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. 2021 Feb 24;16(2):e0247577. doi: 10.1371/journal.pone.0247577

Emergency mortality of non-trauma patients was predicted by qSOFA score

Yufang Li 1,#, Yanxia Guo 1,#, Du Chen 1,*
Editor: Marleen Smits2
PMCID: PMC7904145  PMID: 33626105

Abstract

Objective

This study was aimed to evaluate the performance of quick sequential organ failure assessment (qSOFA) in predicting the emergency department (ED) mortality of non-trauma patients and to expand the application scope of qSOFA score.

Methods

A single, retrospective review of non-trauma patients was conducted in ED between November 1, 2016 and November 1, 2019. The qSOFA score was obtained from vital signs and Glasgow Coma Scale (GCS) score. The outcome was ED mortality. Multivariable logistic regression analysis was performed to explore the association between the qSOFA score and ED mortality. The area under the receiver operating characteristic (AUROC) curve, the best cutoff value, sensitivity and specificity were performed to ascertain the predictive value of the qSOFA score.

Results

228(1.96%) of the 11621 patients were died. The qSOFA score was statistically higher in the non-survival group (P<0.001). The qSOFA score 0 subgroup was used as reference baseline, after adjusting for gender and age, adjusted OR of 1, 2 and 3 subgroups were 4.77 (95%CI 3.40 to 6.70), 18.17 (95%CI 12.49 to 26.44) and 23.63 (95%CI 9.54 to 58.52). All these three subgroups show significantly higher ED mortality compared to qSOFA 0 subgroup (P<0.001). AUROC of qSOFA score was 0.76 (95% CI 0.73 to 0.79). The best cutoff value was 0, sensitivity was 77.63% (95%CI 71.7% to 82.9%), and specificity was 67.2% (95%CI 66.3% to 68.1%).

Conclusion

The qSOFA score was associated with ED mortality in non-trauma patients and showed good prognostic performance. It can be used as a general tool to evaluate non-trauma patients in ED. This is just a retrospective cohort study, a prospective or a randomized study will be required.

Introduction

The emergency department (ED) is a place with many patients, whose illness are diverse and complex, especially non-trauma patients. Emergency physicians and nurses need to focus on critically ill patients, so rapid and accurate identification of patients at high risk of death is the crux to reduce ED mortality and optimize health resources. A variety of clinical tools have been proven to assess outcomes in ED patients, such as modified early warning score (MEWS), national early warning score(NEWS) and Acute Physiology and Chronic Health Evaluation (APACHEⅡ) [1–3]. However, it is inconvenient to use them in a fast-paced ED, because of the cumbersome evaluation process or containing laboratory indicators.

In 2016, a novel tool was proposed to identify patients at high risk of death from sepsis, which was the Quick Sepsis-Related Organ Failure Assessment (qSOFA) [4]. Although practicality remains controversial, several recent studies suggested that qSOFA can predict mortality in noninfectious disease, such as pancreatitis, cirrhosis, Glyphosate poisoning and trauma [5–8]. Because most of the non-trauma patients in the ED died of respiratory failure, circulatory failure and other organ dysfunction, which were included in the definition of "life-threatening organ dysfunction" in sepsis [4,9].

A simple, universal tool that can be quickly calculated at the bedside without any biochemical markers or waiting time will be very useful for emergency physicians to assess patients. It was found that qSOFA fully meets these requirements. It is so easy to remember, because it comprises only three binary variables. Therefore, we used the qSOFA score to conduct a mortality study of non-trauma patients in ED.

Materials and methods

Design and setting

This retrospective cohort study was conducted at the First Affiliated Hospital of Soochow University, a general hospital in China. The data of this study were taken from the hospital electronic medical record system and all the data of patients were collected without identifiable personal information. The study was approved by the Ethics Committees of the First Affiliated Hospital of Soochow University (Ethical Research Batch NO.2020152). The Institutional Review Boards of the Ethics Committees waived the need for informed consent from our study participants due to the retrospective nature of the data. This study conforms to the principles outlined in the Declaration of Helsinki.

