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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Severe sepsis and septic shock are major healthcare problems worldwide, with high mortality and increasing incidence. Before the start of the Surviving Sepsis Campaign (SSC) in 2002, in the USA, there were 300 cases of severe sepsis per 100,000 population and 2.26 cases per 100 hospital discharges; half of those received intensive care. The overall rate of sepsis mortality was 28.6%; mortality increased with age, from 10% in children to 38.4% in those &#62;85 years old. At an average cost of $22,100 per case, the total annual cost was $16.7 billion. The incidence was projected to increase by 1.5% per year.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> An epidemiological study in Spain, that analyzed the 2006&#8211;2011 National Hospital Discharge Registry, reported that overall incidence per year of severe sepsis was 86.97 cases per 100,000 population (increasing from 63.91 cases/100,000 population in 2006 to 105.51 cases/100,000 population in 2011) representing 1.1% of all hospitalisations and 54% of hospitalisations with sepsis. The overall mortality rate during the study period was 37.1 cases per 100,000 population with a significant decrease in mortality rates with an overall annual percent change of &#8722;3.24%,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a> the incidence of severe sepsis attended in the Spanish ICU was 12.4% with high ICU and hospital mortality rates (48.2 and 54.3% respectively),<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">3</span></a> with treatment costing around 500 million euros annually.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the past decade many studies have demonstrated improved survival in septic patients with early administration of appropriate antibiotics,<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">5&#8211;8</span></a> lactate levels measurements,<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">9</span></a> early goal-directed hemodynamic resuscitation,<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a> management with replacement doses of corticosteroids,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> glycemic control,<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a> drotrecogin alfa (activated) administration,<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">13</span></a> and protective mechanical ventilation.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> These therapeutic advances were collected in the first Surviving Sepsis Campaign (SSC) guidelines<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">15,16</span></a> with the intention to reduce sepsis mortality by 25% in five years. The progressive implementation of these recommendations achieved a progressive fall in mortality.<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17,18</span></a> An Spanish study showed that compliance with the resuscitation bundle is associated with improvement in survival in patients with severe sepsis/septic shock,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> also, in 2010, a meta-analysis of all studies comparing outcomes in patients who received bundled care vs. non protocolized care demonstrated a clear association between the use of bundles and lower mortality,<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a> even though most of the original recommendations in bundled care were changed after randomized controlled trials failed to confirm the efficacy of specific sepsis treatments (most of which conform the management bundle),<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">21&#8211;26</span></a> as is reflected in the recently updated SSC guidelines.<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">27,28</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Two recent studies concluded that there has been a secular decrease in severe sepsis mortality. One study analyzed patients pooled from the control groups of 36 randomized controlled trials investigating severe sepsis and compared the 28-day mortality with patients in the administrative Nationwide Inpatient Sample database.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a> The other study analyzed hospital mortality due to severe sepsis from a large database of patients in Australian and New Zealand intensive care units (ICU).<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">30</span></a> Both studies found 1&#8211;3% annual improvement in crude severe sepsis mortality. The mechanism underlying this decline is unclear, but is probably related to improved processes of care.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The Edusepsis study evaluated the impact of a nationwide quality improvement intervention in Spain based on the SSC guidelines, showing an improvement in compliance with treatment recommendations accompanied by a reduction in mortality.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> However, not all the effects of the intervention were sustained; for example, early use of antibiotics decreased in the long-term follow-up. This is especially relevant considering an analysis of the impact of individual components of the resuscitation bundle on mortality in the Edusepsis study found that early empirical antibiotic administration was the most important factor.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">4</span></a> As in other time-dependent pathologies, in sepsis the timeliness and appropriateness of treatments administered in the first hour after the onset of disease can influence outcomes. For all these reasons, a new study was designed to focus specifically on educational interventions about early administration of empirical antibiotics in severe sepsis and septic shock (ABISS-Edusepsis study). Both the original Edusepsis study and the ABISS-Edusepsis study employed a &#8220;control group&#8221; documented before the educational interventions.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The primary objective of the study was to analyze the evolution of sepsis-related mortality in Spanish ICUs since the introduction of the Surviving Sepsis Campaing (SSC) guidelines and the relationship with the improvement of sepsis process-of-care. The secondary objective was to analyze the evolution of sepsis process-of-care by using the sepsis resuscitation bundle.