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

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

The effect of palliative care team intervention and symptom improvement using patient-reported outcomes: a multicenter prospective observational study.

PURPOSE: Hospital-based palliative care teams (HPCTs) are widespread internationally, but multicenter studies about their effectiveness, using patient-reported outcomes (PROs), are limited to Australia and a few other countries. We conducted a multicenter, prospective observational study in Japan to explore the effectiveness of the HPCTs using PROs. METHODS: Nationwide, eight hospitals participated in the study. We included newly referred patients for one month in 2021 and followed them for one month. We asked the patients to complete the Integrated Palliative Care Outcome Scale or the Edmonton Symptom Assessment System as PROs at the time of the intervention, three days later, and weekly after the intervention. RESULTS: A total of 318 participants were enrolled, of whom 86% were patients with cancer, 56% were undergoing cancer treatment, and 20% received the Best Supportive Care. After one week, the following 12 symptoms showed more than a 60% improvement from severe to moderate or less: vomiting (100%), shortness of breath (86%), nausea (83%), practical problems (80%), drowsiness (76%), pain (72%), poor sharing of feelings with family or friends (72%), weakness (71%), constipation (69%), not feeling at peace (64%), lack of information (63%), and sore or dry mouth (61%). Symptoms with improvement from severe/moderate to mild or less were vomiting (71%) and practical problems (68%). CONCLUSION: This multicenter study showed that HPCTs effectively improved symptoms in several severe conditions, as assessed by PROs. This study also demonstrated the difficulty of relieving symptoms in patients in palliative care and the need for improved care.

Do Types of Opioids Matter for Terminal Cancer Dyspnea? A Preliminary Multicenter Cohort Study.

CONTEXT: Dyspnea is among the most distressing symptoms in the last weeks to days of life (terminal dyspnea). While physicians frequently use parenteral opioids other than morphine for terminal dyspnea, little is known about their effects in cancer patients. OBJECTIVES: To explore the effectiveness and safety of parenteral morphine, oxycodone, and hydromorphone for cancer patients with terminal dyspnea. METHODS: This was a secondary analysis of a multicenter cohort study that consecutively enrolled advanced cancer patients with moderate/severe terminal dyspnea. Participating palliative care physicians initiated parenteral opioids (morphine/oxycodone/hydromorphone), utilizing a standardized treatment algorithm. We examined the dyspnea intensity (Integrated Palliative care Outcome Scale [IPOS]) at 24 and 48 hours. RESULTS: Of 108 patients (mean age = 72), 66 (61%), 34 (32%), and 8 (7.4%) received morphine, oxycodone, and hydromorphone, respectively. At 24 hours, mean dyspnea IPOS scores significantly decreased from 3.0 (standard error (SE) = 0.1) at the baseline to 1.6 (0.1), 2.9 (0.1) to 2.0 (0.2), and 3.5 (0.2) to 1.2 (0.4) in the morphine (P < 0.001), oxycodone (P < 0.001), and hydromorphone (P = 0.011) groups, respectively. At 48 hours, the IPOS scores significantly reduced from 2.9 (0.1) at the baseline to 1.4 (0.1), 2.9 (0.1) to 1.6 (0.2), and 3.5 (0.2) to 1.2 (0.2) in the morphine (P < 0.001), oxycodone (P < 0.001), and hydromorphone (P = 0.004) groups, respectively. No significant differences in mean scores were found among the three groups at 24 (P = 0.080) and 48 hours (P = 0.322). Adverse events were rare. CONCLUSION: Parenteral morphine, oxycodone, and hydromorphone may be similarly effective and safe for cancer patients with terminal dyspnea.

Current Management Options for Dyspnea in Cancer Patients.

OPINION STATEMENT: Dyspnea is one of the most frequent and distressing symptoms in patients with advanced cancer. As dyspnea deteriorates patients' quality of life markedly and tends to worsen as the disease progresses, comprehensive assessment and timely treatment of the underlying etiologies are essential. International guidelines recommend various non-pharmacological and pharmacological management options. However, there is a scarcity of confirmatory clinical trials on cancer dyspnea, and the overall level of evidence is weak. Recently, observational and survey studies indicated a wide range of practice patterns of palliative care specialists, providing important insight into the real-world management of dyspnea. In this paper, we summarize current management options for dyspnea in cancer patients, highlight major controversies in the literature, and propose future research directions toward quality care for patients with dyspnea and their families.

