Mayurathan Balachandran, Adrian Pakavakis, Wisam Al-Bassam, David Collins, Raffaele Mandarano, Vineet Sarode, Rinaldo Bellomo, Alastair Brown, Shailesh Bihari, Mozhu Li, Alana Brown, Yahya Shehabi
{"title":"Postoperative 20% Albumin and Cardiac Surgery Associated Kidney Injury, Statistical Analysis Plan and Updated Protocol","authors":"Mayurathan Balachandran, Adrian Pakavakis, Wisam Al-Bassam, David Collins, Raffaele Mandarano, Vineet Sarode, Rinaldo Bellomo, Alastair Brown, Shailesh Bihari, Mozhu Li, Alana Brown, Yahya Shehabi","doi":"10.1101/2024.09.17.24313807","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313807","url":null,"abstract":"Background\u0000The incidence of cardiac surgery associated acute kidney injury (CS-AKI) remains high. Patients who develop AKI after cardiac surgery are at higher risk of persistent renal dysfunction and increased long-term mortality. The risk of CS-AKI is significantly increased in patients with chronic kidney disease and in patients having prolonged bypass for complex surgery. Previous trials of albumin did not show any benefit in prevention of CS-AKI. These trials, however, did not focus on high-risk patients and used albumin as a resuscitation strategy. The aim of ALBICS-AKI is to demonstrate the effect of concentrated albumin infusion on CS-AKI in high-risk patients undergoing cardiac surgery compared with standard care. Methods\u0000ALBICS-AKI is an investigator initiated, multicentre, randomised, open label trial. Seven centres in Australia and Italy will participate in the trial. We will randomise 620 adult patients who will undergo on-pump cardiac surgery with one of the following: an estimated glomerular filtration rate <60 ml/min/1.73m2, combined valve/s, coronary artery, or surgery involving thoracic aorta. Within 6 hours after surgery, a 20% albumin infusion will commence at 20ml/h for 15 hours. All patients will receive standard care as per institutional protocols. The primary outcome is the proportion of patients with AKI according to creatinine based KDIGO definition at hospital discharge or day 28, whichever comes first. Secondary outcomes include Major Adverse Kidney Events at day 28, AKI stage II and III, need for renal replacement therapy, and hospital mortality. Ethics and dissemination The trial was approved by Monash Health Lead Research Committee for Australian sites and by the Italian Medicine Agency for Italian sites. The estimated study completion date is Sep 2024. The results will be presented at major conferences and submitted for publication in peer-reviewed journals. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12619001355167","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ariane Plaisance, Julien Turgeon, Lucas Gomes Souza, France Légaré, Stéphane Turcotte, Nathalie Germain, Tommy Jean, Maude Dionne, Félix Antoine Fortier, Patrick Plante, Diane Tapp, Véronique Gélinas, Emmanuelle Bélanger, Mark H Ebell, Christian Chabot, Tom van de Belt, Alexis F Turgeon, Patrick M Archambault
{"title":"Exploring the impact of a context-adapted decision aid and online training about shared decision making about goals of care with elderly patients in the intensive care unit: a mixed-methods study","authors":"Ariane Plaisance, Julien Turgeon, Lucas Gomes Souza, France Légaré, Stéphane Turcotte, Nathalie Germain, Tommy Jean, Maude Dionne, Félix Antoine Fortier, Patrick Plante, Diane Tapp, Véronique Gélinas, Emmanuelle Bélanger, Mark H Ebell, Christian Chabot, Tom van de Belt, Alexis F Turgeon, Patrick M Archambault","doi":"10.1101/2024.09.07.24313154","DOIUrl":"https://doi.org/10.1101/2024.09.07.24313154","url":null,"abstract":"Purpose: To explore the impact of a context-adapted decision aid and an online training about shared decision-making (SDM) about goals of care on the level of involvement of elderly patients by intensivists in SDM about goals of care and quality of goals of care discussions (GCD) in an intensive care unit. Methods: This was a three-phase before-after mixed-methods implementation study conducted in an ICU in Lévis, Quebec, Canada. We followed the StaRI and COREQ reporting guidelines. We recruited patients aged ≥ 65 and their attending