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. 2020 May 15;15(5):e0232999. doi: 10.1371/journal.pone.0232999

Place-provider-matrix of bystander cardiopulmonary resuscitation and outcomes of out-of-hospital cardiac arrest: A nationwide observational cross-sectional analysis

Dae Kon Kim 1, Sang Do Shin 2,*, Young Sun Ro 3, Kyoung Jun Song 4,5, Ki Jeong Hong 4, So Yeon Joyce Kong 3
Editor: Andrea Ballotta6
PMCID: PMC7228068  PMID: 32413089

Abstract

Aims

This study aims to test the association between the place-provider-matrix (PPM) of bystander cardiopulmonary resuscitation (CPR) and outcomes of out-of-hospital cardiac arrest (OHCA).

Methods

Adult patients with OHCA with a cardiac etiology from 2012 to 2017 in Korea were analyzed, excluding patients who had unknown information on place, type of bystander, or outcome. The PPM was categorized into six groups by two types of places (public versus home) and three types of providers (trained responder (TR), family bystander, and layperson bystander). Outcomes were survival to discharge and good cerebral performance category (CPC) of 1 or 2. Multivariable logistic regression analysis was performed to test the association between PPM group and outcomes with adjustment for potential confounders to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) (reference = Public-TR).

Results

A total of 73,057 patients were analyzed and were categorized into Public-TR (0.6%), Home-TR (0.3%), Public-Family (1.8%), Home-Family (79.8%), Public-Layperson (9.9%), and Home-Layperson (7.6%) groups. Compared with the Public-TR group, the AORs (95% CIs) for survival to discharge were 0.61 (0.35–1.05) in the Home-TR group, 0.85 (0.62–1.17) in the Public-Family group, 0.38 (0.29–0.50) in the Home-Family group, 1.12 (0.85–1.49) in the Public-Layperson group, and 0.42 (0.31–0.57) in the Home-Layperson group. The AORs (95% CIs) for good CPC were 0.58 (0.27–1.25) in the Home-TR group, 0.88 (0.61–1.27) in the Public-Family group, 0.38 (0.28–0.52) in the Home-Family group, 1.20 (0.87–1.65) in the Public-Layperson group, and 0.42 (0.30–0.59) in the Home-Layperson group.

Conclusion

The OHCA outcomes of the Home-Family and Home-Layperson groups were worse than those of the Public-TR group. This finding suggests that OHCA occurring in private places with family or layperson bystanders requires a new strategy, such as dispatching trained responders to the scene to improve CPR outcomes.

Introduction

Out-of-hospital cardiac arrest (OHCA) causes severe mortality around the world. Approximately 30,000 South Koreans, 300,000 Europeans, and 400,000 Americans experience OHCA each year, with survival rates of 3.0% in Korea, 10.3% in Europe and 9.5% in the United States. [1–3]

Rapid cardiopulmonary resuscitation (CPR) and public-access defibrillation (PAD) are the most important components of community CPR programs in treating OHCA. The potential capacity of the bystander is critical for providing rapid CPR and defibrillation. [4] There are three main types of bystanders: trained responders (firefighters, security guards, police officers), family members, and non-family laypersons. Trained responders (TRs) refer to a specific group of individuals who have a high chance of encountering cardiac arrest in daily life because of occupational characteristics and training for CPR situations but who are not part of the officially organized emergency response system in a community. In general, TRs fall between a bystander and first responder according to the Utstein definition of provider. TR services have been regarded as the most basic fundamental programs of the modern emergency medical services (EMS) system. [5, 6] However, TR systems, as a component of community CPR programs, are not well established as part of EMS systems in many countries.

Usually, family or layperson bystanders have little CPR experience, greater fear of performing CPR, and more anxiety regarding legal responsibility than TRs. [7, 8] The quality of CPR by a layperson may be different according to an individual’s self-efficacy in performing CPR. Thus, the quality of CPR cannot be assured to the same extent that it can be when performed by TRs. [4, 9] The type of bystander (TR, family member, and layperson) in the community CPR program is one of the most critical factors related to outcomes after OHCA. Another important factor related to outcomes of OHCA is the place of the cardiac arrest event. [10, 11] OHCA occurring in public places is typically characterized by younger patient age, more ventricular fibrillation (VF) in the initial ECG rhythm, and more attempted CPR by bystanders. Therefore, the final outcomes are much better in OHCA occurring in public places than in OHCA occurring at home. [11]

The place-provider-matrix (PPM) in the community CPR program is a new conceptual framework for stratifying outcomes of OHCA based on a combination of place and provider factors. This matrix combines two important aspects of OHCA: the event place (row) and the bystander characteristic (column), which constitute the basis of rapid CPR and early defibrillation. This framework can be used to evaluate the performance of community CPR programs and outcomes of OHCA more effectively.

We hypothesized that the Public-TR group would exhibit the best survival and good neurologic outcome and that different PPM groups would show worse outcomes. The goal of this study is to compare the demographic findings according to the place-provider matrix and to test whether the PPM group is associated with outcomes after OHCA. In addition, we compared the effect size of the PPM group according to the time of OHCA incidence between day and night.

Methods

Study design and setting

This is a retrospective, nationwide, multicenter and cross-sectional study using the national OHCA registry from 2012 to 2017.

Study setting

According to the 2004 National Emergency Medical Services (EMS) Act, school teachers, sports instructors, public transportation vehicle drivers, safety guards of national parks, and policemen are required to receive CPR education to encourage bystander CPR. In addition, private places where TRs work or reside were designated as mandatory sites for PAD programs in 2008 and 2011 by the EMS Act. This group with mandatory CPR education is referred to as trained responders (TRs). TRs have been required to complete a regular two-hour course of CPR training at least once a year since 2005. [6] TRs are not first responders who respond to medical emergencies in an official capacity as part of an organized medical response team. Rather, they are similar to bystanders but have been trained in CPR because of the higher chance of encountering CPR situations due to occupational characteristics. Therefore, TRs do not have the duty of official calls or dispatches from EMS systems. They voluntarily participate in the CPR situation.

The Korean EMS are based on a single-tiered, fire-based, and government-sponsored system. EMS support a population of approximately 50 million people and provide a basic to intermediate level of ambulance services in sixteen provinces. Emergency Medical Technicians (EMT) can provide CPR at the scene and during transport with automatic external defibrillation (AED) and advanced airway management under direct medical control. Advanced cardiac life support (ACLS) drugs are available in the emergency department (ED) and are limited in most prehospital areas of the country. The PAD program started in 2009, but it was not widely used until recently. [12]

The EDs in Korea are classified into three levels according to resources and functional requirements set by the national government. Level 1 (n = 19) and level 2 (n = 110) EDs have more resources and better facilities for emergency care and emergency physicians to manage patients 24 hours a day and 365 days a year. Level 3 EDs (n = 310) can be staffed by general physicians. The CPR guidelines of international academic societies are generally used and are recommended in clinical practice and research. The 2015 AHA guidelines have recently been accepted as the standard guideline by national academic organizations. [13, 14]

Data source and collection

This study used the Korean OHCA registry constructed from two databases, which included all OHCAs transported by the EMS since 2006. [3, 9, 15] One database consists of an EMS cardiac arrest registry recorded by the EMS providers of the National Fire Agency, and the other consists of a hospital cardiac arrest registry for hospital care and outcomes collected by the Korea Centers for Disease Control and Prevention (CDC). The OHCA case documentation was sent to the Korea CDC and matched with hospital medical records created by trained medical record reviewers who evaluated all hospital records related to the care provided in the ED, intensive care unit, and wards, as well as the outcomes at discharge. The data quality management team, consisting of EMS physicians, epidemiologists, biostatistics experts, and cardiologists, meets monthly and maintains the data quality through education and feedback to medical record reviewers regarding unclear variables during medical record reviews. [6, 13]

This study was reviewed and approved by the institutional review board of the study hospital. The requirement for informed consent was waived because the data variables did not include personal information, and the study process did not result in any risk for patients. [6] The Korea CDC approved the use of the national registry for this study.

Study population

All cases of OHCA of presumed cardiac etiology, with a patient age older than 18 years old, and with CPR attempted by EMS providers from January 2012 to December 2017 were included. A cardiac etiology was presumed in the absence of any other obvious cause, such as trauma, drowning, hanging, overdose, or asphyxia, according to clinical information. Patients whose OHCA was witnessed by EMS providers and who collapsed during ambulance transport or in medical facilities or nursing homes were excluded. Patients with missing information regarding the place of the event, bystander characteristics, and outcomes were excluded.

