Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab.

PURPOSE: To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI). METHODS: Melanoma survivors were identified within two study populations (N = 104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up. RESULTS: Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence (N = 8), existential problems (N = 2), survivor guilt (N = 2), and posttraumatic stress disorder (N = 6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity (N = 8), hepatitis (N = 1), colitis (N = 3), and sarcoidosis (N = 1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF. CONCLUSION: A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920.

Euthanasia embedded in palliative care. Responses to essentialistic criticisms of the Belgian model of integral end-of-life care.

The Belgian model of 'integral' end-of-life care consists of universal access to palliative care (PC) and legally regulated euthanasia. As a first worldwide, the Flemish PC organisation has embedded euthanasia in its practice. However, some critics have declared the Belgian-model concepts of 'integral PC' and 'palliative futility' to fundamentally contradict the essence of PC. This article analyses the various essentialistic arguments for the incompatibility of euthanasia and PC. The empirical evidence from the euthanasia-permissive Benelux countries shows that since legalisation, carefulness (of decision making) at the end of life has improved and there have been no significant adverse 'slippery slope' effects. It is problematic that some critics disregard the empirical evidence as epistemologically irrelevant in a normative ethical debate. Next, rejecting euthanasia because its prevention was a founding principle of PC ignores historical developments. Further, critics' ethical positions depart from the PC tenet of patient centeredness by prioritising caregivers' values over patients' values. Also, many critics' canonical adherence to the WHO definition of PC, which has intention as the ethical criterion is objectionable. A rejection of the Belgian model on doctrinal grounds also has nefarious practical consequences such as the marginalisation of PC in euthanasia-permissive countries, the continuation of clandestine practices and problematic palliative sedation until death. In conclusion, major flaws of essentialistic arguments against the Belgian model include the disregard of empirical evidence, appeals to canonical and questionable definitions, prioritisation of caregiver perspectives over those of patients and rejection of a plurality of respectable views on decision making at the end of life.

Does legal physician-assisted dying impede development of palliative care? The Belgian and Benelux experience.

BACKGROUND: In 2002, physician-assisted dying was legally regulated in the Netherlands and Belgium, followed in 2009 by Luxembourg. An internationally frequently expressed concern is that such legislation could stunt the development of palliative care (PC) and erode its culture. To study this, we describe changes in PC development 2005-2012 in the permissive Benelux countries and compare them with non-permissive countries. METHODS: Focusing on the seven European countries with the highest development of PC, which include the three euthanasia-permissive and four non-permissive countries, we compared the structural service indicators for 2005 and 2012 from successive editions of the European Atlas of Palliative Care. As an indicator for output delivery of services to patients, we collected the amounts of governmental funding of PC 2002-2011 in Belgium, the only country where we could find these data. RESULTS: The rate of increase in the number of structural PC provisions among the compared countries was the highest in the Netherlands and Luxembourg, while Belgium stayed on a par with the UK, the benchmark country. Belgian government expenditure for PC doubled between 2002 and 2011. Basic PC expanded much more than endowment-restricted specialised PC. CONCLUSIONS: The hypothesis that legal regulation of physician-assisted dying slows development of PC is not supported by the Benelux experience. On the contrary, regulation appears to have promoted the expansion of PC. Continued monitoring of both permissive and non-permissive countries, preferably also including indicators of quantity and quality of delivered care, is needed to evaluate longer-term effects.

Characteristics of Belgian "life-ending acts without explicit patient request": a large-scale death certificate survey revisited.

