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array:23 [ "pii" => "S0210569121002874" "issn" => "02105691" "doi" => "10.1016/j.medin.2021.12.005" "estado" => "S300" "fechaPublicacion" => "2022-08-01" "aid" => "1729" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "copyrightAnyo" => "2021" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2022;46:426-35" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0210569121001182" "issn" => "02105691" "doi" => "10.1016/j.medin.2021.05.013" "estado" => "S300" "fechaPublicacion" => "2022-08-01" "aid" => "1680" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2022;46:436-45" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Prior influenza vaccine is not a risk factor for bacterial coinfection in patients admitted to the ICU due to severe influenza" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "436" "paginaFinal" => "445" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La vacuna previa contra la influenza no es un factor de riesgo de coinfección bacteriana en pacientes ingresados en la UCI por influenza severa" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1487 "Ancho" => 2091 "Tamanyo" => 105985 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Match graph evaluation. 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Claverias, X. Daniel, I. Martín-Loeches, P. Vidal-Cortez, F. Gómez-Bertomeu, S. Trefler, R. Zaragoza, M. Borges-Sa, L.F. Reyes, G. Quindós, J. Peman, M. Bodí, E. Díaz, C. Sarvisé, E. Pico, E. Papiol, J. Solé-Violan, J. Marín-Corral, J.J. Guardiola, A. Rodríguez" "autores" => array:21 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Claverias" "email" => array:1 [ 0 => "lauraclaverias@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "X." "apellidos" => "Daniel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Martín-Loeches" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Vidal-Cortez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "F." "apellidos" => "Gómez-Bertomeu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "S." "apellidos" => "Trefler" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 6 => array:3 [ "nombre" => "R." "apellidos" => "Zaragoza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 7 => array:3 [ "nombre" => "M." "apellidos" => "Borges-Sa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 8 => array:3 [ "nombre" => "L.F." "apellidos" => "Reyes" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 9 => array:3 [ "nombre" => "G." "apellidos" => "Quindós" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 10 => array:3 [ "nombre" => "J." "apellidos" => "Peman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] ] ] 11 => array:3 [ "nombre" => "M." "apellidos" => "Bodí" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] ] ] 12 => array:3 [ "nombre" => "E." "apellidos" => "Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">m</span>" "identificador" => "aff0065" ] ] ] 13 => array:3 [ "nombre" => "C." "apellidos" => "Sarvisé" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 14 => array:3 [ "nombre" => "E." "apellidos" => "Pico" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 15 => array:3 [ "nombre" => "E." "apellidos" => "Papiol" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] ] ] 16 => array:3 [ "nombre" => "J." "apellidos" => "Solé-Violan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] ] ] 17 => array:3 [ "nombre" => "J." "apellidos" => "Marín-Corral" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">p</span>" "identificador" => "aff0080" ] ] ] 18 => array:3 [ "nombre" => "J.J." "apellidos" => "Guardiola" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">q</span>" "identificador" => "aff0085" ] ] ] 19 => array:3 [ "nombre" => "A." "apellidos" => "Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] ] ] 20 => array:2 [ "colaborador" => "on behalf of the GETGAG/SEMICYUC Working Group" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:17 [ 0 => array:3 [ "entidad" => "Critical Care Department, Hospital Universitari Joan XXIII, Tarragona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Institut d’Investigació Sanitaria Pere Virgili, Reus, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Multidisciplinary Intensive Care Research Organization (MICRO), Department of Intensive Care Medicine, St James's University Hospital, Dublin, Ireland" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Critical Care Department, Complejo Hospitalario Universitario Ourense, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Microbiology Department, Hospital Universitari Joan XXIII, Tarragona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Critical Care Department, Hospital Dr Peset, Valencia, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Multidisciplinar Sepsis Unit, Critical Care Department, Hospital Son Llàtzer, Palma de Mallorca, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Infectious Diseases Department, Universidad de La Sabana, Chía, Colombia" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Critical Care Department, Clinica Universidad de La Sabana, Chía, Colombia" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Department of Immunology, Microbiology and Parasitology, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Bilbao, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Institute of Sanitary Investigation La Fe, Hospital Universitari I Politècnic La Fe, Valencia, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Critical Care Department URV/IISPV/CIBERES, Hospital Universitari Joan XXIII Tarragona, Spain" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Critical Care Department, Hospital Parc Taulí, Sabadell, Spain" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Critical Care Department, Hospital Valle Hebrón, Barcelona, Spain" "etiqueta" => "n" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Critical Care Department Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain" "etiqueta" => "o" "identificador" => "aff0075" ] 15 => array:3 [ "entidad" => "Critical Care Department, Hospital del Mar, Barcelona, Spain" "etiqueta" => "p" "identificador" => "aff0080" ] 16 => array:3 [ "entidad" => "Department of Pulmonary, Critical Care and Sleep Medicine, University of Louisville, USA" "etiqueta" => "q" "identificador" => "aff0085" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Impacto del aislamiento de <span class="elsevierStyleItalic">Aspergillus</span> spp. en las primeras 24<span class="elsevierStyleHsp" style=""></span>h de ingreso en pacientes críticos con neumonía grave por el virus influenza" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1071 "Ancho" => 1508 "Tamanyo" => 64238 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Cumulative Cox survival curve according to the presence or absence of PA. ICU LOS: Intensive Care Unit length of stay.