Advancing the Care Experience for patients receiving Palliative care as they Transition from hospital to Home (ACEPATH): Codesigning an intervention to improve patient and family caregiver experiences.

BACKGROUND: Returning home from the hospital for palliative-focused care is a common transition, but the process can be emotionally distressing and logistically challenging for patients and caregivers. While interventions exist to aid in the transition, none have been developed in partnership with patients and caregivers. OBJECTIVE: To undergo the initial stages of codesign to create an intervention (Advancing the Care Experience for patients receiving Palliative care as they Transition from hospital to Home [ACEPATH]) to improve the experience of hospital-to-home transitions for adult patients receiving palliative care and their caregiver(s). METHODS: The codesign process consisted of (1) the development of codesign workshop (CDW) materials to communicate key findings from prior research to CDW participants; (2) CDWs with patients, caregivers and healthcare providers (HCPs); and (3) low-fidelity prototype testing to review CDW outputs and develop low-fidelity prototypes of interventions. HCPs provided feedback on the viability of low-fidelity prototypes. RESULTS: Three patients, seven caregivers and five HCPs participated in eight CDWs from July 2022 to March 2023. CDWs resulted in four intervention prototypes: a checklist, quick reference sheets, a patient/caregiver workbook and a transition navigator role. Outputs from CDWs included descriptions of interventions and measures of success. In April 2023, the four prototypes were presented in four low-fidelity prototype sessions to 20 HCPs. Participants in the low-fidelity prototype sessions provided feedback on what the interventions could look like, what problems the interventions were trying to solve and concerns about the interventions. CONCLUSION: Insights gained from this codesign work will inform high-fidelity prototype testing and the eventual implementation and evaluation of an ACEPATH intervention that aims to improve hospital-to-home transitions for patients receiving a palliative approach to care. PATIENT OR PUBLIC CONTRIBUTION: Patients and caregivers with lived experience attended CDWs aimed at designing an intervention to improve the transition from hospital to home. Their direct involvement aligns the intervention with patients' and caregivers' needs when transitioning from hospital to home. Furthermore, four patient/caregiver advisors were engaged throughout the project (from grant writing through to manuscript writing) to ensure all stages were patient- and caregiver-centred.

Long-term bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study.

BACKGROUND: Severe grief is highly distressing and prevalent up to 1 year post-death among people bereaved during the first wave of COVID-19, but no study has assessed changes in grief severity beyond this timeframe. AIM: Understand the trajectory of grief during the pandemic by reassessing grief symptoms in our original cohort 12-18 months post-death. DESIGN: Prospective matched cohort study. SETTINGS/PARTICIPANTS: Family members of decedents who died in an acute care hospital between November 1, 2019 and August 31, 2020 in Ottawa, Canada. Family members of patients who died of COVID (COVID +ve) were matched 2:1 with those who died of non-COVID illness (COVID -ve) during pandemic wave 1 or immediately prior to its onset (pre-COVID). Grief was assessed using the Inventory of Complicated Grief (ICG). RESULTS: Follow-up assessment was completed by 92% (111/121) of family members in the initial cohort. Mean ICG score on the 12-18-month assessment was 19.9 (SD = 11.8), and severe grief (ICG > 25) was present in 28.8% of participants. One-third (33.3%) had either a persistently high (>25) or worsening ICG score (⩾4-point increase between assessments). Using a modified Poisson regression analysis, persistently high or worsening ICG scores were associated with endotracheal intubation in the deceased, but not cause of death (COVID +ve, COVID -ve, pre-COVID) or physical presence of the family member in the final 48 h of life. CONCLUSIONS: Severe grief is a substantial source of psychological morbidity in the wake of the COVID-19 pandemic, persisting more than a year post-death. Our findings highlight an acute need for effective and scalable means of addressing severe grief.

Bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study.

