a b s t r a c t

Background: Targeted temperature management (TTM) can potentially improve the prognosis of patients with out-of-hospital cardiac arrest (OHCA). However, the effectiveness of TTM in older adults remains un- known. Therefore, this study aimed to assess the outcomes of older adult patients with OHCA who under- went TTM.

Methods: This study was a multicenter, retrospective, nationwide observational analysis of the Japanese As- sociation for Acute Medicine out-of-hospital cardiac arrest (JAAM-OHCA) registry. We included patients aged >=18 years who had experienced OHCA and underwent TTM from June 1, 2014, to December 31, 2017, in Japan. The primary outcome was a 1-month neurological favorable outcome, and the secondary outcome was 1-month survival.

Results: A total of 1847 patients were included in the analysis. 79 of 389 patients aged >=75 years (20.3%) had a 1-month neurological favorable outcome compared with 369 of 959 patients aged 18-64 years (38.5%) (adjusted odds ratios, 0.31; 95% confidence interval [CI], 0.21-0.45; P for trend <0.001). With increasing age, 1-month mortality showed an increasing trend; however, there was no significant difference.

Conclusion: In this retrospective nationwide observational study in Japan, neurological outcomes worsened as age increased in patients with OHCA who underwent TTM.

(C) 2023

1. Introduction

Out-of-hospital cardiac arrest (OHCA) is a significant Public health concern world-wide [1]. Aging is also an issue in developed countries and is expected to accelerate further in the future. For example, Japan is an aging society with 28.7% of the population aged >=65 years and 14.9% of the population aged >=75 years [2,3]. As for OHCA, the annual number of patients with OHCA is >120,000, accounting for 75% of

Abbreviations: OHCA, out-of-hospital cardiac arrest; TTM, targeted temperature management; JAAM-OHCA, Japanese Association for Acute Medicine out-of-hospital cardiac arrest; CPR, cardiopulmonary resuscitation; AED, automated external defibrillator; EMS, emergency medical service; VF, ventricular fibrillation; VT, ventricular tachycardia; PEA, pulseless electrical activity; CPC, cerebral performance category; CI, confidence interval.

* Corresponding author.

E-mail address: [email protected] (T. Matsuyama).

patients aged >=65 years and 50% of those aged >=75 years [4]. The sur- vival rate of patients with OHCA remains worse, especially worse in the older adult patients aged >=65 years [5]. Therefore, with the rapid in- crease in number and poor prognosis, we examined the management of older adult patients with OHCA.

targeted temperature management can potentially improve the prognosis of patients with OHCA. International guidelines for car- diopulmonary resuscitation recommend TTM for patients with OHCA who remain comatose after return of spontaneous circulation [6,7]. However, these guidelines have not included age as an indication for TTM. The previous study had compared mortality and neurological out- come between TTM and control for older adults [8]. However, this study was a post-hoc sub-study of randomized controlled trials, not real- world data. The value of the TTM for older adults compared with adults remains unknown. Therefore, we aimed to evaluate the characteristics and outcomes of TTM in older adults with OHCA.

https://doi.org/10.1016/j.ajem.2023.01.027

0735-6757/(C) 2023

1. Methods
   1. Study design, setting, and population

This study was a retrospective analysis of data from the Japanese Association for Acute Medicine out-of-hospital cardiac arrest (JAAM- OHCA) registry, a nationwide hospital-based retrospective observa- tional registry. This registry collected data on 35,000 patients with OHCA from 87 participating emergency medical institutions in Japan. This registry collected both pre- and in-hospital data. The methods and data collected by this registry have been described previously [9].

This study included patients aged >=18 years who experienced OHCA and were treated with TTM between June 1, 2014, and December 31, 2017, in Japan. The exclusion criteria were patients who did not receive resuscitation attempts in the hospital and those who did not have any available pre-hospital data. The study protocol was approved by the in- stitutional review board of each participating hospital. This was an ob- servational registry, and informed consent of the patients and their families was not required to collect information.