Selection of participants

The study was conducted from November 1, 2016 to November 1, 2019. The non-trauma patients who were treated by the physician in the ED were selected using the hospital electronic medical record system. Patients who were under the age of 18 and had a prior terminal illness were excluded in the study. We also excluded dental, dermatological disease, traumatic disease and neurological diseases since they were not managed by the physicians in our ED.

Data collection and processing

The following data were collected from the electronic medical records: age, gender, initial vital signs (systolic blood pressure, respiratory rate, pulse rate, temperature and oximetry), hours in the emergency room (HER) and Glasgow Coma Scale (GCS) score. Researchers can calculate the qSOFA score from these simultaneous (within 2 minutes) records. The qSOFA score was assessed and allocated one point for each of the three variables [4]: systolic BP ≤100 mm Hg, respiratory rate ≥22 breaths per minute, and altered mental status (GCS score ≤13).

Outcome measures

The only outcome for this study was ED mortality. Death after hospitalization and discharge was not recorded. According to the qSOFA score, the patients were divided into four subgroups to assess the association between outcomes and qSOFA.

Data analysis

Continuous variables were tested for normality distribution using Shapiro-Wilk test. Continuous variables of non-normality were expressed as median (P25, P75) and compared using Mann-Whitney test. Categorical variables were expressed as frequencies and percentages and compared using Likelihood-ratio Chi squared test. Logistic regression models were performed to calculate the odds ratios (ORs) of variables for death. Receiver operating characteristic curve were performed to get the area under the curve (AUC). Statistics and plotting were completed by STATA 15.0 software. Two-tailed P<0.05 was considered to be statistically significant.

Results

Comparison of survival group and non-survival group

A total of 11621 patients were involved in the study, of whom 7140(61.44%) were male. 11393(98.04%) patients survived, and 228(1.96%) patients died. The mean age was 62 (47, 73) and 66 (54, 76) respectively. Patients in the survival group were younger than those who were in the non-survival group. And was statistically significant (P = 0.001). The HER were 11 (2, 24) and 7 (2, 22) in the survival and non-survival groups. However, the difference was not statistically significant (P = 0.325) (Table 1).

Table 1. Baseline characteristics.

Variables Survival 11393(98.04%) Non-survival 228(1.96%) P value
Sex 0.040
    Female 4408(38.69%) 73(32.02%)
    Male 6985(61.31%) 155(67.98%)
Age (year) 62(47, 73) 66(54, 76) 0.001
MEWS 2(1,4) 6(3,10) <0.001
qSOFA 0(0, 1) 1(1, 2) <0.001
    0 7657(99.34%) 51(0.66%)
    1 3138(96.82%) 103(3.18%)
    2 558(89.14%) 68(10.86%)
    3 40(86.96) 6(13.04%)
HER (hour) 11(2, 24) 7(2, 22) 0.325
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qSOFA, quick sepsis-related organ failure assessment; MEWS, modified early warning score; HER, hours in the emergency room.

ED Mortality according to qSOFA score

Among all the patients, 7708 patients had a qSOFA score of 0 (66.33%), 3241 patients had a qSOFA score of 1 (27.89%), 626 patients had a qSOFA score of 2 (5.39%), and 46 patients had a qSOFA score of 3 (0.39%). The qSOFA score was significantly higher in the non-survival group (P<0.001) (Table 1). According to the qSOFA score, the ED mortality of subgroup 0, 1, 2, and 3 were 0.6%, 3.28%, 12.06% and 15.38% respectively. Accompany with the increase of the qSOFA score, there is a trend of linear increase in ED mortality.

Predictive performance

The patients were divided into four subgroups according to the qSOFA score. The qSOFA score 0 subgroup was used as reference baseline, the crude ORs of 1, 2 and 3 subgroups were 4.93 (95%CI 3.51 to 6.91), 18.30 (95%CI 12.60 to 26.57) and 22.52 (95%CI 9.15 to 55.46) respectively. After adjusting for gender and age, adjusted ORs of 1, 2 and 3 subgroups were 4.77 (95%CI 3.40 to 6.70), 18.17 (95%CI 12.49 to 26.44) and 23.63 (95%CI 9.54 to 58.52). All these three subgroups show significantly higher ED mortality compared to qSOFA 0 (P<0.001) (Fig 1). ED mortality was associated with the qSOFA score either before or after adjustment for other factors, and an increase in score predicted an increase in mortality. Area under the Receiver operating characteristic curve (AUROC) of qSOFA for predicting ED mortality in non-trauma patients was 0.76 (95% CI 0.73 to 0.79). The best cutoff value determined by Youden index was 0, the corresponding sensitivity was 77.63% (95%CI 71.7% to 82.9%), and specificity was 67.2% (95%CI 66.3% to 68.1%). Meanwhile, the AUROC for MEWS score was 0.79 (95% CI 0.76 to 0.83). The best cutoff value was 4, sensitivity was 64.0% (95%CI 57.4% to 70.3%), and specificity was 86.1% (95%CI 85.4% to 86.7%) (Fig 2). The difference was statistically significant (P = 0.003).