BACKGROUND: The COVID-19 pandemic has caused millions of deaths worldwide, leading to symptoms of grief among the bereaved. Neither the burden of severe grief nor its predictors are fully known within the context of the pandemic. AIM: To determine the prevalence and predictors of severe grief in family members who were bereaved early in the COVID-19 pandemic. DESIGN: Prospective, matched cohort study. SETTING/PARTICIPANTS: Family members of people who died in an acute hospital in Ottawa, Canada between November 1, 2019 and August 31, 2020. We matched relatives of patients who died of COVID (COVID +ve) with those who died of non-COVID illness either during wave 1 of the pandemic (COVID -ve) or immediately prior to its onset (pre-COVID). We abstracted decedents' medical records, contacted family members >6 months post loss, and assessed grief symptoms using the Inventory of Complicated Grief-revised. RESULTS: We abstracted data for 425 decedents (85 COVID +ve, 170 COVID -ve, and 170 pre-COVID), and 110 of 165 contacted family members (67%) consented to participate. Pre-COVID family members were physically present more in the last 48 h of life; the COVID +ve cohort were more present virtually. Overall, 35 family members (28.9%) had severe grief symptoms, and the prevalence was similar among the cohorts (p = 0.91). Grief severity was not correlated with demographic factors, physical presence in the final 48 h of life, intubation, or relationship with the deceased. CONCLUSION: Severe grief is common among family members bereaved during the COVID-19 pandemic, regardless of the cause or circumstances of death, and even if their loss took place before the onset of the pandemic. This suggests that aspects of the pandemic itself contribute to severe grief, and factors that normally mitigate grief may not be as effective.

Adaptation, implementation, and mixed methods evaluation of an interprofessional modular clinical practice guideline for delirium management on an inpatient palliative care unit.

BACKGROUND: Using delirium clinical guidelines may align interprofessional clinical practice and improve the care of delirious patients and their families. The aim of this project was to adapt, implement and evaluate an interprofessional modular delirium clinical practice guideline for an inpatient palliative care unit. METHODS: The setting was a 31-bed adult inpatient palliative care unit within a university-affiliated teaching hospital. Participants for the evaluation were interprofessional team members. Using integration of guideline adaptation and an education initiative, an interprofessional guideline adaptation group developed a face-to-face 'starter kit' module and four online self-learning modules. The mixed methods evaluation comprised pre-and post-implementation review of electronic patient records, an online survey, and analysis of focus groups/ interviews using an iterative, inductive thematic analysis approach. RESULTS: Guideline implementation took 12 months. All palliative care unit staff attended a 'starter kit' session. Overall completion rate of the four e-Learning modules was 80.4%. After guideline implementation, nursing documentation of non-pharmacological interventions occurring before medication administration was observed. There was 60% less scheduled antipsychotic use and an increase in 'as needed' midazolam use. The online survey response rate was 32% (25/77). Most participants viewed the guideline's implementation favourably. Six key themes emerged from the qualitative analysis of interviews and focus groups with ten participants: prior delirium knowledge or experiences, challenges of facilitating change, impacts on practice, collaborative effort of change, importance of standardized guidelines, and utility of guideline elements. CONCLUSIONS: Guideline implementation warrants concerted effort, time, and management support. Interprofessional team support facilitates the modular approach of guideline adaptation and implementation, leading to a change in clinical practice.

Acculturation and Perceptions of a Good Death Among Japanese Americans and Japanese Living in the U.S.