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Respiratory infections caused by the influenza virus can develop severe pneumonia and acute respiratory failure requiring Intensive Care Unit (ICU) admission. One of the possible complications of influenza pneumonia is the presence of community-acquired respiratory co-infection (CARC).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Our group reported an incidence of coinfection close to 17%, and it was observed an independent association of CARC and ICU mortality.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In recent years, the incidence of Influenza-Associated Pulmonary Aspergillosis (IAPA) has increased, and currently the reported incidence rates range from 9% to 23%.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2–5</span></a> The appearance of IAPA worsens the prognosis in mechanically ventilated patients, with a mortality rate reported between 50% and 60%.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,3,6</span></a> However, the incidence of IAPA in critically ill patients and the risks factors related to the development of this entity vary among currently available reports, possibly due to the populations considered, the different definitions used, and the diverse active microbiological search strategies carried out.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Knowing the incidence of <span class="elsevierStyleItalic">Aspergillus</span> spp. isolation (AI) in critically ill patients would help to better characterize the affected type of population and therefore to identify the need to initiate early empirical antifungal treatment. In this context, the aims of our study were to determine the incidence and impact on ICU mortality of AI during the first 24<span class="elsevierStyleHsp" style=""></span>h of admission in a large population of critically ill patients admitted due to proven severe influenza infection.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Material and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This is a secondary analysis of an observational and prospective cohort study. Data were obtained from a voluntary registry created by the Spanish Society of Critical Intensive Medicine and Coronary Units (SEMICYUC, Spanish acronym), in which 184 Spanish ICUs participated between June 2009 and June 2019. The study was approved by the Ethics Committee of the Joan XXIII University Hospital (IRB # 11809) and by each of the participating centers. Informed consent was not obtained from the patients given the observational nature of the study, and the anonymity of the data was guaranteed.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">All consecutive patients who required admission to the ICU with a diagnosis of respiratory infection by influenza A H1N1, A seasonal, B or other virus were included during the period described. The presence of the virus was determined by performing a real-time polymerase chain reaction (rt-PCR) at each hospital, according to the recommendations of the Infectious Diseases Society of America (IDSA).<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Only patients with respiratory symptoms were analyzed, either due to pneumonia, exacerbation of asthma or acute exacerbation of chronic obstructive pulmonary disease (COPD). The clinical diagnosis of pneumonia was determined by the current American Thoracic Society (ATS)/IDSA guidelines, including the presence of 2 or more of the following signs and symptoms: fever (>38<span class="elsevierStyleHsp" style=""></span>°C), cough, bronchial expectoration, and myalgia. These manifestations had to be associated with at least one organ failure (respiratory failure, hemodynamic instability, renal failure or sensorial disturbance). Patients under 15 years and those admitted to the ICU for reasons other than respiratory causes were excluded.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Study variables</span><p id="par0030" class="elsevierStylePara elsevierViewall">Demographic data, comorbidities, laboratory and clinical results were collected. We recorded the need for mechanical ventilation and the presence of shock at ICU admission Severity of illness was determined using the Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. Renal Replacement Therapy (RRT) was recorded during ICU stay.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Definitions of Pulmonary Aspergillosis (PA) and microbiological search for isolation of <span class="elsevierStyleItalic">Aspergillus</span> spp. in respiratory samples</span><p id="par0035" class="elsevierStylePara elsevierViewall">PA diagnosis was defined according to criteria modified recently proposed by Verweij et al.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>: Proven PA was defined by lung biopsy showing invasive fungal elements and <span class="elsevierStyleItalic">Aspergillus</span> spp<span class="elsevierStyleItalic">.</span> growth on culture or positive <span class="elsevierStyleItalic">Aspergillus</span> spp<span class="elsevierStyleItalic">.</span> PCR in tissue. Probable PA was defined with pulmonary infiltrate and bronchoalveolar lavage (BAL) culture OR cavitating infiltrate and positive sputum/tracheal aspirate for <span class="elsevierStyleItalic">Aspergillus</span> spp. Possible PA was defined with pulmonary infiltrate and positive tracheal aspirate or mini-BAL culture.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The diagnostic procedures for <span class="elsevierStyleItalic">Aspergillus</span> spp. active search were not standardized and were requested upon the attending physicians’ consideration. No information regarding levels of galactomannan in BAL or serum were recorded in our general registry of patients with severe influenza virus pneumonia. Therefore, we do not have data in this regard.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Objectives</span><p id="par0045" class="elsevierStylePara elsevierViewall">The primary objective of our study was to determine the incidence of AI in respiratory sample within the first 24<span class="elsevierStyleHsp" style=""></span>h of ICU admission. The secondary objectives were to evaluate the general characteristics of critically ill patients with AI<span class="elsevierStyleItalic">,</span> and to determine the risk factors on ICU mortality in patients with influenza infection.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Qualitative variables were expressed as percentages while quantitative variables, as mean and standard deviation (SD) or median and interquartile range 25–75%. In order to determine clinical differences among groups, the Chi-square and Fisher tests were used for categorical variables, and the Student's <span class="elsevierStyleItalic">t</span> or Mann–Withney <span class="elsevierStyleItalic">U</span> test, for quantitative variables.