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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">The high prevalence of multimorbidity and polypathology is a reality in any healthcare system, especially those that treat populations older than 65 years.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The simultaneous occurrence of chronic diseases increases with age. In Spain, the 2006 national health survey showed that individuals between the ages of 65 and 74 years had an average of 2.8 health problems or chronic diseases, reaching an average of 3.23 in elderly patients older than 75 years. These patients constitute a homogeneous population in terms of complexity, clinical vulnerability, frailty, mortality, functional impairment, polypharmacy, poor health-related quality of life and frequent functional dependence, as well as an increased consumption of healthcare resources. Despite its importance, however, the clinical care of these patients is limited by various problems. Firstly, despite being a very common problem, there is no universally accepted definition for terms such as chronicity, comorbidity, multimorbidity and polypathology. For example, polypathology is a term used to refer to frail elderly patients, polymedicated patients, “overusers” (in the case of primary care) and patients who experience multiple hospitalizations (in the case of hospital care). Although it is not a synonym for any of these concepts, it is intimately linked to all of them. As a result, it is not always easy to identify the population we are referencing.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Secondly, in order for the care of these patients to be efficient, the healthcare system needs to be organized to provide multidisciplinary, integrated healthcare assistance based on the best evidence available, according to the needs of the patient and their family. Clinical practice guidelines (CPGs)<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> have been proposed as tools for facilitating the decision-making process of health professionals. At present, however, CPGs are mainly tools for managing a single disease, based mainly on clinical trials that exclude patients with multiple diseases. In general, CPGs do not address the treatment needed to optimize care for these types of patients.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A national strategy was recently published on the treatment of chronic disease.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Its objectives included the design of tools capable of ensuring effective, safe, efficient, sustainable and proportionate healthcare interventions based on the best scientific evidence available. Faced with the need to deepen the knowledge and debate on the challenge of preparing CPGs for the care of patients with multiple diseases, three scientific societies involved in this national strategy created a workgroup that specifically addresses this topic. The objectives of this workgroup included the following:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0020" class="elsevierStylePara elsevierViewall">Agree on proposed terminology for the definition and scope of the new terms used in the care of these patients.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0025" class="elsevierStylePara elsevierViewall">Review how the CPGs address these types of patients and the ways in which their care is organized.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3.</span><p id="par0030" class="elsevierStylePara elsevierViewall">Create a methodology proposal for the incorporation of comorbidity and polypathology by the groups that develop CPGs.</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">In November 2012, the board of directors of the three scientific societies (the Federation of Community Nursing and Primary Care Associations [FAECAP], the Spanish Society of Internal Medicine [SEMI] and the Spanish Society of Family and Community Medicine [semFYC]) assembled a workgroup with two members per society.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The proposal was recorded in the final document available on the SEMI, SEMFYC and FAECAP websites.<a class="elsevierStyleCrossRef" href="#fn0005"><span class="elsevierStyleSup">b</span></a> The study is a narrative review of the methodological development and preparation of CPGs for patients with comorbidity and multiple diseases. A search was performed of methodology documents concerning CPGs and comorbidity in the TRIP Database, using a nonsystematic exploratory methodology. The search was complemented by tracing the references included in the resulting documents and contacting experts in the development of CPGs. The search period ended February 2013. The document was subsequently reviewed by various national and international experts.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Proposed terminology</span><p id="par0045" class="elsevierStylePara elsevierViewall">The concepts and definitions grouped by comorbidity, medication and patients and their environment are listed below.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Multimorbidity: The concomitant presence of two or more chronic diseases in a patient.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Comorbidity: The presence of various satellite diseases that accompany the primary chronic disease.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Patients with multiple diseases: Patients with chronic diseases included within two or more different predefined categories (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), in which it is difficult to establish primacy, given that the diseases are, in general, equally complex and have similar potentials for destabilization, difficulties in management and mutual interrelationships.