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        "titulo" => "La posici&#243;n prona en los pacientes con COVID-19 y s&#237;ndrome de distr&#233;s respiratorio agudo que recibieron oxigenoterapia convencional&#58; un estudio retrospectivo"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flow chart of patient selection&#46; ARDS&#58; acute respiratory distress syndrome&#59; IMV&#58; invasive mechanical ventilation&#59; NIMV&#58; non-invasive mechanical ventilation&#59; HFNC&#58; high-flow nasal cannula&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Coronavirus disease 2019 &#40;COVID-19&#41; is caused by the severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41;&#44; which emerged in Wuhan &#40;China&#41; in December 2019&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> Although most cases are mild&#44; nearly 20&#37; of patients require hospitalization&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> Despite supportive care&#44; one third of hospitalized patients meet the Berlin criteria for acute respiratory distress syndrome &#40;ARDS&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">3&#44;4</span></a> and may need admission to intensive care unit &#40;ICU&#41;&#46; Overall mortality ranged 21&#8211;26&#37; with advanced age&#44; male sex and comorbidities being the strongest predictors of in-hospital mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Apart from dexamethasone&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> to date the mainstay of treatment if COVID-19 are supplemental oxygen therapy and best supportive care&#44; including invasive mechanical ventilation &#40;IMV&#41; in severe ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> Prone position &#40;PP&#41; is the only technique that has demonstrated to increase survival in patients with severe ARDS receiving IMV&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a> However&#44; due to a sudden increase in hospitalizations&#44; exceeding ICU capacity&#44; PP has been attempted in non-intubated awake patients with COVID-19 and severe ARDS in conventional medical wards&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">10&#8211;12</span></a> despite inconsistent results on the impact of this intervention on mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> In this study&#44; we evaluated the impact on in-hospital mortality of PP in spontaneously breathing patients with COVID-19 and severe ARDS&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This study is based on the data from the SEMI-COVID-19 Registry&#46; This Registry is an ongoing nationwide&#44; multicenter&#44; observational retrospective cohort of adult patients admitted to Spanish hospitals from March 1st&#44; 2020 because of microbiologically confirmed COVID-19&#46; Characteristics of the Registry are detailed elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a> In this study we included patients aged 18&#8211;75 years old who presented pneumonia and severe ARDS &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mmHg&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> during hospitalization&#46; Exclusion criteria were&#58; &#40;a&#41; ICU admission&#44; &#40;b&#41; use of non-invasive mechanical ventilation &#40;NIMV&#41;&#44; &#40;c&#41; use of high-flow nasal cannula &#40;HFNC&#41; oxygen therapy&#44; &#40;d&#41; moderate or severe dependence for activities of daily living &#40;e&#41; solid or hematologic cancer&#44; &#40;f&#41; chronic dialysis&#44; &#40;g&#41; neurodegenerative disease or hemiplegia&#46; The primary outcome was death during hospitalization&#46; Patients in whom PP during spontaneous breathing was used for at least one day were compared to those who did not receive this treatment&#46; PP indication and duration were decided at clinical discretion and this information was not recorded in the registry&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Baseline characteristics between groups were compared using Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test and Fisher&#39;s exact test&#46; Univariate logistic regression was used to estimate the crude effect of prone position on mortality&#44; as well as the effect of those baseline variables that were different between both groups &#40;<span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;10&#41; or considered as clinically relevant&#46; Afterwards&#44; a multivariate logistic regression model was elaborated&#44; including as confounders the variables that showed a univariate effect on mortality or those a priori &#40;outcome-blinded&#41; considered as relevant according to literature review<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> and clinical plausibility &#40;age&#44; sex&#44; Charlson