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Background: Health professionals and medical students have knowledge gaps about the law that governs end-of-life decision-making. There is a lack of dedicated training on end-of-life law and corresponding research on the impact of this type of training. Objective: To examine the impact of online training modules on key concepts of end-of-life law on Australian health professionals' legal knowledge and their self-reported confidence in applying the law in practice. Methods: Online pre- and post-training surveys were completed by training participants. The optional surveys collected demographic data, directly assessed legal knowledge and measured self-reported confidence in applying the law in clinical practice, before and after training. Results: Survey response rates were 66% (pre-training) and 12% (post-training). The final sample for analysis (n = 136 participants with matched pre- and post-training surveys), included nurses, doctors, allied health professionals, medical students and a small number of non-health professionals. Following completion of the online training modules, legal knowledge scores significantly increased overall and across each domain of end-of-life law. Participants were also more confident in applying the law in practice after training (median = 3.0, confident) than before training (median = 2.0, not confident). Conclusions: This study found that completion of online training modules on end-of-life law increased Australian health professionals' legal knowledge and self-reported confidence in applying the law in clinical practice. Participants demonstrated some remaining knowledge gaps after training, suggesting that the training, while effective, should be undertaken as part of ongoing education on end-of-life law. Future research should examine longer term outcomes and impacts of the training. [ABSTRACT FROM AUTHOR]

Introduction: Faced with the ability to maintenance vital functions artificially, new ethical concerns arise among health professionals regarding death. It is been questioned from ethics if the care team should always do everything necessary and possible to prevent the death of a patient. Objective: to analyze the bioethical aspects of limiting therapeutic effort in end-of-life patients, encourage reflection and contribute to improving end-of-life care. Method: a narrative and integrative review of the scientific literature was performed by searching for publications in meta-search engines and databases of PubMed, SciELO and the journal of Nursing Ethics. A total of 6,325 studies published since 2018 were identified and a total of 9 articles were included. Results/Discussion: Issues presented by professionals regarding making-decisions at the end of life, the need to improve training in ethics and aspects related to patients in their last days, palliative care and the limitation of therapeutic effort are described. Only a minority of studies are focused on nursing. Conclusions: professional's decisions are influenced by values, emotions, beliefs and experiences, which, together with the difficulty that sometimes exists to establish an accurate clinical diagnosis, makes it difficult to limit therapeutic effort. It is therefore necessary to improve training in ethics and knowledge about end-of-life processes from professionals. [ABSTRACT FROM AUTHOR]

Background: Palliative care should be seen as a human right and integrated into the healthcare system. Adequate palliative care education is seen as a facilitator to develop the integration of palliative care. Aims: To synthesise evidence of the effect of different teaching methods used in palliative care education to students' competences, knowledge, attitude or skills. Methods: Systematic review. A total of four databases (CINAHL, Eric, PubMed and Scopus) were searched, after which, 16 articles were identified. Findings: Simulations, lectures, films and a humanistic approach all had a positive effect on students' attitudes to care for a dying person. Problem-based learning, simulations and elective courses increased students' knowledge of palliative care. Game interventions in education decreased students' fear of death, while communication with dying patients and relatives became easier. Conclusions: Education interventions had positive effects on students' attitudes and knowledge. However, there is a need for future research into effective palliative care interventions using randomised designs and research about the effects of blended learning. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to develop organizational standards for specialist palliative care for adult patients (OSSPCAP) in Poland. Methods: The National Consultants in Palliative Medicine and Palliative Care Nursing appointed an Expert Group consisting of three physicians -- independent researchers, two nurses and a lawyer to develop the OSSPCAP. The work was done in three stages. 1. Literature analysis (Scopus and PubMed databases) and legislation on palliative care. 2. Questionnaire development using Google Forms and survey of 120 respondents in two rounds using the Delphi method. 3. Analysis of the results by the Expert Group during remote meetings and determination of the final version of the OSSPCAP. Results: The response rate in the first round of the survey was 71 (59.17%) and in the second 56 (46.67%). The first round yielded 73 positive responses (at least 70% criterion) to 97 questions; the second round yielded 21 positive responses to 31 questions. For the remaining ten questions, the Expert Group members discussed the results obtained with at least 50% criterion of positive responses. The results of both rounds were analyzed, and the final version of the document was accepted by all members of the Expert Group. Conclusions: Palliative care was divided into two types (levels): palliative care elements (palliative care approach) and specialist palliative care. In the latter home, inpatient and outpatient care was distinguished with ensuring public funding for all their organizational units by the State, including the integration into the guaranteed benefits. Requirements and procedures for all organizational units of specialist palliative care were depicted. Three specialist inpatient palliative care referral levels were offered taking into account complexity of services for patients, under- and postgraduate education. Principles of qualifying patients for palliative care, the development of research and education in palliative medicine and palliative care nursing were presented. [ABSTRACT FROM AUTHOR]

With perpetual research, management refinement, and increasing survivorship, cancer care is steadily evolving into a chronic disease model. Rehabilitation physicians are quite accustomed to managing chronic conditions, yet, cancer rehabilitation remains unexplored. Palliative care physicians, along with rehabilitationists, are true generalists, who focus on the whole patient and their social context, in addition to the diseased organ system. This, together with palliative care's expertise in managing the panoply of troubling symptoms that beset patients with malignancy, makes them natural allies in the comprehensive management of this patient group from the moment of diagnosis. This article will explore the under-recognized and underused parallels and synergies between the two specialties as well as identifying potential challenges and areas for future growth. [ABSTRACT FROM AUTHOR]

Background: Growing concerns over ethical issues in mentoring in medicine and surgery have hindered efforts to reinitiate mentoring for Palliative Care (PC) physicians following the easing of COVID-19 restrictions. Ranging from the misappropriation of mentee's work to bullying, ethical issues in mentoring are attributed to poor understanding and structuring of mentoring programs, underlining the need for a consistent approach to mentoring practices. Methods: Given diverse practices across different settings and the employ of various methodologies, a novel approach to narrative reviews (NR)s is proposed to summarize, interpret, and critique prevailing data on novice mentoring. To overcome prevailing concerns surrounding the reproducibility and transparency of narrative reviews, the Systematic Evidenced Based Approach (SEBA) adopts a structured approach to searching and summarizing the included articles and employed concurrent content and thematic analysis that was overseen by a team of experts. Results: A total of 18 915 abstracts were reviewed, 62 full text articles evaluated and 41 articles included. Ten themes/categories were ascertained identified including Nature; Stakeholders; Relationship; Approach; Environment; Benefits; Barriers; Assessments; Theories and Definitions. Conclusion: By compiling and scrutinizing prevailing practice it is possible to appreciate the notion of the mentoring ecosystem which sees each mentee, mentor, and host organization brings with them their own microenvironment that contains their respective goals, abilities, and contextual considerations. Built around competency based mentoring stages, it is possible to advance a flexible yet consistent novice mentoring framework. [ABSTRACT FROM AUTHOR]

The lack of integration between public health approaches, cancer care and palliative and end-of-life care in the majority of health systems globally became strikingly evident in the context of the coronavirus disease 2019 (COVID-19) pandemic. At the same time, the collapse of the boundaries between these domains imposed by the pandemic created unique opportunities for intersectoral planning and collaboration. While the challenge of integration is not unique to oncology, the organisation of cancer care and its linkages to palliative care and to global health may allow it to be a demonstration model for how the problem of integration can be addressed. Before the pandemic, the large majority of individuals with cancer in need of palliative care in low- and middle-income countries and the poor or marginalised in high-income countries were denied access. This inequity was highlighted by the COVID-19 pandemic, as individuals in impoverished or population-dense settings with weak health systems have been more likely to become infected and to have less access to medical care and to palliative and end-of-life care. Such inequities deserve attention by government, financial institutions and decision makers in health care. However, there has been no framework in most countries for integrated decision-making that takes into account the requirements of public health, clinical medicine and palliative and end-of-life care. Integrated planning across these domains at all levels would allow for more coordinated resource allocation and better preparedness for the inevitability of future systemic threats to population health. • Integration across public health, clinical medicine and palliative care is needed. • Oncology, palliative care and global health could be a demonstration model. • The pandemic is a dramatic reminder of the need for such integration at all levels. [ABSTRACT FROM AUTHOR]