Variables

The main exposure was the PPM classification, which included the first CPR or defibrillation provider (trained responder, family bystander, and non-family layperson bystander) with stratification by place (public or home). The TR category included firefighters, policemen, public transportation vehicle drivers, school health teachers, sports facility employees, lifeguards, workplace safety employees, travel business employees, and those designated by the EMS Act and regulations. [6] A family bystander (Family) was defined as a family member of the patient. Non-family layperson bystanders (Laypersons) included nearby bystanders, colleagues, friends, and other bystanders. The public places included a public/commercial building, a street/highway, an industrial place, a transport center, a recreation place and a farm. Home places included home residences and dormitories. The PPM was divided into six groups: group 1 (Public-TR), group 2 (Home-TR), group 3 (Public-Family), group 4 (Home-Family), group 5 (Public-Layperson) and group 6 (Home-Layperson).

The variables were general factors, Utstein factors and EMS factors. General factors included gender, patient age, date/time factors such as year, season, weekend, and time. Utstein factors included metropolis, witness, bystander CPR and defibrillation, and primary ECG (shockable versus non-shockable). [16] EMS factors included response time interval (RTI), airway management, EMS defibrillation, and hospital factors (ED level 1 to 4).

Outcome measure

The primary outcome was favorable neurological outcome, defined as cerebral performance category (CPC) scale score of 1 (good cerebral performance) or 2 (moderate cerebral disability) at hospital discharge. The secondary outcome was survival to discharge. The CPC and survival to discharge were determined according to a review of hospital discharge abstract records of the Korea CDC medical record review.

Statistical analysis

A descriptive analysis was performed to examine the distribution of potential risk factors for outcomes among each PPM group. The categorical variables were described using counts and proportions and compared with the chi-square test. The continuous variables were compared using the Wilcoxon rank sum test. A multivariable logistic regression analysis was performed to test the association between the PPM group and outcomes (reference = Public-TR group). Potential confounders, such as gender, age, year, season, weekend, metropolis, witness, bystander CPR, bystander AED, primary ECG, RTI, airway, EMS defibrillation, and ED level, were adjusted. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for outcomes. We performed an interaction analysis to compare the effect size of the arrest time, daytime (06:00–17:59) versus nighttime (18:00–05:59), on the outcomes in the final multivariable logistic models. All analyses were performed using SAS version 9.4 (SAS© Cary, NC, USA).

Results

Demographic findings

Of the 171,534 eligible OHCA patients, 73,057 patients were finally analyzed, excluding patients with noncardiac etiology (n = 45,926), who did not meet the age criteria (n = 1,903), who were not treated by EMS (N = 11,320), with unknown arrest place (N = 11,752), who experienced arrest during ambulance transport (N = 6,957), who collapse in medical facilities/nursing homes (N = 10,141), with unknown bystander information (N = 7,111), with arrest witnessed by a healthcare provider (N = 3,367) and with unknown outcome (N = 0) (Fig 1).

Fig 1. Study flow chart.

Fig 1

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OHCA, out-of-hospital cardiac arrest; EMS, emergency medical services; CPR, cardiopulmonary resuscitation.

Of these 73,057 patients, the number (percent) of patients in each PPM group was 438 (0.6%) in the Public-TR group, 188 (0.3%) in the Home-TR group, 1,319 (1.8%) in the Public-Family group, 58,307 (79.8%) in the Home-Family group, 7,226 (9.9%) in the Public-Layperson group, and 5,579 (7.6%) in the Home-Layperson group. The survival to discharge and good CPC rate of each PPM group were 17.8%/11.6% in the Public-TR group, 8.0%/4.8% in the Home-TR group, 15.5%/10.6% in the Public-Family group, 4.9%/2.8% in the Home-Family group, 21.0%/15.1% in the Public-Layperson group, and 6.1%/3.5% in the Home-Layperson group, respectively (Table 1 and Fig 2). Table 2 describes the demographic findings of variables according to arrest time. The survival to discharge and good CPC rates were 7.7% and 4.9% during the nighttime and 6.4% and 3.9% during the daytime, respectively.

Table 1. Demographics of the study population according to the place-provider-matrix.

Variables All Place-provider-matrix
Trained responder Family bystander Layperson bystander
Public Home Public Home Public Home
N % N % N % N % N % N % N %
All 73057 100.0 438 100.0 188 100.0 1319 100.0 58307 100.0 7226 100.0 5579 100.0
Gender
Female 25719 35.2 82 18.7 52 27.7 414 31.4 21820 37.4 1194 16.5 2157 38.7
Male 47338 64.8 356 81.3 136 72.3 905 68.6 36487 62.6 6032 83.5 3422 61.3
Age
Age<65 26923 36.9 292 66.7 101 53.7 665 50.4 18634 32.0 4755 65.8 2476 44.4
65 = <Age<85 36569 50.1 130 29.7 74 39.4 574 43.5 31092 53.3 2255 31.2 2444 43.8
Age> = 85 9565 13.1 16 3.7 13 6.9 80 6.1 8581 14.7 216 3.0 659 11.8
Median (q1-q3) 71 (58–80) 59 (50–69) 63 (53–76) 64 (54–75) 73 (60–81) 58 (50–70) 68 (55–79)
Year
2012 7732 10.6 71 16.2 37 19.7 145 11.0 6318 10.8 699 9.7 462 8.3
2013 9835 13.5 38 8.7 22 11.7 162 12.3 8300 14.2 792 11.0 521 9.3
2014 12788 17.5 66 15.1 31 16.5 200 15.2 10312 17.7 1197 16.6 982 17.6
2015 14048 19.2 66 15.1 32 17.0 239 18.1 11259 19.3 1288 17.8 1164 20.9
2016 14204 19.4 97 22.1 36 19.1 268 20.3 11181 19.2 1416 19.6 1206 21.6
2017 14450 19.8 100 22.8 30 16.0 305 23.1 10937 18.8 1834 25.4 1244 22.3
Season
Spring 18330 25.1 94 21.5 40 21.3 329 24.9 14611 25.1 1855 25.7 1401 25.1
Summer 16058 22.0 112 25.6 53 28.2 303 23.0 12702 21.8 1638 22.7 1250 22.4
Fall 18082 24.8 103 23.5 42 22.3 340 25.8 14309 24.5 1891 26.2 1397 25.0
Winter 20587 28.2 129 29.5 53 28.2 347 26.3 16685 28.6 1842 25.5 1531 27.4
Weekend
Weekday 41479 56.8 263 60.0 100 53.2 695 52.7 32910 56.4 4160 57.6 3351 60.1
Weekend 31578 43.2 175 40.0 88 46.8 624 47.3 25397 43.6 3066 42.4 2228 39.9
Daytime
Night 26225 35.9 130 29.7 85 45.2 365 27.7 22563 38.7 1715 23.7 1367 24.5
Day 46832 64.1 308 70.3 103 54.8 954 72.3 35744 61.3 5511 76.3 4212 75.5
Variables All Place-provider-matrix
Trained responder Family bystander Layperson bystander
Public Home Public Home Public Home
N % N % N % N % N % N % N %
Metropolis
Non-metropolis 40762 55.8 185 42.2 88 46.8 810 61.4 32347 55.5 3968 54.9 3364 60.3
Metropolis 32295 44.2 253 57.8 100 53.2 509 38.6 25960 44.5 3258 45.1 2215 39.7
Witness
No 40138 54.9 221 50.5 122 64.9 383 29.0 32794 56.2 3127 43.3 3491 62.6
Yes 32919 45.1 217 49.5 66 35.1 936 71.0 25513 43.8 4099 56.7 2088 37.4
Bystander CPR
No 34230 46.9 119 27.2 65 34.6 611 46.3 27509 47.2 2987 41.3 2939 52.7
Yes 38827 53.1 319 72.8 123 65.4 708 53.7 30798 52.8 4239 58.7 2640 47.3
Bystander DEF
No 71644 98.1 375 85.6 149 79.3 1285 97.4 57404 98.5 6968 96.4 5463 97.9
Yes 1413 1.9 63 14.4 39 20.7 34 2.6 903 1.5 258 3.6 116 2.1
Primary ECG
VF/VT 12021 16.5 160 36.5 30 16.0 436 33.1 7238 12.4 3162 43.8 995 17.8
PEA 8849 12.1 58 13.2 25 13.3 208 15.8 6971 12.0 911 12.6 676 12.1
Asystole 52187 71.4 220 50.2 133 70.7 675 51.2 44098 75.6 3153 43.6 3908 70.0
RTI
0–3 3564 4.9 40 9.1 9 4.8 93 7.1 2713 4.7 511 7.1 198 3.5
4–7 32066 43.9 210 47.9 82 43.6 521 39.5 25870 44.4 3144 43.5 2239 40.1
8–11 15823 21.7 80 18.3 40 21.3 317 24.0 12558 21.5 1530 21.2 1298 23.3
12–15 5385 7.4 29 6.6 13 6.9 115 8.7 4187 7.2 544 7.5 497 8.9
16- 16219 22.2 79 18.0 44 23.4 273 20.7 12979 22.3 1497 20.7 1347 24.1
Median (q1-q3) 7 (5–9) 6 (4–8) 7 (5–9) 7 (5–10) 7 (5–9) 7 (5–9) 7 (5–10)
Airway
ETI 3709 5.1 25 5.7 8 4.3 65 4.9 2944 5.0 355 4.9 312 5.6
SGA 20139 27.6 154 35.2 45 23.9 393 29.8 15538 26.6 2375 32.9 1634 29.3
BVM 40600 55.6 225 51.4 114 60.6 679 51.5 32866 56.4 3737 51.7 2979 53.4
PV 8609 11.8 34 7.8 21 11.2 182 13.8 6959 11.9 759 10.5 654 11.7
Variables All Place-provider-matrix
Trained responder Family bystander Layperson bystander
Public Home Public Home Public Home
N % N % N % N % N % N % N %
EMS Defibrillation
No 55633 76.2 249 56.8 146 77.7 762 57.8 46789 80.2 3556 49.2 4131 74.0
Yes 17424 23.8 189 43.2 42 22.3 557 42.2 11518 19.8 3670 50.8 1448 26.0
ED level
Level 1 10347 14.2 76 17.4 32 17.0 233 17.7 8044 13.8 1202 16.6 760 13.6
Level 2 35705 48.9 252 57.5 87 46.3 656 49.7 28432 48.8 3674 50.8 2604 46.7
Level 3 23571 32.3 96 21.9 60 31.9 381 28.9 19110 32.8 2026 28.0 1898 34.0
Level 4 3434 4.7 14 3.2 9 4.8 49 3.7 2721 4.7 324 4.5 317 5.7
Outcomes
Survival to discharge 5010 6.9 78 17.8 15 8.0 204 15.5 2857 4.9 1515 21.0 341 6.1
Good CPC 3099 4.2 51 11.6 9 4.8 140 10.6 1615 2.8 1091 15.1 193 3.5
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CPR, cardiopulmonary resuscitation; DEF, defibrillation; ECG, electrocardiogram; VF, ventricular fibrillation; VT, ventricular tachycardia; PEA, pulseless electrical activity; RTI, response time interval; ETI, endotracheal insertion; SGA, supraglottic airway; BVM, bag-valve mask; PV, positive ventilation; CPC, cerebral performance category

