Intertypic #recombination of #human #parechovirus 4 isolated from #infants with #sepsis-like disease (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Intertypic recombination of human parechovirus 4 isolated from infants with sepsis-like disease

Pekka Kolehmainen, Anu Siponen, Teemu Smura, Hannimari Kallio-Kokkoemail, Olli Vapalahti, Anne Jääskeläinen1, Sisko Tauriainen1

1These authors contributed equally.

DOI: http://dx.doi.org/10.1016/j.jcv.2017.01.001

Publication History: Published online: January 03, 2017 – Accepted: January 2, 2017 – Received in revised form: December 30, 2016 – Received: October 13, 2016

 

Highlights

  • Three HPeV-4 complete coding sequences were determined.
  • The P1 and P2 regions were highly similar to an HPeV-4 from the Netherlands, 2002.
  • Sequence similarity with HPeV-4 was lost in the 3D region indicating recombination.
  • The 2 B to 3A region clustered together with several HPeV-3 strains.
  • A three nucleotide deletion, compared to other HPeV-4s, was found in the 1C region.

 

Abstract

Background

Human parechoviruses (HPeVs) (family Picornaviridae), are common pathogens in young children. Despite their high prevalence, research on their genetic identity, diversity and evolution have remained scarce.

Objectives

Complete coding regions of three previously reported HPeV-4 isolates from Finnish children with sepsis-like disease were sequenced in order to elucidate the phylogenetic relationships and potential recombination events during the evolution of these isolates.

Study design

The isolated viruses were sequenced and aligned with all HPeV complete genome sequences available in GenBank. Phylogenetic trees were constructed and similarity plot and bootscanning methods were used for recombination analysis.

Results

The three HPeV-4 isolates had 99.8% nucleotide sequence similarity. The phylogenetic analysis indicated that capsid-encoding sequences of these HPeV-4 isolates were closely related to other HPeV-4 strains (80.7-94.7% nucleotide similarity), whereas their non-structural region genes 2A to 3C clustered together with several HPeV-1 and HPeV-3 strains, in addition to the HPeV-4 strain K251176-02 (isolated 2002 in the Netherlands), but not with other HPeV-4 strains. However, in 3D-encoding sequence the Finnish HPeV-4 isolates did not cluster with the strain HPeV-4/K251176-02, but instead, formed a distinct group together with several HPeV-1 and HPeV-3 strains. Similarity plot and Bootscan analyses further confirmed intertypic recombination events in the evolution of the Finnish HPeV-4 isolates.

Conclusion

Intertypic recombination event(s) have occurred during the evolution of HPeV-4 isolates from children with sepsis-like disease. However, due to the low number of parechovirus complete genomes available, the precise recombination partners could not be detected. The results suggest frequent intratypic recombination among parechoviruses.

Abbreviations: CDS (coding sequences), HPeV (human parechovirus), NGS (next generation sequencing), nt (nucleotide(s)), UTR (untranslated region)

Keywords: Human parechovirus, HPeV-4, Complete coding sequence, Sepsis-like disease, Recombination, Phylogenetic analysis

Keywords: Parechovirus; Picornavirus; Sepsis.

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#Effect of #Hydrocortisone on Development of #Shock Among Patients With Severe #Sepsis – The #HYPRESS Randomized Clinical Trial (JAMA, abstract)

[Source: JAMA, full page: (LINK). Abstract, edited.]

Original Investigation / Caring for the Critically Ill Patient / November 1, 2016

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis
The HYPRESS Randomized Clinical Trial

Didier Keh, MD1; Evelyn Trips2; Gernot Marx, MD3; et al Stefan P. Wirtz, MD4; Emad Abduljawwad, MD4; Sven Bercker, MD5; Holger Bogatsch, MD2; Josef Briegel, MD6; Christoph Engel, MD7; Herwig Gerlach, MD, PhD, MBA8; Anton Goldmann, MD1; Sven-Olaf Kuhn, MD9; Lars Hüter, MD10; Andreas Meier-Hellmann, MD11; Axel Nierhaus, MD12; Stefan Kluge, MD12; Josefa Lehmke, MD13; Markus Loeffler, MD7; Michael Oppert, MD14; Kerstin Resener, MD15; Dirk Schädler, MD16; Tobias Schuerholz, MD3; Philipp Simon, MD5; Norbert Weiler, MD16; Andreas Weyland, MD17; Konrad Reinhart, MD18; Frank M. Brunkhorst, MD19; for the SepNet–Critical Care Trials Group