BACKGROUND: "Life-ending acts without explicit patient request," as identified in robust international studies, are central in current debates on physician-assisted dying. Despite their contentiousness, little attention has been paid to their actual characteristics and to what extent they truly represent nonvoluntary termination of life. METHODS: We analyzed the 66 cases of life-ending acts without explicit patient request identified in a large-scale survey of physicians certifying a representative sample of deaths (n = 6927) in Flanders, Belgium, in 2007. The characteristics we studied included physicians' labelling of the act, treatment course and doses used, and patient involvement in the decision. RESULTS: In most cases (87.9%), physicians labelled their acts in terms of symptom treatment rather than in terms of ending life. By comparing drug combinations and doses of opioids used, we found that the life-ending acts were similar to intensified pain and symptom treatment and were distinct from euthanasia. In 45 cases, there was at least 1 characteristic inconsistent with the common understanding of the practice: either patients had previously expressed a wish for ending life (16/66, 24.4%), physicians reported that the administered doses had not been higher than necessary to relieve suffering (22/66, 33.3%), or both (7/66, 10.6%). INTERPRETATION: Most of the cases we studied did not fit the label of "nonvoluntary life-ending" for at least 1 of the following reasons: the drugs were administered with a focus on symptom control; a hastened death was highly unlikely; or the act was taken in accordance with the patient's previously expressed wishes. Thus, we recommend a more nuanced view of life-ending acts without explicit patient request in the debate on physician-assisted dying.

Questions and answers on the Belgian model of integral end-of-life care: experiment? Prototype? : "Eu-euthanasia": the close historical, and evidently synergistic, relationship between palliative care and euthanasia in Belgium: an interview with a doctor involved in the early development of both and two of his successors.

This article analyses domestic and foreign reactions to a 2008 report in the British Medical Journal on the complementary and, as argued, synergistic relationship between palliative care and euthanasia in Belgium. The earliest initiators of palliative care in Belgium in the late 1970s held the view that access to proper palliative care was a precondition for euthanasia to be acceptable and that euthanasia and palliative care could, and should, develop together. Advocates of euthanasia including author Jan Bernheim, independent from but together with British expatriates, were among the founders of what was probably the first palliative care service in Europe outside of the United Kingdom. In what has become known as the Belgian model of integral end-of-life care, euthanasia is an available option, also at the end of a palliative care pathway. This approach became the majority view among the wider Belgian public, palliative care workers, other health professionals, and legislators. The legal regulation of euthanasia in 2002 was preceded and followed by a considerable expansion of palliative care services. It is argued that this synergistic development was made possible by public confidence in the health care system and widespread progressive social attitudes that gave rise to a high level of community support for both palliative care and euthanasia. The Belgian model of so-called integral end-of-life care is continuing to evolve, with constant scrutiny of practice and improvements to procedures. It still exhibits several imperfections, for which some solutions are being developed. This article analyses this model by way of answers to a series of questions posed by Journal of Bioethical Inquiry consulting editor Michael Ashby to the Belgian authors.

Expressed wishes and incidence of euthanasia in advanced lung cancer patients.

This study explores expressed wishes and requests for euthanasia (i.e. administration of lethal drugs at the explicit request of the patient), and incidence of end-of-life decisions with possible life-shortening effects (ELDs) in advanced lung cancer patients in Flanders, Belgium. We performed a prospective, longitudinal, observational study of a consecutive sample of advanced lung cancer patients and selected those who died within 18 months of diagnosis. Immediately after death, the pulmonologist/oncologist and general practitioner (GP) of the patient filled in a questionnaire. Information was available for 105 out of 115 deaths. According to the specialist or GP, one in five patients had expressed a wish for euthanasia; and three in four of these had made an explicit and repeated request. One in two of these received euthanasia. Of the patients who had expressed a wish for euthanasia but had not made an explicit and repeated request, none received euthanasia. Patients with a palliative treatment goal at inclusion were more likely to receive euthanasia. Death was preceded by an ELD in 62.9% of patients. To conclude, advanced lung cancer patients who expressed a euthanasia wish were often determined. Euthanasia was performed significantly more among patients whose treatment goal after diagnosis was exclusively palliative.

Felicitometric hermeneutics: interpreting quality of life measurements.

