[For Who Is Comfort Set ?-In Order to Stop Inappropriate Drug Use].

In home healthcare, the usefulness of comfort set(also called emergency kit)is prescribed in advance in preparation for symptoms accompanied by pain. The common symptoms since the terminal phase are, pain, dyspnea, delirium(restlessness), excessive respiratory secretion(death rattle). It is essential for comfort care to change the route of administration of the necessary medication and to minimize distress necessarily by prescribing the comfort set.

Adding items that assess changes in activities of daily living does not improve the predictive accuracy of the Palliative Prognostic Index.

BACKGROUND: Changes in activities of daily living in cancer patients may predict their survival. The Palliative Prognostic Index is a useful tool to evaluate cancer patients, and adding an item about activities of daily living changes might improve its predictive value. AIM: To clarify whether adding an item about activities of daily living changes improves the accuracy of Palliative Prognostic Index. DESIGN: Multicenter prospective cohort study. SETTING: A total of 58 palliative care services in Japan. PARTICIPANTS: Patients aged >20 years diagnosed with locally extensive or metastatic cancer (including hematological neoplasms) who had been admitted to palliative care units, were receiving care by hospital-based palliative care teams, or were receiving home-based palliative care. Palliative care physicians recorded clinical variables at the first assessment and followed up patients 6 months later. RESULTS: A total of 2425 subjects were recruited and 2343 of these had analyzable data. The C-statistic of the original Palliative Prognostic Index was 0.801, and those of modified Palliative Prognostic Indices ranged from 0.793 to 0.805 at 3 weeks. For 6-week survival predictions, the C-statistic of the original Palliative Prognostic Index was 0.802, and those of modified Palliative Prognostic Indices ranged from 0.791 to 0.799. The weighted kappa of the original Palliative Prognostic Index was 0.510, and those of modified Palliative Prognostic Indices ranged from 0.484 to 0.508. CONCLUSION: Adding items about activities of daily living changes to the Palliative Prognostic Index did not improve prognostic value in advanced cancer patients.

Multicenter cohort study on the survival time of cancer patients dying at home or in a hospital: Does place matter?

BACKGROUND: Although the place of death has a great influence on the quality of death and dying for cancer patients, whether the survival time differs according to the place of death is unclear. The primary aim of this study was to explore potential differences in the survival time of cancer patients dying at home or in a hospital. METHODS: This multicenter, prospective cohort study was conducted in Japan from September 2012 through April 2014 and involved 58 specialist palliative care services. RESULTS: Among the 2426 patients recruited, 2069 patients were analyzed for this study: 1582 receiving hospital-based palliative care and 487 receiving home-based palliative care. A total of 1607 patients actually died in a hospital, and 462 patients died at home. The survival of patients who died at home was significantly longer than the survival of patients who died in a hospital in the days' prognosis group (estimated median survival time, 13 days [95% confidence interval (CI), 10.3-15.7 days] vs 9 days [95% CI, 8.0-10.0 days]; P = .006) and in the weeks' prognosis group (36 days [95% CI, 29.9-42.1 days] vs 29 days [95% CI, 26.5-31.5 days]; P = .007) as defined by Prognosis in Palliative Care Study predictor model A. No significant difference was identified in the months' prognosis group. Cox proportional hazards analysis revealed that the place of death had a significant influence on the survival time in both unadjusted (hazard ratio [HR], 0.86; 95% CI, 0.78-0.96; P < .01) and adjusted models (HR, 0.87; 95% CI, 0.77-0.97; P = .01). CONCLUSIONS: In comparison with cancer patients who died in a hospital, cancer patients who died at home had similar or longer survival. Cancer 2016;122:1453-1460. © 2016 American Cancer Society.

Comparison of survival times of advanced cancer patients with palliative care at home and in hospital.

