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Context: Spiritual, existential, and psychological issues represent central components of quality of life (QOL) in palliative care. A better understanding of the dynamic nature underlying these components is essential for the development of interventions tailored to the palliative context.Objectives: The aims were to explore 1) the relationship between spirituality, meaning in life, wishes for hastened death and psychological distress in palliative patients and 2) the extent to which these nonphysical determinants influence QOL.Methods: A cross-sectional study involving face-to-face interviews with Swiss palliative patients was performed, including the Schedule for Meaning in Life Evaluation (SMILE), the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), the Idler Index of Religiosity (IIR), the Hospital Anxiety and Depression Scale (HADS), and the Schedule of Attitudes toward Hastened Death (SAHD). QOL was measured with a single-item visual analogue scale (0-10).Results: Two hundred and six patients completed the protocol (51.5% female; mean age = 67.5 years). The results indicated a significant negative relationship between FACIT-Sp/SMILE and HADS total scores (P = 0.000). The best model for QOL explained 32.8% of the variance (P = 0.000) and included the FACIT-Sp, SMILE, and SAHD total scores, the IIR "private religiosity" score, as well as the HADS "depression" score.Conclusion: Both spiritual well-being and meaning in life appear to be potential protective factors against psychological distress at the end of life. Since nonphysical determinants play a major role in shaping QOL at the end of life, there is a need for the development of meaning-oriented and spiritual care interventions tailored to the fragility of palliative patients. [ABSTRACT FROM AUTHOR]

The combined approach of incubating environmental samples with stable isotope-labeled substrates followed by single-cell analyses through high-resolution secondary ion mass spectrometry (NanoSIMS) or Raman microspectroscopy provides insights into the in situ function of microorganisms. This approach has found limited application in soils presumably due to the dispersal of microbial cells in a large background of particles. We developed a pipeline for the efficient preparation of cell extracts from soils for subsequent single-cell methods by combining cell detachment with separation of cells and soil particles followed by cell concentration. The procedure was evaluated by examining its influence on cell recoveries and microbial community composition across two soils. This approach generated a cell fraction with considerably reduced soil particle load and of sufficient small size to allow single-cell analysis by NanoSIMS, as shown when detecting active N2-fixing and cellulose-responsive microorganisms via 15N2 and 13C-UL-cellulose incubations, respectively. The same procedure was also applicable for Raman microspectroscopic analyses of soil microorganisms, assessed via microcosm incubations with a 13C-labeled carbon source and deuterium oxide (D2O, a general activity marker). The described sample preparation procedure enables single-cell analysis of soil microorganisms using NanoSIMS and Raman microspectroscopy, but should also facilitate single-cell sorting and sequencing. [ABSTRACT FROM AUTHOR]

Introduction: The benefits of integration of palliative care into oncology have become evidence-based. How palliative care is perceived and structured in various settings and countries would be of interest. Method: We used a previously published questionnaire to survey multiple institutions with members in MASCC and ESMO. The survey was made available on the MASCC website for approximately 6 months and repeated requests were made to complete the survey. Comparisons were made between NCI/ESMO designated cancer centers, nondesignated cancer centers, and urban hospitals. Results: One hundred eighty-three different institutions completed this survey, 28 % of ESMO designated centers. Most institutions had palliative care programs and most programs consisted of an inpatient consult service and outpatient clinics. A minority had inpatient palliative care beds and institution supported hospice services. Barriers to palliative care were largely financial. Integration of palliative care into oncology was highly desirable but only a minority of respondents felt that their institution would financially support expanded services and additional palliative care personnel. Designated centers were more likely to have expanded palliative care services. Discussion: Our findings are very similar to those previously published. Multiple studies have demonstrated that though palliative care integration into oncology is highly beneficial as measured by patient related outcomes, there is a great concern about reimbursement for services and budget constraints which prevent expansion of services. Conclusion: Palliative care integration into cancer care is largely through consulting services for inpatients and outpatient clinics. Financial concerns limit integration and expansion of palliative care services. Designated cancer centers have more extensive palliative care services relative to nondesignated cancer centers and urban hospitals. [ABSTRACT FROM AUTHOR]

Background: Palliative care program structure is important to integrating palliative services into cancer care. A first step in understanding the structure of palliative care programs is to survey existing programs. Method: This data was generated from members of MASCC, the European Society of Medical Oncology (ESMO), and the European Association of Palliative Care (EAPC) who completed the surveys on the website. A survey questionnaire was developed using the survey tool developed by Dr. Hui and colleagues by permission which was modified for the purposes of this study. Findings were described in number and percentages. Inferential statistics involved the Fisher's exact test for factors with two levels, chi-Square test for unordered categorical factors with greater than two levels, Cochran-Armitage trend test for ordered categorical factors, and the Wilcoxon rank sum test for measured factors. Results: Sixty-two program leaders completed the survey. Most programs had been in existence greater than 5 years and were led by oncology trained physicians who had an additional specialty. Most programs had consultative services and outpatient clinics with fewer having inpatient beds and institutionally associated hospices. Most programs provided patient continuity. Patients were generally seen late in the course of illness with the average survival of 23 days when seen as inpatients and 40 days when seen as outpatients. Less than half had palliative care fellowship training programs. Most had research structures in place. Discussion: These findings differ from results reported in a previous survey which may reflect a European palliative care program structure. However, there were similarities which include a high inpatient palliative care unit mortality and short survival of patients seen as outpatients, indicating that referrals to palliative care occur late in the course of cancer. Conclusions: This study not only differs in some respects to a previous survey of palliative care programs but also confirms the late referral of patients to palliative care. [ABSTRACT FROM AUTHOR]