By 2060, almost 25% (98 million) of the population is expected to be aged 65 or older. Health care professionals who provide hospice and palliative care are overtasked and demonstrate symptoms of burnout. Narrative medicine and mindfulness interventions create meaningful connections with patients, improve the delivery of patient-centered care, and enhance the health of the caregivers. In this pilot program, health care professionals in hospice and palliative care settings were invited to participate in a study to evaluate the impact of narrative medicine or mindfulness on measures of burnout and empathy. Participants completed baseline and 12-week post-intervention surveys of burnout and empathy, as well as weekly journals of their experience. Mean overall scores for depersonalization were significantly reduced at 12-week post-intervention. There were no significant changes in emotional exhaustion or empathy compared to baseline. This brief, weekly intervention may be beneficial for both patients and health care professionals in the hospice and palliative care setting. [ABSTRACT FROM AUTHOR]

Background: Growing concerns over ethical issues in mentoring in medicine and surgery have hindered efforts to reinitiate mentoring for Palliative Care (PC) physicians following the easing of COVID-19 restrictions. Ranging from the misappropriation of mentee's work to bullying, ethical issues in mentoring are attributed to poor understanding and structuring of mentoring programs, underlining the need for a consistent approach to mentoring practices. Methods: Given diverse practices across different settings and the employ of various methodologies, a novel approach to narrative reviews (NR)s is proposed to summarize, interpret, and critique prevailing data on novice mentoring. To overcome prevailing concerns surrounding the reproducibility and transparency of narrative reviews, the Systematic Evidenced Based Approach (SEBA) adopts a structured approach to searching and summarizing the included articles and employed concurrent content and thematic analysis that was overseen by a team of experts. Results: A total of 18 915 abstracts were reviewed, 62 full text articles evaluated and 41 articles included. Ten themes/categories were ascertained identified including Nature; Stakeholders; Relationship; Approach; Environment; Benefits; Barriers; Assessments; Theories and Definitions. Conclusion: By compiling and scrutinizing prevailing practice it is possible to appreciate the notion of the mentoring ecosystem which sees each mentee, mentor, and host organization brings with them their own microenvironment that contains their respective goals, abilities, and contextual considerations. Built around competency based mentoring stages, it is possible to advance a flexible yet consistent novice mentoring framework. [ABSTRACT FROM AUTHOR]

Objective: To assess advance care planning (ACP) preferences, experiences, and comfort in discussing end-of-life (EOL) care among elderly Latinos. Methods: Patients aged 60 and older from the Los Angeles County and University of Southern California (LAC+USC) Medical Center Geriatrics Clinic (n = 41) participated in this intervention. Trained staff conducted ACP counseling with participants in their preferred language, which included: (a) pre-counseling survey about demographics and EOL care attitudes, (b) discussion of ACP and optional completion of an advance directive (AD), and (c) post-session survey. Results: Patients were primarily Spanish speaking with an average of 2.7 chronic medical conditions. Most had not previously documented (95%) or discussed (76%) EOL wishes. Most were unaware they had control over their EOL treatment (61%), but valued learning about EOL options (83%). Post-counseling, 85% reported comfort discussing EOL goals compared to 66% pre-session, and 88% elected to complete an AD. Nearly half of patients reported a desire to discuss EOL wishes sooner. Conclusions: Elderly Latino patients are interested in ACP, given individualized, culturally competent counseling in their preferred language. Clinical Implications: Patients should be offered the opportunity to discuss and document EOL wishes at all primary care appointments, regardless of health status. Counseling should be completed in the patient's preferred language, using culturally competent materials, and with family members present if this is the patient's preference. Cultural-competency training for providers could enhance the impact of EOL discussions and improve ACP completion rates for Latino patients. [ABSTRACT FROM AUTHOR]

The SPIKES protocol will be discussed in the context of working with a patient who was referred to palliative care in the hospital setting. Palliative care is complex because it is not only medical care but also emotional and spiritual care. Those working in palliative care often explain a diagnosis to the patient, both what the diagnosis is and what it likely means for the future. The SPIKES protocol, a conversational tool for delivering bad news, has applications for social workers. This case study will tell the story of a patient whose fear of death almost cost him the ability to live fully at the end of his life and how the SPIKES tool was implemented in helping this patient understand and come to terms with his diagnosis. [ABSTRACT FROM AUTHOR]

It is increasingly recognised that palliative care research needs to pay more attention to culture if the diverse needs of service users are to be appropriately met. However, in most countries research, practice and policy in palliative care remains predicated upon a specific cultural understanding of the ‘good death’, firmly rooted in a Western world view. In this paper we present the formation of a new multi-disciplinary palliative care research group, explicitly set up along bi-cultural lines – The Te Ārai Palliative Care and End of Life Research Group to face challenges of traditional paradigms of palliative care in the specific context of Aotearoa New Zealand (NZ). We outline the rationale for establishing a research group which meets both Māori (indigenous people of NZ) and conventional Western standards for conducting academic research, describe our bi-cultural framework, and provide examples of how it shaped the design of three recently completed projects. We also situate our experience within the wider international literature, identifying transferable lessons for researchers wanting to do palliative care research with indigenous and minority ethnic and cultural groups. [ABSTRACT FROM AUTHOR]

Aim: Perinatal deaths occurring outside the neonatal intensive care unit (NICU) are rarely recorded in outcome studies, despite having a direct impact on perinatal statistics. Our aim was to investigate the timing and modes of perinatal deaths that occurred outside the NICU and changes over time.Method: We reviewed all perinatal deaths from 22 weeks of gestation onwards, without NICU admissions, during two periods in a Canadian tertiary mother and baby hospital and categorised deaths according to nine specific categories.Results: There were 444 perinatal deaths that satisfied the inclusion criteria. The total number of perinatal deaths increased from 2000 to 2002 (n = 197) and 2007 to 2010 (n = 247). The proportion of foetuses alive at the time of their mother's hospital admission, but then stillborn, decreased. There was a significant increase in terminations for congenital anomalies in the second cohort and a decrease in deaths following induction of labour and comfort care for foetal anomalies.Conclusion: Approaches to end-of-life care changed between the two study periods. Paediatricians should be aware of the epidemiology of perinatal mortality in their own practice, as it has a direct impact on the denominator in NICU outcome studies. [ABSTRACT FROM AUTHOR]

Coping mechanisms are patients' means of adapting to stressful situations and involve psychological and physical changes in behavior. Patients adapt to head and neck cancer in a variety of ways. Head and neck cancers are extremely debilitating, especially in advanced stages of the disease or in end-of-life situations. While an oncology team needs to address the needs of all oncology patients, the advanced terminal patients require special attention. Most of these patients do not cope well with their situation and have a tendency to cease social interactions. Pain is the most frequently experienced medical disability in patients having an end-stage illness experience, and thus an important medical endeavor is to afford dignity to the dying patient facingan incurable disease. In such cases, the medical community should never refuse therapy or to assist a dying patient.In some instances, the patient and family may derive benefit from their religious beliefs. [ABSTRACT FROM AUTHOR]

This article is based on an ethnographic study undertaken to explore whether eight people diagnosed with terminal cancer and their families drew on aspects of their cultural identities to make sense of their journey towards death, and if so, how. Ethnographic methods were supplemented by semistructured interviews. Most participants received medical treatments until close to death and invested much effort, time, and hope in these. Consequently, they made little sense of their palliative referrals. Instead, they accommodated the biomedical cultures of treatment-oriented services, thus delaying their own and their family's preparation for death. Only three participants appeared well prepared one month prior to death. An ecological perspective helped to explain the systemic factors involved in this prioritisation. The authors make recommendations for greater involvement of social workers in palliative care, and for more attention to supporting dying people and their families to make culturally meaningful decisions in the journey toward death. [ABSTRACT FROM AUTHOR]

