A combination of routine laboratory findings and vital signs can predict survival of advanced cancer patients without physician evaluation: a fractional polynomial model.

INTRODUCTION: There have been no reports about predicting survival of patients with advanced cancer constructed entirely with objective variables. We aimed to develop a prognostic model based on laboratory findings and vital signs using a fractional polynomial (FP) model. METHODS: A multicentre prospective cohort study was conducted at 58 specialist palliative care services in Japan from September 2012 to April 2014. Eligible patients were older than 20 years and had advanced cancer. We developed models for predicting 7-day, 14-day, 30-day, 56-day and 90-day survival by using the FP modelling method. RESULTS: Data from 1039 patients were analysed to develop each prognostic model (Objective Prognostic Index for advanced cancer [OPI-AC]). All models included the heart rate, urea and albumin, while some models included the respiratory rate, creatinine, C-reactive protein, lymphocyte count, neutrophil count, total bilirubin, lactate dehydrogenase and platelet/lymphocyte ratio. The area under the curve was 0.77, 0.81, 0.90, 0.90 and 0.92 for the 7-day, 14-day, 30-day, 56-day and 90-day model, respectively. The accuracy of the OPI-AC predicting 30-day, 56-day and 90-day survival was significantly higher than that of the Palliative Prognostic Score or the Prognosis in Palliative Care Study model, which are based on a combination of symptoms and physician estimation. CONCLUSION: We developed highly accurate prognostic indexes for predicting the survival of patients with advanced cancer from objective variables alone, which may be useful for end-of-life management. The FP modelling method could be promising for developing other prognostic models in future research.

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

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

Effect of continuous deep sedation on survival in patients with advanced cancer (J-Proval): a propensity score-weighted analysis of a prospective cohort study.

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.

Survival prediction for advanced cancer patients in the real world: A comparison of the Palliative Prognostic Score, Delirium-Palliative Prognostic Score, Palliative Prognostic Index and modified Prognosis in Palliative Care Study predictor model.

PURPOSE: The aim of this study was to investigate the feasibility and accuracy of the Palliative Prognostic Score (PaP score), Delirium-Palliative Prognostic Score (D-PaP score), Palliative Prognostic Index (PPI) and modified Prognosis in Palliative Care Study predictor model (PiPS model). PATIENTS AND METHODS: This multicentre prospective cohort study involved 58 palliative care services, including 19 hospital palliative care teams, 16 palliative care units and 23 home palliative care services, in Japan from September 2012 to April 2014. Analyses were performed involving four patient groups: those treated by palliative care teams, those in palliative care units, those at home and those receiving chemotherapy. RESULTS: We recruited 2426 participants, and 2361 patients were finally analysed. Risk groups based on these instruments successfully identified patients with different survival profiles in all groups. The feasibility of PPI and modified PiPS-A was more than 90% in all groups, followed by PaP and D-PaP scores; modified PiPS-B had the lowest feasibility. The accuracy of prognostic scores was ⩾69% in all groups and the difference was within 13%, while c-statistics were significantly lower with the PPI than PaP and D-PaP scores. CONCLUSION: The PaP score, D-PaP score, PPI and modified PiPS model provided distinct survival groups for patients in the three palliative care settings and those receiving chemotherapy. The PPI seems to be suitable for routine clinical use for situations where rough estimates of prognosis are sufficient and/or patients do not want invasive procedure. If clinicians can address more items, the modified PiPS-A would be a non-invasive alternative. In cases where blood samples are available or those requiring more accurate prediction, the PaP and D-PaP scores and modified PiPS-B would be more appropriate.

Glasgow prognostic score predicts prognosis for cancer patients in palliative settings: a subanalysis of the Japan-prognostic assessment tools validation (J-ProVal) study.

