The Effects of Bereavement Time on the Relationship Between Coping Strategies and Psychological Distress.

The purpose of this study was to investigate the relationship between bereaved individuals' coping patterns, mental health, and time post-loss. A questionnaire using the Coping with Bereavement Scale (CBS) and the Kessler Psychological Distress Scale (K6) was completed by 173 family members of individuals who died from cancer between August 2013 and March 2016. Confirmatory factor analysis revealed a three-factor solution for the CBS comprised of "life orientation," "avoidance," and "retaining ties" with the deceased. Scores on retaining ties were significantly but weakly correlated with K6 scores; however, the intensity of this relationship increased with more time post-bereavement, and individuals who retained strong ties with the deceased for two years or more demonstrated poorer mental health. Although retaining ties with the deceased might be an adaptive psychological process following bereavement, in this study, long-term persistence with that coping strategy was associated with greater overall psychological distress. Further research is needed to identify optimal coping methods to address evolving needs during the bereavement process.

Bereavement risk assessment of family caregivers of patients with cancer: Japanese version of the Bereavement Risk Assessment Tool.

OBJECTIVES: The Bereavement Risk Assessment Tool (BRAT) seems to be useful in identifying those who are likely to suffer from the more severe consequences of bereavement. To date, however, only a few studies have examined bereavement risk using the BRAT. This study investigated bereavement risk in family caregivers of patients with cancer using the Japanese version of the Bereavement Risk Assessment Tool (BRAT-J). We also investigated the relationship of bereavement risk with psychological distress and resilience among caregivers to determine the validity of the BRAT-J. METHODS: We conducted family psychoeducation in the palliative care unit of Tohoku University Hospital with participants who were recruited in this study. Among the participants, 50 family caregivers provided their written informed consent and were included in this study. Participants were assessed using the BRAT-J and completed the Japanese version of the Kessler Psychological Distress Scale (K6) and the Tachikawa Resilience Scale (TRS). RESULTS: According to the BRAT-J, five individuals (10%) were in the high category of bereavement risk (level 4 or 5). We also found that family caregivers of patients experienced many different pressures, such as facing the unknown; their own work; and insufficient financial, practical, or physical resources. These issues are associated with various mental problems. Additionally, the level of bereavement risk was significantly correlated with K6 scores (ρ = 0.30, p = 0.032), and the TRS score (ρ = -0.44, p = 0.001). These correlations confirmed previous findings and that the BRAT-J can be an efficient screening tool for the bereavement risk of family caregivers of patients with cancer. SIGNIFICANCE OF RESULTS: It appears that the BRAT-J is useful in predicting the likelihood of difficulties or complications in bereavement for family caregivers and could help to provide support with these issues when needed.

Indications and practice of artificial hydration for terminally ill cancer patients.

PURPOSE OF REVIEW: To update medical professionals on the role of artificial hydration in terminally ill cancer patients and to highlight recent research. RECENT FINDINGS: First, we explain dehydration-related symptoms such as sensation of thirst, fatigue, and delirium. A multicenter, double-blinded, placebo-controlled randomized trial showed that artificial hydration did not improve dehydration symptoms, quality of life, or survival in terminally ill cancer patients. Then we explain overhydration-related symptoms such as bronchial secretion, pleural effusion, nausea/vomiting, ascites, and peripheral edema.The establishment of clinical guidelines can contribute to patient well-being by clarifying the best practice recommended from empirical evidence and expert experience available. Among them, we summarize a Japanese guideline for artificial hydration therapy for terminally ill cancer patients, which is evidence based, and address specific clinical questions. SUMMARY: The determinants of the quality of life, dying, and death vary among individuals, and individuality is essential to define what is important for each patient. Clinicians need to make a decision based on the perceived benefits and harms of artificial hydration therapy in individual patient circumstances. Further researches with appropriately powered studies are required to determine which subgroups would benefit from artificial hydration therapy. VIDEO ABSTRACT: http://links.lww.com/COSPC/A6

[Pain management in cancer patients].

