to severe psychological symptom burden, evaluated by the Integrated Palliative Care Outcome Scale (IPOS)-feeling at peace scores of 2-4. In addition, the factors affecting psychological symptoms were investigated. The quality of death was also evaluated upon death using the Good Death Scale score. RESULTS: Out of the total 1896 patients, 156 had malignant wounds (8.2%). Malignant wounds were more common in female and young people. The breast, head, and neck were the most prevalent primary sites. More patients with malignant wounds had IPOS-feeling at peace scores of 2-4 than patients without malignant wounds (41.0% vs. 31.3%, p = 0.024). Furthermore, psychological distress was associated with moderate to severe IPOS-pain and the frequency of dressing changes. The presence of malignant wounds did not affect the quality of death. SIGNIFICANCE OF RESULTS: This study showed increased psychological distress due to malignant wounds. Patients with malignant wounds require psychological support in addition to the treatment of physical symptoms for maintaining their quality of life.

Cross-cultural comparison of continuous deep sedation for advanced cancer patients in East Asian countries: prospective cohort study.

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.

Impact of taste/smell disturbances on dietary intakes and cachexia-related quality of life in patients with advanced cancer.

PURPOSE: Taste and smell are used to enjoy meals; however, impairments of these sensory perceptions seriously impact health and eating habits. This study is aimed at investigating the impact of taste and smell disturbances on dietary intakes and cachexia-related quality of life (QOL) in patients with advanced cancer. METHODS: Using a self-report questionnaire, we surveyed patients with advanced cancer undergoing treatment at 11 palliative care centers. Multivariate analyses were conducted to explore the impact of taste and smell disturbances on dietary intakes and cachexia-related QOL. Dietary intakes were assessed using the Ingesta-Verbal/Visual Analog Scale, while taste and smell disturbances were assessed using an 11-point Numeric Rating Scale (NRS). Cachexia-related QOL was assessed using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS). RESULTS: Overall, 378 patients provided consent to participate. After excluding patients with missing data, data were analyzed for 343 patients. Among them, 35.6% (n = 122; 95% [confidence interval (CI)] 0.28-0.38) and 20.9% (n = 72; 95% CI 0.17-0.25) experienced disturbances in taste (NRS ≥ 1) and smell (NRS ≥ 1), respectively. Multivariate analyses revealed that, independent of performance status and cancer cachexia, taste and smell disturbances were significantly associated with worse dietary intakes and deteriorating FAACT ACS scores. CONCLUSION: More severe taste and smell disturbances were associated with poorer dietary intakes and cachexia-related QOL. Diagnosing and treating such disturbances may improve dietary intakes and cachexia-related QOL, regardless of performance status and cachexia.

Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study.

PURPOSE: Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan. METHODS: This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site. RESULTS: In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE. CONCLUSION: There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.

Feasibility of a fast-track randomized controlled trial of cell-free and concentrated ascites reinfusion therapy for patients with refractory malignant ascites.

BACKGROUND: Malignant ascites often causes discomfort in advanced cancer patients. Paracentesis is the most common treatment modality, but it requires frequently repeated treatment. Cell-free and concentrated ascites reinfusion therapy (CART) may prolong the paracentesis interval, but controlled trials are lacking. We assessed the feasibility of a randomized controlled trial of CART vs. paracentesis alone for patients with refractory malignant ascites. METHODS: This study was an open-label, fast-track, randomized controlled, feasibility trial. Patients admitted to four designated cancer hospitals who received no further anticancer treatments were eligible. Patients were randomly assigned 1:1 to a CART arm or control (simple paracentesis) arm. The feasibility endpoint was the percentage of patients who completed the study intervention. Secondary endpoints included paracentesis-free survival, patient's request on the questionnaire for paracentesis (PRO-paracentesis)-free survival (the period until the patients first reported that they would want paracentesis if indicated), and adverse events. RESULTS: We screened 953 patients for eligibility. Of 61 patients with refractory malignant ascites, 21 patients were determined as eligible. Finally, 20 patients consented and were allocated; 18 patients (90%, 95% CI: 68.3-98.8) completed the study intervention. All patients had an ECOG performance status of 3 or 4. The median drained ascites volume was 3,200 mL in the CART arm and 2,500 mL in the control arm. In the CART arm, the median reinfused albumin volume was 12.6 g. Median paracentesis-free survivals were 5 days (95% CI: 2-6) in the CART arm, and 6 days (3-9) in the control arm. Median PRO-paracentesis-free survivals were 4 days (2-5) and 5 days (1-9), respectively. A total of 73% of patients received paracentesis within 2 days from their first request for the next paracentesis. One patient in the CART arm developed Grade 1 fever. CONCLUSIONS: A fast-track randomized controlled trial of CART for patients with malignant ascites is feasible. The efficacy and safety of CART should be assessed in future trials. PRO-paracentesis-free survival may be a complementary outcome measure with paracentesis-free survival in future trials. TRIAL REGISTRATION: Registered at University Hospital Medical Information Network Clinical Trial Registry as UMIN000031029 . Registered on 28/01/2018.