Systemic Opioids for Dyspnea in Cancer Patients: A Real-world Observational Study.

CONTEXT: Although Systemic opioids are recommended as a pharmacological treatment for cancer-related dyspnea, their effectiveness and safety needs to be investigated in a real-world context OBJECTIVES: To evaluate the effectiveness and safety of systemic regular opioids for dyspnea in cancer patients, in the real-world palliative care practice. METHODS: This was a multicenter prospective observational study. We consecutively enrolled adult cancer patients starting regular opioids (morphine, oxycodone, hydromorphone, or fentanyl) for dyspnea from 12 palliative care services across Japan. We evaluated dyspnea intensity using the Numerical Rating Scale (NRS) and Integrated Palliative Outcome Scale (IPOS) every 24 hours until 72 hours after starting opioids (T1-T3). We also evaluated common opioid-related adverse events (AEs) and other severe AEs. RESULTS: We enrolled 402 cancer patients. The proportion of responders was 68.8% (95%confidence intervals (CI): 0.63-0.74) at T1, 75.7% (95%CI: 0.70-0.81) at T2, and 82.1% (95%CI: 0.76-0.87) at T3. The mean differences in dyspnea NRS from baseline were 1.73 (95%CI: 1.46-1.99) at T1, 1.99 (95%CI: 1.71-2.28) at T2, and 2.47 (95%CI:2.13-2.82) at T3. The most common treatment-emergent AE was somnolence with an incidence of the severe form of approximately 10% throughout the study period. In the multivariate analysis, baseline dyspnea NRS ≥6 had a positive correlation with dyspnea relief by systemic regular opioids, while liver metastasis, clinician-predicted survival days, and opioid tolerance had a negative correlation. CONCLUSION: Regular systemic opioids were effective for dyspnea in real-world cancer patients.

The feasibility and effects of a pharmacological treatment algorithm for cancer patients with terminal dyspnea: A multicenter cohort study.

BACKGROUND: How clinicians treat patients with terminal dyspnea widely varies, which could hamper quality care. We visualized comprehensive pharmacological treatment delivered by palliative care physicians. AIM: To examine adherence to a comprehensive pharmacological treatment algorithm for patients with terminal dyspnea, and to explore its outcomes during 48 h. DESIGN: A multicenter cohort study at five sites (February 2020 to June 2021). SETTING/PARTICIPANTS: We prospectively enrolled consecutive patients with advanced cancer, Eastern Cooperative Oncology Group performance status 3-4, and moderate/severe dyspnea. Participating palliative care physicians initiated algorithm-based treatment. The primary outcome was the proportion of adherence to the treatment algorithm over 24 h (predefined goal, 70%). We evaluated the adherence, goal achievement, and dyspnea level with a numerical rating scale (NRS), as well as adverse events over 48 h. RESULTS: All 108 patients received algorithm-based pharmacological treatment. Among 96 and 87 patients who were alive at 24 and 48 h, respectively, 96 (100%; 95% confidence interval [CI] = 96%-100%) and 82 (94%; 95%CI = 87%-98%) continued to receive the algorithm treatment, respectively, and 66 (69%; 95%CI = 59%-77%) and 64 (74%; 95%CI = 63%-82%) achieved the treatment goals, respectively. Using a complete case analysis with paired t-tests, mean dyspnea NRS scores significantly reduced from 7.3 (standard error, 0.2) at the baseline to 4.9 (0.3) at 24 h (n = 72; p < 0.001), and 7.2 (0.3) at the baseline to 4.6 (0.4) at 48 h (n = 55; p < 0.001). Most adverse events were mild to moderate. CONCLUSIONS: The comprehensive pharmacological treatment algorithm was feasible, and the study data supports its preliminary efficacy and safety. The use of this algorithm may help clinicians improve care for patients with terminal dyspnea.

Anticholinergic drugs for death rattle in dying patients with cancer: multicentre prospective cohort study.