The use of quality of life (QOL) outcomes in clinical trials is increasing as a number of practical, ethical, methodological, and regulatory reasons for their use have become apparent. It is important, then, that QOL measurements and differences between QOL scores be readily interpretable. We study interpretation in two contexts: when determining QOL and when basing decisions on QOL differences. We consider both clinical situations involving individual patients and research contexts, e.g., randomized clinical trials, involving groups of patients. We note the ethical importance of such understanding: proper interpretation and communication facilitate health care decision making. Communication that facilitates interpretation is of moral significance since better communication can attenuate ethical problems and inform choices. Much of what is communication worthy about QOL assessments is determined by the particular QOL instrument used in the assessment and how it is administered. In practice, these choices will be driven by the purpose of the assessment, but, it is argued, to maximize understanding, we should combine the information garnered from traditional standardized QOL instruments, from individualized QOL assessments, and from a recently proposed dialogic paradigm, where QOL is determined by shared conversation regarding the interpretation of texts. And, while some studies can surely succeed using abbreviated methods of administration (e.g., postal surveys may suffice for certain purposes), we will focus on methods of administration involving interviewer-respondent interaction. We suggest that during the QOL elicitation process, interviewer and respondent should engage in a two-way conversation in order to achieve a shared understanding of the "answers" to QOL "questions" and, finally, to reach a shared interpretation of the individual's QOL.

Preferred and actual involvement of advanced lung cancer patients and their families in end-of-life decision making: a multicenter study in 13 hospitals in Flanders, Belgium.

CONTEXT: Death is often preceded by medical decisions that potentially shorten life (end-of-life decisions [ELDs]), for example, the decision to withhold or withdraw treatment. Respect for patient autonomy requires physicians to involve their patients in this decision making. OBJECTIVES: The objective of this study was to examine the involvement of advanced lung cancer patients and their families in ELD making and compare their actual involvement with their previously stated preferences for involvement. METHODS: Patients with Stage IIIb/IV non-small cell lung cancer were recruited by physicians in 13 hospitals and regularly interviewed between diagnosis and death. When the patient died, the specialist and general practitioner were asked to fill in a questionnaire. RESULTS: Eighty-five patients who died within 18 months of diagnosis were studied. An ELD was made in 52 cases (61%). According to the treating physician, half of the competent patients were not involved in the ELD making, one-quarter shared the decision with the physician, and one-quarter made the decision themselves. In the incompetent patients, family was involved in half of cases. Half of the competent patients were involved less than they had previously preferred, and 7% were more involved. Almost all of the incompetent patients had previously stated that they wanted their family involved in case of incompetence, but half did not achieve this. CONCLUSION: In half of the cases, advanced lung cancer patients-or their families in cases of incompetence-were not involved in ELD making, despite the wishes of most of them. Physicians should openly discuss ELDs and involvement preferences with their advanced lung cancer patients.

A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority.

Objectives Locked-in syndrome (LIS) consists of anarthria and quadriplegia while consciousness is preserved. Classically, vertical eye movements or blinking allow coded communication. Given appropriate medical care, patients can survive for decades. We studied the self-reported quality of life in chronic LIS patients. Design 168 LIS members of the French Association for LIS were invited to answer a questionnaire on medical history, current status and end-of-life issues. They self-assessed their global subjective well-being with the Anamnestic Comparative Self-Assessment (ACSA) scale, whose +5 and -5 anchors were their memories of the best period in their life before LIS and their worst period ever, respectively. Results 91 patients (54%) responded and 26 were excluded because of missing data on quality of life. 47 patients professed happiness (median ACSA +3) and 18 unhappiness (median ACSA -4). Variables associated with unhappiness included anxiety and dissatisfaction with mobility in the community, recreational activities and recovery of speech production. A longer time in LIS was correlated with happiness. 58% declared they did not wish to be resuscitated in case of cardiac arrest and 7% expressed a wish for euthanasia. Conclusions Our data stress the need for extra palliative efforts directed at mobility and recreational activities in LIS and the importance of anxiolytic therapy. Recently affected LIS patients who wish to die should be assured that there is a high chance they will regain a happy meaningful life. End-of-life decisions, including euthanasia, should not be avoided, but a moratorium to allow a steady state to be reached should be proposed.