CONTEXT: Acculturation is the phenomenon of the attitudinal changes of individuals who come into continuous contact with another culture. Despite the long history of Japanese immigration to America, little is known about the impact of acculturation on perceptions of a good death. OBJECTIVES: To examine differences in perceptions of a good cancer death among Japanese Americans (JA/A), Japanese living in America (J/A), and the Japanese living in Japan (J/J). METHODS: We administered surveys among JA/A and J/A and used historical J/J data for reference. Primary endpoint was the proportion of respondents who expressed the necessity of core and optional items of the Good Death Inventory. Group differences ≥20% were deemed clinically important. RESULTS: In total, 441 survey responses in America and 2548 in Japan were obtained. More than 80% of respondents consistently considered nine of 10 core items necessary without significant group differences. No core item reached a ≥20% group difference. Three of the eight optional items reached ≥20% group difference: fighting against disease until one's last moment (49%, P < 0.0001; 52%, P < 0.0001; and 73% in JA/A, J/A, and J/J, respectively), knowing what to expect about one's condition in the future (83%, P < 0.0001; 80%, P < 0.0001; and 58%, respectively), and having faith (64%, P = 0.0548; 43%, P = 0.0127; and 38%, respectively). CONCLUSION: Although most core items of a good death were preserved throughout the levels of acculturation, perceptions of some optional items shifted away from Japanese attitudes as individuals became more acculturated. Understanding of different levels of acculturation may help clinicians provide culturally sensitive end-of-life care.

The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer.

BACKGROUND: Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. METHODS AND RESULTS: Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change -4.8[-9.1,-0.1] vs. -0.05%[-4.2, 2.6] in controls,p<0.001) and fat (median [IQR] percent change -6.8%[-15,-0.6] vs. -4.0%[-7.6, 1.3] in controls,p=0.04). Subcutaneous fat was more affected in the treated patients. Sarcopenic patients treated with curcumin(n=15) had survival of 169(115-223) days vs. 299(229-369) sarcopenic controls(p=0.024). No survival difference was found amongst non-sarcopenic patients. CONCLUSIONS: Patients with advanced pancreatic cancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls.

A pilot study of temsirolimus and body composition.

PURPOSE: Body weight and composition play a role in cancer etiology, prognosis, and treatment response. Therefore, we analyzed the weight, body composition changes, and outcome in patients treated with temsirolimus, an mTor inhibitor that has weight loss as one of its side effects. PATIENTS AND METHODS: Sixteen patients with advanced solid tumors treated with temsirolimus were studied; body composition was evaluated utilizing computerized tomography images. Sarcopenia was defined as skeletal muscle index lower than 38.5 cm(2)/m(2) for women and 52.4 cm(2)/m(2) for men. RESULTS: Five of 16 patients (31 %) were men; median age, 60 years. Forty-four percent (7/16) of patients were sarcopenic. Fatigue, anemia, hyperglycemia, and hyperlipidemia were common. Baseline sarcopenia and body composition did not correlate with worse toxicity or treatment outcome. However, there was a trend for greater loss of adipose area (p = 0.07), fat mass (p = 0.09), and adipose index (p = 0.07) for patients with grade 3 or 4 toxicities versus those with grade 1 and 2 side effects. CONCLUSION: Patients with higher grade toxicities tended to lose more body fat, suggesting a possible end-organ metabolic effect of temsirolimus. These observations merit exploration in a larger cohort of patients.

Frequency and predictors of patient deviation from prescribed opioids and barriers to opioid pain management in patients with advanced cancer.

CONTEXT: Approximately 80% of patients with advanced cancer report pain and receive opioids. Information is limited about deviations from prescribed opioid doses and barriers to pain control, but poor opioid adherence has been reported in 49%-70% of patients. OBJECTIVES: To evaluate the frequency and severity of self-reported opioid deviation and barriers to opioid pain management in outpatients with advanced cancer. METHODS: We surveyed 198 patients and collected pain scores (0-10), prescribed opioid dose, confidential patient-reported opioid prescription dose and intake (as long as there was no severe opioid deviation), barriers to pain management (Barriers Questionnaire-II [BQ-II]) scores, and adherence scores. Opioid deviation was defined as <70% or >130% of the prescribed dose. RESULTS: Median patient age was 55 years; 91 (46%) were female. Median pain intensity and morphine equivalent daily dose were 4 (interquartile range=3-7) and 120mg (interquartile range=45-270mg), respectively. Prescribed and patient-reported prescribed doses were highly correlated for regular (r=0.90, P<0.001) and regular plus breakthrough opioid intake (r=0.94, P<0.001). Nineteen (9.6%) patients deviated. Deviation was more frequent in males (P=0.039) and nonwhites (P=0.0270). Nonwhite patients had higher scores on the BQ-II than white patients (P=0.038). Low adherence scores were significantly associated with higher BQ-II scores (1.99±0.80) for lower motivation score vs. 1.61±0.77 for higher score, P=0.007; and 2.13±0.79 for lower knowledge score vs. 1.57±0.72 for higher score, P=0.001. CONCLUSION: Very few patients reported dose deviations, which were mostly toward lower dose. More research is necessary to better characterize the frequency and predictors of opioid deviation in this population.