intensivists. We video-recorded GCD in three phases: Phase I: GCD without a decision aid; Phase II: GCD with a decision aid about goals of care but no online training; and Phase III: GCD with both a decision aid about goals of care following online training about SDM. All GCD recordings were transcribed verbatim. We measured the level of patient engagement by intensivists in SDM about goals of care through the OPTION scale and evaluated GCD quality using the Audit of Communication, Care Planning, and Documentation (ACCEPT) indicators. A qualitative thematic analysis of the encounters transcriptions was also performed. Results: Out of 359 eligible patients, the study included 21 patients (71% males; median age, 77 years; 57% without high school diploma) and 5 intensivists (80% male; median age, 35). Despite completing online training, the decision aid was never used in recorded encounters. We did not perform any tests of statistical significance to compare results in each study phase because of small sample sizes over each phase. OPTION and ACCEPT scores were low in each phase, but physicians did engage in GCD. We found that 76% of the goals of care recorded in medical records after the discussion were consistent with preferences expressed by patients during recorded observations. Several patients expressed confusion about GCD. Barriers identified by intensivists leading GCD include physician attitudes, challenges to performing GCD along with the demands of the intensive care unit, misunderstandings, and lack of training. Facilitators include a patient-centered approach, a clear decision aid, and positive patient attitudes. In future work, an environment that supports physicians in performing GCD, promotes earlier and higher quality patient GCD before admission to the intensive care unit, and encourages meaningful SDM in critical care must be assessed as pathways to successful intensive care unit GCD.\u0000Conclusion: A context-adapted decision aid about goals of care was created in addition to a complementary online training module. The online training was completed by all participating physicians but no increased involvement of patients in SDM during intensive care unit GCD was observed, and use of the decision aid was also not observed. We found several communication barriers that will need to be explored to improve intensive care unit GCD.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Perioperative albumin versus other fluids to prevent cardiac surgery associated kidney injury: a protocol for a systematic review and meta-analysis of randomised trials","authors":"Phoebe Darlison, Alastair Brown, Ary Serpa Neto, Adrian Pakavakis, Mayurathan Balachandran, Yahya Shehabi","doi":"10.1101/2024.09.05.24313089","DOIUrl":"https://doi.org/10.1101/2024.09.05.24313089","url":null,"abstract":"<strong>Background</strong> Acute kidney injury is a common complication following cardiac surgery. Albumin infusions have been proposed as an intervention that reduce the risk of this complication, but existing data have shown heterogenous results. The recent completion of two randomised controlled trial of Albumin infusions in cardiac surgical patients provides the opportunity to conduct a systematic review and meta-analysis to improve the precision of the estimated treatment effect of Albumin infusions in cardiac surgery.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Jeffrey, J Bartholdson Scott, RJ White, E Higginson, M Maes, S Forrest, J Pereira-Dias, S Parmar, E Heasman-Hunt, MD Curran, P Polgarova, J Herre, EE Davenport, S Baker, G Dougan, V Navapurkar, A Conway Morris
