268 results on '"Greg S. Martin"'
Search Results
2. Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial*
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Michael, Waters, James A, McKinnell, Andre C, Kalil, Greg S, Martin, Timothy G, Buchman, Wiebke, Theess, Xiaoying, Yang, Annemarie N, Lekkerkerker, Tracy, Staton, Carrie M, Rosenberger, Rajita, Pappu, Yehong, Wang, Wenhui, Zhang, Logan, Brooks, Dorothy, Cheung, Joshua, Galanter, Hubert, Chen, Divya, Mohan, and Melicent C, Peck
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Critical Care and Intensive Care Medicine - Abstract
Severe cases of COVID-19 pneumonia can lead to acute respiratory distress syndrome (ARDS). Release of interleukin (IL)-33, an epithelial-derived alarmin, and IL-33/ST2 pathway activation are linked with ARDS development in other viral infections. IL-22, a cytokine that modulates innate immunity through multiple regenerative and protective mechanisms in lung epithelial cells, is reduced in patients with ARDS. This study aimed to evaluate safety and efficacy of astegolimab, a human immunoglobulin G2 monoclonal antibody that selectively inhibits the IL-33 receptor, ST2, or efmarodocokin alfa, a human IL-22 fusion protein that activates IL-22 signaling, for treatment of severe COVID-19 pneumonia.Phase 2, double-blind, placebo-controlled study (COVID-astegolimab-IL).Hospitals.Hospitalized adults with severe COVID-19 pneumonia.Patients were randomized to receive IV astegolimab, efmarodocokin alfa, or placebo, plus standard of care. The primary endpoint was time to recovery, defined as time to a score of 1 or 2 on a 7-category ordinal scale by day 28.The study randomized 396 patients. Median time to recovery was 11 days (hazard ratio [HR], 1.01 d; p = 0.93) and 10 days (HR, 1.15 d; p = 0.38) for astegolimab and efmarodocokin alfa, respectively, versus 10 days for placebo. Key secondary endpoints (improved recovery, mortality, or prevention of worsening) showed no treatment benefits. No new safety signals were observed and adverse events were similar across treatment arms. Biomarkers demonstrated that both drugs were pharmacologically active.Treatment with astegolimab or efmarodocokin alfa did not improve time to recovery in patients with severe COVID-19 pneumonia.
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- 2022
3. Dysregulated naive B cells and de novo autoreactivity in severe COVID-19
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Matthew C. Woodruff, Richard P. Ramonell, Natalie S. Haddad, Fabliha A. Anam, Mark E. Rudolph, Tiffany A. Walker, Alexander D. Truong, Adviteeya N. Dixit, Jenny E. Han, Monica Cabrera-Mora, Martin C. Runnstrom, Regina Bugrovsky, Jennifer Hom, Erin C. Connolly, Igor Albizua, Vidhi Javia, Kevin S. Cashman, Doan C. Nguyen, Shuya Kyu, Ankur Singh Saini, Michael Piazza, Christopher M. Tipton, Arezou Khosroshahi, Greg Gibson, Greg S. Martin, Cheryl L. Maier, Annette Esper, Scott A. Jenks, F. Eun-Hyung Lee, and Ignacio Sanz
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B-Lymphocytes ,Post-Acute COVID-19 Syndrome ,Multidisciplinary ,SARS-CoV-2 ,Immunoglobulin G ,Humans ,COVID-19 ,macromolecular substances ,Single-Cell Analysis ,Autoantigens ,Basement Membrane ,Article ,Autoantibodies - Abstract
Severe SARS-CoV-2 infection1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic2–5. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential6–10, although their origins and resolution have remained unclear11. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity12,13, as a dominant feature of severe and critical COVID-19 (refs. 14–18). Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10–15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae.
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- 2022
4. Home-to-hospital distance and outcomes among community-acquired sepsis hospitalizations
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Joshua F. Detelich, Nang Thu Kyaw, Suzanne E. Judd, Aleena Bennett, Henry E. Wang, Michael R. Kramer, Lance A. Waller, Greg S. Martin, and Jordan A. Kempker
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Adult ,Hospitalization ,Epidemiology ,Sepsis ,Humans ,Hospital Mortality ,Prospective Studies ,Hospitals ,Retrospective Studies - Abstract
To examine the hypothesis that longer distance from home-to-hospital is associated with worse outcomes among hospitalizations for community-acquired sepsis.A secondary analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort of 30,239 white and Black US adults greater than or equal to 45 years old was conducted. Self-reported hospitalizations for serious infection between 2003 and 2012 fulfilling 2/4 systemic inflammatory response syndrome criteria were included. Estimated driving distance was derived from geocoded data and evaluated continuously and as quartiles of very close, close, far, very far (3.1, 3.1-5.8, 5.9-11.5, and11.5 miles respectively). The primary outcome was 30-day mortality while the secondary outcome was sequential organ failure assessment (SOFA) score on arrival.Of the 912 hospitalizations for community-acquired sepsis had adequate data for analysis. The median (interquartile range) estimated driving distance was 5.8 miles (3.1,11.7), and 54 (5.9%) experienced the primary outcome. Compared to living very close, participants living very far had a mortality odds ratio of 1.30 (95% CI 0.64,2.62) and presenting SOFA score difference of 0.33 (95% CI -0.03,0.68).Among a national sample of community-acquired sepsis hospitalizations, there was no significant association between home-to-hospital distance and either 30-day mortality or SOFA score on hospital presentation.
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- 2022
5. Designing for simplicity: lessons from Mesa Biotech for microfluidic entrepreneurs and early-stage companies
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Morgan N. Greenleaf, Gregory L. Damhorst, David N. Ku, Eric J. Nehl, Erika A. Tyburski, Oliver Brand, Greg S. Martin, and Wilbur A. Lam
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SARS-CoV-2 ,Microfluidics ,Biomedical Engineering ,COVID-19 ,Humans ,Bioengineering ,General Chemistry ,Pandemics ,Biochemistry ,Article ,Biotechnology - Abstract
The COVID-19 pandemic has proven the need for point-of-care diagnosis of respiratory diseases and microfluidic technology has risen to the occasion. Mesa Biotech (San Diego, CA) originally developed the Accula platform for the diagnosis of influenza A and B and then extended the platform to SARS-CoV-2. Mesa Biotech has experienced tremendous success, culminating in acquisition by Thermo Fisher for up to $550m USD. The Accula microfluidics platform accomplished the leap from the lab to commercial product through clever design and engineering choices. Through information obtained from interviews with key Mesa Biotech leaders and publicly-available documents, we describe the keys to Mesa's success and how they might inform other lab-on-a-chip companies.
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- 2022
6. The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?
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Rui Moreno, Andrew Rhodes, Lise Piquilloud, Glenn Hernandez, Jukka Takala, Hayley B. Gershengorn, Miguel Tavares, Craig M. Coopersmith, Sheila N. Myatra, Mervyn Singer, Ederlon Rezende, Hallie C. Prescott, Márcio Soares, Jean-François Timsit, Dylan W. de Lange, Christian Jung, Jan J. De Waele, Greg S. Martin, Charlotte Summers, Elie Azoulay, Tomoko Fujii, Anthony S. McLean, Jean-Louis Vincent, and Apollo - University of Cambridge Repository
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Organ Dysfunction Scores ,Critical Illness ,Multiple Organ Failure ,HSJ UCI ,610 Medicine & health ,Critical Illness* / therapy ,Critical Care and Intensive Care Medicine ,Prognosis ,Multiple Organ Failure / diagnosis ,Perspective ,Humans ,610 Medizin und Gesundheit ,Critical Illness/therapy ,Multiple Organ Failure/diagnosis - Abstract
The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.
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- 2023
7. Early Albumin Infusion Is Associated With Greater Survival to Discharge Among Patients With Sepsis/Septic Shock Who Develop Severe Acute Kidney Injury Among Patients With Sepsis/Septic Shock Who Develop Severe Acute Kidney Injury
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Karthik, Raghunathan, Jordan A, Kempker, E Anne, Davis, Navreet S, Sindhwani, Santosh, Telang, Kunal, Lodaya, and Greg S, Martin
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Adults hospitalized with sepsis/septic shock commonly develop acute kidney injury (AKI) which imposes a significant burden on the healthcare system. The administration of early human albumin in this patient population may yield more efficient healthcare resource utilization.To examine the association between early use of albumin and time to discharge in adults who develop severe AKI while hospitalized with sepsis/septic shock.Retrospective cohort study using de-identified electronic health records from a national database (Cerner Health Facts; Cerner Corp., Kansas City, MO).Patients (Patients were grouped according to timing of albumin exposure: within less than or equal to 24 hours of admission ("early albumin") or unexposed/exposed late ("nonearly albumin"). A cause-specific hazard model, censoring for death/discharge to hospice, was used to examine the association between "early albumin" and the rate of hospital discharge with clinical stability.Albumin was administered early in 8.6% of cases. Cases with early albumin administration had a median time to discharge of 13.2 days compared with 17.0 in the nonearly group (Log-rankThe use of albumin within 24 hours of hospital admission was associated with a shorter time to discharge and a higher rate of discharge with clinical stability, suggesting an improvement in healthcare resource utilization among patients with sepsis/septic shock who developed stage 3 AKI during hospitalization.