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Design</span><p id="par0030" class="elsevierStylePara elsevierViewall">We designed a cohort study to compare two groups of patients with severe sepsis or septic shock treated in Spanish ICUs during two time periods: the first group (data collected between November and December 2005) was the pre-intervention group in the Edusepsis study, and the second group (data collected between April and June 2011) was the pre-intervention group in the ABISS-Edusepsis study (an ongoing study, in the data analysis phase. <a href="http://www.edusepsis.org/en/abiss-edusepsis.html">http://www.edusepsis.org/en/abiss-edusepsis.html</a>). Only data from ICUs that participated in both studies were included in the present study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Patients and process-of-care and outcome measurements</span><p id="par0035" class="elsevierStylePara elsevierViewall">We used the same inclusion-exclusion criteria and definitions of severe sepsis/septic shock, acute organ dysfunction, and onset of sepsis (time zero) as in the two Edusepsis studies.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">5,31</span></a> Briefly, in both studies, all ICU admissions from the emergency department or from wards and all ICU patients were actively screened daily for severe sepsis or septic shock. Time zero was determined according to the patient&#39;s location within the hospital when sepsis was diagnosed. Researchers recorded data related to ten items (tasks or targets), grouped in the sepsis resuscitation bundle (6 items that should begin immediately and be accomplished within 6<span class="elsevierStyleHsp" style=""></span>h of time zero: lactate measurement, fluids and vasopressors, blood extraction for cultures, administration of broad spectrum antibiotics, achievement of central venous pressure &#8805;8<span class="elsevierStyleHsp" style=""></span>mmHg, and achievement of central venous oxygen saturation &#8805;70%).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Bundle compliance and clinical outcome</span><p id="par0040" class="elsevierStylePara elsevierViewall">The primary outcome measure was hospital mortality and compliance with the individual items of the resuscitation bundle in the established time frames. Compliance was defined as evidence that bundle tasks were done and targets were achieved within the indicated time frame. Secondary outcome measures included 28-day mortality, hospital length of stay, and ICU length of stay.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Descriptive statistics included frequencies and percentages for categorical variables and means, standard deviations, medians, and interquartile ranges for continuous variables. To compare categorical variables between the two study periods, we used chi-square analysis. To compare continuous variables during the two study periods, we used Student&#39;s <span class="elsevierStyleItalic">t</span>-test or the Mann&#8211;Whitney test, as appropriate. We constructed 3 multivariate logistic regression models, with hospital mortality as the dependent variable:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Model I was constructed to assess the protective effect of bundles and includes as independent variables: resuscitation bundle, APACHE II score, age, patient location at sepsis diagnosis, site of infection, and baseline acute organ dysfunctions.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Model II was constructed to assess the difference in mortality between the two study periods adjusted by APACHE II score, age, patient location at sepsis diagnosis, site of infection and baseline acute organ dysfunctions.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Model III was constructed to assess the potential role of bundle compliance in the reduction of the adjusted mortality and includes the same independent variables than Model II adding the resuscitation bundle.</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">Statistical tests were two-tailed and significance was set at 0.05. We used SPSS version 17.0 (SPSS, Chicago, IL, USA) for all analyses.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Ethics committee approval</span><p id="par0070" class="elsevierStylePara elsevierViewall">Each participating centers&#8217; research and ethical review boards approved the study and patients remained anonymous. The need for informed consent was waived in view of the observational and anonymous nature of the study.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">Data from the 41 ICUs participating in both studies were included. All ICUs were medical-surgical and most (86%) were in teaching hospitals training residents. No patients were excluded.</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Patient characteristics</span><p id="par0080" class="elsevierStylePara elsevierViewall">In the two periods, 1348 patients fulfilled criteria for severe sepsis or septic shock (630 patients in the 2005 group and 718 in the 2011 group). Patients in the 2011 group were older and more severely ill. In 2005, sepsis was diagnosed predominantly in the ward, whereas in 2011 sepsis was diagnosed predominantly in the emergency department. Pneumonia was most common infection in 2005 while acute abdominal infection was the predominant infection in 2011. More than 80% of patients in both periods had septic shock. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows patient characteristics in the two periods.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Outcome indicators</span><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> reports the outcome data. Patients in the 2011 group had lower hospital mortality (32.6% vs. 44.0%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0.001) and 28-day mortality (23.0% vs. 36.5%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0.001). No differences were observed in the ICU stay in the surviving populations, but the mean hospital stay was higher in the 2011 group (28.1<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>22.9 vs. 33.9<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>34.2 days; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Change in compliance with bundle items over time</span><p id="par0090" class="elsevierStylePara elsevierViewall">Rates of compliance with resuscitation bundle items increased between the two periods. Compliance with the resuscitation bundle increased from 5.7% in the 2005 group to 9.9% in the 2011 group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.005). <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows compliance with the items in the resuscitation bundle. In 2005, the only two items in the resuscitation bundle for which compliance was higher than 50% were blood extraction for cultures before antibiotic administration (54.8%) and early administration of broad spectrum antibiotics (68.3%); compliance with these two items was similar in 2011. Compliance with the other 4 items was lower than 50% in 2005 and improved significantly in 2011.