Palliative care and end-of-life care for polypathological patients

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We excluded 112 studies regarding competencies related to consent in pediatric diseases, patient autonomy and legal aspects, 620 articles identified in the field of Medicine." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. Sureda-Demeulemeester, C. Ramis-Palmer, A. Sesé-Abad" "autores" => array:3 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Sureda-Demeulemeester" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Ramis-Palmer" ] 2 => array:2 [ "nombre" => "A." 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Polypathology" "titulo" => "Palliative care and end-of-life care for polypathological patients" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "543" "paginaFinal" => "552" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "E. Martinez-Litago, M.C. Martínez-Velasco, M.P. Muniesa-Zaragozano" "autores" => array:3 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Martinez-Litago" "email" => array:1 [ 0 => "elisamartinezlitago@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.C." "apellidos" => "Martínez-Velasco" ] 2 => array:2 [ "nombre" => "M.P." "apellidos" => "Muniesa-Zaragozano" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Hospital San Juan de Dios, Pamplona (Navarra), Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cuidados paliativos y atención al final de la vida en los pacientes pluripatológicos" ] ] "textoCompleto" => "BackgroundPatients afflicted with several chronic diseases in advanced phases have unique healthcare characteristics, which overlap with the physiological changes of aging. Not only are they afflicted with incurable diseases, but these patients also routinely experience pain and other symptoms such as asthenia, insomnia, dyspnea, anxiety, depression, nausea and anorexia, which affect quality of life and survival. Studies on treating these manifestations are scarce, which limits the information for guiding treatment and achieving good symptomatic control.<a class="elsevierStyleCrossRef" href="#bib0335">1</a>Consequently, these patients consume significant healthcare resources. For example, the elderly population, which frequently experiences chronic concomitant processes, are responsible for 40–50% of healthcare expenditures, 30–40% of total drug expenditures and 75% of expenditures for long-term treatments in Spain.<a class="elsevierStyleCrossRefs" href="#bib0340">2,3</a>However, patients with multiple diseases in advanced phases receive fragmented health care of deficient quality that decreases their quality of life.<a class="elsevierStyleCrossRef" href="#bib0350">4</a> Few patients with multiple diseases receive palliative care when necessary, despite the fact that this type of care has shown improvements in the patients’ quality of life, through the planning of care with a comprehensive and multidisciplinary approach.<a class="elsevierStyleCrossRef" href="#bib0355">5</a>According to the World Health Organization, palliative care is an approach for managing any life-threatening process that seeks, beyond healing, to improve the quality of life through the early identification of suffering, with an impeccable assessment and treatment of pain and other physical, psychosocial and spiritual problems.<a class="elsevierStyleCrossRef" href="#bib0360">6</a>According to data from the National Health System Palliative Care Strategy, approximately 30% of patients who die due to nononcologic causes would be eligible for palliative care.<a class="elsevierStyleCrossRef" href="#bib0365">7</a> According to this strategy, the palliative action framework for patients with multiple diseases should be interdisciplinary, and the decision making and administration of care should be shared with the patient, considering both the patient's disease severity and overall impairment.<a class="elsevierStyleCrossRef" href="#bib0370">8</a>Prognostic assessment of patients with advanced nononcologic diseasesHaving 3 or more concomitant diseases significantly increases the risk of death.<a class="elsevierStyleCrossRef" href="#bib0375">9</a> Some cardiometabolic comorbidities such as diabetes, stroke and acute myocardial infarction can increase the mortality rate by 8 fold and reduce life expectancy by up to 15 years.<a class="elsevierStyleCrossRef" href="#bib0375">9</a>Multimorbidity also physically debilitates patients, reducing their autonomy and increasing their risk of cognitive impairment.<a class="elsevierStyleCrossRef" href="#bib0380">10</a> The consequences of multimorbidity are frailty,<a class="elsevierStyleCrossRef" href="#bib0385">11</a> disability and reduced quality of life. In addition, we have the potential effects resulting from interactions between the prescribed drugs, between the drugs and the underlying diseases and between the diseases,<a class="elsevierStyleCrossRef" href="#bib0390">12</a> as well as the deleterious effects of inappropriate prescriptions.<a class="elsevierStyleCrossRef" href="#bib0395">13</a>To decrease uncertainty when addressing patients with multimorbidity, various published studies have developed prognostic and survival indices.<a class="elsevierStyleCrossRefs" href="#bib0400">14–18</a> To date, only the assessment of functional impairment associated with multimorbidity has shown independent prognostic value for mortality.<a class="elsevierStyleCrossRef" href="#bib0425">19</a> It should be emphasized that functional impairment is not always associated with advanced age.The PALIAR study was designed with this complex scenario in mind,<a class="elsevierStyleCrossRef" href="#bib0430">20</a> with the objective of validating the suitability of the defining criteria for terminal-phase nononcologic medical disease as prognostic predictors of mortality risk at 6 months.<a class="elsevierStyleCrossRefs" href="#bib0435">21–23</a> The study evaluated a cohort of 1847 patients and developed a simple tool with the following 6 items: age >85 years, presence of anorexia, dyspnea at rest, pressure ulcers, albumin <2.5mg/dL and an Eastern Cooperative Oncology Group Performance Status ≥3.<a class="elsevierStyleCrossRef" href="#bib0445">23</a> The resulting score, known as the PALIAR index, classifies patients into 4 groups with a different mortality risk at 6 months. This index achieved a notably higher calibration and discriminative power than the Charlson score<a class="elsevierStyleCrossRef" href="#bib0450">24</a> and slightly higher than the Palliative Prognostic Index<a class="elsevierStyleCrossRef" href="#bib0440">22</a> and National Hospice Organization criteria.<a class="elsevierStyleCrossRef" href="#bib0435">21</a>The PALIAR index has also contributed to the external and internal validation of the question “Would you be surprised if this patient died in the next 6–12 months?”<a class="elsevierStyleCrossRef" href="#bib0455">25</a> of the terminal illness criteria of the National Hospice Organization. When the PALIAR index is applied along with the question, the positive predictive value is improved because it eliminates interference resulting from the physician's empathy toward the patient, which induces an overestimation of survival.<a class="elsevierStyleCrossRef" href="#bib0455">25</a>Identifying which polypathological patients are candidates for active and early palliative care is a real challenge, especially considering that progression toward the final phase of nononcologic diseases often fluctuates.<a class="elsevierStyleCrossRef" href="#bib0460">26</a> Pursuing an exact prognostic stratification can therefore hinder the patient's therapeutic approach toward more reasonable objectives, such as those focused on improving the quality of life and preparing the patient's end of life.In advanced disease stages, the border between risk and benefit for a number of diagnostic and therapeutic maneuvers can become blurred. This situation can hinder decision-making in line with good clinical practice while also avoiding falling into nihilism or therapeutic fervor.End of life trajectories. FrailtyIn everyday clinical practice, it is difficult to determine when patients with advanced chronic diseases enter the final phase of their lives. Different trajectories can be described based on the main disease.Neoplastic diseases cause obvious clinical impairment within a short period, and the end of life is usually predictable. These diseases have a lower prevalence of functional impairment before the final stage, with greater relevance ascribed to nutritional problems and the demand for palliative care by patients and their family.<a class="elsevierStyleCrossRef" href="#bib0460">26</a>Organ failure in advanced phases shows a more gradual deterioration and fluctuating course, with acute episodes of worsening and partial recovery and usually have a greater need for healthcare resources due to unscheduled hospitalization and infectious complications.<a class="elsevierStyleCrossRef" href="#bib0460">26</a>In dementia, deterioration is slow and progressive. The prevalence of functional and cognitive impairment and geriatric syndromes is high, and it is associated with practitioners’ lower perception of the need for palliative care.<a class="elsevierStyleCrossRef" href="#bib0460">26</a>Lastly, there is a subgroup of patients who do not fit any of the previously mentioned trajectories. They have no criteria for chronic disease, no indicator is especially prevalent in terms of functionality, nutritional state, demands and needs, and health professionals feel little need to provide palliative care. This group could include frail patients who do not meet the criteria for advanced disease.<a class="elsevierStyleCrossRef" href="#bib0460">26</a>Care plan. Healthcare approachThe development of a palliative care plan can start jointly with the standard care for the patient during their illness trajectory or added at the end of life. This plan requires that the involved practitioners coordinate and prepare unified action protocols.<a class="elsevierStyleCrossRef" href="#bib0465">27</a> The creation of a coordinated circuit facilitates access to the healthcare system, strengthens patient autonomy and improves their home care, thereby avoiding fragmentation and improving the quality of care.<a class="elsevierStyleCrossRef" href="#bib0470">28</a>An established care plan therefore guides the therapeutic efforts and facilitates placement of the patient at the appropriate care level. The home should receive priority for the location of care, and the primary care team should be the foundation on which the care is built. Primary care manages the healthcare resources required to cover the patient's needs and detects the cases of greater complexity that are candidates for more specialized care by palliative care teams.<a class="elsevierStyleCrossRefs" href="#bib0470">28,29</a> Only by following this method can patients continue living in their own environment during the final phases of life, meeting the patients’ expectations to die at home.<a class="elsevierStyleCrossRef" href="#bib0475">29</a>In order to extend the length of time that patients can stay at home, their autonomy should be strengthened and their self-care encouraged, and the family should actively participate in their care. Given that this care model represents a significant burden for the patient's caregivers, the healthcare pathway must be well designed to address the home demands, preventing the caregivers from giving up, which would lead to undesirable hospitalizations.<a class="elsevierStyleCrossRefs" href="#bib0470">28,30</a> The financial repercussions of this self-management process and workload for home care has not yet been adequately assessed.<a class="elsevierStyleCrossRef" href="#bib0480">30</a>Communication with the patient and their environment. Early planning for the end of lifeEstablishing early communication with the patient offers additional time to comprehend the information provided and the disease itself, as well as to better understand the therapeutic limitations and morbidity associated with more intensive therapies. Elderly patients frequently are unaware of the severity of their organ disease. A study based on the follow-up of 25 geriatric patients requested the patients’ subjective assessment of their clinical condition. The participating patients related their symptoms to age and not to the advanced nature of their disease (in this case, heart failure), which even led to therapeutic noncompliance.<a class="elsevierStyleCrossRef" href="#bib0485">31</a>End-of-life care requires training for the healthcare team for a successful care plan.