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Frailty: A syndrome inherently linked to the biological phenomenon of aging, characterized by reduced biological reserves and lower resistance to stress, the result of the deterioration of numerous physiological systems. The syndrome is dominated by an energy and metabolic imbalance, which increases vulnerability to aggressions. There are a number of widely accepted clinical criteria (5) for its diagnosis, of which at least three must be met.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Disability: Difficulty or dependence in performing basic activities of independent life, including the essential functions and necessary tasks of self-care.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Complex chronically ill patient: Patients with concomitant, limiting and progressive diseases with organ failure, in which there is an overuse of health services in all settings, polypharmacy, functional impairment for everyday life activities or a poor social/family situation.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Cluster of chronic diseases: A combination of chronic diseases (clusters) that can be presented as a group in a same patient.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Self-care: A collection of learned and intentional actions that individuals perform by themselves in order to regulate the factors that affect their growth and function, to the benefit of their life, health and wellbeing.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Caregiver: An individual who assumes the responsibility for the daily treatment, support and care of the dependent individual.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Expert patient: Patients able to take responsibility for their own disease and self-care, who know how to identify their symptoms, respond to them and acquire the tools to help them manage the physical, emotional and social impact of the disease, thereby improving their quality of life.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Therapeutic adherence: A term that refers to compliance with both the self-care plan and the prescribed drugs.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Lack of adherence or ineffective management of one's own health is defined as the difficulty in incorporating or maintaining the therapeutic regimen in day-to-day life, in such a way that adherence is partial or inadequate and the results unsatisfactory for achieving the proposed therapeutic objectives.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Noncompliance: A term that refers to patient behavior that does not align with the agreed upon therapy or health promotion plan.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Medication reconciliation: The formal process creating the most complete and accurate list possible of a patient's current medications and comparing the list to those in the patient record or medication orders.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Therapeutic suitability: the process of choosing the patient's therapy in which, by means of the activities of prescription, dispensing, indication, administration and follow-up, we achieve appropriate results for the patient's conditions and circumstances and for those of the community as a whole.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Prognostic aspects of comorbidity and polypathology</span><p id="par0125" class="elsevierStylePara elsevierViewall">If we want to apply a CPG to a patient, it is important to weigh the risks and benefits of the guidelines. Therefore, is significant that the CPGs establish clearly the results expected and the time period in which they develop. This is not always spelled out in current CPGs. It is therefore crucial to first establish a reliable prognosis. However, we currently have no universal implementation tools for patients with multiple diseases. The PROFUND index, developed and validated in 2011, is based on nine easy-to-determine clinical measures and establishes the patient's vital prognosis reliably at 12 months and can be useful for a large portion of these patients.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Second, before implementing the recommendations of a CPG, we must consider the prognostic concept of payoff time. This is the minimum time necessary for the potential benefits of adhering to a recommendation to outweigh the damage.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> It is important to consider this aspect, otherwise we run the risk of proposing interventions that need a period of latency greater than the vital prognosis of a specific patient.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Limitations of clinical practice guidelines</span><p id="par0135" class="elsevierStylePara elsevierViewall">The assessments of the applicability of CPGs to patients with comorbidity and multiple diseases<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14–18</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) have analyzed the following measures: the inclusion of comorbidity/polypathology, creating specific recommendations and quality assessments of the scientific literature on comorbidity, addressing the burden involved in following the recommendations, the patient's preferences and polypharmacy (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). These assessments show us that current CPGs in general are developed for a single health problem. The few studies that address issues of comorbidity do so based on the same pathophysiological basis and do not usually contemplate more than two diseases simultaneously. Additionally, authors of CPGs have found it difficult to find studies that answer questions concerning the care of patients with comorbidity. When these studies are found, they are usually of poor quality.