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Multivariate logistic regression</span><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> (Model I) showed, after to adjust for possible confounders, that compliance with the resuscitation bundle are both associated with lower mortality. In addition, the diagnosis of sepsis when the patient is located at ward or at ICU was independently associated with an increase in hospital mortality compared with sepsis identification in the Emergency Department. Two sites of infection (urinary-tract and soft-tissue) were associated to lower mortality than pneumonia, and two baseline acute organ dysfunctions (respiratory and trombocytopenia) were associated to higher mortality.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">After adjusting for possible confounders (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>, Model II), the 2011 cohort was independently associated with lower hospital mortality (OR 0.64 [0.49&#8211;0.83], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003). When we included in the previous model the compliance with the resuscitation bundle (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>, Model III), the 2011 cohort kept a significant lower adjusted mortality (OR 0.64 [0.531&#8211;0.95], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.021).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">We assessed whether sepsis-related mortality in Spanish ICUs has decreased since the introduction of the Surviving Sepsis Campaign (SSC) guidelines and whether decreases are attributable to bundle compliances and other improvements in sepsis care. We found that compliance with the 6-h and 24-h bundles improved and that 28-day and hospital mortality decreased in this 6 years period, suggesting a sustained effect of the SSC moreover, this reduction in hospital mortality remained significant after adjustments. We also found that compliance with the resuscitation bundle are independent protective factors for mortality. Our results are consistent with recent clinical trials, where the mortality due to septic shock was around 24&#8211;26%,<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a> and with epidemiological studies that show a declining trend in severe sepsis mortality over time.<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">2,33</span></a> We found that 28-day mortality and hospital mortality decreased despite an increase in predicted mortality as evidenced by higher APACHE II scores; these results corroborate those reported in Stevensons et al.&#8217;s<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a> meta-analysis and Kaukonen et al.&#8217;s<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">30</span></a> large epidemiological study. A recently published study of a collaborative change intervention aimed at facilitating adoption of SCC bundles in 218 hospitals over 7.5 years found compliance improved over time and increased compliance is associated with decreased mortality.<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The dramatic decrease in sepsis mortality between 2011 and 2005 probably is multifactorial. Increased bundled care is playing a role but the lack of change in adjusted mortality between Model II and III is suggesting that other uncontrolled factors are also important. Probably, implementing the SSC guidelines beginning in 2005 resulted in earlier diagnosis (reflected in the increased proportion of sepsis diagnosed in the emergency department), and lower treatment variability both among clinicians and within clinicians between patients.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">35</span></a> According to Kaukonen et al.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">30</span></a> perhaps there are other reasons we have not controlled in our study (better source control, more adequate empirical antibiotic therapy, earlier transfer to ICU, better overall management of the septic patient, dissemination of protocols, greater expertise of health workers, increased sensitivity for this disease, greater involvement of health institutions, etc.), that also affect the drop in mortality over time. In addition, in a recently published study<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">36</span></a> was described a number of factors associated with in-hospital mortality among patients with severe sepsis or septic shock (age, active cancer, diabetes, DNR status on ED arrival, lack of fever, hypoglycemia, and intubation) despite receipt of early protocolized resuscitation in the ED, providing insights into aspects of early sepsis care that can be targets for future intervention.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Most process-of-care indicators improved over time, but compliance with two recommended tasks (acquiring blood cultures before antibiotic administration and broad-spectrum antibiotics administration before 3<span class="elsevierStyleHsp" style=""></span>h) did not change. In the 2005 group, these were the two items in the resuscitation bundle with the highest compliance (54.8% and 68.3%, respectively), improved compliance with these tasks should have an important impact on mortality.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">9,13</span></a> Miller et al.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">35</span></a> underlined the importance of these early interventions when they reported that compliance with early resuscitation bundle items was associated with a lower probability of being eligible for later resuscitation and maintenance bundle items, probably reflecting lesser severity due to the improvements brought about by the early treatments.</p><p id="par0120" class="elsevierStylePara elsevierViewall">A recent multicenter cohort study conducted in Holland<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">37</span></a> showed that the implementation of a national program sepsis resulted in improved adherence to sepsis bundles in severe sepsis and septic shock patients and was associated with reduced adjusted in-hospital mortality only in participating ICUs, suggesting direct impact of sepsis screening and application bundle on in-hospital mortality. Our study demonstrated improvements in hemodynamic resuscitation over time. However, recent trials in patients with septic shock failed to demonstrate any benefit of protocolized resuscitation when compared with &#8220;usual care&#8221;.