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Background: Placebo-controlled trials can provide evidence to inform end-of-life care, but it is contested whether asking dying patients to participate in such trials is morally justifiable. To investigate the experiences of these patients is even more complex. Therefore, proxy assessments by relatives can be a good alternative., Aim: To explore the experience of participating in a placebo-controlled trial at the end of life from the perspective of bereaved relatives., Design: Mixed-method study, including questionnaires and interviews., Setting/participants: The SILENCE study was a randomized, double-blind, placebo-controlled trial on the efficacy of scopolamine butylbromide to prevent death rattle. The study was performed in six inpatient hospice facilities. Patients were asked to participate at admission in the hospice. Three months after the death of the patient, bereaved relatives were invited to fill in a questionnaire and to participate in an interview. One hundred four questionnaires were completed and 17 relatives were interviewed., Results: Fourteen percent of the relatives participating in the questionnaire study considered the participation of their loved one in research a bit burdensome and 10% considered it a bit stressful. Seventeen percent thought that it was a bit burdensome for the patient. Eighty-three percent considered participation in this type of research (very) valuable. The in-depth interviews showed that patients and relatives jointly decided about participation in this double-blind placebo-controlled medication trial. Relatives generally respected and felt proud about patients' decision to participate., Conclusion: The large majority of bereaved relatives experienced the participation of their dying love one in this RCT as acceptable and valuable.

Background: Goals of end-of-life care must be adapted to the needs of patients with chronic obstructive pulmonary disease (COPD) who are in the last phase of life. However, identification of those patients is limited by moderate performances of existing prognostic models and by limited validation of the often-recommended surprise question., Aim: To develop a clinical prediction model to predict 1-year mortality in patients with COPD., Design: Prospective study using logistic regression to develop a model in two steps: (1) external validation of the ADO, BODEX, or CODEX models (A = age; B = body mass index; C = comorbidity; D = dyspnea; EX = exacerbations; O = airflow obstruction); (2) updating of best performing model and extending it with the surprise question. Discriminative performance of the new model was assessed using internal-external validation and measured with area under the curve (AUC). A nomogram and web application were developed., Settings/participants: Patients with COPD from five hospitals (September-November 2017)., Results: Of the 358 included patients (median age 69.5 years, 50% male), 63 (17%) died within a year. The ADO index (AUC 0.73) had the best discriminative ability compared to the BODEX (AUC 0.71) or CODEX (AUC 0.68), and was extended with the surprise question. The resulting ADO-surprise question (SQ) model had an AUC of 0.79., Conclusion: The ADO-SQ model offers improved discriminative performance for predicting 1-year mortality compared to the surprise question, ADO, BODEX, or CODEX. A user-friendly nomogram and web application (https://dnieboer.shinyapps.io/copd) were developed. Further external validation of the ADO-SQ in patient groups is needed.

Background: Asian healthcare professionals hold that patients' families play an essential role in advance care planning., Aim: To systematically synthesize evidence regarding Asian patients' perspectives on advance care planning and their underlying motives., Design: Mixed-method systematic review and the development of a conceptual framework (PROSPERO: CRD42018099980)., Data Sources: EMBASE, MEDLINE, Web of Science, and Google Scholar were searched for studies published until July 27, 2020. We included studies concerning seriously-ill Asian patients' perspectives on advance care planning or their underlying motives for engaging or not engaging in it., Results: Thirty-six articles were included; 22 were quantitative and 27 were from high-income countries. Thirty-nine to ninety percent of Asian patients were willing to engage in advance care planning. Our framework highlighted that this willingness was influenced not only by their knowledge of their disease and of advance care planning, but also by their beliefs regarding: (1) its consequences; (2) whether its concept was in accordance with their faith and their families' or physicians' wishes; and (3) the presence of its barriers. Essential considerations of patients' engagement were their preferences: (1) for being actively engaged or, alternatively, for delegating autonomy to others; (2) the timing, and (3) whether or not the conversations would be documented., Conclusion: The essential first step to engaging patients in advance care planning is to educate them on it and on their diseases. Asian patients' various beliefs about advance care planning should be accommodated, especially their preferences regarding their role in it, its timing, and its documentation.

Background: For patients with cancer-related pain, the numeric rating scale is the most frequently used instrument to measure pain intensity. In the literature, it has been suggested to interpret patient-reported ratings of pain in relation to the pain intensity which is acceptable to the individual patient., Aim: We aimed to examine the feasibility and course of acceptable pain intensity., Design: A secondary analysis of a randomized controlled trial that tested the effectiveness of standard care versus standard care supplemented by a pain consultation combined with a patient pain education program., Setting: A total of 72 patients were included from an outpatient oncology clinic of a university hospital. They were diagnosed with cancer-related nociceptive pain with an average pain intensity ⩾4., Results: Most patients (97%) were able to give a score for acceptable pain. Almost half of the patients scored their acceptable pain in the range of moderate to severe. Patients' ratings of acceptable pain were stable; after 8 weeks, 69% of patients had a variation of up to 1 point compared to baseline. However, the mean acceptable pain intensity remained equal in the standard care group (from 4.6 (range: 0-8) to 5.0 (range: 2-8)) and decreased in the intervention group (from 4.6 (range: 2-8) to 3.8 (range: 0-7, p < 0.01), difference between groups p < 0.05)., Conclusion: Measurement of acceptable pain intensity is feasible. Patients with additional pain treatment became more critical and accepted less pain. More research is needed before we can use acceptable pain intensity as a reference for the interpretation of pain ratings.

Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter- and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side-effects and increasing its efficacy., (© 2016 The British Pharmacological Society.)

Background: Insights into symptoms and interventions at the end of life are needed for providing adequate palliative care, but are largely lacking for people with intellectual disabilities (IDs)., Objectives: We aimed at determining the prevalence rates of physician-reported symptoms from the Edmonton Symptom Assessment System (ESAS) at the moment that physicians recognized patient's death in the foreseeable future. In addition, we aimed at exploring provided interventions as reported by physicians in the period between physicians' recognition of death in the foreseeable future and patients' death., Measurements: In this study, 81 physicians for people with IDs (ID-physicians) completed a retrospective survey about their last patient with IDs with a nonsudden death., Results: On average, patients suffered from three of the eight ESAS symptoms. Fatigue (83%), drowsiness (65%), and decreasing intake (57%) were most reported. ID-physicians reported a median number of four interventions. Interventions were mostly aimed at somatic problems, such as pain and shortness of breath. Burdensome interventions such as surgery or artificial respiration were least or not reported. Palliative sedation was provided in a third of all cases., Conclusion: Although ID-physicians reported a variety of their patients' symptoms and of provided interventions at the end of life, using adequate symptom assessment tools suitable for people with IDs and continuous multidisciplinary collaboration in palliative care are essential to capture symptoms as fully as possible.

