Prevalence of the Minimally Conscious State Among Institutionalized Patients in the Netherlands: A Nationwide Study.

BACKGROUND AND OBJECTIVES: The minimally conscious state (MCS) is a prolonged disorder of consciousness (pDoC) and one of the most severe outcomes of acquired brain injury. Prevalence data are scarce. The aim of this study was to establish the nationwide point prevalence of institutionalized patients in MCS in the Netherlands. METHODS: This was a descriptive cross-sectional study in which all 86 Dutch hospitals, all 5 specialized pDoC rehabilitation facilities, and all 274 nursing homes were asked whether they were treating patients with a pDoC on the point prevalence date of September 15, 2021. Each patient's legal representative provided informed consent for their inclusion. Patient level of consciousness was verified using the Coma Recovery Scale-Revised (CRS-R) in a single assessment session performed in the facility of residence by an experienced physician. Data on patient demographics, etiology, level of consciousness, facility of residence, and clinical status were collected from a questionnaire by the treating physician. The prevalence of institutionalized patients in MCS of per 100,000 members of the Dutch population was calculated, based on actual census data. RESULTS: Seventy patients were reported to have a pDoC, of whom 6 were excluded. The level of consciousness was verified for 49 patients while for 15, it could not be verified. Of the patients verified, 38 had a pDoC, of whom 32 were in MCS (mean age 44.8 years, 68.8% male). The prevalence of institutionalized patients in MCS is 0.2-0.3 per 100,000 Dutch inhabitants. Traumatic brain injury was present in 21 of 32 patients (65.6%). Specialized pDoC rehabilitation was received by 17 of 32 patients (53%), with the rest admitted to nursing homes. The most frequent signs of consciousness on the CRS-R were visual pursuit, reproducible movement to command, and automatic motor response. DISCUSSION: This nationwide study revealed a low prevalence of institutionalized patients in MCS in the Netherlands. These findings are now being used to organize pDoC care in this country.

Post-Acute Level Of Consciousness scale revised (PALOC-sr): adaptation of a scale for classifying the level of consciousness in patients with a prolonged disorder of consciousness.

OBJECTIVE: To present an updated version of the 'Post-acute Level Of Consciousness scale' (PALOC-s), in accordance with the latest scientific insights. METHODS: Within the context of a research project, 20 years ago, the PALOC-s was developed for the purpose of following the development of the level of consciousness of young unconscious patients participating in a rehabilitation program. Meanwhile, the understanding of the behavior related to different levels of consciousness has developed and terminology has changed, resulting in the need to revise the PALOC-s. With the preservation of the original description of the eight hierarchical levels of PALOC-s, adaptations are made in the terminology and grouping of these levels. RESULTS AND CONCLUSION: This manuscript presents the revised version of PALOC-sr, which is suitable for use in clinical practice. The validation of this scale is recommended for its optimal use in future (international) research projects.

Clinical and neurophysiological effects of central thalamic deep brain stimulation in the minimally conscious state after severe brain injury.

Deep brain stimulation (DBS) of the central thalamus is an experimental treatment for restoration of impaired consciousness in patients with severe acquired brain injury. Previous results of experimental DBS are heterogeneous, but significant improvements in consciousness have been reported. However, the mechanism of action of DBS remains unknown. We used magnetoencephalography to study the direct effects of DBS of the central thalamus on oscillatory activity and functional connectivity throughout the brain in a patient with a prolonged minimally conscious state. Different DBS settings were used to improve consciousness, including two different stimulation frequencies (50 Hz and 130 Hz) with different effective volumes of tissue activation within the central thalamus. While both types of DBS resulted in a direct increase in arousal, we found that DBS with a lower frequency (50 Hz) and larger volume of tissue activation was associated with a stronger increase in functional connectivity and neural variability throughout the brain. Moreover, this form of DBS was associated with improvements in visual pursuit, a reduction in spasticity, and improvement of swallowing, eight years after loss of consciousness. However, after DBS, all neurophysiological markers remained significantly lower than in healthy controls and objective increases in consciousness remained limited. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of DBS of the central thalamus in humans and suggest that DBS can re-activate dormant functional brain networks, but that the severely injured stimulated brain still lacks the ability to serve cognitive demands.

