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Eating-related distress (ERD) is one type of psychosocial distress among advanced cancer patients and family caregivers. Its alleviation is a key issue in palliative care; however, there is no validated tool for measuring ERD.The purpose of this study was to validate tools for evaluating ERD among patients and family caregivers. The study consisted of a development and validation/retest phase. In the development phase, we made preliminary questionnaires for patients and family caregivers. After face validity and content validity, we performed an exploratory factor analysis and discussed the final adoption of items. In the validation/retest phase, we examined factor validity with an exploratory factor analysis. We calculated Pearson's correlation coefficients between the questionnaire for patients, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cachexia 24 (EORTC QLQ-CAX24) and Pearson's correlation coefficients between the questionnaire for family caregivers and the Caregiver Quality of Life Index-Cancer (CQOLC) for concurrent validity. We calculated Cronbach's alpha coefficients (Cronbach's alpha) and intraclass correlation coefficients (ICCs) for internal consistency and test-retest reliability. We performed the Mann-Whitney U test between the questionnaires and cancer cachexia based on criteria from the international consensus for known-group validity.In the development phase, 162 pairs of patients and family caregivers were asked to participate, and 144 patients and 106 family caregivers responded. In the validation/retest phase, 333 pairs of patients and family caregivers were asked to participate, and 234 patients and 152 family caregivers responded. Overall, 183 patients and 112 family caregivers did the retest. Seven conceptual groups were extracted for the ERD among patients and family caregivers, respectively. Patient factors 1-7 correlated with FAACT ACS (r = -0.63, -0.43, -0.55, -0.40, -0.38, -0.54, -0.38, respectively) and EORTC QLQ-CAX24 (r = 0.58, 0.40, 0.60, 0.49, 0.38, 0.59, 0.42, respectively). Family factors 1-7 correlated with CQOLC (r = -0.34, -0.30, -0.37, -0.37, -0.46, -0.42, -0.40, respectively). The values of Cronbach's alpha and ICC of each factor and all factors of patients ranged from 0.84 to 0.96 and 0.67 to 0.83, respectively. Those of each factor and all factors of family caregivers ranged from 0.84 to 0.96 and 0.63 to 0.84, respectively. The cachexia group of patients had significantly higher scores than the non-cachexia group for each factor and all factors.Newly developed tools for measuring ERD experienced by advanced cancer patients and family caregivers have been validated.

Objective The objective of this survey was to identify areas where doctors have divergent practices in pharmacological treatment for hyperactive delirium in terminally ill patients with cancer. Methods We conducted a survey of Japanese palliative care physicians and liaison psychiatrists. Inquiries were made regarding: (i) choice of drug class in the first-line treatment, (ii) administration methods of the first-line antipsychotic treatment, (iii) starting dose of antipsychotics in the first line treatment and maximum dose of antipsychotics in refractory delirium, and (iv) choice of treatment when the first-line haloperidol treatment failed. Respondents used a five-point Likert scale. Results Regarding choice of drug class in the first-line treatment, more doctors reported that they ‘frequently’ or ‘very frequently’ use antipsychotics only than antipsychotics and benzodiazepine (oral: 73.4 vs. 12.2%; injection: 61.3 vs. 11.6%, respectively). Regarding administration methods of the first-line antipsychotic treatment, the percentage of doctors who reported that they used antipsychotics as needed and around the clock were 55.4 and 68.8% (oral), 49.2 and 45.4% (injection), respectively. There were different opinions on the maximum dose of antipsychotics in refractory delirium. Regarding the choice of treatment when the first-line haloperidol treatment failed, the percentage of doctors who reported that they increased the dose of haloperidol, used haloperidol and benzodiazepines, and switched to chlorpromazine were 47.0, 32.1 and 16.4%, respectively. Conclusions Doctors have divergent practices in administration methods of the first-line antipsychotic treatment, maximum dose of antipsychotics, and choice of treatment when the first-line haloperidol treatment failed. Further studies are needed to determine the optimal treatment.

Background: Patients with life-limiting illnesses frequently experience urinary difficulties, and urinary catheterization is one of the interventions for managing them. However, evidence supporting the effects of urinary catheters on the quality of death (QoD) is lacking in this population. Objectives: To investigate whether urinary catheterization affects QoD in patients with advanced cancer in palliative care units. Design: A secondary analysis of a multicenter, prospective cohort study. Setting/Subjects: The study enrolled consecutive patients with advanced cancer admitted to palliative care units in Japan between January and December 2017. Those who were not catheterized on admission and who died while in a palliative care unit were analyzed. Measurements: QoD was evaluated at death using the Good Death Scale (GDS). Results: Of 885 patients, 297 (33.6%) were catheterized during their palliative care unit stay. Females and patients with a long palliative care unit stay were more likely to be catheterized. In inverse probability-weighted propensity score analysis, patients with urinary catheterization during their palliative care unit stay had higher total GDS scores than those without catheterization (coefficient 0.410, 95% confidence interval 0.068-0.752). In subgroup analyses stratified by sex, age, and length of palliative care unit stay, urinary catheterization was associated with higher total GDS scores in patients younger than 65 years of age and those who died after a palliative care unit stay of 21 days or fewer. Conclusions: This study suggested that urinary catheterization during a palliative care unit stay may have a positive impact on overall QoD in patients with advanced cancer. This study was registered in the UMIN Clinical Trials Registry (UMIN000025457).