Fig 2. Outcomes of out-of-hospital cardiac arrest among place-provider matrix group of bystanders.

Fig 2

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Table 2. Demographic findings according to arrest time.

Variables All Event Time
Night Day
N % N % N %
All 73057 100.0 26225 100.0 46832 100.0
Place-provider-matrix
Public-Trained 438 0.6 130 0.5 308 0.7
Home- Trained 188 0.3 85 0.3 103 0.2
Public-Family 1319 1.8 365 1.4 954 2.0
Home-Family 58307 79.8 22563 86.0 35744 76.3
Public-Layperson 7226 9.9 1715 6.5 5511 11.8
Home-Layperson 5579 7.6 1367 5.2 4212 9.0
Gender
Female 25719 35.2 8755 33.4 16964 36.2
Male 47338 64.8 17470 66.6 29868 63.8
Age
Age<65 26923 36.9 10902 41.6 16021 34.2
65 = <Age<85 36569 50.1 12353 47.1 24216 51.7
Age> = 85 9565 13.1 2970 11.3 6595 14.1
Median (q1-q3) 71 (58–80) 69 (56–79) 72 (59–81)
Year
2012 7732 10.6 2936 11.2 4796 10.2
2013 9835 13.5 3614 13.8 6221 13.3
2014 12788 17.5 4574 17.4 8214 17.5
2015 14048 19.2 5003 19.1 9045 19.3
2016 14204 19.4 5033 19.2 9171 19.6
2017 14450 19.8 5065 19.3 9385 20.0
Season
Spring 18330 25.1 6649 25.4 11681 24.9
Summer 16058 22.0 6013 22.9 10045 21.4
Fall 18082 24.8 6324 24.1 11758 25.1
Winter 20587 28.2 7239 27.6 13348 28.5
Weekend
Weekday 41479 56.8 14894 56.8 26585 56.8
Weekend 31578 43.2 11331 43.2 20247 43.2
Metropolis
Non-metropolis 40762 55.8 14293 54.5 26469 56.5
Metropolis 32295 44.2 11932 45.5 20363 43.5
Witness
No 40138 54.9 13494 51.5 26644 56.9
Yes 32919 45.1 12731 48.5 20188 43.1
Bystander CPR
No 34230 46.9 12082 46.1 22148 47.3
Yes 38827 53.1 14143 53.9 24684 52.7
Bystander DEF
No 71644 98.1 25783 98.3 45861 97.9
Yes 1413 1.9 442 1.7 971 2.1
Primary ECG
VF/VT 12021 16.5 4632 17.7 7389 15.8
PEA 8849 12.1 3132 11.9 5717 12.2
Asystole 52187 71.4 18461 70.4 33726 72.0
RTI
0–3 3564 4.9 1164 4.4 2400 5.1
4–7 32066 43.9 12119 46.2 19947 42.6
8–11 15823 21.7 5428 20.7 10395 22.2
12–15 5385 7.4 1756 6.7 3629 7.7
16- 16219 22.2 5758 22.0 10461 22.3
Median (q1-q3) 7 (5–9) 7 (5–9) 7 (5–10)
Airway
ETI 3709 5.1 1322 5.0 2387 5.1
SGA 20139 27.6 7249 27.6 12890 27.5
BVM 40600 55.6 14510 55.3 26090 55.7
PV 8609 11.8 3144 12.0 5465 11.7
EMS Defibrillation
No 55633 76.2 19695 75.1 35938 76.7
Yes 17424 23.8 6530 24.9 10894 23.3
ED level
Level 1 10347 14.2 3855 14.7 6492 13.9
Level 2 35705 48.9 13091 49.9 22614 48.3
Level 3 23571 32.3 8140 31.0 15431 32.9
Level 4 3434 4.7 1139 4.3 2295 4.9
Outcomes
Survival to discharge 5010 6.9 2024 7.7 2986 6.4
Good CPC 3099 4.2 1273 4.9 1826 3.9
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CPR, cardiopulmonary resuscitation; DEF, defibrillation; ECG, electrocardiogram; VF, ventricular fibrillation; VT, ventricular tachycardia; PEA, pulseless electrical activity; RTI, response time interval; ETI, endotracheal insertion; SGA, supraglottic airway; BVM, bag-valve mask; PV, positive ventilation; CPC, cerebral performance category

Main analysis

Compared to the Public-TR group, the AORs (95% CIs) by PPM group for survival to discharge were 0.61 (0.35–1.05) in the Home-TR group, 0.85 (0.62–1.17) in the Public-Family group, 0.38 (0.29–0.50) in the Home-Family group, 1.12 (0.85–1.49) in the Public-Layperson group, and 0.42 (0.31–0.57) in the Home-Layperson group. The Home-Family and Home-Layperson groups had significantly worse results than the Public-TR group for survival to discharge. The AORs (95% CIs) by PPM group for good CPC were 0.58 (0.27–1.25) in the Home-TR group, 0.88 (0.61–1.27) in the Public-Family group, 0.38 (0.28–0.52) in the Home-Family group, 1.20 (0.87–1.65) in the Public-Layperson group, and 0.42 (0.30–0.59) in the Home-Layperson group. The Home-Family and Home-Layperson groups also had significantly worse results than the Public-TR group for good CPC (Table 3). The AORs (95% CIs) of survival to discharge rate and good CPC rate in the daytime were 0.85 (0.80–0.91) and 0.84 (0.77–0.91), respectively. The outcome results were found to be better at nighttime than in the daytime after adjusting for confounders (Table 4).