Abstract: Context: This is a subset analysis of fatigue data and associated clinical variables collected as part of the European Palliative Care Research Collaborative Computerized Symptom Assessment (CSA) study. The overall aim of CSA was to determine the prevalence of common symptoms in a mixed advanced cancer group using an electronic data collection system. Objectives: This analysis was conducted to identify factors independently associated with fatigue. Methods: Only patient records containing complete data for all three measured blood parameters in the CSA study (C-reactive protein [CRP], hemoglobin, and albumin) were included in our subset analysis (n =720). Participants with locoregional or metastatic disease of all tumor types were included (with or without concurrent palliative anticancer treatment). A large number of symptoms were recorded using a predesigned computer program and widely used symptom measurement scales. Fatigue was measured using a well-validated three-item fatigue scale taken from the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire. A logistic regression model was developed using a cutoff score based on the available normative data to define the presence or the absence of severe fatigue. Results: Cases of fatigue were independently associated with chemotherapy treatment and experiencing other symptoms such as pain and depression. There was a moderate association with hemoglobin level. However, there was no link to cachexia, albumin, or CRP. Conclusion: Severe fatigue is linked with treatment history and hemoglobin levels rather than CRP, mood, and other common symptoms in a mixed advanced cancer group. [Copyright &y& Elsevier]

Abstract: Ghrelin increases food intake and decreases energy expenditure, promoting a positive energy balance. We observed a single case of serious hypothermia during sustained ghrelin treatment in a male subject, suggesting that ghrelin may play a role in the regulation of body temperature. We therefore investigated the effect of ghrelin treatment on body temperature in rodents and humans under controlled conditions. Intriguingly, we could demonstrate ghrelin binding in axon terminals of the medial preoptic area of the hypothalamus located in the vicinity of cold-sensitive neurons. This localization of ghrelin receptors provides a potential anatomical basis for the regulation of body temperature by ghrelin. However, our follow-up studies also indicated that neither a chronic i.c.v. application of ghrelin in rats, nor a single s.c. injection under cold exposure in mice resulted in a relevant decrease in body core temperature. In addition, a four-hour intravenous ghrelin infusion did not decrease body surface temperature in healthy humans. We concluded that while there is a theoretical molecular basis for ghrelin to modify body temperature in mammals, its magnitude is irrelevant under physiologic circumstances. Hypothermia is not likely to represent a serious risk associated with this agent and pathway. [Copyright &y& Elsevier]

Summary: To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m2) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages—precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management. [Copyright &y& Elsevier]

Abstract: Context: Autonomic nervous system dysfunction (AD) is a common syndrome in patients with advanced cancer. It is associated with decreased survival in several patient populations, including diabetes mellitus, heart failure, and neurological diseases. Based on this evidence, we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer. Objectives: The objective of this preliminary study was to test the association between AD, as measured by the standardized Ewing test and heart rate variability (HRV) measures, and survival in this patient population. Methods: We examined the relationship between survival and parameters of AD in subjects who participated in a prospective study of autonomic dysfunction and hypogonadism in male patients with advanced cancer. Eligibility criteria were defined based on the prospective study protocol. We collected demographic information, date of death (obtained from the online Social Security Death Index database), date of study entry, and Ewing and HRV scores. We defined survival as the interval between study entry and date of death. A survival analysis was used to test the association between survival (in days) and Ewing test (0–5) and measures of HRV, including time domain (standard deviation of normal to normal beat interval [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients were still alive at the time of this study and included in the survival analysis as being censored. Results: Forty-seven male patients were included in this study. Median age was 59 years (range: 20–79), and 30 out of 47 (63%) were Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of 47 (80%) of the patients. Median Ewing score was 3 (1–5), indicating moderate to severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002). There was a significant association between abnormal Ewing score and survival (P < 0.0001) and abnormal SDNN HRV and survival (P = 0.056). Conclusion: AD is associated with shorter survival in male patients with advanced cancer. Further longitudinal research in a large cohort is justified based on. [Copyright &y& Elsevier]

Abstract: To assess cancer-related fatigue (CRF), multidimensional questionnaires are required. The aim of this study was to evaluate single-item fatigue (SIF) screening questions—one for global fatigue and three for the fatigue domains (cognitive, emotional, and physical)—for their immediate use in daily oncology practice. Sixty-one fatigued patients with advanced cancer completed SIF assessments (visual analog scales for global fatigue and for fatigue in the cognitive, emotional, and physical domains, respectively), and the Brief Fatigue Inventory (BFI), the Fatigue Assessment Questionnaire (FAQ), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-C30 (QLQ-C30). SIF-global correlated with BFI (r =0.51), and the domain-SIFs correlated with their respective FAQ domains (cognitive r =0.59; affective r =0.45; physical r =0.33) and functional EORTC QLQ-C30 subscales (r =0.62; r =0.42; r =0.34). The SIF-emotional also correlated with HADS-Anxiety (r =0.43) and HADS-Depression (r =0.62). Principal component analysis (domain-SIF; respective FAQ and functional EORTC QLQ-C30 subscales) revealed three clusters and a two-factor model (cognitive/emotional, physical), explaining 74% of variability. Patients with one predominant SIF domain had more domain-tailored fatigue interventions than had patients with mixed SIFs. These data suggest that three simple SIF questions permit rapid assessment of the physical and cognitive and probably the emotional domains of CRF in patients with advanced cancer. [Copyright &y& Elsevier]