• 1. Pre-hospital, in-hospital data collection, and quality control

Pre-hospital data were obtained from the All-Japan Utstein Regis- try of the Fire and Disaster Management Agency and collected ac- cording to the Utstein style [10]. In-hospital data were collected via a web form by the physicians or medical staff in charge at the partic- ipating medical institutions. The anonymized collected data were checked by members of the JAAM-OHCA registry working group. The detailed methodology is described elsewhere [9]. The following data were collected: sex, age, witness status, institution characteris- tics, the presence of a bystander who performed cardiopulmonary resuscitation (CPR), shocked by public access Automated external defibrillator , first documented rhythm upon emergency med- ical service (EMS) arrival (ventricular fibrillation (VF)/pulseless ven- tricular tachycardia (VT), Pulseless electrical activity , asystole, or other), pre-hospital intravenous fluid, pre-hospital adrenaline ad- ministration, pre-hospital advanced airway management, EMS re- suscitation times, cause of cardiac arrest, first documented rhythm upon hospital arrival (VF/pulseless VT, PEA, asystole, or return of spontaneous circulation), coronary angiography, percutaneous coro- nary intervention, extracorporeal membrane oxygen, intra-aortic balloon pumping, TTM, TTM completion, survival status, and neuro- logical outcome one month after cardiac arrest.

All OHCA survivors were followed up for 1 month after cardiac arrest

by the physician in charge. Furthermore, the physician in charge de- scribed the neurological out-come 1 month after cardiac arrest. The neurological outcome was defined using the cerebral performance cat- egory (CPC) scale: category 1, good cerebral performance; category 2, moderate cerebral disability; category 3, severe cerebral disability; cat- egory 4, coma or vegetative state; and category 5, death/brain dead [11].

• 1. Primary and secondary outcome

The primary outcome was a 1-month favorable neurological out- come. favorable neurological outcomes were defined by a CPC scale of 1 or2 [11]. The secondary outcome was 1-month survival.

• 1. Statistical analysis

The patients were divided into the following three groups according to age: (1) aged 18-64, (2) 65-74, and (3) >=75 years [12,13]. The reason for this age grouping was that previous studies evaluating the effect of TTM excluded patients aged >=75 years and compared the prognosis of those aged >=75 years with other groups [8,14]. The data were presented as numbers and proportion (%) of patients in each age group. The pa- tient characteristics of the three groups were analyzed using Fisher’s

exact test for categorical data and Kruskal-Wallis test for continuous data. multiple logistic regression analysis was used to calculate the un- adjusted and adjusted odds ratios. This analysis was adjusted for the fol- lowing factors: age (continuous and categorical variables), sex (male or female), cause of cardiac arrest (cardiac or non-cardiac), bystander wit- ness, bystander CPR, shocked by public access AED, first documented rhythm upon EMS arrival, pre-hospital intravenous fluid, pre-hospital adrenaline, pre-hospital advanced airway management, first docu- mented rhythm upon hospital arrival, coronary angiography, percuta- neous coronary intervention, extracorporeal membrane oxygen, and intra-aortic balloon pumping.

All tests were two sided, and a P value <0.05 was defined statistically significant. All analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama Japan), which is a graphical user interface for R Statistical software version 3.6.2 (The R Foundation for Statistical Computing, Vienna, Austria) [15]. More precisely, it is a modified version of R commander designed to add statistical functions frequently used in biostatistics.

1. Results

In the JAAM-OHCA registry, 34,754 patients with OHCA were regis- tered between June 1, 2014, and December 31, 2017. A total of 4553 pa- tients were excluded because they did not attempt resuscitation at the hospital, had no available pre-hospital data, and were aged <18 years. Of these patients, 1847 patients had TTM and were included in our final analyses. Aged distribution was 959 (11.5%) of 8357 patients aged 18-64 years, 499 (8.0%) of 6232 aged 65-74 years, and 389

(2.5%) of 15,612 aged >=75 years (Fig. 1).

The patient characteristics according to age group are shown in Table 1. In all age groups, there were more males, Cardiac origin of ar- rests, and bystander-witnessed arrests. As for pre-hospital characteris- tics, the proportion of shocked by public access AED and the first documented shockable rhythm by EMS personnel was lower in those aged >=75 years. Regarding in-hospital characteristics, patients aged

>=75 years were less likely to have first documented shockable rhythm upon hospital arrival and underwent coronary angiography, percutane- ous coronary intervention, extracorporeal membrane oxygen, and intra-aortic balloon pumping. The incidence of TTM completion did not differ significantly among between groups according to age. The de- tails of participating institution and patient characteristics according to hospital volume were provided in the Supplementary materials. (Table S1 and Table S2).