Background: In the outpatient oncology clinic, pain management is often inadequate. Incorporating a systematic pain management program into visits is likely to improve this. We implemented an integrated program, including a structured pain assessment, pain treatment protocol and patient education module. In the present study, we investigated whether this intervention improved pain control., Patients and Methods: At seven oncology outpatient clinics, patients were asked to register their pain intensity on a touch screen computer. These scores were made available into their electronic medical records. Additionally, a hospital-wide treatment protocol for cancer-related pain and a patient education module were developed. A data warehouse system enabled us to extract patient data from the electronic medical record anonymously and to use them for analysis. The primary outcome of the study was the percentage of patients with moderate to severe pain [current pain (CPI), NRS > 4] measured during 2 weeks at the start and 6 months after implementation. As secondary outcomes, we studied the percentage of pain registrations in specific patient groups and the percentage of patients treated with a curative and a palliative intention with (moderate-severe) pain. Differences were tested with the χ(2) test., Results: During the first 6 months, 3407 of the 4345 patients (78%) registered their pain intensity on the touch screen computer. The percentage of patients with moderate to severe CPI decreased 32% (P = 0.021): from 12.5% at start to 8.5% after 6 months. More patients in the palliative phase than in the curative phase of their disease registered their pain intensity (82% versus 75%, respectively, P < 0.005), and more patients in the palliative phase experienced moderate to severe pain (23% versus 14%, respectively, P < 0.001)., Conclusion: Pain registration by patients themselves is feasible, provides insight into patients' pain intensity and may improve pain control in outpatients with cancer-related pain., Clinical Trial Number: Because this is an innovation project and not a primary research project, it has no clinical trial number. The protocol and all materials involved were approved by the Institutional Review Board of the Erasmus MC (MEC-2009-324)., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: To identify clinical and genetic factors associated with outcome of opioid treatment., Patients & Methods: We performed an exploratory analysis in a cohort of 353 patients treated with fentanyl, morphine, oxycodone and/or hydromorphone for cancer-related pain, exploring selected clinical and pharmacogenetic factors for a correlation with treatment failure for all and per type of opioid., Results: Use of adjuvant pain medication, intensity of pain at rest and age were associated with treatment failure in the various cohorts. Only the genetic variants rs12948783 (RHBDF2) and rs7016778 (OPRK1) correlated statistically significant in univariate, but not in multivariable analysis., Conclusion: Several clinical and genetic factors were identified that warrant further study to clarify their role and use in opioid treatment.

Purpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route., Methods: Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model., Results: A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed., Conclusions: We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

Background: To improve the quality of end-of-life care, hospitals increasingly appoint palliative care nurse champions., Aim: We investigated the effect of nurse champions on the quality of life during the last 3 days of life and the quality of dying as experienced by bereaved relatives., Design: A controlled before-and-after study (June 2009-July 2012). Halfway, in each of seven intervention wards, two nurse champions were appointed; 11 wards served as control wards. The quality of life during the last 3 days of life, quality of dying and multiple dimensions of quality of dying were compared before and after the introduction of nurse champions., Setting: In a university hospital, each death at non-intensive care units was followed up by an invitation to relatives (10-13 weeks later) to answer a questionnaire., Results: For the two periods, data were collected on 86 and 84 patients in intervention wards and on 108 and 118 patients in control wards (overall response: 52%). In the intervention wards, no differences were found in the quality of life during the last 3 days of life and the quality of dying scores: in both periods, median score for the quality of life during the last 3 days of life was 3.0 and for the quality of dying 7.0. No differences were found in multiple quality of dying dimensions. In control wards, the median quality of dying score was 7.0 pre-intervention and 6.0 post-intervention (p = 0.04). Other scores were comparable with those in intervention wards., Conclusion: Performing a complex intervention study in palliative care proved to be feasible. This study showed no differences in the experiences of bereaved relatives after introduction of nurse champions. The complexity of palliative care in the hospital might require more intensive and longer training of nurse champions., (© The Author(s) 2015.)

Unlabelled: Data on the tolerability of opioids in patients with cancer-related pain are limited. Here, we report a systematic review that includes all published prospective studies reporting adverse events (AEs) of morphine, oxycodone, fentanyl, methadone, or hydromorphone for cancer-related pain in patients naive for these opioids. We included 25 studies describing 31 treatment cohorts, made an overview of study characteristics, and reported rates of AEs per type of opioid. The frequency of the most commonly reported AEs varied widely: nausea from 3 to 85%, vomiting from 4 to 50%, constipation from 5 to 97%, drowsiness from 3 to 88%, and dry mouth from 1 to 94%. There was a large heterogeneity among included studies, especially regarding the assessment and reporting of AEs. We describe how differences in assessment and reporting influence outcome rates. Although AEs are an important issue in daily clinical practice, realistic incidence rates of AEs per type of opioid are unknown because of the immense heterogeneity among studies., Perspective: Although opioid-related adverse events are an important issue when treating cancer-related pain, realistic rates of adverse events per type of opioid are unknown because of immense heterogeneity among studies and lack of systematic assessment and reporting. There is an urgent need for studies with standardized outcome measures and reporting., (Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Context: Most deaths in Western countries occur in hospital, but little is known about factors determining the quality of dying (QOD)., Objectives: The aim was to assess the QOD in hospital as experienced by relatives and identify factors related to QOD., Methods: A cross-sectional study on 18 wards of a university hospital in The Netherlands was conducted, including relatives of patients who died after an admission of more than six hours, from June 2009 to March 2011. Relatives' perceptions of QOD and quality of care and the relation between dimensions of QOD and overall QOD scores were assessed., Results: Two hundred forty-nine relatives participated (51%) and rated overall QOD at 6.3 (SD 2.7; range 0-10). According to relatives, patients suffered from 7.0 (SD 5.8) of 22 symptoms and were at peace with imminent death in 37%. Patients had been aware of imminent death in 26%, and relatives were aware in 49%. Furthermore, 39% of patients and 50% of relatives had said good-bye, and 77% of patients died in the presence of a relative. Symptom alleviation was sufficient in 53%, and in 75%, sufficient efforts had been made to relieve symptoms. Characteristics of QOD and quality of care could be summarized in nine domains, explaining 34% of the variation of QOD scores. Medical, personalized, and supportive care were most strongly related to QOD., Conclusion: Relatives rated QOD as sufficient. A majority of patients and relatives were not sufficiently prepared for imminent death, and relatives experienced many problems. QOD appears to be a multidimensional construct, strongly affected by medical care and staff attentiveness., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