PURPOSE: The Glasgow prognostic score (GPS), which uses C-reactive protein and albumin levels, is a good predictor of prognosis in cancer patients undergoing anti-tumor therapy. The objective of this study was to investigate the correlation between GPS and survival among cancer patients in palliative settings, as findings in such populations have not been well described. METHODS: This was a subanalysis of a multicenter, prospective, cohort study in patients who were adults, diagnosed with advanced cancer, and first referred to palliative care service in Japan. Patients who were not receiving anti-tumor therapy and who had undergone laboratory examinations were eligible. Clinical features were analyzed to investigate prognostic factors. RESULTS: A total of 1160 patients were enrolled (41.6 % female; median age, 72 years). The independent predictors were Eastern Cooperative Oncology Group performance status (ECOG PS) score of 4 (hazard ratio (HR), 1.54), liver metastasis (HR, 1.21), dyspnea (HR, 1.35), edema (HR, 1.25), prognostic performance index (HR, 1.56), neutrophil-lymphocyte ratio (HR, 1.43), and GPS of 2 (HR, 1.36). The sensitivity and specificity for 3-week prognosis of a GPS of 2 were 0.879 and 0.410. Median survival time with GPS of 0, 1, and 2 was 58 days (95 % confidence interval, 48-81), 43 days (37-50), and 21 days (19-24), respectively (log-rank test, p < 0.001). CONCLUSION: The GPS was a good prognostic indicator for cancer patients in palliative settings.

Patient-reported usefulness of peripherally inserted central venous catheters in terminally ill cancer patients.

CONTEXT: Oral administration of medication is often difficult in terminally ill cancer patients, and a subcutaneous route is traditionally one of the most preferred parenteral routes. Recent studies suggest, however, that some patients and families prefer the intravenous route, and peripherally inserted central venous catheters (PICCs) are actively used in oncology settings. Nonetheless, in the palliative care setting, no empirical studies have investigated the patient-perceived usefulness of PICCs. OBJECTIVES: The primary aim of this prospective observational study was to clarify the levels of patient-perceived comfort and convenience, in addition to procedure-related distress, resulting from the use of PICCs by terminally ill cancer patients. RESULTS: Among 219 patients admitted to a palliative care unit during the one-year study period, 39 (18%) patients underwent a PICC insertion trial (a total of 44 procedures were performed because five patients underwent PICC insertion twice). Of the 44 procedures, 38 (86%) were successful, requiring a mean of 23+/-7.9 minutes, without serious procedure-related complications. Patient-reported levels of procedure-related distress were not distressing (68%), slightly distressing (8%), and distressing (24%). Patient-reported comfort levels with parenteral access were becoming more comfortable (94%) and no change (6%). Patient-reported convenience levels of parenteral access were becoming more convenient (94%) and no change (6%). Complications were reversible catheter coagulation (10%), irreversible catheter coagulation (8%), and mild levels of edema of the upper extremity (8%). The PICCs remained in place in 82% of the patients until death. The median period of placement was 15 days, with the longest placement being 81 days. CONCLUSION: PICCs were safely inserted in about 90% of terminally ill cancer patients within about 20 minutes. Although 30% of the patients experienced transient mild procedure-related distress, more than 90% of the patients felt that the parenteral route was more comfortable and convenient after the procedure. PICCs may provide a safe, comfortable, and convenient alternative for terminally ill cancer patients, if placement of the PICC is individualized to the patient situation and after alternatives are considered. Further studies are needed to compare the superiority of the PICC and traditional subcutaneous route to clarify what types of patients are the most suitable for each procedure.

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.

Changes in medical and nursing care in cancer patients transferred from a palliative care team to a palliative care unit.