Towards consensus on visual pursuit and visual fixation in patients with disorders of consciousness. A Delphi study.

BACKGROUND: The aim of this Delphi study was to reach consensus about definition, operationalization and assessment of visual pursuit (VP) and visual fixation (VF). METHODS: In a three-round international Delphi study, clinical and research experts on disorders of consciousness indicated their level of agreement on 87 statements using a 5-point Likert scale. Consensus for agreement was defined by a median of 5, an interquartile range (IQR) ≤ 1, and ≥ 80% indicating moderate or strong agreement. RESULTS: Forty-three experts from three continents participated, 32 completed all three rounds. For VP, the consensus statements with the highest levels of agreement were on the term 'pursuit of a visual stimulus', the description 'ability to follow visually in horizontal and/or vertical plane', a duration > 2 s, tracking in horizontal and vertical planes, and a frequency of more than 2 times per assessment. For VF, consensus statements with the highest levels of agreement were on the term 'sustained VF', the description 'sustained fixation in response to a salient stimulus', a duration of > 2 s and a frequency of 2 or more times per assessment. The assessment factors with the highest levels of agreement were personalized stimuli, the use of eye tracking technology, a patient dependent time of assessment, sufficient environmental light, upright posture, and the necessity to exclude ocular/oculomotor problems. CONCLUSION: This first international Delphi study on VP and VF in patients with disorders of consciousness provides provisional operational definitions and an overview of the most relevant assessment factors.

Intensive neurorehabilitation for patients with prolonged disorders of consciousness: protocol of a mixed-methods study focusing on outcomes, ethics and impact.

BACKGROUND: Prolonged disorders of consciousness (PDOC) are amongst the severest sequelae of acquired brain injury. Evidence regarding epidemiology and rehabilitation outcomes is scarce. These knowledge gaps and psychological distress in families of PDOC patients may complicate clinical decision-making. The complex PDOC care and associated moral dilemmas result in high workload in healthcare professionals. Since 2019, all PDOC patients in the Netherlands have access to intensive neurorehabilitation up to 2 years post-injury provided by one rehabilitation center and four specialized nursing homes. Systematic monitoring of quantitative rehabilitation data within this novel chain of care is done in a study called DOCTOR. The optimization of tailored PDOC care, however, demands a better understanding of the impact of PDOC on patients, their families and healthcare professionals and their views on rehabilitation outcomes, end-of-life decisions and quality of dying. The True Outcomes of PDOC (TOPDOC) study aims to gain insight in the qualitative outcomes of PDOC rehabilitation and impact of PDOC on patients, their families and healthcare professionals. METHODS: Nationwide multicenter prospective cohort study in the settings of early and prolonged intensive neurorehabilitation with a two-year follow-up period, involving three study populations: PDOC patients > 16 years, patients' family members and healthcare professionals involved in PDOC care. Families' and healthcare professionals' views on quality of rehabilitation outcomes, end-of-life decisions and dying will be qualitatively assessed using comprehensive questionnaires and in-depth interviews. Ethical dilemmas will be explored by studying moral deliberations. The impact of providing care to PDOC patients on healthcare professionals will be studied in focus groups. DISCUSSION: To our knowledge, this is the first nationwide study exploring quality of outcomes, end-of-life decisions and dying in PDOC patients and the impact of PDOC in a novel chain of care spanning the first 24 months post-injury in specialized rehabilitation and nursing home settings. Newly acquired knowledge in TOPDOC concerning quality of outcomes in PDOC rehabilitation, ethical aspects and the impact of PDOC will enrich quantitative epidemiological knowledge and outcomes arising from DOCTOR. Together, these projects will contribute to the optimization of centralized PDOC care providing support to PDOC patients, families and healthcare professionals.

