Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1 years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

Initial assessment in emergency departments by chief complaint and respiratory rate.

BACKGROUND: Understanding heterogeneity of the respiratory rate (RR) as a risk stratification marker across chief complaints is important to reduce misinterpretation of the risk posed by outcome events and to build accurate risk stratification tools. This study was conducted to investigate the associations between RR and clinical outcomes according to the five most frequent chief complaints in an emergency department (ED): fever, shortness of breath, altered mental status, chest pain, and abdominal pain. METHODS: This retrospective cohort study examined ED data of all adult patients who visited the ED of a tertiary medical center during April 2018-September 2019. The primary exposure was RR at the ED visit. Outcome measures were hospitalization and mechanical ventilation use. We used restrictive cubic spline and logistic regression models to assess the association of interest. RESULTS: Of 16 956 eligible ED patients, 4926 (29%) required hospitalization; 448 (3%) required mechanical ventilation. Overall, U-shaped associations were found between RR and the risk of hospitalization (eg, using RR = 16 as the reference, the odds ratio [OR] of RR = 32, 6.57 [95% CI 5.87-7.37]) and between RR and the risk of mechanical ventilation. This U-shaped association was driven by patients' association with altered mental status (eg, OR of RR = 12, 2.63 [95% CI 1.25-5.53]). For patients who have fever or shortness of breath, the risk of hospitalization increased monotonously with increased RR. CONCLUSIONS: U-shaped associations of RR with the risk of overall clinical outcomes were found. These associations varied across chief complaints.

Association of Initial Potassium Levels with the Type of Stroke in the Emergency Department.

Serum potassium levels are considered as a marker of cerebrovascular emergencies but there is less clarity on the association between initial serum potassium levels recorded on patient's arrival at the emergency department with the type of stroke. This is a case-control study using data of a tertiary care hospital in Japan from April 2018 to September 2019. We identified adult patients with hemorrhagic stroke including subarachnoid hemorrhage (cases) and those with ischemic stroke (controls). Data on age, sex, chief complaints, vital signs, and initial blood tests were collected. We analyzed the association between serum potassium levels and the type of stroke by drawing a LOWESS curve. Additionally, we fitted a logistic regression model to examine the association of interest. There were 416 stroke patients (158 hemorrhagic and 258 ischemic). The median age was 77 years (IQR: 68, 84), and 54% were male. The mean potassium level was 3.69 ± 0.55 mEq/L for hemorrhagic stroke and 4.08 ± 0.65 mEq/L for ischemic stroke. The LOWESS curve showed that the lower initial potassium level was linearly associated with a greater likelihood of hemorrhagic stroke. In the logistic regression model, the odds ratio for the risk of hemorrhagic stroke per 1 mEq/L lower potassium level was 3.31 (95% confidence interval [CI]: 2.24-5.04). This association remained significant in a multivariable model adjusting for other covariates (OR: 2.62 [95% CI: 1.70-4.16]). Initial potassium level was lower in patients with hemorrhagic stroke compared to those with ischemic stroke.

Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective cohort study.

BACKGROUND: While time in targeted blood glucose range (TIR) 70-140 mg/dL is a known factor associated with mortality in critically ill patients, it remains unclear whether TIR is associated with 28-day mortality under the glycemic control with a less tight target glucose range of 70-180 mg/dL. We aimed to examine whether TIR 70-180 mg/dL was associated with 28-day mortality. METHODS: This is a retrospective cohort study using data from a tertiary care center in Japan collected from January 2016 through October 2019. We included adult patients (aged ≥20 years) admitted to the ICU. We excluded patients 1) with diabetic ketoacidosis patients, 2) discharged within 48 hours, 3) with repeated ICU admissions. We calculated TIR 70-180 mg/dL using the measured blood glucose values (≥3 times per day). The primary outcome was 28-day mortality. We examined the association between TIR and 28-day mortality using a logistic regression and Cox proportional hazard models with a stratification by glycosylated hemoglobin (HbA1c) level of 6.5%. Additionally, we repeated the analyses using the TIR category to assess the optimal TIR. For the sensitivity analysis, we repeated the primary analysis using TIR during the first three days from ICU admission. RESULTS: Of 1,230 patients, the median age was 72 years, 65% were male, and 250 patients (20%) had HbA1c ≥6.5% on admission. In patients with HbA1c <6.5%, TIR <80% was associated with an increased risk of 28-day mortality, with an adjusted odds ratio (OR) of 1.88 (95%CI: 1.36-2.61). Likewise, when using 10% incremental TIR as a categorical variable, lower TIR was associated with a worse 28-day mortality compared with TIR ≥90% (e.g., adjusted OR of TIR <60%, 3.62 [95%CI 2.36-5.53]). Similar associations were found in the analyses using Cox proportional hazards model and using TIR during the first three days. By contrast, in patients with HbA1c ≥6.5%, there was no consistent association of TIR with 28-day mortality. CONCLUSIONS: We found that lower TIR 70-180 mg/dL was associated with a higher 28-day mortality in critically ill patients with HbA1c <6.5%, whereas there was no consistent association in patients with HbA1c ≥6.5%.