</p><p id="par0055" class="elsevierStylePara elsevierViewall">A multivariate analysis was performed using binary logistic regression (linear analysis) to determine the risk factors for developing AI and to determine the association of variables with ICU mortality. In addition, an automatic and non-linear analysis (Chi-square automatic interaction detection [CHAID]) was performed to determine which variables are most closely related to AI.</p><p id="par0060" class="elsevierStylePara elsevierViewall">A CHAID tree is a graphic representation of a series of decision rules. Beginning with a root node that includes all cases, the tree branches are divided into different child nodes that contain a subgroup of cases. The criterion for branching (or partitioning) is selected after examining all possible values of all available predictive variables. In terminal nodes, a grouping of cases is obtained, in such a way that cases are as homogeneous as possible regarding the dependent variable value.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9,10</span></a> CHAID decision trees are nonparametric procedures that make no assumption of underlying data. This algorithm determines how continuous and/or categorical independent variables best combine in order to predict a binary outcome based on “if-then” logic by portioning each independent variable into mutually exclusive subsets founded on homogeneity of the data. For this study, the response variable is the presence or absence of <span class="elsevierStyleItalic">Aspergillus</span> spp. in respiratory samples.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The statistical analysis and the CHAID tree were performed with the statistical program SPSS 20.0 for Windows (IBM). A value of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 is considered significant.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">General characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 4175 patients were included in the initial registry, from which 216 patients were excluded due to lack of clinical outcome on admission, and also 257 other patients, since they had been included in the database but presented influenza infections other than pneumonia, leaving a total of 3702 patients for the present study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The general characteristics of the population are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Incidence and risk factors for <span class="elsevierStyleItalic">Aspergillus</span> spp. isolation</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Aspergillus</span> spp. was isolated in only in 1.13% (42/3702) of the included patients; among them, 4.8% (2/42) met criteria of proven PA, and the rest, 95.2% (40/42), had probable/possible PA. Given the small number of patients with AI and the smaller number of patients with proven PA, and in order to reach stronger comparisons, we considered all cases as AI.</p><p id="par0080" class="elsevierStylePara elsevierViewall">AI patients presented a higher severity of illness according to APACHE II score upon ICU admission, and a greater need for invasive mechanical ventilation (IMV), and vasoactive drugs (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Among AI patients, 19.0 (8/42) had hospital-acquired influenza infection, and a higher incidence regarding non-AI patients (6.5% [239/3660] <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). Only hematological malignancies (21.4% [9/42] vs 7.1% [263/3660]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) and other immunosuppression (16.6% [7/42] vs 5.3% [186/3660]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) were more frequent in AI patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Patients with <span class="elsevierStyleItalic">Aspergillus</span> isolation showed more days of hospitalization previous ICU admission (median 1 day, IQR 1–2 vs median 2 days, IQR 1–5, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05, respectively) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><p id="par0085" class="elsevierStylePara elsevierViewall">All variables that showed statistical significance in the univariate analysis (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), asthma and COPD were included in the multivariate model due to their clinical importance. Male sex (OR: 2.81, 95% CI: 1.24–6.33), presence of asthma (OR: 4.56, 95% CI: 1.87–11.12), nosocomial-acquired influenza infection (OR: 2.40, 95% CI: 1.03–5.61), hematological malignancies (OR: 4.39, 95% CI: 1.92–10.04), HIV (OR: 3.83, 95% CI: 1.08–13.63), and other immunosuppression (such as chronic corticosteroid treatment or chemotherapy) (OR: 4.87, 95% CI: 1.99–11.87) were factors independently associated with AI (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Risk factors for AI by non-parametric CHAID analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">In the CHAID analysis, AI was the dependent variable and age, sex, APACHE II score on hospital admission, presence of shock, asthma, COPD, chronic renal failure, hematologic disease, human immunodeficiency virus (HIV), other immunosuppression and hospital-acquired influenza infection were included as independent variables. A tree with a maximum depth of 3 branches was generated, with a minimum of 50 cases in the parent node and 9 terminal nodes. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the variable most closely associated with AI followed of other immunosuppression as second branch division (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Risk factors associated with mortality</span><p id="par0095" class="elsevierStylePara elsevierViewall">The crude ICU mortality of our cohort was 21.5% (796/3702). ICU mortality in the AI group of patients was 59.5% (25/42), almost three times than that observed in non-AI patients (21.0% [771/3660]) (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Patients who died were older, had a higher level of severity (determined by APACHE II), and more often required invasive mechanical ventilation and vasoactive drugs on admission compared to survivors (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">All significant variables associated with ICU-mortality (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) were included in the multivariate analysis. Hematological disease (OR: 2.62, 95% CI: 1.95–3.51), immunosuppression (OR: 2.05, 95% CI: 1.46–2.88) and AI (OR: 3.24, 95% CI: 1.60–6.53) were the variables independently associated with ICU mortality. Notably, COPD showed a protective effect (OR: 0.74, 95% CI: 0.59–0.93) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">When adjusted, ICU-survival time was determined by Cox hazard proportional analysis, we observed a significant lower survival in AI patients (HR: 1.53, 95% CI: 1.03–2.38) (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">The main finding of our study is that the incidence of AI in respiratory sample of critically ill patients with severe influenza pneumonia is low in Spain, and it was closely associated with crude ICU mortality. Another interesting finding is that COPD did not appear as a AI associated factor, while hematological disease or other causes of immunosuppression were highly related with AI development.