Cancer pain management is expected to become more important because of the growing number of cancer patients in the years to come. To improve cancer pain relief requires understanding and adequate application of the WHO three-step analgesic ladder. Selective cox-2 inhibitors have efficacy in decreasing side effects. Tramadol and a new type of transdermal fentanyl patch that provides 24-hour sustained release of fentanyl is commercially available to alleviate pain. New anti-seizure drugs such as Gabapentin and Pregabalin can be used for neuropathic pain and cancer pain as analgesic adjuvant drugs. They allow simple use than with palliative drugs so far. Palliation of cancer pain requires a multi-discipline approach for intensive management of symptoms.

Treatment efficacy of neural blockade in specialized palliative care services in Japan: a multicenter audit survey.

More than 85% of cancer-related pain is pharmacologically controllable, but some patients require interventional treatments. Although audit assessment of these interventions is of importance to clarify the types of patients likely to receive benefits, there have been no multicenter studies in Japan. The primary aims of this study were (1) to clarify the frequency of neural blockade in certified palliative care units and palliative care teams, (2) determine the efficacy of interventions, and (3) explore the predictors of successful or unsuccessful intervention. All patients who received neural blockade were consecutively recruited from seven certified palliative care units and five hospital palliative care teams in Japan. Primary responsible physicians reported pain intensity on the Support Team Assessment Schedule, performance status, communication levels on the Communication Capacity Scale, presence or absence of delirium, opioid consumption, and adverse effects before and one week after the procedure on the basis of retrospective chart review. A total of 162 interventions in 136 patients were obtained, comprising 3.8% of all patients receiving specialized palliative care services during the study period. Common procedures were epidural nerve block with local anesthetic and/or opioids (n = 84), neurolytic sympathetic plexus block (n = 24), and intrathecal nerve block with phenol (n = 21). There were significant differences in the frequency of neural blockade between palliative care units and palliative care teams (3.1% vs. 4.6%, respectively, P = 0.018), and between institutions whose leading physicians are anesthesiologists or have other specialties (4.8% vs. 1.5%, respectively, P < 0.001). Pain intensity measured on the Support Team Assessment Schedule (2.9 +/- 0.8 to 1.7 +/- 0.9, P < 0.001), performance status (2.7 +/- 1.0 to 2.4 +/- 1.0, P < 0.001), and opioid consumption (248 +/- 348 to 186 +/- 288 mg morphine equivalent/day, P < 0.001) were significantly improved after interventions. There was a tendency toward improvement in the communication level measured on the Communication Capacity Scale. There was no significant improvement in the prevalence of delirium, but six patients (32%) recovered from delirium after interventions. Adverse effects occurred in 9.2%, but all were predictable or transient. No fatal complications were reported. Pain intensity was significantly more improved in patients who survived 28 days or longer than others (P = 0.002). There were no significant correlations of changes in pain intensity with the performance status or previous opioid consumption. In conclusion, neural blockade was performed in 3.8% of cancer patients who received specialized palliative care services in Japan. Neural blockade could contribute to the improvement of pain intensity, performance service status, and opioid consumption without unpredictable serious side effects.

Perceptions of specialized inpatient palliative care: a population-based survey in Japan.

This study aimed to clarify and compare the awareness and perceptions of the specialized inpatient palliative care service. A cross-sectional questionnaire survey was performed on the general population selected by stratified two-stage random sampling (n=2,548) and bereaved families who actually received specialized inpatient palliative care at 12 palliative care units (PCUs) in Japan (n=513). The respondents reported their awareness and perceptions of PCUs. Thirty-eight percent of the general population answered that they had "considerable" or "moderate" knowledge of PCUs, but 24% answered that they had "no" knowledge. Bereaved families who received PCU care (PCU-bereaved families) were likely to have better perceptions of PCUs than the general population: "alleviates pain" (68% of the general population and 87% of PCU-bereaved families agreed), "provides care for families" (67% and 86%, respectively), and "provides compassionate care" (67% and 87%, respectively). Both groups, however, expressed concerns about PCUs: "a place where people only wait to die" (30% and 40%, respectively) and "shortens the patient's life" (8% and 17%, respectively). These perceptions were associated with overall satisfaction with received care, and differed among the 12 PCUs. In conclusion, public awareness of PCUs was insufficient in Japan. Although PCU-bereaved families were generally likely to have better perceptions of PCUs than the general population, both groups shared concerns that a PCU was a place where people only wait to die. To facilitate appropriate use of specialized palliative care services, more efforts to inform the general population about the actual palliative care system are needed. In addition, the role of PCUs might be reconsidered in terms of the continuum of cancer care.

