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.

Influence of dosing pattern of antipsychotics on treatment outcome of delirium in patients with advanced cancer.

BACKGROUND: Clinical guidelines recommend antipsychotics for the treatment of delirium; however, there has been no confirmed recommendation regarding their administrating patterns. This study aims to investigate whether different dosing patterns of antipsychotics (single or multiple administrations) influence the outcomes of delirium treatment. METHODS: This is a secondary analysis of a prospective observational study involving patients with advanced cancer and delirium receiving antipsychotics. The Delirium Rating Scale Revised-98 was administered at baseline and after 72 h of starting pharmacotherapy. Patients were classified into single administration group (received a single dosage within 24 h before the assessment) and multiple administration group (received more than one dosage). RESULTS: A total of 555 patients (single administration 492 (88.6%); multiple administration 63 (11.4%)) were subjected to analyses. The patients in the multiple administration group were more likely to be male, in psycho-oncology consulting settings, with lower performance status, with hyperactive delirium and with severer delirium symptoms. In the multivariate analysis, single administration was significantly associated with better improvement of delirium (p < 0.01, 95% confidence interval: 1.83-5.87) even after controlling covariates. There were no significant differences in the mean dosages of antipsychotics per day in chlorpromazine equivalent (single administration 116.8 mg/day, multiple administration 123.5 mg/day) and the incidence of adverse events between the two groups. CONCLUSIONS: In this observational study sample, Delirium Rating Scale severity score improvement in single administration was higher than that seen in multiple administration. There was no difference in adverse events between the two groups.

Involvement of orthopaedic surgeons for cancer patients in orthopaedic training facilities certified by the Japanese Orthopaedic Association - A nationwide survey.

BACKGROUND: In order to improve cancer care in Japan further, it is now required for orthopaedic surgeons to get actively involved in managing locomotive organs such as bones, muscles and nerves in cancer patients. In 2018, the Japanese Orthopaedic Association (JOA) conducted a questionnaire survey to investigate the current status of cancer treatment at the orthopaedic training facilities certified by the JOA. We analyzed the results of that questionnaire survey, focusing on the data from the core hospitals for cancer care (designated cancer hospitals), to clarify the involvement of orthopaedic surgeons in cancer treatment. MATERIALS AND METHODS: A nationwide survey was conducted in the orthopaedic training facilities certified by the JOA using an online questionnaire from March 15th to 31st, 2018. To clarify the involvement of orthopaedic surgeons in cancer treatment, we analyzed the results of that questionnaire survey, focusing on the data from the designated cancer hospitals in Japan. RESULTS: From the questionnaire survey, it became clear that 24% of the orthopaedic training facilities certified by the JOA are designated cancer hospitals. There were significant differences concerning cancer treatment and the prospect of orthopaedic surgeons' involvement in the treatment for bone metastases between institutions classified according to number of both certified orthopaedic surgeons by the JOA and specialists for bone and soft tissue tumors. In addition, in 45% of the designated cancer hospitals, orthopaedic surgeons treated bone metastases that occur in cancer patients, but in the rest of the institutions, orthopaedic surgeons did not yet adequately respond. CONCLUSION: In order to further improve the locomotive function and quality of life (QOL) in cancer patients, it was seemed to be necessary that all medical professionals engaged in cancer treatment, including orthopaedic surgeons, recognize the importance of locomotive management for cancer patients. In addition, the results of this study suggested that the presence of more than six certified orthopaedic surgeons by the JOA, including one or more specialists for bone and soft tissue tumors, may be able to create an environment conducive to the involvement of orthopaedic surgeons in cancer treatment at the facility.

A decision tree prediction model for a short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions: A secondary analysis of a multicenter and prospective observational study (Phase-R).