Purpose: We investigated the symptoms and prognoses of patients with fungating breast cancer in the palliative care unit setting. Methods: This study was a sub-group analysis of a multicentre, prospective, observational study. Patients admitted to 23 palliative care units in Japan between January and December 2017 were enrolled. Data of patients with breast cancer were extracted. Wecompared demographic characteristics, symptoms, and prognoses by breast cancer skin lesion status. The primary outcome was overall survival. Secondary outcomes included Palliative Prognostic Index (PPI) score, details about skin lesions, and symptom burden. Results:Of 1,896 patients, 131 (6.9%) had breast cancer. In this cohort, 44 (33.6%) patients had skin lesions. Most skin lesions (88%) were on the backand chest. Some skin lesions were associated with skin redness, erosion, necrosis, or fistula. Symptoms included bleeding, exudate, odour, and pain. Twenty-eight patients (63.6%) needed dressing changes and 14 (31.8%) patients experienced bleeding. None died due to bleeding. In the skin lesion group, 32 (72.8%) patients had used opioids equivalent to 38 mg of oral morphine daily, compared to 25 mg in 57 (65.5%) in the non-skin lesion group (p = 0.26). Median PPI scores at hospital admission were 4.5 versus 6.5 (p = 0.08). Median survival was 23 versus 21 days (p = 0.48). Conclusion: Patients with skin lesions had a distinct symptom burden and tended to use a higher dose of opioids. The effect of skin lesions on survival was unclear.

Purpose There is ongoing debate on whether continuous deep sedation (CDS) for psycho-existential suffering is appropriate. We aimed to: 1) to clarify clinical practice of CDS for psycho-existential suffering, and 2) assess its impact on patients’ survival. Methods Advanced cancer patients admitted to 23 palliative care units in 2017 were consecutively enrolled. We compared patients’ characteristics, CDS practices, and survival between those receiving CDS for psycho-existential suffering +/- physical symptoms and only for physical symptoms. Results Of 164 patients analyzed, 14 (8.5%) received CDS for psycho-existential suffering +/- physical symptoms and only one (0.6%) solely for psycho-existential suffering. Patients receiving CDS for psycho-existential suffering, compared with those only for physical symptoms, were likely to have no specific religion (p = 0.025), and desired (78.6 vs. 22.0%, respectively, p p p = 0.037), and lasted for longer (p = 0.029). Dependency, loss of autonomy, and hopelessness were common reasons for psycho-existential suffering that required CDS. The survival time after CDS initiation was longer in patients receiving it for psycho-existential suffering (log-rank, p = 0.021). Conclusion Further studies and debate are warranted to develop feasible treatment strategies for psycho-existential suffering and make the indication and procedure of CDS for psycho-existential sufferingclearer for both international and each culturally-adapted consensus.

Summary: Background & Aims: The prevalence of artificially administered nutrition and hydration (AANH) in different age groups among patients with advanced cancer remains unknown. The present study investigated the current utilization of AANH according to age groups in palliative care units. Methods: This was a secondary analysis of a prospective cohort study. We obtained information on primary nutritional administration routes during the first week of admission and data on the averaged calorie sufficiency rate or total calorie intake on the 7th day of admission. Patients were divided into five age groups (18–39, 40–59, 60–74, 75–89, and 90- years). Among patients receiving AANH, the proportions of higher-calorie AANH were compared between the five age groups. Results: A total of 1453 patients were included. The proportion of patients categorized as receiving nutrition and hydration via the parenteral route was the highest in the 18–39 and 40–59 groups (52.4 and 41.1%, respectively). Among patients receiving AANH (n = 534), the proportions of patients categorized into the

Purpose All five senses (i.e., sight, smell, hearing, taste, and touch) are used to enjoy meals; however, impairments in sensory perception, which are common among cancer patients, seriously impact health and cause eating-related distress. 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 intake and cachexia-related quality of life (QOL). Dietary intake was 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 12-item Functional Assessment of Anorexia/Cachexia Therapy (FAACT) Anorexia/Cachexia Subscale. 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% 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 FAACT Anorexia/Cachexia Subscale scores and dietary intake. Conclusion More severe taste and smell disturbances were associated with poorer dietary intake and cachexia-related QOL. Diagnosing and treating such disturbances may improve dietary intake and cachexia-related QOL, regardless of performance status and cachexia. Additional research is required to establish effective treatment strategies for disturbances in taste and smell.