Author Affiliations: 1Department of Anesthesiology and Intensive Care Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany; 2Clinical Trial Centre Leipzig, Leipzig, Germany; 3Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany; 4Department of Intensive Care Medicine, HELIOS Hospital Bad Saarow, Bad Saarow, Germany; 5Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany; 6Department of Anesthesiology, Klinikum der Ludwig-Maximilians-Universität, München, Germany; 7Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany; 8Department of Anesthesia, Intensive Care Medicine and Pain Management, Vivantes-Klinikum Neukölln, Berlin, Germany; 9Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany; 10Department of Anesthesia and Intensive Care, Zentralklinik Bad Berka, Bad Berka, Germany; 11Department of Anesthesia, Intensive Care Medicine and Pain Management, HELIOS Hospital Erfurt, Erfurt, Germany; 12Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 13Department of Cardiology and Intensive Care Medicine, Vivantes Humboldt Klinikum, Berlin, Germany; 14Department of Emergency and Intensive Care Medicine, Klinikum Ernst von Bergmann, Potsdam, Germany; 15Department of Intensive Care Medicine, HELIOS Hospital Berlin-Buch, Berlin, Germany; 16Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig Holstein, Campus Kiel, Kiel, Germany; 17Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Management, Klinikum Oldenburg Medical Campus Carl von Ossietzky Universität, Oldenburg, Germany; 18Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; 19Center for Clinical Studies, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany

Copyright 2016 American Medical Association. All Rights Reserved. Applicable ARS/DFARS Restrictions Apply to Government Use.

JAMA. 2016;316(17):1775-1785. doi:10.1001/jama.2016.14799

 

Key Points

  • Question – Does adjunctive early hydrocortisone therapy prevent the development of septic shock in patients with severe sepsis who are not in shock?
  • Findings – In this randomized clinical trial that included 380 adults, occurrence of septic shock was not significantly different between patients who received hydrocortisone or placebo (21.2% vs 22.9%, respectively).
  • Meaning – Administration of hydrocortisone did not prevent the development of shock in patients with severe sepsis.

 

Abstract

Importance

Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial.

Objective

To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.

Design, Setting, and Participants

Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock.

Interventions

Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190).

Main Outcomes and Measures

The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]).

Results

The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, −1.8%; 95% CI, −10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, −5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, −5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, −4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia.

Conclusions and Relevance

Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients.

Trial Registration clinicaltrials.gov Identifier: NCT00670254

Keywords: Sepsis; Corticosteroids.

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#Levosimendan for the #Prevention of Acute #Organ #Dysfunction in #Sepsis (N Engl J Med., abstract)

[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]

Original Article

Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis

Anthony C. Gordon, M.D., Gavin D. Perkins, M.D., Mervyn Singer, M.D., Daniel F. McAuley, M.D., Robert M.L. Orme, M.B., Ch.B., Shalini Santhakumaran, M.Sc., Alexina J. Mason, Ph.D., Mary Cross, B.A., Farah Al-Beidh, Ph.D., Janis Best-Lane, M.Sc., David Brealey, M.D., Christopher L. Nutt, M.B., B.Ch., James J. McNamee, M.B., Henrik Reschreiter, M.D., Andrew Breen, M.B., Ch.B., Kathleen D. Liu, M.D., Ph.D., and Deborah Ashby, Ph.D.

October 5, 2016 / DOI: 10.1056/NEJMoa1609409

 

Abstract

Background

Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis.

Methods

We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events.

Results

The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04).

Conclusions

The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia.

(Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.)

Keywords: Research; Abstracts; Sepsis.

——

#Effect of #Hydrocortisone on Development of #Shock Among Patients With Severe #Sepsis – The #HYPRESS Randomized Clinical Trial (JAMA, abstract)

[Source: JAMA, full page: (LINK). Abstract, edited.]