We treated patients with newly diagnosed and large low-grade oligodendroglial tumors with upfront procarbazine, CCNU and vincristine (PCV) in order to delay radiotherapy. Patients were treated with PCV for a maximum of 6 cycles. The response to treatment was defined according to the RANO criteria; in addition change over time of mean tumor diameters (growth kinetics) was calculated. Thirty-two patients were treated between 1998 and 2006, 18 of which were diagnosed with 1p/19q co-deleted tumors. Median follow-up duration was 8 years (range 0.5-13 years). The median overall survival (mOS) was 120 months and the median progression-free survival (mPFS) was 46 months. Growth kinetics showed an ongoing decrease of the mean tumor diameter after completion of chemotherapy, during a median time of 35 months, but an increase of the mean tumor diameter did not herald progression as detected by RANO criteria. 1p/19q co-deletion was associated with a significant increase in OS (mOS 83 months versus not reached for codeleted tumors; p = 0.003)) and PFS (mPFS 35 months versus 67 months for codeleted tumors; p = 0.024). Patients with combined 1p/19q loss had a 10 year PFS of 34 % and the radiotherapy in these patients was postponed for a median period of more than 6 years. This long-term follow-up study indicates that upfront PCV chemotherapy is associated with long PFS and OS and delays radiotherapy for a considerable period of time in patients with low-grade oligodendroglial tumors, in particular with combined 1p/19q loss.

Patients with incurable esophageal cancer (EC) or pancreaticobiliary cancer (PBC) often have multiple symptoms and their quality of life is poor. We investigated which problems these patients experience and how often care is expected for these problems to provide optimal professional care. Fifty-seven patients with incurable EC (N = 24) or PBC (N = 33) from our outpatient clinic completed the validated "Problems and Needs for Palliative Care" (PNPC) questionnaire and two disease-specific quality of life questionnaires, European Organization for Research and Treatment in Cancer (EORTC). Although patients in general had several problems, physical, emotional, and loss of autonomy (LOA) problems were most common. For these physical and emotional problems, patients also expected professional care, although to a lesser extent for LOA problems. Inadequate care was received for fatigue, fear, frustration, and uncertainty. We conclude that an individualized approach based on problems related to physical, emotional, and LOA issues and anticipated problems with healthcare providers has priority in the follow-up policy of patients with incurable upper gastrointestinal cancer. Caregivers should be alert to discuss needs for fatigue, feelings of fear, frustration, and uncertainty.

Background: In hospitals, where care is focused on cure and life prolongation, impending death is often recognized too late. Physician awareness of impending death is a prerequisite for communication with patients and relatives about dying in hospital and providing care that adequately addresses patients' needs., Objective: To examine to what extent physicians are aware of the impending death of their dying patients and if awareness is related with communication and medical care, with quality of life in the last 3 days and quality of dying., Design: Retrospective survey among hospital physicians after patient deaths., Setting/subjects: Patients who died between June 2009 and February 2011 at Erasmus University Medical Center (Rotterdam, The Netherlands)., Measurements: Physician self-reported awareness of impending death, communication with patients and relatives, medical care, quality of life in the last 3 days, and quality of dying., Results: The response rate was 44% (n=228). Physicians reported that they had been aware of the impending death in 67% of their dying patients. If they had been aware, discussing death with patients and relatives was more likely, as well as changing the treatment goal into comfort care or withholding treatment and prescribing opioids in the last 3 days of life. When physicians had been aware of impending death, they rated the quality of dying higher., Conclusions: In two-thirds of deaths, hospital physicians had been aware of impending death of their dying patients. Physician awareness was related with more communication and more appropriate care in the last days of life.

Context: Upper gastrointestinal cancer is associated with a poor prognosis. The multidimensional problems of incurable patients require close monitoring and frequent support, which cannot sufficiently be provided during conventional one to two month follow-up visits to the outpatient clinic., Objectives: To compare nurse-led follow-up at home with conventional medical follow-up in the outpatient clinic for patients with incurable primary or recurrent esophageal, pancreatic, or hepatobiliary cancer., Methods: Patients were randomized to nurse-led follow-up at home or conventional medical follow-up in the outpatient clinic. Outcome parameters were quality of life (QoL), patient satisfaction, and health care consumption, measured by different questionnaires at one and a half and four months after randomization. As well, cost analyses were done for both follow-up strategies in the first four months., Results: In total, 138 patients were randomized, of which 66 (48%) were evaluable. At baseline, both groups were similar with respect to clinical and sociodemographic characteristics and health-related QoL. Patients in the nurse-led follow-up group were significantly more satisfied with the visits, whereas QoL and health care consumption within the first four months were comparable between the two groups. Nurse-led follow-up was less expensive than conventional medical follow-up. However, the total costs for the first four months of follow-up in this study were higher in the nurse-led follow-up group because of a higher frequency of visits., Conclusion: The results suggest that conventional medical follow-up is interchangeable with nurse-led follow-up. A cost utility study is necessary to determine the preferred frequency and duration of the home visits., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Context: Death rattle, or respiratory tract secretion in the dying patient, is a common and potentially distressing symptom in dying patients. Health care professionals often struggle with this symptom because of the uncertainty about management., Objectives: To give an overview of the current evidence on the prevalence of death rattle in dying patients, its impact on patients, relatives, and professional caregivers, and the effectiveness of interventions., Methods: We systematically searched the databases PubMed, Embase, CINAHL, PsychINFO, and Web of Science. English-language articles containing original data on the prevalence or impact of death rattle or on the effects of interventions were included., Results: We identified 39 articles, of which 29 reported on the prevalence of death rattle, eight on its impact, and 11 on the effectiveness of interventions. There is a wide variation in reported prevalence rates (12%-92%; weighted mean, 35%). Death rattle leads to distress in both relatives and professional caregivers, but its impact on patients is unclear. Different medication regimens have been studied, that is, scopolamine, glycopyrronium, hyoscine butylbromide, atropine, and/or octreotide. Only one study used a placebo group. There is no evidence that the use of any antimuscarinic drug is superior to no treatment., Conclusion: Death rattle is a rather common symptom in dying patients, but it is doubtful if patients suffer from this symptom. Current literature does not support the standard use of antimuscarinic drugs in the treatment of death rattle., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Purpose: Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary pegfilgrastim prophylaxis., Methods: Our economic evaluation used a health care perspective and was based on a randomized study in patients with breast cancer with increased risk of FN, comparing primary G-CSF prophylaxis throughout all chemotherapy cycles (G-CSF 1-6 cycles) with prophylaxis during the first two cycles only (G-CSF 1-2 cycles). Primary outcome was cost effectiveness expressed as costs per patient with episodes of FN prevented., Results: The incidence of FN increased from 10% in the G-CSF 1 to 6 cycles study arm (eight of 84 patients) to 36% in the G-CSF 1 to 2 cycles study arm (30 of 83 patients), whereas the mean total costs decreased from € 20,658 (95% CI, € 20,049 to € 21,247) to € 17,168 (95% CI € 16,239 to € 18,029) per patient, respectively. Chemotherapy and G-CSF determined 80% of the total costs. As expected, FN-related costs were higher in the G-CSF 1 to 2 cycles arm. The incremental cost effectiveness ratio for the G-CSF 1 to 6 cycles arm compared with the G-CSF 1 to 2 cycles arm was € 13,112 per patient with episodes of FN prevented., Conclusion: We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of FN prevented.