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14–18</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Methodological proposal</span><p id="par0140" class="elsevierStylePara elsevierViewall">To date, there is no clear consensus on the development of CPGs for patients with comorbidity or multiple diseases, although it is an issue on the agenda of several institutions that prepare CPGs. Based on the studies of the American Thoracic Association (ATS) and the European Respiratory Society (ERS)<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>) and taking into account the GRADE framework<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and the proposals from the new version of the AGREE instrument,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> we have created an initial approach with the following considerations:</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">* Scope and objectives of CPGs: The implications regarding comorbidity and polypathology should be specified in terms of the scope and objectives of the CPGs, based on the experience of the group preparing the CPGs, along with an appropriate literature review on clusters of morbidity. The developer group should consider that it might be more appropriate to create various CPGs on specific comorbidities instead of a single CPG. The National Institute for Health and Care Excellence (NICE), for example, has developed numerous CPGs on diabetes (glycemic control, retinopathy, nephropathy, etc.).</p><p id="par0150" class="elsevierStylePara elsevierViewall">* Clinical questions and the importance of outcomes of interest: When proposing various organizational models for providing health care to this population, we can include their effectiveness in the GPC questions.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is essential that we take into account the fact that the identification of the clusters described in the literature does not cover all potential combinations of chronic processes that can present in clinical practice.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> CPGs should therefore be applied judiciously to complex patients. Thus, an overall assessment of both the patient and their family in their social context is essential. Primary care doctors and nurses play a crucial role as primary specialists in the care of complex chronic patients.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">* Define the available interventions and assess the literature: according to the GRADE criteria for selecting and classifying the key end-points for these patients, taking into account the payoff time.</p><p id="par0160" class="elsevierStylePara elsevierViewall">It is especially important to consider the interventions related to patient self-care, caregivers and the patient's environment. In the case of pharmacological interventions, it is essential to consider the negative consequences that the introduction of multiple drugs represents (interactions, adverse effects, lack of adherence).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">* Assessing the quality of the evidence: GRADE defines the quality of the evidence as the confidence that the effect estimators are appropriate for supporting a decision or recommendation.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> This confidence depends of several factors, which include the risk of bias, inconsistency and imprecision in the results, if the evidence is indirect and if there is publication bias. Given the scarce specific information available for populations with multiple diseases, we are often left with indirectly applicable information and indirect evidence.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Our confidence when extrapolating these findings is therefore lower.</p><p id="par0170" class="elsevierStylePara elsevierViewall">* Values and preferences: Authors of CPGs that include aspects of comorbidity should make a special effort to consider values and preferences when developing the recommendations. Let us imagine a 78-year-old patient with type 2 diabetes of more than 10 years of evolution, osteoarthritis, chronic obstructive pulmonary disease and ischemic heart disease and who is a smoker. If we apply the current NICE CPGs, the patient could receive 11 drugs or more and nine tips on self-care and require more than 40 contacts with the system annually.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Having to take multiple treatments and follow numerous self-care recommendations considerably increases the inconvenience, with the subsequent risk of noncompliance.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> It is therefore crucial to address all possibilities and implications with the patients and their caregivers.</p><p id="par0175" class="elsevierStylePara elsevierViewall">* Balancing risk-benefit/burden of disease to obtain benefits or net damage: There are other factors that must be added to the risk-benefit balance of interventions, a balance that is usually performed by comparing pro and con variables. These factors include the financial cost (for the patient, their community and the healthcare system), as well as the burden of disease to be assumed by patients and their families.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">* Formulating recommendations: The recommendations should be as structured as possible, describing the population of interest, the interventions and comparators and should include specific recommendations for the identified subpopulations of interest. The GRADE system proposes the assessment of four main factors to grade the strength of the recommendations (quality of evidence, benefit-risk balance, values and preferences and costs).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> These factors, in each case, influence the recommendations by increasing or decreasing the chances that they are strong or weak. For example, if their quality is low it is more likely that the recommendation will be weak and vice versa. Moreover, if the costs for either the patient or the healthcare system are high then it is more likely that the recommendation will be weak (and vice versa).