Browsing by Author "Spinella, Philip C."

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    Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
    (Oxford University Press, 2023-03-06) Moffitt, Kristin L.; Nakamura, Mari M.; Young, Cameron C.; Newhams, Margaret M.; Halasa, Natasha B.; Reed, J. Nelson; Fitzgerald, Julie C.; Spinella, Philip C.; Soma, Vijaya L.; Walker, Tracie C.; Loftis, Laura L.; Maddux, Aline B.; Kong, Michele; Rowan, Courtney M.; Hobbs, Charlotte V.; Schuster, Jennifer E.; Riggs, Becky J.; McLaughlin, Gwenn E.; Michelson, Kelly N.; Hall, Mark W.; Babbitt, Christopher J.; Cvijanovich, Natalie Z.; Zinter, Matt S.; Maamari, Mia; Schwarz, Adam J.; Singh, Aalok R.; Flori, Heidi R.; Gertz, Shira J.; Staat, Mary A.; Giuliano, John S., Jr.; Hymes, Saul R.; Clouser, Katharine N.; McGuire, John; Carroll, Christopher L.; Thomas, Neal J.; Levy, Emily R.; Randolph, Adrienne G.; Pediatrics, School of Medicine
    Background: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce. Methods: We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes. Results: Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01-1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05-1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36-2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15-4.62]) was associated with bacterial coinfection. Conclusions: Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.
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    Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents
    (Elsevier, 2021-08-31) Geva, Alon; Patel, Manish M.; Geva, Alon; Patel, Manish M.; Newhams, Margaret M.; Young, Cameron C.; Son, Mary Beth F.; Kong, Michele; Maddux, Aline B.; Hall, Mark W.; Riggs, Becky J.; Singh, Aalok R.; Giuliano, John S.; Hobbs, Charlotte V.; Loftis, Laura L.; McLaughlin, Gwenn E.; Schwartz, Stephanie P.; Schuster, Jennifer E.; Babbitt, Christopher J.; Halasa, Natasha B.; Gertz, Shira J.; Doymaz, Sule; Hume, Janet R.; Bradford, Tamara T.; Irby, Katherine; Carroll, Christopher L.; McGuire, John K.; Tarquinio, Keiko M.; Rowan, Courtney M.; Mack, Elizabeth H.; Cvijanovich, Natalie Z.; Fitzgerald, Julie C.; Spinella, Philip C.; Staat, Mary A.; Clouser, Katharine N.; Soma, Vijaya L.; Dapul, Heda; Maamari, Mia; Bowens, Cindy; Havlin, Kevin M.; Mourani, Peter M.; Heidemann, Sabrina M.; Horwitz, Steven M.; Feldstein, Leora R.; Tenforde, Mark W.; Newburger, Jane W.; Mandl, Kenneth D.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Background Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. Findings Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. Interpretation Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.
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    A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020
    (Oxford University Press, 2022) Schuster, Jennifer E.; Halasa, Natasha B.; Nakamura, Mari; Levy, Emily R.; Fitzgerald, Julie C.; Young, Cameron C.; Newhams, Margaret M.; Bourgeois, Florence; Staat, Mary A.; Hobbs, Charlotte V.; Dapul, Heda; Feldstein, Leora R.; Jackson, Ashley M.; Mack, Elizabeth H.; Walker, Tracie C.; Maddux, Aline B.; Spinella, Philip C.; Loftis, Laura L.; Kong, Michele; Rowan, Courtney M.; Bembea, Melania M.; McLaughlin, Gwenn E.; Hall, Mark W.; Babbitt, Christopher J.; Maamari, Mia; Zinter, Matt S.; Cvijanovich, Natalie Z.; Michelson, Kelly N.; Gertz, Shira J.; Carroll, Christopher L.; Thomas, Neal J.; Giuliano, John S., Jr.; Singh, Aalok R.; Hymes, Saul R.; Schwarz, Adam J.; McGuire, John K.; Nofziger, Ryan A.; Flori, Heidi R.; Clouser, Katharine N.; Wellnitz, Kari; Cullimore, Melissa L.; Hume, Janet R.; Patel, Manish; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Background: It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. Methods: Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. Results: Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). Conclusion: Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.