</p><p id="par0115" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first study to asses the incidence and impact of AI in patients with severe influenza pneumonia within the first 24<span class="elsevierStyleHsp" style=""></span>h of ICU admission. Other studies have evaluated the <span class="elsevierStyleItalic">Aspergillus</span> incidence in an ICU evolution period. This difference makes it difficult to compare between studies. However, given the impact of our results, we believe it is important to highlight some considerations of clinical relevancy.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In our study, AI incidence is notably lower regarding the incidence of IAPA reported by other authors in other countries.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3–5</span></a> The association between pulmonary aspergillosis (PA) and influenza infection or other respiratory viruses has been described previously.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11–14</span></a> This association can respond to various factors. Viral infections directly injure the epithelium of the bronchial mucosa,<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11,12</span></a> facilitating the invasion by fungi present in the respiratory tract. Furthermore, influenza infection alters cytokines levels at both pulmonary and systemic levels, and the function of pulmonary macrophages and T-lymphocytes, producing a certain degree of immunodeficiency that favors <span class="elsevierStyleItalic">Aspergillus</span> spp. infection.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13,14</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The association between PA and viral infection is frequent in immunosuppressed patients. In a cohort of 219 patients receiving an allogeneic transplant,<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> viral respiratory tract infection was shown to be a risk factor for the development of PA (HR: 4.3, 95% CI: 2–9.4). García-Vidal et al.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> reported an 8.8% incidence of IAPA in 57 immunosuppressed patients admitted to hospital due to influenza A(H1N1)pdm09 virus infection during the 2009 pandemic. The same author<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> reported an association between influenza virus infection (HR: 2.5, 95% CI: 1.1–5.8) and parainfluenza (HR: 2.6, 95% CI: 1.6–4.3) with invasive infection by filamentous fungi. However, in critically ill patients IAPA incidence and risk factors are uncertain and highly variable.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17–19</span></a> The low incidence of AI in our population (1.1%) differs from that published in other series. Wauters et al.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> observed a 23% incidence of PA in a cohort of 40 patients with influenza A(H1N1)pdm09 infection. The Dutch/Belgian mycosis study group has recently published<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> an incidence of 19% of IAPA in patients with influenza A(H1N1) virus infection, clearly higher than the 5% observed in the control group of patients admitted for bacterial community-acquired pneumonia. Finally, this group also found a higher incidence of PA within the influenza cohort group of immunocompromised patients versus non-immunocompromised patients (32% vs 14%). These differences with respect to our results may be related to the characteristics of the studied populations, especially regarding the frequency of immunosuppressed patients, as well as the implemented diagnostic methods and the observation period. The determination of galactomannan in BAL, used in some studies<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> for aspergillosis diagnosis, is a rarely used technique (<20%) in invasive mechanically ventilated patients with community-acquired pneumonia <a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>. The importance of immunosuppression in patients with hematological disease as a risk to AI has been confirmed by our automatic CHAID analysis; this relation was described by Vanderbeke et al.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> in a recent review. In this regard, the GLIMP study,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> a multicentric, international, observational point-prevalence study for patients hospitalized due to community-acquired pneumonia, reported that <span class="elsevierStyleItalic">Aspergillus</span><span class="elsevierStyleItalic">fumigatus</span> as the causative pathogen was found more frequently in immunocompromised patients (8 [1.3%] vs 10 [0.4%]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01) and that AIDS (OR: 15.10, 95% CI: 6.36–35.88) and hematological cancer (OR: 4.65, 95% CI: 1.85–11.69) were independent risk factors for <span class="elsevierStyleItalic">A.</span><span class="elsevierStyleItalic">fumigatus</span>.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Male sex, asthma, nosocomial-acquired influenza infection, and immunosuppression were the variables associated with the risk of presenting AI in our cohort of critically ill patients. The relationship between pulmonary disease (e.g., asthma and COPD) and PA has been previously studied. It has been proposed that either the chronic inflammatory disease itself or its management, including chronic corticosteroids treatment and broad-spectrum antibiotic therapy, could be the factors which explain this association.<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">24,25</span></a> Notably, COPD was correlated with a lower risk of AI in our study. In a similar line, Schauwvlieghe et al.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> found that COPD was not an independent risk factor for IAPA (OR: 1.10, 95% CI: 0.53–2.26, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.80). Several studies describe COPD as a risk factor for aspergillosis, especially in patients receiving chronic corticosteroid treatment.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19,26–29</span></a> In our population, the proportion of patients with COPD was similar in the group with and without AI, and within COPD patients, the use of corticosteroids was similar in patients with and without aspergillosis (1.8% vs 1.5% respectively, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.8, data not shown).</p><p id="par0135" class="elsevierStylePara elsevierViewall">The association observed between nosocomial-acquired influenza and AI could be explained by the increased risk of hospitalized patients to acquire influenza as an expression of a subclinical condition of impaired immunity or immuno-paralysis associated with the serious processes that led to hospitalization, something that facilitates the development of opportunistic infections.