Parenteral morphine is widely used for dyspnea of imminently dying cancer patients (terminal dyspnea). However, the efficacy of other opioids such as oxycodone remains largely unknown.To explore the efficacy of parenteral oxycodone vs. morphine by continuous infusion over 24 hours in cancer patients with terminal dyspnea.This was a pre-planned subgroup analysis of a multicenter prospective observational study. Inclusion criteria were advanced cancer patients admitted to palliative care units, Eastern Cooperative Oncology Group performance status = 3-4, and a dyspnea intensity ≥2 on the Integrated Palliative care Outcome Scale (IPOS) for which oxycodone or morphine was initiated by continuous infusion. We measured dyspnea IPOS scores over 24 hours.We analyzed 164 patients who received oxycodone (n = 26) and morphine (n = 138) for dyspnea (median survival = 5 days). The mean age was 70 years, 58 patients (35%) had lung cancer, and 97 (59%) had lung metastases. Complete case analysis revealed that mean dyspnea IPOS scores decreased from 3.0 (standard deviation = 0.7) to 1.5 (0.7) in the oxycodone group (difference in means = 1.5; P 0.001), and from 2.9 (0.7) to 1.6 (1.0) in the morphine group (difference in means = 1.3; P 0.001). No significant between-group differences existed in the IPOS scores at 24 hours (P = 0.753). Adverse events were seen in no and 5 patients in the oxycodone and morphine groups, respectively.Parenteral oxycodone may be equally effective and safe as morphine in the treatment of terminal dyspnea in cancer patients. Future randomized controlled trials should confirm the efficacy and safety of opioids other than morphine for terminal dyspnea.

To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer. 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). 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

ObjectivesThe 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).MethodsThis 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).ResultsOne 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 resultsThe 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.

McMurry coupling is one of the most useful and convenient tools for the preparation of π-conjugated molecules. However, for the synthesis of strained macrocycles containing ethynylene linkages, reduction of ethynylene to vinylene linkage sometimes took place. Especially, for the synthesis of macrocyclic π-extended thiophene hexamers using McMurry coupling of dialdehyde 1 composed of three thienylene, two ethynylene, and two formyl groups, reduction of ethynylenes to vinylenes often takes place to produce unique products in a one-pot procedure, depending on very small steric and electronic effects such as reaction temperature, amounts of titanium reagent, and substituents of thiophene hexamers. The attractive structures and functional properties of reduced thiophene hexamers have been determined using X-ray analysis and OFET measurements.

BackgroundWhere patients receive end-of-life care influences their quality of life.ObjectivesTo clarify the effects of staying in a private or shared room in inpatient hospices.DesignA part of a Japanese multicentre survey to evaluate the quality of end-of-life care.Setting/participants779 bereaved families whose relatives who died from cancer in inpatient hospices.MeasurementsThe primary outcome was family-perceived need for improvement in environment-related professional care. Secondary end-points included: family satisfaction, environment-related family perception, and quality of death and dying (Good Death Inventory: GDI).Results574 responded (73.7%). 300 patients were in a private room from admission to discharge, 47 were in a shared room less than 50% of the time, and the remaining 85 were in a shared room 50% or more. There were significant differences in the need for improvement in shared (vs private) rooms, and in favour of private rooms for: ‘privacy was protected’, ‘easy for visitors to visit’, ‘could discuss sensitive issues with medical staff without concern’, and ‘could visit at night.’, as well as ‘living in calm circumstances’ and ‘spending enough time with family’ of the GDI. Contrarily, significant differences were found in favour of shared rooms for: ‘the patient could interact with other patients’. There was no significant difference in family satisfaction and total score of GDI.ConclusionThere are the advantages and disadvantages of spending one’s final days in a private or shared room, and adjusting rooms according to patients and their families’ values is necessary.

A phenyl-substituted macrocyclic π-extended thiophene hexamer 1, composed of four thienylene-ethynylene and two thienylene-vinylene units, has a solid-state structure in which π–π, CH−π, and van de...

A radical cation, generated from an extended π-conjugated thiophene 6-mer composed of four ethynylene-thienylene and two vinylene-thienylene units, was observed to form a stable three-dimensional π-dimer containing 70 π-electrons. The π-dimer prepared in solution was investigated by using magnetic circular dichroism (MCD), ESR spectroscopy, and UV-vis-NIR absorption spectroscopy. Probing the individual NIR absorption bands showed that the MCD signals can be assigned to the pseudo Faraday A term, indicating that the absorption bands are comprised of nearly degenerate electronic transitions. X-ray crystallographic analysis revealed that the π-dimer has a three-dimensional face-to-face and continuous π-conjugated donutlike structure. Analysis of the UV-vis-NIR and ESR spectra of the π-dimer in the solid state confirmed that it possesses the dimer structure. The prediction made by using TD-DFT calculations that the dimer would have a 70 π-electron diatropic nature was confirmed by using solid state 1H NMR spectroscopy.

Background Although patients with advanced cancer often have poor prognostic awareness, the most effective communication approach for improving prognostic awareness is unclear. In addition, the association between prognostic awareness and preferences for future medical treatment remains unexplored. Materials and Methods We performed a prospective observational study of consecutive patients with advanced or post-operative recurrent non-small cell lung cancer whose disease had progressed after first–line chemotherapy, and their caregivers. We evaluated patterns of clinical discussions about incurability, prognostic awareness, and preference for future medical treatment at baseline and 3 months later. Results We obtained 200 valid responses to the questionnaires at baseline and 147 valid responses 3 months later. In addition, 180 caregivers returned valid responses. A total of 54% of patients and 51% of caregivers had accurate awareness at baseline, and 52% of patients had accurate awareness 3 months later. Multiple logistic regression analysis revealed that patients who were informed about incurability in recent and past discussions were significantly more likely to have accurate awareness 3 months later, compared with those who were only informed recently (adjusted odds ratio 5.08; 95% CI, 1.31-19.78; P = .019). Accurate awareness at 3 months was significantly negatively associated with preference for life-prolonging treatment at 3 months after adjusting for covariates (adjusted odds ratio 0.39; 95% CI, 0.17-0.90; P = .028). Conclusion Patients with advanced cancer who had both recent and past discussions about incurability with their oncologists have more accurate prognostic awareness. Improving prognostic awareness could reduce the preference for life-prolonging treatment.