BACKGROUND: This study aimed to investigate the effectiveness of anticholinergics (AC) for death rattle in dying patients with cancer. METHODS: This is a prospective cohort study enrolled Terminally ill adult (20 years or older) patients with cancer who developed substantial death rattle (Back score ≥2) from 23 palliative care units in Japan. AC treatment for death rattle was prescribed according to primary physician's decision. The primary outcome was the proportion of patients whose death rattle improved, which was defined as a Back score of ≤1. We compared the proportion of improved cases in patients treated with (AC group) and without (non-AC group) AC, controlling potential confounders by employing propensity score weighting. RESULTS: Of the 1896 patients enrolled, we included 196 who developed a substantial death rattle. Of these, 81 received AC. 56.8% in the AC group and 35.4% in the non-AC group had an improved death rattle at 8 hours after baseline. In the weighted analysis, AC group showed significant improvements in death rattle, with an adjusted OR of 4.47 (95% CI 2.04 to 9.78; p=0.0024). All sensitivity analyses achieved essentially the same results. In the subgroup analysis, ACs were strongly associated with death rattle improvement in men, patients with lung cancer, and type 1 death rattle (adjusted OR 5.81, 8.38 and 9.32, respectively). CONCLUSIONS: In this propensity score-weighted analysis, ACs were associated with death rattle improvement in terminally ill patients with cancer who developed substantial death rattle. TRIAL REGISTRATION NUMBER: UMIN-CTR (UMIN00002545).

Comparative study of clinicians' and family members' perceptions of patients' end-of-life experiences.

OBJECTIVE: End-of-life experiences (ELEs), such as deathbed visions (DBVs), have been reported worldwide. However, ELEs have rarely been discussed in clinical practice, possibly because of the different perceptions of ELEs among clinicians and families. Therefore, this study aimed to investigate the differences in perception regarding ELEs, especially DBVs, between clinicians and families. METHODS: We conducted a multicentre, prospective and observational study with patients with cancer. After the patients' death, clinicians recorded their perceptions of patients' ELEs during the palliative care unit admission, and bereaved families responded to a questionnaire about ELEs. The primary outcome was the frequency and concordance of DBVs from the perspective of bereaved family members and clinicians. The second outcome was each group's frequency of terminal lucidity and terminal coincidence. RESULTS: The study included 443 patients. DBVs were reported more frequently by family members than clinicians (14.0% vs 2.7%, p<0.001). Among family members, terminal lucidity and terminal coincidence were observed at 7% and 7.9%, respectively, while only one case each was reported by clinicians. CONCLUSIONS: Clinicians and family members may perceive ELEs differently. Enabling patients and their families to talk about ELEs would assist in optimising grief care.

Symptoms, performance status and phase of illness in advanced cancer: multicentre cross-sectional study of palliative care unit admissions.

OBJECTIVES: To clarify the relationship between Phase of Illness at the time of admission to palliative care units and symptoms of patients with advanced cancer. METHODS: This study was a secondary analysis of the East Asian collaborative cross-cultural Study to Elucidate the Dying process. Palliative physicians recorded data, including Phase of Illness, physical function and the Integrated Palliative care Outcome Scale. We used multinomial logistic regression to analyse ORs for factors associated with Phase of Illness. Twenty-three palliative care units in Japan participated from January 2017 to September 2018. RESULTS: In total, 1894 patients were analysed-50.9% were male, mean age was 72.4 (SD±12.3) years, and Phase of Illness at the time of admission to the palliative care unit comprised 177 (8.9%) stable, 579 (29.2%) unstable, 921 (46.4%) deteriorating and 217 (10.9%) terminal phases. Symptoms were most distressing in the terminal phase for all items, followed by deteriorating, unstable and stable (p<0.001). The stable phase had lower association with shortness of breath (OR 0.73, 95% CI 0.57 to 0.94) and felt at peace (OR 0.73, 95% CI 0.56 to 0.90) than the unstable phase. In the deteriorating phase, weakness or lack of energy (OR 1.20, 95% CI 1.02 to 1.40) were higher, while drowsiness (OR 0.82, 95% CI 0.71 to 0.97) and felt at peace (OR 0.81, 95% CI 0.71 to 0.94) were significantly lower. CONCLUSION: Our study is reflective of the situation in palliative care units in Japan. Future studies should consider the differences in patients' medical conditions and routinely investigate patients' Phase of Illness and symptoms. TRIAL REGISTRARION NUMBER: UMIN000025457.

Morphine May Contribute to Improving Respiratory Failure in Severe COVID-19: A Case Report.

At present, the world is undergoing successive waves of the COVID-19 pandemic. When COVID-19 becomes severe, it causes respiratory failure and symptoms of dyspnoea. The patient's dyspnoea worsens to the IPOS of 3. One COVID-19 patient admitted to our medical institution developed severe illness characterised by hypoxaemia and dyspnoea. In addition to disease-modifying treatments such as remdesivir and dexamethasone, we administered morphine to relieve his dyspnoea. Surprisingly, we observed an improvement in both hypoxaemia and dyspnoea.