OBJECTIVE: There is no widely used prognostic model for delirium in patients with advanced cancer. The present study aimed to develop a decision tree prediction model for a short-term outcome. METHOD: This is a secondary analysis of a multicenter and prospective observational study conducted at 9 psycho-oncology consultation services and 14 inpatient palliative care units in Japan. We used records of patients with advanced cancer receiving pharmacological interventions with a baseline Delirium Rating Scale Revised-98 (DRS-R98) severity score of ≥10. A DRS-R98 severity score of <10 on day 3 was defined as the study outcome. The dataset was randomly split into the training and test dataset. A decision tree model was developed using the training dataset and potential predictors. The area under the curve (AUC) of the receiver operating characteristic curve was measured both in 5-fold cross-validation and in the independent test dataset. Finally, the model was visualized using the whole dataset. RESULTS: Altogether, 668 records were included, of which 141 had a DRS-R98 severity score of <10 on day 3. The model achieved an average AUC of 0.698 in 5-fold cross-validation and 0.718 (95% confidence interval, 0.627-0.810) in the test dataset. The baseline DRS-R98 severity score (cutoff of 15), hypoxia, and dehydration were the important predictors, in this order. SIGNIFICANCE OF RESULTS: We developed an easy-to-use prediction model for the short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions. The baseline severity of delirium and precipitating factors of delirium were important for prediction.

Association of Antipsychotic Dose With Survival of Advanced Cancer Patients With Delirium.

CONTEXT: Delirium is common in patients with advanced cancer, and antipsychotics are widely used for its management. OBJECTIVES: We aimed to explore the association of the antipsychotic dose with survival of terminally ill cancer patients with delirium. METHODS: A secondary analysis of a multicenter prospective observational study was conducted. We enrolled adult advanced cancer patients who developed delirium and received antipsychotics at 14 palliative care units in Japan between September 2015 and May 2016. Hazard ratios of survival after starting antipsychotics between groups with different oral chlorpromazine equivalent doses: low: <100 mg, moderate: 100-200 mg, high: ≥200 mg, were calculated with adjustment for potential confounders using Cox regression. The antipsychotic dose-specific mortality risk was estimated with smooth splines. RESULTS: Of 453 patients enrolled, 422 patients were analyzed. The median antipsychotic dose was 92.6 mg: low-dose (N = 231), moderate-dose (122), and high-dose (69). The median survival of all patients was 11 days. Compared with the low-dose group, the high-dose group showed a significantly shorter survival (HR: 1.46, 95%CI: 1.08-1.98). Smooth splines demonstrated that HR continuously increased as the antipsychotic dose increased. In patients treated with atypical antipsychotics, the high-dose group showed a significantly shorter survival than the low-dose group (HR: 2.86), while in patients treated with typical antipsychotics, survival was not significantly different (0.99). CONCLUSIONS: Higher doses of antipsychotics were associated with increased mortality in terminally ill cancer patients with delirium. To minimize the potential mortality risk, antipsychotics should be started at low doses and titrated carefully.

Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain: a JORTC-PAL16 trial protocol.

INTRODUCTION: Management of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy (CIPN) has already been confirmed in two randomised controlled trials (RCTs) compared with placebo. Duloxetine offers the potential of analgesia in opioid refractory NCP. However, there are no RCT of duloxetine for the management of opioid-refractory NCP as a first line treatment. Both classes of drugs have the potential to reduce NCP, but there has been no head-to-head comparison for the efficacy and safety, especially given differing side effect profiles. METHODS AND ANALYSIS: An international, multicentre, double-blind, dose increment, parallel-arm, RCT is planned. Inclusion criteria include: adults with cancer experiencing NCP refractory to opioids; Brief Pain Inventory (BPI)-item 3 (worst pain) of ≥4; Neuropathic Pain on the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale of ≥12 despite of an adequate trial of regular opioid medication (≥60 mg/day oral morphine equivalent dose). Patients with CIPN are excluded.The study will recruit from palliative care teams (both inpatients and outpatients) in Japan and Australia. Participants will be randomised (1:1 allocation ratio) to duloxetine or pregabalin arm. Dose escalation is until day 14 and from day 14 to 21 is a dose de-escalation period to avoid withdrawal effects. The primary endpoint is defined as the mean difference in BPI item 3 for worst pain intensity over the previous 24 hours at day 14 between groups. A sample size of 160 patients will be enrolled between February 2020 and March 2023. ETHICS AND DISSEMINATION: Ethics approval was obtained at Osaka City University Hospital Certified Review Board and South Western Sydney Local Health District Human Research Ethics Committee. The results of this study will be submitted for publication in international journals and the key findings presented at international conferences. TRIAL REGISTRATION NUMBERS: jRCTs051190097, ACTRN12620000656932.

Evidence-Based Practice Guideline for the Management of Lymphedema Proposed by the Japanese Lymphedema Society.