<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">38&#8211;41</span></a> Although no consensus exists among clinicians regarding optimal hemodynamic monitoring and to date no method has proven superior, the &#8220;usual care&#8221; in these trials includes early identification of septic patients, early antibiotic treatment, and early volume resuscitation measures. The improvement in hemodynamic resuscitation between the two periods in our study is probably due to earlier resuscitation more than greater protocolized resuscitation. One of the most important changes between the two periods was the place where sepsis was diagnosed. The proportion of cases diagnosed in the emergency department increased from 42.5% in 2005 to 72.3% in 2011, and the proportion of cases diagnosed in the wards decreased from 44.1% in 2005 to 22% in 2011. These findings indicate earlier detection of sepsis and hence earlier initiation of treatment. Importantly, in the above-mentioned studies<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">38&#8211;41</span></a> comparing &#8220;usual care&#8221; with protocolized resuscitation, all cases of septic shock benefited from early detection and initiation of treatment, so perhaps earlier diagnosis and treatment rather than differences in how treatment is administered is what determines prognosis. We agree with Levy<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">42</span></a> that the priority should be to establish systems to identify and treat septic patients early.</p><p id="par0125" class="elsevierStylePara elsevierViewall">On the other side, there are several differences between the 2 cohorts: the 2011 group had a higher rate of urinary tract infection and lower rate of respiratory dysfunction (associated to lower mortality), but also those patients were older and had higher APACHE II score (associated to higher mortality); we cannot discard that, despite the adjustments, those differences in the case-mix also influences the difference in mortality.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our study shows several limitations, the participation in both studies was entirely voluntary, and the hospitals that participated are not necessarily representative of those that did not participate; therefore, our findings may not be generalizable. The length of study periods, its nonrandomized design and the lack of control group precludes establishing a causal connection between the improvements in process-of-care variables and outcomes. Thus, although we observed a better compliance with most of the resuscitation bundle in 2011, related with a decrease in mortality, these findings do not necessarily imply a causal relationship between the compliance with sepsis bundles and outcomes.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Moreover, our study was limited to patients admitted to the ICU, and we cannot know how possible improvement in process-of-care variables in other areas of the hospital affected outcomes.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Finally, the latest SSC guidelines reflect some changes in the standard of care at the time of our study, such as the use of hydroxyethyl starch or drotrecogin alfa (activated). Considering these changes actually strengthens conclusions drawn from our results.</p><p id="par0145" class="elsevierStylePara elsevierViewall">In conclusion, the mortality related to severe sepsis/septic shock in Spain, between two cohorts of patients in 2005 and 2011, decreased dramatically attributable to earliness and improvements in sepsis care, including higher compliance with resuscitation bundle. Nevertheless, compliance with some important items of the resuscitation bundle have not improved enough; early administration of effective antimicrobials could further improve outcomes.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Authors&#8217; contributions</span><p id="par0150" class="elsevierStylePara elsevierViewall">Baltasar S&aacute;nchez: data analysis, drafted, translated and corrected the manuscript.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Ricard Ferrer: national coordinator, study design, data analysis, drafted, translated and corrected the manuscript.</p><p id="par0160" class="elsevierStylePara elsevierViewall">David Su&aacute;rez: database development, data analysis, corrected the manuscript.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Eduardo Romay: data collection, corrected the manuscript.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Enrique Piacentini: site coordinator, data collection and corrected the manuscript.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Gemma Gom&aacute;: data collection and corrected the manuscript.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Mar&iacute;a Luisa Mart&iacute;nez: data collection and corrected the manuscript.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Antonio Artigas: project coordinator, drafted and corrected de manuscript.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Ethical responsibilities</span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Protection of people and animals</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors declare that in this research have not been performed experiments on humans or animals.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Data confidentiality</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their workplace about publication of patient data.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Right to privacy and informed consent</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that in this paper does not appear patient data.</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Funding</span><p id="par0205" class="elsevierStylePara elsevierViewall">This work was supported by <span class="elsevierStyleGrantSponsor" id="gs1">Instituto de Salud Carlos III</span>: <span class="elsevierStyleGrantNumber" refid="gs1">PI10/01497</span> and <span class="elsevierStyleGrantNumber" refid="gs1">CM12/00066</span>.</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Conflicts of interest</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To analyze the evolution of sepsis-related mortality in Spanish Intensive Care Units (ICUs) following introduction of the Surviving Sepsis Campaign (SSC) guidelines and the relationship with sepsis process-of-care.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective cohort study was carried out, with the inclusion of all consecutive patients presenting severe sepsis or septic shock admitted to 41 Spanish ICUs during two time periods: 2005 (Edusepsis study pre-intervention group) and 2011 (ABISS-Edusepsis study pre-intervention group).</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Scope</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Patients with severe sepsis or septic shock admitted to Spanish ICUs.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patients</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">All ICU admissions from the emergency department or wards and all ICU patients with a diagnosis of severe sepsis or septic shock. A total of 1348 patients were included: 630 in the 2005 group and 718 in the 2011 group.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Intervention</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">None.