Predictive Factors for the Development of Dyspnea Within 7 Days After Admission Among Terminally Ill Cancer Patients.

BACKGROUND: Predictive factors for the development of dyspnea have not been reported among terminally ill cancer patients. OBJECTIVE: This current study aimed to identify the predictive factors attributed to the development of dyspnea within 7 days after admission among patients with cancer. METHODS: This was a secondary analysis of a multicenter prospective observational study on the dying process among patients admitted in inpatient hospices/palliative care units. Patients were divided into 2 groups: those who developed dyspnea (development group) and those who did not (non-development group). To determine independent predictive factors, univariate and multivariate analyses using the logistic regression model were performed. RESULTS: From January 2017 to December 2017, 1159 patients were included in this analysis. Univariate analysis showed that male participants, those with primary lung cancer, ascites, and Karnofsky Performance Status score (KPS) of ≤40, smokers, and benzodiazepine users were significantly higher in the development group. Multivariate analysis revealed that primary lung cancer (odds ratio [OR]: 2.80, 95% confidence interval [95% CI]: 1.47-5.31; p = 0.002), KPS score (≤40) (OR: 1.84, 95% CI: 1.02-3.31; p = 0.044), and presence of ascites (OR: 2.34, 95% CI: 1.36-4.02; p = 0.002) were independent predictive factors for the development of dyspnea. CONCLUSIONS: Lung cancer, poor performance status, and ascites may be predictive factors for the development of dyspnea among terminally ill cancer patients. However, further studies should be performed to validate these findings.

Research policy in supportive care and palliative care for cancer dyspnea.

BACKGROUND: Dyspnea is a common and distressing symptom in patients with cancer. To improve its management, multicenter confirmatory studies are necessary. Research policy would be useful in conducting these studies. Here, we propose a new research policy for the management of dyspnea in patients with cancer. METHODS: The first draft was developed by a policy working group of 11 specialists in the field of supportive care or palliative care for dyspnea. Then, a provisional draft was developed after review by a research support group (the Japanese Supportive, Palliative and Psychosocial Care Study Group) and five Japanese scientific societies (Japanese Association of Supportive Care in Cancer, Japanese Society of Medical Oncology, Japanese Society of Palliative Medicine, Japanese Association of Rehabilitation Medicine and Japanese Society of Clinical Oncology), and receipt of public comments. RESULTS: The policy includes the following components of research policy on dyspnea: (i) definition of dyspnea, (ii) scale for assessment of dyspnea, (iii) reason for dyspnea or factors associated with dyspnea and (iv) treatment effectiveness outcomes/adverse events. The final policy (Ver1.0) was completed on 1 March 2021. CONCLUSIONS: This policy could help researchers plan and conduct studies on the management of cancer dyspnea.

Effectiveness and safety of opioids for dyspnea in patients with lung cancer: secondary analysis of multicenter prospective observational study.

Background: Patients with lung cancer are more likely to have comorbidities [e.g., interstitial lung disease (ILD)], chronic obstructive pulmonary disease) and metastases that may affect dyspnea and the effectiveness and safety of opioids for dyspnea than other cancer types. Therefore, this study examined the effectiveness and safety of opioids for dyspnea, among the patients with lung cancer. Methods: The present study is a secondary analysis of a multicenter prospective observational study examining the effectiveness and safety of opioids for dyspnea in patients with cancer in Japan. For this secondary analysis, patients with lung cancer with a documented dyspnea Numerical Rating Scale (NRS) at baseline were included. The primary outcome was dyspnea NRS, and Integrated Palliative care Outcome Scale/Support Team Assessment Schedule (IPOS/STAS) scores change between baseline and 24 hours after baseline. As secondary outcomes, we investigated the predictors of opioid effectiveness for dyspnea improvement and adverse events (nausea, somnolence, and delirium). Results: This study analyzed 124 patients with lung cancer with known dyspnea NRS at baseline. The median age was 74, and the Eastern Cooperative Oncology Group performance status of 107 patients were 3-4. Both NRS and IPOS/STAS score of dyspnea significantly improved 24 hours after opioid initiation [-1.64, 95% confidence interval (CI): -2.12 to -1.17, P<0.001; -1.03; 95% CI: -1.21 to -0.85, P<0.001; respectively]. Moreover, the improvement of NRS score was greater than the minimal clinically important difference of 1 point. In the multivariate logistic regression analysis, ILD was significantly associated with a better improvement [(hazard ratio (HR): 3.39, 95% CI: 1.34-11.09, P=0.043]. Somnolence was the most common grade 3-4 adverse event (n=16), followed by delirium (n=9). Conclusions: Opioids were effective and safe for treating dyspnea in patients with lung cancer. Furthermore, lung cancer patients with ILD may benefit more from opioids.