The primary aim of this study was to explore the changes in medical/nursing care in patients who transferred from a palliative care team (PCT) to a palliative care unit (PCU) in the same hospital, and to explore the reasons why new or modified interventions were required. This was a retrospective study of 50 consecutive patients who were transferred from PCT to PCU in a 750-bed general hospital. A trained nurse performed a chart review and recorded the changes in 1) medical/nursing care, 2) help with decision-making within 48 hours after PCU admission, and 3) documentation of family and psycho-existential care. Group discussions among PCT and PCU staff members explored the potential reasons for the changes. Five patients were excluded due to admission periods of shorter than 48 hours. The number of new/modified medical and nursing care interventions after PCU admission averaged 1.9 +/- 1.5 and 1.5 +/- 1.3 per patient, respectively. The most common medical treatments were: reduction in hydration volume, dose titration of opioids, change in opioid administration device, opioid rotation, and addition of NSAIDs and steroids. The most common nursing interventions were: allowing patient to take a bath, changing mattress, use of massage, and discontinuation of bronchial suctioning. In addition, PCU staff newly coordinated opportunities to discuss preferred end-of-life care with primary caregivers in 38% of the cases, family members other than primary caregivers in 16%, and patients in 6.7%. The chart documentation of family care and psycho-existential care increased considerably after PCU admission. The chief reasons for these changes were: under-recognition of the problems and unavailability of treatments (pharmacological treatments), no intention to intervene and recommendations not followed by primary physicians (rehydration therapy), no intention to intervene (nursing care), and no intention to intervene and under-recognition of the problems (help with decision-making). These data demonstrate that many patients under PCT consultation receive new or modified interventions after PCU admission. Potentially useful strategies to strengthen the PCT interventions are: modification of intervention structure to minimize under-recognition of symptoms and decision making problems (e.g., use of standardized assessment tools, regular conferences), changes in the health care system to allow unlicensed drugs, clinical studies to clarify the benefits of artificial hydration therapy, and greater efforts to intervene in the areas of nursing care, help with decision making, family care, and psycho-existential care.

Palliative care team: the first year audit in Japan.

In Japan, palliative care team (PCT) services have been covered by National Health Insurance since 2002. The primary aims of this study were to compare the characteristics of patients who received PCT services with those admitted to palliative care units (PCU), and to clarify the medical treatments and symptom improvement during the first week after consultation with the PCT. This was a prospective audit study of 111 consecutive cancer patients referred to the PCT in Seirei Mikatabara Hospital and a comparison group of 100 consecutive patients admitted to PCU. As a part of daily practice, we prospectively recorded patient symptoms on a structured data collection sheet at the initial assessment and one week later. Symptom severity was measured by the Japanese version of the Schedule for Team Assessment Scale. After PCT consultation, 25% were discharged to home, 43% died in hospital, 40% died after admission to PCU, and 14% were alive at the end of the study period. Compared with PCU patients, PCT patients were significantly younger, had better performance status, were more likely to be referred with the described aim of symptom palliation, and suffered from more serious pain, appetite loss, somnolence, insomnia, anxiety, and delirium. There were significant improvements in symptom scores of pain, nausea, vomiting, constipation, abdominal swelling, dyspnea, sputum, insomnia, and anxiety during the first week in the PCT group. However, no significant improvements were observed in symptom scores of fatigue, dry mouth, somnolence, and delirium. A median of 3 interventions was performed for each patient, and the most common interventions were administration of NSAIDs, opioids, centrally-acting antiemetics, and steroids. These data indicate that a PCT was successfully implemented in Seirei Mikatabara Hospital, and may contribute to symptom improvement in cancer patients.

Neuroleptic malignant syndrome after haloperidol and fentanyl infusion in a patient with cancer with severe mineral imbalance.

This case report describes a terminally ill patient with cancer with severe hypophosphataemia, hypocalcemia, and hypomagnesemia who developed neuroleptic malignant syndrome after administration of a combination of haloperidol and fentanyl. The chief etiology of neuroleptic malignant syndrome in this patient was administration of haloperidol, but fentanyl and coexisting mineral imbalance could have contributed to development of the syndrome. Palliative care clinicians should be aware that neuroleptic malignant syndrome can occur in their patients receiving haloperidol.