Fig 1. Forest plot of crude ORs and adjusted ORs of qSOFA.

Fig 1

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OR, odds ratio; Crude ORs were calculated by univariable logistic regression model. Adjusted ORs were calculated by multivariable logistic regression of qSOFA, sex, age.

Fig 2. Receiver operating characteristic curve of qSOFA and MEWS predicting death.

Fig 2

Open in a new tab

Discussion

As soon as possible, the early identification and rapid response of acute coronary syndrome, sepsis and other critically ill patients with potential death risk can reduce the mortality [10]. This is one of the few studies to clarify the role of qSOFA score in predicting ED mortality in non-trauma patients.

It is shown that the qSOFA score in the ED can predict the mortality of non-trauma patients. The qSOFA score was associated with ED mortality (0 [0.66%], 1 [3.18%], 2 [10.86%], and 3[13.04%]). As the qSOFA score increased from 0 to 3, the ED mortality significantly increased (P<0.001). Thus, the qSOFA score, which can be easily and rapidly calculated, can potentially be used as a general tool to predict death for emergency non-trauma patients.

The qSOFA score has been used as a new tool for sepsis and septic shock [4]. It was developed as a risk stratification tool for patients who are admitted outside the ICU, such as those in ED [11–13]. Seymour et al [11] studied 148,907 suspected infected patients, of whom 4% died. Among encounters with suspected infection outside of the ICU, the predictive validity (AUROC = 0.81; 95%CI, 0.80–0.82) for in-hospital mortality of qSOFA was statistically greater than SOFA and systemic inflammatory response syndrome (SIRS) criteria.

This report led to a bunch of studies in regard to the usefulness of the qSOFA score outside the ICU, some of which were on non-infectious diseases [6–8,12,13]. In patients with glyphosate surfactant herbicide poisoning [7], qSOFA was independently associated with in-hospital mortality. The AUC of qSOFA was as high as 0.841 (95% CI, 0.772–0.895). Singer AJ et al [12] further support its practicability, especially in undifferentiated ED patients. The study included 22,530 patients, who were divided into two subgroups: infected and uninfected. The predictive validity of death in patients with and without suspected infection were similarly high (0.75, 95% CI 0.71 to 0.78 and 0.70, 95% CI 0.65 to 0.74). They were consistent with our study (AUROC = 0.76, 95% CI 0.73 to 0.79). The difference was that our study did not distinguish between infection patients and non-infection ones.

A variety of clinical tools have been demonstrated to predict mortality of patients in ED. APACHEⅡis one of the most commonly used tools, whose accuracy had been confirmed in a large number of clinical studies [14,15]. The disadvantages of the APACHEⅡwere the complex calculation method and depends on laboratory testing [2]. That was not conducive to assess the condition quickly, so it was difficult to be widely used in ED [16].The MEWS and NEWS were also often used to predict the outcome of emergency patients. The MEWS was miscalculated frequently, the probability as high as 18.2% [17]. The potential of NEWS implementation in clinical practice was proved complicated [18]. In addition, there were a number of potential false positives in patients with chronic hypoxemia when using NEWS as the tool [19]. With the application of computer technology, data can be automatically collected and analyzed, these problems can be well solved.

Our study shows that AUROC of qSOFA were lower than MEWS score, the difference was statistically significant. The MEWS score may be a better choice as a triage tool. The performance of the qSOFA in our study was similar to or even better than previous studies [14,20,21]. The advantages of qSOFA over other scores were that it contains only three binary variables and does not require complicated calculations. Therefore, the qSOFA score can be used as a tool to predict ED mortality in non-trauma patients.