Clinical Utility of Bile Duct Axis Deviation for Differential Diagnosis Between Pancreatic Head Cancer and Bile Duct Cancer.

BACKGROUNDS: Differential diagnosis between pancreatic head cancer (PHC) and intrapancreatic bile duct cancer (BDC) is important, but no clinical standard has been established. Here we examine the diagnostic utility of bile duct axis deviation and other clinical factors for this differential diagnosis. METHODS: This study enrolled patients who underwent pancreaticoduodenectomy for PHC or BDC at our center between 2009 and 2016. PHCs in groove or uncinate portions were excluded from analysis. From contrast-enhanced computed tomography images, the bile duct angle (BDA) was measured using three points: the junction of intrahepatic bile ducts, upper pancreatic edge, and Vater papilla. Logistic regression was performed to evaluate the diagnostic performance of BDA and other clinical factors for differential diagnosis. RESULTS: During the study period, 22 PHCs and 31 BDCs were resected. The combination of BDA ≤ 130°, main pancreatic duct diameter ≥ 4.3 mm, and absence of jaundice predicted PHC rather than BDC with an area under the curve of the receiver-operator characteristics curve of .856 (95% confidence interval, .766-.947). CONCLUSION: Clinical findings of larger bile duct axis deviation, main pancreatic duct dilation, and the absence of jaundice may be useful for distinguishing PHC from BDC.

Institution-Specific Machine Learning Models for Prehospital Assessment to Predict Hospital Admission: Prediction Model Development Study.

BACKGROUND: Although multiple prediction models have been developed to predict hospital admission to emergency departments (EDs) to address overcrowding and patient safety, only a few studies have examined prediction models for prehospital use. Development of institution-specific prediction models is feasible in this age of data science, provided that predictor-related information is readily collectable. OBJECTIVE: We aimed to develop a hospital admission prediction model based on patient information that is commonly available during ambulance transport before hospitalization. METHODS: Patients transported by ambulance to our ED from April 2018 through March 2019 were enrolled. Candidate predictors were age, sex, chief complaint, vital signs, and patient medical history, all of which were recorded by emergency medical teams during ambulance transport. Patients were divided into two cohorts for derivation (3601/5145, 70.0%) and validation (1544/5145, 30.0%). For statistical models, logistic regression, logistic lasso, random forest, and gradient boosting machine were used. Prediction models were developed in the derivation cohort. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) and association measures in the validation cohort. RESULTS: Of 5145 patients transported by ambulance, including deaths in the ED and hospital transfers, 2699 (52.5%) required hospital admission. Prediction performance was higher with the addition of predictive factors, attaining the best performance with an AUROC of 0.818 (95% CI 0.792-0.839) with a machine learning model and predictive factors of age, sex, chief complaint, and vital signs. Sensitivity and specificity of this model were 0.744 (95% CI 0.716-0.773) and 0.745 (95% CI 0.709-0.776), respectively. CONCLUSIONS: For patients transferred to EDs, we developed a well-performing hospital admission prediction model based on routinely collected prehospital information including chief complaints.

Validation of chief complaints, medical history, medications, and physician diagnoses structured with an integrated emergency department information system in Japan: the Next Stage ER system.