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Primary endpoints</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ICU mortality, 28-day mortality and Hospital mortality, hospital length of stay, ICU length of stay and compliance with the resuscitation bundle.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Compliance with the resuscitation bundle was significantly greater in the 2011 group (5.7% vs. 9.9%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.005), and was associated to lower mortality (OR 0.602 [0.365&#8211;0.994]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.048). The 2011 group had lower absolute in-hospital mortality (44.0% vs. 32.6%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01), 28-day mortality (36.5% vs. 23.0%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01), and adjusted mortality (OR 0.64 [0.49&#8211;0.83], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Mortality related to severe sepsis or septic shock in Spain decreased between two patient cohorts in 2005 and 2011, and was attributable to earliness and improvement in sepsis care.</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" => "Scope"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Patients"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Intervention"
          ]
          5 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Primary endpoints"
          ]
          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">Analizar la evoluci&oacute;n de la mortalidad relacionada con la sepsis en las unidades de cuidados intensivos (UCI) espa&ntilde;olas desde la introducci&oacute;n de las directrices Surviving Sepsis Campaing y la relaci&oacute;n con el proceso de atenci&oacute;n de la sepsis.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Dise&ntilde;o</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo de cohortes. Se incluyeron de manera consecutiva, todos los pacientes con sepsis grave o shock s&eacute;ptico ingresados en 41 UCI espa&ntilde;olas durante 2 periodos de tiempo: en 2005 (grupo pre-intervenci&oacute;n en el estudio Edusepsis) y en 2011 (grupo pre-intervenci&oacute;n en el estudio ABISS-Edusepsis).</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">&Aacute;mbito</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Pacientes con sepsis grave o shock s&eacute;ptico ingresados en las UCI espa&ntilde;olas.</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Todos los ingresos en UCI procedentes de Urgencias o planta y todos los pacientes de UCI con diagn&oacute;stico de sepsis grave/shock s&eacute;ptico. Se incluyeron 1348 pacientes: 630 del grupo de 2005 y 718 del grupo de 2011.</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intervenci&oacute;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Ninguna.</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variables de inter&eacute;s principal</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Mortalidad en UCI, a 28 d&iacute;as y hospitalaria, estancia en la UCI y en el hospital y cumplimiento con el bundle de reanimaci&oacute;n.</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El cumplimiento del bundle de reanimaci&oacute;n fue significativamente mayor en el grupo de 2011 (5,7 frente a 9,9%, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,005) y se asoci&oacute; con una menor mortalidad (OR 0,602 [0,365 a 0,994], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,048). El grupo de 2011 tuvo una menor mortalidad absoluta hospitalaria (44,0 frente a 32,6%, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,01), mortalidad a los 28 d&iacute;as (36,5 frente a 23,0%, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,01) y mortalidad ajustada (OR 0,64 [0,49 a 0,83], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,001).</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La mortalidad relacionada con la sepsis grave y el shock s&eacute;ptico en Espa&ntilde;a disminuy&oacute; entre las 2 cohortes de pacientes de 2005 y 2011, atribuible a la precocidad y las mejoras en la atenci&oacute;n de la sepsis.</p></span>"
        "secciones" => array:8 [
          0 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Dise&ntilde;o"
          ]
          2 => array:2 [
            "identificador" => "abst0055"
            "titulo" => "&Aacute;mbito"
          ]
          3 => array:2 [
            "identificador" => "abst0060"
            "titulo" => "Pacientes"
          ]
          4 => array:2 [
            "identificador" => "abst0065"
            "titulo" => "Intervenci&oacute;n"
          ]
          5 => array:2 [
            "identificador" => "abst0070"
            "titulo" => "Variables de inter&eacute;s principal"
          ]
          6 => array:2 [
            "identificador" => "abst0075"
            "titulo" => "Resultados"
          ]
          7 => array:2 [
            "identificador" => "abst0080"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "&#9674;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0050">The list of researchers in Edusepsis Study Group is included in <a class="elsevierStyleCrossRef" href="#sec0105">Appendix</a>.</p>"
        "identificador" => "fn1"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Edusepsis Study Group</span>: M&ordf; Mar Cruz (Virgen de la Salud Toledo-Acquaroni); Carmen Fern&aacute;ndez Gonz&aacute;lez (Complejo Hospitalario de Ferrol. Arquitecto Marcide), Paz Merino, Elena Bustamante (Hospital Can Misses); Sandra Barbadillo (Hospital General de Catalu&ntilde;a); Mar&iacute;a de la Cruz Mart&iacute;n, Joaquin Ramon (Centro M&eacute;dico Delfos); Luis Alvarez Rocha (Complexo Hospitalario Universitario de A Coru&ntilde;a); Nestor Bacelar (Cl&iacute;nica Corachan); Bel&eacute;n Jimenez Bartolom&eacute;(Hospital Cl&iacute;nico Universitario Lozano Blesa Zaragoza); Juan Diego Jim&eacute;nez Delgado (Hospital Comarcal Don Benito-Villanueva) Demetrio Carriedo Ule, Ana Mar&iacute;a Dominguez Berrot, Francisco Javier D&iacute;az Dominguez (Complejo Asistencial Universitario de Le&oacute;n); Juan Machado Casas(Complejo Hospitalario de Ja&eacute;n); Clara Laplaza Santos; Manuel Garc&iacute;a-Montesinos; Enrique Marav&iacute; Poma (Complejo Hospitalario de Navarra, Pamplona); Victor L&ograve;pez Ciudad; Pablo Vidal cortes (Complejo Hospitalario de Ourense); Ana Navas, Gemma Gom&agrave;, Mar&iacute;a Luisa Mart&iacute;nez, Antonio Artigas (Hospital de Sabadell, Consorci Hospitalari Parc Tauli); Manuel Castellano Hernandez; Rafael Dom&iacute;nguez (Hospital Alto Guadalquivir, And&uacute;jar); Miguel Mart&iacute;nez, Jose Antonio Fern&aacute;ndez, Fernando Callejo, Mar&iacute;a Jes&uacute;s L&oacute;pez Pueyo (Hospital General Yag&uuml;e); Alec Tallet (Hospital General de Segovia); Pau