Objectives: Treatment of oral mucositis (OM) is challenging. In order to develop and test useful treatment approaches, the development of reliable, reproducible and simpler methods than are currently available for assessment of OM is important. A Patient-Reported Oral Mucositis Symptom (PROMS) scale was assessed in patients with head and neck cancer to determine if the patient-reported OM experience, as determined by using the PROMS scale, correlate with OM assessed by clinician-based scoring tools. Materials and Methods: Fifty patients with head and neck cancer and undergoing radiotherapy consented to participate. They were examined before cancer treatment and twice weekly during 6–7 weeks of therapy and once 4–6 weeks after therapy. Signs of OM were evaluated using the 3 clinician-based scoring tools; NCI-CTCAE v.3, the OMAS criteria and the Total VAS-OMAS. The participants' OM experiences were recorded using PROMS-questionnaires consisting of 10 questions on a visual analogue scale. Spearman rank correlation test were applied between the PROMS scale values and the clinician-determined scores. Repeated measures mixed linear models were applied to appraise the strengths of correlation at the different time points throughout the observation period. Results: Thirty-three participants completed all stages of the study. The participant experience of OM using the PROMS scale demonstrates good correlations (Spearman's Rho 0.65–0.78, p<0.001) with the clinician-determined scores on the group level over all time points and poor to good correlations (Spearman's Rho -0.12–0.70, p<0.001) on the group level at different time points during and after therapy. When mouth opening was problematic, i.e. during the 6th and 7th week after commencing cancer treatment, the Spearman's Rho varied between 0.19 and 0.70 (p<0.001). Conclusion: Patient experience of OM, as reported by the PROMS scale may be a feasible substitute for clinical assessment in situations where patients cannot endure oral examinations. [ABSTRACT FROM AUTHOR]

Background: Advance care planning is considered a central component of good quality palliative care and especially relevant for people who lose the capacity to make decisions at the end of life, which is the case for many nursing home residents with dementia. We set out to investigate to what extent (1) advance care planning in the form of written advance patient directives and verbal communication with patient and/or relatives about future care and (2) the existence of written advance general practitioner orders are related to the quality of dying of nursing home residents with dementia. Methods: Cross-sectional study of deaths (2010) using random cluster-sampling. Representative sample of nursing homes in Flanders, Belgium. Deaths of residents with dementia in a three-month period were reported; for each the nurse most involved in care, GP and closest relative completed structured questionnaires. Findings: We identified 101 deaths of residents with dementia in 69 nursing homes (58% response rate). A written advance patient directive was present for 17.5%, GP-orders for 56.7%. Controlling for socio-demographic/clinical characteristics in multivariate regression analyses, chances of having a higher mean rating of emotional well-being (less fear and anxiety) on the Comfort Assessment in Dying with Dementia scale were three times higher with a written advance patient directive and more specifically when having a do-not-resuscitate order (AOR 3.45; CI,1.1–11) than for those without either (AOR 2.99; CI,1.1–8.3). We found no association between verbal communication or having a GP order and quality of dying. Conclusion: For nursing home residents with dementia there is a strong association between having a written advance directive and quality of dying. Where wishes are written, relatives report lower levels of emotional distress at the end of life. These results underpin the importance of advance care planning for people with dementia and beginning this process as early as possible. [ABSTRACT FROM AUTHOR]

Background: This study aimed to gather insights in physicians' considerations for decisions to either refer for- or to withhold additional diagnostic investigations in nursing home patients with a suspicion of venous thromboembolism. Methods: Our study was nested in an observational study on diagnostic strategies for suspected venous thromboembolism in nursing home patients. Patient characteristics, bleeding-complications and mortality were related to the decision to withhold investigations. For a better understanding of the physicians' decisions, 21 individual face-to-face in-depth interviews were performed and analysed using the grounded theory approach. Results: Referal for additional diagnostic investigations was forgone in 126/322 (39.1%) patients with an indication for diagnostic work-up. ‘Blind’ anticoagulant treatment was initiated in 95 (75.4%) of these patients. The 3month mortality rates were higher for patients in whom investigations were withheld than in the referred patients, irrespective of anticoagulant treatment (odds ratio 2.45; 95% confidence interval 1.40 to 4.29) but when adjusted for the probability of being referred (i.e. the propensity score), there was no relation of non-diagnosis decisions to mortality (odds ratio 1.75; 0.98 to 3.11). In their decisions to forgo diagnostic investigations, physicians incorporated the estimated relative impact of the potential disease; the potential net-benefits of diagnostic investigations and whether performing investigations agreed with established management goals in advance care planning. Conclusion: Referral for additional diagnostic investigations is withheld in almost 40% of Dutch nursing home patients with suspected venous thromboembolism and an indication for diagnostic work-up. We propose that, given the complexity of these decisions and the uncertainty regarding their indirect effects on patient outcome, more attention should be focused on the decision to either use or withhold additional diagnostic tests. [ABSTRACT FROM AUTHOR]

Background: Many liver staging systems that include the tumor stage and the extent of liver function have been developed. However, prognosis assessment for hepatocellular carcinoma (HCC) remains controversial. In this study, the performances of 7 staging systems were compared in a cohort of patients with HCC who underwent non-surgical treatment. Methods: A total of 196 consecutive patients with HCC who underwent non-surgical treatment seen between January 1, 2004, and December 31, 2007, were included. Performances of TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and China integrated score (CIS) have been compared and ranked using concordance index (c-index). Predictors of survival were identified using univariate and multivariate Cox model analyses. Results: The median survival time for the cohort was 7.6 months (95% CI 5.6–9.7). The independent predictors of survival were performance status (P<.001), serum sodium (P<.001), alkaline phosphatase (P<.001), tumor diameter greater than 5 cm (P = .001), portal vein invasion (P<.001), lymph node metastasis (P = .025), and distant metastasis (P = .004). CUPI staging system had the best independent predictive power for survival when compared with the other six prognostic systems. Performance status and serum sodium improved the discriminatory ability of CUPI. Conclusion: In our selected patient population whose main etiology is hepatitis B, CUPI was the most suitable staging system in predicting survival in patients with unresectable HCC. BCLC was the second top-ranking staging system. CLIP, JIS, CIS, and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data. [ABSTRACT FROM AUTHOR]

Background: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. Patients and Methods: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0–24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA). Results: From October 2009 to July 2010, 25 evaluable patients were included. AUC0–24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69–168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration. Conclusions: Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy. Trial Registration: ClinicalTrials.gov NCT01046240 [ABSTRACT FROM AUTHOR]

Background: The long-term and often lifelong relationship of general practitioners (GPs) with their patients is considered to make them the ideal initiators of advance care planning (ACP). However, in general the incidence of ACP discussions is low and ACP seems to occur more often for cancer patients than for those with dementia or heart failure. Objective: To identify the barriers, from GPs' perspective, to initiating ACP and to gain insight into any differences in barriers between the trajectories of patients with cancer, heart failure and dementia. Method: Five focus groups were held with GPs (n = 36) in Flanders, Belgium. The focus group discussions were transcribed verbatim and analyzed using the method of constant comparative analysis. Results: Three types of barriers were distinguished: barriers relating to the GP, to the patient and family and to the health care system. In cancer patients, a GP's lack of knowledge about treatment options and the lack of structural collaboration between the GP and specialist were expressed as barriers. Barriers that occurred more often with heart failure and dementia were the lack of GP familiarity with the terminal phase, the lack of key moments to initiate ACP, the patient's lack of awareness of their diagnosis and prognosis and the fact that patients did not often initiate such discussions themselves. The future lack of decision-making capacity of dementia patients was reported by the GPs as a specific barrier for the initiation of ACP. Conclusion: The results of our study contribute to a better understanding of the factors hindering GPs in initiating ACP. Multiple barriers need to be overcome, of which many can be addressed through the development of practical guidelines and educational interventions. [ABSTRACT FROM AUTHOR]