Fatigue is one of the most frequent symptoms in palliative care patients, reported in .80% of cancer patients and in up to 99% of patients following radio- or chemotherapy. Fatigue also plays a major role in palliative care for noncancer patients, with large percentages of patients with HIV, multiple sclerosis, chronic obstructive pulmonary disease or heart failure reporting fatigue. This paper presents the position of an expert working group of the European Association for Palliative Care (EA PC), evaluating the available evidence on diagnosis and treatment of fatigue in palliative care patients and providing the basis for future discussions. As the expert group feels that culture and language influence the approach to fatigue in different European countries, a focus was on cultural issues in the assessment and treatment of fatigue in palliative care. As a working definition, fatigue was defined as a subjective feeling of tiredness, weakness or lack of energy. Qualitative differences between fatigue in cancer patients and in healthy controls have been proposed, but these differences seem to be only an expression of the overwhelming intensity of cancer-related fatigue. The pathophysiology of fatigue in palliative care patients is not fully understood. For a systematic approach, primary fatigue, most probably related to high load of proinflammatory cytokines and secondary fatigue from concurrent syndromes and comorbidities may be differentiated. Fatigue is generally recognized as a multidimensional construct, with a physical and cognitive dimension acknowledged by all authors. As fatigue is an inherent word only in the English and French language, but not in other European languages, screening for fatigue should include questions on weakness as a paraphrase for the physical dimension and on tiredness as a paraphrase for the cognitive dimension. Treatment of fatigue should include causal interventions for secondary fatigue and symptomatic treatment with pharmacological and nonpharmacological interventions. Strong evidence has been accumulated that aerobic exercise will reduce fatigue levels in cancer survivors and patients receiving cancer treatment. In the final stage of life, fatigue may provide protection and shielding from suffering for the patient and thus treatment may be detrimental. Identification of the time point, where treatment of fatigue is no longer indicated is important to alleviate distress at the end of life. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to determine the impact of physician sitting versus standing on the patient''s preference of physician communication style, and perception of compassion and consult duration. Sixty-nine patients were randomized to watch one of two videos in which the physician was standing and then sitting (video A) or sitting and then standing (video B) during an inpatient consultation. Both video sequences lasted 9.5 minutes. Thirty-five patients (51%) blindly preferred the sitting physician, 16 (23%) preferred the standing, and 18 (26%) had no preference. Patients perceived that their preferred physician was more compassionate and spent more time with the patient when compared with the other physician. There was a strong period effect favoring the second sequence within the video. The patients blinded choice of preference (P =0.003), perception of compassion (P =0.0016), and other attributes favored the second sequence seen in the video. The significant period effect suggests that patients prefer the second option presented, notwithstanding a stated preference for a sitting posture (55/68, 81%). Physicians should ask patients for their preference regarding physician sitting or standing as a way to enhance communication. [Copyright &y& Elsevier]

To characterize a new, one-stop multidisciplinary palliative care (MD) clinic which offers standardized multidisciplinary assessment, specific care recommendations, patient and family education, and on-site counseling, we retrospectively compared the assessments of 138 consecutive patients with advanced cancer referred to the MD clinic and 77 patients referred to a traditional pain and symptom management (PSM) clinic. The two groups were similar in tumor type, demographics, and symptom distress. The MD clinic team (physicians; nurses; pharmacists; physical, speech, and occupational therapists; social workers; chaplains; nutritionists; psychiatric nurse practitioner) delivered 1,066 non-physician recommendations (median 4 per patient, range 0–37). The PSM clinic team made no non-physician recommendations, but referred 14 patients to other medical specialists. In 80 (58%) MD-clinic patients with follow-up 9 days (median) after assessment, significant improvement was observed in pain, nausea, depression, anxiety, sleep, dyspnea, and well-being, but not in fatigue, anorexia, or drowsiness. In 83 patients interviewed after the MD clinic, satisfaction was rated as excellent (5 out of 5) in 86–97% of seven areas. Assessment at an MD clinic results in a high number of patient care recommendations, improved symptoms, and high levels of patient satisfaction. [Copyright &y& Elsevier]

Focuses on the treatment of chronic, non-malignant pain. Need to assess the condition; Emphasis on depression, anxiety, and deconditioning when treating chronic pain; Evaluation of the efficacy of adjuvant drugs to treat the disease.

Opioid-induced sedation is a major complication in patients with cancer pain. This study assessed the effectiveness of donepezil in opioid-induced sedation and related symptoms in patients with cancer pain. Twenty-seven patients who were receiving strong opioids for pain and reported sedation were enrolled. Donepezil 5 mg was given every morning for 7 days. Changes between baseline and Day 7 in sedation, pain, fatigue and other symptoms were evaluated using the Edmonton Symptom Assessment Scale. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Overall usefulness of donepezil was measured by the patient at the end of the study. In 20 evaluable patients, sedation, fatigue, anxiety, well-being, depression, anorexia and problems with sleep were significantly improved. Side effects included nausea, vomiting, diarrhea, muscle and abdominal cramps, and anorexia. Overall, however, the treatment was well tolerated. Donepezil appears to improve sedation and fatigue in patients receiving opioids for cancer pain. Randomized controlled trials of this agent are justified. [Copyright &y& Elsevier]

Presents a study which sought to assess the value of serum macrophage inhibitory factor-related protein (MRP) 8/14 levels in disease progression in persons infected with the human immunodeficiency virus (HIV), while showing how these are markers of intercurrent infections. Details on the study population used in this research; Research methods used; Results of this study.

Information on the Fourth European Association for Palliative Care (EAPC) Research Forum in Venice is presented. Researchers from various disciplines and settings participated in the research community session about research agendas, methodological issues, shared care models and research development.

Ectomycorrhizal fungi live in close association with their host plants and form complex interactions with bacterial/archaeal communities in soil. We investigated whether abundant or rare ectomycorrhizal fungi on root-tips of young beech trees (Fagus sylvatica) shape bacterial/archaeal communities. We sequenced 16S rRNA genes and fungal internal transcribed spacer regions of individual root-tips and used ecological networks to detect the tendency of certain assemblies of fungal and bacterial/archaeal taxa to inhabit the same root-tip (i.e. modularity). Individual ectomycorrhizal root-tips hosted distinct fungal communities associated with unique bacterial/archaeal communities. The structure of the fungal-bacterial/archaeal association was determined by both, dominant and rare fungi. Integrating our data in a conceptual framework suggests that the effect of rare fungi on the bacterial/archaeal communities of ectomycorrhizal root-tips contributes to assemblages of bacteria/archaea on root-tips. This highlights the potential impact of complex fine-scale interactions between root-tip associated fungi and other soil microorganisms for the ectomycorrhizal symbiosis.The bacterial/archaeal and fungal communities inhabiting beech tree root-tips are examined by marker gene sequencing followed by ecological network analysis, highlighting complex interactions in the ectomycorrhizal symbiosis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on the use of trastuzumab in treating women with metastatic breast cancer in the March 15, 2001 issue of the "New England Journal of Medicine."