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Finally, once the guidelines have been written, it is essential that their quality be assessed with validated instruments.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21,25,26</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">* Publication, dissemination and implementation: The factors that play relevant roles in the implementation of a CPG include the quality of the CPG, the expertise, approach and routine of health professionals, the approach and behavior of patients and the organizational and financial limitations.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> However, implementing improvements in patient care is a complex process that requires the combination of various strategies at various levels of the healthcare system and integrating them properly within the existing structures. From this point of view, it is not enough for the CPGs to be excellent. They need to be available at the patients’ point of care and should be easily applicable. New technologies constitute an essential element in this respect.</p><p id="par0190" class="elsevierStylePara elsevierViewall">The implementation and monitoring of CPGs should be realistic and in keeping with the intrinsic characteristics of the subpopulations of interest. For example, the application of indicators from general CPGs to populations with high comorbidity can lead to situations of excessive medicalization and burden, which can be damaging for the patient and their environment (e.g., caregivers).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> As an example, the general objective of metabolic control of glycosylated hemoglobin at 7% is probably not applicable to elderly patients with multiple diseases and a low level of psychosocial support. Furthermore, these more specific and realistic indicators should be sufficiently flexible to account for each patient's unique circumstances. The health authorities should be especially careful when selecting indicators in these circumstances.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusion</span><p id="par0195" class="elsevierStylePara elsevierViewall">The present study constitutes an initial Spanish approach to the methodology challenge of incorporating polypathology and comorbidity into CPGs. The objective is to make CPGs truly useful tools for the decision-making process with this population group, both for practitioners and patients. We need to proceed with a proposed methodology with the participation of more stakeholders (health officials, experts in methodology, caregivers and patients, other scientific societies, etc.). In the context of our national health system, Guiasalud (as the responsible agency for the methodological development of CPGs) is the most appropriate agency for coordinating this process.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">Máximo Bernabeu-Wittel is a member of the Elderly and Polypathological Patient Group of the Spanish Society of Internal Medicine and acts as principal investigator and collaborator in various research projects on polypathology with public funding. Pablo Alonso is a member of the GRADE group. Rafael Rotaeche is a member of the research group Kronikgune on knowledge management and participates in 2 chronicity strategy projects of the Basque Country. Milagros Rico is a member of the Health Services Research Network for Chronic Diseases (REDISECC) and a principal investigator on two publically funded projects on the care of caregivers of chronically ill individuals. The Spanish Society of Internal Medicine, Osatzen (Basque Society of Family and Community Medicine) and the Cochrane Collaboration have received funding from Astra Zeneca for the development of this document. Emilio Casariego has received honoraria from other pharmaceutical companies.</p></span></span>"
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"resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The management of patients with comorbidity and polypathology represents a challenge for all healthcare systems. Clinical practice guidelines (CPGs) have limitations when applied to this population. The aim of this study is to propose the terminology and methodology for optimally approach comorbidity and polypathology in the CPGs. Based on a literature review, we suggest a number of proposals for the approach in different phases of CPG preparation, with special attention to the inclusion of clusters of comorbidity in the initial questions the implementation of indirect evidence, the burden of disease management for patients and their environment, when establishing recommendations, as well as the strategies of dissemination and implementation. These proposals should be developed in greater depth with the implication of more agents in order to have valid and useful tools for this population.</p>"
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"resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La atención a pacientes con comorbilidad y pluripatología supone un reto para cualquier sistema sanitario. Las guías de práctica clínica (GPC) presentan limitaciones cuando se aplican a esta población. El objetivo de este trabajo es realizar una propuesta terminológica y metodológica sobre el abordaje de la comorbilidad y la pluripatología en las GPC. De acuerdo a la revisión bibliográfica efectuada, se sugieren algunas propuestas para su abordaje en las diferentes fases de elaboración de las GPC, con especial atención a la inclusión de los <span class="elsevierStyleItalic">clusters</span> de comorbilidad en las preguntas clínicas iniciales, la incorporación de la evidencia indirecta, el peso de la carga de gestionar la enfermedad para el paciente y su entorno en la formulación de recomendaciones, así como las estrategias de difusión e implementación. Estas propuestas deben desarrollarse en mayor profundidad con la participación de más agentes para disponer de herramientas válidas y útiles en esta población.</p>"