AIM: Emergency department information systems (EDIS) facilitate free-text data use for clinical research; however, no study has validated whether the Next Stage ER system (NSER), an EDIS used in Japan, accurately translates electronic medical records (EMRs) into structured data. METHODS: This is a retrospective cohort study using data from the emergency department (ED) of a tertiary care hospital from 2018 to 2019. We used EMRs of 500 random samples from 27,000 ED visits during the study period. Through the NSER system, chief complaints were translated into 231 chief complaint categories based on the Japan Triage and Acuity Scale. Medical history and physician's diagnoses were encoded using the International Classification of Diseases, 10th Revision; medications were encoded as Anatomical Therapeutic Chemical Classification System codes. Two reviewers independently reviewed 20 items (e.g., presence of fever) for each study component (e.g., chief complaints). We calculated association measures of the structured data by the NSER system, using the chart review results as the gold standard. RESULTS: Sensitivities were very high (>90%) in 17 chief complaints. Positive predictive values were high for 14 chief complaints (≥80%). Negative predictive values were ≥96% for all chief complaints. For medical history and medications, most of the association measures were very high (>90%). For physicians' ED diagnoses, sensitivities were very high (>93%) in 16 diagnoses; specificities and negative predictive values were very high (>97%). CONCLUSIONS: Chief complaints, medical history, medications, and physician's ED diagnoses in EMRs were well-translated into existing categories or coding by the NSER system.

Social withdrawal and testosterone levels in early adolescent boys.

Social withdrawal may lead to mental health problems and can have a large impact on a life course, particularly among boys. To support adolescents with social withdrawal, an integrative understanding of the biological bases would be helpful. Social dominance, a possible opposite of social withdrawal, is known to have positive associations with testosterone levels. A previous study suggested that social withdrawal has a negative relationship with sexual maturity among adolescent boys. However, the relationship between social withdrawal and testosterone in adolescence is unknown. This study aimed to examine whether social withdrawal was negatively associated with testosterone levels in early adolescent boys. Salivary samples were collected from 159 healthy early adolescent boys (mean age [standard deviation]: 11.5 [0.73]) selected from participants of the "population-neuroscience study of the Tokyo Teen Cohort" (pn-TTC). Social withdrawal and confounding factors, such as the secondary sexual characteristics and their age in months, were evaluated by self-administered questionnaires completed by the primary parents. The degree of social withdrawal was assessed with the Child Behaviour Checklist (CBCL). Levels of salivary testosterone, and cortisol as a control, were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Logistic regression was conducted to examine the association between social withdrawal and testosterone levels. A higher risk of social withdrawal was associated with a lower salivary testosterone level after adjustment for age in months (odds ratio 0.55, 95 % confidence interval 0.33-0.94), and the association remained significant after adjusting for body mass index, the degree of anxiety/depression and pubertal stage. Thus, we found a negative relationship between social withdrawal and testosterone levels in early adolescent boys. These findings may help to clarify the biological foundations of and to develop support for social withdrawal.

Predictive Factors of Postoperative Delirium in Patients After Pancreaticoduodenectomy.

BACKGROUND: Postoperative delirium is a common serious complication after various types of surgery. However, the incidence and predictive factors associated with delirium after pancreaticoduodenectomy (PD) have not been investigated. Thus, this study aimed to investigate the incidence and predictive factors of postoperative delirium in patients who underwent PD. METHODS: This study included 155 consecutive patients who underwent PD. Patients with and without postoperative delirium were compared to identify differential patient characteristics. Multivariate regression analysis was used to statistically identify independent predictive factors significantly associated with the development of postoperative delirium. RESULTS: Postoperative delirium developed in 27 (22.4%) of 155 patients. The majority of incidents occurred on postoperative day 2, and the mean delirium duration was 4.6 ± 4.8 days. Patients with postoperative delirium had an older age and a previous history of benzodiazepine use. A multivariate analysis revealed that the development of delirium was significantly correlated with these two factors. Receiver-operator characteristics (ROC) curve analysis of the two factors yielded an area under the ROC curve of 0.823 (0.750-0.896), suggesting good discrimination power. CONCLUSIONS: This study reports on the incidence of postoperative delirium after PD. Furthermore, we identified age and use of benzodiazepines as significant predictive factors for developing delirium after PD. These results contribute to the prediction and treatment of postoperative delirium.