OBJECTIVES: One primary concern about receiving care at home is that survival might be shortened because the quality and quantity of treatment provided at home will be inferior to that given in the hospital. Although our previous study demonstrated a longer survival of those with home-based palliative care (PC), it lacked adjustment for some potential confounders including symptoms and treatments during the stay. We aimed to compare the survival times among advanced cancer patients receiving home-based and hospital-based PC with adjusting for symptoms and treatments. METHOD: We compared survival time of participants who enrolled two multicenter, prospective cohort studies of advanced cancer patients at 45-home-based PC services between July 2017 and December 2017, and at 23-hospital-based PC services between January 2017 and December 2017. We analyzed with stratification by the estimated survival of Days, Weeks, and Months, which were defined by modified Prognosis in Palliative care Study predictor models-A. We conducted a Cox regression analysis with adjusting for potential confounders including symptoms and treatments during the stay. RESULTS: A total of 2,998 patients were enrolled in both studies and 2,878 patients were analyzed; 988 patients receiving home-based PC and 1,890 receiving hospital-based PC. The survival time of patients receiving home-based PC was significantly longer than that of patients receiving hospital-based PC for the Days Prognosis (estimated median survival time: 10 days [95% CI 8.1-11.8] vs. 9 days [95% CI 8.3-10.4], p = 0.157), the Weeks prognosis (32 days [95% CI 28.9-35.4] vs. 22 days [95% CI 20.3-22.9], p < 0.001), and the Months Prognosis, (65 days [95% CI 58.2-73.2] vs. 32 days [95% CI 28.9-35.4], p < 0.001). CONCLUSION: In this cohort of advanced cancer patients with a Weeks or Months prognosis, those receiving home-based PC survived longer than those receiving hospital-based PC after adjusting for symptoms and treatments.

Unresolved Palliative Care Needs of Elderly Non-Cancer Patients at Home: A Multicenter Prospective Study.

INTRODUCTION/OBJECTIVES: There is growing consensus on the benefits of initiating palliative care early in the disease trajectory; however, palliative care needs for non-cancer patients remain to be elucidated. We investigated the trajectory of unresolved palliative care needs of non-cancer patients at home and explored associated factors. METHODS: We conducted a multicenter prospective cohort study of elderly non-cancer patients at home in Japan between Jan 2020 and Dec 2020. Physicians assessed their palliative care needs using the Integrated Palliative Care Outcome Scale (IPOS). Unresolved palliative care needs were defined as IPOS symptoms above 2 (moderate). RESULTS: In total, 785 patients were enrolled. The most frequent unresolved palliative care needs at enrollment were poor mobility (n = 438, 55.8%), followed by weakness/lack of energy (n = 181, 23.1%) and poor appetite (n = 160, 20.4%). Multivariate logistic regression analysis revealed that female and musculoskeletal disease were significantly positively associated with pain at starting home visits (OR = 1.89, P = .015; OR = 2.69, P = .005). In addition, neurological diseases were significantly positively associated with constipation and poor mobility 3 months after starting home visits (OR = 3.75, P = .047; OR = 3.04, P = .009). CONCLUSIONS: The order of the prevalence of unresolved palliative care needs may remain relatively stable over time, even for those receiving home-based palliative care services. We identified several specific diseases and conditions that were significantly associated with unresolved palliative care needs.

Revision of Pharmacological Treatment Recommendations for Cancer Pain: Clinical Guidelines from the Japanese Society of Palliative Medicine.

Background: Pain is one of the most common symptoms in cancer patients. The Japanese Society for Palliative Medicine (JSPM) first published its clinical guidelines for the management of cancer pain in 2010. Since then, more research on cancer pain management has been reported, and new drugs have become available in Japan. Thus, the JSPM has now revised the clinical guidelines using a validated methodology. Methods: This guideline was developed through a systematic review, discussion, and the Delphi method, following a formal guideline development process. Results: Thirty-five recommendations were created: 19 for the pharmacological management of cancer pain, 6 for the management of opioid-induced adverse effects, and 10 for pharmacological treatment procedures. Due to the lack of evidence that directly addressed our clinical questions, most of the recommendations had to be based on consensus among committee members and other guidelines. Discussion: It is critical to continue to build high-quality evidence in cancer pain management, and revise these guidelines accordingly.