Diagnostic models for impending death in terminally ill cancer patients: A multicenter cohort study.

BACKGROUND: Accurately predicting impending death is essential for clinicians to clarify goals of care. We aimed to develop diagnostic models to predict death ≤3 days in cancer patients. METHODS: In this multicenter cohort study, we consecutively enrolled advanced cancer patients admitted to 23 inpatient hospices in 2017. Fifteen clinical signs related to impending death were documented daily from the day when the Palliative Performance Scale (PPS) declined to ≤20-14 days later. We conducted recursive partitioning analysis using the entire data set and performed cross-validation to develop the model (prediction of 3-day impending death-decision tree [P3did-DT]). Then, we summed the number of systems (nervous/cardiovascular/respiratory/musculoskeletal), where any sign was present to underpin P3did score (range = 0-4). RESULTS: Data following PPS ≤20 were obtained from 1396 of 1896 inpatients (74%). The mean age was 73 ± 12 years, and 399 (29%) had gastrointestinal tract cancer. The P3did-DT was based on three variables and had four terminal leaves: urine output (u/o) ≤200 ml/day and decreased response to verbal stimuli, u/o ≤200 ml/day and no decreased response to verbal stimuli, u/o >200 ml/day and Richmond Agitation-Sedation Scale (RASS) ≤-2, and u/o >200 ml/day and RASS ≥-1. The 3-day mortality rates were 80.3%, 53.3%, 39.9%, and 20.6%, respectively (accuracy = 68.3%). In addition, 79.6%, 62.9%, 47.2%, 32.8%, and 17.4% of patients with P3did scores of 4, 3, 2, 1, and 0, respectively, died ≤3 days. CONCLUSION: We successfully developed diagnostic models for death ≤3 days. These may further help clinicians predict impending death and help patients/families prepare for their final days.

The Possibility of Conducting a Clinical Trial on Palliative Care: A Survey of Whether a Clinical Study on Cancer Dyspnea Is Acceptable to Cancer Patients and Their Relatives.

CONTEXT: Conducting randomized controlled trials on palliative care is difficult owing to barriers like fragility of the patients' health status and health care providers' concerns for patients. However, quality randomized controlled trials are required for care improvement. OBJECTIVES: To investigate the willingness of cancer patients and their relatives to participate in a clinical study on cancer dyspnea and identify feasible clinical study designs for this condition. METHODS: A nationwide, cross-sectional, web-based survey was conducted with 206 cancer patients and 206 relatives of cancer patients. Their willingness to participate in clinical studies on cancer dyspnea and factors influencing this willingness were assessed in two scenarios: outpatients receiving anticancer treatment and terminally ill inpatients. RESULTS: About 23% patients and 23% relatives were willing to participate in clinical trials while 40% and 32%, respectively, were unwilling. Factors related to patient participation were quick and easy trials (outpatient 57%, terminally ill 53%) and oral medication with minimal potential side effects (outpatient 48%). Factors related to unwillingness to participate were placebo-controlled trials (outpatient 51%, terminally ill 50%), disagreements about participation between patients and families (outpatient 49%, terminally ill 49%), and continuous injections (outpatient 61%, terminally ill 47%). Compared to patients, relatives responded more reluctantly, especially for patients in terminal care. Conversely, patients were less reluctant in the terminal setting than the outpatient setting. CONCLUSION: Some patients and relatives were reluctant to participate in clinical trials on cancer dyspnea. Thus, trials need to be minimally invasive, quick, and fully explained to and understood by patients and families.

Optimal Paracentesis Volume for Terminally Ill Cancer Patients With Ascites.