Family experience of palliative sedation therapy: proportional vs. continuous deep sedation.

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.

Effect of paracentesis on the survival of patients with terminal cancer and ascites: a propensity score-weighted analysis of the East Asian Collaborative Cross-cultural Study to Elucidate the Dying Process.

PURPOSE: Paracentesis is among the most widely utilized treatments for malignant ascites (MA). However, paracentesis in patients with MA has the potential to be associated with life-shortening effects. Thus, this study aimed to investigate whether paracentesis affected the duration of survival in such patients. METHODS: We performed a post hoc analysis of a prospective multicenter observational study investigating the dying process and end-of-life care in patients with terminal cancer, admitted to 23 palliative care units in Japan. Survival duration was compared between patients who did (paracentesis group) and did not undergo paracentesis (non-paracentesis group). We used inverse probability of treatment weighting (IPTW) to control for baseline covariates between groups. RESULTS: Among the 1896 initially enrolled patients, 568 with ascites were included in the study cohort. Eighty-five (15.0%) patients underwent paracentesis. The primary tumor site was the pancreas (51.9%, n = 295), followed by the gastrointestinal tract (22.7%, n = 129). Non-adjusted median durations of survival were 22 days (95% confidence interval [CI]: 16-25) and 12 days (95% CI: 11-13) in the paracentesis and non-paracentesis groups, respectively (hazard ratio [HR]: 0.69, 95% CI: 0.54-0.88; p = 0.003). The IPTW-adjusted median survival durations were 22 (95% CI: 16-25) and 16 days (95% CI: 12-22) in the paracentesis and non-paracentesis groups, respectively (HR: 0.89, 95% CI: 0.64-1.24; p = 0.492). No serious adverse events occurred in the paracentesis group. CONCLUSIONS: Paracentesis does not negatively affect the survival of patients with cancer and MA and can be a standard treatment in palliative care settings.

Effect of continuous deep sedation on survival in the last days of life of cancer patients: A multicenter prospective cohort study.

BACKGROUND: Continuous deep sedation is ethically controversial with respect to whether it shortens a patient's life. AIM: To examine whether continuous deep sedation shortens patient survival from the day of Palliative Performance Scale decline to 20 (PPS20). DESIGN: A part of a multicenter prospective cohort study (EASED study). SETTING/PARTICIPANTS: We recruited consecutive adult patients with advanced cancer admitted to 23 participating palliative care units in 2017 in Japan. We compared survival from PPS20 between those who did and did not receive continuous deep sedation. Continuous deep sedation was defined as the continuous administration of sedative medication with the intention to keep a patient continuously unconscious to alleviate otherwise uncontrollable symptoms, but the dose of sedatives was adjusted to achieve adequate symptom relief for each patient. The propensity score-weighting method was used to control for potential confounders, and five sensitivity analyses were performed. RESULTS: A total of 1926 patients were enrolled. Patients discharged alive were excluded, and we analyzed 1625 patients of whom 156 (9.6%) received continuous deep sedation. Median survival from PPS20 of 1625 patients was 81 h (95% CI: 77-88). The RASS scores decreased to ⩽-4 was 66% at 24 h. Continuous deep sedation was not associated with a significant survival risk (adjusted hazard ratio: 1.06, 95% CI: 0.85-1.33). All sensitivity analyses, including continuous deep sedation defined as the RASS score was ⩽-4 achieved the essentially the same results. CONCLUSIONS: Continuous deep sedation with careful dose adjustment was not associated with shorter survival in the last days of life in patients with advanced cancer.

Diagnostic accuracy of patient-reported dry mouth as a predictor for oral dryness in terminally ill cancer patients.

PURPOSE: The aim of the study was to determine the diagnostic accuracy of patient-reported dry mouth using an oral moisture-checking device in terminally ill cancer patients. METHODS: The study was conducted following the STARD guidelines, and the participants were recruited prospectively from the Palliative Care Unit, Kyoto Medical Center, Japan, between 1 January 2017 and 30 November 2018. Patients reporting dry mouth were asked to rate oral dryness on a 5-point rating scale. The outcome was oral dryness at the lingual mucosa, measured using an oral moisture-checking device. Receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity, positive and negative predictive values (PPV and NPV), positive and negative likelihood ratios (LR), and overall diagnostic accuracy were calculated. RESULTS: Of 103 participants, the prevalence of oral dryness was 65.0%. ROC analysis indicated that patient-reported dry mouth was a poor predictor of oral dryness, with an area under the curve of 0.616 (95% confidence interval: 0.508-0.723), a sensitivity of 46.3%, a specificity of 75.8%, a PPV of 55.9%, an NPV of 68.1, a positive LR of 1.9, a negative LR of 0.7, and an overall diagnostic accuracy of 64.1%, with a cut-off value of 3 points. CONCLUSION: In conclusion, patient-reported dry mouth is not a useful parameter for the assessment of oral dryness in terminally ill cancer patients.