Survival prediction of patients with advanced cancer: the predictive accuracy of the model based on biological markers.

To determine whether the addition of biological markers to performance status (PS) and physical symptoms would improve survival prediction among patients with advanced cancer, we developed two prediction models with a scoring system based on 294 consecutive patients with advanced cancer (training set), and then tested its validity on another 93 patients (testing set). We assessed the predictive accuracy of the models using receiver-operating characteristic analysis. Albumin (ALB), lactate dehydrogenase (LDH), and lymphocyte percentage (Lymp%) were significantly and independently associated with survival length. For prediction of 60-day survival, the predictive accuracy of Model 2, based on the above biological markers in addition to PS and symptoms, was significantly better than that of Model 1, based on PS and symptoms alone (area under the curve [AUC] for Model 2, 0.80+/-0.03; AUC for Model 1, 0.69+/-0.04; P<0.001). Addition of ALB, LDH, and Lymp% to PS and physical symptoms improved prediction accuracy, especially for longer survival.

Knowledge and beliefs about end-of-life care and the effects of specialized palliative care: a population-based survey in Japan.

To clarify the knowledge and beliefs of the Japanese general population related to legal options, pain medications, communication with physicians, and hydration/nutrition in end-of-life care, and to explore the associations between end-of-life care they had experienced and these beliefs, a questionnaire survey was conducted on two target populations: 5000 general population subjects and 866 bereaved family members of cancer patents who died in 12 palliative care units in Japan. The respondents were requested to report the legal knowledge about end-of-life options, pain-related beliefs, communication-related beliefs, and hydration/nutrition-related beliefs, and their experiences with end-of-life care. A total of 3061 responses were analyzed (effective response rate, 54%). The respondents were classified into six groups: no bereavement experience (n = 949), those who had lost family members within the past 10 years from noncancer diseases at institutions (n = 673), those who lost family members from noncancer disease at home (n = 264), those who lost family members from cancer at institutions other than palliative care units (n = 525), those who lost family members from cancer at home (n = 86), and those who lost family members from cancer at palliative care units (n = 548). Across groups, 32-45% and 50-63% of the respondents stated that treatment withdrawal and double effect act were legal, respectively. Between 34% and 44% believed that cancer pain is not sufficiently relieved, 27-38% believed that opioids shorten life, and 24-33% believed that opioids cause addiction. Communication-related beliefs potentially resulting in barriers to satisfactory end-of-life discussion were identified in 31-40% ("physicians are generally poor at communicating bad news") and in 14-25% ("physicians are not comfortable discussing death"). The bereaved family members of the patients who died in palliative care units were significantly more likely than the other groups to believe that cancer pain is sufficiently relieved, and significantly less likely to believe that opioids shorten life, that opioids cause addiction, that physicians are generally poor at communicating bad news, and that physicians are uncomfortable discussing death. Between 33% and 50% of the respondents, including families from palliative care units, believed "artificial hydration should be continued as the minimum standard until death," while 15-31% agreed that "artificial hydration relieves patient symptoms." A significant proportion of the Japanese general population has beliefs about legal options, pain medications, and communication with physicians that potentially result in barriers to quality end-of-life care. As their experiences in specialized palliative care significantly influenced their belief, systematic efforts to spread quality palliative care activity are of value to lessen these barriers and achieve quality end-of-life care.

Ethical validity of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan.