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> In this regard, patients with AI were admitted in the ICU with a higher median of hospital days previous admission than patients without AI, but these differences were no significant in the multivariate analysis.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Finally, AI patients presented three times greater ICU-mortality than those in whom AI was not present (59% vs 21%). This high mortality coincides with the one published by Schauwvlieghe et al.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> with a mortality of 45% in patients with aspergillosis compared to 20% in the rest of the cohort patients, and with the study published by Vanderbeke et al.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> who observed a mortality of 57% in patients with aspergillosis and influenza infection.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The main strength of our study is that it is a homogeneous, multicenter cohort with a numerous number of critically ill patients with confirmed influenza infection, which allows the results to be generalizable. Nonetheless, we must recognize several limitations. First, it was a secondary analysis of an observational study, and although patients have been included consecutively, we cannot rule out possible biases in reporting the cases; yet, the high number of patients and the rigorous statistical analysis performed minimize these risks and make the results generalizable. Another major limitation is the fact that we cannot confirm proven PA diagnosis in most of our patients because we only have microbiological isolation and imaging tests; furthermore, we do not have information about in how many of our patients a bronchoscopy had been performed and diagnosis was made by BAL. In this way, there is the possibility that “colonized” patients may have been included. However, the low incidence of AI and high associated mortality make this scenario unlikely. Moreover, these are real-world data, because this is what clinician do during the current clinical practice, which makes our results very important for patient care and clinical practice. Another limitation could be related to the low number of patients with AI included. Despite this, the observed differences in mortality have achieved significance with a post-hoc calculated statistical power of 89%. Finally, it is possible that the low incidence observed is due to the lack of an active search investigation through the determination of galactomannan in BAL. Although we cannot rule out this possibility, this technique is not available in all hospitals in Spain.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conclusions</span><p id="par0150" class="elsevierStylePara elsevierViewall">Due to the low incidence of AI in our population of critically ill patients with influenza infection, the extensive use of empirical antifungal treatment in all patients may not be justified. In moderate-high risk patients, the active search for <span class="elsevierStyleItalic">Aspergillus</span> spp. should be systematically implemented.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">This research received no external funding. This study was supported by the Spanish Intensive Care Society (<span class="elsevierStyleGrantSponsor" id="gs1">SEMICYUC</span>) and <span class="elsevierStyleGrantSponsor" id="gs2">Ricardo Barri Casanovas Foundation</span> (Alejandro Rodríguez). The study sponsors have no role in the study design, data collection, data analysis, data interpretation, or writing of the report.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Author contributions</span><p id="par0160" class="elsevierStylePara elsevierViewall">L.C., X.D., I.M.-L., M.B., L.F.R. and A.R. designed the study, design of statistical analyses, and data analysis. All authors except G.Q., J.P, L.F.R. and J.J.G. contributed to the patient's data for the general database. L.C., X.D., I,M-L., M.B., F.G.-B., C.S., E.P., E.D., S.T., J.P., G.Q., J.M-C., L.F.R., J.S.-V., M.B-S., R.Z., J.J.G.., A.R. contributed to critical examination of the paper for important intellectual content and approval of the final manuscript. All authors have read and agreed to the published version of the manuscript.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1747577" "titulo" => "Abstract" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Interventions" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Main variables of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1539499" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1747576" "titulo" => "Resumen" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Pacientes" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Intervenciones" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Variables principales" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1539498" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study variables" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Definitions of Pulmonary Aspergillosis (PA) and microbiological search for isolation of Aspergillus spp. in respiratory samples" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Objectives" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "General characteristics" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Incidence and risk factors for Aspergillus spp. isolation" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Risk factors for AI by non-parametric CHAID analysis" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Risk factors associated with mortality" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Author contributions" ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflicts of interest" ] 12 => array:2 [ "identificador" => "xack617163" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-09-20" "fechaAceptado" => "2021-12-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1539499" "palabras" => array:5 [ 0 => "Influenza" 1 => "IAPA" 2 => "Aspergillosis" 3 => "Critically ill" 4 => "Immunosupression" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1539498" "palabras" => array:5 [ 0 => "Influenza" 1 => "IAPA" 2 => "Aspergilosis" 3 => "Enfermo crítico" 4 => "Inmunosupresión" ] ] ] ] "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="spar0005" class="elsevierStyleSimplePara elsevierViewall">To determine the incidence and impact of <span class="elsevierStyleItalic">Aspergillus</span> spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24<span class="elsevierStyleHsp" style=""></span>h of admission.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Secondary analysis of an observational and prospective cohort study.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Setting</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patients</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Interventions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">None.