Spirituality, religiosity, and spiritual pain among caregivers of patients with advanced cancer.

BACKGROUND: Caregivers of patients with advanced cancer often face physical, social, and emotional distress as well as spiritual pain. Limited research has focused on the spiritual aspects of caregivers' suffering in the palliative care setting. METHODS: We interviewed 43 caregivers of patients with advanced cancer in our palliative care outpatient clinic. We determined demographic characteristics, religious affiliation, and relationship to the patient. Levels of spirituality, religiosity, and spiritual pain were self-reported using numeric rating scales (0 = lowest; 10 = highest). The participants completed various validated questionnaires to assess sleep disturbances, psychosocial distress, coping skills, and quality of life (QOL). RESULTS: The median age was 52 years (range, 21-83); 29 (67%) were women, 34 (78%) were white, 7 (17%) were African American, and 2 (5%) were Hispanic; 39 (91%) were Christian, 1 (2%) was Jewish, and 1 (2%) was agnostic; 37 (86%) were married; 18 (42%) were working full time; and 25 (58%) were spouses. All considered themselves spiritual, and 98% considered themselves religious, with median scores of 8 (interquartile range, 6-10) and 8 (interquartile range, 4-9), respectively. All the caregivers reported that spirituality and religiosity helped them cope with their loved one's illness, and many reported that spirituality and religiosity had a positive impact on their loved one's physical (58%) and emotional (76%) symptoms. Spiritual pain was reported by 23 (58%), with a median score of 5 (interquartile range, 2-8). Caregivers with spiritual pain had higher levels of anxiety (median 10 vs 4; P = .002), depression (6 vs 2; P = .006), and denial (3 vs 2; P = .01); more behavioral disengagement (3 vs 2; P = 0.011) more dysfunctional coping strategies (19 vs 16; P < .001) and worse QOL (70 vs 51; P < .001) than those who did not have spiritual pain. CONCLUSIONS: The majority of caregivers of patients with advanced cancer considered themselves spiritual and religious. Despite this, there is high prevalence of spiritual pain in this population. Caregivers with spiritual pain experienced worse psychological distress and worse QOL. These findings support the importance of spiritual assessment of and spiritual support for caregivers in this setting.

Decisional control preferences of Hispanic patients with advanced cancer from the United States and Latin America.