This study still had several limitations. First, it was a retrospective study, which is subject to selection bias and errors of documentation and data entry. Secondly, the data were derived from a single institution and can’t represent other Settings. Thirdly, the patients who died after hospitalization were not counted as deaths. It is not clear whether these patients are in some way different from those in this cohort, making our conclusions unreliable. Fourthly, we included only non-trauma patients managed by the physicians in ED, neurological diseases were excluded in the study. However, the qSOFA may overperform in population of neurological diseases, in which the ED death was more common. Future multicenter prospective studies need to be continued to complement this study.

In conclusion, the qSOFA score was associated with ED mortality in non-trauma patients, and an increase in score predicted an increase in ED mortality. The qSOFA score is a simple and valuable tool that can be used in ED to predict mortality. Further multicenter prospective studies of the qSOFA score are required before it can be widely used.

Supporting information

S1 Data

(XLS)

Click here for additional data file. (1.7MB, xls)

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Subbe CP, Kruger M, Rutherford P, Gemmel L. Validation of a modified Early Warning Score in medical admissions. Qjm-Monthly Journal of the Association of Physicians. 2001;94(10):521–6. 10.1093/qjmed/94.10.521 . [DOI] [PubMed] [Google Scholar]
  • 2.Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE-II—A SEVERITY OF DISEASE CLASSIFICATION-SYSTEM. Critical Care Medicine. 1985;13(10):818–29. 10.1097/00003246-198510000-00009 . [DOI] [PubMed] [Google Scholar]
  • 3.Royal College of Physicians. National Early Warning Score (NEWS): Standardising the assessment of acute-illness severity in the NHS Report of a working party. London: RCP; 2012. Available from: https://www.rcplondon.ac.uk. [Google Scholar]
  • 4.Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama-Journal of the American Medical Association. 2016;315(8):801–10. 10.1001/jama.2016.0287 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Piano S, Bartoletti M, Tonon M, Baldassarre M, Chies G, Romano A, et al. Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections. Gut. 2018;67(10):1892–9. 10.1136/gutjnl-2017-314324 . [DOI] [PubMed] [Google Scholar]
  • 6.Jin DX, Singh V, Suleiman SL, Banks PA, McNabb-Baltar J. THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) AND QUICK SEQUENTIAL ORGAN FAILURE (QSOFA) SCORE AT PRESENTATION ARE ASSOCIATED WITH POOR OUTCOMES IN ACUTE PANCREATITIS. Gastroenterology. 2017;152(5):S488–S. 10.1016/s0016-5085(17)31815-2 WOS:000403140302027. [DOI] [Google Scholar]
  • 7.Cho YS, Moon JM, Chun BJ, Lee BK. USE OF qSOFA SCORE IN PREDICTING THE OUTCOMES OF PATIENTS WITH GLYPHOSATE SURFACTANT HERBICIDE POISONING IMMEDIATELY UPON ARRIVAL AT THE EMERGENCY DEPARTMENT. Shock. 2019;51(4):447–52. 10.1097/SHK.0000000000001201 . [DOI] [PubMed] [Google Scholar]
  • 8.Miyamoto K, Shibata N, Ogawa A, Nakashima T, Kato S. Prehospital quick sequential organ failure assessment score to predict in-hospital mortality among patients with trauma. Am J Emerg Med. 2019;37(12):2165–70. Epub 2019/03/18. 10.1016/j.ajem.2019.03.007 . [DOI] [PubMed] [Google Scholar]
  • 9.Coopersmith CM, Deutschman CS. The New Sepsis Definitions: Implications for the Basic and Translational Research Communities. Shock. 2017;47(3):264–8. 10.1097/SHK.0000000000000763 . [DOI] [PubMed] [Google Scholar]
  • 10.McNeill G, Bryden D. Do either early warning systems or emergency response teams improve hospital patient survival? A systematic review. Resuscitation. 2013;84(12):1652–67. 10.1016/j.resuscitation.2013.08.006 . [DOI] [PubMed] [Google Scholar]