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Main variables of interest</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">3702 patients were analyzed in this study. AI incidence was 1.13% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>42). Hematological malignancies (OR 4.39, 95% CI 1.92–10.04); HIV (OR 3.83, 95% CI 1.08–13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99–11.87) were factors independently associated with the presence of <span class="elsevierStyleItalic">Aspergillus</span> spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95–3.51), immunosuppression (OR 2.05 95% CI 1.46–2.88) and AI (OR 3.24, 95% CI 1.60–6.53) were variables independently associated with ICU mortality.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for <span class="elsevierStyleItalic">Aspergillus</span> spp. should be implemented.</p></span>" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Interventions" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Main variables of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Determinar la incidencia y el impacto sobre la mortalidad del aislamiento de <span class="elsevierStyleItalic">Aspergillus</span> spp. (AI) en paciente críticos con neumonía por influenza en las primeras 24<span class="elsevierStyleHsp" style=""></span>h de ingreso.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Diseño</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Análisis secundario de estudio de cohortes observacional y prospectivo.</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ámbito</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Unidades de cuidados intensivos (UCI) participantes de forma voluntaria en el registro español de neumonía por influenza grave, desde junio de 2009 hasta junio de 2019.</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Pacientes consecutivos con diagnóstico de neumonía grave por influenza, confirmado por prueba de reacción en cadena de la polimerasa.</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intervenciones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Ninguna.</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variables principales</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Incidencia de AI<span class="elsevierStyleItalic">.</span> Variables demográficas, comorbilidades, necesidad de ventilación mecánica y presencia de <span class="elsevierStyleItalic">shock</span> al ingreso. APACHE II.</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Se analizaron 3.702 pacientes. La incidencia de AI fue del 1,13% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>42). Las neoplasias hematológicas (OR: 4,39; IC 95%: 1,92-10,04); VIH (OR: 3,83; IC 95%: 1,08-13,63) y otras situaciones de inmunosupresión (OR: 4,87; IC 95%: 1,99-11,87) fueron variables que se asociaron de forma independiente con AI. El árbol de decisión de CHAID mostró que la variable neoplasias hematológicas era la más relacionada con la variable <span class="elsevierStyleItalic">Aspergillus</span> spp. con una incidencia del 3,3%. Neoplasias hematológicas (OR: 2,62; IC 95%: 1,95-3,51), inmunosupresión (OR: 2,05; IC 95%: 1,46-2,88) y AI (OR: 3,24; IC 95%: 1,60-6,53) se asociaron de forma independiente con mayor mortalidad en la UCI.</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">El tratamiento antifúngico empírico en nuestra población estaría justificado en los pacientes con inmunosupresión. En los pacientes con riesgo moderado-grave, la búsqueda activa de <span class="elsevierStyleItalic">Aspergillus</span> spp. debería implementarse.</p></span>" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Pacientes" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Intervenciones" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Variables principales" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">The list of researchers of the GETGAG/SEMICYUC Working Group can be consulted in the supplementary material to this article.</p>" "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0180" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0095" ] ] ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2722 "Ancho" => 2175 "Tamanyo" => 188120 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Flow chart. Overview of inclusion process.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1572 "Ancho" => 2750 "Tamanyo" => 223937 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Risk factors of PA. ID: immunosuppression; HIV: human immunodeficiency virus; COPD: chronic obstructive pulmonary disease; APACHE: acute physiology and chronic health evaluation.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2533 "Ancho" => 2925 "Tamanyo" => 443370 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Tree created by the CHAID model.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1489 "Ancho" => 2508 "Tamanyo" => 208238 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Variables associated with mortality in the multivariate analysis.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1071 "Ancho" => 1508 "Tamanyo" => 64238 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Cumulative Cox survival curve according to the presence or absence of PA. ICU LOS: Intensive Care Unit length of stay.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">AI: <span class="elsevierStyleItalic">Aspergillus</span> spp. isolation; APACHE II: acute physiology and chronic health evaluation II; RRT: renal replacement techniques; CRP: C-reactive protein; PCT: procalcitonin; COPD: chronic obstructive pulmonary disease; CHF: congestive heart failure; NMD: neuromuscular disease; HIV: human immunodeficiency virus; IS: immunosuppression; ICU: Intensive Care Unit; SD: standard deviation; IQR: interquartile range.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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">Variables \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">Total <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3702 \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">Non-AI patients <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3660 \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">IA patients <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>42 \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> value \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"><span class="elsevierStyleItalic">Age, years – mean (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.8 (15.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.7 (15.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.6 (13.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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="elsevierStyleItalic">Sex, male – n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2203 (59.