Comparison of the prevalence and associated factors of hyperactive delirium in advanced cancer patients between inpatient palliative care and palliative home care.

BACKGROUND: Hyperactive delirium is known to increase family distress and the burden on health care providers. We compared the prevalence and associated factors of agitated delirium in advanced cancer patients between inpatient palliative care and palliative home care on admission and at 3 days before death. METHODS: This was a post hoc exploratory analysis of two multicenter, prospective cohort studies of advanced cancer patients, which were performed at 23 palliative care units (PCUs) between Jan and Dec 2017, and on 45 palliative home care services between July and Dec 2017. RESULTS: In total, 2998 patients were enrolled and 2829 were analyzed in this study: 1883 patients in PCUs and 947 patients in palliative home care. The prevalence of agitated delirium between PCUs and palliative home care was 5.2% (95% CI: 4.2% - 6.3%) vs. 1.4% (0.7% - 2.3%) on admission (p < 0.001) and 7.6% (6.4% - 8.9%) vs. 5.4% (4.0% - 7.0%) 3 days before death (p < 0.001). However, multivariate logistic regression analysis revealed that the place of care was not significantly associated with the prevalence of agitated delirium at 3 days before death after adjusting for prognostic factors, physical risk factors, and symptoms. CONCLUSIONS: There was no significant difference in the prevalence of agitated delirium at 3 days before death between inpatient palliative care and palliative home care after adjusting for the patient background, prognostic factors, symptoms, and treatment.

Multicenter prospective study on efficacy and safety of octreotide for inoperable malignant bowel obstruction.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of octreotide for malignant bowel obstruction in a multicenter study. METHODS: Terminally ill patients diagnosed with inoperable malignant bowel obstruction were treated with octreotide 300 microg/day. The primary endpoint was the overall improvement rate of subjective abdominal symptoms. The degrees of nausea, vomiting, abdominal pain, distension, anorexia, fatigue, thirst and overall quality of life were evaluated by the self-rating scores selected from the MD Anderson Symptoms Inventory and Kurihara's Face Scale. RESULTS: Forty-nine patients were enrolled in the study, and 46 patients received study treatment, including 17 gastric, 13 colorectal, 7 ovarian and other cancers. The median survival time was 25 days. The number of vomiting episodes significantly correlated with the MD Anderson Symptoms Inventory nausea and vomiting scores (P< 0.001) before octreotide treatment. Of 43 patients evaluable for efficacy, the scores of all the MD Anderson Symptoms Inventory items except abdominal pain and the number of vomiting episodes improved during the first 4 days of octreotide treatment (P< 0.0062). The MD Anderson Symptoms Inventory scores were decreased in 59-72% of patients, and overall quality-of-life scores improved in 56% of patients. No serious adverse events were observed. CONCLUSIONS: The high improvement rate in abdominal symptoms suggested the efficacy of octreotide in terminally ill patients with malignant bowel obstruction.

The Principles of Revised Clinical Guidelines about Palliative Sedation Therapy of the Japanese Society for Palliative Medicine.

Background: When the suffering of a terminally ill patient is intolerable and refractory, sedatives are sometimes used for symptom relief. Objective: To describe the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Design: Consensus methods using the Delphi technique were used. Results: The main principles of the guidelines that were newly defined or developed are as follows: (1) palliative sedation was defined as "administration of sedatives for the purpose of alleviating refractory suffering" (excluding the aim of reducing patient consciousness); (2) palliative sedation was classified according to the method of administration of sedatives: respite sedation versus continuous sedation (including (continuous) proportional sedation and continuous deep sedation); (3) a description of state-of-the-art recommended treatments for difficult symptoms such as delirium, dyspnea, and pain before the symptom was determined as refractory was included; (4) the principle of proportionality was newly defined from an ethical point of view; and (5) families' consent was regarded as being desirable (mandatory in the previous version). Conclusions: We described the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Further consensus building is necessary.