  • 11.Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of Clinical Criteria for Sepsis For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama-Journal of the American Medical Association. 2016;315(8):762–74. 10.1001/jama.2016.0288 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Singer AJ, Ng J, Thode HC, Spiegel R, Weingart S. Quick SOFA Scores Predict Mortality in Adult Emergency Department Patients With and Without Suspected Infection. Annals of Emergency Medicine. 2017;69(4):475–9. 10.1016/j.annemergmed.2016.10.007 . [DOI] [PubMed] [Google Scholar]
  • 13.Hallac A, Puri N, Applebury D, Myers K, Dhumal P, Thatte A, et al. The Value of Quick Sepsis-Related Organ Failure Assessment Scores in Patients With Acute Pancreatitis Who Present to Emergency Departments: A Three-Year Cohort Study. Gastroenterology research. 2019;12(2):67–71. 10.14740/gr1132 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Polita JR, Gomez J, Friedman G, Ribeiro SP. Comparison of APACHE II and three abbreviated APACHE II scores for predicting outcome among emergency trauma patients. Revista Da Associacao Medica Brasileira. 2014;60(4):381–6. 10.1590/1806-9282.60.04.018 . [DOI] [PubMed] [Google Scholar]
  • 15.Godinjak A, Iglica A, Rama A, Tancica I, Jusufovic S, Ajanovic A, et al. Predictive value of SAPS II and APACHE II scoring systems for patient outcome in a medical intensive care unit. Acta medica academica. 2016;45(2):97–103. 10.5644/ama2006-124.165 . [DOI] [PubMed] [Google Scholar]
  • 16.Salluh JIF, Soares M. ICU severity of illness scores: APACHE, SAPS and MPM. Current Opinion in Critical Care. 2014;20(5):557–65. 10.1097/MCC.0000000000000135 . [DOI] [PubMed] [Google Scholar]
  • 17.van Galen LS, Dijkstra CC, Ludikhuize J, Kramer MHH, Nanayakkara PWB. A Protocolised Once a Day Modified Early Warning Score (MEWS) Measurement Is an Appropriate Screening Tool for Major Adverse Events in a General Hospital Population. Plos One. 2016;11(8):12 10.1371/journal.pone.0160811 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Kolic I, Crane S, McCartney S, Perkins Z, Taylor A. Factors affecting response to National Early Warning Score (NEWS). Resuscitation. 2015;90:85–90. 10.1016/j.resuscitation.2015.02.009 . [DOI] [PubMed] [Google Scholar]
  • 19.Spagnolli W, Rigoni M, Torri E, Cozzio S, Vettorato E, Nollo G. Application of the National Early Warning Score (NEWS) as a stratification tool on admission in an Italian acute medical ward: A perspective study. International Journal of Clinical Practice. 2017;71(3–4):8 10.1111/ijcp.12934 . [DOI] [PubMed] [Google Scholar]
  • 20.Mitsunaga T, Hasegawa I, Uzura M, Okuno K, Otani K, Ohtaki Y, et al. Comparison of the National Early Warning Score (NEWS) and the Modified Early Warning Score (MEWS) for predicting admission and in-hospital mortality in elderly patients in the pre-hospital setting and in the emergency department. Peerj. 2019;7:16 10.7717/peerj.6947 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Cattermole GN, Mak SKP, Liow CHE, Ho MF, Hung KYG, Keung KM, et al. Derivation of a prognostic score for identifying critically ill patients in an emergency department resuscitation room. Resuscitation. 2009;80(9):1000–5. 10.1016/j.resuscitation.2009.06.012 . [DOI] [PubMed] [Google Scholar]

Decision Letter 0

Marleen Smits

2 Sep 2020

PONE-D-20-22710

Emergency mortality of medical patients was predicted by qSOFA score

PLOS ONE

Dear Dr. Chen,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Oct 17 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Marleen Smits, PhD

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear Dr. Chen,

You have submitted a related manuscript to PLOS ONE entitled "Predictive value of qSOFA score for death in emergency department resuscitation room among adult trauma patients".

We have considered the overlap between the two papers in light of the journal's policy.

In your paper entitled “Emergency mortality of medical patients was predicted by qSOFA score” the predictive value of qSOFA for death in the ED was examined.

The second paper “Predictive value of qSOFA score for death in emergency department resuscitation room among adult trauma patients” presents a subgroup analysis of trauma patients in the ED resuscitation room. These patients were also included in the study described in the first paper.