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- 2022
8. SCCM/ACCM Guideline and Toolkit Development Pathways
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Sandra L. Kane-Gill, Lori Harmon, Vinay M. Nadkarni, Lewis J. Kaplan, Greg S. Martin, Julie Winkle, and Lauren R. Sorce
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Critical Care ,business.industry ,Guideline ,Critical Care and Intensive Care Medicine ,United States ,Evidence-Based Emergency Medicine ,Intensive Care Units ,Engineering management ,Practice Guidelines as Topic ,Humans ,Medicine ,business ,Patient Care Bundles ,Societies, Medical - Published
- 2021
9. Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States
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Nida Qadir, Raquel R. Bartz, Mary L. Cooter, Catherine L. Hough, Michael J. Lanspa, Valerie M. Banner-Goodspeed, Jen-Ting Chen, Shewit Giovanni, Dina Gomaa, Michael W. Sjoding, Negin Hajizadeh, Jordan Komisarow, Abhijit Duggal, Ashish K. Khanna, Rahul Kashyap, Akram Khan, Steven Y. Chang, Joseph E. Tonna, Harry L. Anderson, Janice M. Liebler, Jarrod M. Mosier, Peter E. Morris, Alissa Genthon, Irene K. Louh, Mark Tidswell, R. Scott Stephens, Annette M. Esper, David J. Dries, Anthony Martinez, Kraftin E. Schreyer, William Bender, Anupama Tiwari, Pramod K. Guru, Sinan Hanna, Michelle N. Gong, Pauline K. Park, Jay S. Steingrub, Kristin Brierley, Julia L. Larson, Ariel Mueller, Tereza Pinkhasova, Daniel Talmor, Imoigele Aisiku, Rebecca Baron, Lauren Fredenburgh, Peter Hou, Anthony Massaro, Raghu Seethala, Duncan Hite, Daniel Brodie, Briana Short, Raquel Bartz, Jordan C. Komisarow, James Blum, Annette Esper, Greg S. Martin, Eileen Bulger, Anna Ungar, Samuel M. Brown, Colin K. Grissom, Eliotte L. Hirshberg, Ithan D. Peltan, Roy G. Brower, Sarina K. Sahetya, R Scott Stephens, John K. Bohman, Hongchuan Coville, Ognjen Gajic, John C. O’Horo, Jorge-Bleik Ataucuri-Vargas, Fiore Mastroianni, Jamie Hirsch, Michael Qui, Molly Stewart, Ebaad Haq, Makrina Kamel, Olivia Krol, Kimberly Lerner, John Marini, Valentina Chiara Bistolfi Amaral, Jill Brown, Michael Brozik, Heidi Kemmer, Janet Obear, Nina Gentile, Kraftin E. Shreyer, Charles Cairns, Cameron Hypes, Josh Malo, Jarrod Mosier, Bhupinder Natt, Scott Hu, Ishan Mehta, Richard Branson, Betty Tsuei, Sanjay Dhar, Ashley Montgomery-Yates, Peter Morris, Tina Chen, Alfredo Lee Chang, Perren Cobb, Estelle Harris, Nate Hatton, Gia Lewis, Stephen McKellar, Sanjeev Raman, Joseph Tonna, Ellen Caldwell, and Sarah Dean
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Pulmonary and Respiratory Medicine ,ARDS ,medicine.medical_specialty ,business.industry ,Mortality rate ,Peak inspiratory pressure ,Critical Care and Intensive Care Medicine ,medicine.disease ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Standardized mortality ratio ,030228 respiratory system ,Interquartile range ,Emergency medicine ,medicine ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,Tidal volume ,Cohort study - Abstract
Background Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. Research Question What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? Study Design and Methods We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pa o 2 to F io 2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed. Results A total of 2,466 patients were enrolled. Median baseline Pa o 2 to F io 2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR. Interpretation Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. Trial Registry ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov
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- 2021
10. Subgenomic RNA Abundance Relative to Total Viral RNA Among Severe Acute Respiratory Syndrome Coronavirus 2 Variants
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Maxwell Su, Sara Ping, Phuong-Vi Nguyen, Alejandra Rojas, Laila Hussaini, Ludy Registre Carmola, Azmain Taz, Julie Sullivan, Greg S Martin, Anne Piantadosi, Magaly Martinez, Wilbur A Lam, Evan J Anderson, and Jesse J Waggoner
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Infectious Diseases ,Oncology - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subgenomic RNA (sgRNA) may indicate actively replicating virus, but sgRNA abundance has not been systematically compared between SARS-CoV-2 variants. sgRNA was quantified in 169 clinical samples by real-time reverse-transcription polymerase chain reaction, demonstrating similar relative abundance among known variants. Thus, sgRNA detection can identify individuals with active viral replication regardless of variant.
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- 2022
11. Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS
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Xian Qiao, Markos G. Kashiouris, Michael L’Heureux, Bernard J. Fisher, Stefan W. Leichtle, Jonathon D. Truwit, Rahul Nanchal, Robert Duncan Hite, Peter E. Morris, Greg S. Martin, Jonathan Sevransky, and Alpha A. Fowler
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Respiratory Distress Syndrome ,Nutrition and Dietetics ,Sepsis ,sepsis ,vitamin C ,glycocalyx ,syndecan-1 ,cell-free DNA ,acute respiratory distress syndrome ,Humans ,Syndecan-1 ,Ascorbic Acid ,Vitamins ,Glycocalyx ,Extracellular Traps ,Cell-Free Nucleic Acids ,Biomarkers ,Food Science - Abstract
(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng/µL (SD 4.20 ng/µL) and 2.65 ng/µL (SD 3.87 ng/µL), respectively, p = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, p = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng/mL (SD 5.57 ng/mL) and 10.83 ng/mL (SD 5.95 ng/mL), respectively, p = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng/mL (95% CI, 0.21 to 1.29, p = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively.
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- 2022
12. Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race
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Jennifer K. Frediani, Ezra Pak-Harvey, Richard Parsons, Adrianna L. Westbrook, William O'Sick, Greg S. Martin, Wilbur A. Lam, and Joshua M. Levy
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Molecular Medicine ,Cell Biology ,Hematology ,Molecular Biology - Published
- 2023
13. Validation of SeptiCyte RAPID to discriminate sepsis from non-infectious systemic inflammation
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Robert Balk, Annette M. Esper, Greg S. Martin, Russell R. Miller, Bert K. Lopansri, John P. Burke, Mitchell Levy, Steven Opal, 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, Krupa Navalkar, Thomas D Yager, Dayle Sampson, James T. Kirk, Silvia Cermelli, Roy F. Davis, and Richard B. Brandon
- Abstract
Background: SeptiCyte RAPID is a molecular test for distinguishing sepsis from non-infectious systemic inflammation. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospective (banked) and prospectively collected patient samples. Methods: The cartridge-based SeptiCyte RAPID assay accepts a PAXgene blood RNA sample and provides sample-to-answer processing in about 1 hour. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (banked) and prospective samples from adult patients in ICU either having systemic inflammatory response syndrome (SIRS), or suspected of sepsis under either the Sepsis-2 or Sepsis-3 definition were tested, and results were compared to a gold standard of clinical evaluation by a blinded, three-physician external panel. A multivariable analysis was performed, in which SeptiScore was combined with other clinical variables. Results: With adjudication under the Sepsis-2 definition, SeptiCyte RAPID performance for the complete cohort (356 retrospective + 63 prospective patients) had Area Under the ROC Curve (AUC) ranging from 0.82-0.85, negative predictive value 0.91 (sensitivity 0.94) for SeptiScores between 0.1 and 5.0 (Band 1, lowest risk of sepsis), and positive predictive value 0.81 (specificity 0.90) for SeptiScores between 7.4 and 15 (Band 4, highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. Comparable results were obtained when the data were reanalyzed under the Sepsis-3 definition. Conclusions: This study validates SeptiCyte RAPID for differentiating patients with sepsis vs. SIRS, on the first day of ICU admission. Trial Registration:NCT01905033(MARS),NCT02127502(VENUS),NCT05469048(NEPTUNE, retrospectively registered) at clinicaltrials.gov. Keywords: sepsis, diagnosis, host response, SIRS, sepsis scoring systems
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- 2022
14. Don't forget about human factors: Lessons learned from COVID-19 point-of-care testing
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Sarah Farmer, Victoria Razin, Amanda Foster Peagler, Samantha Strickler, W. Bradley Fain, Gregory L. Damhorst, Russell R. Kempker, Nira R. Pollock, Oliver Brand, Brooke Seitter, Stacy S. Heilman, Eric J. Nehl, Joshua M. Levy, David S. Gottfried, Greg S. Martin, Morgan Greenleaf, David N. Ku, Jesse J. Waggoner, Elizabeth Iffrig, Robert G. Mannino, Yun F. Wang, Eric Ortlund, Julie Sullivan, Paulina A. Rebolledo, Viviana Clavería, John D. Roback, MacArthur Benoit, Cheryl Stone, Annette Esper, Filipp Frank, and Wilbur A. Lam
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Cultural Studies ,History ,Literature and Literary Theory - Abstract
During the COVID-19 pandemic, the development of point-of-care (POC) diagnostic testing accelerated in an unparalleled fashion. As a result, there has been an increased need for accurate, robust, and easy-to-use POC testing in a variety of non-traditional settings (i.e., pharmacies, drive-thru sites, schools). While stakeholders often express the desire for POC technologies that are "as simple as digital pregnancy tests," there is little discussion of what this means in regards to device design, development, and assessment. The design of POC technologies and systems should take into account the capabilities and limitations of the users and their environments. Such "human factors" are important tenets that can help technology developers create POC technologies that are effective for end-users in a multitude of settings. Here, we review the core principles of human factors and discuss lessons learned during the evaluation process of SARS-CoV-2 POC testing.