The perspective toward hypoactive delirium in the last days of life could be different among physicians.To clarify the attitudes, beliefs, and opinions of palliative care physicians and liaison psychiatrists toward hypoactive delirium in the last days of life and to explore the association among these factors.A nationwide cross-sectional questionnaire survey was conducted among 1667 physicians who were either certified palliative care specialists or liaison psychiatrists. Physicians' agreement with the appropriateness of pharmacological management (e.g., antipsychotics) (one item), their beliefs (11 items), and their opinions (four items) were measured.787 (47%) physicians responded. 481 (62%) agreed to use of medications for hypoactive delirium in the last days of life, whereas 296 (38.1%) disagreed. More than 95% agreed with "hypoactive delirium at the end of life can be considered as a part of natural dying process." Multivariate analysis identified two belief subscales of "hypoactive delirium at the end of life is a natural dying process" and "antipsychotics are futile and harmful in managing hypoactive delirium" had a significant negative correlation with the use of medications. On the other hand, one belief subscale of "hypoactive delirium can be distressing even if patients' consciousness is impaired" had significant positive correlations with the use of medications.Pharmacological management of hypoactive delirium in the last days of life differs depending on physicians' beliefs. Future research is needed to clarify the efficacy and safety of pharmacological management of hypoactive delirium.

Duloxetine has some effect against cancer neuropathic pain (CNP); however, predictors of duloxetine response are unclear. This study sought to identify predictors of duloxetine response in patients with CNP. Patients (N = 70) with CNP unresponsive to or intolerant of opioid–pregabalin combination therapy, with a brief pain inventory-short form (BPI-SF) Item 5 score (average pain) ≥ 4, and with a total hospital anxiety and depression scale score < 20, were randomized to a duloxetine or a placebo group. Multiple linear regression analysis was conducted to identify predictors of duloxetine response as a secondary analysis with the change in the average pain score on day 10 from day 0 as the dependent variable, and the following five covariates; baseline (day 0) average pain score, baseline opioid dose, continuation/discontinuation of pregabalin, and items 20 and 21 score of the short-form McGill pain questionnaire 2 (SF-MPQ-2) as independent variables. Of the four domains (continuous pain, intermittent pain, neuropathic pain, and affective descriptors) score of SF-MPQ-2 on day 0, significant differences were observed in the neuropathic pain domain (p = 0.040) in change on the average pain between day 10 and day 0 in the duloxetine group. Multiple linear regression analysis revealed that patients with a high score for SF-MPQ-2 Item 21 (tingling pain) on day 0 had a significantly greater change in average pain between day 10 and day 0 (p = 0.046). Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.

Context When discussing end-of-life issues with cancer patients, the addition of reassurance statements is considered helpful. However, patients' preferences for such statements have not been systematically demonstrated. Objectives The objectives of this study were to clarify if phrases with additional reassurance statements would be more preferable to phrases without them and explore variables associated with patients' preferences. Methods In a cross-sectional survey, 412 cancer patients assessed their own preferences for phrases with/without additional statements using a six-point scale (1 = not at all preferable; 6 = very preferable). These included the statements of “hope for the best and prepare for the worst” (“hope/prepare”) when discussing prognosis; symptom palliation when discussing code status; and specific goals, continuity of care, and nonabandonment when discussing hospice referral. We evaluated demographic data and the coping style and conducted multivariate regression analysis. Results Compared with the phrase of life expectancy (i.e., median + typical range) alone [mean (SD), 3.5 (1.2); 95% CI, 3.4–3.6], the phrase with the additional “hope/prepare” statement was more preferable [3.8 (1.4); 3.7–3.9]. Compared with the phrase of do-not-resuscitate alone (3.1(1.3); 3.0–3.3), the phrase with the additional statement of symptom palliation was more preferable [3.9 (1.3); 3.7–4.0]. Compared with the phrase of hospice referral alone [3.4 (1.2); 3.3–3.5], phrases with the addition of a specific goal [3.9 (1.0); 3.8–4.0], specific goal and continuity (4.4(1.0); 4.3–4.5), and specific goal, continuity, and nonabandonment [4.8 (1.2); 4.7–4.9] were more preferable. In multivariate analyses, task-oriented coping was significantly correlated with preferences for phrases including additional reassurance statements. Conclusion Cancer patients systematically preferred reassurance statements. In end-of-life discussions, especially with patients with task-oriented coping, clinicians may provide additional reassurance statements.