Table 3. Multivariable logistic regression analysis of outcomes by place-provider-matrix.

Outcomes Total Positive Model 1 Model 2
Survival N N % AOR 95% CI AOR 95% CI
Total 73057 5010 6.9
Public-Trained 438 78 17.8 1.00 1.00
Home-Trained 188 15 8.0 0.46 0.25 0.83 0.61 0.35 1.05
Public-Family 1319 204 15.5 1.05 0.78 1.40 0.85 0.62 1.17
Home-Family 58307 2857 4.9 0.37 0.29 0.48 0.38 0.29 0.50
Public-Layperson 7226 1515 21.0 1.23 0.96 1.59 1.12 0.85 1.49
Home-Layperson 5579 341 6.1 0.40 0.30 0.52 0.42 0.31 0.57
Good CPC
Total 73057 3099 4.2
Public-Trained 438 51 11.6 1.00 1.00
Home-Trained 188 9 4.8 0.45 0.22 0.94 0.58 0.27 1.25
Public-Family 1319 140 10.6 1.18 0.83 1.66 0.88 0.61 1.27
Home-Family 58307 1615 2.8 0.38 0.28 0.51 0.38 0.28 0.52
Public-Layperson 7226 1091 15.1 1.37 1.01 1.85 1.20 0.87 1.65
Home-Layperson 5579 193 3.5 0.38 0.27 0.53 0.42 0.30 0.59
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AOR, adjusted odds ratio; 95% CI, 95% confidence interval; CPC, cerebral performance category

Model 1: adjusted for gender and age

Model 2: adjusted for gender, age, year, season, weekend, daytime, metropolis, and witness

Table 4. Multivariable logistic regression analysis for outcomes by arrest time.

Outcomes Total Positive Model 1 Model 2
Survival N N % AOR 95% CI AOR 95% CI
Total 73057 5010 6.9
Nighttime 26225 2024 7.7 1.00 1.00
Daytime 46832 2986 6.4 0.92 0.86 0.97 0.85 0.80 0.91
Good CPC
Total 73057 3099 4.2
Nighttime 26225 1273 4.9 1.00 1.00
Daytime 46832 1826 3.9 0.92 0.85 0.99 0.84 0.77 0.91
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CPC, cerebral performance category; AOR, adjusted odds ratio; 95% CI, 95% confidence interval

Model 1: adjusted for gender, age and daytime

Model 2: adjusted for gender, age, daytime, year, season, weekend, place-provider matrix group, metropolis, and witness

Interaction analysis

In the interaction model, the AORs (95% CIs) in the Public-Family group were 1.10 (0.90–1.35) in the daytime and 1.28 (1.06–1.53) in the nighttime (18:00–06:00). The other PPM groups did not show significantly different differences between the daytime and nighttime (Table 5).

Table 5. Interaction effect between place-provider-matrix and arrest time.

Outcomes Nighttime Daytime
Survival AOR 95% CI AOR 95% CI
Public-Trained 1.00 1.00
Home-Trained 0.79 0.47 1.32 1.19 0.68 2.08
Public-Family 1.28 1.06 1.53 1.10 0.90 1.35
Home-Family 0.60 0.53 0.68 0.48 0.42 0.55
Public-Layperson 1.69 1.48 1.93 1.61 1.40 1.85
Home-Layperson 0.67 0.57 0.79 0.66 0.56 0.78
Good CPC
Public-Trained 1.00 1.00
Home-Trained 0.85 0.46 1.57 1.09 0.53 2.26
Public-Family 1.30 1.05 1.62 1.27 0.99 1.62
Home-Family 0.58 0.50 0.68 0.46 0.39 0.55
Public-Layperson 1.74 1.48 2.03 1.73 1.45 2.07
Home-Layperson 0.60 0.50 0.73 0.64 0.52 0.80
Open in a new tab

CPC, cerebral performance category; AOR, adjusted odds ratio; 95% CI, 95% confidence interval

Interaction model: adjusted for gender, age, daytime, year, season, weekend, metropolis, witness, and interaction term (place-provider-matrix*daytime)

Discussion

In this study, we discovered that OHCAs that occurred in public places with TRs showed a better OR of survival to discharge and good CPC than those in Home-family and Home-Layperson groups. This result partially corresponded to the study hypothesis. The fact that home places with family and laypersons had lower ORs supported the study hypothesis. However, the fact that the Public-TR, Public-Layperson, Public-Family, and Home-TR groups did not show significant differences was not expected according to the study hypothesis.

It is already known that approximately 80% of OHCAs worldwide occur in private places, such as home residences. [16] However, a higher survival rate and good neurological outcome have been reported in OHCAs occurring in public places. [17] Our study results also correspond to previous findings of other studies. [18] In this study, both outcomes showed higher rates in public places than in home settings, which was independent of bystander type. This fact was shown in our study results showing that there was no significant difference in AORs among the Public-TR, Public-Family and Public-Layperson groups. This result implies that bystander factors are less important in OHCAs occurring in public places. However, in home settings, there were significantly poorer CPR outcomes in the family and layperson bystander groups than in the TR group. [19] This result suggests that we need to supplement the OHCA Home-Family and Home-Layperson groups with additional CPR resources. To improve the poor outcome of OHCA in the Home-Family and Layperson groups, education for family members is essential. More specific education programs for home bystanders, such as elderly individuals or housewives, are needed. Elderly individuals or housewives cannot easily access CPR training as younger employed individuals can. A dispatch-assisted basic life support program, which is a new education protocol, was proposed for home bystanders. In South Korea, if the EMS dispatcher suspects cardiac arrest via phone call, the dispatcher gives instruction about how to perform CPR until EMS providers arrive at the scene. [20]

Other previous studies reported that family members or friends of patients who were admitted to the hospital due to heart-related disease had better self-confidence after CPR training. Family members who could not participate in hospital CPR education were more motivated to attend hospital CPR training. [21, 22] This concept must be extended to populations with other CPR risk factors, such as hypertension, diabetes mellitus, and hyperlipidemia, so that family members can be encouraged to attend the CPR training program.

In the Public-TR and Home-TR groups, the percentage of both outcomes appeared to be better in the Public-TR group. However, after adjusting for confounders, there was no significant difference between the groups. This means that the Home-TR group and the Public-TR group had equivalent outcomes. This finding proposes that a new CPR program using TR is needed to improve the outcome of OHCA occurring at home. If the place of OHCA is a public site with a high bystander CPR rate and good CPR outcomes in the past, novel dispatcher-assisted CPR instruction may be beneficial. [23] In contrast, if OHCA occurs in private places with potentially low bystander CPR rates and worse outcomes, the EMS dispatcher can activate available TRs, such as town safety guards, policemen, or community security officers near the event place to provide early CPR and defibrillation. The program to activate available TRs or general bystanders has been implemented in a previous study. [24]

TR programs including firefighters and policemen demonstrated an increase in survival to discharge rate as well as a decrease in call-to-scene time and call-to-defibrillation time. [25, 26] In our study, we included not only policemen and firefighters but also public transportation vehicle drivers, school health teachers, sports facility employees, lifeguards, workplace safety employees and travel business employees who are likely to witness cardiac arrest in their work place. A greater number of TRs in our study setting was expected to play an important role in improving early bystander response and defibrillation. Equivalent outcomes were observed in both the Public-TR and Home-TR groups. This finding encourages us to designate more potential providers as TRs and to provide regular CPR education and training.

In a previous study, the TR group showed better outcomes than the layperson bystander group regardless of the place of arrest. [6] As a further detailed study, we found similar results, showing that the Home-Family group and the Home-Layperson group had worse outcomes. However, the Public-Layperson group showed a higher rate of survival to discharge and good neurological outcome than the Public-TR group, although the result was not statistically significant in the main analysis after adjusting for confounders. This implies that OHCA in public places is less affected by bystanders than that in home settings. This is because OHCA in public places can be easily witnessed and has a higher chance of early CPR and defibrillation. Furthermore, patients with OHCA in public places would be younger and have fewer medical illnesses since they are able to walk around public places. [27] Likewise, OHCA in public places minimizes the beneficial effect of bystanders. Further research is needed to prove the detailed association between arrest location and bystander characteristics.

