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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival curves &#40;Kaplan&#8211;Meier&#41; in the study population A&#41;&#59; by departments &#40;internal medicine vs&#46; pneumology&#41; B&#41; and according to the compliance with the GOLD C&#41; and GesEPOC D&#41; guidelines criteria in the use of corticosteroids&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; GesEPOC&#44; Spanish COPD Guidelines&#59; GOLD&#44; Global Initiative for Chronic Obstructive Lung Disease guidelines&#59; ICU&#44; intensive care unit&#59; IM&#44; internal medicine&#59; PNEU&#44; pneumology&#46;</p>"
        ]
      ]
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic obstructive pulmonary disease &#40;COPD&#41; is the most common respiratory disease&#44; with a worldwide prevalence of 251 million cases<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and an estimated annual mortality of 5&#37;&#44; according to data from the World Health Organization&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Exacerbations represent a key point in the progression of the disease and are characterized by sustained worsening of the disease beyond the normal daily variations&#44; with an acute onset&#44; resulting in changes in the patient&#8217;s medication or hospitalization&#46; Up to 35&#37; of patients with COPD have at least 1 hospitalization per year&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and up to 30&#37; are re-admitted within 6 months after the discharge&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> These exacerbations have a considerable impact on patients&#8217; state of health and physical capacity and have a cumulative effect on the loss of pulmonary function&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Exacerbation episodes are also independent predictors of disease progression and mortality&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> which increases both in the long term and short term&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The most widely used clinical practice guidelines &#40;CPGs&#41; in our setting for treating COPD exacerbations are those proposed by GOLD<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and the Spanish COPD guidelines &#40;GesEPOC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Among their recommendations&#44; both guidelines include the use of &#946;2-agonists and anticholinergic bronchodilators&#44; systemic corticosteroids&#44; early rehabilitation measures and&#44; in certain circumstances&#44; antibiotherapy&#44; oxygen therapy and noninvasive ventilatory support&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Despite the well-established regimens for managing COPD&#44; the treatment of exacerbations in hospitalized patients is still suboptimal&#44; and little progress has been made in terms of reducing readmissions and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;14</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although there are data in our setting on these patients&#8217; clinical profile and audits on compliance with the CPGs &#40;Escarrabill et al&#46;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> awareness of the effects on patient outcomes of treating the exacerbations is still quite limited&#46; The present study was therefore proposed&#44; with the objectives of determining the clinical characteristics of patients hospitalized for COPD exacerbations in our setting&#44; assessing overall compliance and departmental compliance &#40;internal medicine and pneumology&#41; with the CPG recommendations on clinical management and determining the prognostic impact of COPD exacerbations&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0020" class="elsevierStylePara elsevierViewall">We conducted an observational&#44; longitudinal retrospective study that employed simple randomized sampling to include patients hospitalized for COPD exacerbations in a tertiary hospital&#44; up to the precalculated sample size of 108 &#40;parameter value of 0&#46;5&#44; 95&#37; confidence level&#44; 8&#37; precision and 10&#37; loss rate&#41;&#46; The inclusion criteria were hospitalization in the University Hospital Virgen del Roc&#237;o &#40;Seville&#44; Spain&#41; between January 2015 and December 2015&#44; a primary diagnosis of &#8220;COPD exacerbation&#8221; &#40;ICD-9-CM 491&#46;84 and 518&#46;84&#41; in the hospital discharge report and identification in the local minimum basic data set&#46; The exclusion criterion was a lack of spirometric confirmation prior to the COPD diagnosis in the medical history&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Data collection</span><p id="par0025" class="elsevierStylePara elsevierViewall">From the data available in the minimum basic data set and the digital medical histories&#44; we collected the variables included in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; which basically include demographic data&#44; discharging department&#44; comorbidity according to the age-adjusted Charlson index &#40;Appendix 1a&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> degree of obstruction measured by spirometry within 6 months prior to the index episode &#40;percentage forced expiratory volume in 1&#8239;s&#44; FEV<span class="elsevierStyleInf">1</span>&#37;&#41; &#40;Appendix 1b&#41;&#44; degree of baseline dyspnea &#40;measured with the modified Medical Research Council scale&#41; &#40;Appendix 1c&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> exacerbations in the year prior to the episode&#44; clinical signs &#40;systolic and diastolic blood pressure&#44; heart rate&#44; inspiratory chest wall retraction&#41;&#44; biological variables &#40;oxygen saturation&#44; pH&#44; partial pressure of carbon dioxide&#44; partial pressure of oxygen&#44; eosinophils&#44; leukocytes&#44; lymphocytes&#44; neutrophils&#44; C-reactive protein&#41; and the onset of <span class="elsevierStyleItalic">de novo</span> steroid diabetes or hyperglycemic decompensation&#46; We also collected data on compliance with the GOLD 2014<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and GesEPOC 2012<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> clinical guidelines &#40;those guidelines that were current at the time of the study&#41;&#44; in terms of the clinical assessment and treatment&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">As outcome variables&#44; we included all-cause mortality and readmissions for exacerbations at 3 months and at 1&#8239;year of the hospital discharge&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Throughout the process&#44; we ensured data confidentiality according to current legislation&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The relationship between the qualitative variables was analyzed with the chi-squared test and Fisher&#8217;s exact test&#46; For the quantitative variables&#44; we employed Student&#8217;s t-test after determining the normality of the distribution of values&#46; For non-normality&#44; we employed a nonparametric test &#40;Mann&#8211;Whitney U test&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Using Kaplan&#8211;Meier curves &#40;Mantel&#8211;Cox test&#41;&#44; we compared the mortality and readmissions according to the admitting department and according to the compliance or not with the various treatment recommendations&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Finally&#44; we performed a multivariate analysis using multiple logistic regression&#44; which included the variables with statistical association in the bivariate analysis and other prognostic variables reported in the literature&#44; such as age&#44; the Charlson comorbidity index and the discharging department&#46; Data was available in our study for more than 80&#37; of the cases&#46; We calculated the adjusted odd ratios &#40;OR&#41; with their 95&#37; confidence interval&#46; To assess the yield of each model&#44; we performed a sensitivity analysis with receiver operating characteristics curves&#44; which produced an area under the curve and its 95&#37; confidence interval&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">We performed the analysis with the IBM SPSS Statistics 21 statistical package &#40;IBM Corporation&#44; Armonk&#44; NY&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical aspects</span><p id="par0060" class="elsevierStylePara elsevierViewall">The study was conducted in accordance with the Declaration of Helsinki<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and the pertinent requirements of Spanish law&#46; The study was granted a favorable opinion by the Research Ethics Committee of University Hospital Virgen Macarena and University Hospital Virgen del Roc&#237;o of Seville&#44; Spain&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">We included a total of 108 patients&#44; 81&#46;5&#37; of whom were men&#46; Some 61&#46;1&#37; of the patients were hospitalized in the internal medicine department&#44; and 38&#46;9&#37; were hospitalized in the pneumology department&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents the rest of the study patients&#8217; clinical-demographic characteristics&#46; In terms of the baseline biological characteristics and complementary tests&#44; the internal medicine patients presented higher oxygen saturation and baseline blood glucose levels and lower pH levels&#46; There was a broad use of chest radiography as a complementary test in both departments &#40;95&#46;3&#37;&#41;&#44; and there were no differences between the departments in the other variables&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the patients&#8217; clinical progression according to the admitting department&#46; There were no statistically significant differences in terms of readmissions according to admitting department&#46; The patients hospitalized in the internal medicine department had higher mortality during hospitalization &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;043&#41;&#44; at 3 months &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;028&#41; and at 1 year &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;007&#41;&#46; The survival analysis showed that the mean survival was 827&#46;4 days &#40;95&#37; CI 727&#46;6&#8211;927&#46;3&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; The survival curves according to discharging department showed lower survival for the patients hospitalized in internal medicine &#40;725&#46;1 vs&#46; 984&#46;1 days&#59; log-rank test&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;023&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In terms of the clinical assessment &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; the overall compliance with the CPGs was 63&#37; and was lower for the patients in internal medicine than for those hospitalized in pneumology &#40;56&#46;1&#37; vs&#46; 73&#46;8&#37;&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;063&#41;&#46; Moreover&#44; the patients hospitalized in internal medicine presented less compliance in the assessment of the degree of obstruction according to GOLD &#40;62&#46;1&#37; vs&#46; 85&#46;7&#37;&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;008&#41;&#44; with no significant differences between the two departments in the remaining criteria of compliance&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">In terms of drug treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; we observed overall compliance of 26&#46;9&#37; with the CPG recommendations for the GOLD criteria and 28&#46;7&#37; for GesEPOC&#44; and there were no differences in compliance by department&#46; The mean dosage of systemic corticosteroids employed for the study population was 80&#46;4&#8239;&#177;&#8239;55&#46;9&#8239;mg of prednisone&#47;day&#44; and the mean treatment duration was 5&#46;3&#8239;&#177;&#8239;5&#46;7 days&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">To assess the impact of compliance with the various CPG recommendations on the clinical progression&#44; we first performed a bivariate analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#44; which&#44; for readmissions&#44; showed an association between GOLD guideline compliance for systemic steroid treatment &#40;ADECUA-TX-3&#41; and cumulative readmissions at 1&#8239;year &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;041&#41;&#46; The analysis also showed an association between GesEPOC guideline compliance &#40;ADECUA-TX-6&#41; and readmissions between 3 and 12 months &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;0017&#41;&#46; In terms of mortality&#44; the variable &#8220;GOLD guideline compliance in the use of corticotherapy&#8221; showed an association with hospital mortality &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;004&#41; and short-term mortality &#40;&#60;3 