Background: Secondary lymphedema mostly occurs as an aftereffect of cancer treatment, and it is estimated that 100,000-150,000 patients are affected in Japan. An estimated 3500 patients, develop lymphedema of the lower and upper extremities each year secondary to uterine and breast cancer treatment. Medical reimbursement was first instituted in April 2008 by the Ministry of Health, Labour and Welfare in Japan. Since 2008, we have developed guidelines regarding treatment options for patients with lymphedema based on scientific evidence. This is the third edition of the guidelines established by the Japanese Lymphedema Society (JLES), published in 2018. The JLES Practice Guideline-Making Committee (PGMC) developed 21 clinical questions (CQs). Methods and Results: A review of these 15 CQs was performed in accordance with the methodology for establishing clinical guidelines. The 15 recommendations for each of these CQs were developed and discussed until consensus by the PGMC was reached. Moreover, outside members who had no involvement in these guidelines evaluated the contents using the Appraisal of Guidelines for Research and Evaluation (AGREE) II reporting checklist. Conclusion: These guidelines have been produced for the adequate management of lymphedema by doctors and other medical staff on the lymphedema management team of medical institutes, including nurses, physical technicians, and occupational therapists.

Evaluation of quality indicators near death in older adult cancer decedents in Japan: A nationwide retrospective cohort study.

OBJECTIVES: End-of-life cancer care is important; however, data on hospitalization and costs for older patients have been lacking. We aimed to examine quality indicators and costs for older patients in Japan. METHODS: Using the Diagnosis Procedure Combination database, a national database of acute-care hospitals in Japan, we retrospectively collected data on cancer decedents aged ≥65 years. We evaluated the quality indicators (hospitalizations, length of stay in the hospital, emergency hospitalizations, emergency hospitalizations using an ambulance, intensive care unit [ICU] admissions, length of stay in the ICU, interval between last chemotherapy use and death, and chemotherapy within 14 days before death) and hospitalization costs at 30, 90 and 180 days before death. We compared the outcomes across age groups (65-74, 75-84 and ≥ 85 years). RESULTS: Between January 2011 and March 2015, we identified 369 616 cancer decedents. From 180 to 30 days before death, there were increases in emergency hospitalizations, emergency hospitalizations using an ambulance, and the mean costs per hospital day. Overall, 16.7% of patients receiving chemotherapy last received this treatment on the day before death or the day of death. Costs decreased with increasing age. The group aged ≥85 years had the shortest hospital and ICU stays and the lowest multiple hospitalizations, ICU admissions, chemotherapy within 14 days before death, and costs. CONCLUSIONS: Many older adult patients had emergency hospitalizations and received chemotherapy just prior to death, and there is room for improvement in appropriate end-of-life care. Oldest old patients consumed relatively few medical resources.

Predictors of Morphine Efficacy for Dyspnea in Inpatients with Chronic Obstructive Pulmonary Disease: A Secondary Analysis of JORTC-PAL 07.

Objective: This study aimed to explore the predictors of morphine efficacy in the alleviation of dyspnea in COPD. Background: Dyspnea is prevalent in patients with chronic obstructive pulmonary disease (COPD) and often persists despite conventional treatment. Methods: A secondary analysis of a multi-institutional prospective before-after study was conducted focusing on morphine use for alleviating dyspnea in COPD patients. Subjects included COPD patients with dyspnea at seven hospitals in Japan. Patients received 12 mg/day of oral morphine (or 8 mg/day if they had low body weight or renal impairment). Univariate and multivariate logistic regression analyses were performed with numerical rating scale (NRS) score of the current dyspnea intensity in the evening of day 0, Eastern Cooperative Oncology Group Performance Status (ECOG PS; ≤2 or ≥3), age, and partial arterial pressure of carbon dioxide (PaCO2) as independent factors; an improvement of ≥1 in the evening NRS score of dyspnea from day 0 to 2 was the dependent factor. Results: Thirty-five patients were enrolled in this study between October 2014 and January 2018. Excluding one patient who did not receive the treatment, data from 34 patients were analyzed. In the multivariate analysis, lower PaCO2 was significantly associated with morphine efficacy for alleviating dyspnea (odds ratio [OR] 0.862, 95% confidence interval [CI] 0.747-0.994), whereas the NRS of dyspnea intensity on day 0 (OR 1.426, 95% CI 0.836-2.433), ECOG PS (OR 4.561, 95% CI 0.477-43.565), and patients' age (OR 0.986, 95% CI 0.874-1.114) were not. Discussion: Morphine can potentially alleviate dyspnea in COPD patients with lower PaCO2. Trial registration: UMIN000015288 (http://www.umin.ac.jp/ctr/index.htm).