We found a circadian variation in CPR outcomes, which has been reported by many previous studies. [28–30] The exact mechanism of circadian variation in OHCA outcomes has not yet been discovered. However, there is a general consensus that patient activity or environmental factors influence the outcome rather than the circadian variation in the underlying diseases. Our study analyzed the effect of PPM groups according to event time to compare the effect size of circadian factors. From this study, we found that the PPM consistently contributed to outcomes of OHCA regardless of the event time. However, a significantly different effect size in the PPM group on outcomes according to the time of the event was only observed in the Public-Family group with OHCA at night. It is well known that OHCA at night shows worse outcomes than that occurring in the daytime, but previous studies on circadian variations in OHCA have not analyzed the association between arrest time, bystander and place of arrest. Recent research on circadian differences in OHCA reported that there is no relationship between OHCA outcomes and arrest time. [31] This indicates that further study is required to analyze the multifactorial effect of circadian variation in OHCA.

The PPM analysis revealed that private places are associated with a higher risk of poor OHCA outcomes. However, the risk can be reduced by changing the bystander factor from family or layperson to a trained responder. Further study is needed to determine whether an extended TR program in private places and changes in dispatch protocol for activating TRs can reduce the hazardous effect of private places on outcomes of OHCA.

Limitations

This study has several limitations. First, there is selection bias resulting from the inclusion of only adults with a specific cardiac arrest origin. The inclusion of other populations and individuals with different causes of arrest could have affected the outcomes. Second, exposure variables were collected from the EMS registry. The EMS providers might have received variable information based on the CPR location. This process could have been affected by measurement bias. However, we were unable to test the reliability of the measurements. Although there is a quality assurance program in the fire department for data collection and registry documentation, interrater reliability must be considered. Third, the outcomes (survival to discharge, good CPC) were retrospectively collected from the hospital medical record. This process might have caused detection bias during the medical record review. Furthermore, neurological outcome data were derived from a registry rather than clinical follow-up. The limited follow-up could result in potential bias in regard to outcomes. Fourth, there is a data integrity issue because this study used information from both the prehospital registry and the hospital registry. Fifth, this study was performed in a study setting with a different levels of EMS service. CPR protocols and available medications at the prehospital stage would be different from those in North American and European countries according to national legislation and the local EMS Act. The lack of comparability of the EMS system to other countries would limit international applicability. This generalization issue must be considered in order to appropriately interpret this study. Last, the difference in the absolute number of patients among PPM groups might have affected the statistical analysis and influenced the results.

Conclusion

OHCAs that occurred in the home setting with family and layperson bystander groups showed worse outcomes than those of the Public-TR group. The outcomes among place-provider groups were similar regardless of the time of the OHCA event. The findings suggest that OHCAs occurring at home with family or laypersons require a new strategy, such as expanding the TR program to cover more occupations or dispatching nearby TRs to home settings prior to EMS arrival, as an intermediate step to improve CPR outcomes.

Acknowledgments

This study was supported by the National Emergency Management Agency of Korea and the Korea Centers for Disease Control and Prevention (CDC).

Data Availability

Data cannot be shared publicly because of patient confidentiality. Data are available from the Korea Center for Disease Control and Prevention. Institutional Data Access / Ethics Committee (contact via timthe@gmail.com) for researchers who meet the criteria for access to confidential data.

Funding Statement

This study was supported by the National Emergency Management Agency of Korea and the Korea Centers for Disease Control and Prevention (CDC). The study was funded by the Korea CDC (2012-2016) (Grant No: 2012-E33010-00; 2013-E33015-00; 2014-E33011-00, 2016-E33012-00, and 2017-Private Support Grant).

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Decision Letter 0

Andrea Ballotta

27 Aug 2019

PONE-D-19-14833

Place-Provider-Matrix of Bystander and Outcomes of Out-of-hospital Cardiac Arrest: A Nationwide Observational Cross-Sectional Analysis

PLOS ONE

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Reviewer #1: please see attachment.

I have to apologize,I forgot to finish this following sentence:

- Line 247: the authors state that the home TR group shows equivalent outcomes with the Public-TR group. In table…

should be continued with:

...In table 3, outcome with good CPC in the Public trained group is 11.3% compared to the outcome in the home-trained which is 4.8%. Please clarify your statement.

Reviewer #2: The data analysis at row 203-206 show a best result in survive/cpc for in public/layperson (20,9%/15,0%) respect in public-TR (17,5%/11,3%), but in the conclusions the authors do not discuss this data, and it is strange that in public place layperson had best results than TR; this data do not support the BLSD Training policy.

Is not easy have a clear vision of all the data, may be useful introduce a graphic representation of the survive/cpc ratio in the different group (bar graphic for example).

In “main analysis” at row 210-217 is not clearly explained (for who is not confident with statistic analysis) what is “AORs” and if is better an high value (0,82) or a low value (0,38), for correct interpretation of the data analysis.

Limitations: another limitation is the high difference of absolute number in the group (for example 187 in Home-TR vs 58264 in Home-Family), that may influence the final conclusions.

Table 1 and table 2 are very “long” and is better rewrite the first row (variable, public, home etc) to the top of every page of the table.

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Attachment

Submitted filename: review_PONE-D-19-14833_UrayT.pdf

Click here for additional data file. (89.7KB, pdf)
PLoS One. 2020 May 15;15(5):e0232999. doi: 10.1371/journal.pone.0232999.r002

Author response to Decision Letter 0

4 Dec 2019

Author’s reply to reviewers' comments:

On behalf of authors, thank you for the very valuable comments by the reviewers on our paper. We have attempted to address every point commented on by reviewers in the revised manuscript. While we believe that we have addressed all of the reviewers’ concerns, we would be more than pleased to write additional revisions if needed.

We highlighted all changes in red. Author’s answers or explanations are in blue.

Correspondent author

Sang Do Shin, MD, PhD

 

Ms. Ref. No.: PONE-D-19-14833

Title: Place-Provider-Matrix of Bystander and Outcomes of Out-of-hospital Cardiac Arrest : A Nationwide Observational Cross-Sectional Analysis

Reviewers' comments:

Reviewer: Professor Andrea Ballotta

Major concerns:

Overall, the manuscript would profit from a thorough grammatical revision by an English native speaker.

Statistics:

The authors state in the results and the discussion section, that CPR at a public place with trained responders (TR) shows the highest OR of survival. In contrast, in Table 1 and table 3, survival to discharge after CPR of TR in public with good CPC is 11.3%, whereas survival after layperson bystander CPR in public is 15%. - Please clarify, report these results in table 1 by comparing different percentage including statistical differences (p). Also, the whole discussion has to be adapted.

(ANSWER) Thank you for the review and comments. We edited hypothesis (Line 102-103) and discussion (Line 277-287) for showing higher rate of outcomes in the Public-Layperson bystander. Also, we added p-value to the table 1.

(Revision: Introduction-hypothesis)

We hypothesized that the Public-TR group would show the best effect on survival and good neurologic outcome and different PPM groups would show worse outcomes.

(Revision: Discussion)

In the previous study, TR group showed better outcome compared to layperson bystander regardless of arrest place.(6) As a further detailed research, we found similar result showing Home-Family group and Home-Layperson group with worse outcome. However, the Public-Layperson group showed higher rate of survival to discharge and good neurological outcome compared to the Public-TR group, although the result was not statistically significant in main analysis after adjusting confounders. It implies that OHCA in public place is less affected by bystander than home place. This is because OHCA at public place can be easily witnessed and has higher chance of early CPR and defibrillation. Furthermore, patients with OHCA in public place would be younger and have less medical illness to be able to walk around public place.(19) Likewise, OHCA in public place minimizes the beneficial effect of bystander. Further research is needed to prove detailed association between arrest place and bystander characteristic.

Is the term “trained responders/TR” a new definition created by the authors? Please clarify

(ANSWER) Thank you for the review and comments. Our research team has published previous paper about the effect of bystander difference between trained responder and layperson. (Reference 6) This can be a new concept but many other researchers have consensus about necessity of trained first responder. (Reference 26,27)

6. Park YM, Shin SD, Lee YJ, Song KJ, Ro YS, Ahn KO. Cardiopulmonary resuscitation by trained responders versus lay persons and outcomes of out-of-hospital cardiac arrest: A community observational study. Resuscitation. 2017;118:55-62.

26. Hasselqvist-Ax I, Nordberg P, Herlitz J, Svensson L, Jonsson M, Lindqvist J, et al. Dispatch of Firefighters and Police Officers in Out-of-Hospital Cardiac Arrest: A Nationwide Prospective Cohort Trial Using Propensity Score Analysis. J Am Heart Assoc. 2017;6(10).