Radiological imaging change in a malignant bowel obstruction patient treated with octreotide.

INTRODUCTION: Malignant bowel obstruction (MBO) is a complication in advanced cancer patients with abdominal and pelvic malignancy. Recent research has established the efficacy of octreotide for MBO-related symptom relief. The mechanism that octreotide increases water absorption in case of MBO has not been demonstrated except for experimental animal and normal human model. CASE REPORT: We present a 60-year-old man with pancreatic cancer and MBO treated with octreotide. Radiological imaging showed the disappearance of large-volume fluid retention in the small intestine with alleviating vomiting within 2 days. This radiological change might result from the effect of octreotide increasing water absorption in intestine tract.

Japanese physicians' experiences of terminally ill patients voluntarily stopping eating and drinking: a national survey.

OBJECTIVES: Voluntarily stopping eating and drinking (VSED) could be regarded as a patients' own non-treatment decision that hastens death, which involves patients voluntarily forgoing food and liquid until death. The aims of this study were to investigate the experience of home hospice physicians and palliative care specialists who care for patients during VSED in Japan, and their opinions on continuous deep sedation (CDS) as a means to relieve patient symptoms during VSED. METHODS: 219 home hospice physicians and 695 palliative care specialists across Japan were surveyed by mail questionnaire in 2016. RESULTS: A total of 571 (62%) responses were analysed. A total of 185 (32%) had experience of patients who selected VSED. In response to questions about CDS to provide relief to patients during VSED, the number of physicians who replied that CDS was acceptable was 88 (15%). CONCLUSIONS: In Japan, 32% of physicians surveyed replied that they had experience of caring for patients during VSED in a clinical setting and 15% considered CDS acceptable.

Clinical Guidelines for Management of Gastrointestinal Symptoms in Cancer Patients: The Japanese Society of Palliative Medicine Recommendations.

Background: Gastrointestinal symptoms, including nausea, vomiting, bowel obstruction, ascites, constipation, and anorexia, are common and often refractory in advanced cancer patients. The palliation of gastrointestinal symptoms is important in improving the quality of life of cancer patients, as well as that of their families and caregivers. Currently published clinical guidelines for the management of gastrointestinal symptoms in cancer patients do not comprehensively cover the topics or are not based on a formal process for the development of clinical guidelines. Methods: The Japanese Society for Palliative Medicine (JSPM) developed comprehensive clinical guidelines for the management of gastrointestinal symptoms in cancer patients after a formal guideline development process. Results: This article summarizes the recommendations along with their rationale and a short summary of the development process of the JSPM gastrointestinal symptom management guidelines. We established 31 recommendations, all of which are based on the best available evidence and agreement of expert taskforce members. Discussion: Future clinical studies and continuous guideline updates are required to improve gastrointestinal symptom management in cancer patients.

Terminal delirium: recommendations from bereaved families' experiences.