The Prevalence and Determinants of Neuropsychiatric Symptoms in People With Acquired Brain Injury in Nursing Homes.

OBJECTIVES: Establishing the prevalence and determinants of neuropsychiatric symptoms (NPS) in patients with acquired brain injury (ABI) in nursing homes. DESIGN: Cross-sectional, observational study. SETTING AND PARTICIPANTS: Patients 18-65 years old with ABI in special care units in Dutch nursing homes. METHODS: Nursing homes were recruited through the national expertise network for patients with severe ABI, regional brain injury teams, and by searching the Internet. Patient characteristics were collected through digital questionnaires. NPS were assessed with the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) and the Cohen-Mansfield Agitation Inventory (CMAI), cognition with the Mini-Mental State Examination, and activities of daily living with the Disability Rating Scale. Psychotropic drug use (PDU) was retrieved from the electronic prescription system. Individual NPS were clustered. Associations between determinants and NPS were examined using multilevel multivariate linear regression models. RESULTS: In a population of 118 patients from 12 nursing homes, 73.7% had 1 or more clinically relevant NPS and 81.3% 1 or more agitated behaviors. The most common NPS were agitation, in particular aberrant motor behavior (24.6%), repetitious sentences/questions (35.5%), and constant requests for attention (34.6%), verbal (33.6%) and physical (50.5%) aggression, and irritability (28.0%). Male patients were more likely to display hyperactivity. Being married was associated with less verbally agitated behavior and pain was associated with a higher CMAI total score. PDU increased the likelihood of a higher NPI-NH total score. CONCLUSIONS AND IMPLICATIONS: NPS are common in patients with ABI ≤65 years of age residing in nursing homes. This is a first step to fill in the knowledge gap concerning NPS in this population. An increasing number of patients with severe ABI may survive the acute phase and will reside many years in nursing homes. It is important to shed more light on these NPS, with regard to course, magnitude, and severity, to ultimately develop appropriate care for this vulnerable group of patients.

The Dilemma of Hydrocephalus in Prolonged Disorders of Consciousness.

Prolonged disorders of consciousness (DOC) are considered to be among the most severe outcomes after acquired brain injury. Medical care for these patients is mainly focused on minimizing complications, given that treatment options for patients with unresponsive wakefulness or minimal consciousness remain scarce. The complication rate in patients with DOC is high, both in the acute hospital setting, as in the rehabilitation or long-term care phase. Hydrocephalus is one of these well-known complications and usually develops quickly after acute changes in cerebrospinal fluid (CSF) circulation after different types of brain damage. However, hydrocephalus may also develop with a significant delay, weeks, or even months after the initial injury, reducing the potential for natural recovery of consciousness. In this phase, hydrocephalus is likely to be missed in DOC patients, given that their limited behavioral responsiveness camouflages the classic signs of increased intracranial pressure or secondary normal-pressure hydrocephalus. Moreover, the development of late-onset hydrocephalus may exceed the period of regular outpatient follow-up. Several controversies remain about the diagnosis of clinical hydrocephalus in patients with ventricular enlargement after severe brain injury. In this article, we discuss both the difficulties in diagnosis and dilemmas in the treatment of CSF disorders in patients with prolonged DOC and review evidence from the literature to advance an active surveillance protocol for the detection of this late, but treatable, complication. Moreover, we advocate a low threshold for CSF diversion when hydrocephalus is suspected, even months or years after brain injury.

On the pathophysiology and treatment of akinetic mutism.