months&#41; &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;036&#41;&#46; In the survival analysis&#44; there was also longer patient survival with the appropriate use of corticosteroids according to the GOLD criteria &#40;Mantel&#8211;Cox&#44; 0&#46;009&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#44; which did not appear when applying the GesEPOC criteria &#40;Mantel&#8211;Cox&#44; 0&#46;529&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Finally&#44; in the multivariate analysis&#44; we developed 5 predictive models for the study variables for clinical progression &#40;readmissions at 3 months and at 1&#8239;year and inhospital mortality and mortality at 3 months and at 1&#8239;year&#41;&#46; As prognostic variables&#44; we included age&#44; Charlson index&#44; discharging department and GOLD guideline compliance for steroidal treatment&#44; which was the only compliance variable with a consistent association in the bivariate analysis&#46; The results of this analysis showed that GOLD guideline compliance for steroidal treatment for the study patients was significantly associated with lower hospital mortality &#40;OR&#44; 0&#46;13&#59; 95&#37; CI 0&#46;03&#8211;0&#46;57&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;007&#41; and mortality at 3 months &#40;OR&#44; 0&#46;26&#59; 95&#37; CI 0&#46;07&#8211;1&#46;01&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;05&#41;&#46; We also observed an association between hospitalization in the pneumology department and lower mortality at 1 year &#40;OR&#44; 0&#46;25&#59; 95&#37; CI 0&#46;08&#8211;0&#46;77&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;015&#41;&#46; The predictive models showed an area under the curve of between 0&#46;64 &#40;95&#37; CI 0&#46;53&#8211;0&#46;77&#41; and 0&#46;73 &#40;95&#37; CI 0&#46;58&#8211;0&#46;89&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">To our knowledge&#44; this is the first study conducted in Spain to determine the clinical impact of treatment for severe COPD exacerbations on patient outcomes&#46; The study also provides information on the clinical profile and compliance with the clinical guideline recommendations in the departments where these patients are typically hospitalized &#40;internal medicine and pneumology&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A previous comparative study in Spain analyzed the comorbidities associated with COPD of patients according to whether they were admitted to internal medicine or pneumology&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The authors observed that the 2 populations had differing characteristics and were difficult to compare&#44; as happened in our study&#44; where the comorbidity assessed by the Charlson index was significantly higher among the patients with COPD hospitalized in internal medicine&#44; contributing to greater mortality&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Our study has a number of limitations&#44; the main being the study sample size&#44; which could impair the power of the analysis&#46; However&#44; as with other studies with sample sizes similar to or smaller than ours&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> the sample was sufficient to enable us to define the clinical spectrum and compliance and assess&#44; at least partly&#44; the prognostic impact of compliance with the CPG recommendations&#46; This study involved a single center&#44; which could limit the external validity of the evaluated data&#46; Furthermore&#44; the study&#8217;s retrospective nature&#44; which hindered the recording of certain data&#44; could represent another possible limitation in the scope of our conclusions&#46; In the study design&#44; however&#44; we adjusted the CPG compliance variables to the parameters available in standard clinical practice&#46; We minimized the selection bias through randomization of the sample&#44; thereby avoiding biases such as those of a seasonal nature&#46; Finally&#44; the consistency of the results with the various methodological approaches &#40;bivariate analysis&#44; survival analysis and multiple logistic regression&#41; provided greater strength to the conclusions&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In terms of the results&#44; we should highlight a few findings&#46; Firstly&#44; the study showed that despite improvements in the therapeutic management<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> and follow-up of this disease and in the development of new predictive scales that include the evaluation of comorbidity for better patient stratification&#44;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> mortality after a COPD exacerbation remains very high&#46; This finding is due&#44; at least in part&#44; to the advanced age of the hospitalized patients&#44; the severity of the respiratory disease and the comorbidity burden &#40;measured by the Charlson index&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The study patients&#8217; demographic characteristics are similar to those described in other studies&#44; although most of those studies included patients with much less comorbidity&#44; probably due to the selective inclusion of patients hospitalized in pneumology&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;23</span></a> In our study&#44; only 12&#37; of the patients were women&#44; a figure much lower than that observed in most of the studies&#46; In addition&#44; there were significant differences in the clinical progression between our study and other studies&#46; For example&#44; the rates of readmission and mortality at 3 months were 26&#46;4&#37; and 21&#46;9&#37;&#44; respectively&#44; for our study&#44; while those of the study by L&#243;pez Campos et al&#46; were 35&#46;1&#37; and 10&#46;8&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">In our study&#44; compliance with the recommendations on the clinical assessment was high&#44; with rates ranging from 71&#37; to 100&#37; for the individual recommendations and 63&#37; for overall compliance&#44; findings similar to those observed in other studies&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In terms of the treatment recommendations&#44; the use of short-acting &#946;-2 agonists &#40;with or without short-acting anticholinergic agents&#41; &#40;41&#46;3&#37;&#41; was lower than that reported in a number of studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> This finding reveals high variability in terms of compliance according to the population characteristics&#44; resources of the various respiratory units<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and other factors not yet reported in the literature&#44; such as cardiovascular comorbidity and the high prevalence of atrial fibrillation observed in our study &#40;28&#46;8&#37;&#41;&#44; a limiting factor in the use of short-acting &#946;-2 agonists&#46; Secondly&#44; in terms of compliance with the dosages and treatment duration with systemic steroids&#44; the figures observed in our study &#40;4&#46;6&#37;&#41; were similar to those reported by other authors &#40;5&#37; in the study by Lipari et al&#46;&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> but very different from those reported by others &#40;80&#37; in the study by Harvey et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#41;&#44; which also reflects the significant variability in the compliance with guideline recommendations&#46; Lastly&#44; in terms of compliance with the use of noninvasive mechanical ventilation&#44; we found similar rates to those in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In terms of mortality&#44; we found that greater compliance with the GOLD guideline recommendations on steroidal treatment was associated in our setting with lower hospital mortality and early mortality &#40;at 3 months&#41;&#46; The survival analysis showed greater patient survival with the appropriate use of corticosteroids according to GOLD guideline recommendations&#46; The multivariate analysis revealed an association between GOLD guideline compliance in the appropriate use of corticosteroids and lower hospital mortality and at 3 months&#46; A recent study showed that the use of corticosteroids at high dosages in patients hospitalized for COPD exacerbations was associated with longer hospital stays&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> although this relationship was not observed in another similar study also performed in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Our study found a high rate of hydrocarbon metabolism disorders &#40;39&#46;3&#37;&#41;&#44; including <span class="elsevierStyleItalic">de novo</span> steroid-induced diabetes mellitus &#40;25&#46;5&#37;&#41; and hyperglycemic decompensation &#40;21&#46;5&#37;&#41;&#46; These findings demonstrate the need for optimizing the steroid dosages employed for COPD exacerbations in our patients to minimize the risk of metabolic complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#44;33</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In conclusion&#44; the present study showed that patients hospitalized for COPD in our setting continue to have a poor short-term and medium-term prognosis&#46; The study identified differences in the clinical profile of patients admitted to the internal medicine and pneumology departments&#44; which determine the patients&#8217; prognosis and outcome and that do not seem to be related to a different clinical management&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The study also showed low compliance in our setting with the clinical guideline recommendations and identified areas for improvement&#46; We also confirmed that the appropriate use of systemic steroids is associated with reduced early mortality and medium-term readmissions&#46; However&#44; compliance with the guidelines&#8217; other therapeutic recommendations was not associated in our study with clinical progression&#44; probably as a consequence of the limitations in the power of the analysis&#46; Further studies are therefore needed to determine the true impact on actual clinical practice&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            0 => "Chronic obstructive pulmonary disease"
            1 => "Exacerbation"
            2 => "Compliance"
            3 => "Readmission"
            4 => "Mortality"
            5 => "Comorbidity"
          ]
        ]
      ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1278086"
          "palabras" => array:6 [
            0 => "Enfermedad pulmonar obstructiva cr&#243;nica"
            1 => "Exacerbaci&#243;n"
            2 => "Adecuaci&#243;n"
            3 => "Reingreso"
            4 => "Mortalidad"
            5 => "Comorbilidad"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease &#40;COPD&#41; exacerbation&#44; to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients&#8217; prognosis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methodology</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital&#46; We collected demographic and clinical variables &#40;degree of dyspnoea and obstruction&#44; previous exacerbations&#44; comorbidities&#41;&#44; readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease &#40;GOLD&#41; guidelines and the Spanish COPD guidelines &#40;GesEPOC&#41;&#46; We performed a univariate&#44; multivariate and survival analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">The study included 108 patients&#44; and the mean age was 71&#46;48&#8239;&#177;&#8239;11&#46;65 years&#46; The readmission rate was 26&#46;4&#37; at 3 months and 43&#46;4&#37; at 1 year&#46; The hospital mortality rate was 3&#46;9&#37;&#44; the mortality rate at 3 months was 21&#46;9&#37;&#44; and the mortality rate at 1 year was 27&#46;4&#37;&#46; The patients hospitalised in the internal medicine department had higher mortality during hospitalisation &#40;p&#8239;&#61;&#8239;&#46;043&#41;&#44; at 3 months &#40;p&#8239;&#61;&#8239;&#46;028&#41; and at 1 year &#40;p&#8239;&#61;&#8239;&#46;007&#41; compared with the rates for the pneumology department&#46; Overall compliance with the clinical guidelines was 63&#37; for the clinical evaluation &#40;less for the patients in internal medicine&#58; 56&#46;1&#37; vs&#46; 73&#46;8&#37;&#44; p&#8239;&#61;&#8239;&#46;063&#41;&#46; For the treatment&#44; the compliance was 26&#46;9&#37; for GOLD and 28&#46;7&#37; for GesEPOC&#46; Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions &#40;p&#8239;&#61;&#8239;&#46;041&#41; and hospital mortality &#40;p&#8239;&#61;&#8239;&#46;007&#41; and 3-month mortality &#40;p&#8239;&#61;&#8239;&#46;05&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">The clinical profile of the patients is currently similar to that previously reported&#44; but their clinical progression was poorer&#46; Overall compliance with the clinical guidelines for drug treatment was