Purpose: Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy., Patients and Methods: In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm., Results: After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis)., Conclusion: In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.

The purpose of this study was the psychometric testing of a questionnaire to assess nurses' opinions, subjective norms, perceived difficulties, and knowledge related to palliative care. The 63-item MOVE2PC Questionnaire was tested among 219 nurses in groups differing in education and experience. The intra-rater agreement was moderate to good (к > .5κmax ), and internal consistency was good (alpha = .77). Construct validity was demonstrated by between-groups differences in knowledge, opinions, and perceived difficulties. Responsiveness was shown by improved scores after an education program. Time of completion was 20 minutes, and 99% skipped at most five items, demonstrating feasibility. Findings support the usefulness of the instrument for assessing nurses' knowledge and views on palliative care., (© 2013 Wiley Periodicals, Inc.)

Context: The prevalence of neuropathic pain in patients with cancer pain has been estimated to be around 40%. Neuropathic pain may be caused by tumor invasion and is considered as mixed nociceptive-neuropathic pain, or caused by an anticancer treatment and considered as purely neuropathic pain. The use of adjuvant analgesics in patients with cancer is usually extrapolated from their efficacy in nononcological neuropathic pain syndromes., Objectives: In this systematic review, we sought to evaluate the evidence for the beneficial and adverse effects of pharmacologic treatment of neuropathic cancer pain., Methods: A systematic review of the literature in PubMed and Embase was performed. Primary outcome measures were absolute risk benefit (ARB), defined as the number of patients with a defined degree of pain relief divided by the total number of patients in the treatment group, and absolute risk harm (ARH), defined as the fraction of patients who dropped out as a result of adverse effects., Results: We identified 30 articles that fulfilled our inclusion criteria. Overall, ARB of antidepressants, anticonvulsants, other adjuvant analgesics, or opioids greatly outweighed ARH. There were no significant differences in ARB or ARH between the four groups of medication or between patients with mixed vs. purely neuropathic pain. Because of the low methodological quality of the studies, we could not draw conclusions about the true treatment effect size of the four groups of medications., Conclusion: Once a diagnosis of neuropathic pain has been established in patients with cancer, antidepressants, anticonvulsants, or other adjuvant analgesics should be considered in addition to or instead of opioids., (Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Background: Although the multidimensional nature of cancer-related fatigue is widely accepted, it could be questioned whether fatigue dimensions are expressions of one symptom (multidimensional concept) or expressions of several phenomena that are all called fatigue but actually are separate symptoms (multiple-symptom concept)., Methods: Therefore, we investigated in this review whether physical fatigue and mental fatigue behave differently in cancer patients by studying their intensity in different stages of cancer, their changes in intensity during anti-tumor therapy, the variables to which they are related, and their changes in intensity by interventions on fatigue., Results: In some studies, physical fatigue and mental fatigue behaved similarly: they were both more intense in cancer patients than in healthy controls, and sometimes, they had the same course during anti-tumor therapy, or both improved during an intervention. On the contrary, there were some studies suggesting that physical fatigue and mental fatigue behaved differently: physical fatigue seemed to be more prominent than mental fatigue in some stages of the disease trajectory; several studies reported changes in physical fatigue not accompanied by changes in mental fatigue during anti-tumor therapy or by interventions aimed to relieve fatigue; and physical fatigue and mental fatigue had different correlates., Conclusions: In conclusion, we found some studies in which physical fatigue and mental fatigue behaved differently. These findings might indicate that physical fatigue and mental fatigue are separate phenomena. To prove this multiple-symptom concept, studies on the pathophysiological mechanisms leading either to physical fatigue or to mental fatigue are urgently needed., (Copyright © 2012 John Wiley & Sons, Ltd.)

A 64-year-old woman with metastatic rectal cancer is admitted to the acute palliative care unit of our cancer center because of debilitating fatigue. She had been diagnosed with metastatic disease in 2009, when liver metastases were found 1 year after the primary treatment of her rectal cancer with preoperative radiotherapy and low anterior resection. Since then, she had been treated with resection of liver metastases in 2009 and 2010, palliative combination chemotherapy (oxaliplatin plus capecitabine) after the diagnosis of new liver and lung metastases in 2010, irinotecan in 2011, and then cetuximab until progression. She declined participation in a phase I clinical trial because she was afraid of experiencing adverse effects; she felt relatively well at the time. She had functioned without hindering symptoms until 2 weeks before admission. Her condition had deteriorated markedly since then. At admission, she is bedridden because of progressive fatigue. Furthermore, she complains of dyspnea and nausea and vomits approximately twice per day. She also suffers from pain in the upper abdomen, especially when rising from the bed. She is no longer able to care for her 84-year-old husband or her 40-year-old mentally disabled son, who lives with them. She is aware of her poor prognosis but is not able to share her sorrows with her family.

Context: To improve the management of cancer-related symptoms, systematic screening is necessary, often performed by using 0-10 numeric rating scales. Cut points are used to determine if scores represent clinically relevant burden., Objectives: The aim of this systematic review was to explore the evidence on cut points for the symptoms of the Edmonton Symptom Assessment Scale., Methods: Relevant literature was searched in PubMed, CINAHL®, Embase, and PsycINFO®. We defined a cut point as the lower bound of the scores representing moderate or severe burden., Results: Eighteen articles were eligible for this review. Cut points were determined using the interference with daily life, another symptom-related method, or a verbal scale. For pain, cut point 5 and, to a lesser extent, cut point 7 were found as the optimal cut points for moderate pain and severe pain, respectively. For moderate tiredness, the best cut point seemed to be cut point 4. For severe tiredness, both cut points 7 and 8 were suggested frequently. A lack of evidence exists for nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath. Few studies suggested a cut point below 4., Conclusion: For many symptoms, there is no clear evidence as to what the optimal cut points are. In daily clinical practice, a symptom score ≥4 is recommended as a trigger for a more comprehensive symptom assessment. Until there is more evidence on the optimal cut points, we should hold back using a certain cut point in quality indicators and be cautious about strongly recommending a certain cut point in guidelines., (Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Background: The quality of care of patients dying in the hospital is often judged as insufficient. This article describes the protocol of a study to assess the quality of care of the dying patient and the contribution of an intervention targeted on staff nurses of inpatient wards of a large university hospital in the Netherlands., Methods/design: We designed a controlled before and after study. The intervention is the establishment of a network for palliative care nurse champions, aiming to improve the quality of hospital end-of-life care. Assessments are performed among bereaved relatives, nurses and physicians on seven wards before and after introduction of the intervention and on 11 control wards where the intervention is not applied. We focus on care provided during the last three days of life, covered in global ratings of the quality of life in the last three days of life and the quality of dying, and various secondary endpoints of treatment and care affecting quality of life and dying., Discussion: With this study we aim to improve the understanding of and attention for patients' needs, and the quality of care in the dying phase in the hospital and measure the impact of a quality improvement intervention targeted at nurses.