<a class="elsevierStyleCrossRef" href="#bib0490">32</a> Even today, communication between the patient and their reference physician is centered on curative treatment and resolving intercurrent acute processes. Many patients therefore believe that their physicians do not establish open communication on their treatment plans.<a class="elsevierStyleCrossRef" href="#bib0465">27</a> A study on patients in a cardiac rehabilitation program showed that 96% of those surveyed were interested in establishing a care plan, 15% had discussed the topic with their physicians, and only 10% had reported their wishes for the end of life.<a class="elsevierStyleCrossRef" href="#bib0495">33</a>Active communication needs to be established with the patient on the various possible trajectories in their progression, adapting the information in parallel with the prognosis and establishing various levels of information based on the individual's preferences. This approach is the only way to begin an advanced directive plan and to appropriately adapt the healthcare resources.<a class="elsevierStyleCrossRef" href="#bib0500">34</a>Avoiding dialog, due to uncertainty over the trajectory and disease prognosis, can lead to prescribing invasive treatments or treatments unsuitable for the patient's actual condition.Lastly, we should remember that there is the possibility that this type of approach may be rejected by the patient or relatives, by creating in them a feeling of loss of therapeutic opportunity and abandonment by the healthcare system as they have come to know it. Accepting palliative care is easier if proposed as an adjustment of treatment and not as a restriction.<a class="elsevierStyleCrossRef" href="#bib0505">35</a>Therapeutic approach in advanced disease phasesOnce the end-of-life situation has been identified and accepted, the priority for medical action is symptomatic control, which is understood as the absence of physical, mental or emotional discomfort.<a class="elsevierStyleCrossRef" href="#bib0360">6</a> As recommended in the clinical practice guidelines of palliative care, symptom assessment should consider the patient's overall situation, including not only their clinical circumstances but also the characteristics of their personal and family environment. The assessment should therefore be performed by a multidisciplinary team (regular physician and nurse, psychologist, palliative care expert, social worker, spiritual caregiver, etc.). A systematic anamnesis includes an active search for common symptoms through directed questions that complete the necessary information for a comprehensive approach.<a class="elsevierStyleCrossRefs" href="#bib0510">36,37</a> This search should cover the symptoms and their potential causes or underlying mechanisms so that the therapeutic selection (pharmaceutical or not) is well supported. The recording of each symptom, its treatment and progression in the medical history is important for control and follow-up, as it is for any other patient. All collected information should be explained to the patient and family in simple and understandable terms to minimize uncertainty and facilitate the subsequent approach, especially when symptomatic control is insufficient and when new symptoms or adverse effects arise. The information also provides the necessary understanding to reach a consensus on the treatment objectives and the terms for achieving them.The absence of unified definitions and scales hinders the implementation of studies on the final phases of life. The use of standardized instruments for recording symptoms is therefore recommended, as they provide observer objectivity, standardized patient follow-up and comparisons between groups. Validated analog and scoring scales are especially recommended, such as the Edmonton Symptom Assessment System.<a class="elsevierStyleCrossRef" href="#bib0510">36</a>The treatment of choice for symptomatic control is adjusted according to the patient's disease etiology, comorbidities and wishes. <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> list the most common symptoms at the end of life, the treatment and the recommended dosages for the drugs of choice.<a class="elsevierStyleCrossRefs" href="#bib0515">37–50</a> Special attention should be given to oral care, which significantly affects patient comfort, their ability to maintain oral intake, communication and social relationships and help provide dignity at the end of life. Appropriate daily hygiene and hydration of the lips and oral mucosa are essential, while avoiding the use of irritants (alcohol, lemons, etc.).<a class="elsevierStyleCrossRefs" href="#bib0510">36,37</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>It is also recommended that the entire treatment be reassessed from the new end-of-life perspective, always supported with good communication with the patient and their friends/family, which will help in selecting the drugs to withdraw based on each patient's preferences and needs.<a class="elsevierStyleCrossRefs" href="#bib0580">50–54</a> The drugs typically eligible for deprescription at the end of life are listed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.<a class="elsevierStyleCrossRef" href="#bib0600">54</a> During the patient's last days, all drugs not exclusively designed for symptomatic control should be withdrawn.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Improved survival or improved quality of life has not been demonstrated in these patients with the use of administration routes other than oral for nutrition and hydration. Therefore, whenever possible, the oral route should be used.<a class="elsevierStyleCrossRefs" href="#bib0510">36,55</a> The discomfort and risks of nasogastric tubes or a central pathway outweigh the expected benefits at this stage. Small quantities of food or beverage, when the patient can consume them, are therefore appropriate for maintaining their wellbeing. Artificial hydration is also not exempt from discomfort, risks and adverse effects and is therefore not usually recommended at this stage, except for controlling symptoms that specifically require it. If pathways other than oral (intravenous, nasogastric or other) were started before the final stage, both their withdrawal and maintenance might be appropriate, provided the decision is agreed upon. If the decision is made to keep them (for nutrition, hydration or administering medication), efforts should be made to prevent complications or adverse effects such as infection, edema, polyuria and cardiopulmonary congestion. If the decision is made to withdraw them, symptomatic control should likewise be ensured.<a class="elsevierStyleCrossRefs" href="#bib0510">36,37,55</a>In these stages, current Spanish legislation allows for both the withdrawal and noninitiation of treatment (which would include nutrition and hydration by artificial means), always with the patient's consent or that of their friends and family, as indicated in the General Health Law of 1986, Article 10 and its subsequent implementation in Law 41/2002 on patient autonomy and in the autonomous laws on the rights and guarantees in the process of death.<a class="elsevierStyleCrossRefs" href="#bib0610">56–61</a>Care in the last days of lifeThe care of patients in their last days of life has special relevance due the emotional impact on the patient and their family. The length of this period is not easy to establish but typically includes the complete deterioration of vital functions and functional state, which occurs 3–5 days prior to death. Its presentation varies and can be slow or very slow, depending on the underlying disease, or abrupt if there are additional acute complications.<a class="elsevierStyleCrossRef" href="#bib0640">62</a>Care should cover both the control of physical symptoms and the prevention of psychological suffering resulting from the emotional intensity of the moment, both for the patient and for their family. The memory of a patient's last days can destabilize the mourning period if the family believes that the care was inadequate. Questions regarding the care plan and the technical needs for care should be resolved during this process.<a class="elsevierStyleCrossRef" href="#bib0640">62</a>It is during this period that respect for personal privacy is of special importance, in accordance with the individual's preferences and values. This privacy is also laid down in the autonomous laws on patients’ rights and guarantees during the process of death, as has already been mentioned.<a class="elsevierStyleCrossRef" href="#bib0620">58</a> We need to ensure that individuals receive comprehensive palliative care and that death occurs at the place chosen by the patient or their family.Palliative sedationPalliative sedation is considered an indispensable treatment for relieving or controlling refractory symptoms. This type of sedation consists of administering drugs at dosages and combinations necessary to reduce patient consciousness during the process prior to death, with prior informed consent.<a class="elsevierStyleCrossRef" href="#bib0645">63</a>The estimated administration rate for palliative sedation varies significantly, between 1% and 72% according to the literature.<a class="elsevierStyleCrossRef" href="#bib0650">64</a> This considerable variability has numerous explanations, including the differences in its definition and in the context in which it is applied.<a class="elsevierStyleCrossRefs" href="#bib0645">63–65</a> There are no randomized studies on this subject and limited evidence from observational studies on the efficacy of palliative sedation in term of quality of life and symptom control, compared with patients who do not receive sedation.<a class="elsevierStyleCrossRef" href="#bib0645">63</a> Palliative sedation has not been shown to shorten life.<a class="elsevierStyleCrossRef" href="#bib0645">63</a>It is not unusual for the decision as to when to start palliative sedation to fall on the attending physician. It is uncommon for the patient or their family/friends to request the sedation.<a class="elsevierStyleCrossRef" href="#bib0655">65</a> Ideally, the decision should be agreed upon in a meeting of the multidisciplinary team for palliative care who treat the patient or indicated by a physician with experience in this setting.The literature on palliative sedation refers to patients with cancer in more than 95% of cases.<a class="elsevierStyleCrossRef" href="#bib0645">63</a> The differences observed in its application (between nononcologic and oncologic patients) are more related to clinical aspects than to the specific aspects of the sedation technique. These differences mainly affect the functional state (which is poorer in nononcologic patients) and to the greater participation of patients with cancer in the decision-making process regarding the start of palliative sedation through informed consent.<a class="elsevierStyleCrossRef" href="#bib0655">65</a> It is in these cases that a palliative care team is more often contacted before the start of palliative care. Most of the differences could be explained by the less predictable clinical course of nononcologic patients and their reduced access to palliative care services.<a class="elsevierStyleCrossRef" href="#bib0660">66</a>The most widely used sedative is midazolam; however, to achieve proper symptomatic control, combinations with other drugs are employed, such as morphine (to control pain and dyspnea), butylscopolamine or scopolamine (for rales), haloperidol (an antiemetic used to control delirium) and levomepromazine (for uncontrolled psychomotor agitation with midazolam and haloperidol).Intermittent palliative sedation is another resource that allows the patient and their friends/family to understand the actual effect of sedation and can help with decision making on the sedation depth and duration. This type of sedation is not often used, although its use can be underestimated, because rescue doses administered to control timely symptomatic exacerbations prior to starting continuous sedation are not considered intermittent.<a class="elsevierStyleCrossRef" href="#bib0655">65</a>Subcutaneous is the pathway of choice, especially in the patient's home, because of its simple and effective management and its few local complications (redness or induration at the injection site).