low&#44; and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methodology"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Definir las caracter&#237;sticas cl&#237;nicas de los pacientes hospitalizados en servicios de medicina interna &#40;MI&#41; y neumolog&#237;a por exacerbaciones de la EPOC&#44; evaluar la adecuaci&#243;n a las recomendaciones de las gu&#237;as de pr&#225;ctica cl&#237;nica y conocer su impacto en el pron&#243;stico de los pacientes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodolog&#237;a</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Estudio longitudinal retrospectivo&#46; Se incluyeron aleatoriamente pacientes ingresados por exacerbaci&#243;n de EPOC en un hospital de tercer nivel&#46; Se registraron variables demogr&#225;ficas&#44; cl&#237;nicas &#40;grado de disnea y de obstrucci&#243;n&#44; exacerbaciones previas&#44; comorbilidades&#41;&#44; criterios de adecuaci&#243;n a las gu&#237;as cl&#237;nicas GOLD y GesEPOC y datos de reingresos y mortalidad&#46; Se realiz&#243; un an&#225;lisis univariante&#44; multivariante y de supervivencia&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 108 pacientes y la edad media fue de 71&#44;48&#177;11&#44;65 a&#241;os&#46; Los reingresos a los 3 meses fueron un 26&#44;4&#37; y al a&#241;o un 43&#44;4&#37;&#46; La mortalidad intrahospitalaria fue del 3&#44;9&#37;&#44; a los 3 meses del 21&#44;9&#37;&#44; y al a&#241;o del 27&#44;4&#37;&#46; Los pacientes ingresados en MI tuvieron una mortalidad m&#225;s elevada durante el ingreso &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;043&#41;&#44; a los tres meses &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;028&#41; y al a&#241;o &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;007&#41; respecto a los de neumolog&#237;a&#46; La adecuaci&#243;n global a las gu&#237;as cl&#237;nicas en la evaluaci&#243;n cl&#237;nica fue del 63&#37; &#40;menor en los pacientes de MI&#58; 56&#44;1&#37; vs&#46; 73&#44;8&#37;&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;063&#41;&#44; y en el tratamiento del 26&#44;9&#37; para la GOLD&#44; y del 28&#44;7&#37; para GesEPOC&#46; La adecuaci&#243;n en el uso de corticoides seg&#250;n GOLD se asoci&#243; a menor tasa de reingresos al a&#241;o &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;041&#41; y mortalidad intrahospitalaria &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;007&#41; y a los 3 meses &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;05&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">El perfil cl&#237;nico de los pacientes es actualmente similar al descrito previamente pero su evoluci&#243;n cl&#237;nica fue peor&#46; La adecuaci&#243;n global del tratamiento farmacol&#243;gico a las gu&#237;as cl&#237;nicas es baja&#44; y solo el uso adecuado de esteroides sist&#233;micos se asocia a una reducci&#243;n de la mortalidad precoz y de los reingresos a medio plazo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Metodolog&#237;a"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Please cite this article as&#58; Portol&#233;s-Callej&#243;n A&#44; L&#243;pez-Alfaro R&#44; Gim&#233;nez-Miranda L&#44; L&#243;pez-R&#237;os MC&#44; Varela-Aguilar JM&#44; Calder&#243;n E&#44; et al&#46; Adecuaci&#243;n e impacto pron&#243;stico del tratamiento de las exacerbaciones graves de la enfermedad pulmonar obstructiva cr&#243;nica&#46; Rev Clin Esp&#46; 2020&#59;220&#58;417&#8211;425&#46;</p>"
      ]
    ]
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      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0155" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0055"
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2826
            "Ancho" => 3339
            "Tamanyo" => 360026
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival curves &#40;Kaplan&#8211;Meier&#41; in the study population A&#41;&#59; by departments &#40;internal medicine vs&#46; pneumology&#41; B&#41; and according to the compliance with the GOLD C&#41; and GesEPOC D&#41; guidelines criteria in the use of corticosteroids&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; GesEPOC&#44; Spanish COPD Guidelines&#59; GOLD&#44; Global Initiative for Chronic Obstructive Lung Disease guidelines&#59; ICU&#44; intensive care unit&#59; IM&#44; internal medicine&#59; PNEU&#44; pneumology&#46;</p>"
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      ]
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; AF&#44; atrial fibrillation&#59; DBP&#44; diastolic blood pressure&#59; HR&#44; heart rate&#59; PaCO<span class="elsevierStyleInf">2</span>&#44; partial pressure of carbon dioxide&#59; PaO<span class="elsevierStyleInf">2</span>&#44; partial pressure of oxygen&#59; PMN&#44; polymorphonuclear&#59; Rx&#44; radiography&#59; SatO<span class="elsevierStyleInf">2</span>&#44; oxygen saturation&#59; SBP&#44; systolic blood pressure&#59; SD&#44; standard deviation&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">All values are listed as mean&#8239;&#177;&#8239;SD unless otherwise noted&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Bolded <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;&#46;05&#46;</p>"
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age&#44; years</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">74&#46;06&#8239;&#177;&#8239;11&#46;29&nbsp;\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">67&#46;45&#8239;&#177;&#8239;11&#46;53&nbsp;\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">71&#46;49&#8239;&#177;&#8239;11&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">53 &#40;80&#46;3&#41;&nbsp;\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">35 &#40;83&#46;3&#41;&nbsp;\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">88 &#40;81&#46;5&#41;&nbsp;\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">&#46;693<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#46;21&#8239;&#177;&#8239;4&#46;25&nbsp;\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">7&#46;64&#8239;&#177;&#8239;4&#46;31&nbsp;\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">6&#46;77&#8239;&#177;&#8239;4&#46;31&nbsp;\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">&#46;093<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;36&#8239;&#177;&#8239;1&#46;89&nbsp;\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">4&#46;27&#8239;&#177;&#8239;2&#46;17&nbsp;\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"><span class="elsevierStyleBold">&#46;001</span><a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Dyspnea &#40;MMRC&#41;&#44; n</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;69&#8239;&#177;&#8239;0&#46;68&nbsp;\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">2&#46;95&#8239;&#177;&#8239;1&#46;20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;42&#8239;&#177;&#8239;0&#46;96&nbsp;\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"><span class="elsevierStyleBold">&#46;006</span><a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">GOLD severity&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#8211;2 &#40;mild to moderate&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#8211;4 &#40;severe-very severe&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Average&#44; mean&#8239;&#177;&#8239;SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Number of Anthonisen criteria&#44; mean &#8239;&#177;&#8239;SD</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;084<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">SBP&#44; mm Hg</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">77&#46;1&#8239;&#177;&#8239;14&#46;55&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">HR&#44; bpm</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">99&#46;74&#8239;&#177;&#8239;19&#46;64&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">81&#46;91&#8239;&#177;&#8239;11&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#46;046</span><a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Blood glucose&#44; mmol&#47;L</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8239;&#60;3 months&nbsp;\t\t\t\t\t\t\n
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                  \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">28 &#40;26&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">18 &#40;27&#46;7&#37;&#41;&nbsp;\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">10 &#40;24&#46;4&#37;&#41;&nbsp;\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">&#46;707<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8239;3&#8211;12 months&nbsp;\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
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                  \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">19 &#40;29&#46;2&#37;&#41;&nbsp;\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">13 &#40;31&#37;&#41;&nbsp;\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">&#46;849<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8239;&#60;1&#8239;year&nbsp;\t\t\t\t\t\t\n
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                  \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">46 &#40;43&#46;4&#37;&#41;&nbsp;\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">31 &#40;47&#46;7&#37;&#41;&nbsp;\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
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                  \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">&#46;261<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;5&#93;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;5&#93;<span class="elsevierStyleItalic">Mortality</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>In-hospital&nbsp;\t\t\t\t\t\t\n
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                  \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">15 &#40;13&#46;9&#37;&#41;&nbsp;\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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;19&#46;7&#37;&#41;&nbsp;\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">2 &#40;4&#46;8&#37;&#41;&nbsp;\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"><span class="elsevierStyleBold">&#46;043</span><a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8239;&#60;3 months&nbsp;\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">23 &#40;21&#46;9&#37;&#41;&nbsp;\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">19 &#40;29&#46;2&#37;&#41;&nbsp;\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">4 &#40;10&#37;&#41;&nbsp;\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"><span class="elsevierStyleBold">&#46;028</span><a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#8211;12 months&nbsp;\t\t\t\t\t\t\n
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                  \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">9 &#40;8&#46;7&#37;&#41;&nbsp;\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">7 &#40;10&#46;9&#37;&#41;&nbsp;\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">2 &#40;5&#37;&#41;&nbsp;\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">&#46;477<a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;1&#8239;year&nbsp;\t\t\t\t\t\t\n