Abstract: Purpose: A systematical literature review evaluating the effect of dietary counseling in treating weight loss and improving energy intake in patients with advanced cancer with different stages of cachexia. Principal results: Five publications were retrieved, of which three were randomized. Two out of five studies showed less weight loss with dietary counseling (+1% weight gain vs. −1.5% weight loss, p =0.03, 1.4kg vs. −2kg, p <0.05), two presented positive effect on energy intake (92% of total caloric need vs. 73%, p <0.01, 1865±317kcal vs. 1556±497kcal, ns). Conclusion: Dietary counseling can effect energy intake and body weight, however, apparent heterogeneity between studies is present. Based on these results there is not enough proof of evidence that dietary counseling given to patients with cancer is beneficial for improving weight or energy balance in the different cachexia stages. Nutrition is an essential part of cachexia treatment as it is not considered possible to increase or stabilize weight if nutritional needs are not met. [Copyright &y& Elsevier]

The appendices were incorrectly numbered in the original article. Please see below correcct appendices. [ABSTRACT FROM AUTHOR]

Introduction: Weight loss in cancer patients is a worrisome constitutional change predicting disease progression and shortened survival time. A logical approach to counter some of the weight loss is to provide nutritional support, administered through enteral nutrition (EN) or parenteral nutrition (PN). The aim of this paper was to update the original systematic review and meta-analysis previously published by Chow et al., while also assessing publication quality and effect of randomized controlled trials (RCTs) on the meta-conclusion over time.Methods: A literature search was carried out; screening was conducted for RCTs published in January 2015 up until December 2018. The primary endpoints were the percentage of patients achieving no infection and no nutrition support complications. Secondary endpoints included proportion of patients achieving no major complications and no mortality. Review Manager (RevMan 5.3) by Cochrane IMS and Comprehensive Meta-Analysis (version 3) by Biostat were used for meta-analyses of endpoints and assessment of publication quality.Results: An additional seven studies were identified since our prior publication, leading to 43 papers included in our review. The results echo those previously published; EN and PN are equivalent in all endpoints except for infection. Subgroup analyses of studies only containing adults indicate identical risks across all endpoints. Cumulative meta-analysis suggests that meta-conclusions have remained the same since the beginning of publication time for all endpoints except for the endpoint of infection, which changed from not favoring to favoring EN after studies published in 1997. There was low risk of bias, as determined by assessment tool and visual inspection of funnel plots.Conclusions: The results support the current European Society of Clinical Nutrition and Metabolism guidelines recommending enteral over parenteral nutrition, when oral nutrition is inadequate, in adult patients. Further studies comparing EN and PN for these critical endpoints appear unnecessary, given the lack of change in meta-conclusion and low publication bias over the past decades. [ABSTRACT FROM AUTHOR]

The risk of potential drug-drug interactions (PDI) is poorly studied in oncology. We included 105 patients with advanced non-small-cell lung cancer (NSCLC), 100 patients with advanced breast cancer (BC) and 100 patients of the palliative care unit (PCU) receiving systemic palliative treatment between 2010 and 2015. All patients suffered from advanced incurable cancer and received basic palliative care. PDI were assessed using the hospINDEX of all drugs approved in Switzerland in combination with a specific drug interaction software. Primary study objective was to assess the prognostic impact of PDI per patient cohort using Kaplan-Meier statistics. The median number of comedications was 5 (range 0-15). Major-risk PDI were detected in 74 patients (24.3%). The number of comedications was significantly associated with PDI (p < 0.0001). Major-risk PDI increased from 14% in patients with < 4 comedications to 24% in patients with 4-7 comedications, 40% with 8-11 comedications and 67% in patients with > 11 comedications. Median overall survival (OS) was 8.6 months in NSCLC, 33 months in BC and 1.2 months in PCU patients. PDI were significantly associated with inferior OS in BC (HR = 1.32, 95% CI 1.01-1.74, p = 0.049), but not in NSCLC (HR = 1.11, 95% CI 0.84-1.47, p = 0.45) or PCU (HR = 1.12, 95% CI 0.86-1.45, p = 0.41). PDI remained significantly associated with OS in BC (HR = 1.32, p = 0.049) in the adjusted model. In conclusion, PDI are frequent in patients with advanced cancer and increased caution with polypharmacy is warranted when treating such patients. [ABSTRACT FROM AUTHOR]

Cachexia is a life-threatening disorder affecting an estimated 50–80% of cancer patients. The loss of skeletal muscle mass in patients with cachexia is associated with an increased risk of anticancer treatment toxicity, surgical complications and reduced response. Despite international guidelines, the identification and management of cancer cachexia remains a significant unmet need owing in part to the lack of routine screening for malnutrition and suboptimal integration of nutrition and metabolic care into clinical oncology practice. In June 2020, Sharing Progress in Cancer Care (SPCC) convened a multidisciplinary task force of medical experts and patient advocates to examine the barriers preventing the timely recognition of cancer cachexia, and provide practical recommendations to improve clinical care. This position paper summarises the key points and highlights available resources to support the integration of structured nutrition care pathways. [ABSTRACT FROM AUTHOR]

Purpose: Palliative care referral is primarily based on clinician judgment, contributing to highly variable access. Standardized criteria to trigger automatic referral have been proposed, but it remains unclear how best to apply them in practice. We conducted a Delphi study of international experts to identify a consensus for the use of standardized criteria to trigger automatic referral.Methods: Sixty international experts stated their level of agreement for 14 statements regarding the use of clinician-based referral and automatic referral over two Delphi rounds. A consensus was defined as an agreement of ≥70% a priori.Results: The response rate was 59/60 (98%) for the first round and 56/60 (93%) for the second round. Twenty-six (43%), 19 (32%), and 11 (18%) respondents were from North America, Asia/Australia, and Europe, respectively. The panel reached consensus that outpatient palliative care referral should be based on both automatic referral and clinician-based referral (agreement = 86%). Only 18% felt that referral should be clinician-based alone, and only 7% agreed that referral should be based on automatic referral only. There was consensus that automatic referral criteria may increase the number of referrals (agreement = 98%), facilitate earlier palliative care access, and help administrators to set benchmarks for quality improvement (agreement = 86%).Conclusions: Our panelists favored the combination of automatic referral to augment clinician-based referral. This integrated referral framework may inform policy and program development. [ABSTRACT FROM AUTHOR]