<a class="elsevierStyleCrossRefs" href="#bib0640">62,64</a>In conclusion, we need to establish a coordinated and multidisciplinary care circuit for the early identification of patients with chronic diseases in advanced phases who have palliative needs and to optimize healthcare resources and provide appropriate palliative care that meets the specific needs of each patient. This circuit should involve the medical internist in coordination with primary care physicians, social workers and other professionals from reference departments who provide comprehensive patient care throughout the progression of the disease.The existing scientific literature on symptom control in nononcologic palliative patients is scarce, which requires us to assume a therapeutic management style for these patients similar to that for oncologic patients, for whom there is more evidence.We need to undertake and design studies that clarify the profile of nononcologic palliative patients, both in terms of their healthcare needs and their ideal treatment in the end-of-life stage.Conflict of interestsThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres947409" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec919892" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres947408" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec919893" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Prognostic assessment of patients with advanced nononcologic diseases" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "End of life trajectories. Frailty" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Care plan. Healthcare approach" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Communication with the patient and their environment. Early planning for the end of life" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Therapeutic approach in advanced disease phases" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Care in the last days of life" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Palliative sedation" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-01-31" "fechaAceptado" => "2017-08-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec919892" "palabras" => array:3 [ 0 => "End of life" 1 => "Palliative care" 2 => "Advanced chronic disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec919893" "palabras" => array:3 [ 0 => "Final de vida" 1 => "Atención paliativa" 2 => "Enfermedad crónica avanzada" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Patients with advanced chronic diseases receive fragmented care, which entails high resource consumption and a poor quality of life. Uncertainty in the prognosis and scarce investigation into the importance of symptomatic control in this patient group hinders a proper therapeutic approach.Palliative care teams optimize the use of resources through comprehensive patient care, the optimization of the patient's environment, communication, the preparation of early care plans and the creation of coordinated healthcare circuits, which improve the quality of the patient's care in advanced stages of the disease.In the end-of-life phase, the therapeutic approach is focused on symptomatic control, selecting treatments according to the cause, comorbidities and the patient's wishes. To control refractory symptoms, palliative sedation is considered an indispensable option." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Los pacientes con enfermedades crónicas en fase avanzada reciben una atención sanitaria fragmentada, que conlleva un alto consumo de recursos y una calidad de vida deficiente. La incertidumbre en el pronóstico y la escasa investigación sobre la importancia del control sintomático en este grupo de pacientes dificultan una adecuada actitud terapéutica.Los equipos de cuidados paliativos optimizan el uso de recursos mediante la atención integral del paciente y de su entorno, la comunicación, la elaboración del plan anticipado de cuidados y la creación de circuitos asistenciales coordinados, que mejoran la calidad asistencial del paciente en estadios avanzados de la enfermedad.En la fase de final de vida, el enfoque terapéutico se centra en el control sintomático, seleccionando el tratamiento según la causa, comorbilidades y deseos del paciente. Para el control de los síntomas refractarios la sedación paliativa se considera como una opción indispensable." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Martinez-Litago E, Martínez-Velasco MC, Muniesa-Zaragozano MP. Cuidados paliativos y atención al final de la vida en los pacientes pluripatológicos. Rev Clin Esp. 2017;217:543–552." ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: BZD, benzodiazepines; CAM, confusion assessment method; EOL, end of life; ND, nondrug; WHO, World Health Organization." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Symptom \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommended treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Observations \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Most common symptoms</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Drugs of the WHO analgesic scale Control of associated symptoms (depression, anxiety, dyspnea, etc.) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Do not combine 2nd and 3rd step Careful selection of adjuvants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anxiety \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND: emotional support, adapted exercise BZD: lorazepam, lormetazepam, midazolam Neuroleptics: haloperidol, chlorpromazine, risperidone, olanzapine, quetiapine Antidepressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Assess the required time to the start of the effect in terms of the vital prognosis, especially with antidepressants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Confusion, terminal delirium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Haloperidol (1st line) Levomepromazine (2nd line) BZD: combined with the previous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recommend use of standardized diagnostic tools (CAM or other) Monitor the possible paradoxical effect of BZD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Asthenia, fatigue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Adapted aerobic physical exercise Dexamethasone, methylprednisolone, modafinil, methylphenidate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correction of anemia in highly selected cases (assess adverse effects) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyspnea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Opioids ND: stimulate facial receptors (hand fan, room fan), nasal tubes with air or oxygen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Insomnia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND: sleep hygiene, change time of stimulants, psychological support BZD Sedative antidepressants (trazodone, mirtazapine) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Assess patient's wishes and their need for rest \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nausea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metoclopramide, chlorpropamide Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Review especially constipation, ileus and emetics \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Constipation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND: oral hydration, fiber, mobilization Lactulose, sennosides, magnesium hydroxide with paraffin and polyethylene glycol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Review astringents (opioids, calcium antagonists, diuretics, iron, anticholinergics, serotonergics), hypocalcemia, hypothyroidism, uremia, spinal compression Carefully monitor fecal impaction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diarrhea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Opioids Loperamide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Assess the degree of hydration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anorexia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dexamethasone, prednisone Megestrol acetate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Neither protein supplements or artificial nutrition improve survival in EOL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Other symptoms</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND: inhibit reflux with forced apnea, stimulation of the soft palate Baclofen (with or without omeprazole), metoclopramide, haloperidol, gabapentin, nifedipine, BZD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cough \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stronger or weaker opioids Cloperastine, antihistamines, cromolyn sodium, levodropropizine Bronchodilators Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pruritus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND: soft nonirritating hygiene, hydration (systemic and topical) Antihistamines Paroxetine, gabapentin If opioids: reduce ondansetron If cholestasis: naltrexone, rifampicin, androgens, cholestyramine, sertraline If uremia: phototherapy, antihistamines, mirtazapine, gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Depression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Standard nonspecific treatment of EOL Psychostimulants (alone or combined with antidepressants) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Assess the required time to the start of the antidepressive effect in terms of the vital prognosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dry mouth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND: chewing gum, acidic fruits, candy, ice Artificial saliva Pilocarpine mouthwash \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No need to increase hydration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rales \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduce hydration Lateral decubitus Scopolamine, butylscopolamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604544.png" ] ] ] ] "descripcion" => array:1 [ "en" => "End-of-life symptoms and recommended treatment." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: IM, intramuscular; IV, intravenous; sc, subcutaneous." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="8" align="left" valign="top">Anxiety</td><td class="td" title="table-entry " align="left" valign="top">Chlorpromazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25–100mg/day (in 3 doses) IM, orally (maximum 300mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 100mg orally 1–3 doses/day (maximum 3600mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 0.25mg orally, 1.25–5mg sc, IV (in 3 daily doses) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lorazepam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2–6mg in 2–3 doses orally (maximum 20mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lormetazepam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 0.5mg orally 1–3 doses/day  \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Midazolam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 2.5mg orally, IV, sc 1–6 doses/day  \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Olanzapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5–20mg/day orally 10mg/day IM (maximum 20mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Quetiapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 25mg orally 1–3 doses/day  \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Delirium</td><td class="td" title="table-entry " align="left" valign="top">Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 0.25mg orally, 1–3 doses/day sc, IV: 1.25mg 1–3 doses/day  \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Levomepromazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.5–25mg orally, IV, sc 1–4 doses/day IV infusion: 100mg/24h SC infusion: 50–75mg/24h (maximum 300mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lorazepam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5mg orally 1–3 doses/day (maximum 3mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Midazolam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 2.5mg orally, IV, sc 1–6 doses/day  \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Asthenia, depression</td><td class="td" title="table-entry " align="left" valign="top">Dexamethasone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4mg/24h orally, sc \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Methylphenidate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start: 5–5-0mg orally (maximum 60mg/day orally) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Modafinil \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">From 100mg/day to 200mg/12h orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Dyspnea</td><td class="td" title="table-entry " align="left" valign="top">Morphine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5/4h-20mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oxycodone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5/4h-20mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Nausea</td><td