Torrabadella, Alvaro Salcedo, Claudio Dur&aacute;n (Hospital Universitari Germans Trias i Pujol); Iratxe Seijas (Hospital de Cruces); Teresa Recio G&oacute;mez, Abilio Arrascaeta (San Pedro de Alc&aacute;ntara, C&aacute;ceres); Angel Arenaza, Ana Morillo, Daniel Del Toro, Tom&aacute; s Guzman (Hospital Virgen de la Macarena); Pilar Marco, Izaskun Azkarate (Hospital de Donostia); Isabel Rodr&iacute;guez (Hospital General de Baza); Eduardo Palencia, Pablo Garc&iacute;a Olivares, Patricia Santa Teresa Zamarro (Hospital Gregorio Mara&ntilde;&oacute;n Madrid); Eugenia Yuste (Hospital Universitario San Cecilio); Jordi Sol&eacute; Viol&aacute;n (Hospital Dr Negr&iacute;n. Las Palmas); Jos&eacute; Blanquer, M&oacute;nica Garc&iacute;a (Hospital Cl&iacute;nico Valencia); Juan Carlos Ballesteros (Hospital Universitario de Salamanca); Antonio Blesa, Fernando Mart&iacute;nez, Alejandro Moneo (Hospital San Carlos); Carlos P&eacute;rez (Hospital Santiago Ap&oacute;stol); Jose &Aacute;ngel Berezo, Jes&uacute;s Blanco (Hospital R&iacute;o Hortega Valladolid); Francisco Javier Mart&iacute;n L&oacute;pez (Hospital comarcal Santa Ana, Motril); Ram&oacute;n Vegas Pinto (Hospital de Antequera); Pilar Martinez Trivez (Hospital de Barbastro Huesca); Antonio Reyes Garcia (Hospital de la Princesa de Madrid); Llu&iacute;s Zapata, Paula Vera (Hospital de la Santa Creu i Sant Pau); Eduardo Ant&oacute;n (Hospital de Manacor); Juan Carlos Yebenes (Hospital de Matar&oacute;); Mar&iacute;a de las Olas Cerezo Arias (Hospital de M&eacute;rida); Francisco Garc&iacute;a delgado (Hospital de Montilla); Javier Fierro Ros&oacute;n, Josefa Peinado Rodriguez (Hospital del Poniente, El Ejido); M&ordf; Jes&uacute;s Broch Porcar (Hospital de Sagunto); Mar&iacute;a &Aacute;lvarez (Hospital de Terrassa); Francisco &Aacute;lvarez, M&ordf; Pilar Gracia Arnillas (Hospital del Mar); Francisco Valenzuela (Hospital de Jerez); Patricia Albert de la Cruz (Hospital del Sureste); Rafael Blancas Casero, Blanca L&oacute;pez Matamala (Hospital del Tajo); Monserrat Sis&oacute;n Heredia (Hospital Dr. Jos&eacute; Molina Orosa); Pedro Olaechea, Celia Sa&ntilde;udo (Hospital Galdakao-Usansolo); Jose Manuel Gutierrez Rubio (Hospital General de Albacete); Roberto Reig (Hospital General de Castell&oacute;n); Alfonso Ambr&oacute;s, Julian Ortega (Hospital General de Ciudad Real); Leandro Fajardo Feo (Hospital General de Fuerteventura); Pau Garro (Hospital General de Granollers); Francisco Navarro Pellejero (Hospital General de la Defensa en Zaragoza); Ana Trujillo Alonso (Hospital general de La Palma); Rosa Catal&aacute;n (Hospital General de Vic); Assumpta Rovira, Nicolas Rico (Hospital General Hospitalet de LLobregat); Jose Manuel Allegue Gallego, Luis Herrera Para, Josefa Murcia Paya (Hospital General Universitario Santa Luc&iacute;a, Cartagena); Jos&eacute; C&oacute;rdoba Alonso, Dolores Oca&ntilde;a (Hospital La Inmaculada de Huercal-Overa); Jose Francisco Olea Parejo (Hospital Lucus Augusti, Lugo); Pedro Galdos Anuncibay (Hospital Puerta del Hierro); Manuel Salido Mota (Hospital Regional Universitario Carlos Haya); Mar&iacute;a Jes&uacute;s G&oacute;mez (Hospital General Universitario Reina Sof&iacute;a de Murcia); Ana Isabel Ezpeleta Galindo, Paloma Dorado (Hospital Royo Villanova, Zaragoza); Arantxa Lander Azcona, Rosario Elbaile (Hospital San Jorge, Huesca); Diego Mendoza (Hospital Sant Joan Desp&iacute; Mois&egrave;s Broggi); Francisca Prieto (Hospital de Sta. B&aacute;rbara, Puertollano&#8217;; Luis Vallejo (Hospital SAS La L&iacute;nea); Jose Ignacio Ayestar&aacute;n Rota (Hospital Son Espasses); Marcio Borges (Hospital Son Llatzer); Enrique Piacentini, Ricard Ferrer (Hospital Univerisari M&uacute;tua Terrassa); Josep Maria Sirvent, Sara Herranz Ulldemolins (Hospital Universitari Josep Trueta de Girona); Fernando Iglesias Llaca, Lorena Forcelledo Espina, Francisco Taboada Costa, Jos&eacute; Antonio Gonzalo Guerra (Hospital Universitario Central de Asturias); Leonardo Lorente Ramos&nbsp;(Hospital Universitario Canarias. Tenerife); Helena Ya&ntilde;ez (Hospital universitario de Guadalajara); Ana Loza (Hospital Universitario de Valme); Jose ¿ Miguel Soto, Constantino Tormo (Hospital Universitario Dr. Peset); Borja Suberbiola (Hospital Universitario Marqu&eacute;s de Valdecilla); Domingo Ruiz de la Cuesta Martin, Ignacio Tom&aacute;s Marsilla (Hospital Universitario Miguel Servet Zaragoza); Mar Mart&iacute;n Velasco (Hospital Universitario Nuestra Se&ntilde;ora de Candelaria); Rafael Le&oacute;n L&oacute;pez, Juan Carlos Pozo (Hospital Universitario Reina Sofia de C&oacute;rdoba); Jose &Aacute;ngel Berezo, Jes&uacute;s Blanco (Hospital R&iacute;o Hortega Valladolid); Paula Ram&iacute;rez (Hospital Universitario y Politecnico la Fe); Juan Carlos Ruiz Rodriguez, Jesus Caballero, Adolf Ruiz, Alejandra Garc&iacute;a, Jordi Riera, Javier Sarrapio, (Hospital Universitari Vall d&#8217; Hebron); Carola Gim&eacute;nez Esparza (Hospital Vega Baja orihuela); Ana Carolina Caballero (Hospital Virgen de la Concha, Zamora); Mar&iacute;a Victoria de la Torre, Cristina Salazar (Hospital Virgen Victoria de M&aacute;laga); Carlos Ortiz (Hospital Virgen del Rocio); Eduardo Palencia Herrej&oacute;n, Bego&ntilde;a Bueno (Hospital Infanta Leonor, Madrid); Gumersindo Gonz&aacute;lez, D&iacute;az; Andres Carrillo (Hospital General Universitario Morales Meseguer, Murcia); Manuel Rodr&iacute;guez (Hospital Juan Ramon Jim&eacute;nez); Raquel Valero Gracia (MAZ MATEPSS SUMA Intermutual Zaragoza); Ruth Jorge Garc&iacute;a (Hospital Nuestra Se&ntilde;ora de Gracia Zaragoza); Manuel Quintana, Miguel &Aacute;ngel Taberna (Hospital Nuestra Sra del Prado); Jos&eacute; Carlos Torralba Allu&eacute; (Hospital General Obispo Polanco Teruel); Isidro Prieto del Portillo (Hospital Universitario Ram&oacute;n y Cajal); Jos&eacute; Luis Monz&oacute;n, Adolfo Calvo Mart&iacute;nez (Hospital de Logro&ntilde;o); Ricardo Diaz Abad, Miguel &Aacute;ngel Blasco Navalpotro, Frutos Del Nogal S&aacute;ez, Jes&uacute;s Rebollo Ferreiro, Jos&eacute; Suarez Saiz (Hospital Universitario Severo Ochoa), Mar Gobernado, M&ordf; Jos&eacute; Fernandez Calavia (Hospital de Sta. B&aacute;rbara, Soria); Francisco Jos&eacute; Guerrero, Felipe Ca&ntilde;ada, Milagros Balaguer, Isabel Mert&iacute;n, Carmen L&oacute;pez, Daniel S&aacute;nchez (Hospital Torrec&aacute;rdenas); Jose Mar&iacute;a Bonell (USP H Cl&iacute;nica Palma Planas); Jos&eacute; Casta&ntilde;o (Hospital Universitario Virgen de las Nieves); Hospital Virgen del Puerto, Plasencia).</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Appendix"
            "identificador" => "sec0105"
          ]
        ]
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1270
            "Ancho" => 2086
            "Tamanyo" => 111729
