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

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.

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

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.

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

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

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

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

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.

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

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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.

Submitted filename: Authors reply to reviewers comments.docx

Click here for additional data file.

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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Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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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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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.

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

Click here for additional data file.

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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Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

Reviewers' comments:

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:

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