Both analyses provide valuable information. However by splitting up the results into two separate papers, it seems that there are two studies that provide evidence for the predictive value of qSOFA, while in fact it is only one study. The study population of “Emergency mortality of medical patients was predicted by qSOFA score"" includes the study population of "Predictive value of qSOFA score for death in emergency department resuscitation room among adult trauma patients".

Therefore, we suggest you combine the two papers into one paper.

We look forward to receiving a major revision of “Emergency mortality of medical patients was predicted by qSOFA score", which includes the subgroup analysis of adult trauma patients in the ED resuscitation room.

Kind regards,

Marleen Smits

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PLoS One. 2021 Feb 24;16(2):e0247577. doi: 10.1371/journal.pone.0247577.r002

Author response to Decision Letter 0

28 Sep 2020

Dear Editor,

Thank you for reviewing the manuscript, we read your comments and suggestions carefully.

I'm sorry that the wording of the title of our manuscript may be inaccurate, resulting in your misunderstanding.

In fact, Paper1 (Emergency mortality of medical patients was predicted by qSOFA score) and Paper2 (Predictive value of qSOFA score for death in emergency department resuscitation room among adult trauma patients) were two separate sample studies, conducted by two different researchers (YuFang Li, WenJuan Huang) respectively. The study samples of Paper1 were non-traumatic patients (n=11621) treated by physicians in the emergency room, while the study samples of Paper2 were trauma patients (n=1739) treated by surgeons in the emergency room. Therefore, the research sample of Paper2 is not a subgroup of the research sample of Paper 1, but two different research samples.

In addition, there was considerable discrepancy between their research methods. For example, only age and gender were included in the multivariate regression model for non-traumatic patients to calculate the adjusted OR in Paper 1, but RIS scores reflecting the severity of injuries were added as adjusted variables in Paper2. Therefore, the adjusted OR meanings of these two studies are different.

To sum up, the study population of Paper1 does not include the study population of Paper2, and the research methods are also not exactly the same, so the two papers cannot be combined.

In order to avoid misunderstanding, we decided to revise the title of Paper1 as Emergency mortality of internal medicine patients was predicted by qSOFA score.

Thank you again for all your hard work and generous help.

Kind regards,

Du Chen

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (17KB, docx)

Decision Letter 1

Marleen Smits

27 Oct 2020

PONE-D-20-22710R1

Emergency mortality of internal medicine patients was predicted by qSOFA score

PLOS ONE

Dear Dr. Chen,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 11 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Marleen Smits, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study design and methods appear adequate to answer the research question. However the rationale of the research question and conclusions drawn from the results are inadequate in my opinion. The qSOFA was designed to assess patients with possible sepsis to quickly identify those with increased risk of adverse outcome. In this study the qSOFA is evaluated as a prediction tool for ED mortality in all non-traumatic patients. It is not explained what the clinical use can be. It is good practice in EDs to triage all patients upon arrival. The most important factor determining the triage level is the chance of (ED)mortality. It is not explained if the qSOFA is proposed as a triage system, or that it adds to the existing triage system. Furthermore, the qSOFA score is not compared to the NEWS (or other EWS), as the authors deem these to inconvenient to measure in the ED. However, the respiratory rate is the vital sign that is most time consuming to measure, and NEWS only adds point for the heart rate, SpO2 and body temperature, measurements that can be easily obtained during triage. The conclusion that qSOFA has good performance is relative. Most patients with a high score survive (598/672 patients with qSOFA ≥2), and most non-survivors presented with a qSOFA <2 (154/228 patients). To assess whether this is a good performance, the results should be compared to NEWS and/or triage categories. Lastly, the (revised) title is not clear: the term “emergency mortality” should best be avoided and “internal medicine patients” usually do not include patients presented with cardiac complaints. “Non-trauma patients” appears to be a better representation of the study population.

Reviewer #2: Chen et al. analyse the association between qSOFA score and early mortality in the emergency department in a large cohort of “internal medicine” patients.

I have some suggestions:

- English form is poor and needs revising by a native-english speaker.