Purpose: Several guidelines on the treatment of cancer-related fatigue recommend optimizing treatment of accompanying symptoms. However, evidence for this recommendation from randomized clinical trials is lacking. We investigated whether monitoring and protocolized treatment of physical symptoms alleviates fatigue., Patients and Methods: In all, 152 fatigued patients with advanced cancer were randomly assigned to protocolized patient-tailored treatment (PPT) of symptoms or care as usual. The PPT group had four appointments with a nurse who assessed nine symptoms on a 0 to 10 numeric rating scale (NRS). Patients received a nonpharmacologic intervention for symptoms with a score ≥ 1 and a medical intervention for symptoms with a score ≥ 4. Fatigue dimensions, fatigue NRS score, interference of fatigue with daily life, symptom burden, quality of life, anxiety, and depression were measured at baseline and after 1, 2, and 3 months. Differences between the groups over time were assessed by using mixed modeling., Results: Seventy-six patients were randomly assigned to each study arm. Mean age was 58 ± 10 years, 57% were female, and 65% were given palliative chemotherapy. We found significant improvements over time in favor of PPT for the primary outcome general fatigue (P = .01), with significant group differences at month 1 (effect size, 0.26; P = .007) and month 2 (effect size, 0.35; P = .005). Improvements in favor of PPT were also found for the following secondary outcomes: fatigue dimensions "reduced activity" and "reduced motivation," fatigue NRS, symptom burden, interference of fatigue with daily life, and anxiety (all P ≤ .03)., Conclusion: In fatigued patients with advanced cancer, nurse-led monitoring and protocolized treatment of physical symptoms is effective in alleviating fatigue.

Background: Inflammation may underlie cancer-related fatigue; however, there are no studies that assess the relation between fatigue and cytokines in patients with advanced disease versus patients without disease activity. Furthermore, the relation between cytokines and the separate dimensions of fatigue is unknown. Here, association of plasma levels of inflammatory markers with physical fatigue and mental fatigue was explored in advanced cancer patients and cancer survivors., Methods: A total of 45 advanced cancer patients and 47 cancer survivors completed the subscales Physical Fatigue and Mental Fatigue of the Multidimensional Fatigue Inventory. Plasma concentrations of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1-ra), interleukin-6 (IL-6), interleukin-8 (IL-8), and neopterin were measured. Nonparametric tests were used to assess differences in fatigue intensity and levels of inflammatory markers and to determine correlation coefficients between the fatigue dimensions and inflammatory markers., Results: Compared with cancer survivors, patients with advanced cancer had higher levels of physical fatigue (median 16 vs 9, P < .001) and mental fatigue (median 11 vs 6, P = .01). They also had higher levels of all cytokines (P < .01). In advanced cancer, CRP (r = 0.49, P = .001), IL-6 (r = 0.43, P = .003), IL-1-ra (r = 0.32, P = .03), and neopterin (r = 0.25, P = .10) were correlated with physical but not with mental fatigue. In cancer survivors, only IL-1-ra was related to both physical fatigue (r = 0.24, P = .10) and mental fatigue (r = 0.35, P = .02)., Conclusions: In advanced cancer, inflammation seems to be associated with physical fatigue, but not to mental fatigue. In cancer survivors, there was no convincing evidence that inflammation plays a major role in fatigue., (Copyright © 2012 American Cancer Society.)

Context: Fatigue is a multidimensional symptom experienced physically, cognitively, and emotionally. Research on fatigue experiences in various stages of cancer might help to elucidate the nature of cancer-related fatigue., Objectives: To compare fatigue experiences in advanced cancer patients (ACPs), cancer survivors (CSs), and controls from the general population (GenPop)., Methods: Sixty-three ACPs (no antitumor therapy in the last month and no options for future therapy) were matched for age, sex and diagnosis with 63 CSs (last treatment one to five years ago) and 315 controls. Fatigue was measured unidimensionally with the Numeric Rating Scale and multidimensionally with the Multidimensional Fatigue Inventory., Results: All fatigue levels (general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue) were higher in ACPs than in CSs and controls (P<0.01), whereas fatigue levels were not different between CSs and controls. NRS scores in ACPs and CSs were significantly predicted by the fatigue dimensions physical fatigue and mental fatigue only. Although physical fatigue and mental fatigue were strongly related in the GenPop, the relation was weaker in CSs and not significant in ACPs. In multivariate analyses, only physical fatigue differentiated ACPs from CSs and controls (P<0.01)., Conclusion: ACPs experience fatigue more intensely than CSs and controls when fatigue is measured multidimensionally. Although mental and physical dimensions of fatigue contribute to the overall experience of fatigue in both groups of cancer patients, physical fatigue best differentiated ACPs from both CSs and controls., (Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Purpose: The effectiveness of an opioid rotation to parenteral hydromorphone in advanced cancer patients has never been investigated. Therefore, the purpose of this study was to investigate the analgesic efficacy and side effects of parenteral hydromorphone on serious cancer-related pain., Methods: We included 104 consecutive advanced cancer patients who were extensively pretreated with opioids. They were rotated to parenteral hydromorphone because they failed to achieve adequate pain relief on other opioids. Pain intensity and side effects were daily assessed. The moment of adequate pain control was defined as the first of at least 2 consecutive days when the mean pain intensity at rest was ≤ 4 (on a 0-10 numeric rating scale) and side effects were tolerable., Results: The reasons for rotation to parenteral hydromorphone were inadequate pain control with/without expected delivery problems due to high opioid dosages (n = 61) and intolerable side effects with persistent pain (n = 43). Adequate pain control was achieved in 86 patients (83%) within a mean of 5 days. Eight of 86 patients still had side effects, but these were scored as acceptable. The mean pain intensity at rest decreased from 5.4 [standard deviation (sd) = 2.1] to 2.4 (sd = 1.5; p < 0.001). The median failure-free treatment period was 57 days and covered a substantial part of the median survival of 78 days in the responding patients., Conclusions: In advanced cancer patients with serious unstable cancer-related pain refractory to other opioids, continuous parenteral administration of hydromorphone often results in long-lasting adequate pain control and should be considered even after extensive pretreatment with opioids.