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        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Resuscitation bundle, accomplished within 6<span class="elsevierStyleHsp" style=""></span>h.</p> <p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Abbreviation: CVP: central venous pressure; ScvO<span class="elsevierStyleInf">2</span>: central venous oxygen saturation; ATB: antibiotic.</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
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          0 => array:3 [
            "identificador" => "at1"
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            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation II; SD, standard deviation; ICU, intensive care unit.</p>"
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2005 group<br>(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>630)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2011 group<br>(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>718)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">APACHE II, mean (SD)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20.7 (7.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22.4 (7.9)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age, years, mean (SD)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62.1 (16.7)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64.9 (14.9)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.231&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Sex, male n (%)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">375 (59.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">457 (63.6)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Source n (%)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Emergency department&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">268 (42.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">523 (72.8)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ward&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">278 (44.1)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">158 (22)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ICU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">84 (13.3)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37 (5.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Site of infection, n (%)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pneumonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">243 (38.6)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">218 (30.4)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute abdominal infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">189 (30)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">253 (35.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urinary tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58 (9.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123 (17.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Meningitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 (1.1)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 (1.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Soft-tissue infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 (5.1)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48 (6.7)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 (1.6)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18 (2.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8805;2 sites of infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 (1.6)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81 (12.9)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47 (6.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Baseline acute organ dysfunctions n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cardiovascular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">521 (82.7)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">617 (85.9)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Respiratory&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">408 (64.8)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">314 (43.7)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">462 (73.3)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">415 (57.8)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hyperbilirubinemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">127 (20.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">115 (16)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.072&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">150 (23.8)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">155 (21.6)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.334&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Coagulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">222 (35.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">350 (48.7)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hyperlactatemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">223 (35.4)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">339 (47.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical characteristics of patients, by group.</p>"
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        "etiqueta" => "Table 2"
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          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: SD, standard deviation; ICU, intensive care unit.</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Measurements&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2005 group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2011 group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Hospital mortality, (%)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">277 (44.0)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">234 (32.6)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">28-day mortality, (%)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">230 (36.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">165 (23.0)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Hospital stay</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>, days</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean (SD)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28.1 (22.9)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33.9 (34.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Median [interquartile range]&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21.4 [13.7&#8211;35.8]&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 [13&#8211;42]&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.253&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">ICU stay</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>, <span class="elsevierStyleItalic">days</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean (SD)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12.3 (14.8)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11.2 (14.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.316&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Median [interquartile range]&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7.5 [4.6&#8211;14.7]&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 [3&#8211;13]&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.832&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Outcomes measurements by group.</p>"