- Abstract, Discussion: authors claim that their study is adequate “in predicting the emergency department (ED) mortality”. However, this is a retrospective cohort study, and authors can only observe an association between variables. In order to observe a prediction, a prospective or – better – a randomized study will be required.

- Abstract, Materials and Methods: “internal medicine patients” – please clarify: were these patients the ones admitted to an internal medicine department ? Or this term is adopted to identify generically “medical patients” ? Since authors adopt “ED mortality” as main outcome, I think that authors mean for “internal medicine patients” the ones with medical conditions, however this concept is ambiguous and not clear. Moreover, the analysed cohort is not well characterised, which is a major limitation for the interpretation of the results. Authors must define in the results which medical pathologies were considered (acute myocardial infarction ? sepsis ? septic shock ? acute heart failure ? atrial fibrillation ? pneumonia ? etc.) and which was the prevalence of outcome in each subgroup.

- Materials and Methods, Results: in particular, how many patients affected by infective diagnoses were included in the cohort ? how many with sepsis or septic shock ? was the outcome different in patients admitted for "infective" pathologies and "non-infective" pathologies ?

- Materials and Methods: the exclusion of ischemic stroke is a bias, in my opinion, since it is an acute medical condition burdened by a high mortality. However authors specified this as a limitation of the study. Were other neurologic conditions (status epilepticus, brain haemorrage, and so on) considered in this cohort ?

- Materials and Methods: another point is the absence of comorbidities: authors should at least consider the most common comorbidities in their analyses (COPD, chronic heart failure, cancer, atrial fibrillation, ischemic heart disease, etc.) since several studies associated the complexity of the patient to an increased risk of in-hospital death. This could radically modify the estimates performed in the logistic regression analysis.

- Materials and Methods: a Cox regression analysis considering the time-to-event (time-to-ED death) could considered instead of logistic regression analysis.

- Materials and Methods, Results: authors did not consider patients died after hospitalization from ED. I think, however, that they could present the datum of how many patients were admitted to an ICU, which could be a surrogate of their critical illness, as already done in other similar studies.

- Results, Materials and Methods, Discussion: this study is similar other published papers (for example: https://emj.bmj.com/content/35/6/350), in which qSOFA was observed to perform better than other scores in predicting ED mortality and critical illness. Authors should discuss on what is similar and what is different from what is already known and published.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2021 Feb 24;16(2):e0247577. doi: 10.1371/journal.pone.0247577.r004

Author response to Decision Letter 1

14 Jan 2021

To Reviewer #1

Dear reviewer，thank you very much for your review and suggestions.

Because the qSOFA score contains only three simple binary variables which are easy to get, we wanted to verify the predictive value of qSOFA score for the prognosis of non-trauma patients, including sepsis. The aim is to expand the scope of the qSOFA score and provide a simple assessment tool for non-trauma patients in the emergency department.

Your suggestion to compare the qSOFA score with the MEWS score has been adopted and revised in the manuscript. Our study shows that AUROC of qSOFA is lower than MEWS score, and the difference is statistically significant. But qSOFA scores have less content and are easier to calculate.The MEWS was miscalculated frequently, the probability as high as 18.2% (The 17th reference in the manuscript). Compared to MEWS, the AUC of qSOFA score is slightly lower, but still has good predictive value and can be used as a supplement to the existing triage system.

Finally, thank you for your suggestion to modify the title. We have modified the title as “Emergency mortality of non-trauma patients was predicted by the qSOFA score”.

To Reviewer #2

Dear reviewer，thank you very much for your review and suggestions.

--Abstract, Discussion: It is true, as you said, that although the qSOFA score is associated with ED mortality in non-trauma patients and shows a good prognostic performance, this study is just a retrospective study, a prospective will be required.

--Abstract, Materials and Methods: Your suggestion is very constructive, the concept of internal medical patients is really vague, we have modified the title as ”Emergency mortality of non-trauma patients was predicted by the qSOFA score”.Our aim is to expand the practicability of qSOFA score , especially in undifferentiated non-trauma patients, so we didn’t conduct a subgroup analysis based on medical pathologies.

--Abstract, Materials and Methods: The purpose of our study was to verify the predictive value for the prognosis of non-traumatic patients，expand the scope of qSOFA score and provide a simple assessment tool for all non-trauma patients in the emergency department. And studies have confirmed that the predictive validity of death in patients with and without suspected infection were similarly high (The 12th reference in the manuscript). So we did not deliberately distinguish between the infected and non-infected patients.