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    Early Use of Adjunctive Therapies for Pediatric Acute Respiratory Distress Syndrome: A PARDIE Study
    (American Thoracic Society, 2020-06) Rowan, Courtney M.; Klein, Margaret J.; Hsing, Deyin Doreen; Dahmer, Mary K.; Spinella, Philip C.; Emeriaud, Guillaume; Hassinger, Amanda B.; Piñeres-Olave, Byron E.; Flori, Heidi R.; Haileselassie, Bereketeab; Lopez-Fernandez, Yolanda M.; Chima, Ranjit S.; Shein, Steven L.; Maddux, Aline B.; Lillie, Jon; Izquierdo, Ledys; Kneyber, Martin C.J.; Smith, Lincoln S.; Khemani, Robinder G.; Thomas, Neal J.; Yehya, Nadir; Pediatrics, School of Medicine
    Rationale: Few data exist to guide early adjunctive therapy use in pediatric acute respiratory distress syndrome (PARDS).Objectives: To describe contemporary use of adjunctive therapies for early PARDS as a framework for future investigations.Methods: This was a preplanned substudy of a prospective, international, cross-sectional observational study of children with PARDS from 100 centers over 10 study weeks.Measurements and Main Results: We investigated six adjunctive therapies for PARDS: continuous neuromuscular blockade, corticosteroids, inhaled nitric oxide (iNO), prone positioning, high-frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation. Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index of each therapy; corticosteroids started at the lowest oxygenation index (13.0; interquartile range, 7.6-22.0) and HFOV at the highest (25.7; interquartile range, 16.7-37.3). Continuous neuromuscular blockade was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and extracorporeal membrane oxygenation (3%). Steroids, iNO, and HFOV were associated with comorbidities. Prone positioning and HFOV were more common in middle-income countries and less frequently used in North America. The use of multiple ancillary therapies increased over the first 3 days of PARDS, but there was not an easily identifiable pattern of combination or order of use.Conclusions: The contemporary description of prevalence, combinations of therapies, and oxygenation threshold for which the therapies are applied is important for design of future studies. Region of the world, income, and comorbidities influence adjunctive therapy use and are important variables to include in PARDS investigations.
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    Life-Threatening Bleeding in Children: A Prospective Observational Study
    (Wolters Kluwer, 2021) Leonard, Julie C.; Josephson, Cassandra D.; Luther, James F.; Wisniewski, Stephen R.; Allen, Christine; Chiusolo, Fabrizio; Davis, Adrienne L.; Finkelstein, Robert A.; Fitzgerald, Julie C.; Gaines, Barbara A.; Goobie, Susan M.; Hanson, Sheila J.; Hewes, Hilary A.; Johnson, Laurie H.; McCollum, Mark O.; Muszynski, Jennifer A.; Nair, Alison B.; Rosenberg, Robert B.; Rouse, Thomas M.; Sikavitsas, Athina; Singleton, Marcy N.; Steiner, Marie E.; Upperman, Jeffrey S.; Vogel, Adam M.; Wills, Hale; Winkler, Margaret K.; Spinella, Philip C.; Surgery, School of Medicine
    Objectives: The purpose of our study was to describe children with life-threatening bleeding. Design: We conducted a prospective observational study of children with life-threatening bleeding events. Setting: Twenty-four childrens hospitals in the United States, Canada, and Italy participated. Subjects: Children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under massive transfusion protocol were included. Interventions: Children were compared according bleeding etiology: trauma, operative, or medical. Measurements and main results: Patient characteristics, therapies administered, and clinical outcomes were analyzed. Among 449 enrolled children, 55.0% were male, and the median age was 7.3 years. Bleeding etiology was 46.1% trauma, 34.1% operative, and 19.8% medical. Prior to the life-threatening bleeding event, most had age-adjusted hypotension (61.2%), and 25% were hypothermic. Children with medical bleeding had higher median Pediatric Risk of Mortality scores (18) compared with children with trauma (11) and operative bleeding (12). Median Glasgow Coma Scale scores were lower for children with trauma (3) compared with operative (14) or medical bleeding (10.5). Median time from bleeding onset to first transfusion was 8 minutes for RBCs, 34 minutes for plasma, and 42 minutes for platelets. Postevent acute respiratory distress syndrome (20.3%) and acute kidney injury (18.5%) were common. Twenty-eight-day mortality was 37.5% and higher among children with medical bleeding (65.2%) compared with trauma (36.1%) and operative (23.8%). There were 82 hemorrhage deaths; 65.8% occurred by 6 hours and 86.5% by 24 hours. Conclusions: Patient characteristics and outcomes among children with life-threatening bleeding varied by cause of bleeding. Mortality was high, and death from hemorrhage in this population occurred rapidly.