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- 2022
15. Remote Continuous Glucose Monitoring With a Computerized Insulin Infusion Protocol for Critically Ill Patients in a COVID-19 Medical ICU: Proof of Concept
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Guillermo E. Umpierrez, Georgia Davis, Barbara McLean, Shivani Agarwal, Kathleen Dungan, Citlalli Perez-Guzman, Francisco J. Pasquel, Marina Rabinovich, Limin Peng, Eileen R Faulds, Norma Poindexter, Tara Walker, Joi C. Hester, Debbie Vigliotti, Patricia Hannon, Seema S. Tekwani, Petrena Saunders, and Greg S. Martin
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Blood Glucose ,Male ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Critical Illness ,Point-of-Care Systems ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Proof of Concept Study ,law.invention ,Diabetes Complications ,03 medical and health sciences ,Insulin Infusion Systems ,0302 clinical medicine ,law ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Insulin ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,Advanced and Specialized Nursing ,Mechanical ventilation ,Protocol (science) ,SARS-CoV-2 ,Continuous glucose monitoring ,business.industry ,Critically ill ,Blood Glucose Self-Monitoring ,COVID-19 ,Middle Aged ,medicine.disease ,Intensive care unit ,COVID-19 Drug Treatment ,Novel Communications in Diabetes ,Clinical trial ,Intensive Care Units ,Equipment and Supplies ,Remote Sensing Technology ,Emergency medicine ,Female ,business ,Algorithms - Abstract
OBJECTIVE The use of remote real-time continuous glucose monitoring (CGM) in the hospital has rapidly emerged to preserve personal protective equipment and reduce potential exposures during coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS We linked a hybrid CGM and point-of-care (POC) glucose testing protocol to a computerized decision support system for continuous insulin infusion and integrated a validation system for sensor glucose values into the electronic health record. We report our proof-of-concept experience in a COVID-19 intensive care unit. RESULTS All nine patients required mechanical ventilation and corticosteroids. During the protocol, 75.7% of sensor values were within 20% of the reference POC glucose with an associated average reduction in POC of 63%. Mean time in range (70–180 mg/dL) was 71.4 ± 13.9%. Sensor accuracy was impacted by mechanical interferences in four patients. CONCLUSIONS A hybrid protocol integrating real-time CGM and POC is helpful for managing critically ill patients with COVID-19 requiring insulin infusion.
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- 2021
16. Critical Care Management of the Patient with Clostridioides difficile
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Greg S. Martin, Max W. Adelman, Virginia O. Shaffer, Colleen S. Kraft, and Michael H. Woodworth
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medicine.medical_specialty ,genetic structures ,Critical Care ,Ileus ,Fulminant ,Critical Care and Intensive Care Medicine ,Inflammatory bowel disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Epidemiology ,medicine ,Humans ,Infection control ,Intensive care medicine ,Clostridioides difficile ,business.industry ,Clindamycin ,030208 emergency & critical care medicine ,Fecal Microbiota Transplantation ,medicine.disease ,Anti-Bacterial Agents ,Metronidazole ,030228 respiratory system ,Clostridium Infections ,Vancomycin ,business ,medicine.drug - Abstract
Objectives To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients. Data sources We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles. Study selection We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence. Data extraction We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review. Data synthesis C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk. Conclusions Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.
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- 2020
17. Adequacy of Nasal Self-Swabbing for SARS-CoV-2 Testing in Children
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Jesse J. Waggoner, Miriam B. Vos, Erika A. Tyburski, Phuong-Vi Nguyen, Jessica M. Ingersoll, Candace Miller, Julie Sullivan, Mark Griffiths, Cheryl Stone, Macarthur Benoit, Laura Benedit, Brooke Seitter, Robert Jerris, Joshua M. Levy, Colleen S. Kraft, Sarah Farmer, Amanda Foster, Anna Wood, Adrianna L. Westbrook, Claudia R. Morris, Usha N. Sathian, William Heetderks, Li Li, Kristian Roth, Mary Barcus, Timothy Stenzel, Greg S. Martin, and Wilbur A. Lam
- Abstract
BackgroundThe goal of this study was to characterize the ability of school-aged children to self-collect adequate anterior nares (AN) swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing.MethodsFrom July to August 2021, 287 children, age 4-14 years-old, were prospectively enrolled in the Atlanta area. Symptomatic (n=197) and asymptomatic (n=90) children watched a short instructional video before providing a self-collected AN specimen. Health care workers (HCWs) then collected a second specimen, and useability was assessed by the child and HCW. Swabs were tested side-by-side for SARS-CoV-2. RNase P RNA detection was investigated as a measure of specimen adequacy.ResultsAmong symptomatic children, 87/196 (44.4%) tested positive for SARS-CoV-2 by both self- and HCW-swab. Two children each were positive by self- or HCW-swab; one child had an invalid HCW-swab. Compared to HCW-swabs, self-collected swabs had 97.8% and 98.1% positive and negative percent agreements, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups. Participants ≤8 years-old were less likely than those >8 to be rated as correctly completing self-collection, but SARS-CoV-2 detection did not differ. Based on RNase P RNA detection, 270/287 children (94.1%) provided adequate self-swabs versus 277/287 (96.5%) HCW-swabs (p=0.24) with no difference when stratified by age.ConclusionsChildren, aged 4-14 years-old, can provide adequate AN specimens for SARS-CoV-2 detection when presented with age-appropriate instructional material, consisting of a video and a handout, at a single timepoint. These data support the use of self-collected AN swabs among school-age children for SARS-CoV-2 testing.
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- 2022
18. Where is Omicron? Comparison of SARS-CoV-2 RT-PCR and Antigen Test Sensitivity at Commonly Sampled Anatomic Sites Over the Course of Disease
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Jessica Lin, Jennifer K Frediani, Gregory L Damhorst, Julie A Sullivan, Adrianna Westbrook, Kaleb McLendon, Tyler J Baugh, William H O’Sick, John D Roback, Anne L Piantadosi, Jesse J Waggoner, Leda Bassit, Anuradha Rao, Morgan Greenleaf, Jared W O’Neal, Seegar Swanson, Nira R Pollock, Greg S Martin, Wilbur A Lam, and Joshua M Levy
- Subjects
Article - Abstract
BackgroundUpper respiratory samples for SARS-CoV-2 detection include the gold standard nasopharyngeal (NP) swab, and mid-turbinate (MT) nasal swabs, oropharyngeal (OP) swabs, and saliva. Following the emergence of the omicron (B.1.1.529) variant, limited preliminary data suggest that OP swabs or saliva samples may be more sensitive than nasal swabs, highlighting the need to understand differences in viral load across different sites.MethodsMT, OP, and saliva samples were collected from symptomatic individuals presenting for evaluation in Atlanta, GA, in January 2022. Longitudinal samples were collected from a family cohort following COVID-19 exposure to describe detection of viral targets over the course of infection.ResultsSARS-CoV-2 RNA and nucleocapsid antigen measurements demonstrated a nares-predominant phenotype in a familial cohort. A consistent dominant location for SARS-CoV-2 was not found among 54 individuals. Positive percent agreement for virus detection in MT, OP and saliva specimens were 66.7 [54.1–79.2], 82.2 [71.1–93.4], and 72.5 [60.3–84.8] by RT-PCR, respectively, and 46.2 [32.6–59.7], 51.2 [36.2–66.1], and 72.0 [59.6–84.4] by ultrasensitive antigen assay. The composite of positive MT or OP assay was not significantly different than either alone for both RT-PCR and antigen assay (PPA 86.7 [76.7–96.6] and 59.5 [44.7–74.4], respectively).ConclusionsOur data suggest that SARS-CoV-2 nucleocapsid and RNA exhibited similar kinetics and diagnostic yield in three upper respiratory sample types across the duration of symptomatic disease. Collection of OP or combined nasal and OP samples does not appear to increase sensitivity versus validated nasal sampling for rapid detection of viral antigen.
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- 2022
19. Plasma High‐Resolution Metabolomics Differentiates Adults with Normal Weight Obesity from Lean Individuals
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Jessica A. Alvarez, Thomas R. Ziegler, Greg S. Martin, Dean P. Jones, Phong H. Tran, Ken H. Liu, Qingpo Cai, Miriam B. Vos, Tianwei Yu, and Moriah P. Bellissimo
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Linoleic acid ,Medicine (miscellaneous) ,High resolution ,030209 endocrinology & metabolism ,Disease ,Overweight ,Article ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Metabolomics ,Internal medicine ,Humans ,Medicine ,Obesity ,030212 general & internal medicine ,Nutrition and Dietetics ,business.industry ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Normal weight obesity ,chemistry ,Body Composition ,Female ,medicine.symptom ,business ,Body mass index - Abstract
OBJECTIVE This study explored underlying metabolism-related dysfunction by examining metabolomic profiles in adults categorized as lean, as having normal weight obesity (NWO), or as having overweight/obesity. METHODS Participants (N = 179) had fasting plasma analyzed by liquid chromatography and high-resolution mass spectrometry for high-resolution metabolomics. Body composition was assessed by dual-energy x-ray absorptiometry. NWO was defined as BMI 30% for women and > 23% for men. Differentiating metabolomic features were determined by using linear regression models and likelihood ratio tests with false discovery rate correction. Mummichog was used for pathway and network analyses. RESULTS A total of 222 metabolites significantly differed between the groups at a false discovery rate of q = 0.2. Linoleic acid, β-alanine, histidine, and aspartate/asparagine metabolism pathways were significantly enriched (all P
- Published
- 2019
20. Predictive Value of Isolated Symptoms for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children Tested During Peak Circulation of the Delta Variant
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Adrianna L Westbrook, Laura C Benedit, Jennifer K Frediani, Mark A Griffiths, Nabeel Y Khan, Joshua M Levy, Claudia R Morris, Christina A Rostad, Cheryl L Stone, Julie Sullivan, Miriam B Vos, Jean Welsh, Anna Wood, Greg S Martin, Wilbur Lam, and Nira R Pollock
- Subjects
Microbiology (medical) ,Infectious Diseases ,COVID-19 Testing ,Cough ,Fever ,Rhinorrhea ,SARS-CoV-2 ,Headache ,COVID-19 ,Humans ,Pharyngitis ,Child - Abstract
Background Coronavirus disease 2019 (COVID-19) testing policies for symptomatic children attending US schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with 1 symptom vs ≥2 symptoms, and to examine the predictive capability of isolated symptoms. Methods Participants aged Results Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting 1 symptom (n = 82; odds ratio [OR], 6.00 [95% confidence interval {CI}, 2.70–13.33]) and children reporting ≥2 symptoms (n = 365; OR, 5.25 [95% CI, 2.66–10.38]) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n = 155), but they were not significantly different from each other (OR, 0.88 [95% CI, .52–1.49]). Sensitivity and PPV were highest for isolated fever (33% and 57%, respectively), cough (25% and 32%), and sore throat (21% and 45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity and PPV of isolated congestion/rhinorrhea were 8% and 9%, respectively. Conclusions With high Delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered the highest predictive value.