Background: Cancer-related fatigue (CRF) is a common symptom affecting patients with cancer. There are an increasing number of trials examining potential treatments for CRF. Methylphenidate represents one of the most researched drugs and an up-to-date assessment of the evidence for its use is needed. Trials of methylphenidate for CRF provided inconsistent results. This meta-analysis was aimed at assessing the effect and safety of methylphenidate on CRF. Methods: We comprehensively searched the Pubmed, EMBASE, PSYCHInfo and the Cochrane databases in order to identify published studies on the effect of methylphenidate on CRF. Primary outcomes included fatigue. Secondary outcomes included depression, cognition and adverse effects. Findings: A meta-analysis was conducted on five randomized controlled trials and 498 patients were enrolled. Despite a large placebo effect observed in the studies included, pooled data suggested therapeutic effect of methylphenidate on CRF. Subgroup Analyses showed that the efficacy of methylphenidate on CRF is getting better with prolonging treatment duration, with a MD of −3.70 (95% CI −7.03– −0.37, p = 0.03) for long-time group and a MD of −2.49 (95% CI −6.01–1.03, p = 0.17) for short-time group. In general, there was no impact of methylphenidate on depression and cognition associated with CRF. Adverse events were similar between methylphenidate and placebo groups except that more patients reported vertigo, anxiety, anorexia and nausea in methylphenidate group compared to placebo group. Conclusion: Existing trials of methylphenidate on CRF provided limited evidence for the use of methylphenidate to treat CRF. The absolute numbers still remain small, and further confirmation is needed before firm recommendations on their usage and safety can be made in the treatment of CRF. [ABSTRACT FROM AUTHOR]

Background: End-of-life cancer patients commonly receive more than one type of strong opioid. The three-step analgesic ladder framework of the World Health Organisation (WHO) provides no guidance on multiple opioid prescribing and there is little epidemiological data available to inform practice. This study aims to investigate the time trend of such cases and the associated factors. Methods: Strong opioid prescribing in the last three months of life of cancer patients were extracted from the General Practice Research Database (GPRD). The outcome variable was the number of different types of prescribed non-rescue doses of opioids (1 vs 2–4, referred to as a complex case). Associated factors were evaluated using prevalence ratios (PR) derived from multivariate log-binomial model, adjusting for clustering effects and potential confounding variables. Results: Overall, 26.4% (95% CI: 25.6–27.1%) of 13,427 cancer patients (lung 41.7%, colorectal 19.1%, breast 18.6%, prostate 15.5%, head and neck 5.0%) were complex cases. Complex cases increased steadily over the study period (1.02% annually, 95%CI: 0.42–1.61%, p = 0.048) but with a small dip (7.5% reduction, 95%CI: −0.03 to 17.8%) around the period of the Shipman case, a British primary care doctor who murdered his patients with opioids. The dip significantly affected the correlation of the complex cases with persistent increasing background opioid prescribing (weighted correlation coefficients pre-, post-Shipman periods: 0.98(95%CI: 0.67–1.00), p = 0.011; 0.14 (95%CI: −0.85 to 0.91), p = 0.85). Multivariate adjusted analysis showed that the complex cases were predominantly associated with year of death (PRs vs 2000: 1.05–1.65), not other demographic and clinical factors except colorectal cancer (PR vs lung cancer: 1.24, 95%CI: 1.12–1.37). Conclusion: These findings suggest that prescribing behaviour, rather than patient factors, plays an important role in multiple opioid prescribing at the end of life; highlighting the need for training and education that goes beyond the well-recognised WHO approach for clinical practitioners. [ABSTRACT FROM AUTHOR]

Background: Due to a rising number of deaths from cancer and other chronic diseases a growing number of people experience complex symptoms and require palliative care towards the end of life. However, population-based data on the number of people receiving palliative care in Europe are scarce. The objective of this study is to examine, in four European countries, the number of people receiving palliative care in the last three months of life and the factors associated with receiving palliative care. Methods: Cross-national retrospective study. Over two years (2009–2010), GPs belonging to representative epidemiological surveillance networks in Belgium, the Netherlands, Italy, and Spain registered weekly all deaths of patients (≥18 years) in their practices and the care they received in the last three months of life using a standardized form. Sudden deaths were excluded. Results: We studied 4,466 deaths. GPs perceived to have delivered palliative care to 50% of patients in Belgium, 55% in Italy, 62% in the Netherlands, and 65% in Spain (p<.001). Palliative care specialists attended to 29% of patients in the Netherlands, 39% in Italy, 45% in Spain, and 47% in Belgium (p<.001). Specialist palliative care lasted a median (inter-quartile range) of 15 (23) days in Belgium to 30 (70) days in Italy (p<.001). Cancer patients were more likely than non-cancer patients to receive palliative care in all countries as were younger patients in Italy and Spain with regard to specialist palliative care. Conclusions: Although palliative care is established in the countries studied, there are considerable differences in its provision. Two potentially underserved groups emerge non-cancer patients in all countries and older people in Italy and Spain. Future research should examine how differences in palliative care use relate to both patient characteristics and existing national health care policies. [ABSTRACT FROM AUTHOR]

Background: Surgical site infections (SSI’s) are associated with severe morbidity, mortality and increased health care costs in vascular surgery. Objective: To implement a bundle of care in vascular surgery and measure the effects on the overall and deep-SSI’s rates. Design: Prospective, quasi-experimental, cohort study. Methods: A prospective surveillance for SSI’s after vascular surgery was performed in the Amphia hospital in Breda, from 2009 through 2011. A bundle developed by the Dutch hospital patient safety program (DHPSP) was introduced in 2009. The elements of the bundle were (1) perioperative normothermia, (2) hair removal before surgery, (3) the use of perioperative antibiotic prophylaxis and (4) discipline in the operating room. Bundle compliance was measured every 3 months in a random sample of surgical procedures and this was used for feedback. Results: Bundle compliance improved significantly from an average of 10% in 2009 to 60% in 2011. In total, 720 vascular procedures were performed during the study period and 75 (10.4%) SSI were observed. Deep SSI occurred in 25 (3.5%) patients. Patients with SSI’s (28,5±29.3 vs 10.8±11.3, p<0.001) and deep-SSI’s (48.3±39.4 vs 11.4±11.8, p<0.001) had a significantly longer length of hospital stay after surgery than patients without an infection. A significantly higher mortality was observed in patients who developed a deep SSI (Adjusted OR: 2.96, 95% confidence interval 1.32–6.63). Multivariate analysis showed a significant and independent decrease of the SSI-rate over time that paralleled the introduction of the bundle. The SSI-rate was 51% lower in 2011 compared to 2009. Conclusion: The implementation of the bundle was associated with improved compliance over time and a 51% reduction of the SSI-rate in vascular procedures. The bundle did not require expensive or potentially harmful interventions and is therefore an important tool to improve patient safety and reduce SSI’s in patients undergoing vascular surgery. [ABSTRACT FROM AUTHOR]

Molecular mechanisms leading to pressure ulcer development are scarce in spite of high mortality of patients. Development of pressure ulcers that is initially observed as deep tissue injury is multifactorial. We postulate that biomechanical forces and inflammasome activation, together with ischemia and aging, may play a role in pressure ulcer development. To test this we used a newly-developed bio-mechanical model in which ischemic young and aged human skin was subjected to a constant physiological compressive stress (load) of 300 kPa (determined by pressure plate analyses of a person in a reclining position) for 0.5–4 hours. Collagen orientation was assessed using polarized light, whereas inflammasome proteins were quantified by immunoblotting. Loaded skin showed marked changes in morphology and NLRP3 inflammasome protein expression. Sub-epidermal separations and altered orientation of collagen fibers were observed in aged skin at earlier time points. Aged skin showed significant decreases in the levels of NLRP3 inflammasome proteins. Loading did not alter NLRP3 inflammasome proteins expression in aged skin, whereas it significantly increased their levels in young skin. We conclude that aging contributes to rapid morphological changes and decrease in inflammasome proteins in response to tissue damage, suggesting that a decline in the innate inflammatory response in elderly skin could contribute to pressure ulcer pathogenesis. Observed morphological changes suggest that tissue damage upon loading may not be entirely preventable. Furthermore, newly developed model described here may be very useful in understanding the mechanisms of deep tissue injury that may lead towards development of pressure ulcers. [ABSTRACT FROM AUTHOR]