Comorbidity Index &#40;CCI&#41;&#44; heart failure&#44; altered mental status&#44; and treatment with tocilizumab or corticosteroids&#41;&#46; Beginning with the maximum model containing all the variables&#44; we use an investigator-guided backward elimination method to estimate the final model&#44; iteratively excluding non-significant variables until all variables of the model showed <span class="elsevierStyleItalic">p</span>-values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; The goodness of fit of the model was evaluated with the area under the receiver operating characteristics curve &#40;AUC&#41;&#46; The 95&#37; confidence interval &#40;95&#37; CI&#41; of AUC was calculated using the binomial exact method&#46; All statistical analyses were performed using Stata 15&#46;2&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Until August 31st&#44; 2020&#44; the SEMI-COVID-19 Registry included 17&#44;084 patients&#44; of which 163 presented severe ARDS and met inclusion criteria and did not meet any exclusion criteria &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Prone position was used in 60 patients &#40;36&#46;8&#37;&#41;&#46; Baseline characteristics&#44; treatment received and outcomes in both groups are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Patients who receive PP were younger&#44; had less comorbidity&#44; presented higher C-reactive protein and D-dimer levels at admission&#44; and received more corticosteroids and tocilizumab&#46; Besides&#44; although the proportion of patients with altered mental status at presentation did not meet our pre-specified criteria of <span class="elsevierStyleItalic">p</span>-value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;10 to be considered different between the two groups&#44; we considered the difference clinically relevant &#40;7&#46;8&#37; vs 15&#46;3&#37;&#41;&#46; Ninety out of 163 patients &#40;55&#46;2&#37;&#41; died&#46; Patients who died were older and have more comorbidity &#40;<a class="elsevierStyleCrossRef" href="#sec0010">Supplementary Table 1</a>&#41;&#46; Patients treated with PP presented lower mortality &#40;62&#46;1&#37; vs 43&#46;3&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0229&#41;&#44; with an estimated crude OR of 0&#46;47 &#40;95&#37; CI 0&#46;24&#8211;0&#46;89&#41;&#46; In the adjusted model&#44; use of PP showed a protective effect on mortality &#40;OR 0&#46;42&#44; 95&#37; CI 0&#46;18&#8211;0&#46;98&#41;&#44; after adjusting for age&#44; CCI and altered mental status at presentation &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The AUC of this adjusted model was 0&#46;861 &#40;95&#37; CI 0&#46;799&#8211;0&#46;912&#41;&#46; Although it could be arguable to remove corticosteroids and tocilizumab as confounders in the adjusted analysis&#44; the exclusion of these variables did not modify the protective effect of PP on mortality&#44; and the accuracy of our adjusted model to predict in-hospital death was very good&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Despite PP is a well-established evidence-based practice in patients with typical ARDS undergoing IMV&#44; there is very limited evidence of its use in non-ventilated awake patients and derived mostly from case reports and uncontrolled cohorts using a wide variety of PP protocols&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">13&#44;14</span></a> Besides&#44; in most reports the use of respiratory support is inconsistent&#44; with patients receiving NIMV or HFNC oxygen therapy&#44; thus making very difficult to know the true effect of PP&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> Despite most studies reported an improvement in oxygenation while patients were in PP and even after PP&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a> its impact on hard outcomes such as intubation or death remains unclear&#46; In fact&#44; it has been pointed out that improvement in oxygenation during PP may result in delayed intubation and IMV with eventually poor outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">15</span></a> However&#44; in a recent retrospective cohort with 166 patients&#44; Padr&#227;o et al&#46; studied the impact of PP in patients who required supplemental oxygen &#40;but did not receive NIMV or HFNC oxygen&#41; and found no differences on the need of intubation at 15 days&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a> A possible explanation could be that the benefits of PP are related to a reduction in ventilator-induced lung injury rather than with better oxygenation&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In our study&#44; we excluded older patients because they could have greater comorbidities and most of them would not benefit