CONTEXT: Understanding cancer patients' preferences in decisional roles is important in providing quality care and ensuring patient satisfaction. There is a lack of evidence on decisional control preferences (DCPs) of Hispanic Americans, the fastest growing population in the U.S. OBJECTIVES: The primary aims of this study were to describe DCPs of Hispanics with advanced cancer in the U.S. (HUSs) and compare the frequency of passive DCPs in this population with that of Hispanics with advanced cancer in Latin America (HLAs). METHODS: We conducted a prospective survey of patients with advanced cancer referred to outpatient palliative care clinics in the U.S., Chile, Argentina, and Guatemala. Information was collected on sociodemographic variables, Karnofsky Performance Scale scores, acculturation (Marin Acculturation Assessment Tool), and DCP (Control Preference Scale). Chi-square tests were used to determine the differences in DCPs between HUSs and HLAs. RESULTS: A total of 387 patients were surveyed: 91 in the U.S., 100 in Chile, 94 in Guatemala, and 99 in Argentina. The median age of HUSs was 56 years, 59% were female, and the median Karnofsky Performance Scale score was 60; the corresponding values for HLAs were 60 years, 60%, and 80. HLAs used passive DCP strategies significantly more frequently than HUSs did with regard to the involvement of the family (24% vs. 10%; P=0.009) or the physician (35% vs. 16%; P<0.001), even after age and education were controlled for. Eighty-three percent of HUSs and 82% of HLAs preferred family involvement in decision making (P=non-significant). No significant differences were found in DCPs between poorly and highly acculturated HUSs (P=0.91). CONCLUSION: HUSs had more active DCPs than HLAs did. Among HUSs, acculturation did not seem to play a role in DCP determination. Our findings confirm the importance of family participation for both HUSs and HLAs. However, HUSs were less likely to want family members to make decisions on their behalf.

Concepts and definitions for "supportive care," "best supportive care," "palliative care," and "hospice care" in the published literature, dictionaries, and textbooks.

PURPOSE: Commonly used terms such as "supportive care," "best supportive care," "palliative care," and "hospice care" were rarely and inconsistently defined in the palliative oncology literature. We conducted a systematic review of the literature to further identify concepts and definitions for these terms. METHODS: We searched MEDLINE, PsycInfo, EMBASE, and CINAHL for published peer-reviewed articles from 1948 to 2011 that conceptualized, defined, or examined these terms. Two researchers independently reviewed each citation for inclusion and then extracted the concepts/definitions when available. Dictionaries/textbooks were also searched. RESULTS: Nine of 32 "SC/BSC," 25 of 182 "PC," and 12 of 42 "HC" articles focused on providing a conceptual framework/definition. Common concepts for all three terms were symptom control and quality-of-life for patients with life-limiting illness. "SC" focused more on patients on active treatment compared to other categories (9/9 vs. 8/37) and less often involved interdisciplinary care (4/9 vs. 31/37). In contrast, "HC" focused more on volunteers (6/12 vs. 6/34), bereavement care (9/12 vs. 7/34), and community care (9/12 vs. 6/34). Both "PC" and "SC/BSC" were applicable earlier in the disease trajectory (16/34 vs. 0/9). We found 13, 24, and 17 different definitions for "SC/BSC," "PC," and "HC," respectively. "SC/BSC" was the most variably defined, ranging from symptom management during cancer therapy to survivorship care. Dictionaries/textbooks showed similar findings. CONCLUSION: We identified defining concepts for "SC/BSC," "PC," and "HC" and developed a preliminary conceptual framework unifying these terms along the continuum of care to help build consensus toward standardized definitions.

Outcomes of phase II clinical trials with single-agent therapies in advanced/metastatic non-small cell lung cancer published between 2000 and 2009.

PURPOSE: We analyzed the outcomes of single-agent phase II clinical trials in non-small cell lung cancer (NSCLC) to determine trial parameters that predicted clinical activity. EXPERIMENTAL DESIGN: Data on response rate (RR), progression-free survival (PFS), and overall survival (OS) from all English language, single-agent phase II trials in advanced/metastatic NSCLC indexed by PubMed (January 2000 through December 2009) were abstracted. RESULTS: A total of 143 single-agent phase II trials (7,701 patients) were identified. The median RR was 10%, PFS 2.8 months, and OS 7.6 months. RR and PFS correlated with OS (r = 0.46, P < 0.001, r = 0.52, P < 0.001, respectively) and RR correlated with PFS (r = 0.61, P < 0.001). Treatment arms enriched for patients with molecular targets had a higher median RR (48.8% vs. 9.7%, P = 0.005), longer median PFS (6 vs. 2.8 months, P = 0.005), and OS (11.3 vs. 7.5 months, P = 0.05) as compared with those of unselected patients. In multivariate analysis, only studies enriched for patients with molecular targets or including drugs that eventually gained FDA/EMA approval were associated with a higher RR, and longer PFS/OS. CONCLUSIONS: In phase II trials in NSCLC, RR and PFS correlated with OS. Studies enriched for patients with putative molecular drug targets were associated with higher therapeutic benefit as compared with those of unselected populations.