Background: A simple and accurate survival prediction tool can facilitate decision making processes for hospice patients with advanced cancers. The objectives of this study were to explore the association of cardiac autonomic functions and survival in patients with advanced cancer and to evaluate the prognostic value of heart rate variability (HRV) in 7-day survival prediction. Methods: A prospective study was conducted on 138 patients with advanced cancer recruited from the hospice ward of a regional hospital in southern Taiwan. Information on functional status and symptom burden of the patients was recorded. Frequency-domain HRV was obtained for the evaluation of cardiac autonomic functions at admission. The end point of the study was defined as the survival status at day 7 after admission to the hospice ward. Multivariate logistic regression analyses were performed to evaluate the independent associations between HRV indices and survival of 7 days or less. Results: The median survival time of the patients was 20 days (95% CI, 17–28 days). Results from the multivariate logistic regression analysis indicated that the natural logarithm-transformed high-frequency power (lnHFP) of a value less than 2 (OR = 3.8, p = 0.008) and ECOG performance status of 3 or 4 (OR = 3.4, p = 0.023) were significantly associated with a higher risk of survival of 7 days or less. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve was 0.71 (95% CI, 0.61–0.81). Conclusions: In hospice patients with non-lung cancers, an lnHPF value below 2 at hospice admission was significantly associated with survival of 7 days or less. HRV might be used as a non-invasive and objective tool to facilitate medical decision making by improving the accuracy in survival prediction. [ABSTRACT FROM AUTHOR]

Background: Although the platinum regimen is adopted widely nowadays in spite of the excessive side effects, there is still no international standard for palliative chemotherapy of advanced gastric cancer. This meta-analysis assessed the efficacy and tolerability of platinum versus non–platinum chemotherapy as first-line palliative treatment in patients with inoperable, advanced gastric cancer. Methods: Randomized phase II and III clinical trials on first-line palliative chemotherapy in inoperable, advanced gastric cancer were identified by electronic searches of PubMed, Embase, and the Cochrane Controlled Trial Register, and hand searches of relevant abstract books and reference lists. Response rates, overall survival, and toxicity were analyzed. Depending on whether new-generation agents (S-1, taxanes and irinotecan) were utilized, the non–platinum regimens were divided into two subgroup. Results: Compared to non-platinum regimens containing new-generation agents, the use of platinum-based regimens was associated with better response (risk ratio (RR) = 1.94, 95%CI[1.48, 2.55], p<0.001), an increase of overall survival (hazard ratio (HR) = 0.85, 95%CI[0.78, 0.92], p<0.001), a higher risk of hematological and non-hematological toxicity. No statistically significant increase in response (RR = 1.03, 95%CI [0.85, 1.24], p = 0.76) or overall survival (HR = 1.07, 95%CI [0.88, 1.30], p = 0.49) was found when platinum therapies were compared to new-generation agent based combination regimens. The toxicity of platinum-based regimens was significantly higher for hematologic toxicity, nausea and vomiting, and neurotoxicity, but not for diarrhea and toxic death rate. Conclusion: New-generation agent based combination regimens achieved similar response rate and overall survival as platinum-based therapy that had generally higher side effects. S-1, taxanes and irinotecan seemed to be valid options for patients with inoperable, advanced gastric cancer as first-line chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer. Methodology/Principal Findings: Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m2 twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial) at 12 weeks was 86%. Side effects were of mild intensity (grade I or II) and included nausea (38% of patients), weakness (24%), diarrhea (24%), mucositis (10%), and hand and foot syndrome (7%). Conclusions/Significance: External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is warranted. Trial Registration: ClinicalTrials.gov NCT01784393NCT01784393 [ABSTRACT FROM AUTHOR]

Aim: The terms used to describe care at the end of life (EoL), and its definitions, have evolved over time and reflect the changes in meaning the concept has undergone as the field develops. We explore the remit of EoL care as defined by experts in EoL care, from across Europe and beyond, to understand its current usage and meanings. Method: A qualitative survey attached to a call for expertise on cultural issues in EoL care was sent to experts in the field identified through the literature, European EoL care associations, and conferences targeted at EoL care professionals. Respondents were asked to identify further contacts for snowball recruitment.The responses were analysed using content and discourse analysis. Results: Responses were received from 167 individuals (33% response rate), mainly from academics (39%) and clinical practitioners working in an academic context (23%) from 19 countries in Europe and beyond. 29% of respondents said explicitly that there was no agreed definition of EoL care in practice and only 14% offered a standard definition (WHO, or local institution). 2% said that the concept of EoL care was not used in their country, and 5% said that there was opposition to the concept for religious or cultural reasons. Two approaches were identified to arrive at an understanding of EoL care: exclusively by drawing boundaries through setting time frames, and inclusively by approaching its scope in an integrative way. This led to reflections about terminology and whether defining EoL care is desirable. Conclusion: The global expansion of EoL care contributes to the variety of interpretations of what it means. This complicates the endeavour of defining the field. However, when diversity is taken seriously it can open up new perspectives to underpin the ethical framework of EoL care. [ABSTRACT FROM AUTHOR]

Purpose: End-of-life (EOL) measures are limited in capturing caregiver assessment of the quality of EOL care. Because none include caregiver perception of patient suffering or prolongation of death, we sought to develop and validate the Caregiver Evaluation of Quality of End-of-Life Care (CEQUEL) scale to include these dimensions of caregiver-perceived quality of EOL care. Patients and Methods: Data were derived from Coping with Cancer (CwC), a multisite, prospective, longitudinal study of advanced cancer patients and their caregivers (N = 275 dyads). Caregivers were assessed before and after patient deaths. CEQUEL's factor structure was examined; reliability was evaluated using Cronbach's α, and convergent validity by the strength of associations between CEQUEL scores and key EOL outcomes. Results: Factor analysis revealed four distinct factors: Prolongation of Death, Perceived Suffering, Shared Decision-Making, and Preparation for the Death. Each item loaded strongly on only a single factor. The 13-item CEQUEL and its subscales showed moderate to acceptable Cronbach's α (range: 0.52–0.78). 53% of caregivers reported patients suffering more than expected. Higher CEQUEL scores were positively associated with therapeutic alliance (ρ = .13; p≤.05) and hospice enrollment (z = −2.09; p≤.05), and negatively associated with bereaved caregiver regret (ρ = −.36, p≤.001) and a diagnosis of Posttraumatic Stress Disorder (z = −2.06; p≤.05). Conclusion: CEQUEL is a brief, valid measure of quality of EOL care from the caregiver's perspective. It is the first scale to include perceived suffering and prolongation of death. If validated in future work, it may prove a useful quality indicator for the delivery of EOL care and a risk indicator for poor bereavement adjustment. [ABSTRACT FROM AUTHOR]

Background: BRAF mutation has been investigated as a prognostic factor in metastatic colorectal cancer (mCRC) undergoing anti-EGFR monoclonal antibodies (moAbs), but current results are still inconclusive. The aim of this meta-analysis was to evaluate the relationship between BRAF mutation status and the prognosis of mCRC patients treated with moAbs. Methods: Eligible studies were identified by systematically searching Pubmed, the Cochrane Library, Web of Knowledge, and OVID. Risk ratio (RR) for overall response rate (ORR), Hazard ratios (HRs) for Progression free survival (PFS) and Overall survival (OS) were extracted or calculated. Prespecified subgroup analyses were conducted in KRAS wild-type and in different study types. The source of between-trial variation was explored by sensitivity analyses. Quality assessment was conducted by the Hayden’s criteria. Results: A total of twenty one trials including 5229 patients were identified for the meta-analysis. 343 patients displayed BRAF mutations of 4616 (7.4%) patients with known BRAF status. Patients with BRAF wild-type (WT) showed decreased risks of progression and death with an improved PFS(HR 0.38, 95% confidence intervals 0.29–0.51) and an improved OS (HR 0.35 [0.29–0.42]), compared to BRAF mutant. In KRAS WT population, there were even larger PFS benefit (HR 0.29[0.19,0.43]) and larger OS benefit (HR 0.26 [0.20,0.35]) in BRAF WT. A response benefit for BRAF WT was observed (RR 0.31[0.18,0.53]) in KRAS WT patients, but not observed in unselected patients (RR 0.76 [0.43–1.33]). The results were consistent in the subgroup analysis of different study types. Heterogeneity between trials decreased in the subgroup and explained by sensitivity analysis. No publication bias of ORR, PFS and OS were detected. Conclusions: The results indicate that BRAF mutant is a predictive biomarker for poor prognosis in mCRC patients undergoing anti-EGFR MoAbs therapy, especially in KRAS WT patients. Additional large prospective trials are required to confirm the predictive role of BRAF status. [ABSTRACT FROM AUTHOR]