from ICU admission in a context of pandemic crisis&#46; This scenario happened in the first weeks of COVID-19 pandemic in Spain and other developed countries and is still ongoing in resource-limited settings&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The main strength of our study is the use of a hard endpoint as mortality as the primary outcome&#44; and the large number of patients included in comparison to previous studies on this topic&#46; Besides&#44; contrary to previous reports&#44; our cohort is homogeneous regarding respiratory support&#44; as we only include patients with spontaneous breathing receiving oxygen supply through a conventional oxygen mask &#40;either Venturi masks or rebreathing masks&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">This study also has several limitations&#46; The main one is the lack of detailed information on indication&#44; timing&#44; or duration of PP&#44; and as a result&#44; it is probable that PP was heterogeneous across the cohort&#46; Secondly&#44; we do not have information on the reasons why our patients with severe ARDS were not admitted to the ICU&#44; and given the multicenter nature of the cohort&#44; these reasons could be different between hospitals&#44; potentially resulting in a selection bias&#46; To minimize the risk of selection bias we decided to analyze only COVID-19 patients &#8804;75 years and severe ARDS&#44; as we believe that the main reason these patients remained in conventional wards was the unavailability of ICU resources&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In summary&#44; the use of prone position in non-intubated COVID-19 patients &#8804;75 years with severe ARDS and without additional respiratory support&#44; may be associated with improved survival in situations where ICU beds are not available&#44; suggesting that it could be useful in pandemic crisis scenarios&#46; However&#44; randomized controlled trials are needed to confirm our results and to establish adequate protocols of PP in non-intubated patients&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that there is no conflict of interest to report&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">A complete list of the SEMI-COVID-19 Network members is provided in the <a class="elsevierStyleCrossRef" href="#sec0010">Appendix &#40;Supplementary Material&#41;</a>&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Continuous variables are expressed as median and interquartile range &#91;Q1&#8211;Q3&#93;&#46; Categorical variables are expressed as number and percentage&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">COPD&#58; chronic obstructive pulmonary disease&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Caucasian&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Latin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Smoker status</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;1900&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Former smoker&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Current smoker&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Obesity</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;5950&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Charlson Index</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#91;0&#8211;3&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#91;0&#8211;0&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Hypertension</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Diabetes mellitus</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">COPD</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;8&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Obstructive sleep apnea</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;8&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Heart failure</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">SaO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#47;FiO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">at admission</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">D-dimer &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
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Vol. 58. Issue 3.
Pages 277-280 (March 2022)
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Vol. 58. Issue 3.
Pages 277-280 (March 2022)
Scientific Letter
Prone Position in COVID-19 Patients With Severe Acute Respiratory Distress Syndrome Receiving Conventional Oxygen Therapy: A Retrospective Study
La posición prona en los pacientes con COVID-19 y síndrome de distrés respiratorio agudo que recibieron oxigenoterapia convencional: un estudio retrospectivo
Jose Loureiro-Amigoa,
Corresponding author
jose.loureiro.amigo@gmail.com

Corresponding author.