class="td" title="table-entry " align="left" valign="top">Chlorpromazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25–150mg/day IV, IM (in 3 doses) 15–75mg/day orally (in 3 doses) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Erythromycin (prokinetic) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5–1g/6h IV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.3–0.5mg/6–8h IV, sc \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Metoclopramide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10–20mg/day orally, sc \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Anorexia</td><td class="td" title="table-entry " align="left" valign="top">Dexamethasone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4mg/24h orally, sc, IV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Megestrol acetate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40–800mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prednisone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10–40mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="6" align="left" valign="top">Hypo</td><td class="td" title="table-entry " align="left" valign="top">Baclofen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5–20mg/12h orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chlorpromazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75–200mg/day orally (in 3/4 doses) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">300mg/8h orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3mg/night orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Metoclopramide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10–20mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nifedipine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10–20mg/8h orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="7" align="left" valign="top">Cough</td><td class="td" title="table-entry " align="left" valign="top">Codeine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10–30mg/4–6h orally (maximum 120mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cloperastine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20mg/8h orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dihydrocodeine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12–24mg/8h orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dextromethorphan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15mg/4–6h orally (maximum 30mg/6h) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100–300mg/day orally (maximum 3600mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Levodropropizine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60mg/8h orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Morphine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">From 2.5mg/4h orally, sc \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="8" align="left" valign="top">Pruritus</td><td class="td" title="table-entry " align="left" valign="top">Cholestyramine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4–8mg/day orally in 1–6 doses (maximum 24mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cromolyn \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical at 4%/12h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100–300mg/8h orally (maximum 3600mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mirtazapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15–30mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Naltrexone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25–50mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxetine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10mg/day orally \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rifampicin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5–10mg/kg/day orally (in 1–2 doses) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sertraline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50mg/day orally (maximum 200mg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Rales</td><td class="td" title="table-entry " align="left" valign="top">Butylscopolamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20mg/6–8h IV, sc IV infusion, sc: 100mg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scopolamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5–1mg/6h IV, sc IV infusion, sc: 1.5mg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604545.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Dosage of recommended drugs." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviation: PPS, palliative performance index." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reason for deprescription \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Potential undesirable effects \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiplatelets \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Life expectancy too short to reach effect Risk of bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antimicrobials \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">To be used only if the infection causes discomfort to be controlled (dysuria, respiratory secretions) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiosteoporotic agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Life expectancy too short to reach effect Frequency of adverse effects \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Statins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Life expectancy too short to reach effect Frequency of adverse effects \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoglycemic agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minor intake Unnecessary strict control of blood glucose: less need for measurements \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hyperglycemia (assess leaving minimum dosage necessary to prevent symptoms) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypotensive agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypotensive factors: reduced PPS, clinophilia, asthenia, anorexia, dehydration Other associated drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Progressive withdrawal, avoiding rebound effect (tachycardia, palpitations) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604543.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Drugs susceptible to deprescription at the end of life (alphabetical order)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:66 [ 0 => array:3 [ "identificador" => "bib0335" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Are there differences in the prevalence of palliative care-related problems in people living with advanced cancer and eight non-cancer conditions? A systematic review" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "on behalf of EURO IMPACT" "etal" => false "autores" => array:3 [ 0 => "K. Moens" 1 => "I. Higginson" 2 => "R. Harding" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Pain Symptom Manag" "fecha" => "2014" "volumen" => "48" "paginaInicial" => "660" "paginaFinal" => "677" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0340" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Distribución del gasto sanitario en atención primaria según edad y sexo: un análisis retrospectivo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Aguado" 1 => "D. Rodríguez" 2 => "F. Flor" 3 => "A. Sicras" 4 => "A. Ruiz" 5 => "A. Prados-Torres" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Aten Prim" "fecha" => "2012" "volumen" => "44" "paginaInicial" => "145" "paginaFinal" => "152" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0345" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Problemática específica de los mayores en la prescripción por principio activo. Informe INESME: Prescripción por principio activo: problemática y desafíos" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F. Guillén Llera" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2006" "editorial" => "Instituto de Estudios Médico Científicos" "editorialLocalizacion" => "Madrid" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0350" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased access to palliative care and hospice services: opportunities to improve value in health care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.E. Meier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-0009.2011.00632.x" "Revista" => array:6 [ "tituloSerie" => "Milbank Q" "fecha" => "2011" "volumen" => "89" "paginaInicial" => "343" "paginaFinal" => "380" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21933272" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0355" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The impact of advance care planning on end of life care in elderly patients: randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.M. Detering" 1 => "A.D. Hancock" 2 => "M.C. Reade" 3 => "W. 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Symposium. Polypathology

Palliative care and end-of-life care for polypathological patients

Cuidados paliativos y atención al final de la vida en los pacientes pluripatológicos

E. Martinez-Litago

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elisamartinezlitago@hotmail.com

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, M.C. Martínez-Velasco, M.P. Muniesa-Zaragozano

Servicio de Medicina Interna, Hospital San Juan de Dios, Pamplona (Navarra), Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Patients afflicted with several chronic diseases in advanced phases have unique healthcare characteristics&#44; which overlap with the physiological changes of aging&#46; Not only are they afflicted with incurable diseases&#44; but these patients also routinely experience pain and other symptoms such as asthenia&#44; insomnia&#44; dyspnea&#44; anxiety&#44; depression&#44; nausea and anorexia&#44; which affect quality of life and survival&#46; Studies on treating these manifestations are scarce&#44; which limits the information for guiding treatment and achieving good symptomatic control&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Consequently&#44; these patients consume significant healthcare resources&#46; For example&#44; the elderly population&#44; which frequently experiences chronic concomitant processes&#44; are responsible for 40&#8211;50&#37; of healthcare expenditures&#44; 30&#8211;40&#37; of total drug expenditures and 75&#37; of expenditures for long-term treatments in Spain&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; patients with multiple diseases in advanced phases receive fragmented health care of deficient quality that decreases their quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">4</span></a> Few patients with multiple diseases receive palliative care when necessary&#44; despite the fact that this type of care has shown improvements in the patients&#8217; quality of life&#44; through the planning of care with a comprehensive and multidisciplinary approach&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">According to the World Health Organization&#44; palliative care is an approach for managing any life-threatening process that seeks&#44; beyond healing&#44; to improve the quality of life through the early identification of suffering&#44; with an impeccable assessment and treatment of pain and other physical&#44; psychosocial and spiritual problems&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">According to data from the National Health System Palliative Care Strategy&#44; approximately 30&#37; of patients who die due to nononcologic causes would be eligible for palliative care&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">7</span></a> According to this strategy&#44; the palliative action framework for patients with multiple diseases should be interdisciplinary&#44; and the decision making and administration of care should be shared with the patient&#44; considering both the patient&#39;s disease severity and overall impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prognostic assessment of patients with advanced nononcologic diseases</span><p id="par0030" class="elsevierStylePara elsevierViewall">Having 3 or more concomitant diseases significantly increases the risk of death&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">9</span></a> Some cardiometabolic comorbidities such as diabetes&#44; stroke and acute myocardial infarction can increase the mortality rate by 8 fold and reduce life expectancy by up to 15 years&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Multimorbidity also physically debilitates patients&#44; reducing their autonomy and increasing their risk of