Development of Japanese Versions of the Control Preferences Scale and Information Needs Questionnaire: Role of Decision-Making and Information Needs for Japanese Breast Cancer Patients.

PURPOSE: The importance of shared decision-making (SDM) between physicians and patients is increasingly recognized. In Japan, patients have shown more willingness to participate in treatment if medical professionals provide sufficient information; however, relationships between physicians and patients have traditionally been asymmetric, with patients accepting information from physicians without discussion. To explore the benefits of SDM in cancer treatment, including confidence in treatment decisions, satisfaction with treatment, and trust in healthcare providers, this study developed Japanese versions of the Control Preference Scale (CPS) and Information Needs Questionnaire (INQ). PATIENTS AND METHODS: Reliability and validity of the CPS and INQ were tested with 49 breast cancer patients. RESULTS: The CPS showed good test-retest reliability (kappa coefficient: 0.61, weighted kappa coefficient: 0.61, Kendall's tau coefficient: 0.61) and acceptable criterion validity. The INQ showed adequate consistency; the mean number of circular triads and coefficient of consistency were 3 (range 0-19) and 0.9 (range 0.37-1), respectively. Using the CPS and INQ to identify patients' roles in decision-making and information needs, results further suggested that breast cancer patients in Japan want to participate in SDM. Medical issues, including disease spread and cure, were found to be of high interest, while social and psychological issues, including sexual attractiveness, genetic risk, and family impact, tended to be low. CONCLUSION: The Japanese CPS and INQ can be used to assess patients' needs to improve care. Further, as patients' information needs change along the care trajectory, these tools should be used throughout treatment.

Study protocol for a randomised, placebo-controlled, single-blind phase II study of the efficacy of morphine for dyspnoea in patients with interstitial lung disease (JORTC-PAL 15).

INTRODUCTION: Dyspnoea is common in patients with interstitial lung disease (ILD) and often refractory to conventional treatment. Little is known about the efficacy of systemic morphine for dyspnoea in patients with ILD. The aim of this study is to estimate the efficacy of a single subcutaneous morphine injection for dyspnoea in patients with ILD. METHODS AND ANALYSIS: We will conduct a multicentre, prospective, randomised, placebo-controlled, single-blinded phase II study of a single subcutaneous morphine injection for dyspnoea in patients with ILD. In patients with ILD who have dyspnoea at rest refractory to conventional treatment will be eligible for participation in this study. The morphine dose will be 2 mg. The primary endpoint is changes in dyspnoea intensity from baseline to 60 min after treatment as measured using an 11-point Numerical Rating Scale and compared between the morphine and placebo groups. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the Osaka City University Certified Review Board. The results of this study will be submitted for publication in an international peer-reviewed journal and the findings will be presented at international scientific conferences. TRIAL REGISTRATION NUMBER: jRCTs051190030; pre-results.

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

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

Low-Dose Trazodone for Delirium in Patients with Cancer Who Received Specialist Palliative Care: A Multicenter Prospective Study.

Background: Clinical usefulness of trazodone for delirium in patients receiving palliative care is unclear. Objectives: To examine the safety and effectiveness of trazodone for delirium. Design: A secondary analysis of a multicenter prospective observational study. Setting/Subjects: The setting involves nine psycho-oncology consultation services and 14 inpatient palliative care units in Japan. Measurements: The measurement involves the Delirium Rating Scale (DRS) Revised-98 for effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 for safety assessments. Results: Thirty-eight patients enrolled the study. Mean age was 75 years. After three-day observation, the DRS total score (11.6 ± 5.3 to 8.7 ± 6.5 [difference -2.9, 95% confidence interval -5.3 to -0.5, p = 0.02]); sleep-wake cycle disturbance (p = 0.047), lability of affect (p < 0.001), and motor agitation subscales (p < 0.001) were significantly decreased. The most frequent adverse event was somnolence (n = 9). Conclusions: Low-dose trazodone treatment was generally safe and may be effective in reducing delirium severity.