Preferences of patients with advanced lung cancer regarding the involvement of family and others in medical decision-making.

OBJECTIVE: To explore the preferences of competent patients with advanced lung cancer regarding involvement of family and/or others in their medical decision-making, and their future preferences in case of loss of competence. METHODS: Over 1 year, physicians in 13 hospitals in Flanders, Belgium, recruited patients with initial non-small­cell lung cancer, stage IIIb or IV. The patients were interviewed with a structured questionnaire every 2 months until the fourth interview and every 4 months until the sixth interview. RESULTS: At inclusion, 128 patients were interviewed at least once; 13 were interviewed 6 consecutive times. Sixty-nine percent of patients wanted family members to be involved in medical decision-making and this percentage did not change significantly over time. One third of these patients did not achieve this preference. Ninety-four percent of patients wanted family involvement if they lost competence, 23% of these preferring primary physician control over decision-making, 41% shared physician and family control, and 36% primary family control. This degree of preferred family involvement expressed when competent did not change significantly over time at population level, but did at individual level; almost half the patients changed their minds either way at some point during the observation period. CONCLUSIONS: The majority of patients with lung cancer wanted family involvement in decision-making, and almost all did so in case of future loss of competence. However, as half of the patients changed their minds over time about the degree of family involvement they wanted if they lost competence, physicians should regularly rediscuss a patient's preferences.

Cross-national comparability of the WHOQOL-BREF: a measurement invariance approach.

PURPOSE: To evaluate whether the WHOQOL-BREF measures the QOL construct in the same way across nations. METHODS: Students from Flanders, Belgium and Iran completed the WHOQOL-BREF as part of a larger Quality of Life questionnaire. Their responses were compared using a multi-group confirmatory factor analysis. RESULTS: In general, the QOL construct appears rather similar in both cultures; however, participants from both countries seem to respond differently to particular items of the WHOQOL-BREF. Especially for the physical and psychological domain, this is problematic, because none of their indicators works in the same way across samples. CONCLUSIONS: Notwithstanding some limitations of this study, it must be concluded that the WHOQOL-BREF should only be used with great caution in cross-national comparisons.

Truth-telling at the end of life: a pilot study on the perspective of patients and professional caregivers.

OBJECTIVE: To describe the attitudes towards truth-telling of both terminal patients and professional caregivers, and to determine their perceived barriers to full information exchange. METHODS: In-depth interviews with 17 terminal patients selected through GPs and staff members of Flemish palliative care centres, and 3 focus groups with different professional caregivers. Analysis was based on grounded theory. RESULTS: There was considerable variability in the preferences of patients regarding when and how they wanted to be informed of their diagnosis, prognosis, expected disease course and end-of-life decisions. Major ambivalence was observed regarding the degree to which patients wanted to hear 'the whole truth'. Patients and caregivers agreed that truth-telling should be a 'dosed and gradual' process. Several barriers to more complete and timely truth-telling were identified. CONCLUSION: The preferences of both patients and caregivers for step-by-step--and hence slow and limited--information prevents terminal patients from reaching the level of information needed for informed end-of-life decision-making. PRACTICE IMPLICATIONS: The preference of patients and caregivers to 'dose' the truth may entail some risks, such as a 'Catch 22' situation in which both patients and caregivers wait for a signal from each other before starting a dialogue about impending death.

The role of general practitioners in continuity of care at the end of life: a qualitative study of terminally ill patients and their next of kin.