cognitive impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">10</span></a> The consequences of multimorbidity are frailty&#44;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">11</span></a> disability and reduced quality of life&#46; In addition&#44; we have the potential effects resulting from interactions between the prescribed drugs&#44; between the drugs and the underlying diseases and between the diseases&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">12</span></a> as well as the deleterious effects of inappropriate prescriptions&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">13</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">To decrease uncertainty when addressing patients with multimorbidity&#44; various published studies have developed prognostic and survival indices&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">14&#8211;18</span></a> To date&#44; only the assessment of functional impairment associated with multimorbidity has shown independent prognostic value for mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">19</span></a> It should be emphasized that functional impairment is not always associated with advanced age&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The PALIAR study was designed with this complex scenario in mind&#44;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">20</span></a> with the objective of validating the suitability of the defining criteria for terminal-phase nononcologic medical disease as prognostic predictors of mortality risk at 6 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">21&#8211;23</span></a> The study evaluated a cohort of 1847 patients and developed a simple tool with the following 6 items&#58; age &#62;85 years&#44; presence of anorexia&#44; dyspnea at rest&#44; pressure ulcers&#44; albumin &#60;2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and an Eastern Cooperative Oncology Group Performance Status &#8805;3&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">23</span></a> The resulting score&#44; known as the PALIAR index&#44; classifies patients into 4 groups with a different mortality risk at 6 months&#46; This index achieved a notably higher calibration and discriminative power than the Charlson score<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">24</span></a> and slightly higher than the Palliative Prognostic Index<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">22</span></a> and National Hospice Organization criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">21</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The PALIAR index has also contributed to the external and internal validation of the question &#8220;Would you be surprised if this patient died in the next 6&#8211;12 months&#63;&#8221;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">25</span></a> of the terminal illness criteria of the National Hospice Organization&#46; When the PALIAR index is applied along with the question&#44; the positive predictive value is improved because it eliminates interference resulting from the physician&#39;s empathy toward the patient&#44; which induces an overestimation of survival&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">25</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Identifying which polypathological patients are candidates for active and early palliative care is a real challenge&#44; especially considering that progression toward the final phase of nononcologic diseases often fluctuates&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">26</span></a> Pursuing an exact prognostic stratification can therefore hinder the patient&#39;s therapeutic approach toward more reasonable objectives&#44; such as those focused on improving the quality of life and preparing the patient&#39;s end of life&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In advanced disease stages&#44; the border between risk and benefit for a number of diagnostic and therapeutic maneuvers can become blurred&#46; This situation can hinder decision-making in line with good clinical practice while also avoiding falling into nihilism or therapeutic fervor&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">End of life trajectories&#46; Frailty</span><p id="par0065" class="elsevierStylePara elsevierViewall">In everyday clinical practice&#44; it is difficult to determine when patients with advanced chronic diseases enter the final phase of their lives&#46; Different trajectories can be described based on the main disease&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Neoplastic diseases cause obvious clinical impairment within a short period&#44; and the end of life is usually predictable&#46; These diseases have a lower prevalence of functional impairment before the final stage&#44; with greater relevance ascribed to nutritional problems and the demand for palliative care by patients and their family&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">26</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Organ failure in advanced phases shows a more gradual deterioration and fluctuating course&#44; with acute episodes of worsening and partial recovery and usually have a greater need for healthcare resources due to unscheduled hospitalization and infectious complications&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">26</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In dementia&#44; deterioration is slow and progressive&#46; The prevalence of functional and cognitive impairment and geriatric syndromes is high&#44; and it is associated with practitioners&#8217; lower perception of the need for palliative care&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">26</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Lastly&#44; there is a subgroup of patients who do not fit any of the previously mentioned trajectories&#46; They have no criteria for chronic disease&#44; no indicator is especially prevalent in terms of functionality&#44; nutritional state&#44; demands and needs&#44; and health professionals feel little need to provide palliative care&#46; This group could include frail patients who do not meet the criteria for advanced disease&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Care plan&#46; Healthcare approach</span><p id="par0090" class="elsevierStylePara elsevierViewall">The development of a palliative care plan can start jointly with the standard care for the patient during their illness trajectory or added at the end of life&#46; This plan requires that the involved practitioners coordinate and prepare unified action protocols&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">27</span></a> The creation of a coordinated circuit facilitates access to the healthcare system&#44; strengthens patient autonomy and improves their home care&#44; thereby avoiding fragmentation and improving the quality of care&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">28</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">An established care plan therefore guides the therapeutic efforts and facilitates placement of the patient at the appropriate care level&#46; The home should receive priority for the location of care&#44; and the primary care team should be the foundation on which the care is built&#46; Primary care manages the healthcare resources required to cover the patient&#39;s needs and detects the cases of greater complexity that are candidates for more specialized care by palliative care teams&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">28&#44;29</span></a> Only by following this method can patients continue living in their own environment during the final phases of life&#44; meeting the patients&#8217; expectations to die at home&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">29</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In order to extend the length of time that patients can stay at home&#44; their autonomy should be strengthened and their self-care encouraged&#44; and the family should actively participate in their care&#46; Given that this care model represents a significant burden for the patient&#39;s caregivers&#44; the healthcare pathway must be well designed to address the home demands&#44; preventing the caregivers from giving up&#44; which would lead to undesirable hospitalizations&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">28&#44;30</span></a> The financial repercussions of this self-management process and workload for home care has not yet been adequately assessed&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Communication with the patient and their environment&#46; Early planning for the end of life</span><p id="par0105" class="elsevierStylePara elsevierViewall">Establishing early communication with the patient offers additional time to comprehend the information provided and the disease itself&#44; as well as to better understand the therapeutic limitations and morbidity associated with more intensive therapies&#46; Elderly patients frequently are unaware of the severity of their organ disease&#46; A study based on the follow-up of 25 geriatric patients requested the patients&#8217; subjective assessment of their clinical condition&#46; The participating patients related their symptoms to age and not to the advanced nature of their disease &#40;in this case&#44; heart failure&#41;&#44; which even led to therapeutic noncompliance&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">31</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">End-of-life care requires training for the healthcare team for a successful care plan&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">32</span></a> Even today&#44; communication between the patient and their reference physician is centered on curative treatment and resolving intercurrent acute processes&#46; Many patients therefore believe that their physicians do not establish open communication on their treatment plans&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">27</span></a> A study on patients in a cardiac rehabilitation program showed that 96&#37; of those surveyed were interested in establishing a care plan&#44; 15&#37; had discussed the topic with their physicians&#44; and only 10&#37; had reported their wishes for the end of life&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">33</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Active communication needs to be established with the patient on the various possible trajectories in their progression&#44; adapting the information in parallel with the prognosis and establishing various levels of information based on the individual&#39;s preferences&#46; This approach is the only way to begin an advanced directive plan and to appropriately adapt the healthcare resources&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">34</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Avoiding dialog&#44; due to uncertainty over the trajectory and disease prognosis&#44; can lead to prescribing invasive treatments or treatments unsuitable for the patient&#39;s actual condition&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Lastly&#44; we should remember that there is the possibility that this type of approach may be rejected by the patient or relatives&#44; by creating in them a feeling of loss of therapeutic opportunity and abandonment by the healthcare system as they have come to know it&#46; Accepting palliative care is easier if proposed as an adjustment of treatment and not as a restriction&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Therapeutic approach in advanced disease phases</span><p id="par0130" class="elsevierStylePara elsevierViewall">Once the end-of-life situation has been identified and accepted&#44; the priority for medical action is symptomatic control&#44; which is understood as the absence of physical&#44; mental or emotional discomfort&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">6</span></a> As recommended in the clinical practice guidelines of palliative care&#44; symptom assessment should consider the patient&#39;s overall situation&#44; including not only their clinical circumstances but also the characteristics of their personal and family environment&#46; The assessment should therefore be performed by a multidisciplinary team &#40;regular physician and nurse&#44; psychologist&#44; palliative care expert&#44; social worker&#44; spiritual caregiver&#44; etc&#46;&#41;&#46; A systematic anamnesis includes an active search for common symptoms through directed questions that complete the necessary information for a comprehensive