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"nota" => "<p class="elsevierStyleNotepara" id="npar0030">Please cite this article as: Bernabeu-Wittel M, Alonso-Coello P, Rico-Blázquez M, Rotaeche del Campo R, Sánchez Gómez S, Casariego Vales E. Desarrollo de guías de práctica clínica en pacientes con comorbilidad y pluripatología. Rev Clin Esp. 2014;214:328–335.</p>"
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"nota" => "<p class="elsevierStyleNotepara" id="npar0040"><a class="elsevierStyleInterRef" id="intr0015" href="http://www.fesemi.org/documentos/1368025410/publicaciones/guias/desarrollo-guias-practica-clinica-pacientes-comorbilidad-pluripatologia.pdf">http://www.fesemi.org/documentos/1368025410/publicaciones/guias/desarrollo-guias-practica-clinica-pacientes-comorbilidad-pluripatologia.pdf</a>, <a class="elsevierStyleInterRef" id="intr0020" href="http://www.semfyc.es/pfw_files/cma/Informacion/modulo/documentos/desarrolloGPC.pdf">http://www.semfyc.es/pfw_files/cma/Informacion/modulo/documentos/desarrolloGPC.pdf</a>, <a class="elsevierStyleInterRef" id="intr0025" href="http://www.faecap.com/documents/download/165">http://www.faecap.com/documents/download/165</a>.</p>"
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"nota" => "<p class="elsevierStyleNotepara" id="npar0035">By agreement with the authors and editors, this article will be published simultaneously and in full in the journal Atención Primaria. <a class="elsevierStyleInterRef" id="intr0010" href="http://dx.doi.org/10.1016/j.rce.2014.04.001">http://dx.doi.org/10.1016/j.rce.2014.04.001</a></p>"
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\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>A.1. Heart failure that in a clinically stable state has been in grade 2 of the NYHA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> (symptoms with regular physical activity)<span class="elsevierStyleHsp" style=""></span>A.2. Ischemic heart disease \t\t\t\t\t\t\n
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\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>B.1. Vasculitis and systemic autoimmune diseases<span class="elsevierStyleHsp" style=""></span>B.2. Chronic kidney disease defined as increased creatinine levels (>1.4<span class="elsevierStyleHsp" style=""></span>mg/dL in men, >1.3<span class="elsevierStyleHsp" style=""></span>mg/dL in women) or proteinuria,<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> maintained for three months \t\t\t\t\t\t\n
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\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C.1. Chronic respiratory disease that in a clinically stable state has occurred with:MRC<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> grade 2 dyspnea (dyspnea at a normal pace on a level surface), FEV1 <65% or SaO2 ≤90% \t\t\t\t\t\t\n
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\t\t\t\t\ttop\n
\t\t\t\t">Category D \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>D.1. Chronic inflammatory bowel disease<span class="elsevierStyleHsp" style=""></span>D.2. Chronic liver disease with hepatocellular insufficiency<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> or portal hypertension<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a> data \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Category E</span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>E.1. Stroke<span class="elsevierStyleHsp" style=""></span>E.2. Neurological disease with permanent motor deficit that restricts basic activities of daily life (Barthel index <60)<span class="elsevierStyleHsp" style=""></span>E.3. Neurological disease with permanent cognitive impairment, at least moderate (Pfeiffer with five or more errors) \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Category F</span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>F.1. Symptomatic peripheral arteriopathy<span class="elsevierStyleHsp" style=""></span>F.2. Diabetes mellitus with proliferative retinopathy or symptomatic neuropathy \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Category G</span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>G.1. Chronic anemia due to gastrointestinal losses or acquired blood disorder not responsive to curative treatment, which presents hemoglobin levels <10<span class="elsevierStyleHsp" style=""></span>mg/dL in two measurements separated by more than three months<span class="elsevierStyleHsp" style=""></span>G.2. Solid or hematologically neoplasm not responsive to treatment with intent to heal \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Category H</span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>H.1. Chronic osteoarticular disease that by itself restricts basic activities of daily life (Barthel index <60) \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
"""
]
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"notaPie" => array:5 [
0 => array:3 [
"identificador" => "tblfn0005"
"etiqueta" => "a"
"nota" => "<p class="elsevierStyleNotepara" id="npar0005">Slight restriction of physical activity. Normal physical activity causes dyspnea, angina, fatigue or palpitations.</p>"
]
1 => array:3 [
"identificador" => "tblfn0010"
"etiqueta" => "b"
"nota" => "<p class="elsevierStyleNotepara" id="npar0010">Albumin/creatinine index >300<span class="elsevierStyleHsp" style=""></span>mg/g, microalbuminuria >3<span class="elsevierStyleHsp" style=""></span>mg/dL in urine sample or albumin >300<span class="elsevierStyleHsp" style=""></span>mg/day in 24-h urine or >200<span class="elsevierStyleHsp" style=""></span>μg/min.</p>"
]
2 => array:3 [
"identificador" => "tblfn0015"
"etiqueta" => "c"
"nota" => "<p class="elsevierStyleNotepara" id="npar0015">Unable to maintain the pace of another individual of the same age (walking on a level surface) due to respiratory difficulty or having to stop and rest when walking on a level surface at their own pace.</p>"