Akinetic mutism (AM) is a rare neurological disorder characterized by the presence of an intact level of consciousness and sensorimotor capacity, but with a simultaneous decrease in goal-directed behavior and emotions. Patients are in a wakeful state of profound apathy, seemingly indifferent to pain, thirst, or hunger. It represents the far end within the spectrum of disorders of diminished motivation. In recent years, more has become known about the functional roles of neurocircuits and neurotransmitters associated with human motivational behavior. More specific, there is an increasing body of behavioral evidence that links specific damage of functional frontal-subcortical organization to the occurrence of distinct neurological deficits. In this review, we combine evidence from lesion studies and neurophysiological evidence in animals, imaging studies in humans, and clinical investigations in patients with AM to form an integrative theory of its pathophysiology. Moreover, the specific pharmacological interventions that have been used to treat AM and their rationales are reviewed, providing a comprehensive overview for use in clinical practice.

The patient with severe traumatic brain injury: clinical decision-making: the first 60 min and beyond.

PURPOSE OF REVIEW: There is an urgent need to discuss the uncertainties and paradoxes in clinical decision-making after severe traumatic brain injury (s-TBI). This could improve transparency, reduce variability of practice and enhance shared decision-making with proxies. RECENT FINDINGS: Clinical decision-making on initiation, continuation and discontinuation of medical treatment may encompass substantial consequences as well as lead to presumed patient benefits. Such decisions, unfortunately, often lack transparency and may be controversial in nature. The very process of decision-making is frequently characterized by both a lack of objective criteria and the absence of validated prognostic models that could predict relevant outcome measures, such as long-term quality and satisfaction with life. In practice, while treatment-limiting decisions are often made in patients during the acute phase immediately after s-TBI, other such severely injured TBI patients have been managed with continued aggressive medical care, and surgical or other procedural interventions have been undertaken in the context of pursuing a more favorable patient outcome. Given this spectrum of care offered to identical patient cohorts, there is clearly a need to identify and decrease existing selectivity, and better ascertain the objective criteria helpful towards more consistent decision-making and thereby reduce the impact of subjective valuations of predicted patient outcome. SUMMARY: Recent efforts by multiple medical groups have contributed to reduce uncertainty and to improve care and outcome along the entire chain of care. Although an unlimited endeavor for sustaining life seems unrealistic, treatment-limiting decisions should not deprive patients of a chance on achieving an outcome they would have considered acceptable.

Unexpected emergence from the vegetative state: delayed discovery rather than late recovery of consciousness.

BACKGROUND: The vegetative state, also known as the unresponsive wakefulness syndrome, is one of the worst possible outcomes of acquired brain injury and confronts rehabilitation specialists with various challenges. Emergence to (minimal) consciousness is classically considered unlikely beyond 3-6 months after non-traumatic or 12 months after traumatic etiologies. A growing body of evidence suggests that these timeframes are too narrow, but evidence regarding chances of recovery is still limited. OBJECTIVE: To identify the moment of recovery of consciousness in documented cases of late emergence from a vegetative state. METHODS: Four cases of apparent late recovery of consciousness, identified within a prospective cohort study, were studied in-depth by analyzing medical, paramedical and nursing files and interviewing the patients' families about their account of the process of recovery. RESULTS: All patients were found to have shown signs of consciousness well within the expected time frame (5 weeks-2 months post-ictus). These behaviors, however, went unnoticed or were misinterpreted, leading to a diagnostic delay of several months to over 5 years. Absence of appropriate diagnostics, the use of erroneous terminology, sedative medication but also patient-related factors such as hydrocephalus, language barriers and performance fluctuations are hypothesized to have contributed to the delay. CONCLUSIONS: Delayed recognition of signs of consciousness in patients in a vegetative state may not only lead to suboptimal clinical care, but also to distorted prognostic figures. Discriminating late recovery from the delayed discovery of consciousness, therefore, is vital to both clinical practice and science.

Prevalence of neuropsychiatric symptoms and psychotropic drug use in patients with acquired brain injury in long-term care: a systematic review.