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                  \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">29 &#40;27&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">24 &#40;37&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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 &#40;12&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#46;007</span><a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Compliance variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \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" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0030">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-1 &#40;the GOLD degree of obstruction is included in the history&#41;&nbsp;\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">77 &#40;71&#46;3&#37;&#41;&nbsp;\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">41 &#40;62&#46;1&#37;&#41;&nbsp;\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">36 &#40;85&#46;7&#37;&#41;&nbsp;\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"><span class="elsevierStyleBold">&#46;008</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-2 &#40;the number of previous exacerbation episodes is included in the history&#41;&nbsp;\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">108 &#40;100&#37;&#41;&nbsp;\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">66 &#40;100&#37;&#41;&nbsp;\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">42 &#40;100&#37;&#41;&nbsp;\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">&#46;506&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-3 &#40;comorbidity is included in the history&#41;&nbsp;\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">108 &#40;100&#37;&#41;&nbsp;\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">66 &#40;100&#37;&#41;&nbsp;\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">42 &#40;100&#37;&#41;&nbsp;\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">&#46;506&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-4 &#40;the use of accessory muscles at admission is included in the history&#41;&nbsp;\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">106 &#40;98&#46;1&#37;&#41;&nbsp;\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">66 &#40;100&#37;&#41;&nbsp;\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">40 &#40;95&#46;2&#37;&#41;&nbsp;\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">&#46;149&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-5 &#40;the presence or absence of hemodynamics instability is included in the history&#41;&nbsp;\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">98 &#40;90&#46;7&#37;&#41;&nbsp;\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">61 &#40;92&#46;4&#37;&#41;&nbsp;\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">37 &#40;88&#46;1&#37;&#41;&nbsp;\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">&#46;454&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-6 &#40;chest radiography was performed at admission&#41;&nbsp;\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">102 &#40;95&#46;3&#37;&#41;&nbsp;\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">61 &#40;93&#46;8&#37;&#41;&nbsp;\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">41 &#40;97&#46;6&#37;&#41;&nbsp;\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">&#46;646&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-Global &#40;all previous criteria are met&#41;&nbsp;\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">68 &#40;63&#37;&#41;&nbsp;\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">37 &#40;56&#46;1&#37;&#41;&nbsp;\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">31 &#40;73&#46;8&#37;&#41;&nbsp;\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">&#46;063&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-1SABA-SAMA &#40;GesEPOC and GOLD&#41;&nbsp;\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">43 &#40;41&#46;3&#37;&#41;&nbsp;\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">24 &#40;38&#46;7&#37;&#41;&nbsp;\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">19 &#40;45&#46;2&#37;&#41;&nbsp;\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">&#46;507&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-2Antibiotic therapy &#40;GOLD&#41;&nbsp;\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">65 &#40;63&#46;1&#37;&#41;&nbsp;\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">37 &#40;59&#46;7&#37;&#41;&nbsp;\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">28 &#40;68&#46;3&#37;&#41;&nbsp;\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">&#46;375&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-3 Systemic&#47;inhaled corticosteroids &#40;GOLD&#41;&nbsp;\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">98 &#40;90&#46;7&#37;&#41;&nbsp;\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">58 &#40;87&#46;9&#37;&#41;&nbsp;\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">40 &#40;95&#46;2&#37;&#41;&nbsp;\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">&#46;310&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-4Corticosteroid doses and duration&nbsp;\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">5 &#40;4&#46;6&#37;&#41;&nbsp;\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">3 &#40;4&#46;5&#37;&#41;&nbsp;\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">2 &#40;4&#46;8&#37;&#41;&nbsp;\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">&#46;675&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-5Antibiotic therapy &#40;GesEPOC&#41;&nbsp;\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">77 &#40;74&#46;8&#37;&#41;&nbsp;\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">43 &#40;69&#46;4&#37;&#41;&nbsp;\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">34 &#40;82&#46;9&#37;&#41;&nbsp;\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">&#46;187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-6Systemic corticosteroids &#40;GesEPOC&#41;&nbsp;\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">91 &#40;84&#46;3&#37;&#41;&nbsp;\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">55 &#40;83&#46;3&#37;&#41;&nbsp;\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">36 &#40;85&#46;7&#37;&#41;&nbsp;\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">&#46;952&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-7&#40;PRETEMED&#41;&nbsp;\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">93 &#40;91&#46;2&#37;&#41;&nbsp;\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">53 &#40;86&#46;9&#37;&#41;&nbsp;\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">40 &#40;97&#46;6&#37;&#41;&nbsp;\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">&#46;081&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-Overall-GOLD&nbsp;\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">29 &#40;26&#46;9&#37;&#41;&nbsp;\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">17 &#40;25&#46;8&#37;&#41;&nbsp;\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">12 &#40;28&#46;6&#37;&#41;&nbsp;\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">&#46;748&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-Overall-GesEPOC&nbsp;\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">31 &#40;28&#46;7&#37;&#41;&nbsp;\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">18 &#40;27&#46;3&#37;&#41;&nbsp;\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">13 &#40;31&#37;&#41;&nbsp;\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">&#46;680&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-NIMV &#40;GOLD&#41;&nbsp;\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">31 &#40;60&#46;8&#37;&#41;&nbsp;\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">14 &#40;60&#46;9&#37;&#41;&nbsp;\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">17 &#40;60&#46;8&#37;&#41;&nbsp;\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">&#46;991&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-NIMV &#40;GesEPOC&#41;&nbsp;\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">26 &#40;61&#46;9&#37;&#41;&nbsp;\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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;56&#46;3&#37;&#41;&nbsp;\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">17 &#40;65&#46;4&#37;&#41;&nbsp;\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">&#46;554&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; SABA&#44; short-acting &#223;2-agonist&#59; SAMA&#44; short-acting muscarinic antagonist&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Description of variables&#58; R-TX-1&#58; use of beta 2-agonist and&#47;or short-acting anticholinergic&#59; R-TX-2&#58; use of antibiotherapy according to the GOLD recommendations&#58; in patients with mechanical ventilation and&#47;or following the Anthonisen criteria based on GOLD&#58; &#40;i&#41; presence of purulent sputum or &#40;ii&#41; increased dyspnea&#44; increased sputum volume&#44; increased sputum purulence or &#40;iii&#41; increased sputum purulence and another cardinal symptom&#59; R-TX-3&#58; use of systemic or inhaled corticosteroids during hospitalization&#59; R-TX-4&#58; use of systemic corticosteroids at dosages equivalent to 40&#8211;60&#8239;mg of prednisone&#47;day for 5&#8211;10 days &#40;the corticosteroids administered during the hospitalization and prescribed at discharge are considered&#41;&#59; R-TX-5&#58; use of antibiotherapy according to the GesEPOC recommendations&#58; &#40;i&#41; provided there is a change in sputum color or &#40;ii&#41; in the moderate to severe exacerbation when&#44; in the absence of purulence&#44; there is increased dyspnea and sputum volume or &#40;iii&#41; in highly severe exacerbations&#44; when the patient requires ventilatory assistance&#59; R-TX-6&#58; use of systemic corticosteroids&#59; R-TX-7&#58; use of LMWHs or anticoagulation in patients with an adjusted PRETEMED risk &#62;4&#59; R-TX-Global-GesEPOC&#58; all treatment recommendations in the GesEPOC guidelines are followed &#40;R-TX-1&#8239;&#43;&#8239;R-TX-4&#8239;&#43;&#8239;R-TX-5&#8239;&#43;&#8239;R-TX-6&#41;&#59; R-TX-Global-GOLD&#58; all treatment recommendations in the GOLD guidelines are followed &#40;R-TX-1&#8239;&#43;&#8239;R-TX-2&#8239;&#43;&#8239;R-TX-3&#8239;&#43;&#8239;R-TX-4&#41;&#59; R-NIMV &#40;GesEPOC&#41;&#58; use of NIMV according to the GOLD indications&#58; respiratory acidosis &#40;pH&#8239;&#60;&#8239;7&#46;35&#41; with hypercapnia &#40;PaCO<span class="elsevierStyleInf">2</span>&#8239;&#62;45&#8239;mm&#8239;Hg&#41;&#59; R-NIMV &#40;GOLD&#41;&#58; use of NIMV according to GOLD indications&#58; &#40;i&#41; respiratory acidosis &#40;arterial pH&#8239;&#8804;&#8239;7&#46;35 and&#47;or PaCO<span class="elsevierStyleInf">2</span> &#8805;6&#46;0&#8239;kPa&#44; 45&#8239;mm&#8239;Hg&#41; or &#40;ii&#41; severe dyspnea and use of accessory muscles&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Bolded <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;&#46;05&#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="\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" scope="col">Appropriateness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#91;0&#44;2&#8211;4&#93;Re-admissions</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#91;0&#44;5&#8211;8&#93;Mortality</th></tr><tr title="table-row"><th 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" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#60;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">3&#8211;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#60;1&#8239;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Intrahospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#60;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">3&#8211;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#60;1&#8239;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-1 SABA-SAMA &#40;GOLD&#47;GesEPOC&#41;&nbsp;\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">0&#46;300&nbsp;\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">0&#46;932&nbsp;\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">0&#46;231&nbsp;\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">0&#46;869&nbsp;\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">0&#46;475&nbsp;\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">0&#46;325&nbsp;\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">0&#46;150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-2 Antibiotics &#40;GOLD&#41;&nbsp;\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">0&#46;371&nbsp;\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">0&#46;980&nbsp;\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">0&#46;889&nbsp;\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">0&#46;367&nbsp;\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">0&#46;846&nbsp;\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">0&#46;485&nbsp;\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">0&#46;770&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-3 Corticosteroids &#40;GOLD&#41;&nbsp;\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">0&#46;145&nbsp;\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">0&#46;277&nbsp;\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"><span class="elsevierStyleBold">0&#46;041</span><a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\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">0&#46;004<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\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">0&#46;036<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\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">0&#46;949&nbsp;\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">0&#46;142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-4 Corticosteroids &#40;dose and duration&#41;&nbsp;\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">0&#46;173&nbsp;\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">0&#46;932&nbsp;\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">0&#46;106&nbsp;\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">0&#46;151&nbsp;\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
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Original article
Adequacy and prognostic impact of treatment for severe exacerbation of chronic obstructive pulmonary disease
Adecuación e impacto pronóstico del tratamiento de las exacerbaciones graves de la enfermedad pulmonar obstructiva crónica
A. Portolés-Callejóna, R. López-Alfaroa,b, L. Giménez-Mirandaa,b, M.C. López-Ríosa,b, J.M. Varela-Aguilara,b,c, E. Calderóna,b,c,d, F.J. Medranoa,b,c,d,
Corresponding author
medrano@cica.es

Corresponding author.
a Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain
b Grupo de EPOC de la Sociedad Española de Medicina Interna, Spain
c Grupo de Epidemiología Clínica y Riesgo Vascular, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Sevilla, Spain
d Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival curves &#40;Kaplan&#8211;Meier&#41; in the study population A&#41;&#59; by departments &#40;internal medicine vs&#46; pneumology&#41; B&#41; and according to the compliance with the GOLD C&#41; and GesEPOC D&#41; guidelines criteria in the use of corticosteroids&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; GesEPOC&#44; Spanish COPD Guidelines&#59; GOLD&#44; Global Initiative for Chronic Obstructive Lung Disease guidelines&#59; ICU&#44; intensive care unit&#59; IM&#44; internal medicine&#59; PNEU&#44; pneumology&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic obstructive pulmonary disease &#40;COPD&#41; is the most common respiratory disease&#44; with a worldwide prevalence of 251 million cases<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and an estimated annual mortality of 5&#37;&#44; according to data from the World Health Organization&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Exacerbations represent a key point in the progression of the disease and are characterized by sustained worsening of the disease beyond the normal daily variations&#44; with an acute onset&#44; resulting in changes in the patient&#8217;s medication or hospitalization&#46; Up to 35&#37; of patients with COPD have at least 1 hospitalization per year&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and up to 30&#37; are re-admitted within 6 months after the discharge&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> These exacerbations have a considerable impact on patients&#8217; state of health and physical capacity and have a cumulative effect on the loss of pulmonary function&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Exacerbation episodes are also independent predictors of disease progression and mortality&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> which increases both in the long term and short term&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The most widely used clinical practice guidelines &#40;CPGs&#41; in our setting for treating COPD exacerbations are those proposed by GOLD<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and the Spanish COPD guidelines &#40;GesEPOC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Among their recommendations&#44; both guidelines include the use of &#946;2-agonists and anticholinergic bronchodilators&#44; systemic corticosteroids&#44; early rehabilitation measures and&#44; in certain circumstances&#44; antibiotherapy&#44; oxygen therapy and noninvasive ventilatory support&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Despite the well-established regimens for managing COPD&#44; the treatment of exacerbations in hospitalized patients is still suboptimal&#44; and little progress has been made in terms of reducing readmissions and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;14</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although there are data in our setting on these patients&#8217; clinical profile and audits on compliance with the CPGs &#40;Escarrabill et al&#46;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> awareness of the effects on patient outcomes of treating the exacerbations is still quite limited&#46; The present study was therefore proposed&#44; with the objectives of determining the clinical characteristics of patients hospitalized for COPD exacerbations in our setting&#44; assessing overall compliance and departmental compliance &#40;internal medicine and pneumology&#41; with the CPG recommendations on clinical management and determining the prognostic impact of COPD exacerbations&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0020" class="elsevierStylePara elsevierViewall">We conducted an observational&#44; longitudinal retrospective study that employed simple randomized sampling to include patients hospitalized for COPD exacerbations in a tertiary hospital&#44; up to the precalculated sample size of 108 &#40;parameter value of 0&#46;5&#44; 95&#37; confidence level&#44; 8&#37; precision and 10&#37; loss rate&#41;&#46; The inclusion criteria were hospitalization in the University Hospital Virgen del Roc&#237;o &#40;Seville&#44; Spain&#41; between January 2015 and December 2015&#44; a primary diagnosis of &#8220;COPD exacerbation&#8221; &#40;ICD-9-CM 491&#46;84 and 518&#46;84&#41; in the hospital discharge report and identification in the local minimum basic data set&#46; The exclusion criterion was a lack of spirometric confirmation prior to the COPD diagnosis in the medical history&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Data collection</span><p id="par0025" class="elsevierStylePara elsevierViewall">From the data available in the minimum basic data set and the digital medical histories&#44; we collected the variables included in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; which basically include demographic data&#44; discharging department&#44; comorbidity according to the age-adjusted Charlson index &#40;Appendix 1a&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> degree of obstruction measured by spirometry within 6 months prior to the index episode &#40;percentage forced expiratory volume in 1&#8239;s&#44; FEV<span class="elsevierStyleInf">1</span>&#37;&#41; &#40;Appendix 1b&#41;&#44; degree of baseline dyspnea &#40;measured with the modified Medical Research Council scale&#41; &#40;Appendix 1c&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> exacerbations in the year prior to the episode&#44; clinical signs &#40;systolic and diastolic blood pressure&#44; heart rate&#44; inspiratory chest wall retraction&#41;&#44; biological variables &#40;oxygen saturation&#44; pH&#44; partial pressure of carbon dioxide&#44; partial pressure of oxygen&#44; eosinophils&#44; leukocytes&#44; lymphocytes&#44; neutrophils&#44; C-reactive protein&#41; and the onset of <span class="elsevierStyleItalic">de novo</span> steroid diabetes or hyperglycemic decompensation&#46; We also collected data on compliance with the GOLD 2014<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and GesEPOC 2012<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> clinical guidelines &#40;those guidelines that were current at the time of the study&#41;&#44; in terms of the clinical assessment and treatment&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">As outcome variables&#44; we included all-cause mortality and readmissions for exacerbations at 3 months and at 1&#8239;year of the hospital discharge&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Throughout the process&#44; we ensured data confidentiality according to current legislation&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The relationship between the qualitative variables was analyzed with the chi-squared test and Fisher&#8217;s exact test&#46; For the quantitative variables&#44; we employed Student&#8217;s t-test after determining the normality of the distribution of values&#46; For non-normality&#44; we employed a nonparametric test &#40;Mann&#8211;Whitney U test&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Using Kaplan&#8211;Meier curves &#40;Mantel&#8211;Cox test&#41;&#44; we compared the mortality and readmissions according to the admitting department and according to the compliance or not with the various treatment recommendations&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Finally&#44; we performed a multivariate analysis using multiple logistic regression&#44; which included the variables with statistical association in the bivariate analysis and other prognostic variables reported in the literature&#44; such as age&#44; the Charlson comorbidity index and the discharging department&#46; Data was available in our study for more than 80&#37; of the cases&#46; We calculated the adjusted odd ratios &#40;OR&#41; with their 95&#37; confidence interval&#46; To assess the yield of each model&#44; we performed a sensitivity analysis with receiver operating characteristics curves&#44; which produced an area under the curve and its 95&#37; confidence interval&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">We performed the analysis with the IBM SPSS Statistics 21 statistical package &#40;IBM Corporation&#44; Armonk&#44; NY&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical aspects</span><p id="par0060" class="elsevierStylePara elsevierViewall">The study was conducted in accordance with the Declaration of Helsinki<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and the pertinent requirements of Spanish law&#46; The study was granted a favorable opinion by the Research Ethics Committee of University Hospital Virgen Macarena and University Hospital Virgen del Roc&#237;o of Seville&#44; Spain&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">We included a total of 108 patients&#44; 81&#46;5&#37; of whom were men&#46; Some 61&#46;1&#37; of the patients were hospitalized in the internal medicine department&#44; and 38&#46;9&#37; were hospitalized in the pneumology department&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents the rest of the study patients&#8217; clinical-demographic characteristics&#46; In terms of the baseline biological characteristics and complementary tests&#44; the internal medicine patients presented higher oxygen saturation and baseline blood glucose levels and lower pH levels&#46; There was a broad use of chest radiography as a complementary test in both departments &#40;95&#46;3&#37;&#41;&#44; and there were no differences between the departments in the other variables&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the patients&#8217; clinical progression according to the admitting department&#46; There were no statistically significant differences in terms of readmissions according to admitting department&#46; The patients hospitalized in the internal medicine department had higher mortality during hospitalization &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;043&#41;&#44; at 3 months &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;028&#41; and at 1 year &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;007&#41;&#46; The survival analysis showed that the mean survival was 827&#46;4 days &#40;95&#37; CI 727&#46;6&#8211;927&#46;3&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; The survival curves according to discharging department showed lower survival for the patients hospitalized in internal medicine &#40;725&#46;1 vs&#46; 984&#46;1 days&#59; log-rank test&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;023&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In terms of the clinical assessment &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; the overall compliance with the CPGs was 63&#37; and was lower for the patients in internal medicine than for those hospitalized in pneumology &#40;56&#46;1&#37; vs&#46; 73&#46;8&#37;&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;063&#41;&#46; Moreover&#44; the patients hospitalized in internal medicine presented less compliance in the assessment of the degree of obstruction according to GOLD &#40;62&#46;1&#37; vs&#46; 85&#46;7&#37;&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;008&#41;&#44; with no significant differences between the two departments in the remaining criteria of compliance&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">In terms of drug treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; we observed overall compliance of 26&#46;9&#37; with the CPG recommendations for the GOLD criteria and 28&#46;7&#37; for GesEPOC&#44; and there were no differences in compliance by department&#46; The mean dosage of systemic corticosteroids employed for the study population was 80&#46;4&#8239;&#177;&#8239;55&#46;9&#8239;mg of prednisone&#47;day&#44; and the mean treatment duration was 5&#46;3&#8239;&#177;&#8239;5&#46;7 days&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">To assess the impact of compliance with the various CPG recommendations on the clinical progression&#44; we