27. Stein P, Spahn GH, Muller S, Zollinger A, Baulig W, Bruesch M, et al. Impact of city police layperson education and equipment with automatic external defibrillators on patient outcome after out of hospital cardiac arrest. Resuscitation. 2017;118:27-34.

Line 78- It is not clear, if TRs are called to the scene as first responders or are already on the

scene by chance and perform as bystanders. Please clarify.

(ANSWER) Thank you for the review and comments. We added brief explanation of trained responder in Line 83-84. Trained responder can be called to the scene as first responders or already on the scene by chance and perform as bystanders because of characteristics of their job.

(Revision: Introduction)

Trained responder (TR) refers to the specific population group who has high chance to encounter cardiac arrest or be called to the event scene in daily life in a community.

Per Utstein definition 1, first responders like firefighters or police officers are not "bystanders", since they are part of an organized emergency response system. Therefore, the used definition of “3 types of bystanders” (line 79) should be revised if part of the first responder system.

(ANSWER) Thank you for the review and comments. In South Korea, although trained responders are designated as first responders to encourage bystander CPR by EMS act, TRs do not have legal responsibility for not performing CPR bystander in reality. As we can see in Table 1 and reference 6, CPR cases performed by TR group are extremely low. This study reflected the reality of EMS system in South Korea and that’s why we have divided bystanders into three groups (TR, family, layperson) considering the reality. We added brief explanation about EMS reality in South Korea in Line 86-87)

(Methods: Introduction)

However, TR systems as a component of community CPR program are not well established as part of EMS system in many countries.

Minor concerns:

Abstract:

Line 55. Please add an explanation for the abbreviation “FR” used in line 68.

Please rephrase the conclusion of the abstract.

(ANSWER) Thank you for the review and comments. We changed sentences as follows. (Line 69-70)

(Revision: Abstract)

The OHCA outcomes of the Home-Family and Home-Layperson group were worse than that of the Public-TR group.

Introduction:

Lines 76-77 are unclear / should be revised by a native speaker.

(ANSWER) Thank you for the review and comments. We changed sentences as follows. (Line 79-80)

(Revision: Introduction)

Rapid cardiopulmonary resuscitation (CPR) and Public Access Defibrillation (PAD) are the most important components of community CPR programs in treating OHCA.

Lines 86-88 and 91-92 should be re-written (unclear).

(ANSWER) Thank you for the review and comments. We changed sentences as follows (Line 88-91, 93-95)

(Revision: Introduction)

Usually, family or layperson bystanders have few CPR experiences, more fear of performing CPR, and more anxiety regarding legal responsibility compared to TRs.(7, 8) The quality of CPR by layperson may be different according to individual’s self-efficacy in performing CPR. Thus, the quality of CPR cannot be assured compared to that of TRs.(4, 9)

OHCA occurred at public place has characteristics of typically younger age, more ventricular fibrillation (VF) in the initial ECG rhythm, and more bystander CPR attempted.

Is the PPM a definition / concept that the authors have newly created or does it already exist per definition? This should be clarified.

(ANSWER) Thank you for the review and comments. The concept of PPM is defined in the main context. (Line 97-98) This is a new concept created by authors.

Methods:

The authors should re-consider depicting the study as "prospective" - was data in fact collected prospectively for the study purpose between 2012 and 2017? In lines 135-136 it is also stated that data derive from a (retrospectively assessed) registry.

(ANSWER) Thank you for the review and comments. We made a slight mistake. We changed the sentence as follows. (Line 111)

(Revision: Methods)

This is a retrospective, nationwide, multicenter and cross-sectional study using the national OHCA registry from 2012 to 2017.

Lines 112-119: This paragraph should be shortened.

(ANSWER) Thank you for the review and comments. We changed the paragraph as follows. (Line 115-120)

(Revision: Methods)

In this study setting, school teachers, sports instructors, public transportation vehicle drivers, safety guards of national parks, and policemen were designated as first responders to encourage bystander CPR by the national emergency medical service (EMS) Act in 2004. In addition, those private places where the TRs work or reside are designated as mandatory sites for PAD programs in 2008 and 2011 by the EMS Act. This group that requires mandatory CPR education is called trained responder (TR). TRs are required to finish regular two-hour course of CPR training at least once in a year since 2005.(6)

Does the study have a positive vote by an Ethics Committee or only the approval of the "review board" of the study hospital?

(ANSWER) Thank you for the review and comments. This study was only approved by the institutional review board of the study hospital. Informed consent was waived. This is mentioned in Line 147-149.

(Revision: Methods)

This study was reviewed and approved by the institutional review board of the study hospital. Informed consent was waived because the data variables did not include personal information, and the study process did not cause any risk for patients. (6) The Korea CDC approved the use of national registry for this study.

What exactly was the pool for patient inclusion - was it access to a nationwide database as described in lines 135-136? This is unclear since expressions such as "the study hospital" are repeatedly used throughout the manuscript (this would suggest only one study centre) and since it seems the study only has "approval of the review board of the study hospital" (would it not be necessary to obtain a nationwide approval by multiple Ethic Committees according to GCP?).

(ANSWER) Thank you for the review and comments. The national OHCA registry has developed and constructed by the Korea Centers for Disease Control and Prevention (CDC) on the basis of National Statistics Act since 2008. All data collection of OHCA were approved by one university institutional review board with a waiver of patients consent because the data was collected from hospital medical record review for index case (OHCA) in the electronic EMS database of the national fire department. After deidentification process, the yearly database is completed to be stored at the Korea CDC electronic data server. If a researcher wants to use the data to do a study, the researcher should obtain an approval from the institutional review board (usually researchers’ affiliated institution) and submit the application for data use to the Korea CDC. The Korea CDC review the application and approve the data use on the basis of review guideline for national registry study.

Why were only patients over the age of 19 years included in the final analysis? If this is due to local requirements, please specify.

(ANSWER) Thank you for the review and comments. We tried to include only adult patients with cardiac arrest because pediatrics and adolescents have different physiologic status and cardiac arrest features to adult cardiac arrest. There were no local requirements for including only adult patients.

Line 171. Please add an appropriate reference to “Utstein factors” (see above).

(ANSWER) Thank you for the review and comments. We added an appropriate reference as you have recommended.

(Revision: Methods)

Utstein factors included metropolis, witness, bystander CPR and defibrillation, and primary ECG (shockable versus non-shockable).(16)

Discussion:

Line 232 [... previous research outcomes in other studies]: Please cite and give examples.

(ANSWER) Thank you for the review and comments. We added an appropriate reference as you have recommended. (Line 237-238)

(Revision: Discussion)

Our study findings also correspond to previous research outcomes in other studies.(19)

Given your discussion about poorer outcomes in the group with CA occurring at home, more

literature comparison should be implemented and therefore strengthen your arguments.

(ANSWER) Thank you for the review and comments. We added an appropriate reference as you have recommended. (Line 238-240)

(Revision: Discussion)

The OHCAs occurred in public places showed better survival to discharge and good CPC rate regardless of bystander group. However, in home places, there was significantly poor CPR outcomes in family and layperson bystander groups than TR group.(20)

Line 240 and following paragraphs: You mention dispatcher-assisted BLS - please comment

on the current situation in your country - does it already happen or do you just propose it?

(ANSWER) Thank you for the review and comments. We added brief explanation about dispatcher-assisted BLS status in South Korea. We also added proper reference. Detailed information is written in the reference 21.

(Revision: Discussion)

In South Korea, if EMS dispatcher suspects cardiac arrest via phone call, dispatcher gives CPR instruction about how to do CPR until EMS providers arrive at the scene.(21)

In fact, it is not true that previous studies could not show benefits of e.g. police-first responder systems as stated in line 256. The cited study by Husain et al. explicitly states that in their collective, "survival from out-of-hospital cardiac arrests increased with the implementation of police AED programs".

(ANSWER) Thank you for the review and comments. We edited the paragraph as follows and added appropriate references. (Line 268-276)

(Revision: Discussion)

TR programs including firefighters and policeman demonstrated an increase in survival to discharge rate as well as a decrease in call-to-scene time and call-to-defibrillation time.(26, 27) In our study, we included not only policeman and firefighters but also public transportation vehicle drivers, school health teachers, sports facility employees, lifeguards, workplace safety employees and travel business employees who are likely to witness cardiac arrest in their work place. An extended number of TRs in our study setting was expected to play an important role for improvement of early bystander response and defibrillation. Equivalent outcomes were observed in both Public-TR and Home-TR group. This finding encourages us to designate more potential providers as TR and to provide regular CPR education and training.