Introduction Although various phrases to communicate prognoses based on a certain concept have been proposed, no study has systematically investigated preferences of patients with cancer for actual phrases. We investigated whether phrases with a wider range and additional “hope for the best, and prepare for the worst” (hope/prepare) statement would be more preferable and explored variables associated with patients’ preferences. Materials and Methods In a cross-sectional survey, 412 outpatients with cancer self-assessed their preferences for 13 phrases conveying prognostic information (e.g., phrases with or without median, typical range, and/or best/worst cases, and those with or without a hope/prepare statement) on a 6-point scale (1 = not at all preferable; 6 = very preferable). We evaluated demographic data and the Coping Inventory for Stressful Situations and conducted multivariate regression analysis. Results Regarding phrases with various ranges, the one including the median, typical range, and best/worst cases was more preferable (mean ± SD, 3.8 ± 1.3; 95% confidence interval [CI], 3.6–3.9) than the one with the median and typical range (3.4 ± 1.2; 3.3–3.6) or the one with only the median (3.2 ± 1.3; 3.1–3.3). Concerning the hope/prepare statement, the phrase including the median, typical range, uncertainty, and hope/prepare statement was more preferable (3.8 ± 1.4; 3.7–3.9) than the one without the statement (3.5 ± 1.2; 3.4–3.6). In multivariate analyses, task-oriented coping was significantly correlated with preferences for phrases with explicit information. Conclusion Overall, phrases with a wider range and the hope/prepare statement were preferable to those without them. When patients with cancer ask about prognoses, especially those with task-oriented coping, clinicians may provide explicit information with a wider range and the hope/prepare statement. Implications for Practice Discussing prognoses with patients with advanced cancer is among the most important conversations for clinicians. In this cross-sectional survey to systematically investigate preferences of 412 patients with cancer for phrases conveying prognostic information, phrases with the median, typical range, and best/worst cases and those with the “hope for the best and prepare for the worst” (hope/prepare) statement were the most preferred. When patients with cancer ask about prognoses, clinicians may provide explicit information with a wider range and include the hope/prepare statement.

The benefits of parenteral nutrition and hydration (PNH) in patients with advanced cancer remain unknown. Therefore, we conducted a prospective multicenter cohort study to assess the effects of PNH on survival in patients with malignant bowel obstruction (MBO).The present study was a secondary analysis. Data on primary nutritional administration routes during the first week of admission to palliative care units, i.e., parenteral nutrition and parenteral hydration, were obtained. Data on the averaged calorie sufficiency rate/total calorie intake (75% ≤ or 750 kcal/day ≤ , 50-75% or 500-750 kcal/day, 25-50% or 250-500 kcal/day, and 25% or 250 kcal/day) were also obtained. Participants with MBO were included and divided into two groups: PNH-high (25% ≤ or 250 kcal/day ≤) and PNH-low ( 25% or 250 kcal/day). We performed time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses.Patients were divided into the PNH-high (n = 68) and PNH-low (n = 76) groups. A significant difference was observed in survival rates between the two groups (log-rank P 0.001). Median survival times were 35.5 (95% CI 27-44) and 17.5 (95% CI 13-21) days, respectively. In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the PNH-high group (HR 0.55 (95% CI 0.36-0.83), P = 0.005) than in the PNH-low group.The present results indicated the beneficial effects of PNH for prolonging survival in advanced cancer patients with MBO in palliative care units.

To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer.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).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, p0.001). 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-trend0.001). The most prevalent AE was somnolence (n=15, 18%).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.

Context Previous studies suggest that clinicians' prediction of survival (CPS) may have reduced the accuracy of objective indicators for prognostication in palliative care. Objectives We aimed to examine the accuracy of CPS alone, compared to the original Palliative Prognostic Score (PaP), and five clinical/laboratory variables of the PaP in patients with far advanced cancer. Methods We compared the discriminative accuracy of three prediction models (the PaP-CPS [the score of the categorical CPS of PaP], PaP without CPS [sum of the scores of only the objective variables of PaP], and PaP total score) across 3 settings: inpatient palliative care consultation team, palliative care unit, and home palliative care. We computed the area under receiver operating characteristic curve (AUROC) for 30-day survival and concordance index (C-index) to compare the discriminative accuracy of these three models. Results We included a total of 1534 subjects with median survival of 34.0 days. The AUROC and C-index in the three settings were 0.816–0.896 and 0.732–0.799 for the PaP total score, 0.808–0.884 and 0.713–0.782 for the PaP-CPS, and 0.726–0.815 and 0.672–0.728 for the PaP without CPS, respectively. The PaP total score and PaP-CPS showed similar AUROCs and C-indices across the three settings. The PaP total score had significantly higher AUROCs and C-indices than the PaP without CPS across the three settings. Conclusion Overall, the PaP total score, PaP-CPS, and PaP without CPS showed good discriminative performances. However, the PaP total score and PaP-CPS were significantly more accurate than the PaP without CPS.