Purpose: The purpose of this research is to study to what extent dying patients are aware of the imminence of death, whether such awareness is associated with patient characteristics, symptoms and acceptance of dying, and whether medical records and nurses' and family caregivers' views on patients' awareness of dying agree., Methods: Nurses and family caregivers of 475 deceased patients from three different care settings in the southwest Netherlands were requested to fill out questionnaires. The two groups were asked whether a patient had been aware of the imminence of death. Also, medical records were screened for statements indicating that the patient had been informed of the imminence of death., Results: Nurses completed questionnaires about 472 patients, family caregivers about 280 patients (response 59%). According to the medical records, 51% of patients had been aware of the imminence of death; according to nurses, 58%; according to family caregivers, 62%. Patients who, according to their family caregiver, had been aware of the imminence of death were significantly more often in peace with dying and felt more often that life had been worth living. Inter-rater agreement on patients' awareness of dying was fair (Cohen's kappa = 0.23-0.31)., Conclusions: Being aware of dying is associated with acceptance of dying, which supports the idea that open communication in the dying phase can contribute to the quality of the dying process. However, views on whether or not patients are aware of the imminence of death diverge between different caregivers. This suggests that communication in the dying phase of patients is open for improvement.

Alternative temozolomide regimens have been proposed to overcome O(6)-methylguanine-DNA methyltransferase mediated resistance. We investigated the efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression of a glioblastoma during or after chemo-radiation with temozolomide or a recurrence of another type of glioma after radiotherapy and at least one line of chemotherapy. Patients received ddTMZ at 100-150 mg/m(2)/d (days 1-7 and 15-21 in cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the response was assessed by MRI using the RANO criteria; complete and partial responses were considered objective responses. Fifty-three patients were included. The median number of cycles of ddTMZ was 4 (range 1-12). Eight patients discontinued chemotherapy because of toxicity. Two of 24 patients with a progressive glioblastoma had an objective response; progression free survival at 6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma without combined 1p and 19q loss had an objective response and PFS-6 in these patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss had an objective response; PFS-6 in these patients was 62%. This study indicates that ddTMZ is safe and effective in recurrent glioma, despite previous temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior efficacy of this schedule as compared to the standard day 1-5 every 4 weeks schedule.

Background: Multidisciplinary palliative care teams (PCTs) are increasingly employed for cancer patients. However, relatively few studies have prospectively assessed the clinical effectiveness of inpatient PCTs. Our aim was to evaluate the effectiveness of a multidisciplinary PCT for hospitalised cancer patients in a large university hospital in The Netherlands., Methods: Clinical data and duration of hospitalisation were prospectively collected between January 2007 and December 2008. A group of cancer pain patients from 2006 served as a historical control., Results: The number of consultations increased from 130 in 2006 to 235 in 2008. The reason for consultation changed from pain in 98% of consultations in 2006 to a diversity of palliative symptoms in 2008. In 2008 a significant decrease in mean pain intensity, including a 70% reduction in severe pain, occurred within 24 h following consultation, although the authors did not demonstrate that the effectiveness of the PCT in 2007 and 2008 surpassed that of routine oncological care including pain control in 2006. Similarly, the median severity for 7 out of 10 items from the Edmonton Symptom Assessment System (ESAS) decreased significantly within 72 h following consultation. The median number of days in hospital for patients for whom the PCT was consulted decreased from 14 days in 2006 to 10 days in 2008., Conclusions: The authors conclude that a multidisciplinary PCT for clinical cancer patients may have a positive effect on pain, on ESAS symptoms and on duration of hospitalisation.

Background: Palliative sedation (PS) is necessary in a significant percentage of patients dying on an acute palliative care unit (PCU). Common indications are terminal restlessness, pain and dyspnoea. On our PCU, terminal restlessness was the main indication for PS but pain was the most prevalent symptom during admission. Because delirium is often drug induced in terminal cancer patients and opioids are amongst the most frequently implicated drugs, we hypothesised that the underlying pain problem and its treatment might have been related to the need for sedation., Patients and Methods: To test this hypothesis, we did a retrospective analysis on the use of medication with potential cognitive side-effects, focusing on analgesics, in 68 patients who died on the PCU after PS and 89 patients who died without PS., Results: Ultimately sedated patients used opioids in significantly higher doses; they were more often treated with a rotation to another opioid and with amitriptyline. The dose of opioids used at various time points between admission and death was strongly related to the probability of PS., Conclusions: Our findings support the hypothesis that, although pain was not the main indication for PS, pain and its treatment might have been primarily related to the need for palliative sedation in this patient cohort., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

According to the international literature the prevalence of chronic pain is high. In the general population prevalence rates of chronic pain vary widely, from 2% to 40%. In nursing homes and homes for the elderly, higher prevalence rates of 45% to 80% have been reported. Prevalence rates in district nursing care in general, however, are lacking. This article is a report of a one-day survey to assess the prevalence and intensity of acute and chronic pain in Dutch district nursing care. We found that the prevalence of pain in patients with district nursing care is high and similar to reported prevalence rates in nursing homes and homes for elderly.

Aim: The PRISMA project is aiming to co-ordinate research priorities, measurement and practice in end-of-life (EOL) care in Europe. As part of PRISMA we undertook a questionnaire survey and a subsequent workshop to (1) identify clinical priorities for EOL care research in Europe and propose a future research agenda and (2) identify barriers to EOL care research, and possibilities and solutions to improve the research., Methods: Thirty participants selected among the principally medical survey responders from 25 European countries attended. Twenty-six answered a preparatory pre-workshop questionnaire based on the survey results. Group work was a main part of the workshop., Results: Consensus was reached on the following priorities for EOL cancer care research in Europe: symptomatology, issues related to care of the dying, and policy and organisation of services. Methodology was regarded important in all areas, including assessment/measurement and classification. Symptom research should particularly emphasise pain, fatigue, cachexia, delirium and breathlessness. Research should move from descriptive to interventional studies. The lack of consensus on definitions and outcomes was identified as a substantial research barrier. Other barriers were related to capacity and funding, environment and culture and knowledge transfer and dissemination. These areas are interrelated and should not be addressed in isolation., Conclusion: Consensus was obtained on priority areas and research nature for EOL care research in the next years, and a model for addressing barriers was developed., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the effects of epoetin alfa on patient-reported outcomes (PROs) in patients with breast cancer receiving myelotoxic chemotherapy., Materials and Methods: Women with hemoglobin concentrations ≤ 12.0 g/dl and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-3 were randomized 1:1 to receive epoetin alfa (10,000 IU 3 times weekly) or best standard care (BSC) during chemotherapy. The primary endpoint was the change from baseline in the total anemia subscale assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire after 12 weeks of treatment. The fatigue and nonfatigue subscales from the FACT-An, the Cancer Linear Analog Scale (CLAS), hemoglobin changes, ECOG PS score, tumor response, overall survival, and safety also were evaluated., Results: Of 223 patients randomized, 216 constituted the modified intent-to-treat population. Percentage changes in the total anemia subscale of the FACT-An were significantly different between epoetin alfa treatment (14.2%) and BSC (-0.5%; p = .002), favoring epoetin alfa; so were changes in the FACT-An fatigue subscale (epoetin alfa, 17.5%; BSC, -0.9%; p = .003) and nonfatigue subscale (epoetin alfa, 8.8%; BSC, 0.2%; p = .008). Similar results were observed with the CLAS. Hemoglobin concentrations > 12 g/dl were more common with epoetin alfa (62.0%) than with BSC (27.6%). Tumor response, ECOG PS score, 12-month survival rate, and the incidence of serious treatment-emergent adverse events were similar between groups., Conclusion: Early intervention with epoetin alfa was well tolerated and improved anemia-related PROs in patients with breast cancer receiving myelotoxic chemotherapy.