, Cecilia Suárez-Carantoñab, Isabel Oriola, Cristina Sánchez-Díazb, Ana Coloma-Condea, Luis Manzano-Espinosab,c, Manuel Rubio-Rivasd, Barbara Otero-Perpiñáe, María Mercedes Ferreiro-Mazón Jenarof, Ainara Coduras-Erdozaing, José Luis Garcia-Klepzigh, Derly Vargas-Parrai, Paula M. Pesqueira-Fontánj, Isabel Fiteni-Merak, Gema María García-Garcíal, José Jiménez-Torresm, Pablo Rodríguez-Cortésn, Clara Costo-Murielo, Francisco Arnalich-Fernándezp, Arturo Arteroq..., Francisco Javier Carrasco-Sánchezr, Joaquín Escobar-Sevillas, José Nicolás Alcalá-Pedrajast, Ricardo Gómez-Huelgasu, José-Manuel Ramos-Rincónv, On behalf of the SEMI-COVID-19 Network Ver más
a Infectious Diseases Unit – Internal Medicine Department, Moisès Broggi Hospital, Sant Joan Despí, Barcelona, Spain
b Internal Medicine Department, Ramón y Cajal Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
c Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
d Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain
e Internal Medicine Department, 12 de Octubre University Hospital, Madrid, Spain
f Internal Medicine Department, Gregorio Marañón Hospital, Madrid, Spain
g Internal Medicine Department, Santa Marina Hospital, Bilbao, Spain
h Internal Medicine Department, Hospital Clínico San Carlos, Madrid, Spain
i Internal Medicine Department, Hospital Universitario Río Hortega, Gerencia Regional de Salud de Castilla y Leon (SACYL), Valladolid, Spain
j Internal Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
k Internal Medicine Department, Royo Villanova Hospital, Zaragoza, Spain
l Internal Medicine Department, Complejo Hospitalario Universitario de Badajoz, Badajoz, Spain
m Unidad de Gestión Clínica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
n Internal Medicine Department, La Princesa Hospital, Madrid, Spain
o Internal Medicine Department, Regional University Hospital of Málaga, Málaga, Spain
p Internal Medicine Department, La Paz-Cantoblanco University Hospital, Madrid, Spain
q Internal Medicine Department, Dr. Peset University Hospital, Valencia, Spain
r Internal Medicine Department, Juan Ramón Jiménez Hospital, Huelva, Spain
s Internal Medicine Department, Virgen de las Nieves University Hospital, Granada, Spain
t Internal Medicine Department, Hospital Comarcal de Pozoblanco, Córdoba, Spain
u Internal Medicine Department, Regional University Hospital of Málaga, Biomedical Research Institute of Málaga (IBIMA), University of Málaga (UMA), Málaga, Spain
v Department of Clinical Medicine, Miguel Hernandez University of Elche, Alicante, Spain
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Scientific Letter
Prone Position in COVID-19 Patients With Severe Acute Respiratory Distress Syndrome Receiving Conventional Oxygen Therapy: A Retrospective Study
La posición prona en los pacientes con COVID-19 y síndrome de distrés respiratorio agudo que recibieron oxigenoterapia convencional: un estudio retrospectivo
Jose Loureiro-Amigoa,
Corresponding author
jose.loureiro.amigo@gmail.com

Corresponding author.
, Cecilia Suárez-Carantoñab, Isabel Oriola, Cristina Sánchez-Díazb, Ana Coloma-Condea, Luis Manzano-Espinosab,c, Manuel Rubio-Rivasd, Barbara Otero-Perpiñáe, María Mercedes Ferreiro-Mazón Jenarof, Ainara Coduras-Erdozaing, José Luis Garcia-Klepzigh, Derly Vargas-Parrai, Paula M. Pesqueira-Fontánj, Isabel Fiteni-Merak, Gema María García-Garcíal, José Jiménez-Torresm, Pablo Rodríguez-Cortésn, Clara Costo-Murielo, Francisco Arnalich-Fernándezp, Arturo Arteroq..., Francisco Javier Carrasco-Sánchezr, Joaquín Escobar-Sevillas, José Nicolás Alcalá-Pedrajast, Ricardo Gómez-Huelgasu, José-Manuel Ramos-Rincónv, On behalf of the SEMI-COVID-19 Network Ver más
a Infectious Diseases Unit – Internal Medicine Department, Moisès Broggi Hospital, Sant Joan Despí, Barcelona, Spain
b Internal Medicine Department, Ramón y Cajal Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
c Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
d Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain
e Internal Medicine Department, 12 de Octubre University Hospital, Madrid, Spain
f Internal Medicine Department, Gregorio Marañón Hospital, Madrid, Spain
g Internal Medicine Department, Santa Marina Hospital, Bilbao, Spain
h Internal Medicine Department, Hospital Clínico San Carlos, Madrid, Spain
i Internal Medicine Department, Hospital Universitario Río Hortega, Gerencia Regional de Salud de Castilla y Leon (SACYL), Valladolid, Spain
j Internal Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
k Internal Medicine Department, Royo Villanova Hospital, Zaragoza, Spain