The benefits of artificial nutrition and hydration in patients with advanced cancer remain unknown. Therefore, we conducted a prospective study to evaluate effects of enteral nutrition (EN) and parenteral nutrition and hydration (PNH) on survival in palliative care units.This study involved a secondary analysis of a multicenter cohort study. Data of primary nutritional administration routes during the first week after admission (oral intake, enteral tube feeding, parenteral nutrition, parenteral hydration, poor oral intake) were obtained. Data of averaged calorie sufficiency rate/total calorie intake [high (75% ≤ or 750 kcal/day ≤), moderate (50-75% or 500-750 kcal/day), low (25-50% or 250-500 kcal/day), very low (25% or250 kcal/day)] were also obtained. After investigating the implementation of artificial nutrition and hydration, participants were divided into three groups according to the nutritional administration route and calorie sufficiency rate/total calorie intake: EN, PNH, and control. We conducted time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses.Patients were divided into the EN group (n = 730), PNH group (n = 190), and control group (n = 533). Differences in survival rates among the three groups were significant (Log-rank P 0.001). Median survival times were 43.0 (95% CI 40-46), 33.0 (95% CI 29-37), and 15.0 (95% CI 14-16) days, respectively (P 0.001). In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the EN group and PNH groups (HR 0.43 [95% CI 0.37-0.49], P 0.001; and HR 0.52 [95% CI 0.44-0.62], P 0.001, respectively) than in the control group.This study indicated the clinical benefits of EN and PNH for patients with advanced cancer. Nevertheless, managing symptoms to improve oral intake is essential before initiation of PNH, because EN was superior to PNH.

There are few studies on bereaved caregivers' perceptions of physician behavior toward death pronouncement. Although previous research indicates that most caregivers are satisfied with physician behavior toward death pronouncement at home hospices, bereaved caregivers' perceptions of death pronouncement in palliative care units (PCUs) have not been investigated.The aim was to examine bereaved caregivers' perceptions of physician behavior toward death pronouncement in PCUs.This was a cross-sectional questionnaire survey of bereaved caregivers who had lost a family member in a PCU. Measures were based on a previous study to assess bereaved caregivers' evaluations of physician behavior toward death pronouncement.Of 861 questionnaires sent to bereaved caregivers, 480 responses were analyzed. Overall, 86% of bereaved caregivers were satisfied with physician behavior toward death pronouncement. Logistic regression analysis revealed three predictors of caregiver satisfaction: "Polite behavior" (odds ratio [OR]: 0.12; 95% confidence intervals [CI]: 0.03-0.46; p 0.01), "Physician introduced himself/herself to family" (OR: 0.3; 95% CI: 0.1-0.8; p = 0.02), and "Physician confirmed death automatically or routinely" (OR: 11.6; 95% CI: 4.7-28.4; p 0.01). Caregivers whose family member's death was confirmed by the primarily responsible physician were significantly more satisfied than those whose family member's death was confirmed by an unfamiliar physician.Most caregivers who lost family members in PCUs were satisfied by the physicians' behavior toward death pronouncement. Politeness was one of the most important factors associated with caregiver satisfaction.

A Saturn-like 1:1 complex composed of macrocyclic oligothiophene E-8T7A and C60 fullerene (C60 ) was synthesized to investigate the interaction between macrocyclic oligothiophenes and C60 in solution and the solid state. Because the Saturn-like 1:1 complex E-8T7A⋅C60 is mainly stabilized by van der Waals interactions between C60 and the sulfur atoms of the E-8T7A macrocycle, C60 is rather weakly incorporated inside the macro-ring in solution. However, in the solid state the Saturn-like 1:1 complex preferentially formed single crystals or nanostructured polymorphs. Interestingly, X-ray analysis and theoretical calculations exhibited hindered rotation of C60 in the Saturn-like complex due to interactions between C60 and the sulfur atoms. Furthermore, the photoinduced charge transfer (CT) interaction between E-8T7A and C60 in solution was investigated by using femtosecond transient absorption (TA) spectroscopy. The ultrafast TA spectral changes in the photoinduced absorption bands were attributed to the CT process in the Saturn-like structure.

Dimer 2, trimer 3, hexamer 6, octamer 8, and decamer 10 of 4,4′′-diethynyl-4′,5′-dioctyl-o-terphenyl 1 were synthesized by using copper(II) acetate-mediated Eglington coupling reaction of 1 in pyridine or pyridine–methanol. Although dimer 2 and trimer 3 were formed as major products under high dilution conditions, large oligomers such as hexamer 6, octamer 8, and decamer 10 were obtained in moderate total yield under standard Eglington conditions. The MALDI-TOF MS and GPC behavior of large oligomers exhibit the formation of giant macrocycles 3 nm diameter and 2–4 nm long in one-pot procedure.

Objectives The purpose of this study was (a) to describe the end-of-life experience of family caregivers of cancer patients, (b) to describe talking about death and dying of the patient to minor children, and (c) to examine the association of family caregivers' experiences by their characteristics and talking about death and dying of the patient. Methods A cross-sectional nationwide survey of bereaved family caregivers was conducted. In total, 968 questionnaires were sent to bereaved family caregivers, and 711 were completed and returned. Fifty-three responses indicating patients had minor children were analyzed. Univariate analysis and principal component analysis were performed. Results Family caregivers' experiences were divided into 3 domains by principal component analysis: protect children from the patient's imminent death, little regard for the children, and worry and concern about the children's emotional reaction. Family caregivers' common experiences were as follows: “I wanted to know how the children felt,” “I wanted to avoid making the children confused,” and “I did not have much time to talk with and/or play with the children.” About 30% of family caregivers reported that they “did not talk” about death and dying of patients to minor children. Spouses of patients and family caregivers who did not talk about death tended to experience distress and worry. Conclusions Most family caregivers experienced worry and fear regarding minor children's emotional reaction; therefore, clinicians need to explain children's emotional and psychological reactions to family caregivers when a patient is at the end-of-life.