Aims: The palliative care has spread rapidly worldwide in the recent two decades. The development of hospice services in rural areas usually lags behind that in urban areas. The aim of our study was to investigate whether the urban-rural disparity widens in a country with a hospital-based hospice system. Methods: From the nationwide claims database within the National Health Insurance in Taiwan, admissions to hospices from 2000 to 2006 were identified. Hospices and patients in each year were analyzed according to geographic location and residence. Results: A total of 26,292 cancer patients had been admitted to hospices. The proportion of rural patients to all patients increased with time from 17.8% in 2000 to 25.7% in 2006. Although the numbers of beds and the utilizations in both urban and rural hospices expanded rapidly, the increasing trend in rural areas was more marked than that in urban areas. However, still two-thirds (898/1,357) of rural patients were admitted to urban hospices in 2006. Conclusions: The gap of hospice utilizations between urban and rural areas in Taiwan did not widen with time. There was room for improvement in sufficient supply of rural hospices or efficient referral of rural patients. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the number of individuals lacking the mental capacity to participate in decisions about their own healthcare is increasing. Due to the ageing global population and advancing medical treatments, there are now many more people living longer with neurological disorders, such as dementia, acquired brain injuries, and intellectual disabilities. Many of these individuals have feeding difficulties and may require artificial nutrition. However, little is known about the decision-making process; the evidence base is uncertain and often ethically complex. Using the exemplar of artificial nutrition, the objective of this review is to examine how treatment decisions are made when patients are at risk of lacking capacity. Methods and Findings: We undertook a systematic review according to PRISMA guidelines to determine who was involved in decisions, and what factors were considered. We searched PubMed, AMED, CINAHL, EMBASE, PsychINFO, and OpenSigle for quantitative and qualitative studies (1990–2011). Citation, reference, hand searches and expert consultation were also undertaken. Data extraction and quality assessment were undertaken independently and in duplicate. We utilised Thomas and Harden’s ‘Thematic Synthesis’ for analysis. Sixty-six studies met inclusion criteria, comprising data from 40 countries and 34,649 patients, carers and clinicians. Six themes emerged: clinical indications were similar across countries but were insufficient alone for determining outcomes; quality of life was the main decision-making factor but its meaning varied; prolonging life was the second most cited factor; patient’s wishes were influential but not determinative; families had some influence but were infrequently involved in final recommendations; clinicians often felt conflicted about their roles. Conclusions: When individuals lack mental capacity, decisions must be made on their behalf. Dynamic interactive factors, such as protecting right to life, not unnecessarily prolonging suffering, and individual preferences, need to be addressed and balanced. These findings provide an outline to aid clinical practice and develop decision-making guidelines. [ABSTRACT FROM AUTHOR]

Background: Perianal infection is a common problem for patients with acute leukemia. However, neutropenia and bleeding tendency are relatively contraindicated to surgical intervention. The epidemiology, microbiology, clinical manifestations and outcomes of perianal infection in leukemic patients are also rarely discussed. Method: The medical records of 1102 adult patients with acute leukemia at a tertiary medical center in Taiwan between 2001 and 2010 were retrospectively reviewed and analyzed. Result: The prevalence of perianal infection was 6.7% (74 of 1102) in adult patients with acute leukemia. Twenty-three (31%) of the 74 patients had recurrent episodes of perianal infections. Patients with acute myeloid leukemia had higher recurrent rates than acute lymphoblastic leukemia patients (p = 0.028). More than half (n = 61, 53%) of the perianal infections were caused by gram-negative bacilli, followed by gram-positive cocci (n = 36, 31%), anaerobes (n = 18, 15%) and Candida (n = 1, 1%) from pus culture. Eighteen patients experienced bacteremia (n = 24) or candidemia (n = 1). Overall 41 (68%) of 60 patients had polymicrobial infection. Escherichia coli (25%) was the most common micro-organism isolated, followed by Enterococcus species (22%), Klebsiella pneumoniae (13%), and Bacteroides species (11%). Twenty-five (34%) of 74 patients received surgical intervention. Acute leukemia patients with surgically managed anal fistulas tended to have fewer recurrences (p = 0.067). Four (5%) patients died within 30 days after diagnosis of perianal infection. Univariate analysis of 30-day survival revealed the elderly (≧ 65 years) (p = 0.015) and patients with shock (p<0.001) had worse outcome. Multivariate analysis showed septic shock to be the independent predictive factor of 30-day crude mortality of perianal infections (p = 0.016). Conclusion: Perianal infections were common and had high recurrence rate in adult patients with acute leukemia. Empirical broad-spectrum antibiotics with anaerobic coverage should be considered. Shock independently predicted 30-day crude mortality. Surgical intervention for perianal infection remains challenging in patients with acute leukemia. [ABSTRACT FROM AUTHOR]

Background: End-of-life-care is often poor in individuals with dementia. Advanced care planning (ACP) has the potential to improve end-of-life care in dementia. Commonly ACP is completed in the last six months of life but in dementia there may be problems with this as decision-making capacity and ability to communicate necessarily decrease as the disease progresses. Choosing the right time to discuss ACP with people with dementia may be challenging given the duration of the illness may be up to nine years. Aims: To explore the acceptability of discussing ACP with people with memory problems and mild dementia shortly after diagnosis. Methods: In-depth interviews were conducted with 12 patients and eight carers who had participated in ACP discussions and six staff members from a memory clinic and a community mental health team who had either conducted or attended the discussions for training purposes. Results: Patients and carers found ACP a positive intervention that helped them think about the future, enabled people with dementia to make their wishes known, and resulted in their feeling relieved and less worried about the future. The importance of sharing the ACP documentation between health service providers was highlighted. Conclusions: This qualitative evaluation of ACP in early dementia has encouragingly positive results which support the wider application of the intervention in memory services and community mental health teams. Strategies are suggested to support the implementation of ACP further in clinical practice. [ABSTRACT FROM AUTHOR]

The purposes of this study were to evaluate for differences in phenotypic and genotypic characteristics in women who did and did not develop lymphedema (LE) following breast cancer treatment. Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n = 155) and without LE (n = 387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease and a higher number of lymph nodes removed. Genetic associations were identified for four genes (i.e., lymphocyte cytosolic protein 2 (rs315721), neuropilin-2 (rs849530), protein tyrosine kinase (rs158689), vascular cell adhesion molecule 1 (rs3176861)) and three haplotypes (i.e., Forkhead box protein C2 (haplotype A03), neuropilin-2 (haplotype F03), vascular endothelial growth factor-C (haplotype B03)) involved in lymphangiogensis and angiogenesis. These genetic associations suggest a role for a number of lymphatic and angiogenic genes in the development of LE following breast cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy. Methods: Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%. Results: More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%. Conclusions: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. Trial Registration: ClinicalTrials.gov NCT00637975 [ABSTRACT FROM AUTHOR]