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      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
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          "leyenda" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation II; OR, odd ratio; CI, confidence interval; ICU, intensive care unit; UTI, urinary tract infection.</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR (95% CI)<br>Model I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.018 (1.009&#8211;1.027)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">APACHE-II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.087 (1.066&#8211;1.109)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Source</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ward<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2.007 (1.522&#8211;2.646)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ICU<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2.396 (1.541&#8211;3.726)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Site of infection</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>UTI<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.287 (0.173&#8211;0.476)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Soft-tissue infection<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.414 (0.221&#8211;0.776)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Baseline acute organ dysfunctions</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Respiratory&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.438 (1.076&#8211;1.923)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.288 (1.016&#8211;1.896)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.039&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Treatment bundle</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Resuscitation bundle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.602 (0.365&#8211;0.994)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.048&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0130" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation II; OR, odd ratio; CI, confidence interval; ICU, intensive care unit; UTI, urinary tract infection; NA, not applicable.</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR (95% CI)<br>Model II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR (95% CI)<br>Model III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">2011 group</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.64 (0.49&#8211;0.83)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.64 (0.531&#8211;0.95)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.016 (1.008&#8211;1.025)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.019 (1.01&#8211;1.027)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">APACHE-II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.104 (1.084&#8211;1.124)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.092 (1.07&#8211;1.114)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Source</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ward<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.796 (1.362&#8211;2.367)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.849 (1.39&#8211;2.458)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ICU<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2.168 (1.4&#8211;3.357)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2.191 (1.397&#8211;3.334)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Site of infection</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>UTI<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.277 (0.172&#8211;0.445)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.295 (0.178&#8211;0.449)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Soft-tissue infection<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.437 (0.234&#8211;0.817)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.418 (0.223&#8211;0.784)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Baseline acute organ dysfunctions</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Respiratory&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.378 (1.028&#8211;1.846)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.032&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.356 (1.01&#8211;1.821)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.362 (0.998&#8211;1.859)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.052&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1.371 (1.003&#8211;1.874)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.048&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Treatment bundle</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Resuscitation bundle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.634 (0.378&#8211;1.032)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">Multivariate analysis of factors associated with mortality, Models II and III; only significant variables are shown.</p>"
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:42 [
            0 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D.C. Angus"
                            1 => "W.T. Linde-Zwirble"
                            2 => "J. Lidicker"
                            3 => "G. Clermont"
                            4 => "J. Carcillo"
                            5 => "M.R. Pinsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2001"
                        "volumen" => "29"
                        "paginaInicial" => "1303"
                        "paginaFinal" => "1310"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11445675"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology and recent trends of severe sepsis in Spain: a nationwide population-based analysis (2006&#8211;2011)"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C. Bouza"
                            1 => "T. L&oacute;pez-Cuadrado"
                            2 => "Z. Saz-Parkinson"
                            3 => "J.M. Amate-Blanco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12879-014-0717-7"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Infect Dis"
                        "fecha" => "2014"
                        "volumen" => "14"
                        "paginaInicial" => "3863"
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