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- 2021
21. Predictive value of isolated symptoms for diagnosis of SARS-CoV-2 infection in children tested during peak circulation of the delta variant
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Adrianna L. Westbrook, Laura C. Benedit, Jennifer K Frediani, Mark A. Griffiths, Nabeel Y. Khan, Joshua M. Levy, Claudia R. Morris, Christina A. Rostad, Cheryl L. Stone, Julie Sullivan, Miriam B. Vos, Jean Welsh, Anna Wood, Greg S. Martin, Wilbur Lam, and Nira R. Pollock
- Abstract
BackgroundCOVID-19 testing policies for symptomatic children attending U.S. schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for SARS-CoV-2 testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with one versus ≥2 symptoms, and to examine the predictive capability of isolated symptoms.MethodsParticipants ≤ 18 years presenting for clinical SARS-CoV-2 molecular testing in six sites in urban/suburban/rural Georgia (July-October, 2021; delta variant predominant) were queried about individual symptoms. Participants were classified into three groups: asymptomatic, one symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the three groups were compared. Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) for isolated symptoms were calculated by fitting a saturated Poisson model.ResultsOf 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting one symptom (n=82; OR=6.00, 95% CI: 2.70-13.33) and children reporting ≥2 symptoms (n=365; OR=5.25: 2.66-10.38) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n=155), but they were not significantly different from each other (OR=0.88: 0.52-1.49). Sensitivity/PPV were highest for isolated fever (33%/57%), cough (25%/32%), and sore throat (21%/45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity/PPV of isolated congestion/rhinorrhea were 8%/9%.ConclusionsWith high delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered highest predictive value.Key pointsIn an area with high community prevalence of the delta variant, children presenting with one symptom were as likely as those with two or more symptoms to test positive for SARS-CoV-2 infection. Isolated symptoms should be considered in testing decisions.
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- 2021
22. Single-Amplicon Multiplex Real-Time Reverse Transcription-PCR with Tiled Probes To Detect SARS-CoV-2 spike Mutations Associated with Variants of Concern
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Ann Chahroudi, Anne Piantadosi, Jessica Ingersoll, Greg S. Martin, Heath L. Bradley, Samuel D. Stampfer, Jesse J. Waggoner, Raymond F. Schinazi, Leda Bassit, Max Su, Wilbur A. Lam, Victoria Stittleburg, Maud Mavigner, Nils Schoof, Ahmed Babiker, Anuradha Rao, Katherine Immergluck, Colleen S. Kraft, and Vi Nguyen
- Subjects
Microbiology (medical) ,variants ,Mutation ,SARS-CoV-2 ,COVID-19 ,Reverse Transcription ,Amplicon ,Biology ,Real-Time Polymerase Chain Reaction ,medicine.disease_cause ,molecular epidemiology ,Molecular biology ,DNA sequencing ,Reverse transcriptase ,Real-time polymerase chain reaction ,Virology ,diagnostics ,medicine ,Humans ,RNA, Viral ,SNP ,Multiplex ,Primer (molecular biology) - Abstract
To provide an accessible and inexpensive method to surveil for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, we developed a multiplex real-time reverse transcription-PCR (rRT-PCR) assay, the Spike single-nucleotide polymorphism (SNP) assay, to detect specific mutations in the spike receptor binding domain. A single primer pair was designed to amplify a 348-bp region of spike, and probes were initially designed to detect K417, E484K, and N501Y. The assay was evaluated using characterized variant sample pools and residual nasopharyngeal samples. Variant calls were confirmed by SARS-CoV-2 genome sequencing in a subset of samples. Subsequently, a fourth probe was designed to detect L452R. The lower limit of 95% detection was 2.46 to 2.48 log10 genome equivalents (GE)/ml for the three initial targets (∼1 to 2 GE/reaction). Among 253 residual nasopharyngeal swabs with detectable SARS-CoV-2 RNA, the Spike SNP assay was positive in 238 (94.1%) samples. All 220 samples with threshold cycle (CT) values of
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- 2021
23. Lessons Learned from In-Person Conferences in the Times of COVID-19
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Maryam Ehteshami, Carlos León Edgar, Lucia Yunuen Delgado Ayala, Michael Hagan, Greg S. Martin, Wilbur Lam, and Raymond F. Schinazi
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Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,COVID-19 ,scientific meeting ,in-person conferences ,rapid antigen testing ,risk mitigation ,Hep-DART - Abstract
Scientific societies and conference secretariats have recently resumed in-person meetings after a long pause owing to the COVID-19 pandemic. Some safety measures continue to be implemented at these in-person events to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With increased numbers of waves of infection, caused by the emergence of SARS-CoV-2 variants, additional information is needed to ensure maximal safety at in-person events. The MEX-DART case study was conducted at the in-person Hep-DART 2021 conference, which was held in Los Cabos, Mexico, in December 2021. Many COVID-19 safety measures were implemented, and incidence of SARS-CoV-2 infection during the conference was tested onsite. In this study, we highlight the specific conditions and safety measures set in place at the conference. In addition to vaccination requirements, social distancing, and mask wearing, daily rapid testing was implemented for the duration of the conference. At the end of the 4-day meeting, none of the 166 delegates (and family members attending the conference) had tested antigen positive for SARS-CoV-2. Two delegates tested positive in the week after the conference; the timing of their positive test result suggests that they contracted the virus during their travels home or during postconference vacationing. We believe that this model can serve as a helpful template for organizing future in-person meetings in the era of COVID-19 and any other respiratory virus pandemics of the future. While the outcomes of this case study are encouraging, seasonal surges in respiratory virus infections such as SARS-CoV-2, RSV, and influenza virus incidence suggest that continued caution is warranted.
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- 2022
24. Pulmonary Edema II: Noncardiogenic Pulmonary Edema
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Greg S. Martin, Gerald W. Staton, and Annette M. Esper
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medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,Pulmonary edema ,medicine.disease ,business - Published
- 2021
25. Pulmonary Edema I: Cardiogenic Pulmonary Edema
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Annette M. Esper, Gerald W. Staton, and Greg S. Martin
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medicine.medical_specialty ,Cardiogenic pulmonary edema ,business.industry ,Internal medicine ,medicine ,Cardiology ,business ,Pulmonary edema ,medicine.disease - Abstract
There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome). This review focuses on cardiogenic pulmonary edema and describes the general approach to patients with suspected cardiogenic pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of cardiogenic pulmonary edema are reviewed. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with cardiogenic pulmonary edema and treatment options. This review contains 3 figures, 4 tables, and 29 references Keywords: cardiogenic pulmonary edema, congestive heart failure, pulmonary edema, Starling’s law
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- 2021
26. The Evolution of Toolkits and Bundles to Improve the Care of Sepsis Patients
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Greg S, Martin, Sandra L, Kane-Gill, Vinay, Nadkarni, Lauren R, Sorce, Lewis J, Kaplan, Maurizio, Cecconi, Elie, Azoulay, Jean-Louis, Teboul, Lui, Forni, and Jozef, Kesecioglu
- Subjects
Intensive Care Units ,Clinical Protocols ,Resuscitation ,Sepsis ,Humans ,Shock, Septic ,Patient Care Bundles - Published
- 2021
27. Serial Measurements of Protein Biomarkers in Sepsis-Induced Acute Respiratory Distress Syndrome
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Philip, Yang, Elizabeth, Iffrig, Frank, Harris, Andre L, Holder, Greg S, Martin, and Annette M, Esper
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Critical Care and Intensive Care Medicine - Abstract
The role of early, serial measurements of protein biomarkers in sepsis-induced acute respiratory distress syndrome (ARDS) is not clear.To determine the differences in soluble receptor for advanced glycation end-products (sRAGEs), angiopoietin-2, and surfactant protein-D (SP-D) levels and their changes over time between sepsis patients with and without ARDS.Prospective observational cohort study of adult patients admitted to the medical ICU at Grady Memorial Hospital within 72 hours of sepsis diagnosis.Plasma sRAGE, angiopoietin-2, and SP-D levels were measured for 3 consecutive days after enrollment. The primary outcome was ARDS development, and the secondary outcome of 28-day mortality. The biomarker levels and their changes over time were compared between ARDS and non-ARDS patients and between nonsurvivors and survivors.We enrolled 111 patients, and 21 patients (18.9%) developed ARDS. The three biomarker levels were not significantly different between ARDS and non-ARDS patients on all 3 days of measurement. Nonsurvivors had higher levels of all three biomarkers than did survivors on multiple days. The changes of the biomarker levels over time were not different between the outcome groups. Logistic regression analyses showed association between day 1 SP-D level and mortality (odds ratio, 1.52; 95% CI, 1.03-2.24;Among critically ill patients with sepsis, sRAGE, angiopoietin-2, and SP-D levels were not significantly different between ARDS and non-ARDS patients but were higher in nonsurvivors compared with survivors. The trend toward higher levels of sRAGE and SP-D, but not of angiopoietin-2, in ARDS patients may indicate the importance of epithelial injury in sepsis-induced ARDS. Changes of the biomarker levels over time were not different between the outcome groups.