-- Materials and Methods: All the non-trauma patients included in this study were treated by physicians, while neurological diseases were treated by neurologist, so they were not included in the study.

-- Materials and Methods: This is a retrospective study that extracted information from the hospital emergency electronic record system. The time of onset, complications, ICU admission, and other information were not recorded. To sum up, this study does have some limitations in design.

-- Materials and Methods: The Cox regression you proposed instead of logistic regression was indeed very good. However, since our system only has the time of register, we cannot accurately calculate the time from onset to death. After careful consideration, logistic regression analysis was still used.

-- Materials and Methods, Results: The only outcome of our study was ED mortality, so we did not consider post-admission deaths and ICU admissions of non-traumatic patients.

-- Results, Materials and Methods, Discussion: In the discussion section, we have compared the results with those of some published studies, especially those that, like our studies, target people who are not sepsis(References to articles 6-8 and 12-13 in the manuscript). The predictive performance of qSOFA score and MEWS score was also compared in the results and discussion section.

Attachment

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Decision Letter 2

Marleen Smits

28 Jan 2021

PONE-D-20-22710R2

Emergency mortality of non-trauma patients was predicted by the qSOFA score

PLOS ONE

Dear Dr. Chen,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

Please address the comment of reviewer 1 that the MEWS gives a better prediction, which should lead to an adjustment of the conclusions of the manuscript. Moreover, please have a native English speaker check the language in the paper.

==============================

Please submit your revised manuscript by Mar 14 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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We look forward to receiving your revised manuscript.

Kind regards,

Marleen Smits, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I acknowledge the additional analysis of the MEWS by the authors. However, in accordance with other research, the MEWS gives a better prediction, which is in my opinion reason to adjust the conclusions of the manuscript. The AUROC is not the most indicative measure to assess the added value. The sens, spec, PPV and NPV at the cutoff point used in clinical practice are more important. For qSOFA a score of 2 or higher is used to identify high risk patients. At this cutoff point sensitivity is 32% and specificity 96%. According to the ROC curve, at the optimal cutoff point of MEWS sens is about 50% with spec of 97-98%. This is a major difference, not shown in the relatively small difference in AUROC. The arguments that MEWS is to complicated to use in the ED and scores are often miscalculated are not valid when the score are automatically calculated which is becoming more and more standard practice. The manuscript school be revised, either more in support of the use of MEWS/NEWS (early warning scoring systems can vary substantially and may also be compared), or as a validation of the prediction of mortality of qSOFA (without concluding it should be used in triage).

Reviewer #2: I have read the authors' responses and the reviewed article. Authors answered to most of the questions and the overall quality of the paper improved after revision. However, English form is still not fair for publication in an international journal. I recommend to deeply revise the English form (best if the revision is done by a native-English-speaker) in all the sections of the paper.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 Feb 24;16(2):e0247577. doi: 10.1371/journal.pone.0247577.r006

Author response to Decision Letter 2

7 Feb 2021

To Reviewer #1

Dear reviewer，thank you very much for your review and suggestions.

We have calculated best cutoff values, sensitivity and specificity for qSOFA score and MEWS score based on the Yoden index (listed in the results section of the manuscript).

Indeed, due to the widespread use of computers, the complexity and error-prone nature of MEWS score are negligible problems, so we clearly suggest that MEWS was a better choice as a triage tool.

According to the results of the study,the qSOFA score can be used as a tool to predict ED mortality in non-trauma patients.

To Reviewer #2

Dear reviewer，thank you very much for your review and suggestions.

The English form has been deeply modified.

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (17.2KB, docx)

Decision Letter 3

Marleen Smits

10 Feb 2021

Emergency mortality of non-trauma patients was predicted by the qSOFA score

PONE-D-20-22710R3

Dear Dr. Chen,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Marleen Smits, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Marleen Smits

15 Feb 2021

PONE-D-20-22710R3

Emergency mortality of non-trauma patients was predicted by qSOFA score

Dear Dr. Chen:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Marleen Smits

Academic Editor

PLOS ONE

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