Objectives: The Distress Thermometer (DT) is a promising instrument to get insight into distress experienced by cancer patients. At our Family Cancer Clinic the DT, including an adapted problem list, was completed by 100 women at increased risk of developing hereditary breast cancer (mean age 45.2 years; SD: 10.5). Additionally, the women filled in either the Hospital Anxiety and Depression Scale as psychological component (n=48) or the somatic subscale of the Symptom Checklist-90 as somatic component (n=50) to identify associations with the DT-score. Further, the women filled in an evaluation form., Results: The median score on the DT was 2 (range: 0-9). With regression analysis adjusted for age, the contribution of mood and somatic complaints, respectively, was investigated. The standardized regression coefficient for anxiety was 0.32 (ns), for depression 0.14 (ns) and for the somatic subscale 0.49 (p<0.001). The explained variance for anxiety and depression was 16%, and for somatic complaints 24%. The differences between the coefficients were not significant. Evaluation forms were returned by 73 women. In 50% of the cases, the physician had discussed the DT/problem list, which was appreciated by the majority of these women (80%). Sixty-two percent of the women would recommend the use of the DT for other patients., Conclusion: The use of the DT/problem list seems promising for the current population, and was appreciated by the majority of the women. As mood and somatic complaints did not differ significantly in explaining the experienced distress, other candidate factors need to be examined.

Data on the experiences of relatives during continuous palliative sedation are scarce. Because these relatives may be the ones most closely involved with the patient, it is important to evaluate the possible burdens that they experience. We aimed to explore and evaluate concerns of relatives during continuous palliative sedation of their family members admitted to an acute palliative care unit. Through retrospective multidisciplinary record research, we obtained data on concerns of the relatives during the period that continuous palliative sedation took place. From October 2001 to October 2004, 45 patients died after starting continuous palliative sedation. In 51% of the cases, the relatives expressed concerns after starting the therapy. Concerns could be distinguished into three main themes: concerns about the aim of continuous palliative sedation (27%), concerns related to the well-being of the patient (29%), and concerns related to the well-being of relatives themselves (18%). Patient and sedation characteristics did not differ significantly between sedations in which relatives did and did not express concerns, except for the duration of the sedation. The median duration of the continuous palliative sedation when concerns were expressed was 46 hours, compared with 19.5 hours when this was not the case (P<0.05). Both the nature and extent of the concerns suggest that relatives are in need of continuous information and professional guidance during continuous palliative sedation of their family members. Availability of caregiver guidance and clear process documentation are crucial and indispensable in providing this.

The aim of this paper is to identify the major barriers hindering adequate pain management and critically review interventions aiming to overcome them. We searched relevant literature on PubMed published between January 1986 and April 2007. The most frequently mentioned barriers for both patients and professionals were knowledge deficits, inadequate pain assessment and misconceptions regarding pain. Four interventions were identified: patient education, professional education, pain assessment and pain consultation. These interventions were never combined in multidisciplinary study protocols. Most RCTs included small groups of patients and reported no power analysis. Studies on professional education and pain assessment did not evaluate patients' outcomes. In 5 of 11 RCTs on patient education, pain intensity decreased statistically significantly. In two RCTs on pain consultation, patients' pain decreased statistically significantly, although the adequacy of pain treatment did not change. In conclusion, international guidelines on multidisciplinary interventions in pain management are partly substantiated by clinical trials.

Background: In Anglo-Saxon countries, high prevalence rates of pain have been reported for elderly living in nursing homes, residential homes and for community-dwelling elderly. No information on pain prevalence is available for elderly living in Dutch residential homes., Methods: We performed an explorative study on pain prevalence, characteristics and treatment in three residential homes in Rotterdam, the Netherlands. Residents were interviewed using a standardized pain questionnaire., Results: The overall prevalence of pain was 69%. In case of pain, it was chronic in 93% of residents. Present pain and mean pain during the preceding week were substantial (numeric rating scale 4) in 68% and 85% of residents, respectively. Of the residents with pain, 22% did not receive any analgesics and only 3% was prescribed a strong opioid. When analgesics were prescribed, they were given only 'as needed' in 31% of residents. In a majority of residents, pain interfered with daily living and mood. Almost 60% of the elderly was convinced that pain is a part of ageing, 70% indicated that they did not always report their pain to the caregivers. Thirty-seven percent was satisfied with the caregivers' and 39% with the doctors' attention towards pain., Conclusions: The pain prevalence rate in Dutch residential homes is similar to rates found in other Anglo-Saxon countries. Furthermore, they are also comparable to rates reported from European nursing homes. Pain treatment is insufficient and although pain interferes with daily activities and mood, elderly tend to accept pain as an unavoidable part of aging.

Palliative sedation is undergoing extensive debate. The aims of this study were to describe the practice of palliative sedation at a specialized acute palliative care unit and to study whether patients who received palliative sedation differed from patients who did not. We performed a systematic retrospective analysis of the medical and nursing records of all 157 cancer patients who died at the acute palliative care unit between 2001 and 2005. Palliative sedation, defined as continuous deep sedation prior to death, was used for 43% of all deceased patients. In 87% of the sedated patients, it was started in the last two days before death. Sedated and nonsedated patients did not differ in survival after admission (eight days vs. seven days, P=0.12). Sedated patients were younger (55 years vs. 59 years, P=0.04) and more often had malignancies of the digestive tract (P<0.01). In both groups, common symptoms at admission were pain (79% vs. 87%, P=0.23), constipation, (40% vs. 48%, P=0.46), and dyspnea (32% vs. 29%, P=0.77). On the day that palliative sedation was started, sedated patients more often suffered from dyspnea and delirium than nonsedated patients at a comparable day before death. The most important indications for palliative sedation were terminal restlessness (60%) and dyspnea (46%). We conclude that at the studied acute palliative care unit, patients who ultimately received palliative sedation did not have symptoms different than nonsedated patients at admission, but on the day at which the sedation was started, they suffered more often from delirium and dyspnea.