l Internal Medicine Department, Complejo Hospitalario Universitario de Badajoz, Badajoz, Spain
m Unidad de Gestión Clínica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
n Internal Medicine Department, La Princesa Hospital, Madrid, Spain
o Internal Medicine Department, Regional University Hospital of Málaga, Málaga, Spain
p Internal Medicine Department, La Paz-Cantoblanco University Hospital, Madrid, Spain
q Internal Medicine Department, Dr. Peset University Hospital, Valencia, Spain
r Internal Medicine Department, Juan Ramón Jiménez Hospital, Huelva, Spain
s Internal Medicine Department, Virgen de las Nieves University Hospital, Granada, Spain
t Internal Medicine Department, Hospital Comarcal de Pozoblanco, Córdoba, Spain
u Internal Medicine Department, Regional University Hospital of Málaga, Biomedical Research Institute of Málaga (IBIMA), University of Málaga (UMA), Málaga, Spain
v Department of Clinical Medicine, Miguel Hernandez University of Elche, Alicante, Spain
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        "titulo" => "La posici&#243;n prona en los pacientes con COVID-19 y s&#237;ndrome de distr&#233;s respiratorio agudo que recibieron oxigenoterapia convencional&#58; un estudio retrospectivo"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flow chart of patient selection&#46; ARDS&#58; acute respiratory distress syndrome&#59; IMV&#58; invasive mechanical ventilation&#59; NIMV&#58; non-invasive mechanical ventilation&#59; HFNC&#58; high-flow nasal cannula&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Coronavirus disease 2019 &#40;COVID-19&#41; is caused by the severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41;&#44; which emerged in Wuhan &#40;China&#41; in December 2019&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> Although most cases are mild&#44; nearly 20&#37; of patients require hospitalization&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> Despite supportive care&#44; one third of hospitalized patients meet the Berlin criteria for acute respiratory distress syndrome &#40;ARDS&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">3&#44;4</span></a> and may need admission to intensive care unit &#40;ICU&#41;&#46; Overall mortality ranged 21&#8211;26&#37; with advanced age&#44; male sex and comorbidities being the strongest predictors of in-hospital mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Apart from dexamethasone&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> to date the mainstay of treatment if COVID-19 are supplemental oxygen therapy and best supportive care&#44; including invasive mechanical ventilation &#40;IMV&#41; in severe ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> Prone position &#40;PP&#41; is the only technique that has demonstrated to increase survival in patients with severe ARDS receiving IMV&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a> However&#44; due to a sudden increase in hospitalizations&#44; exceeding ICU capacity&#44; PP has been attempted in non-intubated awake patients with COVID-19 and severe ARDS in conventional medical wards&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">10&#8211;12</span></a> despite inconsistent results on the impact of this intervention on mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> In this study&#44; we evaluated the impact on in-hospital mortality of PP in spontaneously breathing patients with COVID-19 and severe ARDS&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This study is based on the data from the SEMI-COVID-19 Registry&#46; This Registry is an ongoing nationwide&#44; multicenter&#44; observational retrospective cohort of adult patients admitted to Spanish hospitals from March 1st&#44; 2020 because of microbiologically confirmed COVID-19&#46; Characteristics of the Registry are detailed elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a> In this study we included patients aged 18&#8211;75 years old who presented pneumonia and severe ARDS &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mmHg&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> during hospitalization&#46; Exclusion criteria were&#58; &#40;a&#41; ICU admission&#44; &#40;b&#41; use of non-invasive mechanical ventilation &#40;NIMV&#41;&#44; &#40;c&#41; use of high-flow nasal cannula &#40;HFNC&#41; oxygen therapy&#44; &#40;d&#41; moderate or severe dependence for activities of daily living &#40;e&#41; solid or hematologic cancer&#44; &#40;f&#41; chronic dialysis&#44; &#40;g&#41; neurodegenerative disease or hemiplegia&#46; The primary outcome was