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    Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children
    (Oxford University Press, 2023) Halasa, Natasha B.; Spieker, Andrew J.; Young, Cameron C.; Olson, Samantha M.; Newhams, Margaret M.; Amarin, Justin Z.; Moffitt, Kristin L.; Nakamura, Mari M.; Levy, Emily R.; Soma, Vijaya L.; Talj, Rana; Weiss, Scott L.; Fitzgerald, Julie C.; Mack, Elizabeth H.; Maddux, Aline B.; Schuster, Jennifer E.; Coates, Bria M.; Hall, Mark W.; Schwartz, Stephanie P.; Schwarz, Adam J.; Kong, Michele; Spinella, Philip C.; Loftis, Laura L.; McLaughlin, Gwenn E.; Hobbs, Charlotte V.; Rowan, Courtney M.; Bembea, Melania M.; Nofziger, Ryan A.; Babbitt, Christopher J.; Bowens, Cindy; Flori, Heidi R.; Gertz, Shira J.; Zinter, Matt S.; Giuliano, John S.; Hume, Janet R.; Cvijanovich, Natalie Z.; Singh, Aalok R.; Crandall, Hillary A.; Thomas, Neal J.; Cullimore, Melissa L.; Patel, Manish M.; Randolph, Adrienne G.; Pediatric Intensive Care Influenza; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Background: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. Methods: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. Results: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78-2.15; P = .32). Conclusions: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.
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    Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome
    (AMA, 2021-03) LaRovere, Kerri L.; Riggs, Becky J.; Poussaint, Tina Y.; Young, Cameron C.; Newhams, Margaret M.; Maamari, Mia; Walker, Tracie C.; Singh, Aalok R.; Dapul, Heda; Hobbs, Charlotte V.; McLaughlin, Gwenn E.; Son, Mary Beth F.; Maddux, Aline B.; Clouser, Katharine N.; Rowan, Courtney M.; McGuire, John K.; Fitzgerald, Julie C.; Gertz, Shira J.; Shein, Steven L.; Munoz, Alvaro Coronado; Thomas, Neal J.; Irby, Katherine; Levy, Emily R.; Staat, Mary A.; Tenforde, Mark W.; Feldstein, Leora R.; Halasa, Natasha B.; Giuliano, John S.; Hall, Mark W.; Kong, Michele; Carroll, Christopher L.; Schuster, Jennifer E.; Doymaz, Sule; Loftis, Laura L.; Tarquinio, Keiko M.; Babbitt, Christopher J.; Nofziger, Ryan A.; Kleinman, Lawrence C.; Keenaghan, Michael A.; Cvijanovich, Natalie Z.; Spinella, Philip C.; Hume, Janet R.; Wellnitz, Kari; Mack, Elizabeth H.; Michelson, Kelly N.; Flori, Heidi R.; Patel, Manish M.; Randolph, Adrienne G.; Overcoming COVID-19 Investigators; Gaspers, Mary G; Typpo, Katri V; Sanders, Ronald C; Schwarz, Adam J; Harvey, Helen; Zinter, Matt S; Mourani, Peter M; Coates, Bria M; Bhoojhawon, Guru; Havlin, Kevin M; Montgomery, Vicki L; Sullivan, Janice E; Bradford, Tamara T; Bembea, Melania M; Lipton, Susan V; Graciano, Ana Lia; Chen, Sabrina R; Kucukak, Suden; Newburger, Jane W; Carroll, Ryan W; Fernandes, Neil D; Yager, Phoebe H; Marohn, Kimberly L; Heidemann, Sabrina M; Cullimore, Melissa L; McCulloh, Russell J; Horwitz, Steven M; Li, Simon; Walsh, Rowan F; Ratner, Adam J; Soma, Vijaya L; Gillen, Jennifer K; Zackai, Sheemon P; Ackerman, Kate G; Cholette, Jill M; Harwayne-Gidansky, Ilana; Hymes, Saul R; Overby, Philip J; Schwartz, Stephanie P; Lansell, Amanda N; Koncicki, Monica L; Carcillo, Joseph; Fink, Ericka; Kimura, Dai; Bowens, Cindy; Crandall, Hillary; Smith, Lincoln S; Cengiz, Pelin; Pediatrics, School of Medicine
    Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.