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- 2022
28. Concordance of SARS-CoV-2 Results in Self-collected Nasal Swabs vs Swabs Collected by Health Care Workers in Children and Adolescents
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Jesse J. Waggoner, Miriam B. Vos, Erika A. Tyburski, Phuong-Vi Nguyen, Jessica M. Ingersoll, Candace Miller, Julie Sullivan, Mark Griffiths, Cheryl Stone, Macarthur Benoit, Laura Benedit, Brooke Seitter, Robert Jerris, Joshua M. Levy, Colleen S. Kraft, Sarah Farmer, Amanda Peagler, Anna Wood, Adrianna L. Westbrook, Claudia R. Morris, Usha N. Sathian, William Heetderks, Li Li, Kristian Roth, Mary Barcus, Timothy Stenzel, Greg S. Martin, and Wilbur A. Lam
- Subjects
Male ,Adolescent ,SARS-CoV-2 ,Health Personnel ,COVID-19 ,General Medicine ,Specimen Handling ,Self-Testing ,COVID-19 Testing ,Cross-Sectional Studies ,Child, Preschool ,RNA, Viral ,Humans ,Female ,Child ,Original Investigation - Abstract
IMPORTANCE: Despite the expansion of SARS-CoV-2 testing, available tests have not received Emergency Use Authorization for performance with self-collected anterior nares (nasal) swabs from children younger than 14 years because the effect of pediatric self-swabbing on SARS-CoV-2 test sensitivity is unknown. OBJECTIVE: To characterize the ability of school-aged children to self-collect nasal swabs for SARS-CoV-2 testing compared with collection by health care workers. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 197 symptomatic children and adolescents aged 4 to 14 years old. Individuals were recruited based on results of testing in the Children’s Healthcare of Atlanta system from July to August 2021. EXPOSURES: Children and adolescents were given instructional material consisting of a short instructional video and a handout with written and visual steps for self-swab collection. Participants first provided a self-collected nasal swab. Health care workers then collected a second specimen. MAIN OUTCOMES AND MEASURES: The primary outcome was SARS-CoV-2 detection and relative quantitation by cycle threshold (Ct) in self- vs health care worker–collected nasal swabs when tested with a real-time reverse transcriptase–polymerase chain reaction test with Emergency Use Authorization. RESULTS: Among the study participants, 108 of 194 (55.7%) were male and the median age was 9 years (IQR, 6-11). Of the 196 participants, 87 (44.4%) tested positive for SARS-CoV-2 and 105 (53.6%) tested negative by both self- and health care worker–collected swabs. Two children tested positive by self- or health care worker–collected swab alone; 1 child had an invalid health care worker swab. Compared with health care worker–collected swabs, self-collected swabs had 97.8% (95% CI, 94.7%-100.0%) and 98.1% (95% CI, 95.6%-100.0%) positive and negative percent agreement, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups (mean [SD] Ct, self-swab: 26.7 [5.4] vs health care worker swab: 26.3 [6.0]; P = .65). CONCLUSIONS AND RELEVANCE: After hearing and seeing simple instructional materials, children and adolescents aged 4 to 14 years self-collected nasal swabs that closely agreed on SARS-CoV-2 detection with swabs collected by health care workers.
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- 2022
29. Impact of repeated nasal sampling on detection and quantification of SARS-CoV-2
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Paulina A. Rebolledo, Russell R. Kempker, Mark D. Gonzalez, Greg S. Martin, Julie Sullivan, Jennifer K. Frediani, Jesse J. Waggoner, Jared O’Neal, Anna Wood, Erika A. Tyburski, Wilbur A. Lam, Joshua M. Levy, Janet Figueroa, and Miriam B. Vos
- Subjects
Adult ,Male ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Concordance ,Turbinates ,Sensitivity and Specificity ,Article ,Specimen Handling ,COVID-19 Testing ,Internal medicine ,Humans ,Medicine ,Sampling (medicine) ,Child ,Aged ,Aged, 80 and over ,Multidisciplinary ,SARS-CoV-2 ,business.industry ,Laboratory techniques and procedures ,COVID-19 ,Infant ,Reproducibility of Results ,Middle Aged ,Viral infection ,Child, Preschool ,Clinical diagnosis ,Female ,Test performance ,Sample collection ,business - Abstract
The impact of repeated sample collection on COVID-19 test performance is unknown. The FDA and CDC currently recommend the primary collection of diagnostic samples to minimize the perceived risk of false-negative findings. We therefore evaluated the association between repeated sample collection and test performance among 325 symptomatic patients undergoing COVID-19 testing in Atlanta, GA. High concordance was found between consecutively collected mid-turbinate samples with both molecular (n = 74, 100% concordance) and antigen-based (n = 147, 97% concordance, kappa = 0.95, CI = 0.88–1.00) diagnostic assays. Repeated sample collection does not decrease COVID-19 test performance, demonstrating that multiple samples can be collected for assay validation and clinical diagnosis.
- Published
- 2021
30. Multidisciplinary assessment of the Abbott BinaxNOW SARS-CoV-2 point-of-care antigen test in the context of emerging viral variants and self-administration
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Eric J. Nehl, Erika A. Tyburski, Kristie Le, Leda Bassit, Wilbur A. Lam, Sarah Farmer, Amanda Foster, Janet Figueroa, Claudia R. Morris, Anuradha Rao, CaDeidre Washington, Miriam B. Vos, Allie Suessmith, Greg S. Martin, John D. Roback, María Cristina Cordero, Jennifer K. Frediani, Raymond F. Schinazi, Ann Chahroudi, Paulina A. Rebolledo, Russell R. Kempker, Jared O’Neal, Beverly Barton Rogers, Yun F. Wang, Julie Sullivan, Mark D. Gonzalez, Anna Wood, Robert C. Jerris, Maud Mavigner, Joshua M. Levy, Nils Schoof, Cheryl Stone, Thanuja Ramachandra, Jesse J. Waggoner, Annette M. Esper, and Van Leung-Pineda
- Subjects
medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Science ,Point-of-Care Systems ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Context (language use) ,Sensitivity and Specificity ,Article ,COVID-19 Serological Testing ,03 medical and health sciences ,0302 clinical medicine ,Limit of Detection ,Internal medicine ,Pandemic ,medicine ,Humans ,030212 general & internal medicine ,Point of care ,Multidisciplinary ,SARS-CoV-2 ,business.industry ,COVID-19 ,Usability ,Self-Testing ,Viral infection ,Rapid antigen test ,Medicine ,Infectious diseases ,business ,Viral load ,030217 neurology & neurosurgery - Abstract
While there has been significant progress in the development of rapid COVID-19 diagnostics, as the pandemic unfolds, new challenges have emerged, including whether these technologies can reliably detect the more infectious variants of concern and be viably deployed in non-clinical settings as “self-tests”. Multidisciplinary evaluation of the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW, a widely used rapid antigen test, included limit of detection, variant detection, test performance across different age-groups, and usability with self/caregiver-administration. While BinaxNOW detected the highly infectious variants, B.1.1.7 (Alpha) first identified in the UK, B.1.351 (Beta) first identified in South Africa, P.1 (Gamma) first identified in Brazil, B.1.617.2 (Delta) first identified in India and B.1.2, a non-VOC, test sensitivity decreased with decreasing viral loads. Moreover, BinaxNOW sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups. Overall, these data indicate that while BinaxNOW accurately detects the new viral variants, as rapid COVID-19 tests enter the home, their already lower sensitivities compared to RT-PCR may decrease even more due to user error.
- Published
- 2021
31. Plasma high-resolution metabolomic phenotyping of lean mass in a United States adult cohort
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Jessica A. Alvarez, Dean P. Jones, Greg S. Martin, Thomas R. Ziegler, and Moriah P. Bellissimo
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Adult ,Male ,medicine.medical_specialty ,media_common.quotation_subject ,Medicine (miscellaneous) ,Body Mass Index ,Metabolomics ,Absorptiometry, Photon ,Internal medicine ,medicine ,Metabolome ,Humans ,media_common ,Nutrition and Dietetics ,business.industry ,Catabolism ,Convalescence ,Metabolism ,Middle Aged ,United States ,Endocrinology ,Cross-Sectional Studies ,Cohort ,Lean body mass ,Female ,business ,Body mass index - Abstract
BACKGROUND Rapid loss of lean mass during catabolic states is associated with impaired convalescence and increased mortality rates. An understanding of metabolic pathways related to lean mass is needed to enable future interventions designed to combat malnutrition. This study assessed the plasma metabolome in relation to lean mass in clinically stable working adults in a US cohort. METHODS This cross-sectional study included 180 adults (mean ± SD, aged 49.7 ± 10.0 years; body mass index, 27.3 ± 5.5 kg/m2 ; 64% female [n=116]). Fasting plasma was analyzed using high-resolution metabolomics (HRM) via liquid chromatography/mass spectrometry. Lean mass was assessed by dual-energy x-ray absorptiometry and expressed as lean mass index (LMI, lean mass kg/height m2 ). Multiple linear regression, metabolic pathway enrichment, and module analyses were used to characterize systemic metabolism associated with LMI. RESULTS Of 5360 metabolites used in analyses, 593 were related to LMI, either upregulated or downregulated (P < .05). These were enriched within 11 metabolic pathways, including branched-chain amino acid degradation, metabolism of alanine and aspartate and other amino acids, butyrate, purines, and niacin metabolism. Module analysis revealed central associations between LMI and L-glutamate, L-leucine/L-isoleucine, L-valine, L-phenylalanine, L-methionine, and L-aspartate, among other validated metabolites. CONCLUSION These novel plasma HRM data demonstrate the wide-reaching associations of lean mass with systemic metabolism in a single snapshot. Such data may inform targeted nutrition support interventions designed to mitigate loss of lean mass and promote regaining skeletal muscle mass and function after illness or injury.