Although palliative sedation therapy is often required in terminally ill cancer patients to achieve acceptable symptom relief, empirical data supporting the ethical validity of this approach are lacking. The primary aim of this study was to systematically investigate whether empirical evidence supports the ethical validity of sedation. This was a multicenter, prospective, observational study, which was conducted by 21 specialized palliative care units in Japan. One-hundred two consecutive adult cancer patients who received continuous deep sedation were enrolled. Continuous deep sedation was defined as the continuous use of sedative medications to relieve intolerable and refractory distress by achieving almost or complete unconsciousness until death. Prior to the study, we conceptualized the ethical validity of sedation from the viewpoints of physicians' intent, proportionality, and autonomy. Sedation was performed mainly with midazolam and phenobarbital. The initial doses of midazolam and phenobarbital were 1.5 mg/hour and 20 mg/hour, respectively. Main administration routes were continuous subcutaneous infusion and continuous intravenous infusion, and no rapid intravenous injection was reported. Of 59 patients who received artificial hydration or could intake adequate fluids/foods orally before sedation, 63% received artificial hydration therapy after sedation, and in the remaining patients, artificial hydration was withheld or withdrawn due to fluid retention symptoms and/or patient wishes. Of 66 patients who were able to verbally express themselves, 95% explicitly stated that symptoms were intolerable. The etiologies of the symptoms requiring sedation were primarily related to the progression of the underlying malignancy, such as cancer cachexia and organ failure, and standard palliative treatments had failed: steroids in 68% of patients with fatigue, opioids in 95% of patients with dyspnea, antisecretion medications in 75% of patients with bronchial secretion, antipsychotic medications in 74% of patients with delirium, and opioids in all patients with pain. On the basis of the Palliative Prognostic Index, 94% of the patients were predicted to die within 3 weeks. Before sedation, 67% of the patients expressed explicit wishes for sedation. In the remaining 34 patients, previous wishes for sedation were noted in 4 patients, and in the other 30 patients, the families were involved in the decision-making process. The chief reason for patient non-involvement in the decision making was cognitive impairment. These data indicate that palliative sedation therapy performed in specialized palliative care units in Japan generally followed the principles of double effect, proportionality, and autonomy.

Efficacy and safety of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan.

Although palliative sedation therapy is often required in terminally ill cancer patients, its efficacy and safety are not sufficiently understood. The primary aims of this multicenter observational study were to 1) explore the efficacy and safety of palliative sedation therapy, and 2) identify the factors contributing to inadequate symptom relief and complications, using a prospective study design, clearly defined measurement methods, and a consecutive sample from 21 specialized palliative care units in Japan. A sample of 102 consecutive adult cancer patients who received continuous deep sedation were enrolled. Physicians prospectively evaluated the intensity of patient symptoms, communication capacity, respiratory rate, and complications related to sedation. Symptoms were measured on the Agitation Distress Scale, the Memorial Delirium Assessment Scale, and the ad hoc symptom severity scale (0 = no symptoms, 1 = mild and tolerable symptoms, 2 = intolerable symptoms for less than 15 minutes in the previous one hour, and 3 = intolerable symptoms continuing for more than 15 minutes in the previous one hour). Inadequate symptom relief was defined as presence of hyperactive delirium (item 9 of the Memorial Delirium Assessment Scale >or=2) or grade 2 or 3 symptom intensity 4 hours after sedation. The degree of communication capacity was measured on the Communication Capacity Scale. Palliative sedation therapy succeeded in symptom alleviation in 83% of the cases. Median time elapsed before patients initially had one continuous hour of deep sedation was 60 minutes, but 49% of the patients awakened once after falling into a deeply sedated state. The percentage of patients who were capable of explicit communication decreased from 40% before sedation to 7.1% 4 hours after sedation, and the mean Communication Capacity Score significantly decreased to the level of 15 points (P < 0.001). The respiratory rates did not significantly decrease after sedation (18 +/- 9.0 to 16 +/- 9.4/min, P = 0.62), but respiratory and/or circulatory suppression (respiratory rate

Late referrals to specialized palliative care service in Japan.

PURPOSE: To clarify the bereaved family's perceptions about the appropriateness of timing when physicians first referred patients to palliative care units, and to identify the factors contributing to family-perceived late referrals. SUBJECTS AND METHODS: A multicenter questionnaire survey was conducted on 630 bereaved family members of cancer patents who were admitted to palliative care units in Japan. A total of 318 responses were analyzed (effective response rate, 62%). RESULTS: Half of the bereaved family members regarded the timing of referrals to palliative care units as late or very late, while less than 5% of families reported early referrals (very late [19%, n = 59], late [30%, n = 96], appropriate [48%, n = 151], early [1.6%, n = 5], and very early [2.2%, n = 7]). Multiple regression analyses revealed that the independent determinants of family-perceived late referrals were: family belief before admission that palliative care shortens the patient's life, insufficient in-advance discussion about preferred end-of-life care between patients/families and physicians, families' insufficient preparation for changes of patient conditions, and hospital admission before referrals. CONCLUSION: In Japan, the timing of referrals to palliative care units was late or very late from the families' perspectives. The independent determinants of family-perceived late referrals were: family misconception about palliative care, inadequate communication with physicians, and families' insufficient preparation for deterioration of patients' conditions. Systematic strategies to overcome these barriers would contribute to providing appropriate palliative care at all stages of cancer.