Context Cachexia is commonly found in cancer patients and has profound consequences; yet there is only one questionnaire that examines the patient's perspective. Objective To report a rigorously developed module for patient self-reported impact of cancer cachexia. Methods Module development followed published guidelines. Patients from across the cancer cachexia trajectory were included. In Phase 1, health-related quality of life (HRQOL) issues were generated from a literature review and interviews with patients in four countries. The issues were revised based on patient and health care professional (HCP) input. In Phase 2, questionnaire items were formulated and translated into the languages required for Phase 3, the pilot phase, in which patients from eight countries scored the relevance and importance of each item, and provided qualitative feedback. Results A total of 39 patients and 12 HCPs took part in Phase 1. The literature review produced 68 HRQOL issues, with 22 new issues arising from the patient interviews. After patient and HCP input, 44 issues were formulated into questionnaire items in Phase 2. One hundred ten patients took part in Phase 3. One item was reworded, and 20 items were deleted as a consequence of patient feedback. Conclusions The QLQ-CAX24 is a cancer cachexia-specific questionnaire, comprising 24 items, for HRQOL assessment in clinical trials and practice. It contains five multi-item scales (food aversion, eating and weight-loss worry, eating difficulties, loss of control, and physical decline) and four single items. [ABSTRACT FROM AUTHOR]

This article synthesizes the presentations and conclusions of an international symposium on Phase 1 oncology trials, palliative care, and ethics held in 2014. The purpose of the symposium was to discuss the intersection of three independent trends that unfolded in the past decade. First, large-scale reviews of hundreds of Phase I trials have indicated there is a relatively low risk of serious harm and some prospect of clinical benefit that can be meaningful to patients. Second, changes in the design and analysis of Phase I trials, the introduction of "targeted" investigational agents that are generally less toxic, and an increase in Phase I trials that combine two or more agents in a novel way have changed the conduct of these trials and decreased fears and apprehensions about participation. Third, the field of palliative care in cancer has expanded greatly, offering symptom management to late-stage cancer patients, and demonstrated that it is not mutually exclusive with disease-targeted therapies or clinical research. Opportunities for collaboration and further research at the intersection of Phase 1 oncology trials and palliative care are highlighted. [ABSTRACT FROM AUTHOR]

Introduction Research in palliative care (PC) is often regarded as challenging due to the vulnerability of the population and other peculiarities. We aim to systematically identify barriers to research in PC in the literature. Methods The electronic databases CINAHL, MEDLINE were searched for papers published in the last 25 years. Citations and then abstracts were screened for inclusion. Original papers were included on first-level analysis. On a second level reviews, reports, and position papers were analyzed. Papers containing a direct patient report were specifically analyzed. Barriers were categorized (ethical considerations, financial and time expenses, study design and methodology, human resources and politics) and results quantified. Results Twenty-one original papers and 65 other papers were included. Five studies involved patients directly, five were systematic reviews, three were study experiences, and seven were surveys or workshop reports. Most papers originated from UK, USA, or Norwegian Universities. Ethics and methods were the most often mentioned categories on both levels. Accrual, attrition, and gatekeeping were frequently named barriers. Complex invasive studies or possible side effects hinder patients' participation, as patients are often willing to participate for altruistic motivations. Discussion Barriers to PC research are ethical concerns and methodological challenges. Possible strategies to overcome methodological barriers include international collaborative efforts to include more patients and improve study designs. Ethical barriers indicate the need for patient involvement in the research development process and tailoring research specifically to the PC population. [ABSTRACT FROM AUTHOR]

Context Oncologists perform a range of pharmacological and nonpharmacological interventions to manage the symptoms of outpatients with advanced cancer. Objectives The aim of this study was to develop and test a symptom management performance checklist (SyMPeC) to review medical charts. Methods First, the content of the checklist was determined by consensus of an interprofessional team. The SyMPeC was tested using the data set of the SAKK 96/06 E-MOSAIC (Electronical Monitoring of Symptoms and Syndromes Associated with Cancer) trial, which included six consecutive visits from 247 patients. In a test data set (half of the data) of medical charts, two people extracted and quantified the definitions of the parameters (content validity). To assess the inter-rater reliability, three independent researchers used the SyMPeC on a random sample (10% of the test data set), and Fleiss's kappa was calculated. To test external validity, the interventions retrieved by the SyMPeC chart review were compared with nurse-led assessment of patient-perceived oncologists' palliative interventions. Results Five categories of symptoms were included: pain, fatigue, anorexia/nausea, dyspnea, and depression/anxiety. Interventions were categorized as symptom specific or symptom unspecific. In the test data set of 123 patients, 402 unspecific and 299 symptom-specific pharmacological interventions were detected. Nonpharmacological interventions ( n = 242) were mostly symptom unspecific. Fleiss's kappa for symptom and intervention detections was K = 0.7 and K = 0.86, respectively. In 1003 of 1167 visits (86%), there was a match between SyMPeC and nurse-led assessment. Seventy-nine percent (195 of 247) of patients had no or one mismatch. Conclusion Chart review by SyMPeC seems reliable to detect symptom management interventions by oncologists in outpatient clinics. Nonpharmacological interventions were less symptom specific. A template for documentation is needed for standardization. [ABSTRACT FROM AUTHOR]