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- 2021
32. Diagnosis of acute serious illness: the role of point-of-care technologies
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Greg S. Martin, Erika A. Tyburski, Gregory L. Damhorst, Wilbur A. Lam, and Oliver Brand
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0303 health sciences ,medicine.medical_specialty ,Diagnostic information ,business.industry ,Emerging technologies ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Commercialization ,Article ,Biomaterials ,Care setting ,03 medical and health sciences ,Acute care ,medicine ,0210 nano-technology ,Intensive care medicine ,business ,030304 developmental biology ,Point of care - Abstract
Access to rapid diagnostic information is a core value of point-of-care (POC) technology. This is particularly relevant in acute, emergency, and critical care settings where diagnostic speed and precision directly guide the management of patients with potentially life-threatening conditions. Many POC diagnostics described in the literature, however, remain largely unproven and have yet to enter the market entirely. Only a few have traversed the translation and commercialization pathways to reach widespread clinical adoption. Moreover, even technologies that have successfully translated to the patient bedside still frequently lack an evidence base showing improvement of clinical outcomes. In this review, we present aspects of diagnosis of acute life-threatening diseases and describe the potential role of POC technologies, emphasizing the available evidence of clinical outcomes. Finally, we discuss what is needed to identify clinically meaningful new technologies and translate them toward the long-promised goal of better health through rapid POC diagnosis.
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- 2021
33. A global accounting of sepsis
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Greg S. Martin and Jordan A. Kempker
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medicine.medical_specialty ,business.industry ,Incidence ,Incidence (epidemiology) ,MEDLINE ,General Medicine ,Global Health ,medicine.disease ,Article ,Global Burden of Disease ,Sepsis ,Global health ,Humans ,Medicine ,business ,Intensive care medicine - Abstract
Summary Background Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. Methods We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. Findings In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. Interpretation Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. Funding The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.
- Published
- 2020
34. Immune checkpoint inhibition in sepsis: a Phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab
- Author
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June Ye, Ihab G. Girgis, Timothy E Albertson, Florian B. Mayr, Ian M. Catlett, Richard S. Hotchkiss, Mark Tidswell, Scott C. Brakenridge, Greg S. Martin, Lyle L. Moldawer, Michael W. Donnino, Raquel R. Bartz, Dennis M. Grasela, Pauline K. Park, Derek C. Angus, Craig M. Coopersmith, Matthew J. Delano, Elizabeth Colston, Elliott D. Crouser, and Sachin Yende
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Population ,Critical Care and Intensive Care Medicine ,law.invention ,Sepsis ,Double-Blind Method ,Randomized controlled trial ,Pharmacokinetics ,law ,Internal medicine ,Humans ,Immunologic Factors ,Medicine ,education ,Aged ,education.field_of_study ,business.industry ,Organ dysfunction ,Immunosuppression ,HLA-DR Antigens ,Middle Aged ,medicine.disease ,Nivolumab ,Female ,medicine.symptom ,business ,Cytokine storm ,Biomarkers - Abstract
Sepsis-associated immunosuppression increases hospital-acquired infection and viral reactivation risk. A key underlying mechanism is programmed cell death protein-1 (PD-1)-mediated T-cell function impairment. This is one of the first clinical safety and pharmacokinetics (PK) assessments of the anti-PD-1 antibody nivolumab and its effect on immune biomarkers in sepsis. Randomized, double-blind, parallel-group, Phase 1b study in 31 adults at 10 US hospital ICUs with sepsis diagnosed ≥ 24 h before study treatment, ≥ 1 organ dysfunction, and absolute lymphocyte count ≤ 1.1 × 103 cells/μL. Participants received one nivolumab dose [480 mg (n = 15) or 960 mg (n = 16)]; follow-up was 90 days. Primary endpoints were safety and PK parameters. Twelve deaths occurred [n = 6 per study arm; 40% (480 mg) and 37.5% (960 mg)]. Serious AEs occurred in eight participants [n = 1, 6.7% (480 mg); n = 7, 43.8% (960 mg)]. AEs considered by the investigator to be possibly drug-related and immune-mediated occurred in five participants [n = 2, 13.3% (480 mg); n = 3, 18.8% (960 mg)]. Mean ± SD terminal half-life was 14.7 ± 5.3 (480 mg) and 15.8 ± 7.9 (960 mg) days. All participants maintained > 90% receptor occupancy (RO) 28 days post-infusion. Median (Q1, Q3) mHLA-DR levels increased to 11,531 (6528, 19,495) and 11,449 (6225, 16,698) mAbs/cell in the 480- and 960-mg arms by day 14, respectively. Pro-inflammatory cytokine levels did not increase. In this sepsis population, nivolumab administration did not result in unexpected safety findings or indicate any ‘cytokine storm’. The PK profile maintained RO > 90% for ≥ 28 days. Further efficacy and safety studies are warranted. NCT02960854.
- Published
- 2019
35. Immune Checkpoint Inhibition in Sepsis
- Author
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Florian B. Mayr, Elizabeth Colston, Richard S. Hotchkiss, Craig M. Coopersmith, Greg S. Martin, Elliott D. Crouser, Lyle L. Moldawer, Scott C. Brakenridge, Ian M. Catlett, Dennis M. Grasela, Derek C. Angus, Ihab G. Girgis, Pauline K. Park, Sachin Yende, and June Ye
- Subjects
biology ,business.industry ,Cell ,030208 emergency & critical care medicine ,biochemical phenomena, metabolism, and nutrition ,Pharmacology ,Critical Care and Intensive Care Medicine ,medicine.disease ,Placebo ,Immune checkpoint ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,030228 respiratory system ,Pharmacokinetics ,Monoclonal ,medicine ,biology.protein ,Antibody ,business - Abstract
Objectives:To assess for the first time the safety and pharmacokinetics of an antiprogrammed cell death-ligand 1 immune checkpoint inhibitor (BMS-936559; Bristol-Myers Squibb, Princeton, NJ) and its effect on immune biomarkers in participants with sepsis-associated immunosuppression.Design:Randomize
- Published
- 2019
36. Crystalloids vs. colloids for fluid resuscitation in the Intensive Care Unit: A systematic review and meta-analysis
- Author
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Paul Bassett and Greg S. Martin
- Subjects
Resuscitation ,medicine.medical_specialty ,Central Venous Pressure ,Critical Care ,Critical Illness ,Hydroxyethyl starch ,Critical Care and Intensive Care Medicine ,law.invention ,Hydroxyethyl Starch Derivatives ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,law ,Albumins ,Humans ,Medicine ,Colloids ,Intensive care medicine ,business.industry ,Critically ill ,Hemodynamics ,Central venous pressure ,030208 emergency & critical care medicine ,Crystalloid Solutions ,medicine.disease ,Shock, Septic ,Intensive care unit ,Intensive Care Units ,030228 respiratory system ,Shock (circulatory) ,Meta-analysis ,Fluid Therapy ,Gelatin ,Isotonic Solutions ,medicine.symptom ,business ,medicine.drug - Abstract
Guidelines recommend crystalloids for fluid resuscitation in sepsis/shock and switching to albumin in cases where crystalloids are insufficient. We evaluated hemodynamic response to crystalloids/colloids in critically ill adults.The primary research question was: "Are crystalloids sufficient for volume replacement in severe indications (intensive care unit [ICU]/critical illness)?" Randomized, controlled trials (RCTs) were identified using PubMed and EMBASE, and screened against predefined inclusion/exclusion criteria. Meta-analyses were performed on extracted data.Fifty-five RCTs (N = 27,036 patients) were eligible. Central venous pressure was significantly lower with crystalloids than with albumin, hydroxyethyl starch (HES), or gelatin (all p .001). Mean arterial pressure was significantly lower with crystalloids vs. albumin (mean difference [MD]: -3.5 mm Hg; p = .03) or gelatin (MD: -9.2 mm Hg; p = .02). Significantly higher volumes of crystalloids were administered vs. HES (MD: +1775 mL); volume administered was numerically higher vs. albumin (MD: +1985 mL). Compared with the albumin group, cardiac index was significantly lower in the crystalloid group (MD: -0.6 L/min/mCrystalloids were less efficient than colloids at stabilizing resuscitation endpoints; guidance on when to switch is urgently required.