{"title":"Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes","authors":"M Jeffrey, J Bartholdson Scott, RJ White, E Higginson, M Maes, S Forrest, J Pereira-Dias, S Parmar, E Heasman-Hunt, MD Curran, P Polgarova, J Herre, EE Davenport, S Baker, G Dougan, V Navapurkar, A Conway Morris","doi":"10.1101/2024.09.02.24312971","DOIUrl":"https://doi.org/10.1101/2024.09.02.24312971","url":null,"abstract":"Pneumonia is the leading infectious disease killer worldwide and commonly requires admission to critical care. Despite its prevalence, the underpinning biology of severe pneumonia remains incompletely understood. We performed multifaceted assessments of bronchoalveolar transcriptome, cytokines, microbiology, and clinical features to biologically dissect a cohort of patients with suspected severe pneumonia. Our data revealed three lung-restricted transcriptionally defined severe pneumonia endotypes (termed ‘Pneumotypes’ (Pn)). All three Pneumotypes had comparable clinical presentations and severity of respiratory failure but critically had divergent outcomes. Pn1, the most common, was characterised by low alveolar cytokines, expanded tolerogenic macrophages and epithelial damage. Pn3 was characterised by neutrophil-monocyte infiltration, IL-6-STAT3 activation and longer duration of mechanical ventilation. Pn2 displayed the fastest resolution, exhibiting a balanced immune response and epithelial-endothelial repair signatures. Our work has identified mechanistically distinct phenotypes in the lungs of patients with suspected pneumonia and acute lung injury, providing new targets for personalised therapy.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannes Kühtreiber, Daniel Bormann, Melanie Salek, Thomas Haider, Caterina Selina Mildner, Marie-Therese Lingitz, Clemens Aigner, Christine Radtke, Hendrik Jan Ankersmit, Michael Mildner
{"title":"The impact of burn trauma on glycocalyx derangement","authors":"Hannes Kühtreiber, Daniel Bormann, Melanie Salek, Thomas Haider, Caterina Selina Mildner, Marie-Therese Lingitz, Clemens Aigner, Christine Radtke, Hendrik Jan Ankersmit, Michael Mildner","doi":"10.1101/2024.09.02.24312926","DOIUrl":"https://doi.org/10.1101/2024.09.02.24312926","url":null,"abstract":"Burn injuries often lead to severe complications, including acute respiratory distress syndrome (ARDS), driven in part by systemic inflammation and glycocalyx disruption. In this study, we analyzed the sera of 28 patients after burn trauma and utilized transcriptomic analyses to decipher the impact of burn injury on glycocalyx derangement. We observed significant upregulation of immune cell-derived degrading enzymes, particularly matrix metalloproteinase-8 (MMP8), which correlated with increased immune cell infiltration and glycocalyx derangement. Serum analysis of burn patients revealed significantly elevated levels of shed glycocalyx components and MMP8, both correlating with the presence of inhalation injury. Consequently, treatment of human in vitro lung tissue models with MMP8 induced significant glycocalyx shedding in both, the endothelium and epithelium. Together our data suggest MMP8 as a contributor of glycocalyx disruption and lung injury post-burn.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brady Page, Raphaëlle Klitting, Matthias G. Pauthner, Steven Steinhubl, Stephan Wegerich, Margaret Kaiser, Foday Alhasan, Edwin Konuwa, Veronica Koroma, Ibrahim Sumah, Jenneh Brima, Tiangay Kallon, Brima Jusu, Sia Mator-Mabay, Isata Massaquoi, Mohamed Kamara, Fatima Kamara, Emilia Jaward, Angella Massally, Zainab Kanneh, Michelle McGraw, John Schieffelin, Donald Grant, Kristian G. Andersen
{"title":"Continuous vital sign monitoring of individuals with acute Lassa fever using wearable biosensor devices","authors":"Brady Page, Raphaëlle Klitting, Matthias G. Pauthner, Steven Steinhubl, Stephan Wegerich, Margaret Kaiser, Foday Alhasan, Edwin Konuwa, Veronica Koroma, Ibrahim Sumah, Jenneh Brima, Tiangay Kallon, Brima Jusu, Sia Mator-Mabay, Isata Massaquoi, Mohamed Kamara, Fatima Kamara, Emilia Jaward, Angella Massally, Zainab Kanneh, Michelle McGraw, John Schieffelin, Donald Grant, Kristian G. Andersen","doi":"10.1101/2024.08.29.24312749","DOIUrl":"https://doi.org/10.1101/2024.08.29.24312749","url":null,"abstract":"<strong>Background</strong> Lassa fever is a fulminant viral illness associated with high in-hospital mortality. This disease constitutes a serious public health concern in West Africa, in particular Nigeria and the Mano River Union region (Guinea, Liberia, and Sierra Leone). In Sierra Leone, continuous monitoring of critically ill patients is hindered by a lack of equipment and personnel.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henry R. Hsu, Praba Sekhar, Jahnavi Grover, David H. Tian, Ciaran Downey, Ben Maudlin, Chathuri Dissanayake, Mark Dennis