OBJECTIVE: Little is known about the prevalence of neuropsychiatric symptoms (NPS) and psychotropic drug use (PDU) in patients below the age of 65 years with acquired brain injury (ABI) in long-term care. The objective of this study was to review the literature about the prevalence of NPS and PDU. METHODS: A systematic literature search of English, Dutch and German articles in Pubmed, EMBASE, PsycINFO and CINAHL was performed with the use of MeSH and free-text terms. RESULTS: Six articles met the inclusion criteria. The place of residence was mainly a nursing home and most studies were conducted in a population of patients with traumatic brain injury. Sample sizes varied from 40 to 26,472 residents and NPS were assessed with different assessment instruments. Depressive symptoms were most common with a prevalence ranging from 13.9% to 39.3%. Two studies reported PDU in which tranquillizers (59%) were the most prevalent psychotropic drugs followed by anticonvulsants (35%) and antidepressants (26-34%). CONCLUSIONS: Patients with ABI experience lifelong consequences, regardless the cause of ABI, that have a high impact on them and their surroundings. More insight into the magnitude of NPS and PDU, through prevalence studies, is necessary to achieve suitable provision of care for these patients.

Are visual functions diagnostic signs of the minimally conscious state? an integrative review.

Visual pursuit (VP) and visual fixation (VF) have been recognized as the first signs of emerging consciousness and, therefore, are considered indicative of the minimally conscious state (MCS). However, debate exists about their status as they are considered either conscious reactions or reflexes. The aim of this study is to review the evidence of the definition, operationalization, and assessment of VP and VF in unconscious patients. PubMed and EMBASE were searched for relevant papers between May 26, 1994 and October 1, 2016. In addition, an internet search was done to identify other relevant papers, reports and manuals of assessment methods. Papers were included if the definition, operationalization, or assessment method of VP and VF was discussed in patients with disorders of consciousness. We identified 2364 articles, of which 38 were included. No uniform definitions of VP and VF were found. VP and VF were operationalized differently, depending on which scale was used. The Coma Recovery Scale-revised and the Sensory Tool to Assess Responsiveness were the only diagnostic scales found; the other scales were developed to monitor DOC patients. The use of a mirror was the most sensitive method for detecting VP and VF. The literature about the importance VP and VF in relation with consciousness is controversial. This integrative review shows a lack of consensus regarding the definition, operationalization, and assessment of VP and VF. International consensus development about the definition, operationalization, and assessment of VP and VF is recommended.

Moral dilemmas and conflicts concerning patients in a vegetative state/unresponsive wakefulness syndrome: shared or non-shared decision making? A qualitative study of the professional perspective in two moral case deliberations.

BACKGROUND: Patients in a vegetative state/ unresponsive wakefulness syndrome (VS/UWS) pose ethical dilemmas to those involved. Many conflicts occur between professionals and families of these patients. In the Netherlands physicians are supposed to withdraw life sustaining treatment once recovery is not to be expected. Yet these patients have shown to survive sometimes for decades. The role of the families is thought to be important. The aim of this study was to make an inventory of the professional perspective on conflicts in long-term care of patients in VS/UWS. METHODS: A qualitative study of transcripts on 2 Moral Deliberations (MD's) in 2 cases of patients in VS/UWS in long-term care facilities. RESULTS: Six themes emerged: 1) Vision on VS/UWS; 2) Treatment and care plan; 3) Impact on relationships; 4) Feelings/attitude; 5) Communication; 6) Organizational aspects. These themes are related to professionals and to what families had expressed to the professionals. We found conflicts as well as contradictory feelings and thoughts to be a general feature in 4 of these themes, both in professionals and families. Conflicts were found in several actors: within families concerning all 6 themes, in nurse teams concerning the theme treatment and care plan, and between physicians concerning all 6 themes. CONCLUSIONS: Different visions, different expectations and hope on recovery, deviating goals and contradictory feelings/thoughts in families and professionals can lead to conflicts over a patient with VS/UWS. Key factors to prevent or solve such conflicts are a carefully established diagnosis, clarity upon visions, uniformity in treatment goals and plans, an open and empathic communication, expertise and understanding the importance of contradictory feelings/thoughts. Management should bridge conflicts and support their staff, by developing expertise, by creating stability and by facilitating medical ethical discourses. Shared compassion for the patient might be a key to gain trust and bridge the differences from non-shared to shared decision making.