- Published
- 2019
37. Society of Critical Care Medicine Presidential Address-50th Annual Congress, February 2021
- Author
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Greg S. Martin
- Subjects
Patient Care Team ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Evidence-Based Medicine ,Critical Care ,Critically ill ,business.industry ,Download ,media_common.quotation_subject ,Critical Illness ,Warranty ,Intensivist ,Critical Care and Intensive Care Medicine ,United States ,Intensive Care Units ,Presidential address ,Critical illness ,medicine ,Humans ,Quality (business) ,Intensive care medicine ,business ,Societies, Medical ,media_common - Abstract
To address the need for critically ill patients around the world to receive high quality critical care from trained professionals, SCCM created the Fundamentals of Critical Care Support, or FCCS, course THRIVE was instrumental in characterizing the post-intensive care syndrome, and SCCM has made PICS a common expression in the critical care lexicon and helped to develop strategies that may one day eliminate PICS as a consequence of critical illness These, and other remarkable women leaders at SCCM, laid the groundwork for our Women in Critical Care KEG-one of the first and most active groups of its kind in critical care medicine I am a better intensivist and a better person for having met all of the incredibly talented critical care colleagues who volunteer their time to serve on the SCCM Council, and so many of our leaders on SCCM committees and within our regional SCCM chapters as well as our international collaborators and colleagues [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )
- Published
- 2021
38. Secondary Bacterial Pneumonias and Bloodstream Infections in Patients Hospitalized with COVID-19
- Author
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Max W. Adelman, Divya R. Bhamidipati, Alfonso C. Hernandez-Romieu, Ahmed Babiker, Michael H. Woodworth, Chad Robichaux, David J. Murphy, Sara C. Auld, Colleen S. Kraft, Jesse T. Jacob, Scott Arno, Theresa Barnes, William Bender, James M. Blum, Gaurav Budhrani, Stephanie Busby, Laurence Busse, Mark Caridi-Scheible, David Carpenter, Nikulkumar Chaudhari, Craig M. Coopersmith, Gordon Dale, Lisa Daniels, Johnathan A. Edwards, Jane Fazio, Babar Fiza, Eliana Gonzalez, Ria Gripaldo, Charles Grodzin, Robert Groff, Max Hockstein, Dan Hunt, Craig S. Jabaley, Greg S. Martin, Samer Melham, Nirja Mehta, Chelsea Modlin, Jung Park, Deepa Patel, Cindy Powell, Amit Prabhakar, Jeeyon Rim, Ramzy Rimawi, Nicholas Scanlon, Milad Sharifpour, Bashar Staitieh, Michael Sterling, Jonathan Suarez, Colin Swenson, Nancy Thakkar, Alexander Truong, Hima Veeramachaneni, Alvaro Velasquez, Aimee Vester, Michael Waldmann, Max Weinmann, Thanushi Wynn, and Joel Zivot
- Subjects
Pulmonary and Respiratory Medicine ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Coinfection ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,Bacterial Infections ,Virology ,Hospitalization ,Sepsis ,Pneumonia, Bacterial ,Medicine ,Humans ,In patient ,Letters ,business - Published
- 2021
39. The RADx Tech Clinical Studies Core: A Model for Academic Based Clinical Studies
- Author
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Bryan Buchholz, Matthew L Robinson, Miriam B. Vos, Greg S. Martin, Chad J. Achenbach, Risha Nayee, Stephenie C. Lemon, Jennifer K. Frediani, Allison Blodgett, Nathaniel Hafer, Bruce A. Barton, Oliver Brand, Leona Wells, Rebecca Cleeton, Nisha Fahey, Denise R. Dunlap, David D. McManus, Robert L. Murphy, Yukari C. Manabe, Cheryl Stone, Jared O’Neal, Laura Gibson, Jeffrey E. Olgin, Wilbur A. Lam, and John Broach
- Subjects
Protocol (science) ,medicine.medical_specialty ,Emergency Use Authorization ,\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$in\ vitro$\end{document} diagnostics ,Computer science ,business.industry ,SARS-CoV-2 ,Point-of-care testing ,Public health ,Data management ,Computer applications to medicine. Medical informatics ,RADx Tech: A New Paradigm for MedTech Development ,rapid acceleration of diagnostics ,R858-859.7 ,COVID-19 ,+ ,+ %24in%5C+vitro%24<%2Ftex-math>+<%2Finline-formula>+<%2Fnamed-content>+diagnostics%22"> $in\ vitro$ Commercialization ,Engineering management ,point-of-care testing ,Software deployment ,General partnership ,Medical technology ,medicine ,R855-855.5 ,business - Abstract
The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADxSM) Tech initiative to support the development and commercialization of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care test devices. The primary objective of the Clinical Studies Core (CSC) was to perform SARS-CoV-2 device studies involving diverse populations and settings. Within a few months, the infrastructure for clinical studies was developed, including a master protocol, digital study platform, data management system, single IRB, and multi-site partnerships. Data from some studies are being used to support Emergency Use Authorization of novel SARS-CoV-2 test devices. The CSC reduced the typical time and cost of developing medical devices and highlighted the impactful role of academic and NIH partnership in addressing public health needs at a rapid pace during a global pandemic. The structure, deployment, and lessons learned from this experience are widely applicable to future in vitro diagnostic device clinical studies.
- Published
- 2021
40. Future potential of Rapid Acceleration of Diagnostics (RADx Tech) in molecular diagnostics
- Author
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Yukari C. Manabe, Greg S. Martin, Wilbur A. Lam, Steven C. Schachter, Denise R. Dunlap, and Sally M. McFall
- Subjects
0301 basic medicine ,Necessity is the mother of invention ,Coronavirus disease 2019 (COVID-19) ,Computer science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Point-of-Care Systems ,Diagnostic test ,Molecular diagnostics ,Communicable Diseases ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,Acceleration ,030104 developmental biology ,0302 clinical medicine ,Risk analysis (engineering) ,Molecular Diagnostic Techniques ,Point-of-Care Testing ,030220 oncology & carcinogenesis ,Paradigm shift ,Genetics ,Molecular Medicine ,Humans ,Molecular Biology - Abstract
While necessity is the mother of invention, anomalies have formed the basis for most disruptive discoveries that seed innovations in the sciences. They provide the impetus for paradigm change withi...
- Published
- 2021
41. Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial
- Author
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Laurence W. Busse, David F. Gaieski, Kert Viele, Samuel K. Nwosu, Carmen C. Polito, Lindsay M. Eyzaguirre, Richard E. Rothman, Craig M. Coopersmith, Katherine Lyn Nugent, Christopher J. Lindsell, Christine DeWilde, David N. Hager, Caroline C. Rudolph, Jonathan E. Sevransky, Alex Hall, Jessica S. Marlin, Roger J. Lewis, David W. Wright, Michelle N. Gong, Greg S. Martin, Alpha A. Fowler, Todd W. Rice, Anna McGlothlin, Brooks Moore, Samuel M. Brown, Jeremiah S. Hinson, Fred Sanfilippo, Gabor D. Kelen, Akram Khan, Michael H. Hooper, Erin P. Ricketts, E. Wesley Ely, Gordon R. Bernard, Timothy G. Buchman, and Mark Levine
- Subjects
Adult ,Male ,medicine.medical_specialty ,Randomization ,Hydrocortisone ,Organ Dysfunction Scores ,Critical Illness ,Anti-Inflammatory Agents ,Ascorbic Acid ,Placebo ,01 natural sciences ,law.invention ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,Interquartile range ,Intensive care ,Internal medicine ,Medicine ,Humans ,Vasoconstrictor Agents ,030212 general & internal medicine ,Thiamine ,0101 mathematics ,Aged ,business.industry ,010102 general mathematics ,Correction ,General Medicine ,Vitamins ,Length of Stay ,Middle Aged ,medicine.disease ,Ascorbic acid ,Intensive care unit ,Respiration, Artificial ,Treatment Outcome ,Early Termination of Clinical Trials ,Drug Therapy, Combination ,Female ,business ,Respiratory Insufficiency - Abstract
Importance Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. Objective To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. Design, setting, and participants Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. Interventions Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. Main outcomes and measures The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. Results Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. Conclusions and relevance Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. Trial registration ClinicalTrials.gov Identifier: NCT03509350.
- Published
- 2021
42. The Evolution of Toolkits and Bundles to Improve the Care of Sepsis Patients
- Author
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Jean-Louis Teboul, Greg S. Martin, Sandra L. Kane-Gill, Vinay M. Nadkarni, Lui G. Forni, Jozef Kesecioglu, Lewis J. Kaplan, Lauren R. Sorce, Maurizio Cecconi, and Elie Azoulay
- Subjects
Sepsis ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine ,Critical Care and Intensive Care Medicine ,Intensive care medicine ,medicine.disease ,business - Published
- 2021
43. HOSPITAL FLUID CULTURE IMPACTS OUTCOME IN SEVERE SEPSIS AND SEPTIC SHOCK PATIENTS
- Author
-
Aftab Alam, Jennifer Sahatjian, Keith Corl, Steven Q. Simpson, Douglas Hansell, Walter T. Linde-Zwirble, Andre Holder, Ivor S. Douglas, Greg S. Martin, and Heath Latham
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Septic shock ,medicine ,Cardiology and Cardiovascular Medicine ,Critical Care and Intensive Care Medicine ,Intensive care medicine ,business ,medicine.disease ,Outcome (game theory) ,Severe sepsis - Published
- 2021
44. Machine Learning Methods to Predict Acute Respiratory Failure and Acute Respiratory Distress Syndrome
- Author
-
Greg S. Martin, Patricia C. Cheung, An-Kwok Ian Wong, Rishikesan Kamaleswaran, and Andre Holder
- Subjects
Big Data ,Review ,Acute respiratory distress ,Machine learning ,computer.software_genre ,01 natural sciences ,intubation ,03 medical and health sciences ,High morbidity ,0302 clinical medicine ,Artificial Intelligence ,Computer Science (miscellaneous) ,Medicine ,Disease process ,Acute respiratory failure ,030212 general & internal medicine ,0101 mathematics ,Oxygen supply ,acute respiratory failure ,lcsh:T58.5-58.64 ,lcsh:Information technology ,business.industry ,010102 general mathematics ,prediction ,acute respiratory distress syndrome ,machine learning ,Artificial intelligence ,business ,computer ,Information Systems - Abstract
Acute respiratory failure (ARF) is a common problem in medicine that utilizes significant healthcare resources and is associated with high morbidity and mortality. Classification of acute respiratory failure is complicated, and it is often determined by the level of mechanical support that is required, or the discrepancy between oxygen supply and uptake. These phenotypes make acute respiratory failure a continuum of syndromes, rather than one homogenous disease process. Early recognition of the risk factors for new or worsening acute respiratory failure may prevent that process from occurring. Predictive analytical methods using machine learning leverage clinical data to provide an early warning for impending acute respiratory failure or its sequelae. The aims of this review are to summarize the current literature on ARF prediction, to describe accepted procedures and common machine learning tools for predictive tasks through the lens of ARF prediction, and to demonstrate the challenges and potential solutions for ARF prediction that can improve patient outcomes.