approach&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">36&#44;37</span></a> This search should cover the symptoms and their potential causes or underlying mechanisms so that the therapeutic selection &#40;pharmaceutical or not&#41; is well supported&#46; The recording of each symptom&#44; its treatment and progression in the medical history is important for control and follow-up&#44; as it is for any other patient&#46; All collected information should be explained to the patient and family in simple and understandable terms to minimize uncertainty and facilitate the subsequent approach&#44; especially when symptomatic control is insufficient and when new symptoms or adverse effects arise&#46; The information also provides the necessary understanding to reach a consensus on the treatment objectives and the terms for achieving them&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The absence of unified definitions and scales hinders the implementation of studies on the final phases of life&#46; The use of standardized instruments for recording symptoms is therefore recommended&#44; as they provide observer objectivity&#44; standardized patient follow-up and comparisons between groups&#46; Validated analog and scoring scales are especially recommended&#44; such as the Edmonton Symptom Assessment System&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">36</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The treatment of choice for symptomatic control is adjusted according to the patient&#39;s disease etiology&#44; comorbidities and wishes&#46; <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> list the most common symptoms at the end of life&#44; the treatment and the recommended dosages for the drugs of choice&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">37&#8211;50</span></a> Special attention should be given to oral care&#44; which significantly affects patient comfort&#44; their ability to maintain oral intake&#44; communication and social relationships and help provide dignity at the end of life&#46; Appropriate daily hygiene and hydration of the lips and oral mucosa are essential&#44; while avoiding the use of irritants &#40;alcohol&#44; lemons&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">36&#44;37</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">It is also recommended that the entire treatment be reassessed from the new end-of-life perspective&#44; always supported with good communication with the patient and their friends&#47;family&#44; which will help in selecting the drugs to withdraw based on each patient&#39;s preferences and needs&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">50&#8211;54</span></a> The drugs typically eligible for deprescription at the end of life are listed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">54</span></a> During the patient&#39;s last days&#44; all drugs not exclusively designed for symptomatic control should be withdrawn&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Improved survival or improved quality of life has not been demonstrated in these patients with the use of administration routes other than oral for nutrition and hydration&#46; Therefore&#44; whenever possible&#44; the oral route should be used&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">36&#44;55</span></a> The discomfort and risks of nasogastric tubes or a central pathway outweigh the expected benefits at this stage&#46; Small quantities of food or beverage&#44; when the patient can consume them&#44; are therefore appropriate for maintaining their wellbeing&#46; Artificial hydration is also not exempt from discomfort&#44; risks and adverse effects and is therefore not usually recommended at this stage&#44; except for controlling symptoms that specifically require it&#46; If pathways other than oral &#40;intravenous&#44; nasogastric or other&#41; were started before the final stage&#44; both their withdrawal and maintenance might be appropriate&#44; provided the decision is agreed upon&#46; If the decision is made to keep them &#40;for nutrition&#44; hydration or administering medication&#41;&#44; efforts should be made to prevent complications or adverse effects such as infection&#44; edema&#44; polyuria and cardiopulmonary congestion&#46; If the decision is made to withdraw them&#44; symptomatic control should likewise be ensured&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">36&#44;37&#44;55</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In these stages&#44; current Spanish legislation allows for both the withdrawal and noninitiation of treatment &#40;which would include nutrition and hydration by artificial means&#41;&#44; always with the patient&#39;s consent or that of their friends and family&#44; as indicated in the General Health Law of 1986&#44; Article 10 and its subsequent implementation in Law 41&#47;2002 on patient autonomy and in the autonomous laws on the rights and guarantees in the process of death&#46;<a class="elsevierStyleCrossRefs" href="#bib0610"><span class="elsevierStyleSup">56&#8211;61</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Care in the last days of life</span><p id="par0160" class="elsevierStylePara elsevierViewall">The care of patients in their last days of life has special relevance due the emotional impact on the patient and their family&#46; The length of this period is not easy to establish but typically includes the complete deterioration of vital functions and functional state&#44; which occurs 3&#8211;5 days prior to death&#46; Its presentation varies and can be slow or very slow&#44; depending on the underlying disease&#44; or abrupt if there are additional acute complications&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">62</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Care should cover both the control of physical symptoms and the prevention of psychological suffering resulting from the emotional intensity of the moment&#44; both for the patient and for their family&#46; The memory of a patient&#39;s last days can destabilize the mourning period if the family believes that the care was inadequate&#46; Questions regarding the care plan and the technical needs for care should be resolved during this process&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">62</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">It is during this period that respect for personal privacy is of special importance&#44; in accordance with the individual&#39;s preferences and values&#46; This privacy is also laid down in the autonomous laws on patients&#8217; rights and guarantees during the process of death&#44; as has already been mentioned&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">58</span></a> We need to ensure that individuals receive comprehensive palliative care and that death occurs at the place chosen by the patient or their family&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Palliative sedation</span><p id="par0175" class="elsevierStylePara elsevierViewall">Palliative sedation is considered an indispensable treatment for relieving or controlling refractory symptoms&#46; This type of sedation consists of administering drugs at dosages and combinations necessary to reduce patient consciousness during the process prior to death&#44; with prior informed consent&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">63</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The estimated administration rate for palliative sedation varies significantly&#44; between 1&#37; and 72&#37; according to the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">64</span></a> This considerable variability has numerous explanations&#44; including the differences in its definition and in the context in which it is applied&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">63&#8211;65</span></a> There are no randomized studies on this subject and limited evidence from observational studies on the efficacy of palliative sedation in term of quality of life and symptom control&#44; compared with patients who do not receive sedation&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">63</span></a> Palliative sedation has not been shown to shorten life&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">63</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">It is not unusual for the decision as to when to start palliative sedation to fall on the attending physician&#46; It is uncommon for the patient or their family&#47;friends to request the sedation&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">65</span></a> Ideally&#44; the decision should be agreed upon in a meeting of the multidisciplinary team for palliative care who treat the patient or indicated by a physician with experience in this setting&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The literature on palliative sedation refers to patients with cancer in more than 95&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">63</span></a> The differences observed in its application &#40;between nononcologic and oncologic patients&#41; are more related to clinical aspects than to the specific aspects of the sedation technique&#46; These differences mainly affect the functional state &#40;which is poorer in nononcologic patients&#41; and to the greater participation of patients with cancer in the decision-making process regarding the start of palliative sedation through informed consent&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">65</span></a> It is in these cases that a palliative care team is more often contacted before the start of palliative care&#46; Most of the differences could be explained by the less predictable clinical course of nononcologic patients and their reduced access to palliative care services&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">66</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The most widely used sedative is midazolam&#59; however&#44; to achieve proper symptomatic control&#44; combinations with other drugs are employed&#44; such as morphine &#40;to control pain and dyspnea&#41;&#44; butylscopolamine or scopolamine &#40;for rales&#41;&#44; haloperidol &#40;an antiemetic used to control delirium&#41; and levomepromazine &#40;for uncontrolled psychomotor agitation with midazolam and haloperidol&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Intermittent palliative sedation is another resource that allows the patient and their friends&#47;family to understand the actual effect of sedation and can help with decision making on the sedation depth and duration&#46; This type of sedation is not often used&#44; although its use can be underestimated&#44; because rescue doses administered to control timely symptomatic exacerbations prior to starting continuous sedation are not considered intermittent&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">65</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Subcutaneous is the pathway of choice&#44; especially in the patient&#39;s home&#44; because of its simple and effective management and its few local complications &#40;redness or induration at the injection site&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">62&#44;64</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">In conclusion&#44; we need to establish a coordinated and multidisciplinary care circuit for the early identification of patients with chronic diseases in advanced phases who have palliative needs and to optimize healthcare resources and provide appropriate palliative care that meets the specific needs of each patient&#46; This circuit should involve the medical internist in coordination with primary care physicians&#44; social workers and other professionals from reference departments who provide comprehensive patient care throughout the progression of the disease&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The existing scientific literature on symptom control in nononcologic palliative patients is scarce&#44; which requires us to assume a therapeutic management style for these patients similar to that for oncologic patients&#44; for whom there is more evidence&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">We need to undertake and design studies that clarify the profile of nononcologic palliative patients&#44; both in terms of their healthcare needs and their ideal treatment in the end-of-life stage&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interests</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Prognostic assessment of patients with advanced nononcologic diseases"
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          "titulo" => "End of life trajectories&#46; Frailty"