The Liverpool Care Pathway (LCP) is aimed at improving care and communication in the dying phase. The authors studied whether use of the LCP affects relatives' retrospective evaluation of communication and their level of bereavement. An intervention study was conducted. During the baseline period, usual care was provided to dying patients. During the intervention period, the LCP was used for 79% of the patients. In total, bereaved relatives filled in a questionnaire for 57% of the patients, on average 4 months after death. In the intervention period, relatives had lower bereavement levels when compared with relatives in the baseline period (P = .01). Communication was evaluated similarly for both periods. We conclude that LCP use during the dying phase seems to moderately contribute to lower levels of bereavement in relatives.

We studied the effect of the Liverpool Care Pathway (LCP) on the documentation of care, symptom burden and communication in three health care settings. Between November 2003 and February 2005 (baseline period), the care was provided as usual. Between February 2005 and February 2006 (intervention period), the LCP was used for all patients for whom the dying phase had started. After death of the patient, a nurse and a relative filled in a questionnaire. In the baseline period, 219 nurses and 130 relatives filled in a questionnaire for 220 deceased patients. In the intervention period, 253 nurses and 139 relatives filled in a questionnaire for 255 deceased patients. The LCP was used for 197 of them. In the intervention period, the documentation of care was significantly more comprehensive compared with the baseline period, whereas the average total symptom burden was significantly lower in the intervention period. LCP use contributes to the quality of documentation and symptom control.

Cancer related fatigue (CRF), defined as a persistent subjective sense of tiredness related to cancer or cancer treatment that interferes with daily functioning, is highly prevalent and probably the most underestimated and insufficiently treated complication in cancer patients. Therefore, unravelling the pathogenesis of CRF is of great importance allowing the identification of novel therapeutic targets. It is generally believed that the pathogenesis is multicausal, explaining why most therapeutic interventions directed towards only one potential causative factor are unsuccessful. In this regard, it is of interest that increased activity of pro-inflammatory cytokines might be a common denominator causing CRF. Detailed insight in the central role of increased activity of pro-inflammatory cytokines in CRF will hopefully offer an effective approach in the treatment of CRF by affecting a broad array of proposed causative factors such as anaemia, disturbances of the hypothalamic-pituitary-adrenal axis and altered brain serotonin metabolism.

Adherence to analgesics in cancer patients has scarcely been studied. In this study, the Medication Event Monitoring System (MEMS) and medication diaries were compared with respect to feasibility and adherence measurements. Forty-six outpatients with nociceptive pain caused by cancer were asked to use MEMS for their analgesics and to record their medication usage in a diary for four weeks. Seventy-nine percent of the patients used MEMS for the full four-week period; 70% did so for the diary. The majority of patients were satisfied with both MEMS and diary. Adherence data assessed by MEMS and diary were comparable. Patients used the amount of analgesics adequately (taking adherence: 87%) but took them irregularly (timing adherence: 53%). Subgroup analyses in patients using single and multiple analgesic regimens confirmed the comparable suitability of both methods. MEMS and a medication diary are equally useful for analgesic adherence measurement in cancer patients with pain.

Introduction: Previous studies have shown that most people prefer to die at their own home. We investigated whether physicians or bereaved relatives in retrospect differently appreciate the dying of patients in an institution or at home., Materials and Methods: Of 128 patients with incurable cancer who were followed in the last phase of their lives, 103 passed away during follow-up. After death, physicians filled out a written questionnaire for 102 of these patients, and 63 bereaved relatives were personally interviewed., Results: Of 103 patients, 49 died in an institution (mostly a hospital), and 54 died at home (or in two cases in a home-like situation). Patients who had been living with a partner relatively often died at home. Bereaved relatives knew of the patient's wish to die at home in 25 out of 63 cases; 20 of these patients actually died at home. Thirty-one patients had no known preference concerning their place of dying. Most symptoms and the care provided to address them were equally prevalent in patients dying in an institution and patients dying at home. Bereaved relatives were in general quite satisfied about the provision of medical and nursing care in both settings., Conclusion: We conclude that most patients' preferences concerning the place of dying can be met. In about half of all cases, patients do not seem to have a clear preference concerning their place of dying, which is apparently not a major concern for many people. We found no indication that dying in an institution or at home involves major differences in the process and quality of dying.

Insufficient awareness of cancer pain, including breakthrough pain, inadequate analgesic prescriptions, and nonadherence contribute to inadequate cancer pain management. There are insufficient data about the contribution of each of these factors. In a cross-sectional survey among 915 adult cancer outpatients, pain was assessed by the Brief Pain Inventory. Breakthrough pain was defined as a worst pain intensity rated as "7 or more" and an average pain intensity rated as "6 or less" in patients on "around-the-clock" (ATC) analgesics. The Pain Management Index (PMI) was calculated to measure the quality of treatment. Adherence was considered inadequate when below 100% of the dose prescribed. Pain was present in 27% of patients. Worst pain was rated as moderate in 26%, and as severe in 54%. Breakthrough pain was present in 45% of patients with ATC medication. The PMI indicated inadequate treatment in 65% of patients. The proportions of patients adherent to ATC analgesics varied from 59% (tramadol) to 91% (Step 3 opioids). The management of cancer pain will benefit most from improving analgesic prescriptions and patient adherence.

Although fatigue is a multidimensional concept, multidimensional fatigue is rarely investigated in hospitalised cancer patients. We determined the levels and correlates of multidimensional fatigue in 100 advanced cancer patients admitted for symptom control. Fatigue dimensions were general fatigue (GF), physical fatigue (PF), reduced activity (RA), reduced motivation (RM) and mental fatigue (MF). Investigated correlates were tumour load, prior anti-tumour treatment, medication use, haemoglobin levels, serum biochemical variables, physical symptoms and mood. Median GF, PF and RA scores were very high; median RM and MF scores were moderate, and differed from the GF, PF and RA scores. Multiple regression analyses showed that symptoms and mood correlated with all fatigue dimensions. Each fatigue dimension had different relationships with other factors. Hospitalised advanced cancer patients differ in fatigue levels depending on the fatigue dimension, and each fatigue dimension has different correlates. The results confirm that fatigue should be regarded as a multidimensional concept.