- Published
- 2020
45. Covid-19 will not 'magically disappear': Why access to widespread testing is paramount
- Author
-
Paul E. George, Claire L. Stokes, Leda C. Bassit, Ann Chahroudi, Janet Figueroa, Mark A. Griffiths, Stacy Heilman, David N. Ku, Eric J. Nehl, Traci Leong, Joshua M. Levy, Russell R. Kempker, Robert G. Mannino, Maud Mavigner, Sunita I. Park, Anuradha Rao, Paulina A. Rebolledo, John D. Roback, Beverly B. Rogers, Raymond F. Schinazi, Allie B. Suessmith, Julie Sullivan, Erika A. Tyburski, Miriam B. Vos, Jesse J. Waggoner, Yun F. (Wayne) Wang, Jen Madsen, Daniel S. Wechsler, Clinton H. Joiner, Greg S. Martin, and Wilbur A. Lam
- Subjects
2019-20 coronavirus outbreak ,Financing, Government ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Point-of-care testing ,Cost-Benefit Analysis ,Public-Private Sector Partnership ,MEDLINE ,Public-Private Sector Partnerships ,Sensitivity and Specificity ,Health Services Accessibility ,COVID-19 Testing ,Inventions ,Commentaries ,Pandemic ,Medicine ,Coronavirus Nucleocapsid Proteins ,Humans ,Antigens, Viral ,Pandemics ,business.industry ,SARS-CoV-2 ,COVID-19 ,Hematology ,Public relations ,United States ,National Institutes of Health (U.S.) ,Evaluation Studies as Topic ,Point-of-Care Testing ,COVID-19 Nucleic Acid Testing ,Spike Glycoprotein, Coronavirus ,Commentary ,RNA, Viral ,Reagent Kits, Diagnostic ,business - Published
- 2020
46. Point-of-Care Technology Research Network: An evolving model for collaborative translational research in biomedical engineering
- Author
-
Bryan Buchholz, Sally M. McFall, Wilbur A. Lam, Charlotte A. Gaydos, Jue Chen, Tiffani Bailey Lash, Steve Schachter, Oliver Brand, John M. Parrish, David D. McManus, Yukari C. Manabe, Robert L. Murphy, Greg S. Martin, Todd Merchak, and Penny Ford Carleton
- Subjects
0303 health sciences ,Low resource ,Technology research ,Computer science ,Point-of-care testing ,Best practice ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,Translational research ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Commercialization ,Article ,Biomaterials ,03 medical and health sciences ,Key (cryptography) ,0210 nano-technology ,030304 developmental biology ,Point of care ,Biomedical engineering - Abstract
As the healthcare system evolves from a centralized, hospital- and office-based model to an emphasis on patient-centric care delivered in decentralized settings from the community and/or home to low resource settings domestically and internationally, some Point-of-Care Technologies (POCT) have become important and others may soon become important in facilitating care. These portable diagnostic and monitoring devices enable moving care closer to the patient. We review recent developments in a national model to accelerate the development of POCT, specifically the Point-of-Care Technology Research Network (POCTRN), comprising a multi-center scientific network supported by a coordinating center. We summarize the history of the Network, and then describe the primary objectives and key activities of the Network and highlight the role of a new coordinating center providing administrative and infrastructure support. POCTRN is committed to building evidence-based best practices for high-quality translation and commercialization in biomedical engineering to maximize clinical impact of Point-of-Care Technologies.
- Published
- 2020
47. Assessment of the Abbott BinaxNOW SARS-CoV-2 rapid antigen test against viral variants of concern
- Author
-
Anuradha Rao, Leda Bassit, Jessica Lin, Kiran Verma, Heather B. Bowers, Kimberly Pachura, Morgan Greenleaf, Julie Sullivan, Eric Lai, Richard S. Creager, Thomas Pribyl, John Blackwood, Anne L. Piantadosi, Raymond Schinazi, Greg S. Martin, and Wilbur A. Lam
- Subjects
Multidisciplinary - Abstract
As the emergence of SARS-CoV-2 variants brings the global pandemic to new levels, the performance of current rapid antigen tests against variants of concern and interest (VOC/I) is of significant public health concern. Here, we report assessment of the Abbot BinaxNOW COVID-19 Antigen Self-Test. Using genetically sequenced remnant clinical samples collected from individuals positive for SARS-CoV-2, we assessed the performance of BinaxNOW against the variants that currently pose public health threats. We measured the limit of detection of BinaxNOW against various VOC/I in a blinded manner. BinaxNOW successfully detected the Omicron (B.1.1.529), Mu (B.1.621), Delta (B.1.617.2), Lambda (C.37), Gamma (P.1), Alpha (B.1.1.7), Beta (B.1.351), Eta (B.1.525), and P.2 variants and at low viral concentrations. BinaxNOW also detected the Omicron variant in individual remnant clinical samples. Overall, these data indicate that this inexpensive and simple-to-use, FDA-authorized and broadly distributed rapid test can reliably detect Omicron, Delta, and other VOC/I.
- Published
- 2022
48. Sepsis Epidemiology Across the International Classification of Diseases, 9th Edition, to International Classification of Diseases, 10th Edition, Chasm-A Direct Application of the Institute for Health Metrics and Evaluation Case Definition to Hospital Discharge Data
- Author
-
Greg S. Martin, Kristina E. Rudd, Henry E. Wang, and A Jordan Kempker
- Subjects
medicine.medical_specialty ,Cross-sectional study ,Psychological intervention ,MEDLINE ,Critical Care and Intensive Care Medicine ,Medicare ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,International Classification of Diseases ,Severity of illness ,Epidemiology ,medicine ,Humans ,Hospital Mortality ,business.industry ,Incidence ,030208 emergency & critical care medicine ,medicine.disease ,Patient Discharge ,United States ,Cross-Sectional Studies ,030228 respiratory system ,Family medicine ,Cohort ,business ,Medicaid - Abstract
Objectives Describe the epidemiology of sepsis across the transition from the International Classification of Diseases, 9th Edition, and International Classification of Diseases, 10th Edition, coding systems, evaluating estimates of two previously published International Classification of Diseases, 10th Edition, coding strategies. Design Serial cross-sectional analysis. Setting Healthcare Utilization Project's annual Nationwide Inpatient Sample of U.S. hospital discharges, 2012-2017. Patients Discharges greater than or equal to 18 years old, which met one of the three case definitions for sepsis. For the records using International Classification of Diseases, 9th Edition, we used previously published modified Angus criteria, and for records using International Classification of Diseases, 10th Edition, we deployed a case definition used by the Centers for Medicare & Medicaid Services and a case definition developed by the Institute for Health Metrics and Evaluation. Interventions None. Measurements and main results During the study period, there were discontinuities in the sepsis incidence estimates using the modified Angus International Classification of Diseases, 9th Edition, criteria in 2014 and either Centers for Medicare & Medicaid Services or Institute for Health Metrics and Evaluation International Classification of Diseases, 10th Edition, criteria in 2016. In 2014, there were an estimated 1,009 cases (95% CI, 989-1,030) of modified Angus sepsis per 100,000 persons, whereas in 2016, there were 709 cases (95% CI, 694-724) of Centers for Medicare & Medicaid Services sepsis and 1,498 cases (95% CI, 1,471-1,092) of Institute for Health Metrics and Evaluation sepsis per 100,000 persons. Furthermore, the Institute for Health Metrics and Evaluation definition identified a sepsis cohort with similar hospital characteristics but a younger age distribution, higher proportion of women, lower severity of illness, and lower hospital mortality. Conclusions The Institute for Health Metrics and Evaluation International Classification of Diseases, 10th Edition, coding strategy for identifying sepsis may capture a larger patient population within administrative datasets that are different from those identified with previously deployed International Classification of Diseases-based methods. Further work is required to determine the optimal International Classification of Diseases, 10th Edition, coding strategy for use in hospital discharge data.
- Published
- 2020
49. A scalable workflow to characterize the human exposome
- Author
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Matthew R. Smith, Michael Koval, Carmen J. Marsit, Chunyu Ma, David C. Neujahr, Konstantinos N. Lazaridis, Greg S. Martin, Young-Mi Go, Dean P. Jones, Karan Uppal, Kurt D. Pennell, Douglas I. Walker, Xin Hu, Michael Orr, Gary W. Miller, Brian D. Juran, and Yongliang Liang
- Subjects
Exposome ,Population level ,Computer science ,Science ,General Physics and Astronomy ,General Biochemistry, Genetics and Molecular Biology ,Gas Chromatography-Mass Spectrometry ,Article ,Workflow ,Sample volume ,Humans ,Metabolomics ,Profiling (computer programming) ,Multidisciplinary ,Mass spectrometry ,Small molecules ,General Chemistry ,Reference Standards ,Data science ,Contemporary science ,Risk factors ,Human plasma ,Scalability ,Environmental Pollutants ,Environmental Monitoring - Abstract
Complementing the genome with an understanding of the human exposome is an important challenge for contemporary science and technology. Tens of thousands of chemicals are used in commerce, yet cost for targeted environmental chemical analysis limits surveillance to a few hundred known hazards. To overcome limitations which prevent scaling to thousands of chemicals, we develop a single-step express liquid extraction and gas chromatography high-resolution mass spectrometry analysis to operationalize the human exposome. We show that the workflow supports quantification of environmental chemicals in human plasma (200 µL) and tissue (≤100 mg) samples. The method also provides high resolution, sensitivity and selectivity for exposome epidemiology of mass spectral features without a priori knowledge of chemical identity. The simplicity of the method can facilitate harmonization of environmental biomonitoring between laboratories and enable population level human exposome research with limited sample volume., Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.
- Published
- 2020
50. 36 Item Short Form Survey Health Transition Question and Changes in Various Physiologic and Patient Related Outcome Measures in Patients with Idiopathic Pulmonary Fibrosis
- Author
-
Srihari Veeraraghavan, Jordan A. Kempker, Mohleen Kang, and Greg S. Martin
- Subjects
Idiopathic pulmonary fibrosis ,Pediatrics ,medicine.medical_specialty ,business.industry ,medicine ,Outcome measures ,In patient ,medicine.disease ,business - Published
- 2020
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