Comparison between patient-reported and clinician-reported outcomes: Validation of the Japanese version of the Integrated Palliative care Outcome Scale for staff.

OBJECTIVES: The goal of palliative and supportive care is to improve patients' quality of life (QoL). Patient-reported outcome measures (PROMs) are the gold standard for the assessment of QoL and symptoms; however, when self-reporting is complicated, PROMs are often substituted with proxy-reported outcome measures, such as clinician-reported outcome measures. The objective of this study was to assess the validity and reliability of the Japanese version of the Integrated Palliative care Outcome Scale (IPOS) for staff (IPOS-Staff). METHODS: This multicenter, cross-sectional observational study was conducted concurrently with the validation of the IPOS for patients (IPOS-Patient). Japanese adult patients with cancer and their staff were recruited. We assessed the characteristics of the patients and staff members, missing values, prevalence, and total IPOS scores. For the analysis of criterion validity, intra-rater, and inter-rater reliability, we calculated intraclass correlations (ICCs). RESULTS: One hundred and forty-three patients completed the IPOS-Patient, and 79 medical staff members completed the IPOS-Staff. The most common missing values from IPOS-Staff were Family Anxiety (3.5%) and Sharing Feelings (3.5%). Over half of the patients scored themselves moderate or worse for Poor Mobility, Anxiety, and Family Anxiety, while staff members scored patients moderate or worse for Weakness, Anxiety, and Family Anxiety. For criterion validity (patient-staff agreement) as well as intra-rater and inter-rater reliability, ICCs ranged from 0.114 (Sharing Feelings) to 0.826 (Nausea), 0.720 (Anxiety) to 0.933 (Nausea), and -0.038 (Practical Problems) to 0.830 (Nausea), respectively. SIGNIFICANCE OF RESULTS: The IPOS-Staff is easy to respond to; it has fair validity and reliability for physical items but poor for psycho-social items. By defining the context and objectives of its use and interpretation, the IPOS-Staff can be a useful tool for measuring outcomes in adult patients with cancer who cannot complete self-evaluations.

Are common delirium assessment tools appropriate for evaluating delirium at the end of life in cancer patients?

OBJECTIVES: The objectives of this study are to investigate how many advanced cancer patients became unconscious or non-communicative after pharmacological treatment for delirium, and to explore whether existing delirium assessment tools can successfully evaluate its severity at the end of life. METHODS: This was a secondary analysis of a registry study that examined the efficacy and safety of antipsychotics for advanced cancer patients with delirium. A total of 818 patients were recruited from 39 specialized palliative care services in Japan. The severity of delirium was measured using the Richmond Agitation-Sedation Scale-Palliative care version, the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Nursing Delirium Screening Scale (Nu-DESC) on Day 3. Data from 302 patients with motor anxiety with an Agitation Distress Scale score ≥2 on Day 0 were analyzed for this study. The patients were categorized into four treatment response groups: complete response (CR: no agitation and fully communicative), partial response (PR: no/mild agitation and partially communicative), unconscious/non-communicative (UC), and no change (NC). RESULTS: On Day 3, 29 (10%; 95% confidence intervals [CI], 7-13) and 2 (1%; 95% CI, 0-2) patients became unconscious and non-communicative, respectively. Forty-four patients were categorized as CR, 97 as PR, 31 as UC, and 96 as NC. The scores of the DRS-R-98 and Nu-DESC in the UC group were rated higher than patients in the NC group were. CONCLUSIONS: A considerable number of cancer patients with delirium became unconscious or non-communicative. Existing delirium assessment tools may be inappropriate for measuring the severity of delirium in end-of-life.

The Functional Palliative Prognostic Index: a scoring system for functional prognostication of patients with advanced cancer.

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

Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase-R).

BACKGROUND: Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy. SUBJECTS, MATERIALS, AND METHODS: We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data-recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2). RESULTS: Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy. CONCLUSION: Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure. IMPLICATIONS FOR PRACTICE: Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.

Efficacy and safety of reinfusion of concentrated ascitic fluid for malignant ascites: a concept-proof study.