{"title":"Predictors of successful weaning from Veno-Arterial Extracorporeal Membrane Oxygenation (V-A ECMO): A Systematic Review and Meta-analysis","authors":"Henry R. Hsu, Praba Sekhar, Jahnavi Grover, David H. Tian, Ciaran Downey, Ben Maudlin, Chathuri Dissanayake, Mark Dennis","doi":"10.1101/2024.08.30.24312815","DOIUrl":"https://doi.org/10.1101/2024.08.30.24312815","url":null,"abstract":"<strong>Background</strong> Venoarterial extracorporeal membrane oxygenation (V-A ECMO) use to support patients in cardiac failure is increasing. Despite this increased use, predicting successful weaning from ECMO can be challenging, no uniform guidelines on weaning exist. Therefore, we completed a systematic review to evaluate prognostic factors that predict successful weaning from V-A ECMO.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert Balk, Annette M Esper, Greg S Martin, Russell R Miller, Bert K Lopansri, John P Burke, Mitchell Levy, Richard E Rothman, Franco R d'Alessio, Venkataramana K Sidhaye, Neil R Aggarwal, Jared A Greenberg, Mark Yoder, Gourang Patel, Emily Gilbert, Jorge P Parada, Majid Afshar, Jordan A Kempker, Tom van der Poll, Marcus J Schultz, Brendon P Scicluna, Peter M C Klein-Klouwenberg, Janice Liebler, Emily Blodget, Santhi Kumar, Winnie Mei, Krupa Navalkar, Thomas D Yager, Dayle Sampson, James T Kirk, Silvia Cermelli, Roy F Davis, Richard B Brandon
{"title":"Rapid and robust identification of sepsis using SeptiCyte RAPID in a heterogenous patient population","authors":"Robert Balk, Annette M Esper, Greg S Martin, Russell R Miller, Bert K Lopansri, John P Burke, Mitchell Levy, Richard E Rothman, Franco R d'Alessio, Venkataramana K Sidhaye, Neil R Aggarwal, Jared A Greenberg, Mark Yoder, Gourang Patel, Emily Gilbert, Jorge P Parada, Majid Afshar, Jordan A Kempker, Tom van der Poll, Marcus J Schultz, Brendon P Scicluna, Peter M C Klein-Klouwenberg, Janice Liebler, Emily Blodget, Santhi Kumar, Winnie Mei, Krupa Navalkar, Thomas D Yager, Dayle Sampson, James T Kirk, Silvia Cermelli, Roy F Davis, Richard B Brandon","doi":"10.1101/2024.08.26.24312552","DOIUrl":"https://doi.org/10.1101/2024.08.26.24312552","url":null,"abstract":"Background: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study we present results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS, and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: 1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. 2) Principal component analysis and k-means clustering analysis, to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eunicia Ursu, Ana Mikolic, Sonny Thiara, Noah D Silverberg, Denise Foster, William Panenka, Nishtha Parag, Mypinder S Sekhon, Donald E.G. Griesdale
{"title":"Post-discharge health-related quality of life, cognitive function, disability, risk of post-traumatic stress disorder, and depression amongst the survivors of venovenous extracorporeal membrane oxygenation (VV-ECMO) during the COVID-19 pandemic: a nested cohort study protocol","authors":"Eunicia Ursu, Ana Mikolic, Sonny Thiara, Noah D Silverberg, Denise Foster, William Panenka, Nishtha Parag, Mypinder S Sekhon, Donald E.G. Griesdale","doi":"10.1101/2024.08.22.24312450","DOIUrl":"https://doi.org/10.1101/2024.08.22.24312450","url":null,"abstract":"<strong>Background</strong> Veno-venous extra-corporeal membrane oxygenation (VV ECMO) is a form of\u0000mechanical respiratory support for critically ill patients with severe acute respiratory distress syndrome (ARDS). Using a large intravenous line in a closed circuit, blood is removed from the patient and passed through a hollow fiber membrane where oxygen is added and carbon dioxide is removed. The oxygenated blood is then reinfused into the patient. Overt neurologic injury (ischemic stroke or intracerebral hemorrhage) occurs in approximately 20% of patients who receive VV ECMO. However, it is unclear if there is additional unrecognized neurologic disability amongst patients who survive VV ECMO. As such, we will perform a cohort study nested within our existing prospective study of patients who underwent VV ECMO during the COVID 19 pandemic. We expect to ascertain long-term patient reported and performance-based outcomes in greater than 60% of survivors of VV-ECMO. This study will provide important patient-centric long-term outcomes in contrast to the majority of existing studies of patients on VV-ECMO which focus solely on short-term survival.