Table 2 shows the outcome according to the age groups. Overall, 572 of 1847 patients (31.0%) had 1-month favorable neurological outcome; 369 of 959 (38.5%) aged 18-64 years, 124 of 499 (24.8%) aged 65-74 years, 79 of 389 (20.3%) aged >=75 years. In the multivariable logistic re- gression analyses, increasing age was associated with a higher risk of poor neurological outcomes (i.e., patients aged >=75 years vs. patients aged 18-64 years, adjusted odds ratios, 0.31; 95% confidence interval [CI], 0.21-0.45; P for trend <0.001). Furthermore, the 1-month survival rate showed a decreasing trend with age, but there was no sig- nificant difference in the multivariable logistic regression analysis (i.e., patients aged >=75 years vs. patients aged 18-64 years, adjusted odds ratios, 0.75; 95% CI, 0.56-1.01; P for trend, 0.004).

Table 3 demonstrates the association between the characteristics and outcomes of OHCA in patients aged >=75 years who underwent TTM. Of these, 209 of 389 (53.7%) patients survived 1-month after car- diac arrest and 79 of 389 (20.3%) had good neurological outcomes. The proportion of shocked by public access AED, first documented rhythm upon EMS arrival, and first documented rhythm upon hospital arrival were statistically significant regarding both 1-month survival and good neurological outcome (P < 0.001). In addition, the cardiac or- igin of cardiac arrest was statistically associated with good neurological outcomes (P < 0.001).

Fig. 1. Flowchart of patient inclusion in this study. TTM, targeted temperature management.

1. Discussion

In this retrospective analysis of a nationwide Registry of patients with OHCA in Japan, we assessed the characteristics and outcomes of TTM in older adult patients with OHCA. We found, in patients after OHCA who underwent TTM, increasing age was associated with signifi- cantly worsened 1-month neurological outcome. Although there was no significant association between increasing age and 1-month mortality, there was a tendency to decrease 1-month mortality with age. Further- more, our results showed that shocked by public access AED, shockable first documented rhythms upon EMS arrival, and shockable first docu- mented rhythms upon hospital arrival might be factors for favorable neuro-logical outcomes among patients aged >=75 years who underwent TTM. Our study from a leading aging country will be helpful for the de- velopment of resuscitation strategies for older adult patients with OHCA.

The effectiveness of TTM in OHCA has been reported in several pre- vious studies [16-18]. These studies indicated that TTM has the potential to improve outcomes in adult patients with OHCA. However, previous randomized controlled trials excluded patients aged >=75 years [16,17], and a prospective observational study included a few patients aged

>=75 years [18]. Little is known about the characteristics and outcomes of TTM in patients aged >=75 years. The post-hoc sub-study of the TTM trial reported the outcomes of TTM in older adults [8]. This study showed an association between age and increased mortality in patients with OHCA treated with TTM, while patients with cardiac arrest of non- cardiac origin were excluded. Furthermore, this study was a secondary analysis of a randomized controlled trial, and the external validity was

limited. The international guidelines recommend TTM for the cause of non-cardiac origin as well as the cardiac origin [7], and further research on TTM, which includes all causes of cardiac arrest in older adults, is needed. Thus, we enrolled patients after OHCA who underwent TTM with and without shockable rhythm. The proportion of patients with first documented shockable rhythm upon EMS arrival and hospital ar- rival was statistically higher in the high-volume center group compared with the other groups. The proportion of patients with first documented shockable rhythm in our study was lower than that in a previous land- mark study [19,20]. Our study was based on these previous studies, and it was important to include both patients aged >=75 years and those with all causes of cardiac arrest who underwent TTM.

Our study showed a lower probability of patients aged >=75 years

who underwent TTM than those aged 18-64 and 65-74 years. These re- sults might imply that the indication criteria for TTM seemed more se- vere in the real world, although the actual protocol for TTM at each institution was unknown. Despite this, the prognosis of OHCA treated with TTM is still worse in patients aged >=75 years compare to younger patients. This result might have been due to several reasons. First, the incidence of VF/pulseless VT in the patients aged >=75 years was lower than that in the patients aged 18-64 and 65-74 years in our study. Our findings were consistent with those of a previous study [21]. PEA and asystole were associated with worse outcomes compared with shockable rhythm [22]. A previous study showed that older age and co- morbidity were associated with PEA and asystole [23]. Older patients might have had a higher proportion of comorbidities compared with younger patients, leading to PEA and asystole. Therefore, older patients treated with TTM in our study might have had worse outcomes. Second,