The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment.

To provide additional pharmacokinetic evidence for the oral-to-parenteral relative potency ratio of 1:2 to 1:3 for chronic morphine use in a palliative care setting, we determined the plasma concentrations of morphine and its major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in hospitalized advanced cancer patients maintained on long-term oral or intravenous morphine. There were significant linear correlations between daily doses of morphine and plasma concentrations (molar base) of morphine, M3G and M6G for both routes of administration. The oral-to-intravenous relative ratios of the regression coefficients were 2.9 for morphine and 1.8 for morphine + M6G. The morphine kinetic variables were not significantly influenced by any hepato-renal biochemical markers. These results support the commonly used oral-to-intravenous relative potency ratio of 1:2 to 1:3 in patients with cancer pain receiving chronic morphine treatment.

[Use of propofol for painful procedures in cancer pain management].

BACKGROUND: Patients with intractable cancer pain often require non-pharmacological analgesic treatment that is accompanied by procedure-related pain. Previous works have shown that propofol infusion in adjunction to regional anesthesia provides appropriate sedation during such painful procedures. However, there are a few reports of its use to reduce procedure-related pain in terminal cancer patients. We report cases of propofol sedation during percutaneous vertebroplasty (PVP) in patients with metastatic vertebral compression fracture. METHODS: Propofol was infused during PVP in eleven cancer patients after obtaining written informed consent. The infusion rate of propofol was adjusted using a target-controlled infusion pump to achieve appropriate sedation levels under monitoring bispectral index of the electroencepharogram. Hepatic and renal functions were evaluated using common serum markers, which were determined using standard hospital laboratory methods. RESULTS: The duration of the procedure was 65.5 +/- 5.5 (mean +/- SD) min. The required infusion rate was 8.66 +/- 1.50 mg.kg-1.hr-1. The interval from the termination of the infusion until emergence was 10.7 +/- 4.2 min. No life-threatening complications or significant changes in liver and renal functions were observed. CONCLUSIONS: Propofol can be used effectively and safely for sedation during PVP in terminal cancer patients.

[The attempt to standardize treatment protocols for cancer-related hypercalcemia: developing a data-based flowchart].

We developed a flowchart for the treatment of cancer-related hypercalcemia based on the review of previous reports. The treatment protocols were standardized in each group of four different ranges of serum calcium concentration (< 12, 12-14, 14-16, < 16 mg/dl). In each Ca range, specific treatment was adjusted according to the clinical evaluation of symptoms and progression of illness of the patients.

[Serum lactate dehydrogenase and CD4+/CD8+ lymphocyte ratio predict survival in terminally ill cancer patients].

Accurate estimation of survival is important for effective palliative medicine of patients with cancer. In most clinical practice, however, the life expectancy has been predicted based on subjective evaluations. The purpose of this study was to find objective biological markers that can contribute to accurate prediction of survival in terminally ill cancer patients. Consecutive terminally ill cancer patients admitted to the Palliative Care Center in Tohoku University hospital from January to May 2001 were approached for this study. Forty-eight blood samples were obtained from 25 patients who provided a written informed consent. Common serum enzyme markers were determined using standard hospital laboratory methods. Cellular immunity status was evaluated by peripheral blood lymphocyte-subset analysis using flow cytometry. Mean patient survival was 33.5 +/- 21.6 (1-80) days. Multiple regression analysis revealed that lactate dehydrogenase (LDH) and the CD4+/CD8+ ratio were significantly associated with survival (r = 0.64, p < 0.0001). Further prospective studies are warranted to validate the usefulness of these determinants for accurate prediction of survival.