Although delirium is a common complication in terminally ill cancer patients and can cause considerable distress for family members, little is known about effective care strategies for terminal delirium. The primary aims of this study were 1) to clarify the distress levels of bereaved families and their perceived necessity of care; and 2) to explore the association between these levels and family-reported professional care practice, family-reported patient behavior, and their interpretation of the causes of delirium. A multicenter questionnaire survey was conducted on 560 bereaved family members of cancer patients who developed delirium during their final two weeks in eight certified palliative care units across Japan. We obtained 402 effective responses (response rate, 72%) and, as 160 families denied delirium episodes, 242 responses were analyzed. The bereaved family members reported that they were very distressed (32%) and distressed (22%) about the experience of terminal delirium. On the other hand, 5.8% reported that considerable or much improvement was necessary, and 31% reported some improvement was necessary in the professional care they had received. More than half of the respondents had ambivalent wishes, guilt and self-blame, and worries about staying with the patient. One-fourth to one-third reported that they felt a burden concerning proxy judgments, burden to others, acceptance, and helplessness. High-level emotional distress and family-perceived necessity of improvement were associated with a younger family age; male gender; their experience of agitation and incoherent speech; their interpretation of the causes of delirium as pain/physical discomfort, medication effects, or mental weakness/death anxiety; and their perception that medical staff were not present with the family, not respecting the patient's subjective world, not explaining the expected course with daily changes, and not relieving family care burden. In terminal delirium, a considerable number of families experienced high levels of emotional distress and felt some need for improvement of the specialized palliative care service. Control of agitation symptoms with careful consideration of ambivalent family wishes, providing information about the pathology of delirium, being present with the family, respecting the patient's subjective world, explaining the expected course with daily changes, and relieving family care burden can be useful care strategies.

[Gabapentin mitigates neuropathic pain in cancer patients--a case report].

A 64-year-old male underwent low anterior resection of the rectum for rectal cancer. Five years later, he suffered neuropathic cancer pain on the left-posterior surface of his thigh caused by sacral invasion of the recurrence site. His neuropathic pain was not sufficiently responsive to the combination therapy of opioids, non-steroidal antiinflammatory drugs (NSAIDs), continuous infusion of subcutaneous ketamine and oral mexiletine. Gabapentin, which has been suggested as an adjuvant analgesic for neuropathic pain introduced orally, rapidly and significantly alleviated his pain and we could subsequently dispense with ketamine and mexiletine. No adverse effect was seen during this treatment. The present case indicates that gabapentin would be one of the most effective adjuvant analgesics for neuropathic cancer pain.

C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative care.

BACKGROUND: The association between C-reactive protein (CRP) level, symptoms, and activities of daily living (ADL) in advanced cancer patients is unclear. METHODS: Secondary data analysis of a multicenter prospective cohort study consisted of 2426 advanced cancer patients referred to palliative care settings was conducted to examine the cross-sectional relationships between CRP level, symptoms, and ADL disabilities. Laboratory data, symptoms, ADL, and manual muscle testing (MMT) results were obtained at baseline. Participants were divided into four groups: low (CRP < 1 mg/dl), moderate (1 = < CRP <5 mg/dl), high (5 = < CRP < 10 mg/dl), and very high CRP (10 mg/dl = < CRP). The proportions of eight symptoms, five ADL disabilities, and three categories of MMT according to the CRP groups were tested by chi-square tests. Multiple-adjusted odd ratios (ORs) were calculated by using ordinal logistic regression after adjustment for age, gender, site of primary cancer, metastatic disease, performance status, chemotherapy, and setting of care. RESULTS: A total of 1702 patients were analysed. Positive rates of symptoms and ADL disabilities increased with increasing CRP level. In the very high-CRP group, rates of positivity for anorexia, fatigue, and weight loss were 89.8%, 81.0%, and 79.2%, respectively, and over 70% of patients received assistance for bathing, dressing, going to the toilet, and transfer. The grade of MMT also deteriorated with increasing CRP level. Adjusted ORs for the accumulated symptoms significantly increased with increasing CRP level in the moderate-CRP, high-CRP, and very high-CRP groups [1.6 (95% confidence interval 1.2-2.0), P < 0.001; 2.5 (1.9-3.2), P < 0.001; 3.5 (2.7-4.6), P < 0.001, respectively]. Adjusted ORs for the accumulated ADL disabilities significantly increased in the very high-CRP groups [2.1 (1.5-2.9), P < 0.001]. CONCLUSIONS: Associations between CRP level, symptoms, and ADL were observed in advanced cancer patients receiving palliative care.