Association between ambulance use and hospitalization costs among heart failure patients.

Heart failure is the main cause of hospitalization, which burdens the healthcare system. Although many hospitalizations for heart failure follow ambulance use, it is unknown whether ambulance use increases hospitalization costs. Using the Diagnosis Procedure Combination database in Japan, we examined all hospitalizations of patients with heart failure from April 2014 to March 2015. Patients were divided into those with and those without ambulance use. We performed a multiple regression analysis to examine the association between ambulance use and total hospitalization costs, adjusting for age, sex, length of day, and activities of daily living. We identified 126,067 hospitalizations for heart failure. The percentages of ambulance use were 29%, 27%, 30%, and 50% among patients with NYHA Functional Classification I, II, III, and IV, respectively. For patients categorized as NYHA I (n = 9,700), multiple linear regression analysis revealed that ambulance use was significantly associated with higher hospitalization cost (coefficient 723 USD; 95% confidence interval 109-1337; p = 0.021). Even for heart failure patients with NYHA I, ambulances were frequently used. Ambulance use was independently associated with increased hospital costs. Future research is needed on transitional care to limit unnecessary ambulance use.

Morphine for dyspnoea in chronic obstructive pulmonary disease: a before-after efficacy study.

OBJECTIVES: Dyspnoea in patients with chronic obstructive pulmonary disease (COPD) is frequent and often persists despite conventional treatment. This study aimed to evaluate the efficacy and safety of oral morphine for dyspnoea in Japanese COPD patients. METHODS: We conducted a multi-institutional, prospective, before-after study of morphine in COPD patients with dyspnoea at rest in seven hospitals. Patients received 12 mg of oral morphine per day (or 8 mg per day if low body weight or renal impairment). Primary outcome was change in the numerical rating scale (NRS) of current dyspnoea in the evening from Day 0 to Day 2. Secondary outcomes included changes in dyspnoea intensity in the evening from Day 0 to Day 1, dyspnoea intensity between the morning from Day 0 to Day 1 and Day 2, vital signs, nausea, somnolence, anorexia and other adverse events (AEs). RESULTS: A total of 35 patients were enrolled in this study between October 2014 and January 2018. One patient did not receive study treatment. Data from 34 patients was analysed. The NRS of dyspnoea intensity in the evening significantly decreased from 3.9 on Day 0 (95% CI: 3.1 to 4.8) to 2.4 on Day 2 (95% CI: 1.7 to 3.1; p=0.0002). Secondary outcomes significantly improved in a similar manner. There were no apparent changes in the mean scores of the opioid-related AEs and vital signs. One patient experienced grade 3 lung infection not associated with morphine. Other AEs were mild. CONCLUSION: Oral morphine is effective in alleviating dyspnoea in Japanese COPD patients. Trial registration UMIN000015288 (http://www.umin.ac.jp/ctr/index.htm).

Prevalence of Extrapyramidal Symptoms in Cancer Patients Referred to Palliative Care: A Multicenter Observational Study (JORTC PAL12).

BACKGROUND: Neuroleptics are commonly used in palliative care settings. However, adverse events of neuroleptics, known as extrapyramidal symptoms (EPSs), might be overlooked in clinical practice. We conducted this study to explore the prevalence of EPSs in palliative care setting. METHODS: This multicenter, prospective, observational study included patients who 1) were referred to either a specialist palliative care team or a palliative care unit, 2) had a diagnosis of cancer, and 3) were ≥20 years of age. We investigated the prevalence of EPSs and medications used. The primary outcome was the overall Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) score. RESULTS: Between November 2015 and October 2016, 149 patients from 5 centers in Japan were enrolled. The median age was 67 years (range: 21-88 years) and the study population included 81 men (54.4%). The cancer types included lung (55 patients, 36.9%), upper gastrointestinal tract (5, 3.3%), hepatobiliary (19, 12.8%); breast (12, 8.1%); head and neck (10, 6.7%), gynecologic (10, 6.7%), genitourinary (10, 6.7%), and others (28, 18.8%). The median Karnofsky performance status was 60 (20-100). Most patients (86.6%) did not experience delirium. Thirty-nine (26.2%) patients received one or more EPS-inducing medications. EPSs occurred in 4 (2.7%) patients with a cutoff score of 5 points for 5 parkinsonism items in DIEPSS. CONCLUSION: A lower frequency (<3%) of patients than expected in this population had EPSs. Therefore, we concluded that an interventional study is not feasible. However, medications that cause EPSs are often used in palliative care; therefore, a longitudinal study is warranted. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) (UMIN000019810) on 16, November, 2015.