Outcomes of laparoscopic cholecystectomy for xanthogranulomatous cholecystitis.

Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory disease of the gallbladder with distinct histopathological characteristics. Laparoscopic cholecystectomy (LC) is currently the standard treatment for gallbladder disease. However, the outcomes of LC for XGC have not been completely investigated, due to the rarity of XGC. The present study aimed to assess the surgical outcomes of LC for XGC. Among 3,037 patients undergoing cholecystectomy between 2005 and 2017 at our institution, 58 patients (1.9%) were diagnosed with XGC based on histopathology. Of the patients, LC was performed in 38 (65.5%), and they were enrolled in the present study. The outcome of LC for XGC in the cases was assessed, and was compared with outcomes of LC for other diseases. The average operation time was 109±36 min, and average intraoperative blood loss was 58±85 ml. LC was converted to open cholecystectomy in 6 (15.8%) of the 38 cases. No operative mortality occurred. One patient developed postoperative complications greater than grade II in the Clavien-Dindo classification, and the mean postoperative hospital stay was 6.1±5.8 days. Based on previous reports and the nature of XGC itself, the outcomes reported herein of LC for XGC seemed acceptable. It should be also noted that LC for XGC exhibited a higher conversion rate compared with LC than other benign gallbladder diseases, implying that LC for XGC remains challenging.

Dietary Inflammatory Index Is Associated with Risk of All-Cause and Cardiovascular Disease Mortality but Not with Cancer Mortality in Middle-Aged and Older Japanese Adults.

BACKGROUND: The Dietary Inflammatory Index (DII) is a comprehensive, literature-derived index for assessing the effect of dietary constituents on inflammatory biomarkers. Several studies have shown an association between DII score and mortality, but there are limited prospective studies in Asian populations. OBJECTIVES: The aim of this study was to investigate the association between DII score and risk of all-cause, total cardiovascular disease (CVD), stroke, coronary heart disease (CHD), total cancer, digestive cancer, and noncancer/non-CVD mortality in the Japanese population. METHODS: A total of 58,782 Japanese participants aged 40-79 y who were enrolled in the Japan Collaborative Cohort Study during 1988-1990 were included in the analysis. DII scores were calculated based on a food-frequency questionnaire. HRs and 95% CIs for mortality according to DII quintiles were estimated using Cox proportional hazards models. RESULTS: During the median follow-up period of 19.3 y, a total of 11,693 participants died. The multivariable HR for all-cause mortality for the highest compared with the lowest DII quintiles was 1.13 (95% CI: 1.05, 1.21). For CVD mortality, the highest multivariable HRs were 1.30 (95% CI: 1.13, 1.49), 1.29 (95% CI: 1.05, 1.59), and 1.30 (95% CI: 0.96, 1.76) for total CVD, stroke, and CHD, respectively. No significant associations were observed between DII and risk of total cancer, digestive cancer, and noncancer/non-CVD mortality. CONCLUSION: Our findings suggest that a higher DII was associated with an increased risk of all-cause and CVD mortality among Japanese adults.

Population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC): Cohort longitudinal study to explore the neurobiological substrates of adolescent psychological and behavioral development.