Patients characteristics of out-of-hospital cardiac arrest	according to the age (n = 1847)
		Age 18-64 years		Age 65-74 years		age >= 75 years	P value
		n = 959		n = 499		n = 389
Male, n (%)		741 (77.3)		382 (76.6)		278 (71.5)	0.072
Cause of cardiac arrest, n (%)	Cardiac	761 (79.4)		399 (80.0)		270 (69.4)	<0.001
	Non-cardiac	198 (20.6)		100 (20.0)		119 (30.6)
cardiac arrest of cardiac origin, n (%)	Acute coronary syndrome	333 (34.7)		213 (42.7)		112 (28.8)	<0.001
	Medical origin except ACS	289 (30.1)		119 (23.8)		79 (20.3)
	Non-medical origin	139 (14.5)		67 (13.4)		79 (20.3)
Pre-hospital characteristics Bystander witness, n (%)		735 (76.6)		399 (80.0)		299 (76.9)	0.329
Bystander CPR, n (%)		506 (52.8)		222 (44.5)		184 (47.3)	0.007
Shocks by a public access AED, n (%)		108 (11.3)		55 (11.0)		25 (6.4)	0.022
First documented rhythm upon EMS arrival, n (%)	VF, Pulseless VT	521 (54.3)		250 (50.1)		127 (32.6)	<0.001
	PEA	204 (21.3)		112 (22.4)		136 (35.0)
	Asystole	136 (14.2)		93 (18.6)		88 (22.6)
	Other	98 (10.2)		44 (8.8)		38 (9.8)
Intravenous fluid, n (%)		369 (38.5)		211 (42.4)		155 (40.1)	0.354
Adrenaline, n (%)		278 (29.0)		166 (33.3)		109 (28.1)	0.151
Advanced airway management, n (%)		399 (41.6)		231 (46.3)		173 (44.5)	0.209
EMS resuscitation times, min, median (Q1-Q3)	EMS response time (call to contact with a patient)	8 (6-10)		8 (6-9)		8 (6-9)	0.409
	Hospital arrival time (call to hospital arrival)	35 (25-39)		34 (25-39)		34 (25-38)	0.676
In-hospital characteristics First documented rhythm at hospital arrival, n (%)	VF, Pulseless VT	238 (24.8)		92 (18.4)		42 (10.8)	<0.001
	PEA	195 (20.3)		136 (27.3)		104 (26.7)
	Asystole	163 (17.0)		90 (18.0)		80 (20.6)
	ROSC	363 (37.9)		181 (36.3)		163 (41.9)
CAG, n (%)		639 (66.6)		334 (66.9)		186 (47.8)	<0.001
PCI, n (%)		288 (30.0)		186 (37.3)		102 (26.2)	0.001
ECMO, n (%)		358 (37.3)		139 (27.9)		48 (12.3)	<0.001
IABP, n (%)		343 (35.8)		172 (34.5)		83 (21.3)	<0.001
TTM completion, n (%)		746 (77.8)		367 (73.5)		282 (72.5)	0.015

ACS, acute coronary syndrome; CPR, cardiopulmonary resuscitation; AED, automated external defibrillator; EMS, emergency medical services; VF, ventricular fibrillation; VT, ventricular tachycardia; PEA, pulseless electric activity; ROSC, return of spontaneous circulation; CAG, cor-onary angiography; PCI, percutaneous coronary intervention; ECMO, extracorporeal mem- brane oxygenation; IABP, intra-aortic balloon pumping.

older patients may have biological mechanisms that make TTM less ef- fective. Little is known about the biological mechanisms by which TTM prevents brain injury following cardiac arrest. Microglia play key path- ophysiological roles in neuroinflammation in central Nervous system disorders such as hypoxic-ischemic brain injury [24]. Hypothermia inhibited microglial activation and reduced the neuroinflammation re- sponse in animal models of ischemic brain [25]. In an aged animal model of traumatic brain injury, aging was associated with increased ac- tivation of microglia that contribute to neuroinflammation [26]. There- fore, increased neuroinflammation in older patients might have reduced the effect of TTM. With the aging of the population rapidly, a previous study reported that the number of OHCA cases in patients aged >=75 years is increasing annually, accounting for 50% of all OHCA cases [3,12]. However, there was little known evidence of treatment for post-resuscitation care in patients aged >=75 years. As there was a

much higher incidence of OHCA in patients aged >=75 years, randomized controlled trials for TTM focusing on patients aged >=75 years are required.