\u0000<strong>Methods and analysis</strong> We will include 39 patients who survived VV-ECMO and ascertain patient\u0000reported and performance-based outcomes through phone interviews. We will measure: i) Health Related Quality of Life (HRQoL) using the EQ 5D 5L, ii) cognitive function using the T-MoCA Short, iii) disability using the World Health Organization Disability Assessment Scale (WHODAS) 2.0, iv) post traumatic stress disorder (PTSD) using the Impact of Event Scale 6 (IES 6), and v) depression using the Patient Health Questionnaire 9 (PHQ-9).\u0000<strong>Ethics and dissemination</strong> The results from the analysis of the study data will be disseminated through presentation of a scientific abstract at international conference, and submission of a\u0000manuscript in a peer-reviewed critical care medicine journal. The study ethical approval\u0000has been obtained from the University of British Columbia (UBC) Clinical Research\u0000Ethics Board (REB)(H21 00033) and the Vancouver Coastal Health Research Institute\u0000(V21 00033).","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vern Eric Kerchberger, Joel Brennan McNeil, Neil Zheng, Diana Chang, Carrie Rosenberger, Angela J Rogers, Julie A Bastarache, QiPing Feng, WeiQi Wei, Lorraine B Ware
{"title":"Electronic health record biobank cohort recapitulates an association between the MUC5B promoter polymorphism and ARDS in critically ill adults.","authors":"Vern Eric Kerchberger, Joel Brennan McNeil, Neil Zheng, Diana Chang, Carrie Rosenberger, Angela J Rogers, Julie A Bastarache, QiPing Feng, WeiQi Wei, Lorraine B Ware","doi":"10.1101/2024.08.26.24312498","DOIUrl":"https://doi.org/10.1101/2024.08.26.24312498","url":null,"abstract":"Background: Large population-based DNA biobanks linked to electronic health records (EHRs) may provide advantages over traditional study designs for identifying genetic drivers of ARDS.\u0000Research Question: Can ARDS be identified in an EHR biobank, and can this approach validate a previously reported genetic risk factor for ARDS?\u0000Study Design and Methods: We analyzed two genotyped cohorts from one academic medical center: a prospective biomarker study of critically ill adults (VALID cohort), and hospitalized participants in a de-identified EHR biobank (BioVU). ARDS status was assessed by clinician-investigator review in VALID and an EHR-derived algorithm in BioVU (EHR-ARDS). We tested the association between the MUC5B promoter polymorphism (rs35705950) with development of ARDS/EHR-ARDS in each cohort.\u0000Results: In VALID, 2,795 patients were included, age was 55 [43, 66] (median [IQR]) years, and 718 (25.7%) developed ARDS. In BioVU, 9,025 hospitalized participants were included, age was 60 [48, 70] , and 1,056 (11.7%) developed EHR-ARDS. We observed a significant interaction between age and rs35705950 on ARDS risk in VALID: in older patients rs35705950 was associated with increased ARDS risk (OR: 1.44; 95%CI 1.08-1.92; p=0.012) whereas among younger patients this effect was attenuated (OR: 0.84; 95%CI: 0.62-1.14; p=0.26). In BioVU, rs35705950 was associated with increased risk for EHR-ARDS among all participants (OR: 1.20; 95%CI: 1.00-1.43, p=0.043) and this relationship did not vary by age. The polymorphism was also associated with more severe oxygenation impairment among BioVU participants who required mechanical ventilation.\u0000Interpretation: The MUC5B promoter polymorphism was associated with ARDS in two cohorts of at-risk hospitalized adults. Although age-related effect modification was observed only in the prospective biomarker cohort, the EHR cohort identified a consistent association between MUC5B and ARDS risk regardless of age and a novel association with oxygenation impairment. Our study highlights the potential for EHR biobanks to enable precision-medicine ARDS studies.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}