PURPOSE: Malignant ascites is one of the symptoms causing discomfort in advanced cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is one treatment modality, but controlled trials are limited. The primary aim of this study was to explore the efficacy and safety of CART, as well as their predictors, to obtain data for planning a further controlled trial. METHODS: This was a single center retrospective cohort study in patients with refractory malignant ascites. Consecutive adult patients who underwent CART were enrolled. The primary endpoints were the time to next paracentesis and seven patient-reported symptoms (e.g., abdominal pain and distension). The secondary endpoints were adverse events, laboratory findings, and physical findings. RESULTS: A total of 104 CART procedures for 51 patients were analyzed. The median time to next paracentesis was 27 days (95% CI, 21-35). Intensities of all seven symptoms were significantly improved after CART (p < 0.0001 for all symptoms). Grade 3 hypotension occurred during one procedure, and mild fever occurred in 5%. Total protein, albumin, and estimated glomerular filtration rate were significantly increased. Hemorrhagic ascites, ascites white blood cell count, serum total protein, and lymphocyte percentages were the independent predictors of the time to next paracentesis. CONCLUSION: The effects of reinfusion of concentrated ascitic fluid may be maintained for 1 month, being potentially longer than that of total paracentesis alone. This study had no comparison groups and examined the short-term effect. A randomized controlled study to compare the long-term effects of total paracentesis alone vs. CART is necessary.

Efficacy of two types of palliative sedation therapy defined using intervention protocols: proportional vs. deep sedation.

PURPOSE: This study investigated the effect of two types of palliative sedation defined using intervention protocols: proportional and deep sedation. METHODS: We retrospectively analyzed prospectively recorded data of consecutive cancer patients who received the continuous infusion of midazolam in a palliative care unit. Attending physicians chose the sedation protocol based on each patient's wish, symptom severity, prognosis, and refractoriness of suffering. The primary endpoint was a treatment goal achievement at 4 h: in proportional sedation, the achievement of symptom relief (Support Team Assessment Schedule (STAS) ≤ 1) and absence of agitation (modified Richmond Agitation-Sedation Scale (RASS) ≤ 0) and in deep sedation, the achievement of deep sedation (RASS ≤ - 4). Secondary endpoints included mean scores of STAS and RASS, deep sedation as a result, and adverse events. RESULTS: Among 398 patients who died during the period, 32 received proportional and 18 received deep sedation. The treatment goal achievement rate was 68.8% (22/32, 95% confidence interval 52.7-84.9) in the proportional sedation group vs. 83.3% (15/18, 66.1-100) in the deep sedation group. STAS decreased from 3.8 to 0.8 with proportional sedation at 4 h vs. 3.7 to 0.3 with deep sedation; RASS decreased from + 1.2 to - 1.7 vs. + 1.4 to - 3.7, respectively. Deep sedation was needed as a result in 31.3% (10/32) of the proportional sedation group. No fatal events that were considered as probably or definitely related to the intervention occurred. CONCLUSION: The two types of intervention protocol well reflected the treatment intention and expected outcomes. Further, large-scale cohort studies are promising.

Narrative review of malignant ascites: epidemiology, pathophysiology, assessment, and treatment.

BACKGROUND AND OBJECTIVE: Malignant ascites (MA) is common in patients with advanced cancer, and about 60% of patients with MA experience distressing symptoms. In addition, MA has been identified as a poor prognostic factor, therefore, making the management of MA an important issue. We aimed to review literature describing MA provide a narrative synthesis of relevant studies. METHODS: A literature search of articles published between 1971 and May 2023 was performed in PubMed, and Cochrane library using the words "ascites/malignant ascites" and the theme of each section. Authors independently selected the articles used and summarized. Finally, this manuscript was obtained consensus through discussed among all authors. KEY CONTENT AND FINDINGS: The pathophysiological mechanism of ascites formation involves increased vascular permeability and impaired fluid drainage through the lymphatic system, which explain the occurrence of peritoneal carcinomatosis, portal hypertension due to liver tumors, liver cirrhosis in the background of hepatocellular carcinoma, and Budd-Chiari syndrome caused by tumor occlusion of the hepatic vein. The efficacy and safety of various treatments and procedures have been investigated previously; however, no treatment guidelines have been established yet. Diuretics and paracentesis are often selected as the first lines of treatment. Intraperitoneal drug administration (catumaxomab, bevacizumab, aflibercept, hyperthermic intraperitoneal chemotherapy, triamcinolone), indwelling peritoneal catheters, peritoneovenous shunting, and cell-free and concentrated ascites reinfusion therapy are commonly used to manage refractory ascites. A new device for this purpose is alfapump, which transfers ascites fluid from the peritoneum into the urinary bladder. In addition, thoracic epidural analgesia may be effective for managing ascites-related symptoms. CONCLUSIONS: Despite these options, no standard treatment for MA has been established yet because few trials have been conducted in this area. There are many issues to be investigated, and future research and treatment development are expected.

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.

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.

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.