death during hospitalization&#46; Patients in whom PP during spontaneous breathing was used for at least one day were compared to those who did not receive this treatment&#46; PP indication and duration were decided at clinical discretion and this information was not recorded in the registry&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Baseline characteristics between groups were compared using Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test and Fisher&#39;s exact test&#46; Univariate logistic regression was used to estimate the crude effect of prone position on mortality&#44; as well as the effect of those baseline variables that were different between both groups &#40;<span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;10&#41; or considered as clinically relevant&#46; Afterwards&#44; a multivariate logistic regression model was elaborated&#44; including as confounders the variables that showed a univariate effect on mortality or those a priori &#40;outcome-blinded&#41; considered as relevant according to literature review<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> and clinical plausibility &#40;age&#44; sex&#44; Charlson Comorbidity Index &#40;CCI&#41;&#44; heart failure&#44; altered mental status&#44; and treatment with tocilizumab or corticosteroids&#41;&#46; Beginning with the maximum model containing all the variables&#44; we use an investigator-guided backward elimination method to estimate the final model&#44; iteratively excluding non-significant variables until all variables of the model showed <span class="elsevierStyleItalic">p</span>-values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; The goodness of fit of the model was evaluated with the area under the receiver operating characteristics curve &#40;AUC&#41;&#46; The 95&#37; confidence interval &#40;95&#37; CI&#41; of AUC was calculated using the binomial exact method&#46; All statistical analyses were performed using Stata 15&#46;2&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Until August 31st&#44; 2020&#44; the SEMI-COVID-19 Registry included 17&#44;084 patients&#44; of which 163 presented severe ARDS and met inclusion criteria and did not meet any exclusion criteria &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Prone position was used in 60 patients &#40;36&#46;8&#37;&#41;&#46; Baseline characteristics&#44; treatment received and outcomes in both groups are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Patients who receive PP were younger&#44; had less comorbidity&#44; presented higher C-reactive protein and D-dimer levels at admission&#44; and received more corticosteroids and tocilizumab&#46; Besides&#44; although the proportion of patients with altered mental status at presentation did not meet our pre-specified criteria of <span class="elsevierStyleItalic">p</span>-value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;10 to be considered different between the two groups&#44; we considered the difference clinically relevant &#40;7&#46;8&#37; vs 15&#46;3&#37;&#41;&#46; Ninety out of 163 patients &#40;55&#46;2&#37;&#41; died&#46; Patients who died were older and have more comorbidity &#40;<a class="elsevierStyleCrossRef" href="#sec0010">Supplementary Table 1</a>&#41;&#46; Patients treated with PP presented lower mortality &#40;62&#46;1&#37; vs 43&#46;3&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0229&#41;&#44; with an estimated crude OR of 0&#46;47 &#40;95&#37; CI 0&#46;24&#8211;0&#46;89&#41;&#46; In the adjusted model&#44; use of PP showed a protective effect on mortality &#40;OR 0&#46;42&#44; 95&#37; CI 0&#46;18&#8211;0&#46;98&#41;&#44; after adjusting for age&#44; CCI and altered mental status at presentation &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The AUC of this adjusted model was 0&#46;861 &#40;95&#37; CI 0&#46;799&#8211;0&#46;912&#41;&#46; Although it could be arguable to remove corticosteroids and tocilizumab as confounders in the adjusted analysis&#44; the exclusion of these variables did not modify the protective effect of PP on mortality&#44; and the accuracy of our adjusted model to predict in-hospital death was very good&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Despite PP is a well-established evidence-based practice in patients with typical ARDS undergoing IMV&#44; there is very limited evidence of its use in non-ventilated awake patients and derived mostly from case reports and uncontrolled cohorts using a wide variety of PP protocols&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">13&#44;14</span></a> Besides&