BACKGROUND Survival prediction systems such as the Palliative Prognostic Index (PPI), which includes the Palliative Performance Scale (PPS), are used to estimate survival for terminally ill patients. Oncologists are, however, less familiar with the PPS in comparison with the Eastern Cooperative Oncology Group (ECOG) performance status (PS). This study was designed to validate a simple survival prediction system for oncologists, the Performance Status–Based Palliative Prognostic Index (PS-PPI), which is a modified form of the PPI based on the ECOG PS. METHODS This multicenter, prospective cohort study enrolled all consecutive patients who were referred to 58 palliative care services in Japan. The primary responsible physicians rated the variables required to calculate the PS-PPI and the PPI. Patient survival in these risk groups was compared, and the sensitivity and specificity of the PS-PPI and the PPI were evaluated. Patients were subclassified as patients receiving care from in-hospital palliative care teams, palliative care units, or home-based palliative care services. Subsets of patients receiving chemotherapy were also analyzed. RESULTS This study included 2346 patients. Survival predictions based on the PPI and the PS-PPI differed significantly among the 3 risk groups (P 0.78 for predicting survival at all times, from 3 weeks to 180 days. CONCLUSIONS In predicting the prognosis of patients with advanced cancer, the PS-PPI was as accurate as the PPI. The PS-PPI was useful for short- and long-term survival prediction and for the prediction of survival for patients undergoing chemotherapy. Cancer 2017;123:1442–1452. © 2016 American Cancer Society.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Duloxetine has some effect against cancer neuropathic pain (CNP); however, predictors of duloxetine response are unclear. This study sought to identify predictors of duloxetine response in patients with CNP. Methods: Patients (N = 70) with CNP unresponsive to or intolerant of opioid–pregabalin combination therapy, with a brief pain inventory-short form (BPI-SF) Item 5 score (average pain) ≥ 4, and with a total hospital anxiety and depression scale score < 20, were randomized to a duloxetine or a placebo group. Multiple linear regression analysis was conducted to identify predictors of duloxetine response as a secondary analysis with the change in the average pain score on day 10 from day 0 as the dependent variable, and the following five covariates; baseline (day 0) average pain score, baseline opioid dose, continuation/discontinuation of pregabalin, and items 20 and 21 score of the short-form McGill pain questionnaire 2 (SF-MPQ-2) as independent variables. Results: Of the four domains (continuous pain, intermittent pain, neuropathic pain, and affective descriptors) score of SF-MPQ-2 on day 0, significant differences were observed in the neuropathic pain domain (p = 0.040) in change on the average pain between day 10 and day 0 in the duloxetine group. Multiple linear regression analysis revealed that patients with a high score for SF-MPQ-2 Item 21 (tingling pain) on day 0 had a significantly greater change in average pain between day 10 and day 0 (p = 0.046). Conclusion: Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.

Context Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails. Objectives We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy. Methods A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]–Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases. Results Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P = 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P = 0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n = 15) of patients in Group D vs. 18.2% (n = 6) in Group P (P = 0.02); 32.4% (n = 11) vs. 3.0% (n = 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P = 0.002). Conclusion Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine.

Three new macrocyclic π-extended thiophene hexamers composed of four thienylene-ethynylene and two thienylene-vinylene units with or without four alkyl substituents have been synthesized. Despite similar shape-persistent structures in solution, the alkyl substituents control the solid-state structures and morphologies. The unsubstituted hexamer exhibited a planar conformation with a theoretically predicted structure in the solid state; however, the planar hexamer with four ethyl substituents formed a closely stacked columnar crystal structure to exhibit π-π interactions. Interestingly, the hexamer with four butyl substituents adopted both planar and twisted conformations in the solid state, exhibiting polymorphism based on induced-fit stacking of molecules. Thus, the butyl-substituted hexamer produces a mixture of yellow, orange, and red single crystals from toluene/acetone, and X-ray analysis revealed six different conformations. Consequently, the small structural difference in the macrocycles causes a key effect on their functional properties in the solid state, and their morphology governs electrical conductivity and organic field-effect-transistor activity. The polymorphism of the hexamers was applied to the switching of film morphology.

Plasma C-reactive protein (CRP) levels are elevated in patients with advanced cancer.To investigate CRP as a prognostic marker in palliative settings.This multicenter prospective cohort study comprised 2426 patients. Laboratory data were obtained at baseline, and all patients were followed until death or six months after their enrollment. A total of 1511 patients were eligible for the analyses. They were divided into four groups: low-CRP (CRP1 mg/dL), moderate-CRP (1 ≤ CRP5 mg/dL), high-CRP (5 ≤ CRP 10 mg/dL), and very high-CRP (10 mg/dL ≤ CRP) groups. Survival was investigated by the Kaplan-Meier method with the log-rank test. The 30-, 60-, and 90-day mortality rates were tested by Chi-squared tests. Univariate- and multivariate-adjusted hazard ratios (HRs) and 95% CIs in each group were calculated using Cox proportional hazard models.Survival rate decreased and mortality rate increased with increasing CRP level. The differences in survival and 30-, 60-, and 90-day mortality rates among the groups were statistically significant (P 0.001). Baseline CRP level was significantly associated with a higher risk of mortality after adjustment for age, gender, primary tumor site, metastasis, chemotherapy, Eastern Cooperative Oncology Group Performance Status, and setting of care (moderate-CRP: HR 1.47 [95% CI 1.24-1.73], high-CRP: HR 2.09 [95% CI 1.74-2.50], and very high-CRP: HR 2.55 [95% CI 2.13-3.05] vs. low-CRP).Clear dose-effect relationships between elevated CRP levels and prognoses indicate that CRP could be useful in predicting prognoses in patients with advanced cancer.