Original Investigation | October 03, 2016  | Caring for the Critically Ill Patient

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis – The HYPRESS Randomized Clinical Trial

FREE / ONLINE FIRST

Didier Keh, MD1; Evelyn Trips2; Gernot Marx, MD3; Stefan P. Wirtz, MD4; Emad Abduljawwad, MD4; Sven Bercker, MD5; Holger Bogatsch, MD2; Josef Briegel, MD6; Christoph Engel, MD7; Herwig Gerlach, MD, PhD, MBA8; Anton Goldmann, MD1; Sven-Olaf Kuhn, MD9; Lars Hüter, MD10; Andreas Meier-Hellmann, MD11; Axel Nierhaus, MD12; Stefan Kluge, MD12; Josefa Lehmke, MD13; Markus Loeffler, MD7; Michael Oppert, MD14; Kerstin Resener, MD15; Dirk Schädler, MD16; Tobias Schuerholz, MD3; Philipp Simon, MD5; Norbert Weiler, MD16; Andreas Weyland, MD17; Konrad Reinhart, MD18; Frank M. Brunkhorst, MD19 ; for the SepNet–Critical Care Trials Group

Author Affiliations: 1Department of Anesthesiology and Intensive Care Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany; 2Clinical Trial Centre Leipzig, Leipzig, Germany; 3Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany; 4Department of Intensive Care Medicine, HELIOS Hospital Bad Saarow, Bad Saarow, Germany; 5Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany; 6Department of Anesthesiology, Klinikum der Ludwig-Maximilians-Universität, München, Germany; 7Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany; 8Department of Anesthesia, Intensive Care Medicine and Pain Management, Vivantes-Klinikum Neukölln, Berlin, Germany; 9Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany; 10Department of Anesthesia and Intensive Care, Zentralklinik Bad Berka, Bad Berka, Germany; 11Department of Anesthesia, Intensive Care Medicine and Pain Management, HELIOS Hospital Erfurt, Erfurt, Germany; 12Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 13Department of Cardiology and Intensive Care Medicine, Vivantes Humboldt Klinikum, Berlin, Germany; 14Department of Emergency and Intensive Care Medicine, Klinikum Ernst von Bergmann, Potsdam, Germany; 15Department of Intensive Care Medicine, HELIOS Hospital Berlin-Buch, Berlin, Germany; 16Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig Holstein, Campus Kiel, Kiel, Germany; 17Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Management, Klinikum Oldenburg Medical Campus Carl von Ossietzky Universität, Oldenburg, Germany; 18Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; 19Center for Clinical Studies, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany

JAMA. Published online October 03, 2016. doi:10.1001/jama.2016.14799

 

ABSTRACT

Importance 

Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial.

Objective 

To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.

Design, Setting, and Participants 

Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock.

Interventions 

Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190).

Main Outcomes and Measures 

The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]).

Results 

The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, −1.8%; 95% CI, −10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, −5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, −5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, −4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia.

Conclusions and Relevance 

Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients.

Trial Registration  clinicaltrials.gov Identifier: NCT00670254

Keywords: Research; Abstracts; Sepsis; Corticosteroids.

——

#CLUSTER OF #HUMAN #PARECHOVIRUS #INFECTIONS AS THE PREDOMINANT CAUSE OF #SEPSIS IN #NEONATES AND #INFANTS, LEICESTER, #UK, 8 MAY-2 AUGUST 2016 (@eurosurveillanc, abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Eurosurveillance, Volume 21, Issue 34, 25 August 2016 / Rapid communication

CLUSTER OF HUMAN PARECHOVIRUS INFECTIONS AS THE PREDOMINANT CAUSE OF SEPSIS IN NEONATES AND INFANTS, LEICESTER, UNITED KINGDOM, 8 MAY TO 2 AUGUST 2016

JW Tang 1 2 , CW Holmes 1 , FA Elsanousi 1 , A Patel 1 , F Adam 1 , R Speight 3 , S Shenoy 3 , D Bronnert 3 , G Stiefel 3 , P Sundaram 3 , S Pande 3 , A Sridhar 3 , V Kairamkonda 3 , S Bandi 3

Author affiliations: 1. Clinical Microbiology and Virology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom; 2. Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom; 3. Leicester Childrens Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom

Correspondence: Julian Tang (julian.tang@uhl-tr.nhs.uk)

Citation style for this article: Tang JW, Holmes CW, Elsanousi FA, Patel A, Adam F, Speight R, Shenoy S, Bronnert D, Stiefel G, Sundaram P, Pande S, Sridhar A, Kairamkonda V, Bandi S. Cluster of human parechovirus infections as the predominant cause of sepsis in neonates and infants, Leicester, United Kingdom, 8 May to 2 August 2016. Euro Surveill. 2016;21(34):pii=30326. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.34.30326