OBJECTIVES: Exploring terminal patients' perceptions of GPs' role in delivering continuous end-of-life care and identifying barriers to this. DESIGN: Qualitative interview study with patients (two consecutive interviews). SETTING: Primary care Belgium. PARTICIPANTS: Seventeen terminally ill cancer patients, informed about diagnosis and prognosis. RESULTS: Terminal patients attribute a pivotal role to GPs in different aspects of two types of continuity. Relational continuity: having an ongoing relationship with the same GP, of which important aspects are eg, keeping in touch after referral and feeling responsible for the patient. Informational continuity: use of information on past events and personal circumstances to provide individualised care, of which important aspects are eg, exchange of information between GPs, specialists and care facilities. Patients also identify barriers to continuity eg, lack of time and of GPs' initiative. CONCLUSIONS: At the end of life when physicians can no longer rely on biomedical models of diagnosis-therapy-cure, patients' perspectives are of utmost importance. This qualitative study made it possible to gain insights into terminal patients' perceptions of continuous primary end-of-life care. It clarifies the concept and identifies barriers to it.

End-of-life decisions among cancer patients compared with noncancer patients in Flanders, Belgium.

PURPOSE: Incidence studies reported more end-of-life decisions with possible/certain life-shortening effect (ELDs) among cancer patients than among noncancer patients. These studies did not correct for the different proportions of sudden/unexpected deaths of cancer versus noncancer patients, which could have biased the results. We investigated incidences and characteristics of ELDs among nonsudden cancer and noncancer deaths. METHODS: We sampled 5,005 certificates of all deaths in 2001 (Flanders, Belgium) stratified for ELD likelihood. Questionnaires were mailed to the certifying physicians. Data were corrected for stratification and nonresponse. RESULTS: The response rate was 59%. Among 2,128 nonsudden deaths included, ELDs occurred in 74% of cancer versus 50% of noncancer patients (P < .001). Symptom alleviation with possible life-shortening effect occurred more frequently among cancer patients (P < .001); nontreatment decisions occurred less frequently (P < .001). The higher incidence of lethal drug use among cancer patients did not hold after correcting for patient age. Half of the cancer patients who died after an ELD were incompetent to make decisions compared with 76% of noncancer patients (P < .001). Discussion with patients and relatives was similar in both groups. In one fifth of all patients the ELD was not discussed. CONCLUSION: ELDs are common in nonsudden deaths. The different incidences for symptom alleviation with possible life-shortening effect and nontreatment decisions among cancer versus noncancer patients may be related to differences in dying trajectories and in timely recognition of patient needs. The end-of-life decision-making process is similar for both groups: consultation of patients and relatives can be improved in a significant minority of patients.

Communication on end-of-life decisions with patients wishing to die at home: the making of a guideline for GPs in Flanders, Belgium.

BACKGROUND: Communication with patients on end-of-life decisions is a delicate topic for which there is little guidance. AIM: To describe the development of a guideline for GPs on end-of-life communication with patients who wish to die at home, in a context where patient autonomy and euthanasia are legally regulated. DESIGN OF STUDY: A three-phase process (generation, elaboration and validation). In the generation phase, literature findings were structured and then prioritised in a focus group with GPs of a palliative care consultation network. In the elaboration phase, qualitative data on patients' and caregivers' perspectives were gathered through a focus group with next-of-kin, in-depth interviews with terminal patients, and four quality circle sessions with representatives of all constituencies. In the validation phase, the acceptability of the draft guideline was reviewed in bipolar focus groups (GPs-nurses and GPs-specialists). Finally, comments were solicited from experts by mail. SETTING: Primary home care in Belgium. SUBJECTS: Participants in this study were terminal patients (n = 17), next-of-kin of terminal patients (n = 17), GPs (n = 25), specialists (n = 3), nurses (n = 8), other caregivers (n = 2) and experts (n = 41). RESULTS: Caregivers and patients expressed a need for a comprehensive guideline on communication in end-of-life decisions. Four major communication themes were prioritised: truth telling; exploration of the patient's wishes regarding the end of life; dealing with disproportionate interventions; and dealing with requests for euthanasia in the terminal phase of life. Additional themes required special attention in the guideline: continuity of care by the GP; communication on foregoing food and fluid; and technical aspects of euthanasia. CONCLUSION: It was feasible to develop a guideline by combining the three cornerstones of evidence-based medicine: literature search, patient values and professional experience.