BackgroundFew studies have been conducted on the experiences of children of terminally ill patients or hospital-based medical professionals supporting such children.AimThis study explored distress among individuals whose parents died of cancer in childhood and among hospital-based medical professionals supporting such children.DesignA qualitative study.Setting/participantsThe sample was 12 adults whose parents had died of cancer in childhood and 20 hospital-based medical professionals supporting children of patients’ with terminal cancer. In-depth interviews were conducted, focusing on the distress experienced by the participants. The data were analysed thematically.ResultsAmong adults whose parents died of cancer in childhood, we identified themes related to the period before death (eg, concealing the parent's illness), the time of death (eg, alienation due to isolation from the parent), soon after death (eg, fear and shock evoked by the bizarre circumstances, regrets regarding the relationship with the deceased parent before death), several years thereafter (ie, distinctive reflection during adolescence, prompted by the parent's absence) and the present time (ie, unresolved feelings regarding losing the parent). We identified seven themes among the medical professionals (eg, lack of knowledge/experience with children, the family's attempts to shield the child from the reality of death, estrangement from the family once they leave the hospital).ConclusionsAn important finding of the study is that the participants’ grief reaction to their parents’ deaths during childhood was prolonged. Moreover, hospital medical professionals may find it difficult to directly support affected children. Comprehensive support involving organisations (eg, local communities) may be necessary for children who have lost a parent.

Summary Background Continuous deep sedation (CDS) before death is a form of palliative sedation therapy that has become a focus of strong debate, especially with respect to whether it shortens survival. We aimed to examine whether CDS shortens patient survival using the propensity score-weighting method, and to explore the effect of artificial hydration during CDS on survival. Methods This study was a secondary analysis of a large multicentre prospective cohort study that recruited and followed up patients between Sept 3, 2012, and April 30, 2014, from 58 palliative care institutions across Japan, including hospital palliative care settings, inpatient palliative care units, and home-based palliative care services. Adult patients (aged ≥20 years) with advanced cancer who received care through the participating palliative care services were eligible for this secondary analysis. Patients with missing data for outcome variables or who lived for more than 180 days were excluded. We compared survival after enrolment between patients who did and did not receive CDS. We used a propensity score-weighting method to control for patient characteristics, disease status, and symptom burden at enrolment. Findings Of 2426 enrolled patients with advanced cancer, we excluded 289 (12%) for living longer than 180 days and 310 (13%) with missing data, leaving an analysis population of 1827 patients. 269 (15%) of 1827 patients received CDS. Unweighted median survival was 27 days (95% CI 22–30) in the CDS group and 26 days (24–27) in the no CDS group (median difference −1 day [95% CI −5 to 4]; HR 0·92 [95% CI 0·81–1·05]; log-rank p=0·20). After propensity-score weighting, these values were 22 days (95% CI 21–24) and 26 days (24–27), respectively (median difference −1 day [95% CI −6 to 4]; HR 1·01 [95% CI 0·87–1·17]; log-rank p=0·91). Age (p interaction =0·67), sex (p interaction =0·26), performance status (p interaction =0·90), and volume of artificial hydration (p interaction =0·14) did not have an effect modification on the association between sedation and survival, although care setting did have a significant effect modification (p interaction =0·021). Interpretation CDS does not seem to be associated with a measurable shortening of life in patients with advanced cancer cared for by specialised palliative care services, and could be considered a viable option for palliative care in this setting. Funding Japanese National Cancer Center Research and Development Fund.

BACKGROUND To improve palliative care practice, the need for patients-reported outcome measures is increasing globally. The Integrated Palliative care Outcome Scale (IPOS) is a streamlined outcome scale developed to comprehensively evaluate patients' distress. The goal of this study is to assess the reliability and validity of IPOS-Japanese version in cancer patients. METHODS This is a multicenter, cross-sectional observational study. We assessed the missing values, prevalence, test-retest reliability, criterion validity and known-group validity in Japanese adult cancer patients. Patients provided responses to IPOS, European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and Functional Assessment of Chronic Illness Therapy- Spiritual 12 (FACIT-Sp12). Our medical staff provided responses to Support Team Assessment Schedule (STAS). RESULTS One hundred forty-two patients were enrolled at six palliative care facilities. Missing values accounted for less than 1% of most items, with a maximum of 2.8%. The prevalence of symptoms was 17.7-88.7%. The intra-class correlation coefficient ranged from 0.522 to 0.951. The range of correlation coefficients with EORTC-QLQ-C30, FACIT-Sp12 and STAS as gold standards was 0.013 to 0.864 (absolute values). Total IPOS scores were positively correlated with Eastern Corporative Oncology Group Performance Status (P < 0.001). CONCLUSION IPOS-Japanese version is a valid and reliable tool. The scale is useful in assessing physical, psychological, social and spiritual symptoms and in measuring outcomes of adult cancer patients in Japan.