Background: Existential distress is an important factor affecting psychological well-being in cancer patients. We studied occurrence and predictors of demoralization, a syndrome of existential distress, in particular the interaction of age, gender, and curative vs. palliative treatment phase. Methods: A cross-sectional sample of N = 750 patients with different tumor sites was recruited from in- and outpatient treatment facilities. Patients completed the following self-report questionnaires: Demoralization Scale, Patient Health Questionnaire-9, Illness-Specific Social Support Scale Short Version-8, and physical problems list of the NCCN Distress Thermometer. Moderated multiple regression analyses were conducted. Results: We found high demoralization in 15% and moderate demoralization in 8% of the sample. Curative vs. palliative treatment phase moderated the impact of age and gender on demoralization (three-way interaction: b = 1.30, P = .02): the effect of age on demoralization was negative for women receiving palliative treatment (b = −.26, P = .02) and positive for men receiving palliative treatment (b = .25, P = .03). Effects of age and gender were not significant among patients receiving curative treatment. Female gender was associated with higher demoralization among younger patients receiving palliative treatment only. Analyses were controlled for significant effects of the number of physical problems (b = 6.10, P<.001) and social support (b = −3.17, P<.001). Conclusions: Existential distress in terms of demoralization is a relevant problem within the spectrum of cancer-related distress. It is associated with a complex interaction of demographic and medical patient characteristics; existential challenges related to palliative treatment may exacerbate the impact of age- and gender-related vulnerability factors on demoralization. Psychosocial interventions should acknowledge this interaction in order to address the individual nature of existential distress in subgroups of cancer patients. [ABSTRACT FROM AUTHOR]

Background: Culture shapes how people understand illness and death, but few studies examine whether acculturation influences patients’ end-of-life treatment preferences and medical care. Methods and Findings: In this multi-site, prospective, longitudinal cohort study of terminally-ill cancer patients and their caregivers (n = 171 dyads), trained interviewers administered the United States Acculturation Scale (USAS). The USAS is a 19-item scale developed to assess the degree of “Americanization” in first generation or non-US born caregivers of terminally-ill cancer patients. We evaluated the internal consistency, concurrent, criterion, and content validity of the USAS. We also examined whether caregivers’ USAS scores predicted patients’ communication, treatment preferences, and end-of-life medical care in multivariable models that corrected for significant confounding influences (e.g. education, country of origin, English proficiency). The USAS measure was internally consistent (Cronbach α = 0.98); and significantly associated with US birthplace (r = 0.66, P<0.0001). USAS scores were predictive of patients’ preferences for prognostic information (AOR = 1.31, 95% CI:1.00–1.72), but not comfort asking physicians’ questions about care (AOR 1.23, 95% CI:0.87–1.73). They predicted patients’ preferences for feeding tubes (AOR = 0.68, 95% CI:0.49–0.99) and wish to avoid dying in an intensive care unit (AOR = 1.36, 95% CI:1.05–1.76). Scores indicating greater acculturation were also associated with increased odds of patient participation in clinical trials (AOR = 2.20, 95% CI:1.28–3.78), compared with lower USAS scores, and greater odds of patients receiving chemotherapy (AOR = 1.59, 95% CI:1.20–2.12). Conclusion: The USAS is a reliable and valid measure of “Americanization” associated with advanced cancer patients’ end-of-life preferences and care. USAS scores indicating greater caregiver acculturation were associated with increased odds of patient participation in cancer treatment (chemotherapy, clinical trials) compared with lower scores. Future studies should examine the effects of acculturation on end-of-life care to identify patient and provider factors that explain these effects and targets for future interventions to improve care (e.g., by designing more culturally-competent health education materials). [ABSTRACT FROM AUTHOR]

Background: Making treatment decisions in anticipation of possible future incapacity is an important part of patient participation in end-of-life decision-making. This study estimates and compares the prevalence of GP-patient end-of-life treatment discussions and patients’ appointment of surrogate decision-makers in Italy, Spain, Belgium and the Netherlands and examines associated factors. Methods: A cross-sectional, retrospective survey was conducted with representative GP networks in four countries. GPs recorded the health and care characteristics in the last three months of life of 4,396 patients who died non-suddenly. Prevalences were estimated and logistic regressions were used to examine between country differences and country-specific associated patient and care factors. Results: GP-patient discussion of treatment preferences occurred for 10%, 7%, 25% and 47% of Italian, Spanish, Belgian and of Dutch patients respectively. Furthermore, 6%, 5%, 16% and 29% of Italian, Spanish, Belgian and Dutch patients had a surrogate decision-maker. Despite some country-specific differences, previous GP-patient discussion of primary diagnosis, more frequent GP contact, GP provision of palliative care, the importance of palliative care as a treatment aim and place of death were positively associated with preference discussions or surrogate appointments. A diagnosis of dementia was negatively associated with preference discussions and surrogate appointments. Conclusions: The study revealed a higher prevalence of treatment preference discussions and surrogate appointments in the two northern compared to the two southern European countries. Factors associated with preference discussions and surrogate appointments suggest that delaying diagnosis discussions impedes anticipatory planning, whereas early preference discussions, particularly for dementia patients, and the provision of palliative care encourage participation. [ABSTRACT FROM AUTHOR]

Background: Discrepancy between preferred and actual place of death is common in cancer patients. While previous research has elucidated the factors associated with congruence between patients' preferred and actual place of death, it is not known how the perspective of the family influences the place of death. This study examined whether family preference for place of death mediates the relationship between patient preference and actual place of death. Methods: A total of 258 cancer patients (home death, n = 142; hospital death, n = 116) who had received terminal care in Japan were analyzed. Measures included patients' demographic variables, patient and family preferences for place for death, actual place of death, patients' functional status, use and intensity of home care, availability of inpatient bed, living arrangement, and amount of extended family support. Results: Patient-family congruence on preferred place of death was 66% in patients who died at home and 47% in patients who died at other places (kappa coefficient: 0.20 and 0.25, respectively). In a multiple logistic regression model, patients were more likely to die at home when patients were male (odds ratio [OR], 95% confidence interval [CI]: 2.53, 1.06–6.05) and when their family preferred death at home (OR, 95% CI: 37.37, 13.82–101.03). A Sobel test revealed that family preference mediated the relationship between patient preference and place of death (p<0.05). Conclusions: This study is, to our knowledge, the first to unveil the role of the family in the relationship between patient preference and place of death in Japan. In order to honor patients' wishes to die at home, supporting caregivers in the family may be an essential component of terminal care. [ABSTRACT FROM AUTHOR]

Many published studies reflect the growing application of complementary and alternative medicine, particularly Chinese herbal medicine (CHM) use in combination with conventional cancer therapy for advanced non-small cell lung cancer (NSCLC), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with conventional chemotherapy (CT) in the treatment of advanced NSCLC. Publications in 11 electronic databases were extensively searched, and 24 trials were included for analysis. A sum of 2,109 patients was enrolled in these studies, at which 1,064 patients participated in CT combined CHM and 1,039 in CT (six patients dropped out and were not reported the group enrolled). Compared to using CT alone, CHM combined with CT significantly increase one-year survival rate (RR = 1.36, 95% CI = 1.15–1.60, p = 0.0003). Besides, the combined therapy significantly increased immediate tumor response (RR = 1.36, 95% CI = 1.19–1.56, p<1.0E−5) and improved Karnofsky performance score (KPS) (RR = 2.90, 95% CI = 1.62–5.18, p = 0.0003). Combined therapy remarkably reduced the nausea and vomiting at toxicity grade of III–IV (RR = 0.24, 95% CI = 0.12–0.50, p = 0.0001) and prevented the decline of hemoglobin and platelet in patients under CT at toxicity grade of I–IV (RR = 0.64, 95% CI = 0.51–0.80, p<0.0001). Moreover, the herbs that are frequently used in NSCLC patients were identified. This systematic review suggests that CHM as an adjuvant therapy can reduce CT toxicity, prolong survival rate, enhance immediate tumor response, and improve KPS in advanced NSCLC patients. However, due to the lack of large-scale randomized clinical trials in the included studies, further larger scale trials are needed. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to determine for the first time the prevalence and severity of multidimensional problems in a population newly diagnosed with HIV at outpatient clinics in Africa. Methods: Recently diagnosed patients (within previous 14 days) were consecutively recruited at 11 HIV clinics in Kenya and Uganda. Participants completed a validated questionnaire, the African Palliative Outcome Scale (POS), with three underpinning factors. Ordinal logistic regression was used to evaluate risk factors for prevalence and severity of physical, psychological, interpersonal and existential problems. Results: There were 438 participants (62% female, 30% with restricted physical function). The most prevalent problems were lack of help and advice (47% reported none in the previous 3 days) and difficulty sharing feelings. Patients with limited physical function reported more physical/psychological (OR = 3.22) and existential problems (OR = 1.54) but fewer interpersonal problems (OR = 0.50). All outcomes were independent of CD4 count or ART eligibility. Conclusions: Patients at all disease stages report widespread and burdensome multidimensional problems at HIV diagnosis. Newly diagnosed patients should receive assessment and care for these problems. Effective management of problems at diagnosis may help to remove barriers to retention in care. [ABSTRACT FROM AUTHOR]