[Efficacy of controlled-release oxycodone for dyspnea in cancer patients--three case series].

Dyspnea is a common symptom in patients with advanced cancer. Systemic morphine administration has been reported as an effective pharmacological treatment to control dyspnea. However, there have been few reports on similar effects of alternative opioids except for morphine. To evaluate the effect of controlled-release oxycodone on the relief of dyspnea, we investigated three cases with opioid substitution from subcutaneous morphine to oral oxycodone. In all cases, both opioids provided equivalent effects for the palliation of cancer dyspnea with no significant adverse effects. Future studies in the appropriate clinical designs will be needed to confirm our findings.

[Olanzapine use in cancer patients for refractory vomiting].

Recent investigations suggest the efficacy of olanzapine in cancer patients with intractable vomiting or chemotherapy-induced nausea. Olanzapine,indicated for schizophrenia in Japan, has an affinity for multiple neurotransmitter receptors including dopaminergic, serotonergic, histaminergic, adrenergic and muscarinic receptors. This pharmacological activity thus has a potential role in the treatment of nausea and vomiting. In the present study, olanzapine was given to five cancer patients with refractory vomiting to standard medications. In 3 cases, olanzapine resolved vomiting completely and also improved anorexia, In 2 cases, vomiting was controlled for a limited period. No adverse effect was observed. These results suggest olanzapine is a useful agent for the management of both vomiting and anorexia.

[The opioid combination of transdermal fentanyl and sustained release morphine for refractory cancer pain--a case report].

Transdermal fentanyl (TDF) has been increasingly administered for the management of cancer pain. Occasionally, some patients fail to obtain poor analgesic effects with its dose escalation. We discuss a case of a 44-year-old male diagnosed with lung cancer with back pain caused by bone metastasis. He was administered a TDF of 75 microg/hr with good pain relief on admission. With time, the dose escalation to 300 microg/hr induced neuroexcitatory adverse effects without pain improvement. The conversion to 150 microg/hr TDF and sustained-release oral morphine 360 mg/day provided effective pain control. This clinical phenomenon demonstrated a possible association with the development of opioid tolerance. Although several experimental approaches regarding partial opioid substitution or combining different opioids for better pain control were suggested, the basic studies of opioid tolerance do not justify conclusions. In this case, partial opioid rotation and opioid combination were beneficial approaches to pain management.

Why people accept opioids: role of general attitudes toward drugs, experience as a bereaved family, information from medical professionals, and personal beliefs regarding a good death.

CONTEXT: Many surveys have evaluated patient-related barriers to pain management. OBJECTIVES: To explore associations between a preference for opioids and general attitudes toward drugs, the experience and information received as a bereaved family, and beliefs regarding a good death. METHODS: A cross-sectional survey, performed in 2010, of bereaved families of patients with cancer in palliative care units across Japan. Questionnaires were sent to 997 families. RESULTS: A total of 66% of families responded. Of these, 224 responses were excluded because the family declined to participate in the study (n = 38), the patient was not receiving any opioid analgesics, and there were missing data (n = 164), or data were missing for the primary end points (n = 22). Thus, 432 responses were finally analyzed (43%). In total, 26%, 41%, and 31% of family members stated that they strongly want to receive, want to receive, or slightly want to receive opioids if needed in the future, respectively. Determinants associated with a preference for receiving opioid treatment were the following: a general appreciation of the drugs (P = 0.005), witnessing an improvement in the patient's quality of life as a result of pain relief (P = 0.003), information provided by medical professionals that the opioid could be discontinued if side effects developed (P = 0.042), and the belief that a good death was one that was free from pain and physical distress (P < 0.001). CONCLUSION: More than 90% of bereaved families whose relatives were treated with opioid analgesics reported a preference to receive opioid analgesics for the treatment of cancer pain, if necessary, in the future.