CONTEXT: Patients with malignant ascites often suffer from distressing symptoms, especially in their end-of-life stage. Although paracentesis is the most common treatment modality to alleviate such symptoms, the optimal volume of paracentesis is not known. OBJECTIVES: To explore the efficacy and safety of paracentesis by the drainage volume for terminally ill cancer patients with malignant ascites. METHODS: This was part of a multicenter prospective observational study (EASED study). Consecutive adult patients with advanced cancer admitted to 23 participating palliative care units were eligible. We analyzed patients with malignant ascites who received paracentesis. We compared paracentesis-free survival (PFS) using Cox regression among three groups with different paracentesis volumes: minimum: ≤ 1500 mL, small: 1500-2500 mL, and moderate: > 2500 mL. Trends of the difference in the numerical rating scale of abdominal distension (0-10) and adverse events were compared among the 3 groups. RESULTS: Of the 1926 patients enrolled, 673 developed ascites (symptomatic, n = 374 and asymptomatic, n = 299). Finally, we analyzed 87 patients with paracentesis. Median PFS was 7 days. Compared with a moderate volume, small-volume paracentesis was not a significant risk for shorter PFS (HR: 1.14, 95% CI: 0.69-1.93), while a minimum volume was a significant risk (HR: 2.34). The abdominal distension intensity significantly decreased after paracentesis (median: 7.5 to 4.0), while the difference did not significantly increase as the volume of paracentesis rose (P = 0.61). No severe adverse event was observed. CONCLUSION: Even small-volume paracentesis could alleviate abdominal distension of terminally ill cancer patients with malignant ascites without shortening the paracentesis interval compared with moderate-volume paracentesis. Small-volume paracentesis was a well-balanced treatment for these patients.

Visualizing How to Use Parenteral Opioids for Terminal Cancer Dyspnea: A Pilot, Multicenter, Prospective, Observational Study.

CONTEXT: How physicians use opioids for dyspnea in imminently dying cancer patients (terminal dyspnea) varies markedly, which could hamper quality care. OBJECTIVES: To examine the adherence to an algorithm-based treatment for terminal dyspnea, and explore its outcomes over 24 hours. METHODS: This was a pre-planned subgroup analysis of a multicenter prospective observational study. Inclusion criteria were: advanced cancer patients admitted to palliative care units, ECOG performance status = 3-4, and a dyspnea intensity ≥2 on the Integrated Palliative care Outcome Scale (IPOS). We developed an algorithm to visualize how palliative care physicians would use parenteral opioids. Participating physicians (palliative care specialists) initiated parenteral opioids, choosing whether to use the algorithm based on their preference. We measured the adherence rate to the algorithm over 24 hours (predefined goal = 70%), and compared dyspnea IPOS scores and adverse events between patients with and without algorithm-based treatment. RESULTS: Of 164 patients (median survival = 5 days), 71 (43%) received algorithm-based treatment, and 70 (99%; 95% confidence interval = 92%-100%) adhered to it over 24 hours. In a complete case analysis, mean dyspnea IPOS scores significantly decreased from 2.9 (standard error = 0.1) to 1.5 (0.1) in the algorithm group (n = 54; P < 0.001), and 2.9 (0.1) to 1.6 (0.1) in the non-algorithm group (n = 72; P < 0.001). There was no significant between-group difference in changes in dyspnea IPOS scores (P = 0.65). Adverse events were rare (n = 5). CONCLUSION: The algorithm-based treatment was feasible, and might be as effective and safe as the usual care by palliative care specialists. Its implementation may help physicians provide quality care for terminal dyspnea.

How Successful Is Parenteral Oxycodone for Relieving Terminal Cancer Dyspnea Compared With Morphine? A Multicenter Prospective Observational Study.

CONTEXT: 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. OBJECTIVES: To explore the efficacy of parenteral oxycodone vs. morphine by continuous infusion over 24 hours in cancer patients with terminal dyspnea. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Palliative care physicians' perspectives of management for terminally ill cancer patients with death rattle: a nationwide survey.

Death rattle occurs during the last days of life, and relatives of those afflicted frequently report that it is very distressful. However, there is no effective treatment for it. The purpose of this study was to investigate the perceptions of Japanese palliative care physicians in clinical practice in Japan. We conducted a nationwide survey of 268 physicians via an anonymous, self-report questionnaire. We assessed pharmacological and non-pharmacological management and anticholinergic agent choice. One hundred eighty-nine physicians (70.5%) returned the questionnaires. Fifty-five participants (29.1%) treating patients with Type-1 (real death rattle) and 36 participants (19%) treating patients with Type-2 (pseudo-death rattle) death rattle reported that they would frequently administer an anticholinergic agent. One-fourth would administer scopolamine butylbromide or scopolamine hydrobromide. In conclusion, more Japanese palliative care physicians thought that anticholinergic agents might be effective for treating Type-1 death rattle rather than Type-2. Further clinical trials of these agents are needed.

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

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