Ten-to-twelve years after specialized neurorehabilitation of young patients with severe disorders of consciousness: A follow-up study.

OBJECTIVE: To explore the long-term outcome of young patients with disorders of consciousness who had received intensive neurorehabilitation. METHODS: A cross-sectional cohort study, in which the survival, level of consciousness, functional independence, mobility, communication and living situation were determined by means of a structured questionnaire. The cohort consisted of 44 children and young adults, originally either in a prolonged Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS, n = 33) or a Minimally Conscious State (MCS, n = 11) who had received a specialized neurorehabilitation programme 10-12 years earlier. RESULTS: Response rate was 72% (34/44). Eleven patients were deceased, 10 of whom were in VS/UWS or MCS at discharge from the programme. Of the remaining 23 patients, 19 were conscious. Twelve lived independently, of whom six required some household support. One conscious patient lived permanently in a long-term care facility. All other patients lived either independently or with their parents. None of the VS/UWS or MCS patients showed any functional recovery. CONCLUSION: Two main long-term outcome scenarios can be recognized. Two-thirds of the participating patients who were conscious at programme discharge were able to live independently, whereas almost two-thirds of the participating patients who were in VS/UWS or MCS at discharge subsequently died.

Changes in Prescribed Drugs Between Admission and the End of Life in Patients Admitted to Palliative Care Facilities.

BACKGROUND: The aim of prescribing medication in palliative end-of-life care should be symptom control. Data are lacking regarding the prescription of medication at the end of life. AIM: To investigate the prescription of medication in patients at the end of life in palliative care facilities. DESIGN, SETTING, AND PARTICIPANTS: An observational multicenter study in 7 inpatient palliative care facilities. Participants were adults with an estimated life expectancy of less than 3 months. The study was conducted from February 1, 2012, to January 1, 2013. RESULTS: A total of 155 patients were enrolled. On average, patients were prescribed 6.1 drugs at the moment of admission and 4.6 drugs on the day of death. The prescription of analgesics, psycholeptics, and drugs for functional gastrointestinal disorders increased from admission until death. In general, these are drug classes prescribed for symptom control. All other drug classes decreased between admission and the day of death, including different drug classes for the treatment of comorbid disease, such as anticoagulants, beta-blocking agents, drugs used in diabetes, and lipid-modifying agents. CONCLUSIONS AND RELEVANCE: A reduction in the total amount of medication is seen between admission and death in the palliative care facilities. Although there is an increase in prescribed symptom-specific medication and a reduction in medication prescribed for comorbid disease, there are still patients dying with medication not used for symptom control. This increases pill burden and indicates that physicians need to develop guidelines and educational programs for decreasing medication for comorbidities at the end of life.

The vegetative state: prevalence, misdiagnosis, and treatment limitations.