We described the differences in characteristics between good and poor favorable outcomes in patients aged >=75 years with OHCA who un- derwent TTM. We found that shocked by public access AED, shockable rhythm on EMS arrival, and a shockable rhythm at hospital arrival are likely to be better for both 1-month neurological outcome and mortality in patients with OHCA aged >=75 years who underwent TTM, which was similar to the results of a previous study [27]. While there might already be strict indications for TTM in older adults, further study is needed to establish criteria for indication of TTM in older adults, especially in pa- tients aged >=75 years.

This study has several limitations. First, this retrospective study was not performed with randomization of patient selection. Second, this

Table 2

Unadjusted and adjusted odds ratios for 1-month favorable neurological outcome and 1-month survival according to the age groups

Age 18-64 years (n = 959)	369/959 (38.5)	Ref		Ref
Age 65-74 years (n = 499)	124/499 (24.8)	0.53	(0.42-0.67)	0.44	(0.32-0.61)
Age >= 75 years (n = 389)	79/389 (20.3)	0.41	(0.31-0.54)	0.31	(0.21-0.45)
P for trend		< 0.001		< 0.001
1-month survival
Age 18-64 years (n = 959)	554/959 (57.8)	Ref		Ref
Age 65-74 years (n = 499)	278/499 (55.7)	0.92	(0.74-1.14)	0.88	(0.68-1.15)
Age >= 75 years (n = 389)	209/389 (53.7)	0.85	(0.67-1.08)	0.75	(0.56-1.01)
P for trend		0.036		0.004

Number of cases, n (%) unadjusted OR? (95% CI) adjusted OR? (95% CI) 1-month favorable neurological outcome (CPC 1 or 2)

CPC, cerebral performance category; OR, odds ratios; CI, confidence interval.

* Adjusted for Age, Sex, Cause of cardiac arrest, Bystander witness, Bystander CPR, Shocked by public access AED, First documented rhythm upon EMS arrival, Pre-hospital intravenous

fluid, Pre-hospital advanced airway management, Pre-hospital adrenaline administration, First documented rhythm upon hospital arrival, CAG, PCI, ECMO, IABP.

Table 3

Characteristics and outcomes of out-of-hospital cardiac arrest in patients aged >=75 years who underwent targeted temperature management (n = 389)

1-month survival 1-month CPC

		Survival (n = 209)	Not survival (n = 180)	P value	CPC 1 or 2 (n = 79)	CPC 3-5 (n = 310)	P value
Age, median (Q1-Q3)		80 (77-83)	81 (77-84)	0.154	79 (76-82)	81 (77-84)	<0.001
Male, n (%)		154 (73.7)	124 (68.9)	0.312	57 (72.2)	221 (71.3)	1
Cause of cardiac arrest, n (%)	Cardiac	155 (74.2)	115 (63.9)	0.036	72 (91.1)	198 (63.9)	<0.001
	Non-cardiac	54 (25.8)	65 (36.1)		7 (8.9)	112 (36.1)
cardiac arrest of cardiac origin, n (%)	Acute coronary syndrome	64 (30.6)	48 (26.7)	0.053	36 (45.6)	76 (24.5)	0.007
	Medical origin except ACS	53 (25.4)	26 (14.4)		25 (31.6)	54 (17.4)
	Non-medical origin	38 (18.2)	41 (22.8)		11 (13.9)	68 (21.9)
Prehospital characteristics
Bystander witness, n (%)		169 (80.9)	130 (72.2)	0.054	67 (84.8)	232 (74.8)	0.073
Bystander CPR, n (%)		106 (50.7)	78 (43.3)	0.155	41 (51.9)	143 (46.1)	0.379
Shocks by a public access AED, n (%)		23 (11.0)	2 (1.1)	<0.001	15 (19.0)	10 (3.2)	<0.001
First documented rhythm upon EMS arrival, n (%)	VF, Pulseless VT	87 (41.6)	40 (22.2)	<0.001	51 (64.5)	76 (24.5)	<0.001
	PEA	66 (31.6)	70 (38.9)		7 (8.9)	129 (41.6)
	Asystole	31 (14.8)	57 (31.7)		2 (2.5)	86 (27.7)
	Other	25 (12.0)	13 (7.2)		19 (24.1)	19 (6.1)
Intravenous fluid, n (%)		84 (40.2)	71 (39.4)	1	19 (24.1)	136 (43.9)	0.001
Adrenaline, n (%)		53 (25.4)	56 (31.1)	0.213	7 (8.9)	102 (32.9)	<0.001
Advanced airway management, n (%)		90 (43.1)	83 (46.1)	0.609	23 (29.1)	150 (48.4)	0.003
In-hospital characteristics First documented rhythm upon hospital arrival, n (%)	VF, pulseless VT	26 (12.5)	16 (8.9)	<0.001	15 (19.0)	27 (8.7)	<0.001
	PEA	39 (18.7)	65 (36.1)		3 (3.8)	101 (32.6)
	Asystole	25 (12.0)	55 (30.6)		3 (3.8)	77 (24.8)
	ROSC	119 (56.9)	44 (24.4)		58 (73.4)	105 (33.9)
CAG, n (%)		114 (54.5)	72 (40.0)	0.004	60 (75.9)	126 (40.6)	<0.001
PCI, n (%)		58 (27.8)	44 (24.4)	0.489	30 (38.0)	72 (23.2)	0.01
ECMO, n (%)		11 (5.3)	37 (20.6)	<0.001	4 (5.1)	44 (14.2)	0.033
IABP, n (%)		40 (19.1)	43 (23.9)	0.266	19 (24.1)	64 (20.6)	0.539