AIM: Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. Our understanding of how the maturation of endocrine, epigenetics, and brain circuit may underlie psychological development in adolescence, however, has not been integrated. Here, we introduce our research project, the population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC), a longitudinal study to explore the neurobiological substrates of development during adolescence. METHODS: Participants in the first wave of the pn-TTC (pn-TTC-1) study were recruited from those of the TTC study, a large-scale epidemiological survey in which 3171 parent-adolescent pairs were recruited from the general population. Participants underwent psychological, cognitive, sociological, and physical assessment. Moreover, adolescents and their parents underwent magnetic resonance imaging (MRI; structural MRI, resting-state functional MRI, and magnetic resonance spectroscopy), and adolescents provided saliva samples for hormone analysis and for DNA analysis including epigenetics. Furthermore, the second wave (pn-TTC-2) followed similar methods as in the first wave. RESULTS: A total of 301 parent-adolescent pairs participated in the pn-TTC-1 study. Moreover, 281 adolescents participated in the pn-TTC-2 study, 238 of whom were recruited from the pn-TTC-1 sample. The instruction for data request is available at: http://value.umin.jp/data-resource.html. CONCLUSION: The pn-TTC project is a large-scale and population-neuroscience-based survey with a plan of longitudinal biennial follow up. Through this approach we seek to elucidate adolescent developmental mechanisms according to biopsychosocial models. This current biomarker research project, using minimally biased samples recruited from the general population, has the potential to expand the new research field of population neuroscience.

Association between average daily television viewing time and the incidence of ovarian cancer: findings from the Japan Collaborative Cohort Study.

PURPOSE: Seventy-five percent of epidemiological studies have reported that sedentary behavior is associated with ovarian cancer incidence. Although Japan has one of the most sedentary populations, with median sitting times of 7 h/day, this association has not been investigated. This study aimed to elucidate the association between average daily television (TV) viewing time, which is a major sedentary behavior, and the incidence of ovarian cancer in a large-scale nationwide cohort study in Japan. METHODS: A total of 34,758 female participants aged 40-79 years without a history of cancer at baseline were included in the study. The inverse probability weighted competing risk model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the incidence of ovarian cancer. RESULTS: During a median follow-up of 19.4 years, 59 participants developed ovarian cancer (ICD-10: C56), 2,706 participants developed other types of cancer, and 4,318 participants died. Participants who watched TV for ≥ 5 h/day were more likely to develop ovarian cancer than those who watched TV for < 2 h/day (HR 2.15; 95% CI 1.54-2.99). CONCLUSION: Our findings suggest that reducing the amount of time spent sedentarily may be beneficial for preventing ovarian cancer.

Surgical Apgar score for predicting complications after hepatectomy for hepatocellular carcinoma.

BACKGROUND: Surgical Apgar score (SAS) was recently proposed as a simple predictor of postoperative complications. A few studies have shown the utility of the SAS in some kinds of surgeries, but it has not been investigated in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). METHODS: This study included 158 patients undergoing hepatectomy for HCC. The association between SAS and postoperative complications was examined. The patients had postoperative morbidities classified as Clavien-Dindo grade II or higher. Multivariate regression analysis was performed to identify independent factors that significantly influenced the development of postoperative complications. RESULTS: Postoperative complications developed in 28 (17.7%) of the 158 patients. The proportion of cases with complications was significantly inversely correlated with SAS (Spearman rank correlation 0.829). The SAS was significantly lower in cases with complications than those without complications (5.6 ± 1.3 points versus 6.6 ± 1.3 points, P = 0.0004). Comparisons between patients with and without complication showed that preoperative serum albumin level and operation time, as well as SAS, were associated with complications. Multivariate analysis revealed that postoperative complications significantly correlated with the SAS. CONCLUSIONS: This study demonstrated the clinical utility of SAS in predicting the development of postoperative complications after hepatectomy for HCC.

The influence of excluding patients with bystander return of spontaneous circulation in the current OHCA database.

BACKGROUND: The effect of bystander interventions has been extensively evaluated by cerebral function after 1 month post-resuscitation. However, patients who received bystander cardiopulmonary resuscitation (BCPR) and achieved the return of spontaneous circulation (ROSC) before the arrival of the emergency medical system (EMS) are routinely defined with an unknown electrocardiogram (ECG) and are usually excluded before analysis. The aim is to determine the influence of excluding patients with unknown first monitored rhythm, which includes cases of bystander ROSC, from the out-of-hospital cardiac arrest (OHCA) database. METHODS: This nationwide population-based observational study was conducted in Japan using Utstein data from 2011 to 2014. In total, 91,995 patients with bystander-witnessed cardiogenic OHCA received resuscitation attempts in the pre-hospital setting. These patients were divided into three groups by the first monitored rhythm upon EMS arrival. We analysed the differences of datasets that included and excluded the unknown group and determined the effect on outcomes by multivariate logistic regression and odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: When the unknown group was excluded from the data, the adjusted odds ratio (AOR) of cardiopulmonary resuscitation (CPR) to favourable cerebral performance category (CPC) 1 or 2 was decreased (conventional CPR: AOR, 1.90 to 1.58; chest-compression-only CPR: AOR, 2.08 to 1.69) compared to the unknown group's inclusion. Conversely, the AOR of public-access defibrillation (PAD) was increased (AOR, 4.51 to 6.13). CONCLUSIONS: The exclusion of unknown ECGs from a dataset may lose ROSC patients by bystander CPR, causing selection bias to affect outcomes.