Reporting of funding sources and conflict of interest in the supportive and palliative oncology literature.

CONTEXT: The reporting of funding support and conflict of interest has not been examined in the supportive/palliative oncology literature. OBJECTIVES: We examined the frequency of funding and conflict of interest reporting and various study characteristics associated with such reporting. METHODS: We systematically searched MEDLINE PubMed, PsycInfo, EMBASE, ISI Web of Science, and CINAHL for original studies related to palliative care and cancer in the first six months of 2004 and 2009. For each article, we reviewed the study design, research topic, journal type, and reporting of funding and conflict of interest. RESULTS: Three hundred forty-four (41%) and 504 (59%) of 848 articles were from 2004 and 2009, respectively. Five hundred two of 848 (59%) studies reported no funding sources, whereas 216 (26%), 70 (8%), 34 (4%), and 26 (3%) reported one, two, three, and four or more sources, respectively. Key funding sources included governmental agencies (n=182/848, 21%), philanthropic foundations (n=163/848, 19%), university departments (n=76/848, 9%), and industry (n=27/848, 3%). Conflict of interest was not reported in 436 of 848 (51%) studies, and only 94 of 848 (11%) explicitly stated no conflict of interest. Other than extramural funding, conflict of interest reporting of any kind was extremely rare (mostly less than 1%). Conflict of interest reporting increased between 2004 and 2009 (39% vs. 55%, P<0.001). Both funding and conflict of interest reporting were associated with prospective studies, larger sample sizes, nontherapeutic studies, North American authors, and publication in palliative care/oncology journals (P≤0.008 for all comparisons). CONCLUSION: A majority of supportive/palliative oncology studies did not report funding sources and conflict of interest, raising the need for standardization.

Evaluation of the clinical relevance of body composition parameters in patients with cancer metastatic to the liver treated with hepatic arterial infusion chemotherapy.

The association between body composition parameters and toxicity from hepatic arterial infusion (HAI) chemotherapy regimens has not been analyzed. We assessed data from patients with advanced cancer and liver metastases treated on a clinical trial of a regimen of HAI oxaliplatin combined with systemic 5-fluorouracil/leucovorin and bevacizumab. Correlations between patient characteristics, response, and toxicity and body composition data taken from CT images were analyzed. Forty-eight of 57 patients (mean age 56 yr; 60% women) had available CT scans. The most common diagnosis was colorectal cancer (22/48, 46%); 30/48 patients (63%) had body mass index (BMI) ≥25 kg/m(2). Twenty (42%) of 48 patients were sarcopenic. Grade 3-4 adverse events did not differ among patients with and without sarcopenia or according to BMI. The median survival (95% C]) was 167 (128-206) days for sarcopenic and 280 (214-346) days for nonsarcopenic patients (P = 0.271). Among patients treated at the maximum tolerated dose, the median survival was 103 days for sarcopenic and 312 days for nonsarcopenic patients (P = 0.173). Sarcopenia was present in 30% (6/20) of patients with reduction in tumor size posttreatment, and in 52% (14/27) of patients with increased tumor size (P = 0.171). In conclusion, body composition was not significantly associated with toxicities or survival in our small sample.

Body composition, symptoms, and survival in advanced cancer patients referred to a phase I service.