INTRODUCTION: Patients in a vegetative state/unresponsive wakefulness syndrome (VS/UWS) open their eyes spontaneously, but show only reflexive behavior. Although VS/UWS is one of the worst possible outcomes of acquired brain injury, its prevalence is largely unknown. This study's objective was to map the total population of hospitalized and institutionalized patients in VS/UWS in the Netherlands: prevalence, clinical characteristics, and treatment limitations. METHODS: Nationwide point prevalence study on patients in VS/UWS at least 1 month after acute brain injury in hospitals, rehabilitation centers, nursing homes, institutions for people with intellectual disability, and hospices; diagnosis verification by a researcher using the Coma Recovery Scale-revised (CRS-r); gathering of demographics, clinical characteristics, and treatment limitations. RESULTS: We identified 33 patients in VS/UWS, 24 of whose diagnoses could be verified. Patients were on average 51 years old with a mean duration of VS/UWS of 5 years. The main etiology was hypoxia sustained during cardiac arrest and resuscitation. More than 50% of patients had not received rehabilitation services. Most were given life-sustaining treatment beyond internationally accepted prognostic boundaries regarding recovery of consciousness. Seventeen (39%) of 41 patients presumed to be in VS/UWS were found to be at least minimally conscious. CONCLUSIONS: Results translate to a prevalence of 0.1 to 0.2 hospitalized and institutionalized VS/UWS patients per 100,000 members of the general population. This small figure may be related to the legal option to withhold or withdraw life-sustaining treatment, including artificial nutrition and hydration. On the other hand, this study shows that in certain cases, physicians continue life-prolonging treatment for up to 25 years. Patients have poor access to rehabilitation and are at substantial risk for misdiagnosis.

Prevalence differences of patients in vegetative state in The Netherlands and Vienna, Austria: a comparison of values and ethics.

OBJECTIVE: Little is known about prevalence of persistent vegetative state/unresponsive wakefulness syndrome and comparisons between countries. The aim of this column was to explore reasons for the comparable count of patients in vegetative state found in prevalence studies in nursing homes in 1 European country (Netherlands) compared with a single European city (Vienna, Austria). DESIGN: The column is based on a literature review of vegetative state in The Netherlands and Vienna in the period 2007-2008, in the context of professional interactions with families and physicians of patients in vegetative state. In addition, in both countries, families and physicians were interviewed to illustrate views. RESULTS: Comparable between the 2 settings are the population characteristics and the definition of, and criteria, for vegetative state. A difference can be found in the development of authoritative policy guidelines in the Netherlands, after public debates and jurisdiction, which did not exist in Vienna at the time. There also seem to be different societal values concerning rehabilitation and end-of-life decisions for patients in vegetative state. DISCUSSION: The most important explanation for the vegetative state prevalence differences between the Netherlands and Vienna can be found in the different societal values about patients in vegetative state and their treatment and rehabilitation. In the Netherlands, life prolonging medical treatment, including artificial nutrition and hydration, is considered futile and can be withdrawn if there is no prospect of recovery. In Vienna, however, patients in vegetative state are regarded as severely disabled and in need of long-term rehabilitation and social reintegration. There is no end-of-life discussion in this context.

Decision making about change of medication for comorbid disease at the end of life: an integrative review.

The main goal of palliative care is to improve quality of life by treating symptoms in patients with life-threatening illnesses. Most patients suffer from more than five severe comorbidities in the last 6 months of life. However, for patients receiving palliative care, interventions to prevent possible long-term complications of these comorbidities are no longer the primary aim of care. This paper aimed to review the literature regarding decision making about medication for comorbid disease at the end of life, defined as a life expectancy <3 months, and to formulate preliminary recommendations based on the existing literature. An integrative review approach was used. We searched the MEDLINE, EMBASE, and CINAHL databases. Papers were included if they had been published in the English language between 1 January 1995 and 31 December 2013, with an abstract. Additional studies were identified by searching bibliographies. Factors to consider when systematically reviewing medications are the goals of care, remaining life expectancy, treatment targets, time until benefit, number needed to treat, number needed to harm, and adverse drug reactions. Existing research focuses particularly on the use of certain drug classes during end-of-life care, including statins, antihypertensive agents, anticoagulants, antihyperglycaemic agents and antibiotics. Based on the results of this review, we made preliminary recommendations for these medication groups. Medication that does not benefit the patient in any way should be avoided. The aim of medication at the end of life should be symptom control. There is a need for prospective trials to give further insight into the decision-making process of medication management at the end of life.