Alcohol consumption and mortality from aortic disease among Japanese men: The Japan Collaborative Cohort study.

BACKGROUND AND AIMS: Only a few population-based prospective studies have examined the association between alcohol consumption and abdominal aortic aneurysm, and the results are inconsistent. Moreover, no evidence exists for aortic dissection. We examined the effect of alcohol consumption on risk of mortality from aortic diseases. METHODS: A total of 34,720 men from the Japan Collaborative Cohort study, aged 40-79 years, without history of cardiovascular disease and cancer at baseline 1988 and 1990 were followed up until the end of 2009 for their mortality and its underlying cause. Hazard ratios of mortality from aortic diseases were estimated according to alcohol consumption categories of never-drinkers, ex-drinkers, regular drinkers of ≤30 g, and >30 g ethanol per day. RESULTS: During the median 17.9-year follow-up period, 45 men died of aortic dissection and 41 men died of abdominal aortic aneurysm. Light to moderate drinkers of ≤30 g ethanol per day had lower risk of mortality from total aortic disease and aortic dissection compared to never-drinkers. The respective multivariable hazard ratios (95% confidence intervals) were 0.46 (0.28-0.76) for total aortic disease and 0.16 (0.05-0.50) for aortic dissection. Heavy drinkers of >30 g ethanol per day did not have reduced risk of mortality from total aortic disease, albeit had risk variation between aortic dissection and abdominal aortic aneurysm. CONCLUSIONS: Light to moderate alcohol consumption was associated with reduced mortality from aortic disease among Japanese men.

Favorable neurological outcomes by early epinephrine administration within 19 minutes after EMS call for out-of-hospital cardiac arrest patients.

OBJECTIVE: To evaluate the time-independent effect of the early administration of epinephrine (EPI) on favorable neurological outcome (as CPC [cerebral performance category] 1-2) at 1 month in patients with out-of-hospital cardiac arrest. MATERIALS AND METHODS: A total of 119 639 witnessed cardiac arrest patients from 2008 to 2012 were eligible for this nationwide, prospective, population-based observational study. Patients were divided into EPI group (n = 20 420) and non-EPI group (n = 99 219). To determine the time-dependent effects of EPI, EPI-administered patients were divided into 4 groups as follows: early EPI (5-18 min), intermediate EPI (19-23 min), late EPI (24-29 min), and very late EPI (30-62 min), respectively. Multiple logistic regression analyses and adjusted odds ratios (AORs) were determined for CPC 1-2 at 1 month (primary outcome) and field return of spontaneous circulation (as secondary outcome) among the groups. RESULTS: The EPI and non-EPI group had identical background, but EPI group shows higher incidence public access defibrillation and emergency medical technician defibrillation delivered than the non-EPI group. The differences were clinically negligible. Higher return of spontaneous circulation rate (18.0%) and lower CPC 1-2 (2.9%) shown in the EPI group than in the non-EPI group (9.4% and 5.2%). In the time dependent analysis, CPC 1 to 2 was greatest in the early EPI group (AOR, 2.49; 95% confidence interval [CI], 1.90-3.27), followed by the intermediate EPI group (AOR, 1.53; 95% CI, 1.14-2.05) then the late EPI group (AOR, 0.71; 95% CI, 0.47-1.08) as reference. CONCLUSION: Early EPI administration within 19 minutes after emergency medical service call independently improved the neurological outcome compared with late EPI (24-29 minutes) administration in patients with out-of-hospital cardiac arrest.