BACKGROUND: Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown. METHODS: We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)≥25 kg/m² was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria. RESULTS: Most patients were overweight (n = 65, 63%); 53 patients were sarcopenic (51%), including 79% of patients with a BMI<25 kg/m² and 34% of those with BMI≥25 kg/m². Sarcopenic patients were older and less frequently African-American. Symptom burden did not differ among patients classified according to BMI and presence of sarcopenia. Median (95% confidence interval) survival (days) varied according to body composition: 215 (71-358) (BMI<25 kg/m²; sarcopenic), 271 (99-443) (BMI<25 kg/m²; non-sarcopenic), 484 (286-681) (BMI≥25 kg/m²; sarcopenic); 501 d (309-693) (BMI≥25 kg/m²; non-sarcopenic). Higher muscle index and gastrointestinal cancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index. CONCLUSIONS: Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI≥25 kg/m², independent of symptom burden. Body composition variables were predictive of clinically relevant survival differences, which is potentially important in developing Phase I studies.

The lack of standard definitions in the supportive and palliative oncology literature.

CONTEXT: Multiple organizations have raised concerns about the lack of standard definitions for terminology in the supportive and palliative oncology literature. OBJECTIVES: We aimed to determine 1) the frequency of 10 commonly used terms in the supportive and palliative oncology literature, 2) the proportion of articles that provided definitions for each term, and 3) how each term was defined. METHODS: We systematically searched MEDLINE, PubMed, PsycINFO, the Cochrane Library, Embase, ISI Web of Science, and Cumulative Index to Nursing and Allied Health Literature for original studies, review articles, and systematic reviews related to palliative care and cancer in the first six months of 2004 and 2009. We counted the number of occurrences for "palliative care," "supportive care," "best supportive care," "hospice care," "terminal care," "end-of-life," "terminally ill," "goals of care," "actively dying," and "transition of care" in each article, reviewed them for the presence of definitions, and documented the journal characteristics. RESULTS: Among the 1213 articles found, 678 (56%) were from 2009. "Palliative care" and "end-of-life" were the most frequently used terms. "Palliative care," "end-of-life," and "terminally ill" appeared more frequently in palliative care journals, whereas "supportive care" and "best supportive care" were used more often in oncology journals (P<0.001). Among 35 of 601 (6%) articles with a definition for "palliative care," there were 16 different variations (21 of 35 articles used the World Health Organization definition). "Hospice care" had 13 definitions among 13 of 151 (9%) articles. "Supportive care" and other terms were rarely defined (less than 5% of articles that used the term). CONCLUSION: Our findings highlight the lack of definitional clarity for many important terms in the supportive and palliative oncology literature. Standard definitions are needed to improve administrative, clinical, and research operations.

R1507, an anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, and EWS/FLI-1 siRNA in Ewing's sarcoma: convergence at the IGF/IGFR/Akt axis.

A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt.

Changes in symptoms and inpatient mortality: a study in advanced cancer patients admitted to an acute palliative care unit in a comprehensive cancer center.

CONTEXT: Although several symptoms have been shown to predict survival, little is known of the roles of symptom changes in predicting inpatient death. OBJECTIVES: To determine the association between changes in symptoms and inpatient mortality among advanced cancer patients in an acute palliative care unit (APCU). METHODS: We retrospectively reviewed the medical records of 166 consecutive cancer patients admitted to our APCU from the emergency center (EC) or clinic from June 2006 to December 2007. We recorded symptom severity and presence of delirium on admission (baseline) and on the third, fourth, or fifthth day, whichever appeared first (follow-up). The primary endpoint was the vital status at discharge. Univariate (UVA) and multivariate analyses (MVA) were used to estimate the odds of inpatient death. RESULTS: One hundred and thirty-four patients (80.7%) were discharged alive and 32 (19.3%) died in the APCU. All symptoms significantly improved at follow-up. In UVA, persistent delirium was significantly associated with inpatient mortality (odds ratio [OR] 2.59, 95% confidence interval [CI 1] 0.09-6.17, p = 0.031), although presence of baseline delirium was not. MVA revealed that greater risk of dying was jointly correlated with a high level of baseline dyspnea (OR 1.35, 95% CI 1.13-1.61, p = 0.001) and drowsiness (OR 1.25, 95% CI 1.04-1.50, p = 0.02), low level of baseline anxiety (OR 0.83, 95% CI 0.70-0.99, p = 0.038), and transfer from EC (OR 6.78, 95% CI 1.99-23.14, p = 0.002). Worsened depression was significantly related with death in UVA (OR 1.30, 95% CI 1.08-1.56, p < 0.001), but not in MVA. CONCLUSION: Changes in certain symptoms, such as worsened depression and persistent delirium, might be important predictors of inpatient death.