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          "titulo" => "Care plan&#46; Healthcare approach"
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          "titulo" => "Communication with the patient and their environment&#46; Early planning for the end of life"
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          "titulo" => "Therapeutic approach in advanced disease phases"
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          "titulo" => "Care in the last days of life"
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            0 => "Final de vida"
            1 => "Atenci&#243;n paliativa"
            2 => "Enfermedad cr&#243;nica avanzada"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients with advanced chronic diseases receive fragmented care&#44; which entails high resource consumption and a poor quality of life&#46; Uncertainty in the prognosis and scarce investigation into the importance of symptomatic control in this patient group hinders a proper therapeutic approach&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Palliative care teams optimize the use of resources through comprehensive patient care&#44; the optimization of the patient&#39;s environment&#44; communication&#44; the preparation of early care plans and the creation of coordinated healthcare circuits&#44; which improve the quality of the patient&#39;s care in advanced stages of the disease&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In the end-of-life phase&#44; the therapeutic approach is focused on symptomatic control&#44; selecting treatments according to the cause&#44; comorbidities and the patient&#39;s wishes&#46; To control refractory symptoms&#44; palliative sedation is considered an indispensable option&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con enfermedades cr&#243;nicas en fase avanzada reciben una atenci&#243;n sanitaria fragmentada&#44; que conlleva un alto consumo de recursos y una calidad de vida deficiente&#46; La incertidumbre en el pron&#243;stico y la escasa investigaci&#243;n sobre la importancia del control sintom&#225;tico en este grupo de pacientes dificultan una adecuada actitud terap&#233;utica&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los equipos de cuidados paliativos optimizan el uso de recursos mediante la atenci&#243;n integral del paciente y de su entorno&#44; la comunicaci&#243;n&#44; la elaboraci&#243;n del plan anticipado de cuidados y la creaci&#243;n de circuitos asistenciales coordinados&#44; que mejoran la calidad asistencial del paciente en estadios avanzados de la enfermedad&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En la fase de final de vida&#44; el enfoque terap&#233;utico se centra en el control sintom&#225;tico&#44; seleccionando el tratamiento seg&#250;n la causa&#44; comorbilidades y deseos del paciente&#46; Para el control de los s&#237;ntomas refractarios la sedaci&#243;n paliativa se considera como una opci&#243;n indispensable&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Martinez-Litago E&#44; Mart&#237;nez-Velasco MC&#44; Muniesa-Zaragozano MP&#46; Cuidados paliativos y atenci&#243;n al final de la vida en los pacientes pluripatol&#243;gicos&#46; Rev Clin Esp&#46; 2017&#59;217&#58;543&#8211;552&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BZD&#44; benzodiazepines&#59; CAM&#44; confusion assessment method&#59; EOL&#44; end of life&#59; ND&#44; nondrug&#59; WHO&#44; World Health Organization&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Symptom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommended treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Observations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Most common symptoms</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Drugs of the WHO analgesic scale<br>Control of associated symptoms &#40;depression&#44; anxiety&#44; dyspnea&#44; etc&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Do not combine 2nd and 3rd step<br>Careful selection of adjuvants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anxiety&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&#58; emotional support&#44; adapted exercise<br>BZD&#58; lorazepam&#44; lormetazepam&#44; midazolam<br>Neuroleptics&#58; haloperidol&#44; chlorpromazine&#44; risperidone&#44; olanzapine&#44; quetiapine<br>Antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Assess the required time to the start of the effect in terms of the vital prognosis&#44; especially with antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Confusion&#44; terminal delirium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Haloperidol &#40;1st line&#41;<br>Levomepromazine &#40;2nd line&#41;<br>BZD&#58; combined with the previous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recommend use of standardized diagnostic tools &#40;CAM or other&#41;<br>Monitor the possible paradoxical effect of BZD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Asthenia&#44; fatigue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Adapted aerobic physical exercise<br>Dexamethasone&#44; methylprednisolone&#44; modafinil&#44; methylphenidate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Correction of anemia in highly selected cases &#40;assess adverse effects&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dyspnea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Opioids<br>ND&#58; stimulate facial receptors &#40;hand fan&#44; room fan&#41;&#44; nasal tubes with air or oxygen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Insomnia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&#58; sleep hygiene&#44; change time of stimulants&#44; psychological support<br>BZD<br>Sedative antidepressants &#40;trazodone&#44; mirtazapine&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Assess patient&#39;s wishes and their need for rest&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Metoclopramide&#44; chlorpropamide<br>Haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Review especially constipation&#44; ileus and emetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Constipation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&#58; oral hydration&#44; fiber&#44; mobilization<br>Lactulose&#44; sennosides&#44; magnesium hydroxide with paraffin and polyethylene glycol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Review astringents &#40;opioids&#44; calcium antagonists&#44; diuretics&#44; iron&#44; anticholinergics&#44; serotonergics&#41;&#44; hypocalcemia&#44; hypothyroidism&#44; uremia&#44; spinal compression<br>Carefully monitor fecal impaction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Opioids<br>Loperamide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Assess the degree of hydration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anorexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dexamethasone&#44; prednisone<br>Megestrol acetate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Neither protein supplements or artificial nutrition improve survival in EOL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Other symptoms</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&#58; inhibit reflux with forced apnea&#44; stimulation of the soft palate<br>Baclofen &#40;with or without omeprazole&#41;&#44; metoclopramide&#44; haloperidol&#44; gabapentin&#44; nifedipine&#44; BZD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Stronger or weaker opioids<br>Cloperastine&#44; antihistamines&#44; cromolyn sodium&#44; levodropropizine<br>Bronchodilators<br>Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&#58; soft nonirritating hygiene&#44; hydration &#40;systemic and topical&#41;<br>Antihistamines<br>Paroxetine&#44; gabapentin<br>If opioids&#58; reduce ondansetron<br>If cholestasis&#58; naltrexone&#44; rifampicin&#44; androgens&#44; cholestyramine&#44; sertraline<br>If uremia&#58; phototherapy&#44; antihistamines&#44; mirtazapine&#44; gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Depression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Standard nonspecific treatment of EOL<br>Psychostimulants &#40;alone or combined with antidepressants&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Assess the required time to the start of the antidepressive effect in terms of the vital prognosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dry mouth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&#58; chewing gum&#44; acidic fruits&#44; candy&#44; ice<br>Artificial saliva<br>Pilocarpine mouthwash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No need to increase hydration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rales&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reduce hydration<br>Lateral decubitus<br>Scopolamine&#44; butylscopolamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; IM&#44; intramuscular&#59; IV&#44; intravenous&#59; sc&#44; subcutaneous&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="8" align="left" valign="top">Anxiety</td><td class="td" title="table-entry  " align="left" valign="top">Chlorpromazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#8211;100<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;in 3 doses&#41; IM&#44; orally<br>&#40;maximum 300<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 100<span class="elsevierStyleHsp" style=""></span>mg orally 1&#8211;3 doses&#47;day<br>&#40;maximum 3600<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 0&#46;25<span class="elsevierStyleHsp" style=""></span>mg orally&#44; 1&#46;25&#8211;5<span class="elsevierStyleHsp" style=""></span>mg sc&#44; IV<br> &#40;in 3 daily doses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lorazepam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;6<span class="elsevierStyleHsp" style=""></span>mg in 2&#8211;3 doses orally<br>&#40;maximum 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lormetazepam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg orally 1&#8211;3 doses&#47;day<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Midazolam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg orally&#44; IV&#44; sc 1&#8211;6 doses&#47;day<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Olanzapine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally<br>10<span class="elsevierStyleHsp" style=""></span>mg&#47;day IM<br>&#40;maximum 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Quetiapine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 25<span class="elsevierStyleHsp" style=""></span>mg orally 1&#8211;3 doses&#47;day<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">Delirium</td><td class="td" title="table-entry  " align="left" valign="top">Haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 0&#46;25<span class="elsevierStyleHsp" style=""></span>mg orally&#44; 1&#8211;3 doses&#47;day<br>sc&#44; IV&#58; 1&#46;25<span class="elsevierStyleHsp" style=""></span>mg 1&#8211;3 doses&#47;day<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Levomepromazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;5&#8211;25<span class="elsevierStyleHsp" style=""></span>mg orally&#44; IV&#44; sc 1&#8211;4 doses&#47;day<br>IV infusion&#58; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h<br>SC infusion&#58; 50&#8211;75<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h<br>&#40;maximum 300<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lorazepam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5<span class="elsevierStyleHsp" style=""></span>mg orally 1&#8211;3 doses&#47;day<br>&#40;maximum 3<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Midazolam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg orally&#44; IV&#44; sc 1&#8211;6 doses&#47;day<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Asthenia&#44; depression</td><td class="td" title="table-entry  " align="left" valign="top">Dexamethasone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h orally&#44; sc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Methylphenidate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start&#58; 5&#8211;5-0<span class="elsevierStyleHsp" style=""></span>mg orally &#40;maximum 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Modafinil&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">From 100<span class="elsevierStyleHsp" style=""></span>mg&#47;day to 200<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Dyspnea</td><td class="td" title="table-entry  " align="left" valign="top">Morphine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;5&#47;4<span