Background. How to assess cachexia is a barrier both in research and in clinical practice. This study examines the need for assessing both reduced food intake and loss of appetite, to see if these variables can be used interchangeably. A secondary aim is to assess the variance explained by food intake, appetite and weight loss by using tumor-related factors, symptoms and biological markers as explanatory variables. Material and methods. One thousand and seventy patients with incurable cancer were registered in an observational, cross sectional multicenter study. A total of 885 patients that had complete data on food intake (PG-SGA), appetite (EORTC QLQ-C30) and weight loss were included in the present analysis. The association between reduced food intake and appetite loss was assessed using Spearman's correlation. To find the explained variance of the three symptoms a multivariate analysis was performed. Results. The mean age was 62 years with a mean survival of 247 days and a mean Karnofsky performance status of 72. Thirteen percent of the patients who reported eating less than normal had good appetite and 25% who had unchanged or increased food intake had reduced appetite. Correlation between appetite loss and food intake was 0.50. Explained variance for the regression models was 44% for appetite loss, 27% for food intake and only 13% for weight loss. Conclusion. Both appetite loss and food intake should be assessed in cachectic patients since conscious control of eating may sometimes overcome appetite loss. The low explained variance for weight loss is probably caused by the need for more knowledge about metabolism and inflammation, and is consistent with the cancer cachexia definition that claims that in cachexia weight loss is not caused by reduced food intake alone. The questions concerning appetite loss from EORTC-QLQ C30 and food intake from PG-SGA seem practical and informative when dealing with advanced cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Context: Cancer cachexia syndrome (CCS) is often accompanied by psychosocial consequences (PSC). To alleviate PSC, a systematic assessment method is required. Currently, few assessment tools are available (e.g., Functional Assessment of Anorexia/Cachexia Therapy). There is no systematic assessment tool that captures the PSC of CCS. Objectives: To develop a pilot item bank to assess the PSC of CCS. Methods: A total of 132 questions, generated from patient answers in a previous study, were reduced to 121 items by content analysis and evaluation by multidisciplinary experts (doctor, nutritionists, and nurses). In our two-step, cross-sectional study, patients, judged by staff to have PSC of CCS, were included, and the questions were randomly allocated to the patients. Questions were evaluated for understandability and triggering emotions, and patients were asked to provide a response using a four-point Likert scale. Subsequently, problematic questions were revised, reformulated, and retested. Results: A total of 20 patients with a variety of tumor types participated. Of the 121 questions, 31 had to be reformulated after Step 1 and were retested in Step 2, after which seven were again evaluated as not being perfectly comprehensible. In Step 1, 22 questions were found to trigger emotions, but no item required remodeling. Item performance using the Likert scale revealed no consistent floor or ceiling effects. Our final pilot question bank comprised 117 questions. Conclusion: The final item bank contains questions that are understood and accepted by the patients. This item bank now needs to be developed into a measurement tool that groups items into domains and can be used in future research studies. [Copyright &y& Elsevier]

The article discusses the pain of neuropathic cancer patients. It states that the patients were treated with more analgesics than with nociceptive cancer pain. Computer assessment on symptoms, functions and quality of life was recorded. It was found that physical, cognitive and social function was worse in patients with neuropathic cancer. The sensitivity and specificity of pain DETECT for identifying neuropathic cancer pain was less accurate than when used in non-cancer populations.

Abstract: Context: Cancer cachexia is debilitating and affects most patients with advanced cancer. Because treatment options are poor, the psychosocial effects of cancer cachexia always should be assessed and psychosocial support provided. Objectives: To review the existing evidence of psychosocial effects of cancer cachexia with the aim of identifying factors that might be modified to improve outcomes. Methods: We carried out a systematic literature search in MEDLINE and Embase. The search string included key words for the topics “advanced cancer,” “cancer cachexia,” and “psychosocial effects.” Publications were selected by two reviewers. The search was complemented by a hand search. Results: Nineteen studies were included. The available information revealed mechanisms leading to, various presentations of, and coping strategies for psychosocial effects of cancer cachexia in both patients and their carers. Not all those affected manage the effects of the condition constructively. A number of clinically important adverse reactions have been identified. The main causes for negative psychosocial effects are a lack of knowledge of the irreversible nature of cancer cachexia and unsuccessful attempts to increase body weight with altered patterns of nutritional intake. Depending on patients' and their carers' coping resources, psychosocial effects may escalate or decrease. Early identification of psychosocial effects creates the potential for psychosocial interventions that improve the quality of life of those affected. Our analysis engendered a broader conceptualization of the psychosocial effects of cancer cachexia, leading to a number of suggestions for psychosocial interventions with the potential for providing relief. Conclusion: The concept of psychosocial effects in cancer cachexia has the potential to sensitize health care professionals to cachexia-related problems and inform their clinical management of the condition. [Copyright &y& Elsevier]

Abstract: Context: Symptom assessment by computers is only effective if it provides valid results and is perceived as useful for clinical use by the end users: patients and health care providers. Objectives: To identify factors associated with discontinuation, time expenditure, and patient preferences of the computerized symptom assessment used in an international multicenter data collection project: the European Palliative Care Research Collaborative-Computerized Symptom Assessment. Methods: Cancer patients with incurable metastatic or locally advanced disease were recruited from 17 centers in eight countries, providing 1017 records for analyses. Observer-based registrations and patient-reported measures on pain, depression, and physical function were entered on touch screen laptop computers. Results: The entire assessment was completed by 94.9% (n =965), with median age 63 years (range 18–91 years) and median Karnofsky Performance Status (KPS) score of 70 (range 20–100). Predictive factors for noncompletion were higher age, lower KPS, and more pain (P ≤0.012). Time expenditure among completers increased with higher age, male gender, Norwegian nationality, number of comorbidities, and lower physical functioning (P ≤0.007) but was inversely related to pain levels and tiredness (P ≤0.03). Need for assistance was predicted by higher age, nationality other than Norwegian, lower KPS, and lower educational level (P <0.001). More than 50% of patients preferred computerized assessment to a paper and pencil version. Conclusion: The high completion rate shows that symptom assessment by computers is feasible in patients with advanced cancer. However, reduced performance status reduces compliance and increases the need for assistance. Future work should aim at identifying the minimum set of valid screening questions and refine the software to optimize symptom assessment and reduce respondent burden in frail patients. [Copyright &y& Elsevier]