Line 247: the authors state that the home TR group shows equivalent outcomes with the Public-TR group. In table 3, outcome with good CPC in the Public trained group is 11.3% compared to the outcome in the home-trained which is 4.8%. Please clarify your statement.

(ANSWER) Thank you for the review and comments. We changed the sentence as follows. (Line 257-259)

(Revision: Discussion)

In the public-TR and Home-TR group, the percentage of both outcomes seemed like that the public-TR group showed better outcomes. However, after adjusting confounders, it showed no statistical significance between both groups. This means that the home-TR group showed equivalent outcomes with the public-TR group.

Line 250/251: sentence not clear, please rephrase.

(ANSWER) Thank you for the review and comments. We changed the sentence as follows. (Line 261-263)

(Revision: Discussion)

If the place of OHCA is public site where showed high bystander CPR rate and good CPR outcomes in the past, a novel dispatcher-assisted CPR instruction may be beneficial.(24)

Line 265: Please add more up-to-date references about the topic of circadian variation of OHCA.

(ANSWER) Thank you for the review and comments. We added proper references as recommended. (Line 288)

(Revision: Discussion)

We found a circadian variation of CPR outcomes which has been reported by many previous studies.(28-30)

Concerning the day/night findings, the statement in lines 270-271 [A significantly...] is

unclear and needs to be rewritten.

(ANSWER) Thank you for the review and comments. We changed the statement as follows. (Line 293-299)

(Revision: Discussion)

From this study, we found the PPM consistently contributed to outcomes of OHCA regardless of event time of OHCA. However, statistically different effect size of PPM group on outcomes according to time of the event was only observed in the Public-Family group with OHCA at nighttime. It is well-known that OHCA at night shows worse outcome than daytime, but the previous researches about circadian variation of OHCA has not analyzed the association between arrest time, bystander and arrest place as far as we know. This indicates further study is required to analyze multi-factorial effect of circadian variation in OHCA.

Please state the - in your opinion - novelty of your findings.

(ANSWER) Thank you for the review and comments. We stated the importance of this study result as follows. (Line 300-304)

(Revision: Discussion)

The PPM analysis has revealed that private place is exposed to higher risk of poor OHCA outcomes. However, the risk can be reduced by changing bystander factor from family or layperson to trained responder. Further study is needed whether an extended TR program into the private place and change of dispatch protocol for activating TR can reduce the hazardous effect of private place on outcomes and improve outcomes of OHCA or not.

Limitations:

Are patients also followed-up clinically until hospital discharge as part of your registry? Or did you only - as stated - deduct CPC-levels from general documentation such as discharge papers? This is susceptible to considerable bias and should be emphasized more, also in the "Methods" section.

(ANSWER) Thank you for the review and comments. As mentioned before, this study is a registry study. The trained medical record reviewers hired by the Korea CDC evaluate all hospital records including ED care, ICU care and outcome status at patients discharge. This process is described in Data source and collection in Methods part. (Line 141-146)

Why would "CPR protocols and medications be very different from North America or

Europe" (lines 291-292) when you stated before you adhere to current international CPR guidelines?

(ANSWER) Thank you for the review and comments. Korean EMS providers cannot use epinephrine in CPR situation without medical director’s indication by EMS Act. Although the situation is slowly changing with tremendous effort of EMS physicians, there are many legal and administrative hurdles to catch up the level of EMS providers in North America or European countries. We added a brief explanation about different EMS environment in South Korea.

(Revision: Discussion)

CPR protocols and available medications at prehospital stage would be different from North American and European countries according to national legislation and local EMS act.

Reviewer #2

The data analysis at row 203-206 show a best result in survive/cpc for in public/layperson (20,9%/15,0%) respect in public-TR (17,5%/11,3%), but in the conclusions the authors do not discuss this data, and it is strange that in public place layperson had best results than TR; this data do not support the BLSD Training policy.

(ANSWER) Thank you for the review and comments. We applied your comment and changed the sentence as follows. (Line 239-241)

(Revision: Discussion)

This fact was proven in our study that there was no statistical difference in AORs among public-TR, public-family and public-layperson groups. This result implies that bystander factor is less important in OHCA occurred in public places.

Is not easy have a clear vision of all the data, may be useful introduce a graphic representation of the survive/cpc ratio in the different group (bar graphic for example).

(ANSWER) Thank you for the review and comments. We added Fig 2 for graphical explanation. (Please see Figure 2) The ratios (good CPC/survival) looks similar, which were not presented in the Figure 2. The ratios were as follows; All (0.6), Trained responder, public (0.6), Trained responder, home (0.6), Family bystander, public (0.7), Family bystander, home (0.6), Layperson bystander, public (0.7), and Layperson bystander, home (0.6).

(Revision: Result)

Please see Figure 2.

In “main analysis” at row 210-217 is not clearly explained (for who is not confident with statistical analysis) what is “AORs” and if is better a high value (0,82) or a low value (0,38), for correct interpretation of the data analysis.

(ANSWER) Thank you for the review and comments. We applied your comment and changed the sentence as follows. (Line 216-217, 220-221)

(Revision: Result)

The home-family and home-layperson group had statistically worse result than public-TR group for survival to discharge.

The home-family and home-layperson group also had statistically worse result than public-TR group for good CPC.

Limitations: another limitation is the high difference of absolute number in the group (for example 187 in Home-TR vs 58264 in Home-Family), that may influence the final conclusions.

(ANSWER) Thank you for the review and comments. We applied your comment and changed the sentence as follows. (Line 321-322)

(Revision: Limitation)

Lastly, the difference of absolute number of patients among PPM groups might have affected statistical analysis and influenced the results.

Table 1 and table 2 are very “long” and is better rewrite the first row (variable, public, home etc) to the top of every page of the table.

(ANSWER) Thank you for the review and comments. The editorial office will revise the tables based on the publishing form after finishing the revision.

Attachment

Submitted filename: Authors reply to reviewers comments.docx

Click here for additional data file. (53.9KB, docx)

Decision Letter 1

Andrea Ballotta

15 Jan 2020

PONE-D-19-14833R1

Place-Provider-Matrix of Bystander and Outcomes of Out-of-hospital Cardiac Arrest: A Nationwide Observational Cross-Sectional Analysis

PLOS ONE

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Dear authors thank you for your efforts. The manuscript looks better although it needs some other improvement. Take in to account the first reviewer's comment especially and go promply to the revision of the paper.

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Reviewers' comments:

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Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

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Reviewer #2: Yes

**********

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**********

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Reviewer #2: Yes

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Reviewer #1: I thank the authors for their thorough revision of their manuscript and the many points that they could clarify and improve through it. However, in my opinion, there are still a few concerns that must be sufficiently addressed in order to render the manuscript eligible for publication.

Major conerns:

- The manuscript (including the abstract and tables/figures) still is in definitive need of a thorough grammatical revision by an English native speaker. It is not fit to be read by an international audience at the moment.

- The matter of the term “trained responder” is still not resolved. According to Utstein guidelines that should be adhered to, first responders are not bystanders. I understand that in your communities, there are trained persons that work in environments that are likely to be place of a CA. If a CA happens there, then I would call the CPR providers “bystanders”, even if they are specially trained. BUT if they are called or dispatched in any way, they are called “first responders”.

- I think what you should focus on is: 1) Introducing a detailed definition and re-writing the paragraphs where this process is described. Also, describe the calling / dispatching process of TRs in detail. At the moment, it is very confusing. 2) Add a sub-group analyses of a) the cases in which the TRs were real “bystanders” and b) the cases where they were called/dispatched to a CA event. By this, a little structure would be added in this rather confusing topic.

- I still do not fully understand the course your study took when it comes to Ethics Votes. Was the whole registry approved by a proper Ethics Board that is in accordance with international good scientific practice guidelines or was your study in particular approved? If your “review boards” are Ethics Boards, please state so. If not, you might have to present a proper Ethics’ Vote.

- It is a clear limitation that neurological outcomes are derived from registry data rather than clinical follow-up, as you explained after my initial question. Please add this to your Limitations section.

- I was not aware of the EMS situation in South Korea, thank you for the insight. However, also this must be added to the Limitations section because due to the limited comparability to other countries (e.g. in Europe or the USA), also your results are of limited applicability internationally.