class="elsevierStyleHsp" style=""></span>h-20<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oxycodone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;5&#47;4<span class="elsevierStyleHsp" style=""></span>h-20<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">Nausea</td><td class="td" title="table-entry  " align="left" valign="top">Chlorpromazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#8211;150<span class="elsevierStyleHsp" style=""></span>mg&#47;day IV&#44; IM &#40;in 3 doses&#41;<br>15&#8211;75<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally &#40;in 3 doses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Erythromycin &#40;prokinetic&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5&#8211;1<span class="elsevierStyleHsp" style=""></span>g&#47;6<span class="elsevierStyleHsp" style=""></span>h IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;3&#8211;0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;6&#8211;8<span class="elsevierStyleHsp" style=""></span>h IV&#44; sc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Metoclopramide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&#44; sc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Anorexia</td><td class="td" title="table-entry  " align="left" valign="top">Dexamethasone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h orally&#44; sc&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Megestrol acetate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#8211;800<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#8211;40<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">Hypo</td><td class="td" title="table-entry  " align="left" valign="top">Baclofen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chlorpromazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">75&#8211;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally &#40;in 3&#47;4 doses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">300<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>mg&#47;night orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Metoclopramide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nifedipine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="7" align="left" valign="top">Cough</td><td class="td" title="table-entry  " align="left" valign="top">Codeine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#8211;30<span class="elsevierStyleHsp" style=""></span>mg&#47;4&#8211;6<span class="elsevierStyleHsp" style=""></span>h orally<br>&#40;maximum 120<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cloperastine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dihydrocodeine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#8211;24<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dextromethorphan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg&#47;4&#8211;6<span class="elsevierStyleHsp" style=""></span>h orally<br>&#40;maximum 30<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#8211;300<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally<br>&#40;maximum 3600<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Levodropropizine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Morphine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">From 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;4<span class="elsevierStyleHsp" style=""></span>h orally&#44; sc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="8" align="left" valign="top">Pruritus</td><td class="td" title="table-entry  " align="left" valign="top">Cholestyramine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#8211;8<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally in 1&#8211;6 doses<br>&#40;maximum 24<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cromolyn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical at 4&#37;&#47;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#8211;300<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h orally<br>&#40;maximum 3600<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mirtazapine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#8211;30<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Naltrexone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#8211;50<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxetine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rifampicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#8211;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day orally &#40;in 1&#8211;2 doses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sertraline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally<br>&#40;maximum 200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Rales</td><td class="td" title="table-entry  " align="left" valign="top">Butylscopolamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>mg&#47;6&#8211;8<span class="elsevierStyleHsp" style=""></span>h IV&#44; sc<br>IV infusion&#44; sc&#58; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scopolamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5&#8211;1<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h IV&#44; sc<br>IV infusion&#44; sc&#58; 1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Dosage of recommended drugs&#46;</p>"
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      ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>&#58; PPS&#44; palliative performance index&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reason for deprescription&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Potential undesirable effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiplatelets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Life expectancy too short to reach effect<br>Risk of bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antimicrobials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">To be used only if the infection causes discomfort to be controlled &#40;dysuria&#44; respiratory secretions&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiosteoporotic agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Life expectancy too short to reach effect<br>Frequency of adverse effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Statins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Life expectancy too short to reach effect<br>Frequency of adverse effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoglycemic agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minor intake<br>Unnecessary strict control of blood glucose&#58; less need for measurements&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hyperglycemia &#40;assess leaving minimum dosage necessary to prevent symptoms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypotensive agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypotensive factors&#58; reduced PPS&#44; clinophilia&#44; asthenia&#44; anorexia&#44; dehydration<br>Other associated drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Progressive withdrawal&#44; avoiding rebound effect &#40;tachycardia&#44; palpitations&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Drugs susceptible to deprescription at the end of life &#40;alphabetical order&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:66 [
            0 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Are there differences in the prevalence of palliative care-related problems in people living with advanced cancer and eight non-cancer conditions&#63; A systematic review"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "on behalf of EURO IMPACT"
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46; Moens"
                            1 => "I&#46; Higginson"
                            2 => "R&#46; Harding"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Pain Symptom Manag"
                        "fecha" => "2014"
                        "volumen" => "48"
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                        "paginaFinal" => "677"
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                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Distribuci&#243;n del gasto sanitario en atenci&#243;n primaria seg&#250;n edad y sexo&#58; un an&#225;lisis retrospectivo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Aguado"
                            1 => "D&#46; Rodr&#237;guez"
                            2 => "F&#46; Flor"
                            3 => "A&#46; Sicras"
                            4 => "A&#46; Ruiz"
                            5 => "A&#46; Prados-Torres"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
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                        "fecha" => "2012"
                        "volumen" => "44"
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            ]
            2 => array:3 [
              "identificador" => "bib0345"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Problem&#225;tica espec&#237;fica de los mayores en la prescripci&#243;n por principio activo&#46; Informe INESME&#58; Prescripci&#243;n por principio activo&#58; problem&#225;tica y desaf&#237;os"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "F&#46; Guill&#233;n Llera"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2006"
                        "editorial" => "Instituto de Estudios M&#233;dico Cient&#237;ficos"
                        "editorialLocalizacion" => "Madrid"
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            ]
            3 => array:3 [
              "identificador" => "bib0350"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased access to palliative care and hospice services&#58; opportunities to improve value in health care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "D&#46;E&#46; Meier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1468-0009.2011.00632.x"
                      "Revista" => array:6 [
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                        "fecha" => "2011"
                        "volumen" => "89"
                        "paginaInicial" => "343"
                        "paginaFinal" => "380"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21933272"
                            "web" => "Medline"
                          ]
                        ]
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            ]
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              "identificador" => "bib0355"
              "etiqueta" => "5"
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46;M&#46; Detering"
                            1 => "A&#46;D&#46; Hancock"
                            2 => "M&#46;C&#46; Reade"
                            3 => "W&#46; Silvester"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2010"
                        "volumen" => "340"
                        "paginaInicial" => "c1345"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20332506"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "WHO definition of palliative care&#46; Available from&#58; <a href="http://www.who.int/cancer/palliative/definition/en/">http&#58;&#47;&#47;www&#46;who&#46;int&#47;cancer&#47;palliative&#47;definition&#47;en&#47;</a> &#91;accessed 06&#46;03&#46;17&#93;&#46;"
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Estrategia de cuidados paliativos en el sistema nacional de salud&#46; Available from&#58; <a href="http://www.mspsi.es/organizacion/sns/planCalidadSNS/docs/paliativos/cuidadospaliativos.pdf">http&#58;&#47;&#47;www&#46;mspsi&#46;es&#47;organizacion&#47;sns&#47;planCalidadSNS&#47;docs&#47;paliativos&#47;cuidadospaliativos&#46;pdf</a> &#91;accessed 12&#46;03&#46;17&#93;&#46;"
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Cuidados paliativos no oncol&#243;gicos&#58; enfermedad terminal y factores pron&#243;sticos&#46; Available from&#58; <a href="http://www.secpal.com/cuidados-paliativos-no-oncologicos-enfermedad-terminal-y-factores-pronosticos">http&#58;&#47;&#47;www&#46;secpal&#46;com&#47;cuidados-paliativos-no-oncologicos-enfermedad-terminal-y-factores-pronosticos</a> &#91;accessed 12&#46;03&#46;17&#93;&#46;"
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multimorbidity and mortality in older adults&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "B&#46;P&#46; Nunes"
                            1 => "T&#46; Flores"
                            2 => "G&#46;I&#46; Mielke"
                            3 => "E&#46; Thum&#233;"
                            4 => "L&#46;A&#46; Facchini"
                          ]
                        ]
                      ]
                    ]
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Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2017.08.003

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