The objective of this study was to identify, through a consensus process, the essential practices in primary palliative care. A three-phase study was designed. Phase 1 methods included development of a working group; a literature review; development of a baseline list of practices; and identification of levels of intervention. In Phase 2, physicians, nurses, and nurse aides ( n = 425) from 63 countries were asked in three Delphi rounds to rate the baseline practices as essential or nonessential and select the appropriate levels of intervention for each. In Phase 3, representatives of 45 palliative care organizations were asked to select and rank the 10 most important practices resulting from Phase 2. Scores (1-10) were assigned to each, based on the selected level of importance. Results of Phase 1 were a baseline list of 140 practices. Three levels of intervention were identified: Identification/Evaluation; Diagnosis; and Treatment/Solution measures. In Phase 2, the response rates (RR) for the Delphi rounds were 96.5%, 73.6%, and 71.8%, respectively. A consensus point (≥80% agreement) was applied, resulting in 62 practices. In Phase 3, RR was 100%. Forty-nine practices were selected and ranked. ' Evaluation, Diagnosis and Treatment of Pain' scored the highest (352 points). The working group (WG) arranged the resulting practices in four categories: Physical care needs, Psychological/Emotional/Spiritual care needs, Care Planning and Coordination, and Communication. The IAHPC List of Essential Practices in Palliative care may help define appropriate primary palliative care and improve the quality of care delivered globally. Further studies are needed to evaluate their uptake and impact. [ABSTRACT FROM AUTHOR]

Abstract: Context: In surgical and clinical oncology, there is a growing need for patient-centered outcomes that are responsive, meaningful, and fit for purpose. Objectives: The aim of this study was to validate physical activity (PA) monitoring as a responsive outcome measure at different stages of disease and treatment, by verifying correlations between PA, performance score, and quality of life (QoL). Methods: Daily life PA of 162 cancer patients, monitored by a device that records time sitting/lying, time standing, time walking, number of steps taken, and walking cadence, was compared with 20 healthy volunteers. In a subgroup of patients, functional status and QoL were assessed using the World Health Organization/Eastern Cooperative Oncology Group and the Karnofsky Performance Status scores and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire. Results: The PA of patients with resectable gastrointestinal cancer did not differ significantly from controls. In contrast, patients with advanced cancer took 45% fewer steps and spent an extra 2.8 hours/day lying/sitting (P =0.001). Patients undergoing neoadjuvant chemotherapy and surgery (5–6 weeks after operation) experienced a similar reduction in PA. There were significant correlations between PA and the physical and role domains as well as fatigue subscale of the EORTC QLQ-C30 scale. Conclusion: Objective PA scores correlate significantly with disease stage, functional status, and QoL of patients with cancer. Therefore, activity monitoring can make meaningful objective estimates of patient function in response to cancer and its treatment and may provide surrogate outcomes of QoL. [Copyright &y& Elsevier]

Background: In patients with advanced, incurable cancer, anticancer treatment may be used to alleviate cancer-related symptoms, but monitoring of them in daily practice is rarely done. We aim to test the effectiveness of a real-time symptom and syndrome assessment using the E-MOSAIC software installed in handheld computer generating a longitudinal monitoring sheet (LoMoS) provided to the oncologists in a phase III setting. Methods: In this prospective multicentre cluster randomized phase-III trial patients with any incurable solid tumor and having defined cancer related symptoms, who receive new outpatient chemotherapy in palliative intention (expected tumor-size response rate ≤20%) are eligible. Immediately before the weekly visit to oncologists, all patients complete with nurse assistance the E-MOSAIC Assessment: Edmonton Symptom Assessment Scale, ≤3 additional symptoms, estimated nutritional intake, body weight, Karnofsky and medications for pain and cachexia. Experienced oncologists will be randomized to receive the LoMoS or not. To minimize contamination, LoMoS are removed from the medical charts after visits. Primary endpoint is the difference in global quality of life (items 29 & 30 of EORTC-QlQ-C30) between baseline and last study visit at week 6, with a 10 point between-arm difference considered to be clinically relevant. 20 clusters (=oncologists) per treatment arm with 4-8 patients each are aimed for to achieve a significance level of 5% and a power of 80% in a mixed model approach. Selected co- variables are included in the model for adjustment. Secondary endpoints include patient-perceived patient-physician communication symptom burden over time, and oncologists' symptom management performance (predefined thresholds of symptoms compared to oncologists' pharmacological, diagnostic or counselling actions [structured chart review]). Discussion: This trial will contribute to the research question, whether structured, longitudinal monitoring of patients' multidimensional symptoms, indicators for symptom management, and clinical benefit outcomes can influence patients' quality of life and symptom distress, in a setting of routine oncology practice. Trial registration: Current Controlled Trials NCT00477919 [ABSTRACT FROM AUTHOR]

Abstract: Background: The concept of cancer-related anorexia/cachexia is evolving as its mechanisms are better understood. To support consensus processes towards an updated definition and classification system, we systematically reviewed the literature for items and domains associated with involuntary weight loss in cancer. Methods: Two search strings (cachexia, cancer) explored five databases from 1976 to 2007. Citations, abstracts and papers were included if they were original work, in English/German language, and explored an item to distinguish advanced cancer patients with variable degrees of involuntary weight loss. The items were grouped into the 5 domains proposed by formal expert meetings. Results: : Of 14,344 citations, 1275 abstracts and 585 papers reviewed, 71 papers were included (6325 patients; 40–50% gastrointestinal, 10–20% lung cancer). No single domain or item could consistently distinguish cancer patients with or without weight loss or having various degrees of weight loss. Anorexia and decreased nutritional intake were unexpectedly weakly related with weight loss. Explanations for this could be the imprecise measurement methods for nutritional intake, symptom interactions, and the importance of systemic inflammation as a catabolic drive. Data on muscle mass and strength is scarce and the impact of cachexia on physical and psychosocial function has not been widely assessed. Conclusions: Current data support a modular concept of cancer cachexia with a variable combination of reduced nutritional intake and catabolic/hyper-metabolic changes. The heterogeneity in the literature revealed by this review underlines the importance of an agreed definition and classification of cancer cachexia. [Copyright &y& Elsevier]