Quantity, design, and scope of the palliative oncology literature.

The current state of the palliative oncology literature is unclear. We examined and compared the quantity, research design, and research topics of palliative oncology publications in the first 6 months of 2004 with the first 6 months of 2009. We systematically searched MEDLINE, PsychInfo, EMBASE, ISI Web of Science, and CINAHL for original studies, review articles, and systematic reviews related to "palliative care" and "cancer" during the first 6 months of 2004 and 2009. Two physicians reviewed the literature independently and coded the study characteristics with high inter-rater reliability. We found a consistent decrease in the proportion of oncology studies related to palliative care between 2004 and 2009, despite an absolute increase in the total number of palliative oncology studies. Combining the two time periods, the most common original study designs were case report/series, cross-sectional studies, and qualitative studies. Randomized controlled trials comprised 6% of all original studies. The most common topics were physical symptoms, health services research, and psychosocial issues. Communication, decision making, spirituality, education, and research methodologies all represented <5% of the literature. Comparing 2004 with 2009, we found an increase in the proportion of original studies among all palliative oncology publications but no significant difference in study design or research topic. We identified significant deficiencies in the quantity, design, and scope of the palliative oncology literature. Further effort and resources are necessary to improve the evidence base for this important field.

Spirituality, religiosity, and spiritual pain in advanced cancer patients.

CONTEXT: Spirituality, religiosity, and spiritual pain may affect advanced cancer patients' symptom expression, coping strategies, and quality of life. OBJECTIVES: To examine the prevalence and intensity of spirituality, religiosity, and spiritual pain, and how spiritual pain was associated with symptom expression, coping, and spiritual quality of life. METHODS: We interviewed 100 advanced cancer patients at the M.D. Anderson palliative care outpatient clinic in Houston, TX. Self-rated spirituality, religiosity, and spiritual pain were assessed using numeric rating scales (0=lowest, 10=highest). Patients also completed validated questionnaires assessing symptoms (Edmonton Symptom Assessment Scale [ESAS] and Hospital Anxiety and Depression Scale), coping (Brief COPE and Brief R-COPE), the value attributed by the patient to spirituality/religiosity in coping with cancer (Systems of Belief Inventory-15R), and spiritual quality of life (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being-Expanded [FACIT-Sp-Ex]). RESULTS: The median age was 53 years (range 21-85) and 88% were Christians. Almost all patients considered themselves spiritual (98%) and religious (98%), with a median intensity of 9 (interquartile range 7-10) of 10 and 9 (range 5-10) of 10, respectively. Spiritual pain was reported in 40 (44%) of 91 patients, with a median score of 3 (1-6) among those with spiritual pain. Spiritual pain was significantly associated with lower self-perceived religiosity (7 vs. 10, P=0.002) and spiritual quality of life (FACIT-Sp-Ex 68 vs. 81, P=0.001). Patients with spiritual pain reported that it contributed adversely to their physical/emotional symptoms (P<0.001). There was a trend toward increased depression, anxiety, anorexia, and drowsiness, as measured by the ESAS, among patients with spiritual pain (P<0.05), although this was not significant after Bonferroni correction. CONCLUSION: A vast majority of advanced cancer patients receiving palliative care considered themselves spiritual and religious. Spiritual pain was common and was associated with lower self-perceived religiosity and spiritual quality of life.