]
3 => array:3 [
"identificador" => "tblfn0020"
"etiqueta" => "d"
"nota" => "<p class="elsevierStyleNotepara" id="npar0020">INR >1.7, albumin <3.5<span class="elsevierStyleHsp" style=""></span>g/dL, bilirubin >2<span class="elsevierStyleHsp" style=""></span>mg/dL.</p>"
]
4 => array:3 [
"identificador" => "tblfn0025"
"etiqueta" => "e"
"nota" => "<p class="elsevierStyleNotepara" id="npar0025">Defined as the presence of clinical, laboratory, ultrasound or endoscopic data.</p>"
]
]
]
"descripcion" => array:1 [
"en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Functional definition of patients with multiple diseases, those who present chronic diseases defined in two or more of the following clinical categories.</p>"
]
]
1 => array:7 [
"identificador" => "tbl0010"
"etiqueta" => "Table 2"
"tipo" => "MULTIMEDIATABLA"
"mostrarFloat" => true
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"tabla" => array:1 [
"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"><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black">Author and year \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black">No. CPGs \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black">Topics \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black">Measures of assessment \t\t\t\t\t\t\n
\t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Boyd<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> (2005, USA) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">9 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Arterial hypertension, heart failure, stable angina, atrial fibrillation, hypercholesterolemia, diabetes, osteoarthritis, COPD and osteoporosis \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Inclusion of comorbidity in the questions- Quality of the evidence- Specific recommendations- Treatment burden- Patient preference \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Fortin<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> (2011, Canada) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">16 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Dyslipidemia, renal failure, heart failure, anticoagulation, obesity, atrial fibrillation, peripheral arteriopathy, COPD, osteoporosis, rheumatoid arthritis, diabetes, asthma, dementia, glaucoma, anxiety, hypertension \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Inclusion of comorbidity in the questions- Quality of the evidence – specific recommendations- Treatment burden- Patient preference- Polypharmacy \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Hughes<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> (2013, NICE) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">5 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Diabetes, secondary cardiovascular prevention, osteoarthritis, COPD, depression \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Inclusion of comorbidity in the questions- Specific recommendations- Patient preference- Compliance \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Lugtenberg<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> (2011, International) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">20 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">COPD, depression, type 2 diabetes, osteoarthritis \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Inclusion of comorbidity in the questions- Quality of the evidence- Specific recommendations \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Vitry<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> (2008, Australia) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">17 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">Asthma, breast cancer, prostate cancer, acute coronary syndrome, COPD, secondary cardiovascular prevention, arterial hypertension, type 2 diabetes, osteoporosis, psychosocial care for patients with cancer, dementia, depression, schizophrenia, stroke rehabilitation, heart failure \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Inclusion of comorbidity in the questions- Quality of the evidence- Specific recommendations- Treatment burden- Patient preference \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
"""
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0 => "xTab529103.png"
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"descripcion" => array:1 [
"en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Assessments of CPGs and comorbidity.</p>"
]
]
2 => array:8 [
"identificador" => "tbl0015"
"etiqueta" => "Table 3"
"tipo" => "MULTIMEDIATABLA"
"mostrarFloat" => true
"mostrarDisplay" => false
"fuente" => "<span class="elsevierStyleItalic">Source:</span> Adapted and extended by Boyd et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>"
"tabla" => array:1 [
"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"><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black">Criteria \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t" style="border-bottom: 2px solid black">Met (<span class="elsevierStyleItalic">N</span>) \t\t\t\t\t\t\n
\t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Topics developed</span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Includes the elderly \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">8 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patients with comorbidity \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">9 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Elderly with comorbidity \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">3 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Quality of the evidence</span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Includes the elderly \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">9 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patients with comorbidity \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">12 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Elderly with comorbidity \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">3 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Recommendations</span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Specific for patients with 1 comorbidity \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">15 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Specific for patients with 2 comorbidities \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">3 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Specific for patients with more than 2 comorbidities \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">1 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Treatment burden</span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Benefits of treatment over time according to life expectancy \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">9 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Discussion on the workload for patient and caregivers \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">6 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Discussion on the financial cost for patients \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">4 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Discussion on quality of life \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">13 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patient preference \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">9 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " colspan="2" align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleItalic">Use of medication</span></td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Description of adverse effects \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">16 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adaptation to adverse effects \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">12 \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Interactions \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">10 \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
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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"><td class="td" title="\n
\t\t\t\t\ttable-head\n
\t\t\t\t " align="left" valign="\n
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\t\t\t\t" style="border-bottom: 2px solid black">Steps \t\t\t\t\t\t\n
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\t\t\t\t" style="border-bottom: 2px solid black">How to \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
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\t\t\t\t " align="left" valign="\n
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\t\t\t\t" style="border-bottom: 2px solid black">For COPD \t\t\t\t\t\t\n
\t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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\t\t\t\t " align="left" valign="\n
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\t\t\t\t">1. Define all the problems of a specific patient. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
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\t\t\t\t">- Ask the patients.- Review the literature. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
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\t\t\t\t">- Define the main problem for the patients (dyspnea, edema, depression). \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
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\t\t\t\t">2. List the outcomes of interest for patients with multiple diseases in the order of importance (reduced number of hospitalizations, improvement in the dyspnea) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Use tools to make the values and preferences explicit (visual analog scale). \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Use techniques to prioritize among dyspnea, hospitalizations, etc. \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">3. Define the possible interventions. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Review the literature (prioritize systematic reviews) supported by experts as to what is applicable. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">-Long-acting beta2-agonists, diuretics, beta blockers, and antidepressants (to what extent is the patient willing to take some medications alone). \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">4. Assess whether the benefits and risks differ among the various populations (especially in populations with comorbidity). \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Evaluate subgroups/heterogeneity.- Do the clinical trials include subgroups and do they make sense?- Do they have a different pathophysiology?- Applicability of the evidence. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Long-acting beta2-agonists can worsen dyspnea in patients with COPD and heart failure.The treatment of dyspnea reduces depression. \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">5. Assess the greatest net benefit possible (in terms of damage, disadvantages, values and preferences) in the various populations and present summaries of the evidence to the panel that makes the recommendations. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Systematically judge the benefits against the potential drawbacks after considering all interventions.- Provide explanations to the patients. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
\t\t\t\t\ttable-entry\n
\t\t\t\t " align="left" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">- Beta blockers with greater net benefit in the population of interest- Antidepressant treatment is the second option with greatest net benefit- Long-acting beta2-agonists and diuretics have a lower net benefit when compared to beta blockers. Patients can prioritize taking only beta blockers and antidepressants. \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
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