Received:11 August 2016; Accepted:25 August 2016

 

Abstract

We report an unusually high number of cases (n = 26) of parechovirus infections in the cerebrospinal fluid (CSF) of neonates and infants admitted with sepsis in the United Kingdom during 8 May to 2 August 2016. Although such infections in neonates and infants are well-documented, parechovirus has not been routinely included in many in-house and commercial PCR assays for CSF testing. Clinicians should consider routine parechovirus testing in young children presenting with sepsis.

Keywords: Research; Abstracts; Parechovirus; Sepsis; UK.

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Severe #Sepsis and #Septic #Shock Associated with #Chikungunya Virus #Infection, #Guadeloupe, 2014 (@CDC_EIDjournal, abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract.]

Volume 22, Number 5—May 2016 / Dispatch

Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014

Amélie Rollé, Kinda Schepers, Sylvie Cassadou, Elodie Curlier, Benjamin Madeux, Cécile Hermann-Storck, Isabelle Fabre, Isabelle Lamaury, Benoit Tressières, Guillaume Thiery, and Bruno Hoen

Author affiliations: Centre Hospitalier Universitaire, Pointe-à-Pitre, France (A. Rollé, K. Schepers, E. Curlier, B. Madeux, C. Hermann-Storck, I. Fabre, I. Lamaury, G. Thiery, B. Hoen); Cellule Interrégionale d’Epidémiologie Antilles-Guyane, Institut de Veille Sanitaire, Gourbeyre, France (S. Cassadou); Centre d’Investigation Clinique 1424, Institut National de la Santé et de la Recherche Médicale, Pointe-à-Pitre (B. Tressières, B. Hoen); Université des Antilles, Faculté de Médecine Hyacinthe Bastaraud, Pointe-à-Pitre (G. Thiery, B. Hoen)

 

Abstract

During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.

Keywords: Research; Abstracts, Chikungunya Fever; Sepsis; Septic Shock.

——

#Assessment of #Clinical #Criteria for #Sepsis: For the 3rd Intl Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) (JAMA, abstract)

[Source: The Journal of the American Medical Association, full page: (LINK). Abstract, edited.]

Original Investigation | February 23, 2016 | Caring for the Critically Ill Patient

Assessment of Clinical Criteria for Sepsis:  For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [      ]

FREE

Christopher W. Seymour, MD, MSc1,2; Vincent X. Liu, MD, MSc3; Theodore J. Iwashyna, MD, PhD4,5,6; Frank M. Brunkhorst, MD7; Thomas D. Rea, MD, MPH8; André Scherag, PhD9; Gordon Rubenfeld, MD, MSc10; Jeremy M. Kahn, MD, MSc1,2; Manu Shankar-Hari, MD, MSc11; Mervyn Singer, MD, FRCP12; Clifford S. Deutschman, MD, MS13; Gabriel J. Escobar, MD4,5,6; Derek C. Angus, MD, MPH1,2

Author Affiliations: 1Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 2Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, Pennsylvania
3Division of Research, Kaiser Permanente, Oakland, California 4Department of Internal Medicine, University of Michigan, Ann Arbor 5Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan 6Australia and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 7Center for Clinical Studies, Jena University Hospital, Jena, Germany 8Division of General Internal Medicine, University of Washington, Seattle 9Research Group Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany 10Trauma, Emergency, and Critical Care Program, Sunnybrook Health Sciences Centre; Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada 11Critical Care Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, England 12Bloomsbury Institute of Intensive Care Medicine, University College London, London, England 13Feinstein Institute for Medical Research, Hofstra–North Shore–Long Island Jewish School of Medicine, Steven and Alexandra Cohen Children’s Medical Center, New Hyde Park, New York

JAMA. 2016;315(8):762-774. doi:10.1001/jama.2016.0288. Published online

 

ABSTRACT

Importance

The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown.

Objective

To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis.

Design, Settings, and Population

Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013.

Exposures

Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation).

Main Outcomes and Measures

For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC).

Results

In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75-0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome.

Conclusions and Relevance

Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis.

Keywords: Research; Abstracts; Sepsis.

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