first performed a bivariate analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#44; which&#44; for readmissions&#44; showed an association between GOLD guideline compliance for systemic steroid treatment &#40;ADECUA-TX-3&#41; and cumulative readmissions at 1&#8239;year &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;041&#41;&#46; The analysis also showed an association between GesEPOC guideline compliance &#40;ADECUA-TX-6&#41; and readmissions between 3 and 12 months &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;0017&#41;&#46; In terms of mortality&#44; the variable &#8220;GOLD guideline compliance in the use of corticotherapy&#8221; showed an association with hospital mortality &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;004&#41; and short-term mortality &#40;&#60;3 months&#41; &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;036&#41;&#46; In the survival analysis&#44; there was also longer patient survival with the appropriate use of corticosteroids according to the GOLD criteria &#40;Mantel&#8211;Cox&#44; 0&#46;009&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#44; which did not appear when applying the GesEPOC criteria &#40;Mantel&#8211;Cox&#44; 0&#46;529&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Finally&#44; in the multivariate analysis&#44; we developed 5 predictive models for the study variables for clinical progression &#40;readmissions at 3 months and at 1&#8239;year and inhospital mortality and mortality at 3 months and at 1&#8239;year&#41;&#46; As prognostic variables&#44; we included age&#44; Charlson index&#44; discharging department and GOLD guideline compliance for steroidal treatment&#44; which was the only compliance variable with a consistent association in the bivariate analysis&#46; The results of this analysis showed that GOLD guideline compliance for steroidal treatment for the study patients was significantly associated with lower hospital mortality &#40;OR&#44; 0&#46;13&#59; 95&#37; CI 0&#46;03&#8211;0&#46;57&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;007&#41; and mortality at 3 months &#40;OR&#44; 0&#46;26&#59; 95&#37; CI 0&#46;07&#8211;1&#46;01&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;05&#41;&#46; We also observed an association between hospitalization in the pneumology department and lower mortality at 1 year &#40;OR&#44; 0&#46;25&#59; 95&#37; CI 0&#46;08&#8211;0&#46;77&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;&#46;015&#41;&#46; The predictive models showed an area under the curve of between 0&#46;64 &#40;95&#37; CI 0&#46;53&#8211;0&#46;77&#41; and 0&#46;73 &#40;95&#37; CI 0&#46;58&#8211;0&#46;89&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">To our knowledge&#44; this is the first study conducted in Spain to determine the clinical impact of treatment for severe COPD exacerbations on patient outcomes&#46; The study also provides information on the clinical profile and compliance with the clinical guideline recommendations in the departments where these patients are typically hospitalized &#40;internal medicine and pneumology&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A previous comparative study in Spain analyzed the comorbidities associated with COPD of patients according to whether they were admitted to internal medicine or pneumology&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The authors observed that the 2 populations had differing characteristics and were difficult to compare&#44; as happened in our study&#44; where the comorbidity assessed by the Charlson index was significantly higher among the patients with COPD hospitalized in internal medicine&#44; contributing to greater mortality&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Our study has a number of limitations&#44; the main being the study sample size&#44; which could impair the power of the analysis&#46; However&#44; as with other studies with sample sizes similar to or smaller than ours&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> the sample was sufficient to enable us to define the clinical spectrum and compliance and assess&#44; at least partly&#44; the prognostic impact of compliance with the CPG recommendations&#46; This study involved a single center&#44; which could limit the external validity of the evaluated data&#46; Furthermore&#44; the study&#8217;s retrospective nature&#44; which hindered the recording of certain data&#44; could represent another possible limitation in the scope of our conclusions&#46; In the study design&#44; however&#44; we adjusted the CPG compliance variables to the parameters available in standard clinical practice&#46; We minimized the selection bias through randomization of the sample&#44; thereby avoiding biases such as those of a seasonal nature&#46; Finally&#44; the consistency of the results with the various methodological approaches &#40;bivariate analysis&#44; survival analysis and multiple logistic regression&#41; provided greater strength to the conclusions&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In terms of the results&#44; we should highlight a few findings&#46; Firstly&#44; the study showed that despite improvements in the therapeutic management<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> and follow-up of this disease and in the development of new predictive scales that include the evaluation of comorbidity for better patient stratification&#44;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> mortality after a COPD exacerbation remains very high&#46; This finding is due&#44; at least in part&#44; to the advanced age of the hospitalized patients&#44; the severity of the respiratory disease and the comorbidity burden &#40;measured by the Charlson index&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The study patients&#8217; demographic characteristics are similar to those described in other studies&#44; although most of those studies included patients with much less comorbidity&#44; probably due to the selective inclusion of patients hospitalized in pneumology&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;23</span></a> In our study&#44; only 12&#37; of the patients were women&#44; a figure much lower than that observed in most of the studies&#46; In addition&#44; there were significant differences in the clinical progression between our study and other studies&#46; For example&#44; the rates of readmission and mortality at 3 months were 26&#46;4&#37; and 21&#46;9&#37;&#44; respectively&#44; for our study&#44; while those of the study by L&#243;pez Campos et al&#46; were 35&#46;1&#37; and 10&#46;8&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">In our study&#44; compliance with the recommendations on the clinical assessment was high&#44; with rates ranging from 71&#37; to 100&#37; for the individual recommendations and 63&#37; for overall compliance&#44; findings similar to those observed in other studies&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In terms of the treatment recommendations&#44; the use of short-acting &#946;-2 agonists &#40;with or without short-acting anticholinergic agents&#41; &#40;41&#46;3&#37;&#41; was lower than that reported in a number of studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> This finding reveals high variability in terms of compliance according to the population characteristics&#44; resources of the various respiratory units<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and other factors not yet reported in the literature&#44; such as cardiovascular comorbidity and the high prevalence of atrial fibrillation observed in our study &#40;28&#46;8&#37;&#41;&#44; a limiting factor in the use of short-acting &#946;-2 agonists&#46; Secondly&#44; in terms of compliance with the dosages and treatment duration with systemic steroids&#44; the figures observed in our study &#40;4&#46;6&#37;&#41; were similar to those reported by other authors &#40;5&#37; in the study by Lipari et al&#46;&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> but very different from those reported by others &#40;80&#37; in the study by Harvey et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#41;&#44; which also reflects the significant variability in the compliance with guideline recommendations&#46; Lastly&#44; in terms of compliance with the use of noninvasive mechanical ventilation&#44; we found similar rates to those in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In terms of mortality&#44; we found that greater compliance with the GOLD guideline recommendations on steroidal treatment was associated in our setting with lower hospital mortality and early mortality &#40;at 3 months&#41;&#46; The survival analysis showed greater patient survival with the appropriate use of corticosteroids according to GOLD guideline recommendations&#46; The multivariate analysis revealed an association between GOLD guideline compliance in the appropriate use of corticosteroids and lower hospital mortality and at 3 months&#46; A recent study showed that the use of corticosteroids at high dosages in patients hospitalized for COPD exacerbations was associated with longer hospital stays&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> although this relationship was not observed in another similar study also performed in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Our study found a high rate of hydrocarbon metabolism disorders &#40;39&#46;3&#37;&#41;&#44; including <span class="elsevierStyleItalic">de novo</span> steroid-induced diabetes mellitus &#40;25&#46;5&#37;&#41; and hyperglycemic decompensation &#40;21&#46;5&#37;&#41;&#46; These findings demonstrate the need for optimizing the steroid dosages employed for COPD exacerbations in our patients to minimize the risk of metabolic complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#44;33</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In conclusion&#44; the present study showed that patients hospitalized for COPD in our setting continue to have a poor short-term and medium-term prognosis&#46; The study identified differences in the clinical profile of patients admitted to the internal medicine and pneumology departments&#44; which determine the patients&#8217; prognosis and outcome and that do not seem to be related to a different clinical management&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The study also showed low compliance in our setting with the clinical guideline recommendations and identified areas for improvement&#46; We also confirmed that the appropriate use of systemic steroids is associated with reduced early mortality and medium-term readmissions&#46; However&#44; compliance with the guidelines&#8217; other therapeutic recommendations was not associated in our study with clinical progression&#44; probably as a consequence of the limitations in the power of the analysis&#46; Further studies are therefore needed to determine the true impact on actual clinical practice&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease &#40;COPD&#41; exacerbation&#44; to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients&#8217; prognosis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methodology</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital&#46; We collected demographic and clinical variables &#40;degree of dyspnoea and obstruction&#44; previous exacerbations&#44; comorbidities&#41;&#44; readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease &#40;GOLD&#41; guidelines and the Spanish COPD guidelines &#40;GesEPOC&#41;&#46; We performed a univariate&#44; multivariate and survival analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">The study included 108 patients&#44; and the mean age was 71&#46;48&#8239;&#177;&#8239;11&#46;65 years&#46; The readmission rate was 26&#46;4&#37; at 3 months and 43&#46;4&#37; at 1 year&#46; The hospital mortality rate was 3&#46;9&#37;&#44; the mortality rate at 3 months was 21&#46;9&#37;&#44; and the mortality rate at 1 year was 27&#46;4&#37;&#46; The patients hospitalised in the internal medicine department had higher mortality during hospitalisation &#40;p&#8239;&#61;&#8239;&#46;043&#41;&#44; at 3 months &#40;p&#8239;&#61;&#8239;&#46;028&#41; and at 1 year &#40;p&#8239;&#61;&#8239;&#46;007&#41; compared with the rates for the pneumology department&#46; Overall compliance with the clinical guidelines was 63&#37; for the clinical evaluation &#40;less for the patients in internal medicine&#58; 56&#46;1&#37; vs&#46; 73&#46;8&#37;&#44; p&#8239;&#61;&#8239;&#46;063&#41;&#46; For the treatment&#44; the compliance was 26&#46;9&#37; for GOLD and 28&#46;7&#37; for GesEPOC&#46; Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions &#40;p&#8239;&#61;&#8239;&#46;041&#41; and hospital mortality &#40;p&#8239;&#61;&#8239;&#46;007&#41; and 3-month mortality &#40;p&#8239;&#61;&#8239;&#46;05&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">The clinical profile of the patients is currently similar to that previously reported&#44; but their clinical progression was poorer&#46; Overall compliance with the clinical guidelines for drug treatment was low&#44; and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Definir las caracter&#237;sticas cl&#237;nicas de los pacientes hospitalizados en servicios de medicina interna &#40;MI&#41; y neumolog&#237;a por exacerbaciones de la EPOC&#44; evaluar la adecuaci&#243;n a las recomendaciones de las gu&#237;as de pr&#225;ctica cl&#237;nica y conocer su impacto en el pron&#243;stico de los pacientes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodolog&#237;a</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Estudio longitudinal retrospectivo&#46; Se incluyeron aleatoriamente pacientes ingresados por exacerbaci&#243;n de EPOC en un hospital de tercer nivel&#46; Se registraron variables demogr&#225;ficas&#44; cl&#237;nicas &#40;grado de disnea y de obstrucci&#243;n&#44; exacerbaciones previas&#44; comorbilidades&#41;&#44; criterios de adecuaci&#243;n a las gu&#237;as cl&#237;nicas GOLD y GesEPOC y datos de reingresos y mortalidad&#46; Se realiz&#243; un an&#225;lisis univariante&#44; multivariante y de supervivencia&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 108 pacientes y la edad media fue de 71&#44;48&#177;11&#44;65 a&#241;os&#46; Los reingresos a los 3 meses fueron un 26&#44;4&#37; y al a&#241;o un 43&#44;4&#37;&#46; La mortalidad intrahospitalaria fue del 3&#44;9&#37;&#44; a los 3 meses del 21&#44;9&#37;&#44; y al a&#241;o del 27&#44;4&#37;&#46; Los pacientes ingresados en MI tuvieron una mortalidad m&#225;s elevada durante el ingreso &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;043&#41;&#44; a los tres meses &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;028&#41; y al a&#241;o &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;007&#41; respecto a los de neumolog&#237;a&#46; La adecuaci&#243;n global a las gu&#237;as cl&#237;nicas en la evaluaci&#243;n cl&#237;nica fue del 63&#37; &#40;menor en los pacientes de MI&#58; 56&#44;1&#37; vs&#46; 73&#44;8&#37;&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;063&#41;&#44; y en el tratamiento del 26&#44;9&#37; para la GOLD&#44; y del 28&#44;7&#37; para GesEPOC&#46; La adecuaci&#243;n en el uso de corticoides seg&#250;n GOLD se asoci&#243; a menor tasa de reingresos al a&#241;o &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;041&#41; y mortalidad intrahospitalaria &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;007&#41; y a los 3 meses &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#44;05&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">El perfil cl&#237;nico de los pacientes es actualmente similar al descrito previamente pero su evoluci&#243;n cl&#237;nica fue peor&#46; La adecuaci&#243;n global del tratamiento farmacol&#243;gico a las gu&#237;as cl&#237;nicas es baja&#44; y solo el uso adecuado de esteroides sist&#233;micos se asocia a una reducci&#243;n de la mortalidad precoz y de los reingresos a medio plazo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
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          1 => array:2 [
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            "titulo" => "Metodolog&#237;a"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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      ]
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Please cite this article as&#58; Portol&#233;s-Callej&#243;n A&#44; L&#243;pez-Alfaro R&#44; Gim&#233;nez-Miranda L&#44; L&#243;pez-R&#237;os MC&#44; Varela-Aguilar JM&#44; Calder&#243;n E&#44; et al&#46; Adecuaci&#243;n e impacto pron&#243;stico del tratamiento de las exacerbaciones graves de la enfermedad pulmonar obstructiva cr&#243;nica&#46; Rev Clin Esp&#46; 2020&#59;220&#58;417&#8211;425&#46;</p>"
      ]
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      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0155" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0055"
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2826
            "Ancho" => 3339
            "Tamanyo" => 360026
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival curves &#40;Kaplan&#8211;Meier&#41; in the study population A&#41;&#59; by departments &#40;internal medicine vs&#46; pneumology&#41; B&#41; and according to the compliance with the GOLD C&#41; and GesEPOC D&#41; guidelines criteria in the use of corticosteroids&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; GesEPOC&#44; Spanish COPD Guidelines&#59; GOLD&#44; Global Initiative for Chronic Obstructive Lung Disease guidelines&#59; ICU&#44; intensive care unit&#59; IM&#44; internal medicine&#59; PNEU&#44; pneumology&#46;</p>"
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        "etiqueta" => "Table 1"
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            "identificador" => "at0010"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; AF&#44; atrial fibrillation&#59; DBP&#44; diastolic blood pressure&#59; HR&#44; heart rate&#59; PaCO<span class="elsevierStyleInf">2</span>&#44; partial pressure of carbon dioxide&#59; PaO<span class="elsevierStyleInf">2</span>&#44; partial pressure of oxygen&#59; PMN&#44; polymorphonuclear&#59; Rx&#44; radiography&#59; SatO<span class="elsevierStyleInf">2</span>&#44; oxygen saturation&#59; SBP&#44; systolic blood pressure&#59; SD&#44; standard deviation&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">All values are listed as mean&#8239;&#177;&#8239;SD unless otherwise noted&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Bolded <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;&#46;05&#46;</p>"
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">71&#46;49&#8239;&#177;&#8239;11&#46;79&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">53 &#40;80&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35 &#40;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">88 &#40;81&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;693<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#46;64&#8239;&#177;&#8239;4&#46;31&nbsp;\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">6&#46;77&#8239;&#177;&#8239;4&#46;31&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#46;093<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#46;27&#8239;&#177;&#8239;2&#46;17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#46;001</span><a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;95&#8239;&#177;&#8239;1&#46;20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;42&#8239;&#177;&#8239;0&#46;96&nbsp;\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"><span class="elsevierStyleBold">&#46;006</span><a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\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">&nbsp;\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">&nbsp;\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">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">GOLD severity&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#8211;2 &#40;mild to moderate&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13 &#40;31&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#8211;4 &#40;severe-very severe&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Average&#44; mean&#8239;&#177;&#8239;SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">HR&#44; bpm</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Blood glucose&#44; mmol&#47;L</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13 &#40;19&#46;7&#37;&#41;&nbsp;\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">2 &#40;4&#46;8&#37;&#41;&nbsp;\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"><span class="elsevierStyleBold">&#46;043</span><a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8239;&#60;3 months&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;29&#46;2&#37;&#41;&nbsp;\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">4 &#40;10&#37;&#41;&nbsp;\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"><span class="elsevierStyleBold">&#46;028</span><a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#8211;12 months&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">9 &#40;8&#46;7&#37;&#41;&nbsp;\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">7 &#40;10&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;5&#37;&#41;&nbsp;\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">&#46;477<a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;1&#8239;year&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">29 &#40;27&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">24 &#40;37&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">5 &#40;12&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#46;007</span><a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th 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" scope="col" style="border-bottom: 2px solid black">Compliance variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total &#40;n&#8239;&#61;&#8239;108&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pneumology &#40;n&#8239;&#61;&#8239;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0030">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Clinical assessment</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-1 &#40;the GOLD degree of obstruction is included in the history&#41;&nbsp;\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">77 &#40;71&#46;3&#37;&#41;&nbsp;\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">41 &#40;62&#46;1&#37;&#41;&nbsp;\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">36 &#40;85&#46;7&#37;&#41;&nbsp;\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"><span class="elsevierStyleBold">&#46;008</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-2 &#40;the number of previous exacerbation episodes is included in the history&#41;&nbsp;\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">108 &#40;100&#37;&#41;&nbsp;\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">66 &#40;100&#37;&#41;&nbsp;\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">42 &#40;100&#37;&#41;&nbsp;\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">&#46;506&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-3 &#40;comorbidity is included in the history&#41;&nbsp;\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">108 &#40;100&#37;&#41;&nbsp;\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">66 &#40;100&#37;&#41;&nbsp;\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">42 &#40;100&#37;&#41;&nbsp;\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">&#46;506&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-4 &#40;the use of accessory muscles at admission is included in the history&#41;&nbsp;\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">106 &#40;98&#46;1&#37;&#41;&nbsp;\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">66 &#40;100&#37;&#41;&nbsp;\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">40 &#40;95&#46;2&#37;&#41;&nbsp;\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">&#46;149&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-5 &#40;the presence or absence of hemodynamics instability is included in the history&#41;&nbsp;\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">98 &#40;90&#46;7&#37;&#41;&nbsp;\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">61 &#40;92&#46;4&#37;&#41;&nbsp;\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">37 &#40;88&#46;1&#37;&#41;&nbsp;\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">&#46;454&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-6 &#40;chest radiography was performed at admission&#41;&nbsp;\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">102 &#40;95&#46;3&#37;&#41;&nbsp;\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">61 &#40;93&#46;8&#37;&#41;&nbsp;\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">41 &#40;97&#46;6&#37;&#41;&nbsp;\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">&#46;646&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-EVALUA-Global &#40;all previous criteria are met&#41;&nbsp;\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">68 &#40;63&#37;&#41;&nbsp;\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">37 &#40;56&#46;1&#37;&#41;&nbsp;\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">31 &#40;73&#46;8&#37;&#41;&nbsp;\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">&#46;063&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-1SABA-SAMA &#40;GesEPOC and GOLD&#41;&nbsp;\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">43 &#40;41&#46;3&#37;&#41;&nbsp;\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">24 &#40;38&#46;7&#37;&#41;&nbsp;\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">19 &#40;45&#46;2&#37;&#41;&nbsp;\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">&#46;507&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-2Antibiotic therapy &#40;GOLD&#41;&nbsp;\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">65 &#40;63&#46;1&#37;&#41;&nbsp;\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">37 &#40;59&#46;7&#37;&#41;&nbsp;\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">28 &#40;68&#46;3&#37;&#41;&nbsp;\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">&#46;375&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-3 Systemic&#47;inhaled corticosteroids &#40;GOLD&#41;&nbsp;\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">98 &#40;90&#46;7&#37;&#41;&nbsp;\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">58 &#40;87&#46;9&#37;&#41;&nbsp;\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">40 &#40;95&#46;2&#37;&#41;&nbsp;\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">&#46;310&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-4Corticosteroid doses and duration&nbsp;\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">5 &#40;4&#46;6&#37;&#41;&nbsp;\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">3 &#40;4&#46;5&#37;&#41;&nbsp;\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">2 &#40;4&#46;8&#37;&#41;&nbsp;\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">&#46;675&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-5Antibiotic therapy &#40;GesEPOC&#41;&nbsp;\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">77 &#40;74&#46;8&#37;&#41;&nbsp;\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">43 &#40;69&#46;4&#37;&#41;&nbsp;\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">34 &#40;82&#46;9&#37;&#41;&nbsp;\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">&#46;187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-6Systemic corticosteroids &#40;GesEPOC&#41;&nbsp;\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">91 &#40;84&#46;3&#37;&#41;&nbsp;\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">55 &#40;83&#46;3&#37;&#41;&nbsp;\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">36 &#40;85&#46;7&#37;&#41;&nbsp;\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">&#46;952&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-7&#40;PRETEMED&#41;&nbsp;\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">93 &#40;91&#46;2&#37;&#41;&nbsp;\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">53 &#40;86&#46;9&#37;&#41;&nbsp;\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">40 &#40;97&#46;6&#37;&#41;&nbsp;\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">&#46;081&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-Overall-GOLD&nbsp;\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">29 &#40;26&#46;9&#37;&#41;&nbsp;\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">17 &#40;25&#46;8&#37;&#41;&nbsp;\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">12 &#40;28&#46;6&#37;&#41;&nbsp;\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">&#46;748&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-TX-Overall-GesEPOC&nbsp;\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">31 &#40;28&#46;7&#37;&#41;&nbsp;\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">18 &#40;27&#46;3&#37;&#41;&nbsp;\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">13 &#40;31&#37;&#41;&nbsp;\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">&#46;680&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-NIMV &#40;GOLD&#41;&nbsp;\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">31 &#40;60&#46;8&#37;&#41;&nbsp;\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">14 &#40;60&#46;9&#37;&#41;&nbsp;\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">17 &#40;60&#46;8&#37;&#41;&nbsp;\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">&#46;991&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>R-NIMV &#40;GesEPOC&#41;&nbsp;\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">26 &#40;61&#46;9&#37;&#41;&nbsp;\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">9 &#40;56&#46;3&#37;&#41;&nbsp;\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">17 &#40;65&#46;4&#37;&#41;&nbsp;\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">&#46;554&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; SABA&#44; short-acting &#223;2-agonist&#59; SAMA&#44; short-acting muscarinic antagonist&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Description of variables&#58; R-TX-1&#58; use of beta 2-agonist and&#47;or short-acting anticholinergic&#59; R-TX-2&#58; use of antibiotherapy according to the GOLD recommendations&#58; in patients with mechanical ventilation and&#47;or following the Anthonisen criteria based on GOLD&#58; &#40;i&#41; presence of purulent sputum or &#40;ii&#41; increased dyspnea&#44; increased sputum volume&#44; increased sputum purulence or &#40;iii&#41; increased sputum purulence and another cardinal symptom&#59; R-TX-3&#58; use of systemic or inhaled corticosteroids during hospitalization&#59; R-TX-4&#58; use of systemic corticosteroids at dosages equivalent to 40&#8211;60&#8239;mg of prednisone&#47;day for 5&#8211;10 days &#40;the corticosteroids administered during the hospitalization and prescribed at discharge are considered&#41;&#59; R-TX-5&#58; use of antibiotherapy according to the GesEPOC recommendations&#58; &#40;i&#41; provided there is a change in sputum color or &#40;ii&#41; in the moderate to severe exacerbation when&#44; in the absence of purulence&#44; there is increased dyspnea and sputum volume or &#40;iii&#41; in highly severe exacerbations&#44; when the patient requires ventilatory assistance&#59; R-TX-6&#58; use of systemic corticosteroids&#59; R-TX-7&#58; use of LMWHs or anticoagulation in patients with an adjusted PRETEMED risk &#62;4&#59; R-TX-Global-GesEPOC&#58; all treatment recommendations in the GesEPOC guidelines are followed &#40;R-TX-1&#8239;&#43;&#8239;R-TX-4&#8239;&#43;&#8239;R-TX-5&#8239;&#43;&#8239;R-TX-6&#41;&#59; R-TX-Global-GOLD&#58; all treatment recommendations in the GOLD guidelines are followed &#40;R-TX-1&#8239;&#43;&#8239;R-TX-2&#8239;&#43;&#8239;R-TX-3&#8239;&#43;&#8239;R-TX-4&#41;&#59; R-NIMV &#40;GesEPOC&#41;&#58; use of NIMV according to the GOLD indications&#58; respiratory acidosis &#40;pH&#8239;&#60;&#8239;7&#46;35&#41; with hypercapnia &#40;PaCO<span class="elsevierStyleInf">2</span>&#8239;&#62;45&#8239;mm&#8239;Hg&#41;&#59; R-NIMV &#40;GOLD&#41;&#58; use of NIMV according to GOLD indications&#58; &#40;i&#41; respiratory acidosis &#40;arterial pH&#8239;&#8804;&#8239;7&#46;35 and&#47;or PaCO<span class="elsevierStyleInf">2</span> &#8805;6&#46;0&#8239;kPa&#44; 45&#8239;mm&#8239;Hg&#41; or &#40;ii&#41; severe dyspnea and use of accessory muscles&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Bolded <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;&#46;05&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Appropriateness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#91;0&#44;2&#8211;4&#93;Re-admissions</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#91;0&#44;5&#8211;8&#93;Mortality</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \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" scope="col" style="border-bottom: 2px solid black">&#60;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">3&#8211;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#60;1&#8239;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Intrahospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#60;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">3&#8211;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#60;1&#8239;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-1 SABA-SAMA &#40;GOLD&#47;GesEPOC&#41;&nbsp;\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">0&#46;300&nbsp;\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">0&#46;932&nbsp;\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">0&#46;231&nbsp;\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">0&#46;869&nbsp;\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">0&#46;475&nbsp;\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">0&#46;325&nbsp;\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">0&#46;150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-2 Antibiotics &#40;GOLD&#41;&nbsp;\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">0&#46;371&nbsp;\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">0&#46;980&nbsp;\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">0&#46;889&nbsp;\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">0&#46;367&nbsp;\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">0&#46;846&nbsp;\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">0&#46;485&nbsp;\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">0&#46;770&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-3 Corticosteroids &#40;GOLD&#41;&nbsp;\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">0&#46;145&nbsp;\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">0&#46;277&nbsp;\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"><span class="elsevierStyleBold">0&#46;041</span><a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\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">0&#46;004<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\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">0&#46;036<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\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">0&#46;949&nbsp;\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">0&#46;142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-4 Corticosteroids &#40;dose and duration&#41;&nbsp;\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">0&#46;173&nbsp;\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">0&#46;932&nbsp;\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">0&#46;106&nbsp;\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">0&#46;151&nbsp;\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">0&#46;303&nbsp;\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">0&#46;486&nbsp;\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">0&#46;257&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-5 Antibiotic therapy &#40;GesEPOC&#41;&nbsp;\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">0&#46;695&nbsp;\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">0&#46;274&nbsp;\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">0&#46;396&nbsp;\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">0&#46;880&nbsp;\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">0&#46;627&nbsp;\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">0&#46;682&nbsp;\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">0&#46;826&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R-TX-6 Corticosteroids &#40;GesEPOC&#41;&nbsp;\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
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Original language: English
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