Minor concerns:

- My request concerning the inclusion of only patients over 19 years aimed at the – in my opinion – international definition of “adults” for people over 18 years and not 19 – please state why you chose 19.

- The sentence “The OHCAs…” (lines 239-240) is still not clear, please re-phrase.

- You might want to add the contradicting results of up-to-date literature to your statement that time-of-day influences outcomes (for example Schriefl C et al., Time of out-of-hospital cardiac arrest is not associated with outcome in a metropolitan area: A multicenter cohort study.Resuscitation 2019).

Reviewer #2: no more comments

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2020 May 15;15(5):e0232999. doi: 10.1371/journal.pone.0232999.r004

Author response to Decision Letter 1

31 Mar 2020

Author’s reply to reviewers' comments:

On behalf of authors, thank you for the very valuable comments by the reviewers on our paper. I am very sorry for late revision. We have been fighting with the COVID-19 pandemic for the last two months.

.

We have attempted to address every point commented on by reviewers in the revised manuscript. While we believe that we have addressed all of the reviewers’ concerns, we would be more than pleased to write additional revisions if needed.

We highlighted all changes in red. Author’s answers or explanations are in blue.

Correspondent author

Sang Do Shin, MD, PhD

Ms. Ref. No.: PONE-D-19-14833

Title: Place-Provider-Matrix of Bystander and Outcomes of Out-of-hospital Cardiac Arrest: A Nationwide Observational Cross-Sectional Analysis

Reviewers' comments:

Major concerns:

- The manuscript (including the abstract and tables/figures) still is in definitive need of a thorough grammatical revision by an English native speaker. It is not fit to be read by an international audience at the moment.

(ANSWER) Thank you for the review and comments. The manuscript was revised again for grammatical revision by native speakers.

- The matter of the term “trained responder” is still not resolved. According to Utstein guidelines that should be adhered to, first responders are not bystanders. I understand that in your communities, there are trained persons that work in environments that are likely to be place of a CA. If a CA happens there, then I would call the CPR providers “bystanders”, even if they are specially trained. BUT if they are called or dispatched in any way, they are called “first responders”.

(ANSWER) Thank you for the review and comments. We tried to explain the term “trained responder” more specifically in the introduction and method paragraph. We added brief explanation of trained responder in Line 84-88, 118-120 and 124-128.

(Revision: Introduction, line 84-88)

Trained responders (TRs) refer to a specific group of individuals who have a high chance of encountering cardiac arrest in daily life because of occupational characteristics and training for CPR situations but who are not part of the officially organized emergency response system in a community. In general, TRs fall between a bystander and first responder according to the Utstein definition of provider.

(Revision: Method, line 118-120)

According to the 2004 National Emergency Medical Services (EMS) Act, school teachers, sports instructors, public transportation vehicle drivers, safety guards of national parks, and policemen are required to receive CPR education to encourage bystander CPR.

(Revision: Method, line 124-128)

TRs are not first responders who respond to medical emergencies in an official capacity as part of an organized medical response team. Rather, they are similar to bystanders but have been trained in CPR because of the higher chance of encountering CPR situations due to occupational characteristics. Therefore, TRs do not have the duty of official calls or dispatches from EMS systems. They voluntarily participate in the CPR situation.

- I think what you should focus on is: 1) Introducing a detailed definition and re-writing the paragraphs where this process is described. Also, describe the calling / dispatching process of TRs in detail. At the moment, it is very confusing. 2) Add a sub-group analyses of a) the cases in which the TRs were real “bystanders” and b) the cases where they were called/dispatched to a CA event. By this, a little structure would be added in this rather confusing topic.

(ANSWER) Thank you for the review and comments. The revised paragraphs in the above comment can be a reply for this comment. No different in calling and dispatching process of TRs. Just we can identify the TR groups from the EMS CPR registry. The dispatch for CPR is under the same protocol. You asked a subgroup analysis for the case in which the TRs were “real bystander”. But we have analyzed the bystanders as subgroup such as “Trained responder, Family bystander, and Layperson bystander” The Layperson bystander and Family bystanders are part of general (real) bystanders, not trained bystanders

- I still do not fully understand the course your study took when it comes to Ethics Votes. Was the whole registry approved by a proper Ethics Board that is in accordance with international good scientific practice guidelines or was your study in particular approved? If your “review boards” are Ethics Boards, please state so. If not, you might have to present a proper Ethics’ Vote.

(ANSWER) Thank you for the review and comments. The OHCA database had been constructed by the government par (Korea Centers for Disease Control and Prevention). When a researcher wants to use the database for a research, he or she should get permission of data use using a data request form and Korea CDC review and decide to permit or not the use of data. When a research request the data, he or she also get approval of the IRB at each institution. Our institutional review board has reviewed and approved our specific research.

- It is a clear limitation that neurological outcomes are derived from registry data rather than clinical follow-up, as you explained after my initial question. Please add this to your Limitations section.

(ANSWER) Thank you for the review and comments. We added additional explanation of limitation in Line 327-328.

(Revision: Limitation)

Furthermore, neurological outcome data were derived from a registry rather than clinical follow-up. The limited follow-up could result in potential bias in regard to outcomes.

- I was not aware of the EMS situation in South Korea, thank you for the insight. However, also this must be added to the Limitations section because due to the limited comparability to other countries (e.g. in Europe or the USA), also your results are of limited applicability internationally.

(ANSWER) Thank you for the review and comments. We added additional explanation of limitation in Line 329-333.

(Revision: Limitation)

Fifth, this study was performed in a study setting with a different levels of EMS service. CPR protocols and available medications at the prehospital stage would be different from those in North American and European countries according to national legislation and the local EMS Act. The lack of comparability of the EMS system to other countries would limit international applicability.

Minor concerns:

- My request concerning the inclusion of only patients over 19 years aimed at the – in my opinion – international definition of “adults” for people over 18 years and not 19 – please state why you chose 19.

(ANSWER) Thank you for the review and comments. We changed inclusion criteria age to over 18 years old. The relevant paragraphs of methods, results, and discussion were revised and Tables and Figure were changed due to the criteria.

- The sentence “The OHCAs…” (lines 239-240) is still not clear, please re-phrase.

(ANSWER) Thank you for the review and comments. We re-phrased the sentence in line 248-249.

(Revision: Discussion)

In this study, both outcomes showed higher rates in public places than in home settings, which was independent of bystander type.

- You might want to add the contradicting results of up-to-date literature to your statement that time-of-day influences outcomes (for example Schriefl C et al., Time of out-of-hospital cardiac arrest is not associated with outcome in a metropolitan area: A multicenter cohort study. Resuscitation 2019).

(ANSWER) Thank you for the review and comments. We added additional explanation in line 308-309.

(Revision: Discussion)

Recent research on circadian differences in OHCA reported that there is no relationship between OHCA outcomes and arrest time.

Attachment

Submitted filename: Authors reply to reviewers comments _ V2.docx

Click here for additional data file. (23.4KB, docx)

Decision Letter 2

Andrea Ballotta

28 Apr 2020

Place-Provider-Matrix of Bystander Cardiopulmonary Resuscitation and Outcomes of Out-of-hospital Cardiac Arrest: A Nationwide Observational Cross-Sectional Analysis

PONE-D-19-14833R2

Dear Dr. Shin,

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

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With kind regards,

Andrea Ballotta

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Congratulations!!!!! "nulla obsta" to the acceptance for publication of your revised manuscript.

Reviewers' comments:

Acceptance letter

Andrea Ballotta

5 May 2020

PONE-D-19-14833R2

Place-Provider-Matrix of Bystander Cardiopulmonary Resuscitation and Outcomes of Out-of-hospital Cardiac Arrest: A Nationwide Observational Cross-Sectional Analysis

Dear Dr. Shin:

I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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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With kind regards,

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on behalf of

Dr. Andrea Ballotta

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: review_PONE-D-19-14833_UrayT.pdf

    Click here for additional data file. (89.7KB, pdf)
    Attachment

    Submitted filename: Authors reply to reviewers comments.docx

    Click here for additional data file. (53.9KB, docx)
    Attachment

    Submitted filename: Authors reply to reviewers comments _ V2.docx

    Click here for additional data file. (23.4KB, docx)

    Data Availability Statement

    Data cannot be shared publicly because of patient confidentiality. Data are available from the Korea Center for Disease Control and Prevention. Institutional Data Access / Ethics Committee (contact via timthe@gmail.com) for researchers who meet the criteria for access to confidential data.

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