ACS, acute coronary syndrome; CPR, cardiopulmonary resuscitation; AED, automated external defibrillator; EMS, emergency medical services; VF, ventricular fibrillation; VT, ventricular tachycardia; PEA, pulseless electric activity; ROSC, return of spontaneous circulation; CAG, coronary angiography; PCI, percutaneous coronary intervention; ECMO, extracorporeal mem- brane oxygenation; IABP, intra-aortic balloon pumping; CPC, cerebral performance category.

registry did not describe past medical history, social history, and medi- cations, although it described age, sex, and pre- and in-hospital inter- ventions. These factors may have affected the outcomes. The impact of covariates should be evaluated in future studies. Third, the TTM protocol was not standardized for each institution. Because the method of the Temperature control device, target temperature, and duration was dif- ferent among facilities, these factors might have affected the outcome. However, the appropriate target temperature and duration are still de- bated [19,20], and the impact may be limited. Moreover, the inclusion protocols for TTM at each participating institution were not available in this registry. According to the recommendations by the international guidelines for TTM [6,7], this study enrolled patients with OHCA who underwent TTM with and without shockable rhythm. In addition, TTM was expensive, invasive, and required medical resources. Therefore, most patients in this study may have been reasonable candidates for TTM based on their characteristics. Fourth, this study may have had a risk of selection bias. Deciding to perform TTM, it was s probable that the patients with Multiple comorbidities or those whose families did not hope for treatment might not have received TTM. This might have under-evaluated the patients aged >=75 years, who had worse outcomes. In addition, after TTM induction, it would have also been possible to withdraw TTM early in older patients. However, the incidence of TTM completion did not differ significantly among the groups according to age. Incomplete TTM might have had little impact on primary and sec- ondary outcomes. Fifth, this study was conducted in Japan, and whether the results of this study can be applied to other countries needs to be examined.

1. Conclusions

In this retrospective, nationwide, observational study in Japan, we found that the neurological outcomes of patients with OHCA who un- derwent TTM worsened with in-creasing age. With the aging of the

population, the number of older adult patients with OHCA is expected to increase further, and it is necessary to discuss the management of TTM in this population.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

Institutional review board statement

This study protocol was approved by the Institutional Review Board of each participating hospital.

Informed consent statement

The study protocol was approved by the institutional review board of each participating hospital. Patient consent was waived due to the observational study and de-identification of personal data.

Duplicate publication

None.

CRediT authorship contribution statement Satoshi Nakajima: Writing - original draft, Methodology, Investiga-

tion, Formal analysis, Data curation, Conceptualization. Tasuku Matsu- yama: Writing - review & editing, Supervision, Methodology, Conceptualization. Nobunaga Okada: Writing - review & editing, Methodology. Kenji Kandori: Writing - review & editing, Methodology. Asami Okada: Writing - review & editing, Methodology. Yohei Okada: Writing - review & editing, Methodology. Tetsuhisa Kitamura:

Writing - review & editing, Methodology. Bon Ohta: Supervision, Pro- ject administration.

Data availability statement

Not applicable.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influ- ence the work reported in this paper.

Acknowledgments

We appreciated to all members and institution of the JAAM-OHCA registry. The participating institutions of the JAAM-OHCA registry are listed at the following URL: http://www.jaamohca-web.com/list/.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2023.01.027.

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