Objective: The HIV/AIDS epidemic has evolved with an increasing burden in older adults. We assessed for knowledge about aging and HIV/AIDS, among clinicians in Kampala district, Uganda. Methods: A cross-sectional survey of 301 clinicians complemented by 9 key-informant interviews between May and October 2011. Data was analyzed by multivariable logistic regression for potential determinants of clinician knowledge about HIV/AIDS in older adults, estimating their adjusted Odds Ratios (aOR) and 95% confidence intervals (95% CI) using Stata 11.2 software. Results: Two-hundred and sixty-two questionnaires (87.7%) were returned. Respondents had a median age of 30 years (IQR 27–34) and 57.8% were general medical doctors. The mean knowledge score was 49% (range 8.8%–79.4%). Questions related to co-morbidities in HIV/AIDS (non-AIDS related cancers and systemic diseases) and chronic antiretroviral treatment toxicities (metabolic disorders) accounted for significantly lower scores (mean, 41.7%, 95% CI: 39.3%–44%) compared to HIV/AIDS epidemiology and prevention (mean, 65.7%, 95% CI: 63.7%–67.7%). Determinants of clinician knowledge in the multivariable analysis included (category, aOR, 95% CI): clinician age (30–39 years; 3.28∶1.65–9.75), number of persons with HIV/AIDS seen in the past year (less than 50; 0.34∶0.14–0.86) and clinical profession (clinical nurse practitioner; 0.31∶0.11–0.83). Having diploma level education had a marginal association with lower knowledge about HIV and aging (p = 0.09). Conclusion: Our study identified gaps and determinants of knowledge about HIV/AIDS in older adults among clinicians in Kampala district, Uganda. Clinicians in low and middle income countries could benefit from targeted training in chronic care for older adults with HIV/AIDS and long-term complications of antiretroviral treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to translate the Distress Thermometer (DT) into Indonesian, test its validity in Indonesian women with breast cancer and determine norm scores of the Indonesian DT for clinically relevant distress. Methods: First, the original version of the DT was translated using a forward and backward translation procedure according to the guidelines. Next, a group of 120 breast cancer patients who were treated at the Outpatient Surgical Oncology Clinic in Hasan Sadikin Hospital in Indonesia completed a standard socio-demographic form, the DT and the Problem List, the Hospital Anxiety and Depression Scale (HADS) and the WHO Quality of Life (WHOQOL-BREF). Results: Receiver operating characteristic (ROC) curve analyses identified an area under the curve = 0.81 when compared to the HADS cutoff score of 15. A cutoff score of 5 on the DT had the best sensitivity (0.81) and specificity (0.64). Patients who scored above this cutoff reported more problems in the practical, family, emotional, spiritual/religious and physical domains (30 out of 36 problems, p-value<0.05) than patients below the cutoff score. Patients at advanced stages of cancer experienced more emotional and physical problems. Patient's distress level was negatively correlated with overall quality of life, general health and all quality of life domains. Conclusions: The DT was found to be a valid tool for screening distress in Indonesian breast cancer patients. We recommend using a cutoff score of 5 in this population. [ABSTRACT FROM AUTHOR]

Background: The United Kingdom has led the world in the development of children's palliative care. Over the past two decades, the illness trajectories of children with life-limiting conditions have extended with new treatments and better home-based care. Future planning is a critically under-researched aspect of children's palliative care globally. This paper describes the development, implementation and evaluation of innovative child and parent-held palliative care planning resources. The resources were designed to facilitate parent and child thinking and engagement in future planning, and to determine care preferences and preferred locations of care for children with life-limiting conditions from diagnosis onwards. These resources fill a significant gap in palliative care planning before the end-of-life phase. Methods: Drawing on contemporaneous research on producing evidence-based children's health information, we collaborated with leading children's not-for-profit organisations, parents, children, and professionals. A set of resources (My Choices booklets) were developed for parents and children and evaluated using interviews (parents, children, professionals) and questionnaires (professionals) and an open web-based consultation. Results: Parents and children responded in three ways: Some used the booklets to produce detailed written plans with clear outcomes and ideas about how best to achieve desired outcomes. Others preferred to use the booklet to help them think about potential options. Remaining parents found it difficult to think about the future and felt there was no point because they perceived there to be no suitable local services. Professionals varied in confidence in their ability to engage with families to plan ahead and identified many challenges that prevented them from doing so. Few families shared their plans with professionals. Parents and children have far stronger preferences for home-care than professionals. Conclusion: The My Choices booklets were revised in light of findings, have been endorsed by Together for Short Lives, and are free to download in English and Welsh for use by parents and young people globally. More work needs to be done to support families who are not yet receptive to planning ahead. Professionals would benefit from more training in person-centred approaches to future planning and additional communications skills to increase confidence and ability to engage with families to deliver sensitive palliative care planning. [ABSTRACT FROM AUTHOR]

Background The construct of 'meaning in life' (MiL) has raised the interest of clinicians working in psycho-oncology and end-of-life care. It has become a topic of scientific investigation where diverse assessment approaches have been applied. Aims: We present a comprehensive systematic review of existing MiL assessment instruments. Methods Electronic searches of articles published in English peer-reviewed journals were performed in Psycinfo, Medline, Embase and Cinahl. Instruments are appraised with regard to ten measurement properties. Results In total, 59 nomothetic and idiographic MiL instruments were identified. Most instruments were developed in North America and meet basic psychometric criteria. They assess presence of and search for MiL, crisis and sources of MiL, meaning making, meaningful activity, MiL in the context of illness, breadth, depth, and other structural indicators. These aspects are largely consistent with existing MiL definitions. Nine out of 59 instruments included cancer populations in test development. Conclusions This overview of available instruments underscores the complexity of the construct and might assist researchers to select an appropriate instrument for their research needs. Finally, it points to the need for more integrative theorizing and research on MiL. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article describes models for restructuring a clinical initiative to enhance palliative care in the intensive care unit (ICU). Two models for ICU-palliative care integration are reported, the consultative model and the integrative model. Planning an ICU-palliative care initiative involves assessment of resources, stakeholders and ICU care. According to studies, palliative care consultation is linked with reductions in use of non-beneficial ICU treatments, length of ICU stay and conflict over care goals.

This paper argues that because it is a matter of dispute whether to assist suicide is ever morally right, the question whether assisted suicide should be legal should be decided independently of the moral issue and with reference to whether to assist suicide is genuinely to carry out the wishes of the person requesting it. It is then argued that it is possible to devise a set of criteria, based on those used in the Netherlands with regard to euthanasia, which would allow assisted suicide when the request is reasonable and genuine, but keep it illegal under other circumstances. It is further argued that there is no evidence that legalizing assisted suicide will lead us down the slippery slope to involuntary euthanasia. Finally, the question is raised to whether these assisted suicides should be legalized or, as at the moment in the UK, simply not prosecuted, but, as is about to happen, with the criteria for non-prosecution made explicit. It is suggested that, although it is in some ways both irrational and unjust, non-prosecution is politically easier to achieve and also more cautious as a first move. [ABSTRACT FROM AUTHOR]