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2170 (59.3) \t\t\t\t\t\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">33 (78.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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="elsevierStyleItalic">APACHE II – mean (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.0 (7.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.9 (7.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.4 (7.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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="elsevierStyleItalic">Mechanical ventilation – n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2936 (79.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2984 (79.1) \t\t\t\t\t\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 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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="elsevierStyleItalic">Vasoactive drugs – n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1899 (51.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1868 (51) \t\t\t\t\t\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 (74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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="elsevierStyleItalic">RRT – n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">375 (10.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">368 (10.1) \t\t\t\t\t\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 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.19 \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="elsevierStyleItalic">CRP, mg/dl – mean (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (13.7–100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.0 (13.2–100) \t\t\t\t\t\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">35.5 (19.6–186) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 \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="elsevierStyleItalic">PCT, ng/ml – median (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.7 (0.2–4.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.7 (0.2–4.3) \t\t\t\t\t\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">1.6 (0.5–4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 \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="elsevierStyleItalic">Nosocomial influenza – n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">247 (6.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">239 (6.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Type of influenza virus – n (%)</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>A H1N1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2620 (70.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2590 (70.8) \t\t\t\t\t\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">30 (71.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.92 \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>A seasonal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">764 (20.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">756 (20.6) \t\t\t\t\t\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">8 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.79 \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>B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">283 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">279 (7.6) \t\t\t\t\t\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 (9.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.64 \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>Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 (0.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 (1) \t\t\t\t\t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Comorbidities – n (%)</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>Asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">367 (9.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">360 (9.8) \t\t\t\t\t\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 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.18 \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>COPD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">908(24.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">894 (24.4) \t\t\t\t\t\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(33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.20 \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>CHF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">447 (12.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">442 (12.1) \t\t\t\t\t\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 (12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-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>CRD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">314 (8.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">308 (8.4) \t\t\t\t\t\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">6 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 \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>Pregnancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">460 (12.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">458 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 \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>Obesity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1178 (31.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1165 (31.8) \t\t\t\t\t\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 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-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>NMD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106 (2.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106 (2.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \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>Autoimmune disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">149 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">147 (4.0) \t\t\t\t\t\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 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.68 \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>HIV positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83 (2.3) \t\t\t\t\t\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 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 \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>Hematological disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">272 (7.