Purpose: Mobility is an important aspect of physical functioning, but feasible and validated self-report assessment instruments for palliative patients are lacking. This study is a part of the European Palliative Research Network research programme, aiming to develop an internationally endorsed assessment tool for symptoms and functioning in palliative cancer care. The specific aim of the present study is to assess psychometric properties of a mobility item bank, with regards to uni-dimensionality, functional coverage, redundant items and gaps in the scale.Methods: A cross-sectional study with 604 responses from palliative cancer and 186 from chronic pain patients (mean age 59 ± 14 years, 55% female) was performed. A tablet computer with a touch- sensitive screen was used for data collection. An item pool of 21 mobility items, ranging from sitting without support to running were presented in random order, each scored on a four-category scale rating the difficulty in performing the activity. Psychometric properties were assessed by exploratory factor analysis, internal consistency and item response theory.Results: The mobility scale can be regarded as uni-dimensional and has good internal consistency (Cronbach's alpha  =  0.97). Items had a wide functional coverage from low to high functioning. Two items were with poor psychometric properties and two redundant items were removed. There were no obvious gaps in the scale.Conclusions: The psychometric properties of the scale are good and the next step is to make a pre-programmed version of the scale to be used in a pan-European study. [ABSTRACT FROM AUTHOR]

Abstract: Context: The Edmonton Symptom Assessment System (ESAS) is a widely used, self-report symptom intensity tool for assessing nine common symptoms in palliative care, with ratings ranging from 0 (none, best) to 10 (worst). Based on a “think-aloud” study of 20 advanced cancer patients, the ESAS was revised (ESAS-r). Objectives: To compare the consistency of patients’ symptom ratings and obtain patient perspectives regarding ease of understanding and completion between the ESAS and ESAS-r. Methods: Cognitively intact patients (n =160) were recruited from eight palliative care sites in Canada and Switzerland, using cross-sectional sampling (20 per site). Consenting patients completed the ESAS, ESAS-r, and a structured interview. Intraclass correlation coefficients (ICCs) were calculated to assess rating consistency. Results: In total, 1046 patients were screened. One hundred sixty were enrolled and evaluable (female 51%, median age 61 [range 34–92], lung cancer 26%, gastrointestinal cancer 22%). Mean ESAS scores ranged from 1.2 (nausea, standard deviation [SD] 2.1) to 4.3 (appetite, SD 3.3). ICCs ranged from 0.65 to 0.83, with lowest scores (<0.8) for drowsiness, appetite, and well-being. Although most patients rated both versions as very easy or easy to understand and complete, the ESAS-r was significantly easier to understand than the ESAS (P =0.008). Significantly, more patients preferred the ESAS-r (39%) than the ESAS (14%, P <0.001) because of its definitions, clarity, and format. Conclusion: The ESAS-r retains core elements of the ESAS, with improved interpretation and clarity of symptom intensity assessment. It represents the next generation of ESAS development, with further validation recommended for drowsiness, appetite, and well-being. [Copyright &y& Elsevier]

Introduction: Involuntary weight loss, the defining factor of cachexia, is a common consequence of advanced cancer.Discussion: This review summarizes the actual cachexia definitions and classification systems (NCCTG-studies, Loprinzi et al.; PG-SGA, Ottery et al.; Cachexia Consensus Conference, Evans et al; Cancer Cachexia Study Group, Fearon et al.; and SCRINIO Working group, Bozzetti et al.).We describe the ongoing development of a new classification system for cancer cachexia, which is based on literature reviews and Delphi processes within the European Palliative Care Research Collaborative. The review describes the evolving understanding of the pathophysiological mechanisms of cachexia and outlines an overview on treatment options.Conclusion: In this review an outlook on the requirements of a new decision guiding instrument is given and the challenges in clinical decision making in palliative are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Assessment of individual patients’ distress is a cornerstone of clinical care for advanced cancer. Patients’ ability to fill out lengthy questionnaires is compromised by many factors. Computer-adaptive tests (CAT) offer a promising approach to developing tailored instruments, that administer only items relevant to the individual patient. A systematic review of the literature about CATs in medical databases was conducted. Based on the results, a method for developing a CAT was designed that requires nine steps: (1) build an item pool; (2) administer the items to a predefined sample in a calibration study; (3) eliminate inappropriate items; (4) examine whether all items are influenced by a single dominant trait; (5) calibrate the items to the best-fitting item response theory (IRT) model; (6) evaluate items’ parameter equivalence across subgroups; (7) build an item bank with the calibrated items; (8) develop the CAT; and (9) pilot test the developed CAT. CAT offers the chance to extend the usefulness of patient-reported outcome (PRO) measurements from clinical studies to daily clinical practice. [Copyright &y& Elsevier]

Introduction: One of the key targets for metastatic cancer cells is the skeleton. Once metastatic cells are established within the bone matrix, skeletal integrity becomes increasingly compromised. Bone lesions lead to various complications, including bone pain, fractures and spinal cord compression.Mechanisms Of Bone Pain: Bone pain is debilitating and affects quality of life of the patient. In addition, it increases the use of health care resources. Many patients with metastatic bone disease experience substantial bone pain despite state-of-the-art systemic analgesic treatment. Incident pain is the predominant pain syndrome.Treatment Options For Bone Pain: Typically, this syndrome requires moderate baseline analgesia with increased on-demand doses. Other techniques for treating bone pain, including radiation therapy, neuraxial application of analgesics, nerve blocks and local stabilisation procedures, should be considered. In addition, therapy with bisphosphonates targeting bone-specific pain is an important strategy. This review discusses the various management options for bone pain arising from metastatic bone disease. [ABSTRACT FROM AUTHOR]