The efficacy of specialised rehabilitation using the Op-reha Guide for cancer patients in palliative care units: protocol of a multicentre, randomised controlled trial (JORTC-RHB02).

BACKGROUND: Although rehabilitation is recommended for terminal cancer patients, the specific components and methods of such programs are poorly documented. No studies to date have examined the effectiveness of rehabilitation for terminal cancer patients. This study aims to evaluate the efficacy of a new intervention for rehabilitation therapists, using the Op-reha Guide (Guide to Optimal and Patient-Centred Rehabilitation Practice for Patients in Palliative Care Units [PCUs]) in rehabilitation practice. This guide consists of recommended actions and attitudes for rehabilitation therapists and aims to optimise therapists' actions according to the patient's needs and condition. It shares goals with terminal cancer patients to maintain their activities of daily living (ADL). METHODS: This study uses a multicentre, prospective, randomised controlled trial (RCT) design with two parallel groups in PCUs where specialised rehabilitation will be routinely performed for terminal cancer patients by rehabilitation therapists. Participants will be randomised (1:1) to intervention (the Op-reha Guide) and control groups (usual rehabilitation). We will then conduct an observational study in PCUs that do not perform specialised rehabilitation for terminal cancer patients; this will be considered the usual care group, and the efficacy of usual rehabilitation will be quantitatively evaluated. Inclusion criteria are hospitalisation in PCU, European Cooperative Oncology Group Performance Status of 2 or 3, and clinical estimation of life expectancy of 3 weeks or more. Patients with severe symptom burden will be excluded. We hypothesise that the Op-reha Guide will be more effective in maintaining the ADL of terminal cancer patients hospitalised in PCUs than usual rehabilitation. The primary endpoint is defined as the change in (total) modified Barthel Index from baseline to Day 22. Quality of life will be a secondary endpoint. In total, 135 patients will be recruited from 16 Japanese sites between July 2019 and December 2021. DISCUSSION: This will be the first trial to evaluate the efficacy of specialised rehabilitation for terminal cancer patients hospitalised in PCUs, and will contribute to the evidence on the efficacy of implementing rehabilitation for terminal cancer patients. TRIAL REGISTRATION: UMIN-CTR, UMIN000037298 R000042525 (date of registration 7 July 2019).

Safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer: A large-scale multicenter prospective observational study in real-world palliative care settings.

OBJECTIVE: To clarify the safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer receiving palliative care. METHODS: This was a prospective observational study involving consecutive patients with advanced cancer and delirium receiving antipsychotics in inpatient hospices or psycho-oncology settings. Adjusted mean scores of the Delirium Rating Scale Revised-98 (DRS; range: 0-39) were calculated at baseline and Day 3 using generalized estimating equations. Adverse events over 7 days were evaluated. RESULTS: Data from 756 patients were analyzed (Mage = 72 ± 11 years, 62% male, 48% bedridden). The adjusted mean DRS score significantly decreased after antipsychotics administration (21.5 [95% confidence interval 19.5 to 23.4] to 20.8 [18.9 to 22.8], p = 0.03, effect size [ES] = 0.02). Significant improvement was associated with age of 75 or older (ES = 0.07), better performance status (0.32), longer estimated prognosis (0.25), psycho-oncological consultation settings (0.20), hyperactive (0.14) or mix-motor subtypes (0.24) of delirium, and quetiapine administration (0.19); significant deterioration was observed in patients with "days" prognosis (0.18). Extrapyramidal symptoms (9.8%) and somnolence (8.5%) were the most prevalent adverse events. CONCLUSIONS: The use of antipsychotics as part of comprehensive delirium management was safe and may provide some symptomatic benefits for patients with terminal illness and delirium. Along with adequate non-pharmacological interventions, judicious use of antipsychotics is still recommended.

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.