Evidence map›Paper›PMID 27552618›Full record

Observational studyJAMA

Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger.

Prashant Mahajan, Nathan Kuppermann, Asuncion Mejias, Nicolas Suarez, Damien Chaussabel, T Charles Casper, Bennett Smith, Elizabeth R Alpern, Jennifer Anders, Shireen M Atabaki and 30 more

Erratum issuedAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in JAMA. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 109 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Risk of serious bacterial infections in pediatric patients with hyperpyrexia.Journal of the American College of Emergency Physicians open · 2024
    Article
  20. Article

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

40 authors.

Prashant MahajanDivision of Emergency Medicine, Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit.
Nathan KuppermannDepartments of Emergency Medicine and Pediatrics, University of California, Davis, School of Medicine, Sacramento.
Asuncion MejiasDivision of Pediatric Infectious Diseases and Center for Vaccines and Immunity, Nationwide Children's Hospital and The Ohio State University, Columbus.
Nicolas SuarezDivision of Pediatric Infectious Diseases and Center for Vaccines and Immunity, Nationwide Children's Hospital and The Ohio State University, Columbus.
Damien ChaussabelBenaroya Research Institute, Virginia Mason and Sidra Medical and Research Center, Seattle, Washington, and Doha, Qatar.
T Charles CasperDepartment of Pediatrics, University of Utah, Salt Lake City.
Bennett SmithDivision of Pediatric Infectious Diseases and Center for Vaccines and Immunity, Nationwide Children's Hospital and The Ohio State University, Columbus.
Elizabeth R AlpernDivision of Emergency Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania7Now at Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Jennifer AndersDepartment of Pediatrics, Johns Hopkins University, Baltimore, Maryland.
Shireen M AtabakiDivision of Emergency Medicine, Department of Pediatrics, Children's National Medical Center, George Washington School of Medicine and Health Sciences, Washington, DC.
Jonathan E BennettDivision of Pediatric Emergency Medicine, Alfred I. DuPont Hospital for Children, Nemours Children's Health System, Wilmington, Delaware.
Stephen BlumbergDepartment of Pediatrics, Jacobi Medical Center, Albert Einstein College of Medicine, New York, New York.
Bema BonsuSection of Emergency Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.
Dominic BorgialliDepartment of Emergency Medicine, Hurley Medical Center and University of Michigan, Flint.
Anne BrayerDepartments of Emergency Medicine and Pediatrics, University of Rochester Medical Center, Rochester, New York.
Lorin BrowneDepartments of Pediatrics and Emergency Medicine, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee.
Daniel M CohenSection of Emergency Medicine, Department of Pediatrics, Nationwide Children's Hospital and The Ohio State University, Columbus.
Ellen F CrainDivision of Pediatric Emergency Medicine, Alfred I. DuPont Hospital for Children, Nemours Children's Health System, Wilmington, Delaware.
Andrea T CruzSections of Emergency Medicine and Infectious Diseases, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston.
Peter S DayanDivision of Emergency Medicine, Department of Pediatrics, Columbia University College of Physicians & Surgeons, New York, New York.
Rajender GattuDivision of Emergency Medicine, Department of Pediatrics, University of Maryland Medical Center, Baltimore.
Richard GreenbergDepartment of Pediatrics, Primary Children's Medical Center, University of Utah, Salt Lake City.
John D HoyleDepartment of Emergency Medicine, Helen DeVos Children's Hospital of Spectrum Health, Grand Rapids, Michigan22Now with the Departments of Emergency Medicine and Pediatrics, Western Michigan University Homer Stryker, MD, School of Medicine, Kalamazoo.
David M JaffeDepartment of Pediatrics, St Louis Children's Hospital, Washington University, St Louis, Missouri24Now with the Division of Pediatric Emergency Medicine, University of California San Francisco School of Medicine.
Deborah A LevineDepartment of Pediatrics, Bellevue Hospital New York University Langone Center, New York.
Kathleen LillisDepartment of Pediatrics, Women and Children's Hospital of Buffalo, State University of New York at Buffalo.
James G LinakisDepartment of Emergency Medicine and Pediatrics, Hasbro Children's Hospital and Brown University, Providence, Rhode Island.
Jared MuenzerDepartment of Pediatrics, Bellevue Hospital New York University Langone Center, New York28Now with the Department of Emergency Medicine, Phoenix Children's Hospital, Phoenix, Arizona.
Lise E NigrovicDepartment of Pediatrics, Boston Children's Hospital, Harvard University, Boston, Massachusetts.
Elizabeth C PowellDivision of Emergency Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Alexander J RogersDepartments of Emergency Medicine and Pediatrics, University of Michigan, Ann Arbor.
Genie RooseveltDepartment of Pediatrics, Children's Hospital Colorado, University of Colorado-Denver, Aurora.
Richard M RuddyDivision of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Mary SaundersDepartment of Pediatrics, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee35Now with Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora.
Michael G TunikDepartment of Pediatrics, Bellevue Hospital, New York University Langone Medical Center, New York.
Leah TzimenatosDepartment of Emergency Medicine, University of California, Davis School of Medicine, Sacramento.
Melissa VitaleDivision of Pediatric Emergency Medicine, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
J Michael DeanDepartment of Pediatrics, University of Utah, Salt Lake City.
Octavio RamiloDivision of Pediatric Infectious Diseases and Center for Vaccines and Immunity, Nationwide Children's Hospital and The Ohio State University, Columbus.
Pediatric Emergency Care Applied Research Network (PECARN)

Funding

RNA Biosignatures in the Emergency Evaluation of Febrile InfantsR01HD062477 · NICHD · WAYNE STATE UNIVERSITY · PI KUPPERMANN, NATHAN, MAHAJAN, PRASHANT · 2010 to 2014
$3.2M
NICHD NIH HHS R01 HD062477NICHD NIH HHS R01HD062477PHS HHS H34MCO8509PHS HHS U03MC00001PHS HHS U03MC00003PHS HHS U03MC00006PHS HHS U03MC00007PHS HHS U03MC00008PHS HHS U03MC22684PHS HHS U03MC22685
6 · The paper itself

Abstract

importanceYoung febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns ("RNA biosignatures") in response to infections may provide an alternative diagnostic approach.

objectiveTo assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections. DESIGN, SETTING, AND

participantsProspective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type. EXPOSURE: RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections. MAIN OUTCOMES AND MEASURES: Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores.

resultsOf 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections-including 32 with bacteremia and 15 with urinary tract infections-and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and 95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43). CONCLUSIONS AND RELEVANCE: In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice.

Indexed as

BacteremiaBacterial InfectionsBiomarkersCase-Control StudiesDiagnostic Tests, RoutineEmergency Service, HospitalFemaleFeverGenetic MarkersHumansInfantInfant, NewbornMaleMeningitis, BacterialMicroarray AnalysisProspective StudiesBiomarkersGenetic MarkersRNA

Identifiers

PMID27552618
PMCPMC5122927

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.