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">263 (7.2) \t\t\t\t\t\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">9 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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>Other IS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">193 (5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">186 (5.1) \t\t\t\t\t\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 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-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="elsevierStyleItalic">Days until ICU admission, days – median (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1–2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1–2) \t\t\t\t\t\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 (1–5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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="elsevierStyleItalic">ICU LOS, days – median (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (4–19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (4–18) \t\t\t\t\t\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">14.5 (6–22.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.17 \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="elsevierStyleItalic">Hospital LOS, days – median (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (10–29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (10–29) \t\t\t\t\t\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">21.5 (10.8–30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.42 \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="elsevierStyleItalic">Mortality – n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">796 (21.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">771 (21.1) \t\t\t\t\t\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">25 (59.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">General characteristics of the population.</p>" ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">SD: standard deviation; APACHE: acute physiologic and chronic health evaluation; AI: <span class="elsevierStyleItalic">Aspergillus</span> spp. isolation; COPD: chronic obstructive pulmonary disease; CHF: chronic heart failure; CRF: chronic renal failure; HIV: human immunodeficiency virus; IS: immunosuppression.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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">Survivors<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2906 \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">Non-survivors<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>796 \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> value \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">Age, years – median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.8 (15.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.3 (15.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">Sex, male – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1691 (58.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">512 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">APACHE II – median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.7 (7.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.5 (8.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">Mechanical ventilation – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2173 (74.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">763 (95.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">Vasoactive drugs – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1276 (43.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">623 (78.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">Nosocomial influenza – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">165 (5.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (10.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">AI – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">COPD – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">747 (24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">191 (22.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.4 \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">Asthma – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">327 (10.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (6.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">CHF – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">390 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">141 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">CRF – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">242 (7.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">113 (13.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">HIV – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 (1.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (3.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">Hematological disease – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">161 (5.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">126 (14.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \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">Other IS – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">135 (4.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 (9.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the population depending on mortality.</p>" ] ] 7 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 119612 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased incidence of co-infection in critically ill patients with influenza" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Martin-Loeches" 1 => "J. Schultz" 2 => "M. Vincent" 3 => "J.L. Alvarez-Lerma" 4 => "F. Bos" 5 => "L.D.J. Solé-Violán" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-016-4578-y" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2017" "volumen" => "43" "paginaInicial" => "48" "paginaFinal" => "58" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27709265" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0160" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influenza-associated aspergillosis in critically ill patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.L. Van De Veerdonk" 1 => "E. Kolwijck" 2 => "P.P.A. Lestrade" 3 => "C.J. Hodiamont" 4 => "B.J.A. Rijnders" 5 => "J. Van Paassen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2017" "volumen" => "196" "paginaInicial" => "524" "paginaFinal" => "527" "itemHostRev" => array:3 [ "pii" => "S0140673620306279" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0165" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.F.A.D. Schauwvlieghe" 1 => "B.J.A. Rijnders" 2 => "N. Philips" 3 => "R. Verwijs" 4 => "L. Vanderbeke" 5 => "C. Van Tienen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(18)30274-1" "Revista" => array:6 [ "tituloSerie" => "Lancet Respir Med" "fecha" => "2018" "volumen" => "6" "paginaInicial" => "782" "paginaFinal" => "792" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30076119" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0170" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Invasive aspergillosis complicating pandemic influenza A (H1N1) infection in severely immunocompromised patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Garcia-Vidal" 1 => "P. Barba" 2 => "M. Arnan" 3 => "A. Moreno" 4 => "I. Ruiz-Camps" 5 => "C. 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